Synthesis of acyclic and cyclic amines using iron-catalyzed nitrene group transfer

Abstract

The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more CH groups, catalyzed by a Fe.sup.II-dipyrromethene complex. The acyclic secondary amines are thought to be formed through an intermolecular nitrene transfer. Also provided herein are methods of synthesizing protected (e.g., Boc- or Fmoc-protected) cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) by reacting an azide that bears one or more CH groups, catalyzed by a Fe.sup.II-dipyrromethene complex. The protected cyclic secondary amines are thought to be formed through an intramolecular nitrene transfer and may be subsequently deprotected to yield cyclic secondary amines.

Claims

1. A method of preparing a compound of Formula (II-1): ##STR00150## or a salt thereof, the method comprising reacting an azide of Formula (F), or a salt thereof, with a ferrous compound of Formula (G), or a salt thereof: ##STR00151## wherein: W is selected from the group consisting of mesityl and 2,6-dichlorophenyl; each occurrence of X is independently selected from the group consisting of O, S, NR.sup.c, and C(R.sup.d).sub.2; R.sup.c is selected from the group consisting of hydrogen, a nitrogen protecting group, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; each one of R.sup.7, R.sup.8, R.sup.9, and R.sup.10, and each occurrence of R.sup.d, are independently selected from the group consisting of hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, OR.sup.e, N(R.sup.e).sub.2, SR.sup.e, CN, C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, C(NR.sup.e)N(R.sup.e).sub.2, NO.sub.2, NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, NR.sup.eC(O)N(R.sup.e).sub.2, OC(O)R.sup.e, OC(O)OR.sup.e, OC(O)N(R.sup.e).sub.2, and ON(R.sup.e).sub.2; each occurrence of R.sup.e is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, and a sulfur protecting group when attached to a sulfur atom, or two R.sup.e groups are joined to form an optionally substituted heterocyclic ring; or two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form an optionally substituted carbocyclyl or optionally substituted heterocyclic ring; Y is selected from the group consisting of N(R.sup.f).sub.3, R.sup.fOR.sup.f, R.sup.fSR.sup.f, optionally substituted heterocyclyl, and optionally substituted heteroaryl; each occurrence of R.sup.f is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; and n is 1, 2, 3, 4, or 5.

2. The method of claim 1, further comprising reacting the compound of Formula (II-1), or a salt thereof, with di-t-butyl dicarbonate (Boc.sub.2O) to provide a compound of Formula (II-2-A), or a salt thereof, or with 9-fluorenylmethyl N-succinimidyl carbonate (Fmoc-OSuc) to provide a compound of Formula (II-2-B), or a salt thereof: ##STR00152##

3. The method of claim 2, further comprising deprotecting the compound of Formula (II-2-A) or (II-2-B), or a salt thereof, to provide a cyclic amine of Formula (II-3): ##STR00153## or a salt thereof.

4. The method of claim 3, wherein the deprotection step comprises reacting an acidic compound, a nucleophilic compound, or a reductive compound with the compound of Formula (II-2-A), or a salt thereof, or reacting a nucleophilic compound, a basic compound, a reductive compound, or an oxidative compound with the compound of Formula (II-2-B), or a salt thereof, to provide the cyclic amine of Formula (II-3), or a salt thereof.

5. The method of claim 1, wherein R.sup.7 and R.sup.8 are each hydrogen.

6. The method of claim 1, wherein R.sup.7 is hydrogen; and R.sup.8 is optionally substituted alkyl.

7. The method of claim 1, wherein R.sup.7 and R.sup.8 are each optionally substituted alkyl.

8. The method of claim 1, wherein Y is R.sup.fOR.sup.f; and each occurrence of R.sup.f is independently optionally substituted alkyl.

9. The method of claim 1, wherein Y is optionally substituted heterocyclyl.

10. The method of claim 1, wherein Y is optionally substituted tetrahydrofuran or optionally substituted tetrahydropyran.

11. The method of claim 1, wherein Y is optionally substituted heteroaryl.

12. The method of claim 1, wherein Y is optionally substituted pyridine.

13. The method of claim 1, wherein n is 2.

14. The method of claim 1, wherein n is 3.

15. The method of claim 1, wherein n is 4.

16. The method of claim 1, wherein W is mesityl.

17. The method of claim 1, wherein W is 2,6-dichlorophenyl.

18. The method of claim 1, wherein Y is diethyl ether.

19. The method of claim 1, wherein the ferrous compound of Formula (G) is of Formula (3A): ##STR00154##

20. The method of claim 1, wherein the ferrous compound of Formula (G) is of Formula (3B): ##STR00155##

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIGS. 1A-D show exemplary X-ray crystal structures of Fe.sup.II-dipyrromethene complexes useful in catalyzing CH bond amination reactions.

(2) FIG. 2 illustrates a proposed mechanism of an intermolecular CH amination reaction catalyzed by Fe.sup.II-dipyrromethene complex 3A to yield acyclic secondary amines.

(3) FIG. 3 illustrates a proposed mechanism of an intramolecular CH amination reaction catalyzed by Fe.sup.II-dipyrromethene complex 3A to yield cyclic amines.

(4) FIGS. 4A-D are exemplary X-ray crystal structures of Fe.sup.IIICl (cyclic amine)-dipyrromethene complexes.

(5) FIGS. 5A-D are exemplary solid-state core structures of Fe.sup.IIICl (cyclic amine)-dipyrromethene complexes. (A) (.sup.AdL)FeCl(2-C.sub.2H.sub.3NHC.sub.4H.sub.7) 8; (B) (.sup.AdL)FeCl(2-Ph-NHC.sub.4H.sub.7) 9; (C) (.sup.AdL)FeCl(2-Et-NHC.sub.4H.sub.7) 10; (D) (.sup.AdL)FeCl(2,2-Me.sub.2-NHC.sub.4H.sub.7) 11. Thermal ellipsoids were set at the 50% probability level. Average bond lengths () for: FeN.sub.dipyrrin 2.046(3), 2.062(3); FeN3, 2.145(3); FeCl, 2.266(4).

(6) FIG. 6 shows a X-ray crystal structure of (S)-2-methyl-2-phenylpyrrolidine iron-bound adduct 20 obtained from a reaction of (R)-2-phenyl-5-azidopentane (95% enantiomeric excess (ee)) with stoichiometric quantities of compound 3A.

(7) FIGS. 7A-C are exemplary solid-state core structures of Fe.sup.IIICl (cyclic amine)-dipyrromethene complexes. (A) (.sup.AdL)FeCl(2-C.sub.2H.sub.3NHC.sub.5H.sub.9) 12; (B) (.sup.AdL)FeCl(2,2-Me.sub.2-5,5-Me.sub.2-NHC.sub.5H.sub.6) 21; (C) (.sup.AdL)FeCl(2,2-Me.sub.2-4-(t-Bu)-NHC.sub.3H.sub.3) 22. Thermal ellipsoids were set at the 50% probability level.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION

(8) A class of electrophilic complexes has been synthesized that are capable of mediating CH bond functionalization through transiently-formed, or metastable, transition states. Using dipyrromethene ligand platforms as truncated models of the porphyrin platform found in P450 hydroxylase enzymes, it has been observed that the reactivity from the ferrous-ligand constructs mirrors their porphyrin analogs. Illustrated in FIG. 1 are exemplary dipyrromethene ligand platforms that may be useful in the present invention. All these Fe.sup.II-dipyrromethene complexes show a high-spin state (S=2). Catalytic CH bond (e.g., a sp.sup.3 CH bond) amination has been observed from the reaction of organic azides RN.sub.3 with Fe.sup.II coordination complex 1 to form Fe.sup.III(imido) complex 2 (Scheme 3). Shown in Table 1 are mass spectrometric data indicating the formation of 2.

(9) ##STR00015##

(10) TABLE-US-00001 TABLE 1 Mass spectrometric data (TOF/ESI) of Fe.sup.III (imido) complex 2. R Calculated m/z [M + H].sup.+ Observed m/z [M + H].sup.+ Ad 648.4318 648.4284 t-Bu 570.3848 570.3851 Ph 590.3535 590.3509 Mes 632.4004 632.3965 Ts 668.3310 668.3306

(11) The iron-catalyzed amination reaction is useful with a variety of organic azides and has shown reactivity with a range of organic substrates to form acyclic and cyclic secondary amines. For example, linear azides can be intramolecularly aminated to form pyrrolidine or piperidine derivatives having an array of ring-substitutions, including heteroatom-bearing functional groups. It is well known in the art that the azides employed in the inventive methods can be prepared using a variety of synthetic methods. For example, alkyl azides may be made by ring-opening an epoxide using a nucleophilic compound (e.g., a Grignard reagent or alkyl lithium reagent) to afford a terminal alcohol, followed by conversion of the terminal alcohol to the corresponding azide. See, e.g., Corey et al., J. Am. Chem. Soc., 1992, 114, 1906-1908, incorporated herein by reference. Aryl azides may be prepared through a copper(II)-catalyzed conversion of organoboron compounds. See, e.g., Grimes et al., Synthesis, 2010, 1441-1448, incorporated herein by reference. Acyl azides may be synthesized by reacting carboxylic acids with trichloroacetonitrile, triphenylphosphine, and sodium azide. See, e.g., Kim et al., Synlett, 2008, 2072-2074, incorporated herein by reference.

(12) Therefore, by iron-catalyzed nitrene group transfer into tertiary, secondary, and primary CH bonds, a wide range of functionalized products (e.g., acyclic and cyclic secondary amines) can be readily synthesized. For example, acyclic secondary amines may be prepared by an intermolecular reaction of an azide with a CH source, catalyzed by a Fe.sup.II-dipyrromethene complex, e.g., compound 3A shown in FIG. 1D. Cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) may be synthesized by an intramolecular reaction of an azide that bears one or more CH groups, catalyzed by a Fe.sup.II-dipyrromethene complex, e.g., compound 3A (FIG. 1D). These reactions generate little waste and are useful in the synthesis of fine chemicals and pharmaceuticals.

(13) ##STR00016##
Synthesis of Acyclic Secondary Amines

(14) In one aspect, the present invention provides methods of preparing compounds of Formula (I), which are acyclic secondary amines:

(15) ##STR00017##
and salts and stereoisomers thereof, the method comprising the steps of:

(16) reacting an azide of Formula (A), or a salt or stereoisomer thereof, with a ferrous compound of Formula (B), or a salt or stereoisomer thereof, to provide a ferric compound of Formula (C), or a salt or stereoisomer thereof:

(17) ##STR00018##

(18) reacting the ferric compound of Formula (C), or a salt or stereoisomer thereof, with a compound of Formula (D) or (E), or a salt or stereoisomer thereof, to provide a compound of Formula (I), or a salt or stereoisomer thereof:

(19) ##STR00019##
wherein:

(20) Z is selected from the group consisting of mesityl and 2,6-dichlorophenyl;

(21) R.sup.1 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;

(22) each one of R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is independently selected from the group consisting of hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, OR.sup.a, N(R.sup.a).sub.2, SR.sup.a, CN, C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, C(NR.sup.a)N(R.sup.a).sub.2, NO.sub.2, NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, NR.sup.aC(O)N(R.sup.a).sub.2, OC(O)R.sup.a, OC(O)OR.sup.a, OC(O)N(R.sup.a).sub.2, and ON(R.sup.a).sub.2;

(23) optionally two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 groups are joined to form an optionally substituted carbocyclyl or optionally substituted heterocyclic ring;

(24) each occurrence of R.sup.a is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, and a sulfur protecting group when attached to a sulfur atom, or optionally two R.sup.a groups are joined to form an optionally substituted heterocyclic ring;

(25) L is selected from the group consisting of N(R.sup.b).sub.3, R.sup.bOR.sup.b, R.sup.bSR.sup.b, optionally substituted heterocyclyl, and optionally substituted heteroaryl; and

(26) each occurrence of R.sup.b is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl.

(27) In compounds described herein, Z is selected from the group consisting of mesityl and 2,6-dichlorophenyl. In certain embodiments, Z is mesityl. In certain embodiments, Z is 2,6-dichlorophenyl.

(28) In compounds of Formula (I), R.sup.1 is a substituent on the nitrogen atom. In compounds of Formula (A), R.sup.1 is a substituent on the azide group. In certain embodiments, R.sup.1 is substituted alkyl. In certain embodiments, R.sup.1 is unsubstituted alkyl. In certain embodiments, R.sup.1 is C.sub.1-6 alkyl. In certain embodiments, R.sup.1 is methyl. In certain embodiments, R.sup.1 is ethyl. In certain embodiments, R.sup.1 is propyl. In certain embodiments, R.sup.1 is butyl. In certain embodiments, R.sup.1 is t-butyl. In certain embodiments, R.sup.1 is Ad. In certain embodiments, R.sup.1 is substituted alkenyl. In certain embodiments, R.sup.1 is unsubstituted alkenyl. In certain embodiments, R.sup.1 is vinyl. In certain embodiments, R.sup.1 is substituted alkynyl. In certain embodiments, R.sup.1 is unsubstituted alkynyl. In certain embodiments, R.sup.1 is ethynyl. In certain embodiments, R.sup.1 is substituted carbocyclyl. In certain embodiments, R.sup.1 is unsubstituted carbocyclyl. In certain embodiments, R.sup.1 is cyclopropyl. In certain embodiments, R.sup.1 is cyclobutyl. In certain embodiments, R.sup.1 is cyclopentyl. In certain embodiments, R.sup.1 is cyclohexyl. In certain embodiments, R.sup.1 is cycloheptyl. In certain embodiments, R.sup.1 is substituted heterocyclyl. In certain embodiments, R.sup.1 is unsubstituted heterocyclyl. In certain embodiments, R.sup.1 is substituted aryl. In certain embodiments, R.sup.1 is unsubstituted aryl. In certain embodiments, R.sup.1 is substituted phenyl. In certain embodiments, R.sup.1 is tolyl. In certain embodiments, R.sup.1 is 4-tolyl. In certain embodiments, R.sup.1 is Mes. In certain embodiments, R.sup.1 is unsubstituted phenyl. In certain embodiments, R.sup.1 is substituted naphthyl. In certain embodiments, R.sup.1 is unsubstituted naphthyl. In certain embodiments, R.sup.1 is substituted heteroaryl. In certain embodiments, R.sup.1 is unsubstituted heteroaryl. In certain embodiments, R.sup.1 is monocyclic heteroaryl. In certain embodiments, R.sup.1 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.1 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.1 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.1 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.1 is tetrazolyl. In certain embodiments, R.sup.1 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.1 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.1 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.1 is triazinyl. In certain embodiments, R.sup.1 is tetrazinyl. In certain embodiments, R.sup.1 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.1 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.1 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.1 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.1 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.1 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.1 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.1 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.1 is C(NR.sup.a)R.sup.a. In certain embodiments, R.sup.1 is C(NR.sup.a)OR.sup.a. In certain embodiments, R.sup.1 is C(NR.sup.a)N(R.sup.a).sub.2. In certain embodiments, R.sup.1 is C(O)R.sup.a. In certain embodiments, R.sup.1 is C(O)OR.sup.a. In certain embodiments, R.sup.1 is C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.1 is a nitrogen protecting group. In certain embodiments, R.sup.1 is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, or Ts.

(29) Compounds of Formulae (I), (D), and (E) each include a substituent R.sup.2. In certain embodiments, R.sup.2 is H. In certain embodiments, R.sup.2 is halogen. In certain embodiments, R.sup.2 is F. In certain embodiments, R.sup.2 is Cl. In certain embodiments, R.sup.2 is Br. In certain embodiments, R.sup.2 is I (iodine). In certain embodiments, R.sup.2 is substituted acyl. In certain embodiments, R.sup.2 is unsubstituted acyl. In certain embodiments, R.sup.2 is C(O)R.sup.a. In certain embodiments, R.sup.2 is acetyl. In certain embodiments, R.sup.2 is C(O)OR.sup.a. In certain embodiments, R.sup.2 is C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.2 is substituted alkyl. In certain embodiments, R.sup.2 is unsubstituted alkyl. In certain embodiments, R.sup.2 is C.sub.1 alkyl. In certain embodiments, R.sup.2 is methyl. In certain embodiments, R.sup.2 is ethyl. In certain embodiments, R.sup.2 is propyl. In certain embodiments, R.sup.2 is butyl. In certain embodiments, R.sup.2 is Ad. In certain embodiments, R.sup.2 is substituted alkenyl. In certain embodiments, R.sup.2 is unsubstituted alkenyl. In certain embodiments, R.sup.2 is vinyl. In certain embodiments, R.sup.2 is substituted alkynyl. In certain embodiments, R.sup.2 is unsubstituted alkynyl. In certain embodiments, R.sup.2 is ethynyl. In certain embodiments, R.sup.2 is substituted carbocyclyl. In certain embodiments, R.sup.2 is unsubstituted carbocyclyl. In certain embodiments, R.sup.2 is cyclopropyl. In certain embodiments, R.sup.2 is cyclobutyl. In certain embodiments, R.sup.2 is cyclopentyl. In certain embodiments, R.sup.2 is cyclohexyl. In certain embodiments, R.sup.2 is cycloheptyl. In certain embodiments, R.sup.2 is substituted heterocyclyl. In certain embodiments, R.sup.2 is unsubstituted heterocyclyl. In certain embodiments, R.sup.2 is substituted aryl. In certain embodiments, R.sup.2 is unsubstituted aryl. In certain embodiments, R.sup.2 is substituted phenyl. In certain embodiments, R.sup.2 is unsubstituted phenyl. In certain embodiments, R.sup.2 is substituted naphthyl. In certain embodiments, R.sup.2 is unsubstituted naphthyl. In certain embodiments, R.sup.2 is substituted heteroaryl. In certain embodiments, R.sup.2 is unsubstituted heteroaryl. In certain embodiments, R.sup.2 is monocyclic heteroaryl. In certain embodiments, R.sup.2 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.2 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.2 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.2 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.2 is tetrazolyl. In certain embodiments, R.sup.2 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.2 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.2 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.2 is triazinyl. In certain embodiments, R.sup.2 is tetrazinyl. In certain embodiments, R.sup.2 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.2 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.2 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.2 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.2 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.2 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.2 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.2 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.2 is OR.sup.a. In certain embodiments, R.sup.2 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.2 is SR.sup.a. In certain embodiments, R.sup.2 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.2 is N(R.sup.a).sub.2. In certain embodiments, R.sup.2 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.2 is CN. In certain embodiments, R.sup.2 is SCN. In certain embodiments, R.sup.2 is C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, or C(NR.sup.a)N(R.sup.a).sub.2. In certain embodiments, R.sup.2 is C(O)R.sup.a, C(O)OR.sup.a, or C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.2 is NO.sub.2. In certain embodiments, R.sup.2 is NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, or NR.sup.aC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.2 is OC(O)R.sup.a, OC(O)OR.sup.a, or OC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.2 is ON(R.sup.a).sub.2.

(30) Compounds of Formulae (I), (D), and (E) each include a substituent R.sup.3. In certain embodiments, R.sup.3 is H. In certain embodiments, R.sup.3 is halogen. In certain embodiments, R.sup.3 is F. In certain embodiments, R.sup.3 is Cl. In certain embodiments, R.sup.3 is Br. In certain embodiments, R.sup.3 is I (iodine). In certain embodiments, R.sup.3 is substituted acyl. In certain embodiments, R.sup.3 is unsubstituted acyl. In certain embodiments, R.sup.3 is C(O)R.sup.a. In certain embodiments, R.sup.3 is acetyl. In certain embodiments, R.sup.3 is C(O)OR.sup.a, In certain embodiments, R.sup.3 is C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.3 is substituted alkyl. In certain embodiments, R.sup.3 is unsubstituted alkyl. In certain embodiments, R.sup.3 is C.sub.1-6 alkyl. In certain embodiments, R.sup.3 is methyl. In certain embodiments, R.sup.3 is ethyl. In certain embodiments, R.sup.3 is propyl. In certain embodiments, R.sup.3 is butyl. In certain embodiments, R.sup.3 is Ad. In certain embodiments, R.sup.3 is substituted alkenyl. In certain embodiments, R.sup.3 is unsubstituted alkenyl. In certain embodiments, R.sup.3 is vinyl. In certain embodiments, R.sup.3 is substituted alkynyl. In certain embodiments, R.sup.3 is unsubstituted alkynyl. In certain embodiments, R.sup.3 is ethynyl. In certain embodiments, R.sup.3 is substituted carbocyclyl. In certain embodiments, R.sup.3 is unsubstituted carbocyclyl. In certain embodiments, R.sup.3 is cyclopropyl. In certain embodiments, R.sup.3 is cyclobutyl. In certain embodiments, R.sup.3 is cyclopentyl. In certain embodiments, R.sup.3 is cyclohexyl. In certain embodiments, R.sup.3 is cycloheptyl. In certain embodiments, R.sup.3 is substituted heterocyclyl. In certain embodiments, R.sup.3 is unsubstituted heterocyclyl. In certain embodiments, R.sup.3 is substituted aryl. In certain embodiments, R.sup.3 is unsubstituted aryl. In certain embodiments, R.sup.3 is substituted phenyl. In certain embodiments, R.sup.3 is unsubstituted phenyl. In certain embodiments, R.sup.3 is substituted naphthyl. In certain embodiments, R.sup.3 is unsubstituted naphthyl. In certain embodiments, R.sup.3 is substituted heteroaryl. In certain embodiments, R.sup.3 is unsubstituted heteroaryl. In certain embodiments, R.sup.3 is monocyclic heteroaryl. In certain embodiments, R.sup.3 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.3 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.3 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.3 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.3 is tetrazolyl. In certain embodiments, R.sup.3 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.3 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.3 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.3 is triazinyl. In certain embodiments, R.sup.3 is tetrazinyl. In certain embodiments, R.sup.3 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.3 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.3 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.3 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.3 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.3 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.3 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.3 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.3 is OR.sup.a. In certain embodiments, R.sup.3 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.3 is SR.sup.a. In certain embodiments, R.sup.3 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.3 is N(R.sup.a).sub.2. In certain embodiments, R.sup.3 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.3 is CN. In certain embodiments, R.sup.3 is SCN. In certain embodiments, R.sup.3 is C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, or C(NR.sup.a)N(R.sup.a).sub.2. In certain embodiments, R.sup.3 is C(O)R.sup.a, C(O)OR.sup.a, or C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.3 is NO.sub.2. In certain embodiments, R.sup.3 is NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, or NR.sup.aC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.3 is OC(O)R.sup.a, OC(O)OR.sup.a, or OC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.3 is ON(R.sup.a).sub.2.

(31) Compounds of Formulae (I), (D), and (E) each include a substituent R.sup.4. In certain embodiments, R.sup.4 is H. In certain embodiments, R.sup.4 is halogen. In certain embodiments, R.sup.4 is F. In certain embodiments, R.sup.4 is Cl. In certain embodiments, R.sup.4 is Br. In certain embodiments, R.sup.4 is I (iodine). In certain embodiments, R.sup.4 is substituted acyl. In certain embodiments, R.sup.4 is unsubstituted acyl. In certain embodiments, R.sup.4 is C(O)R.sup.a. In certain embodiments, R.sup.4 is acetyl. In certain embodiments, R.sup.4 is C(O)OR.sup.a. In certain embodiments, R.sup.4 is C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.4 is substituted alkyl. In certain embodiments, R.sup.4 is unsubstituted alkyl. In certain embodiments, R.sup.4 is C.sub.1-6 alkyl. In certain embodiments, R.sup.4 is methyl. In certain embodiments, R.sup.4 is ethyl. In certain embodiments, R.sup.4 is propyl. In certain embodiments, R.sup.4 is butyl. In certain embodiments, R.sup.4 is Ad. In certain embodiments, R.sup.4 is substituted alkenyl. In certain embodiments, R.sup.4 is unsubstituted alkenyl. In certain embodiments, R.sup.4 is vinyl. In certain embodiments, R.sup.4 is substituted alkynyl. In certain embodiments, R.sup.4 is unsubstituted alkynyl. In certain embodiments, R.sup.4 is ethynyl. In certain embodiments, R.sup.4 is substituted carbocyclyl. In certain embodiments, R.sup.4 is unsubstituted carbocyclyl. In certain embodiments, R.sup.4 is cyclopropyl. In certain embodiments, R.sup.4 is cyclobutyl. In certain embodiments, R.sup.4 is cyclopentyl. In certain embodiments, R.sup.4 is cyclohexyl. In certain embodiments, R.sup.4 is cycloheptyl. In certain embodiments, R.sup.4 is substituted heterocyclyl. In certain embodiments, R.sup.4 is unsubstituted heterocyclyl. In certain embodiments, R.sup.4 is substituted aryl. In certain embodiments, R.sup.4 is unsubstituted aryl. In certain embodiments, R.sup.4 is substituted phenyl. In certain embodiments, R.sup.4 is unsubstituted phenyl. In certain embodiments, R.sup.4 is substituted naphthyl. In certain embodiments, R.sup.4 is unsubstituted naphthyl. In certain embodiments, R.sup.4 is substituted heteroaryl. In certain embodiments, R.sup.4 is unsubstituted heteroaryl. In certain embodiments, R.sup.4 is monocyclic heteroaryl. In certain embodiments, R.sup.4 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.4 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.4 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.4 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.4 is tetrazolyl. In certain embodiments, R.sup.4 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.4 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.4 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.4 is triazinyl. In certain embodiments, R.sup.4 is tetrazinyl. In certain embodiments, R.sup.4 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.4 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.4 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.4 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.4 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.4 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.4 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.4 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.4 is OR.sup.a. In certain embodiments, R.sup.4 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.4 is SR.sup.a. In certain embodiments, R.sup.4 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.4 is N(R.sup.a).sub.2. In certain embodiments, R.sup.4 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.4 is CN. In certain embodiments, R.sup.4 is SCN. In certain embodiments, R.sup.4 is C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, or C(NR.sup.a)N(R.sup.a).sub.2. In certain embodiments, R.sup.4 is C(O)R.sup.a, C(O)OR.sup.a, or C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.4 is NO.sub.2. In certain embodiments, R.sup.4 is NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, or NR.sup.aC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.4 is OC(O)R.sup.a, OC(O)OR.sup.a, or OC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.4 is ON(R.sup.a).sub.2.

(32) Compounds of Formulae (I), (D), and (E) each include a substituent R.sup.5. In certain embodiments, R.sup.5 is H. In certain embodiments, R.sup.5 is halogen. In certain embodiments, R.sup.5 is F. In certain embodiments, R.sup.5 is Cl. In certain embodiments, R.sup.5 is Br. In certain embodiments, R.sup.5 is I (iodine). In certain embodiments, R.sup.5 is substituted acyl. In certain embodiments, R.sup.5 is unsubstituted acyl. In certain embodiments, R.sup.5 is C(O)R.sup.a. In certain embodiments, R.sup.5 is acetyl. In certain embodiments, R.sup.5 is C(O)OR.sup.a. In certain embodiments, R.sup.5 is C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.5 is substituted alkyl. In certain embodiments, R.sup.5 is unsubstituted alkyl. In certain embodiments, R.sup.5 is C.sub.1-6 alkyl. In certain embodiments, R.sup.5 is methyl. In certain embodiments, R.sup.5 is ethyl. In certain embodiments, R.sup.5 is propyl. In certain embodiments, R.sup.5 is butyl. In certain embodiments, R.sup.5 is Ad. In certain embodiments, R.sup.5 is substituted alkenyl. In certain embodiments, R.sup.5 is unsubstituted alkenyl. In certain embodiments, R.sup.5 is vinyl. In certain embodiments, R.sup.5 is substituted alkynyl. In certain embodiments, R.sup.5 is unsubstituted alkynyl. In certain embodiments, R.sup.5 is ethynyl. In certain embodiments, R.sup.5 is substituted carbocyclyl. In certain embodiments, R.sup.5 is unsubstituted carbocyclyl. In certain embodiments, R.sup.5 is cyclopropyl. In certain embodiments, R.sup.5 is cyclobutyl. In certain embodiments, R.sup.5 is cyclopentyl. In certain embodiments, R.sup.5 is cyclohexyl. In certain embodiments, R.sup.5 is cycloheptyl. In certain embodiments, R.sup.5 is substituted heterocyclyl. In certain embodiments, R.sup.5 is unsubstituted heterocyclyl. In certain embodiments, R.sup.5 is substituted aryl. In certain embodiments, R.sup.5 is unsubstituted aryl. In certain embodiments, R.sup.5 is substituted phenyl. In certain embodiments, R.sup.5 is unsubstituted phenyl. In certain embodiments, R.sup.5 is substituted naphthyl. In certain embodiments, R.sup.5 is unsubstituted naphthyl. In certain embodiments, R.sup.5 is substituted heteroaryl. In certain embodiments, R.sup.5 is unsubstituted heteroaryl. In certain embodiments, R.sup.5 is monocyclic heteroaryl. In certain embodiments, R.sup.5 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.5 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.5 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.5 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.5 is tetrazolyl. In certain embodiments, R.sup.5 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.5 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.5 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.5 is triazinyl. In certain embodiments, R.sup.5 is tetrazinyl. In certain embodiments, R.sup.5 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.5 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.5 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.5 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.5 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.5 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.5 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.5 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.5 is OR.sup.a. In certain embodiments, R.sup.5 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.5 is SR.sup.a. In certain embodiments, R.sup.5 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.5 is N(R.sup.a).sub.2. In certain embodiments, R.sup.5 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.5 is CN. In certain embodiments, R.sup.5 is SCN. In certain embodiments, R.sup.5 is C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, or C(NR.sup.a)N(R.sup.a).sub.2. In certain embodiments, R.sup.5 is C(O)R.sup.a, C(O)OR.sup.a, or C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.5 is NO.sub.2. In certain embodiments, R.sup.5 is NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, or NR.sup.aC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.5 is OC(O)R.sup.a, OC(O)OR.sup.a, or OC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.5 is ON(R.sup.a).sub.2.

(33) Compounds of Formulae (I), (D), and (E) each include a substituent R.sup.6. In certain embodiments, R.sup.6 is H. In certain embodiments, R.sup.6 is halogen. In certain embodiments, R.sup.6 is F. In certain embodiments, R.sup.6 is Cl. In certain embodiments, R.sup.6 is Br. In certain embodiments, R.sup.6 is I (iodine). In certain embodiments, R.sup.6 is substituted acyl. In certain embodiments, R.sup.6 is unsubstituted acyl. In certain embodiments, R.sup.6 is C(O)R.sup.a. In certain embodiments, R.sup.6 is acetyl. In certain embodiments, R.sup.6 is C(O)OR.sup.a. In certain embodiments, R.sup.6 is C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.6 is substituted alkyl. In certain embodiments, R.sup.6 is unsubstituted alkyl. In certain embodiments, R.sup.6 is C.sub.1-6 alkyl. In certain embodiments, R.sup.6 is methyl. In certain embodiments, R.sup.6 is ethyl. In certain embodiments, R.sup.6 is propyl. In certain embodiments, R.sup.6 is butyl. In certain embodiments, R.sup.6 is Ad. In certain embodiments, R.sup.6 is substituted alkenyl. In certain embodiments, R.sup.6 is unsubstituted alkenyl. In certain embodiments, R.sup.6 is vinyl. In certain embodiments, R.sup.6 is substituted alkynyl. In certain embodiments, R.sup.6 is unsubstituted alkynyl. In certain embodiments, R.sup.6 is ethynyl. In certain embodiments, R.sup.6 is substituted carbocyclyl. In certain embodiments, R.sup.6 is unsubstituted carbocyclyl. In certain embodiments, R.sup.6 is cyclopropyl. In certain embodiments, R.sup.6 is cyclobutyl. In certain embodiments, R.sup.6 is cyclopentyl. In certain embodiments, R.sup.6 is cyclohexyl. In certain embodiments, R.sup.6 is cycloheptyl. In certain embodiments, R.sup.6 is substituted heterocyclyl. In certain embodiments, R.sup.6 is unsubstituted heterocyclyl. In certain embodiments, R.sup.6 is substituted aryl. In certain embodiments, R.sup.6 is unsubstituted aryl. In certain embodiments, R.sup.6 is substituted phenyl. In certain embodiments, R.sup.6 is unsubstituted phenyl. In certain embodiments, R.sup.6 is substituted naphthyl. In certain embodiments, R.sup.6 is unsubstituted naphthyl. In certain embodiments, R.sup.6 is substituted heteroaryl. In certain embodiments, R.sup.6 is unsubstituted heteroaryl. In certain embodiments, R.sup.6 is monocyclic heteroaryl. In certain embodiments, R.sup.6 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.6 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.6 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.6 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.6 is tetrazolyl. In certain embodiments, R.sup.6 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.6 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.6 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.6 is triazinyl. In certain embodiments, R.sup.6 is tetrazinyl. In certain embodiments, R.sup.6 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.6 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.6 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.6 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.6 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.6 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.6 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.6 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.6 is OR.sup.a. In certain embodiments, R.sup.6 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.6 is SR.sup.a. In certain embodiments, R.sup.6 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.6 is N(R.sup.a).sub.2. In certain embodiments, R.sup.6 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.6 is CN. In certain embodiments, R.sup.6 is SCN. In certain embodiments, R.sup.6 is C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, or C(NR.sup.a)N(R.sup.a).sub.2. In certain embodiments, R.sup.6 is C(O)R.sup.a, C(O)OR.sup.a, or C(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.6 is NO.sub.2. In certain embodiments, R.sup.6 is NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, or NR.sup.aC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.6 is OC(O)R.sup.a, OC(O)OR.sup.a, or OC(O)N(R.sup.a).sub.2. In certain embodiments, R.sup.6 is ON(R.sup.a).sub.2.

(34) In certain embodiments, at least one R.sup.a is H. In certain embodiments, at least one R.sup.a is substituted acyl. In certain embodiments, at least one R.sup.a is unsubstituted acyl. In certain embodiments, at least one R.sup.a is acetyl. In certain embodiments, at least one R.sup.a is substituted alkyl. In certain embodiments, at least one R.sup.a is unsubstituted alkyl. In certain embodiments, at least one R.sup.a is C.sub.1-6 alkyl. In certain embodiments, at least one R.sup.a is methyl. In certain embodiments, at least one R.sup.a is ethyl. In certain embodiments, at least one R.sup.a is propyl. In certain embodiments, at least one R.sup.a is butyl. In certain embodiments, at least one R.sup.a is substituted alkenyl. In certain embodiments, at least one R.sup.a is unsubstituted alkenyl. In certain embodiments, at least one R.sup.a is vinyl. In certain embodiments, at least one R.sup.a is substituted alkynyl. In certain embodiments, at least one R.sup.a is unsubstituted alkynyl. In certain embodiments, at least one R.sup.a is ethynyl. In certain embodiments, at least one R.sup.a is substituted carbocyclyl. In certain embodiments, at least one R.sup.a is unsubstituted carbocyclyl. In certain embodiments, at least one R.sup.a is cyclopropyl. In certain embodiments, at least one R.sup.a is cyclobutyl. In certain embodiments, at least one R.sup.a is cyclopentyl. In certain embodiments, at least one R.sup.a is cyclohexyl. In certain embodiments, at least one R.sup.a is cycloheptyl. In certain embodiments, at least one R.sup.a is substituted heterocyclyl. In certain embodiments, at least one R.sup.a is unsubstituted heterocyclyl. In certain embodiments, at least one R.sup.a is substituted aryl. In certain embodiments, at least one R.sup.a is unsubstituted aryl. In certain embodiments, at least one R.sup.a is substituted phenyl. In certain embodiments, at least one R.sup.a is unsubstituted phenyl. In certain embodiments, at least one R.sup.a is substituted heteroaryl. In certain embodiments, at least one R.sup.a is unsubstituted heteroaryl. In certain embodiments, at least one R.sup.a is substituted pyridyl. In certain embodiments, at least one R.sup.a is unsubstituted pyridyl. In certain embodiments, at least one R.sup.a is a nitrogen protecting group when attached to a nitrogen atom. In certain embodiments, at least one R.sup.a is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, or Ts when attached to a nitrogen atom. In certain embodiments, at least one R.sup.a is an oxygen protecting group when attached to an oxygen atom. In certain embodiments, at least one R.sup.a is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to an oxygen atom. In certain embodiments, two R.sup.a groups are joined to form a substituted heterocyclic ring. In certain embodiments, two R.sup.a groups are joined to form an unsubstituted heterocyclic ring. In certain embodiments, two R.sup.a groups are joined to form a substituted heteroaryl ring. In certain embodiments, two R.sup.a groups are joined to form an unsubstituted heteroaryl ring. In certain embodiments, OR.sup.a is not OH when OR.sup.a is attached to a carbon atom of a CC bond. In certain embodiments, N(R.sup.a).sub.2 is not NH.sub.2 when N(R.sup.a).sub.2 is attached to a carbon atom of a CC bond. In certain embodiments, SR.sup.a is not SH when SR.sup.a is attached to a carbon atom of a CC bond.

(35) In compounds of Formulae (I), (D), and (E), any two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 groups may be joined to form a optionally substituted carbocyclyl ring or optionally substituted heterocyclic ring. In certain embodiments, R.sup.2 and R.sup.3 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.2 and R.sup.3 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.2 and R.sup.4 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.2 and R.sup.4 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.2 and R.sup.5 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.2 and R.sup.5 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.2 and R.sup.6 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.2 and R.sup.6 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.3 and R.sup.4 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.3 and R.sup.4 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.3 and R.sup.5 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.3 and R.sup.5 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.3 and R.sup.6 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.3 and R.sup.6 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.4 and R.sup.5 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.4 and R.sup.5 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.4 and R.sup.6 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.4 and R.sup.6 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.5 and R.sup.6 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.5 and R.sup.6 are joined to form a optionally substituted heterocyclic ring.

(36) In compounds of Formulae (I), (D), and (E) represents a single bond with any stereochemistry (e.g., geometric isomer). In certain embodiments, in compounds of Formulae (I) and (D), R.sup.4 is cis to R.sup.5 and trans to R.sup.6. In certain embodiments, in compounds of Formulae (I) and (D), R.sup.4 is trans to R.sup.5 and cis to R.sup.6. In certain embodiments, in compounds of Formula (E), R.sup.4 is cis to R.sup.2 and trans to R.sup.3. In certain embodiments, in compounds of Formula (E), R.sup.4 is trans to R.sup.2 and cis to R.sup.3.

(37) In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen. In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen; and R.sup.5 or R.sup.6 is optionally substituted alkyl. In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen; and R.sup.5 or R.sup.6 is C.sub.1-12 alkyl. In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen; and R.sup.5 or R.sup.6 is C.sub.1-6 alkyl. In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen; and R.sup.5 or R.sup.6 is optionally substituted aryl. In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen; and R.sup.5 or R.sup.6 is optionally substituted phenyl. In certain embodiments, R.sup.2 and R.sup.3 are each hydrogen; and R.sup.5 or R.sup.6 is phenyl.

(38) In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen. In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen; and R.sup.5 or R.sup.6 is optionally substituted alkyl. In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen; and R.sup.5 or R.sup.6 is C.sub.1-12 alkyl. In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen; and R.sup.5 or R.sup.6 is C.sub.1-6 alkyl. In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen; and R.sup.5 or R.sup.6 is optionally substituted aryl. In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen; and R.sup.5 or R.sup.6 is optionally substituted phenyl. In certain embodiments, R.sup.2, R.sup.3, and R.sup.4 are each hydrogen; and R.sup.5 or R.sup.6 is phenyl.

(39) In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is optionally substituted alkyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is C.sub.1-12 alkyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is C.sub.1-6 alkyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is optionally substituted alkenyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is C.sub.1-12 alkenyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is C.sub.1-6 alkenyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is optionally substituted alkynyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is C.sub.1-12 alkynyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is C.sub.1-6 alkynyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is optionally substituted aryl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is optionally substituted phenyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is phenyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each hydrogen; and R.sup.6 is optionally substituted heteroaryl.

(40) In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen; and R.sup.5 is optionally substituted alkyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen; and R.sup.5 is C.sub.1-12 alkyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen; and R.sup.5 is C.sub.1-6 alkyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen; and R.sup.5 is optionally substituted aryl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen; and R.sup.5 is optionally substituted phenyl. In certain embodiments, R.sup.2, R.sup.3, R.sup.4, and R.sup.6 are each hydrogen; and R.sup.5 is phenyl.

(41) In certain embodiments, the compound of Formula (D) is of the formula:

(42) ##STR00020##
and the compound of Formula (I) is of the formula:

(43) ##STR00021##
In certain embodiments, the compound of Formula (D) is of the formula:

(44) ##STR00022##
and the compound of Formula (I) is of the formula:

(45) ##STR00023##
In certain embodiments, the compound of Formula (D) is of the formula:

(46) ##STR00024##
and the compound of the Formula (I) is of the formula:

(47) ##STR00025##

(48) In certain embodiments, the compound of Formula (D) is of the formula:

(49) ##STR00026##
and the compound of the Formula (I) is of the formula:

(50) ##STR00027##
In certain embodiments, the compound of Formula (D) is of the formula:

(51) ##STR00028##
and the compound of the Formula (I) is of the formula:

(52) ##STR00029##

(53) In certain embodiments, the compound of Formula (D) is of the formula:

(54) ##STR00030##
and the compound of the Formula (I) is of the formula:

(55) ##STR00031##
In certain embodiments, the compound of Formula (D) is of the formula:

(56) ##STR00032##
and the compound of the Formula (I) is of the formula:

(57) ##STR00033##

(58) In certain embodiments, the compound of Formula (D) is of the formula:

(59) ##STR00034##
and the compound of the Formula (I) is of the formula:

(60) ##STR00035##
In certain embodiments, the compound of Formula (D) is of the formula:

(61) ##STR00036##
and the compound of the Formula (I) is of the formula:

(62) ##STR00037##

(63) In certain embodiments, the compound of Formula (D) is of the formula:

(64) ##STR00038##
and the compound of the Formula (I) is of the formula:

(65) ##STR00039##
In certain embodiments, the compound of Formula (D) is of the formula:

(66) ##STR00040##
and the compound of the Formula (I) is of the formula:

(67) ##STR00041##

(68) Compounds of Formula (B) include a ligand L attached to the Fe.sup.II atom. L may be any ligand capable of binding to the Fe.sup.II atom to form a coordination complex. In certain embodiments, L is a compound including one or more electron donating moieties. In certain embodiments, L a compound including one or more heteroatoms. In certain embodiments, L is a solvent. In certain embodiments, L is N(R.sup.b).sub.3. In certain embodiments, L is NEt.sub.3. In certain embodiments, L is (i-Pr).sub.2NEt. In certain embodiments, L is R.sup.bOR.sup.b. In certain embodiments, L is R.sup.bOR.sup.b; and each occurrence of R.sup.b is independently optionally substituted alkyl. In certain embodiments, L is R.sup.bOR.sup.b; and each occurrence of R.sup.b is independently C.sub.1-6 alkyl. In certain embodiments, L is diethyl ether. In certain embodiments, L is methyl t-butyl ether. In certain embodiments, L is R.sup.bSR.sup.b. In certain embodiments, L is dimethyl sulfide. In certain embodiments, L is diethyl sulfide. In certain embodiments, L is substituted heterocyclyl. In certain embodiments, L is unsubstituted heterocyclyl. In certain embodiments, L is substituted tetrahydrofuran. In certain embodiments, L is 2-methyltetrahydrofuran. In certain embodiments, L is unsubstituted tetrahydrofuran. In certain embodiments, L is substituted tetrahydropyran. In certain embodiments, L is unsubstituted tetrahydropyran. In certain embodiments, L is substituted heteroaryl. In certain embodiments, L is unsubstituted heteroaryl. In certain embodiments, L is substituted pyridine. In certain embodiments, L is 2,6-lutidine. In certain embodiments, L is unsubstituted pyridine.

(69) In certain embodiments, at least one R.sup.b is substituted alkyl. In certain embodiments, at least one R.sup.b is unsubstituted alkyl. In certain embodiments, at least one R.sup.b is C.sub.1-6 alkyl. In certain embodiments, at least one R.sup.b is methyl. In certain embodiments, at least one R.sup.b is ethyl. In certain embodiments, at least one R.sup.b is propyl. In certain embodiments, at least one R.sup.b is butyl. In certain embodiments, at least one R.sup.b is Ad. In certain embodiments, at least one R.sup.b is substituted alkenyl. In certain embodiments, at least one R.sup.b is unsubstituted alkenyl. In certain embodiments, at least one R.sup.b is vinyl. In certain embodiments, at least one R.sup.b is substituted alkynyl. In certain embodiments, at least one R.sup.b is unsubstituted alkynyl. In certain embodiments, at least one R.sup.b is ethynyl. In certain embodiments, at least one R.sup.b is substituted carbocyclyl. In certain embodiments, at least one R.sup.b is unsubstituted carbocyclyl. In certain embodiments, at least one R.sup.b is cyclopropyl. In certain embodiments, at least one R.sup.b is cyclobutyl. In certain embodiments, at least one R.sup.b is cyclopentyl. In certain embodiments, at least one R.sup.b is cyclohexyl. In certain embodiments, at least one R.sup.b is cycloheptyl. In certain embodiments, at least one R.sup.b is substituted heterocyclyl. In certain embodiments, at least one R.sup.b is unsubstituted heterocyclyl. In certain embodiments, at least one R.sup.b is substituted aryl. In certain embodiments, at least one R.sup.b is unsubstituted aryl. In certain embodiments, at least one R.sup.b is substituted phenyl. In certain embodiments, at least one R.sup.b is unsubstituted phenyl. In certain embodiments, at least one R.sup.b is substituted heteroaryl. In certain embodiments, at least one R.sup.b is unsubstituted heteroaryl. In certain embodiments, at least one R.sup.b is substituted pyridyl. In certain embodiments, at least one R.sup.b is unsubstituted pyridyl.

(70) Shown in FIG. 2 is a proposed mechanism for the intermolecular CH amination reaction of an azide RN.sub.3 (e.g., AdN.sub.3) and a CH source RCH.sub.3 (e.g., PhMe), catalyzed by a Fe.sup.IICl(L)-dipyrromethene complex (e.g., 3A), to yield an acyclic secondary amine RNHR (e.g., AdNHCH.sub.2Ph). First, the Fe.sup.IICl(L)-dipyrromethene complex undergoes a ligand exchange to form Fe.sup.IICl(N.sub.3R) (e.g., Fe.sup.IICl(N.sub.3Ad))-dipyrromethene complex. The Fe.sup.IICl(N.sub.3R)-dipyrromethene complex reacts with the CH source RCH.sub.3 (e.g., PhMe) to release a molecule of N.sub.2 and form Fe.sup.IIICl(.NR) (e.g., Fe.sup.IIICl(.NAd))-dipyrromethene complex (a Fe.sup.III(imido) complex). Hydrogen transfer from RCH.sub.3 to the Fe.sup.III(imido) complex gives rise to Fe.sup.IIICl(NHR) (e.g., Fe.sup.IIICl(NHAd))-dipyrromethene complex and RCH.sub.2. radical. A radical recombination furnishes the CH amination product RNHR (e.g., AdNHCH.sub.2Ph), regenerates the Fe.sup.IICl(L)-dipyrromethene complex, and therefore, completes the catalytic cycle. The net effect of such a reaction is that a nitrene group RN: (e.g., AdN:) is transferred to a CH source RCH.sub.3 (e.g., PhMe). The mechanism for a similar reaction using compound 3B as the catalyst instead of 3A is similar to or the same as the mechanism described herein.

(71) The steps of the methods of the invention may be performed under any suitable conditions. A suitable condition is a combination of physical and chemical parameters under which an intended product (e.g., an acyclic or cyclic amine) or intermediate may be formed using the inventive methods. A suitable condition may include a suitable solvent, such as an organic solvent (e.g., benzene, toluene, xylene, acetone, acetonitrile (ACN), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), dimethysulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), 2-pyrrolidone, tetrahydrofuran (THF), or a mixture thereof). In certain embodiments, the suitable solvent is benzene.

(72) A suitable condition may also include a suitable temperature under which one or more steps of a method of the invention are performed. In certain embodiments, the suitable temperature is at least about 0 C., at least about 20 C., at least about 23 C., at least about 25 C., at least about 40 C., at least about 60 C., at least about 65 C., at least about 80 C., at least about 100 C., or at least about 120 C. In certain embodiments, the suitable temperature is lower than about 120 C., lower than about 100 C., lower than about 80 C., lower than about 65 C., lower than about 60 C., lower than about 40 C., lower than about 25 C., lower than about 23 C., lower than about 20 C., or lower than about 0 C. Combinations of the above-referenced ranges are also possible (e.g., a suitable temperature of at least about 0 C. and lower than about 65 C.). Other ranges are also possible. In certain embodiments, the suitable temperature is about 0 C. In certain embodiments, the suitable temperature is about 23 C. In certain embodiments, the suitable temperature is about 60 C. In certain embodiments, the suitable temperature is about 65 C. A suitable temperature may be a variable temperature during one or more steps of a method of the invention.

(73) A suitable condition may also include a suitable pressure under which one or more steps of the inventive methods are performed. In certain embodiments, the suitable pressure is about 1 atmosphere. A suitable pressure may also be higher or lower than 1 atmosphere.

(74) A suitable condition may also include a suitable atmosphere under which one or more steps of the inventive methods are performed. In certain embodiments, the suitable atmosphere is air. In certain embodiments, the suitable atmosphere is an inert atmosphere. In certain embodiments, the suitable atmosphere is a nitrogen or argon atmosphere.

(75) A suitable condition may also include a suitable time duration that one or more steps of a method of the invention last. In certain embodiments, the suitable time duration is in the order of minutes, hours (e.g., about 6 or about 12 hours), or days (e.g., about 1 day).

(76) A suitable condition may also include irradiation with microwave, shielding from ambient light, and/or agitating (e.g., stirring). One or more intermediates resulting from a step of a method of the invention may be isolated and/or purified, and the isolated and/or purified intermediates may be reacted in a next step of the method. The isolated and/or purified intermediates may be substantially pure or may contain one or more other components, such as reagents and solvents employed in the step yielding the intermediates and byproducts. The one or more intermediates may also be reacted in a next step without being isolated and/or purified.

(77) Synthesis of Coordination Complexes of Cyclic Secondary Amines and a Ferrous Compound

(78) The present invention also provides methods of preparing compounds of Formula (II-1), which are coordination complexes of cyclic secondary amines and a ferrous compound:

(79) ##STR00042##
and salts and stereoisomers thereof, the method comprising the steps of:

(80) reacting an azide of Formula (F), or a salt or stereoisomer thereof, with a ferrous compound of Formula (G), or a salt or stereoisomer thereof:

(81) ##STR00043##
wherein:

(82) W is selected from the group consisting of mesityl and 2,6-dichlorophenyl;

(83) each occurrence of X is independently selected from the group consisting of O, S, NR.sup.c, and C(R.sup.d).sub.2;

(84) R.sup.c is selected from the group consisting of hydrogen, a nitrogen protecting group, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;

(85) each one of R.sup.7, R.sup.8, R.sup.9, and R.sup.10, and each occurrence of R.sup.d, are independently selected from the group consisting of hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, OR.sup.e, N(R.sup.e).sub.2, SR.sup.e, CN, C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, C(NR.sup.e)N(R.sup.e).sub.2, NO.sub.2, NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, NR.sup.eC(O)N(R.sup.e).sub.2, C(O)R.sup.e, OC(O)OR.sup.e, OC(O)N(R.sup.e).sub.2, and ON(R.sup.e).sub.2;

(86) each occurrence of R.sup.e is independently selected from the group consisting of hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, and a sulfur protecting group when attached to a sulfur atom, or optionally two R.sup.e groups are joined to form an optionally substituted heterocyclic ring;

(87) optionally two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form an optionally substituted carbocyclyl or optionally substituted heterocyclic ring;

(88) Y is selected from the group consisting of N(R.sup.f).sub.3, R.sup.fOR.sup.f, R.sup.fSR.sup.f, optionally substituted heterocyclyl, and optionally substituted heteroaryl;

(89) each occurrence of R.sup.f is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; and

(90) n is 1, 2, 3, 4, or 5.

(91) In compounds described herein, W is selected from the group consisting of mesityl and 2,6-dichlorophenyl. In certain embodiments, W is mesityl. In certain embodiments, W is 2,6-dichlorophenyl.

(92) In compounds of Formulae (II-1) and (F), each occurrence of X is independently selected from the group consisting of O, S, NR.sup.c, and C(R.sup.d).sub.2. In certain embodiments, at least one X is O. In certain embodiments, at least one X is S. In certain embodiments, at least one X is NR.sup.c. In certain embodiments, at least one X is N(C.sub.1-6 alkyl)-. In certain embodiments, at least one X is N(Me)-. In certain embodiments, at least one X is NH. In certain embodiments, at least one X is C(R.sup.d).sub.2. In certain embodiments, at least one X is C(C.sub.1-6 alkyl).sub.2-. In certain embodiments, at least one X is C(Me).sub.2-. In certain embodiments, at least one X is C(Et).sub.2-. In certain embodiments, at least one X is C(Pr).sub.2. In certain embodiments, at least one X is C(Bu).sub.2-. In certain embodiments, at least one X is C(C.sub.1-6 alkenyl).sub.2-. In certain embodiments, at least one X is C(vinyl).sub.2-. In certain embodiments, at least one X is C(allyl).sub.2-. In certain embodiments, at least one X is CH(4-butenyl)-. In certain embodiments, at least one X is C(C.sub.1-6 alkynyl).sub.2-. In certain embodiments, at least one X is C(ethynyl).sub.2-. In certain embodiments, at least one X is CH(R.sup.d). In certain embodiments, at least one X is CH(C.sub.1-6 alkyl)-. In certain embodiments, at least one X is CH(Me)-. In certain embodiments, at least one X is CH(Et)-. In certain embodiments, at least one X is C(Pr).sub.2. In certain embodiments, at least one X is C(Bu).sub.2-. In certain embodiments, at least one X is CH(C.sub.1-6 alkenyl)-. In certain embodiments, at least one X is CH(vinyl)-. In certain embodiments, at least one X is CH(allyl)-. In certain embodiments, at least one X is CH(4-butenyl)-. In certain embodiments, at least one X is CH(C.sub.1-6 alkynyl)-. In certain embodiments, at least one X is CH(ethynyl)-. In certain embodiments, at least one X is CH(aryl)-. In certain embodiments, at least one X is CH(Ph)-. In certain embodiments, at least one X is CH(heteroaryl)-. In certain embodiments, at least one X is CH(pyridyl)-. In certain embodiments, at least one X is CH(OR.sup.e). In certain embodiments, at least one X is CH(O-aryl)-. In certain embodiments, at least one X is CH(OPh)-. In certain embodiments, at least one X is CH(OC.sub.1-6 alkyl)-. In certain embodiments, at least one X is CH(OH). In certain embodiments, at least one X is CH(N(R.sup.e).sub.2). In certain embodiments, at least one X is CH(N(C.sub.1-6 alkyl).sub.2)-. In certain embodiments, at least one X is CH(NH.sub.2). In certain embodiments, at least one X is CH(C(O)OR.sup.e). In certain embodiments, at least one X is CH(C(O)OMe)-. In certain embodiments, at least one X is CH(C(O)OEt)-. In certain embodiments, at least one X is CH.sub.2.

(93) In compounds of Formulae (II-1) and (F), when X is NR.sup.c, R.sup.c is a substituent on the nitrogen atom. In certain embodiments, at least one R.sup.c is H. In certain embodiments, at least one R.sup.c is substituted alkyl. In certain embodiments, at least one R.sup.c is unsubstituted alkyl. In certain embodiments, at least one R.sup.c is C.sub.1-6 alkyl. In certain embodiments, at least one R.sup.c is methyl. In certain embodiments, at least one R.sup.c is ethyl. In certain embodiments, at least one R.sup.c is propyl. In certain embodiments, at least one R.sup.c is butyl. In certain embodiments, at least one R.sup.c is t-butyl. In certain embodiments, at least one R.sup.c is Ad. In certain embodiments, at least one R.sup.c is substituted alkenyl. In certain embodiments, at least one R.sup.c is unsubstituted alkenyl. In certain embodiments, at least one R.sup.c is vinyl. In certain embodiments, at least one R.sup.c is substituted alkynyl. In certain embodiments, at least one R.sup.c is unsubstituted alkynyl. In certain embodiments, at least one R.sup.c is ethynyl. In certain embodiments, at least one R.sup.c is substituted carbocyclyl. In certain embodiments, at least one R.sup.c is unsubstituted carbocyclyl. In certain embodiments, at least one R.sup.c is cyclopropyl. In certain embodiments, at least one R.sup.c is cyclobutyl. In certain embodiments, at least one R.sup.c is cyclopentyl. In certain embodiments, at least one R.sup.c is cyclohexyl. In certain embodiments, at least one R.sup.c is cycloheptyl. In certain embodiments, at least one R.sup.c is substituted heterocyclyl. In certain embodiments, at least one R.sup.c is unsubstituted heterocyclyl. In certain embodiments, at least one R.sup.c is substituted aryl. In certain embodiments, at least one R.sup.c is unsubstituted aryl. In certain embodiments, at least one R.sup.c is substituted phenyl. In certain embodiments, at least one R.sup.c is tolyl. In certain embodiments, at least one R.sup.c is 4-tolyl. In certain embodiments, at least one R.sup.c is Mes. In certain embodiments, at least one R.sup.c is unsubstituted phenyl. In certain embodiments, at least one R.sup.c is substituted naphthyl. In certain embodiments, at least one R.sup.c is unsubstituted naphthyl. In certain embodiments, at least one R.sup.c is substituted heteroaryl. In certain embodiments, at least one R.sup.c is unsubstituted heteroaryl. In certain embodiments, at least one R.sup.c is monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is 5-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.c is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.c is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.c is tetrazolyl. In certain embodiments, at least one R.sup.c is 6-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.c is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.c is triazinyl. In certain embodiments, at least one R.sup.c is tetrazinyl. In certain embodiments, at least one R.sup.c is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, at least one R.sup.c is a monocyclic heteroaryl fused with phenyl. In certain embodiments, at least one R.sup.c is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, at least one R.sup.c is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, at least one R.sup.c is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.c is a nitrogen protecting group. In certain embodiments, at least one R.sup.c is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, or Ts.

(94) In compounds of Formulae (II-1) and (F), when X is C(R.sup.d).sub.2, at least one R.sup.d is a substituent on the carbon atom. In certain embodiments, at least one R.sup.d is H. In certain embodiments, at least one R.sup.d is halogen. In certain embodiments, at least one R.sup.d is F. In certain embodiments, at least one R.sup.d is Cl. In certain embodiments, at least one R.sup.d is Br. In certain embodiments, at least one R.sup.d is I (iodine). In certain embodiments, at least one R.sup.d is substituted acyl. In certain embodiments, at least one R.sup.d is unsubstituted acyl. In certain embodiments, at least one R.sup.d is C(O)R.sup.e. In certain embodiments, at least one R.sup.d is acetyl. In certain embodiments, at least one R.sup.d is C(O)OR.sup.e. In certain embodiments, at least one R.sup.d is C(O)N(R.sup.e).sub.2. In certain embodiments, at least one R.sup.d is substituted alkyl. In certain embodiments, at least one R.sup.d is unsubstituted alkyl. In certain embodiments, at least one R.sup.d is C.sub.1-6 alkyl. In certain embodiments, at least one R.sup.d is methyl. In certain embodiments, at least one R.sup.d is ethyl. In certain embodiments, at least one R.sup.d is propyl. In certain embodiments, at least one R.sup.d is butyl. In certain embodiments, at least one R.sup.d is Ad. In certain embodiments, at least one R.sup.d is substituted alkenyl. In certain embodiments, at least one R.sup.d is unsubstituted alkenyl. In certain embodiments, at least one R.sup.d is vinyl. In certain embodiments, at least one R.sup.d is substituted alkynyl. In certain embodiments, at least one R.sup.d is unsubstituted alkynyl. In certain embodiments, at least one R.sup.d is ethynyl. In certain embodiments, at least one R.sup.d is substituted carbocyclyl. In certain embodiments, at least one R.sup.d is unsubstituted carbocyclyl. In certain embodiments, at least one R.sup.d is cyclopropyl. In certain embodiments, at least one R.sup.d is cyclobutyl. In certain embodiments, at least one R.sup.d is cyclopentyl. In certain embodiments, at least one R.sup.d is cyclohexyl. In certain embodiments, at least one R.sup.d is cycloheptyl. In certain embodiments, at least one R.sup.d is substituted heterocyclyl. In certain embodiments, at least one R.sup.d is unsubstituted heterocyclyl. In certain embodiments, at least one R.sup.d is substituted aryl. In certain embodiments, at least one R.sup.d is unsubstituted aryl. In certain embodiments, at least one R.sup.d is substituted phenyl. In certain embodiments, at least one R.sup.d is unsubstituted phenyl. In certain embodiments, at least one R.sup.d is substituted naphthyl. In certain embodiments, at least one R.sup.d is unsubstituted naphthyl. In certain embodiments, at least one R.sup.d is substituted heteroaryl. In certain embodiments, at least one R.sup.d is unsubstituted heteroaryl. In certain embodiments, at least one R.sup.d is monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is 5-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.d is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.d is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.d is tetrazolyl. In certain embodiments, at least one R.sup.d is 6-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.d is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one R.sup.d is triazinyl. In certain embodiments, at least one R.sup.d is tetrazinyl. In certain embodiments, at least one R.sup.d is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, at least one R.sup.d is a monocyclic heteroaryl fused with phenyl. In certain embodiments, at least one R.sup.d is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, at least one R.sup.d is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, at least one R.sup.d is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, at least one R.sup.d is OR.sup.e. In certain embodiments, at least one R.sup.d is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, at least one R.sup.d is SR.sup.e. In certain embodiments, at least one R.sup.d is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, at least one R.sup.d is N(R.sup.e).sub.2. In certain embodiments, at least one R.sup.d is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, at least one R.sup.d is CN. In certain embodiments, at least one R.sup.d is SCN. In certain embodiments, at least one R.sup.d is C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, or C(NR.sup.e)N(R.sup.e).sub.2. In certain embodiments, at least one R.sup.d is C(O)R.sup.e, C(O)OR.sup.e, or C(O)N(R.sup.e).sub.2. In certain embodiments, at least one R.sup.d is NO.sub.2. In certain embodiments, at least one R.sup.d is NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, or NR.sup.eC(O)N(R.sup.e).sub.2. In certain embodiments, at least one R.sup.d is OC(O)R.sup.e, OC(O)OR.sup.e, or OC(O)N(R.sup.e).sub.2. In certain embodiments, at least one R.sup.d is ON(R.sup.e).sub.2.

(95) In certain embodiments, n is 1. In certain embodiments, n is 2. In certain embodiments, n is 3. In certain embodiments, n is 4. In certain embodiments, n is 5.

(96) Compounds of Formulae (II-1) and (F) include a substituent R.sup.7. In certain embodiments, R.sup.7 is H. In certain embodiments, R.sup.7 is halogen. In certain embodiments, R.sup.7 is F. In certain embodiments, R.sup.7 is Cl. In certain embodiments, R.sup.7 is Br. In certain embodiments, R.sup.7 is I (iodine). In certain embodiments, R.sup.7 is substituted acyl. In certain embodiments, R.sup.7 is unsubstituted acyl. In certain embodiments, R.sup.7 is C(O)R.sup.e. In certain embodiments, R.sup.7 is acetyl. In certain embodiments, R.sup.7 is C(O)OR.sup.e. In certain embodiments, R.sup.7 is C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is substituted alkyl. In certain embodiments, R.sup.7 is unsubstituted alkyl. In certain embodiments, R.sup.7 is C.sub.1-6 alkyl. In certain embodiments, R.sup.7 is methyl. In certain embodiments, R.sup.7 is ethyl. In certain embodiments, R.sup.7 is propyl. In certain embodiments, R.sup.7 is butyl. In certain embodiments, R.sup.7 is Ad. In certain embodiments, R.sup.7 is substituted alkenyl. In certain embodiments, R.sup.7 is unsubstituted alkenyl. In certain embodiments, R.sup.7 is vinyl. In certain embodiments, R.sup.7 is substituted alkynyl. In certain embodiments, R.sup.7 is unsubstituted alkynyl. In certain embodiments, R.sup.7 is ethynyl. In certain embodiments, R.sup.7 is substituted carbocyclyl. In certain embodiments, R.sup.7 is unsubstituted carbocyclyl. In certain embodiments, R.sup.7 is cyclopropyl. In certain embodiments, R.sup.7 is cyclobutyl. In certain embodiments, R.sup.7 is cyclopentyl. In certain embodiments, R.sup.7 is cyclohexyl. In certain embodiments, R.sup.7 is cycloheptyl. In certain embodiments, R.sup.7 is substituted heterocyclyl. In certain embodiments, R.sup.7 is unsubstituted heterocyclyl. In certain embodiments, R.sup.7 is substituted aryl. In certain embodiments, R.sup.7 is unsubstituted aryl. In certain embodiments, R.sup.7 is substituted phenyl. In certain embodiments, R.sup.7 is unsubstituted phenyl. In certain embodiments, R.sup.7 is substituted naphthyl. In certain embodiments, R.sup.7 is unsubstituted naphthyl. In certain embodiments, R.sup.7 is substituted heteroaryl. In certain embodiments, R.sup.7 is unsubstituted heteroaryl. In certain embodiments, R.sup.7 is monocyclic heteroaryl. In certain embodiments, R.sup.7 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.7 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.7 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.7 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.7 is tetrazolyl. In certain embodiments, R.sup.7 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.7 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.7 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.7 is triazinyl. In certain embodiments, R.sup.7 is tetrazinyl. In certain embodiments, R.sup.7 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.7 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.7 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.7 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.7 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.7 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.7 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.7 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.7 is OR.sup.e. In certain embodiments, R.sup.7 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.7 is SR.sup.e. In certain embodiments, R.sup.7 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.7 is N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.7 is CN. In certain embodiments, R.sup.7 is SCN. In certain embodiments, R.sup.7 is C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, or C(NR.sup.e)N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is C(O)R.sup.e, C(O)OR.sup.e, or C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is NO.sub.2. In certain embodiments, R.sup.7 is NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, or NR.sup.eC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is OC(O)R.sup.e, OC(O)OR.sup.e, or OC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is ON(R.sup.e).sub.2.

(97) Compounds of Formulae (II-1) and (F) also include a substituent R.sup.8. In certain embodiments, R.sup.8 is H. In certain embodiments, R.sup.8 is halogen. In certain embodiments, R.sup.8 is F. In certain embodiments, R.sup.8 is Cl. In certain embodiments, R.sup.8 is Br. In certain embodiments, R.sup.8 is I (iodine). In certain embodiments, R.sup.8 is substituted acyl. In certain embodiments, R.sup.8 is unsubstituted acyl. In certain embodiments, R.sup.8 is C(O)R.sup.e. In certain embodiments, R.sup.8 is acetyl. In certain embodiments, R.sup.8 is C(O)OR.sup.e. In certain embodiments, R.sup.8 is C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is substituted alkyl. In certain embodiments, R.sup.8 is unsubstituted alkyl. In certain embodiments, R.sup.8 is C.sub.1-6 alkyl. In certain embodiments, R.sup.8 is methyl. In certain embodiments, R.sup.8 is ethyl. In certain embodiments, R.sup.8 is propyl. In certain embodiments, R.sup.8 is butyl. In certain embodiments, R.sup.8 is Ad. In certain embodiments, R.sup.8 is substituted alkenyl. In certain embodiments, R.sup.8 is unsubstituted alkenyl. In certain embodiments, R.sup.8 is vinyl. In certain embodiments, R.sup.8 is substituted alkynyl. In certain embodiments, R.sup.8 is unsubstituted alkynyl. In certain embodiments, R.sup.8 is ethynyl. In certain embodiments, R.sup.8 is substituted carbocyclyl. In certain embodiments, R.sup.8 is unsubstituted carbocyclyl. In certain embodiments, R.sup.8 is cyclopropyl. In certain embodiments, R.sup.8 is cyclobutyl. In certain embodiments, R.sup.8 is cyclopentyl. In certain embodiments, R.sup.8 is cyclohexyl. In certain embodiments, R.sup.8 is cycloheptyl. In certain embodiments, R.sup.8 is substituted heterocyclyl. In certain embodiments, R.sup.8 is unsubstituted heterocyclyl. In certain embodiments, R.sup.8 is substituted aryl. In certain embodiments, R.sup.8 is unsubstituted aryl. In certain embodiments, R.sup.8 is substituted phenyl. In certain embodiments, R.sup.8 is unsubstituted phenyl. In certain embodiments, R.sup.8 is substituted naphthyl. In certain embodiments, R.sup.8 is unsubstituted naphthyl. In certain embodiments, R.sup.8 is substituted heteroaryl. In certain embodiments, R.sup.8 is unsubstituted heteroaryl. In certain embodiments, R.sup.8 is monocyclic heteroaryl. In certain embodiments, R.sup.8 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.8 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.8 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.8 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.8 is tetrazolyl. In certain embodiments, R.sup.8 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.8 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.8 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.8 is triazinyl. In certain embodiments, R.sup.8 is tetrazinyl. In certain embodiments, R.sup.8 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.8 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.8 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.8 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.8 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.8 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.8 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.8 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.8 is OR.sup.e. In certain embodiments, R.sup.8 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.8 is SR.sup.e. In certain embodiments, R.sup.8 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.8 is N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.8 is CN. In certain embodiments, R.sup.8 is SCN. In certain embodiments, R.sup.8 is C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, or C(NR.sup.e)N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is C(O)R.sup.e, C(O)OR.sup.e, or C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is NO.sub.2. In certain embodiments, R.sup.8 is NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, or NR.sup.eC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is OC(O)R.sup.e, OC(O)OR.sup.e, or OC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is ON(R.sup.e).sub.2.

(98) Compounds of Formulae (II-1) and (F) further include a substituent R.sup.9. In certain embodiments, R.sup.9 is H. In certain embodiments, R.sup.9 is halogen. In certain embodiments, R.sup.9 is F. In certain embodiments, R.sup.9 is Cl. In certain embodiments, R.sup.9 is Br. In certain embodiments, R.sup.9 is I (iodine). In certain embodiments, R.sup.9 is substituted acyl. In certain embodiments, R.sup.9 is unsubstituted acyl. In certain embodiments, R.sup.9 is C(O)R.sup.e. In certain embodiments, R.sup.9 is acetyl. In certain embodiments, R.sup.9 is C(O)OR.sup.e. In certain embodiments, R.sup.9 is C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is substituted alkyl. In certain embodiments, R.sup.9 is unsubstituted alkyl. In certain embodiments, R.sup.9 is C.sub.1-6 alkyl. In certain embodiments, R.sup.9 is methyl. In certain embodiments, R.sup.9 is ethyl. In certain embodiments, R.sup.9 is propyl. In certain embodiments, R.sup.9 is butyl. In certain embodiments, R.sup.9 is Ad. In certain embodiments, R.sup.9 is substituted alkenyl. In certain embodiments, R.sup.9 is unsubstituted alkenyl. In certain embodiments, R.sup.9 is vinyl. In certain embodiments, R.sup.9 is substituted alkynyl. In certain embodiments, R.sup.9 is unsubstituted alkynyl. In certain embodiments, R.sup.9 is ethynyl. In certain embodiments, R.sup.9 is substituted carbocyclyl. In certain embodiments, R.sup.9 is unsubstituted carbocyclyl. In certain embodiments, R.sup.9 is cyclopropyl. In certain embodiments, R.sup.9 is cyclobutyl. In certain embodiments, R.sup.9 is cyclopentyl. In certain embodiments, R.sup.9 is cyclohexyl. In certain embodiments, R.sup.9 is cycloheptyl. In certain embodiments, R.sup.9 is substituted heterocyclyl. In certain embodiments, R.sup.9 is unsubstituted heterocyclyl. In certain embodiments, R.sup.9 is substituted aryl. In certain embodiments, R.sup.9 is unsubstituted aryl. In certain embodiments, R.sup.9 is substituted phenyl. In certain embodiments, R.sup.9 is unsubstituted phenyl. In certain embodiments, R.sup.9 is substituted naphthyl. In certain embodiments, R.sup.9 is unsubstituted naphthyl. In certain embodiments, R.sup.9 is substituted heteroaryl. In certain embodiments, R.sup.9 is unsubstituted heteroaryl. In certain embodiments, R.sup.9 is monocyclic heteroaryl. In certain embodiments, R.sup.9 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.9 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.9 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.9 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.9 is tetrazolyl. In certain embodiments, R.sup.9 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.9 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.9 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.9 is triazinyl. In certain embodiments, R.sup.9 is tetrazinyl. In certain embodiments, R.sup.9 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.9 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.9 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.9 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.9 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.9 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.9 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.9 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.9 is OR.sup.e. In certain embodiments, R.sup.9 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.9 is SR.sup.e. In certain embodiments, R.sup.9 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.9 is N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.9 is CN. In certain embodiments, R.sup.9 is SCN. In certain embodiments, R.sup.9 is C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, or C(NR.sup.e)N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is C(O)R.sup.e, C(O)OR.sup.e, or C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is NO.sub.2. In certain embodiments, R.sup.9 is NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, or NR.sup.eC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is OC(O)R.sup.e, OC(O)OR.sup.e, or OC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is ON(R.sup.e).sub.2.

(99) Compounds of Formulae (II-1) and (F) still include a substituent R.sup.10. In certain embodiments, R.sup.10 is H. In certain embodiments, R.sup.10 is halogen. In certain embodiments, R.sup.10 is F. In certain embodiments, R.sup.10 is Cl. In certain embodiments, R.sup.10 is Br. In certain embodiments, R.sup.10 is I (iodine). In certain embodiments, R.sup.10 is substituted acyl. In certain embodiments, R.sup.10 is unsubstituted acyl. In certain embodiments, R.sup.10 is C(O)R.sup.e. In certain embodiments, R.sup.10 is acetyl. In certain embodiments, R.sup.10 is C(O)OR.sup.e. In certain embodiments, R.sup.10 is C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.10 is substituted alkyl. In certain embodiments, R.sup.10 is unsubstituted alkyl. In certain embodiments, R.sup.10 is C.sub.1-6 alkyl. In certain embodiments, R.sup.10 is methyl. In certain embodiments, R.sup.10 is ethyl. In certain embodiments, R.sup.10 is propyl. In certain embodiments, R.sup.10 is butyl. In certain embodiments, R.sup.10 is Ad. In certain embodiments, R.sup.10 is substituted alkenyl. In certain embodiments, R.sup.10 is unsubstituted alkenyl. In certain embodiments, R.sup.10 is vinyl. In certain embodiments, R.sup.10 is substituted alkynyl. In certain embodiments, R.sup.10 is unsubstituted alkynyl. In certain embodiments, R.sup.10 is ethynyl. In certain embodiments, R.sup.10 is substituted carbocyclyl. In certain embodiments, R.sup.10 is unsubstituted carbocyclyl. In certain embodiments, R.sup.10 is cyclopropyl. In certain embodiments, R.sup.10 is cyclobutyl. In certain embodiments, R.sup.10 is cyclopentyl. In certain embodiments, R.sup.10 is cyclohexyl. In certain embodiments, R.sup.10 is cycloheptyl. In certain embodiments, R.sup.10 is substituted heterocyclyl. In certain embodiments, R.sup.10 is unsubstituted heterocyclyl. In certain embodiments, R.sup.10 is substituted aryl. In certain embodiments, R.sup.10 is unsubstituted aryl. In certain embodiments, R.sup.10 is substituted phenyl. In certain embodiments, R.sup.10 is unsubstituted phenyl. In certain embodiments, R.sup.10 is substituted naphthyl. In certain embodiments, R.sup.10 is unsubstituted naphthyl. In certain embodiments, R.sup.10 is substituted heteroaryl. In certain embodiments, R.sup.10 is unsubstituted heteroaryl. In certain embodiments, R.sup.10 is monocyclic heteroaryl. In certain embodiments, R.sup.10 is 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.10 is 5-membered monocyclic heteroaryl, wherein only one of the five atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.10 is 5-membered monocyclic heteroaryl, wherein only two of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.10 is 5-membered monocyclic heteroaryl, wherein only three of the five atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.10 is tetrazolyl. In certain embodiments, R.sup.10 is 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.10 is 6-membered monocyclic heteroaryl, wherein only one of the six atoms in the ring of the heteroaryl is selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.10 is 6-membered monocyclic heteroaryl, wherein only two of the six atoms in the ring of the heteroaryl are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, R.sup.10 is triazinyl. In certain embodiments, R.sup.10 is tetrazinyl. In certain embodiments, R.sup.10 is bicyclic heteroaryl, wherein the point of attachment may be at any atom of the heteroaryl, as valency permits. In certain embodiments, R.sup.10 is a monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.10 is a 5-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.10 is a 6-membered monocyclic heteroaryl fused with phenyl. In certain embodiments, R.sup.10 is a monocyclic heteroaryl fused with another monocyclic heteroaryl. In certain embodiments, R.sup.10 is a 5-membered monocyclic heteroaryl fused with another 5-membered monocyclic heteroaryl. In certain embodiments, R.sup.10 is a 5-membered monocyclic heteroaryl fused with a 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.10 is a 6-membered monocyclic heteroaryl fused with another 6-membered monocyclic heteroaryl. In certain embodiments, R.sup.10 is OR.sup.e. In certain embodiments, R.sup.10 is OH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.10 is SR.sup.e. In certain embodiments, R.sup.10 is SH when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.10 is N(R.sup.e).sub.2. In certain embodiments, R.sup.10 is NH.sub.2 when attached to an sp.sup.3 carbon atom. In certain embodiments, R.sup.10 is CN. In certain embodiments, R.sup.10 is SCN. In certain embodiments, R.sup.10 is C(NR.sup.e)R.sup.e, C(NR.sup.e)OR.sup.e, or C(NR.sup.e)N(R.sup.e).sub.2. In certain embodiments, R.sup.10 is C(O)R.sup.e, C(O)OR.sup.e, or C(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.10 is NO.sub.2. In certain embodiments, R.sup.10 is NR.sup.eC(O)R.sup.e, NR.sup.eC(O)OR.sup.e, or NR.sup.eC(O)N(R.sup.e). In certain embodiments, R.sup.10 is OC(O)R.sup.e, OC(O)OR.sup.e, or OC(O)N(R.sup.e).sub.2. In certain embodiments, R.sup.10 is ON(R.sup.e).sub.2.

(100) In certain embodiments, at least one R.sup.e is H. In certain embodiments, at least one R.sup.e is substituted acyl. In certain embodiments, at least one R.sup.e is unsubstituted acyl. In certain embodiments, at least one R.sup.e is acetyl. In certain embodiments, at least one R.sup.e is substituted alkyl. In certain embodiments, at least one R.sup.e is unsubstituted alkyl. In certain embodiments, at least one R.sup.e is C.sub.1-6 alkyl. In certain embodiments, at least one R.sup.e is methyl. In certain embodiments, at least one R.sup.e is ethyl. In certain embodiments, at least one R.sup.e is propyl. In certain embodiments, at least one R.sup.e is butyl. In certain embodiments, at least one R.sup.e is substituted alkenyl. In certain embodiments, at least one R.sup.e is unsubstituted alkenyl. In certain embodiments, at least one R.sup.e is vinyl. In certain embodiments, at least one R.sup.e is substituted alkynyl. In certain embodiments, at least one R.sup.e is unsubstituted alkynyl. In certain embodiments, at least one R.sup.e is ethynyl. In certain embodiments, at least one R.sup.e is substituted carbocyclyl. In certain embodiments, at least one R.sup.e is unsubstituted carbocyclyl. In certain embodiments, at least one R.sup.e is cyclopropyl. In certain embodiments, at least one R.sup.e is cyclobutyl. In certain embodiments, at least one R.sup.e is cyclopentyl. In certain embodiments, at least one R.sup.e is cyclohexyl. In certain embodiments, at least one R.sup.e is cycloheptyl. In certain embodiments, at least one R.sup.e is substituted heterocyclyl. In certain embodiments, at least one R.sup.e is unsubstituted heterocyclyl. In certain embodiments, at least one R.sup.e is substituted aryl. In certain embodiments, at least one R.sup.e is unsubstituted aryl. In certain embodiments, at least one R.sup.e is substituted phenyl. In certain embodiments, at least one R.sup.e is unsubstituted phenyl. In certain embodiments, at least one R.sup.e is substituted heteroaryl. In certain embodiments, at least one R.sup.e is unsubstituted heteroaryl. In certain embodiments, at least one R.sup.e is substituted pyridyl. In certain embodiments, at least one R.sup.e is unsubstituted pyridyl. In certain embodiments, at least one R.sup.e is a nitrogen protecting group when attached to a nitrogen atom. In certain embodiments, at least one R.sup.e is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, or Ts when attached to a nitrogen atom. In certain embodiments, at least one R.sup.e is an oxygen protecting group when attached to an oxygen atom. In certain embodiments, at least one R.sup.e is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to an oxygen atom. In certain embodiments, two R.sup.e groups are joined to form a substituted heterocyclic ring. In certain embodiments, two R.sup.e groups are joined to form an unsubstituted heterocyclic ring. In certain embodiments, two R.sup.e groups are joined to form a substituted heteroaryl ring. In certain embodiments, two R.sup.e groups are joined to form an unsubstituted heteroaryl ring.

(101) In compounds of Formulae (II-1) and (F), any two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups may be joined to form a optionally substituted carbocyclyl ring, or optionally substituted heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclopropyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclobutyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclopentyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclohexyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cycloheptyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclooctyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclononyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted cyclodecyl ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted 4-membered heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted 5-membered heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted 6-membered heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted 7-membered heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.e, and R.sup.d groups are joined to form a optionally substituted 8-membered heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.e, and R.sup.d groups are joined to form a optionally substituted 9-membered heterocyclic ring. In certain embodiments, two of R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.c, and R.sup.d groups are joined to form a optionally substituted 10-membered heterocyclic ring. In certain embodiments, R.sup.7 and R.sup.8 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.7 and R.sup.8 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.7 and R.sup.9 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.7 and R.sup.9 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.7 and R.sup.10 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.7 and R.sup.10 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.7 and R.sup.c are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.7 and R.sup.c are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.7 and R.sup.d are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.7 and R.sup.d are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.8 and R.sup.9 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.8 and R.sup.9 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.8 and R.sup.10 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.8 and R.sup.10 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.8 and R.sup.c are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.8 and R.sup.c are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.8 and R.sup.d are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.e and R.sup.d are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.9 and R.sup.10 are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.9 and R.sup.10 are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.9 and R.sup.c are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.9 and R.sup.c are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.9 and R.sup.d are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.9 and R.sup.d are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.10 and R.sup.c are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.10 and R.sup.c are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.10 and R.sup.d are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.10 and R.sup.d are joined to form a optionally substituted heterocyclic ring. In certain embodiments, R.sup.c and R.sup.d are joined to form a optionally substituted carbocyclyl ring. In certain embodiments, R.sup.c and R.sup.d are joined to form a optionally substituted heterocyclic ring.

(102) In certain embodiments, R.sup.7 and R.sup.8 are each independently selected from the group consisting of substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, and unsubstituted alkynyl. In certain embodiments, R.sup.7 and R.sup.8 are each independently selected from the group consisting of substituted alkyl and unsubstituted alkyl. In certain embodiments, R.sup.7 and R.sup.8 are each C.sub.1-6 alkyl. In certain embodiments, R.sup.7 and R.sup.8 are each methyl. In certain embodiments, R.sup.7 and R.sup.8 are each independently selected from the group consisting of methyl, ethyl, propyl, and butyl.

(103) In certain embodiments, R.sup.7 is optionally substituted alkyl; and R.sup.8 is optionally substituted aryl. In certain embodiments, R.sup.7 is optionally substituted alkyl; and R.sup.8 is optionally substituted phenyl. In certain embodiments, R.sup.7 is C.sub.1-6 alkyl; and R.sup.8 is optionally substituted aryl. In certain embodiments, R.sup.7 is C.sub.1-6 alkyl; and R.sup.8 is optionally substituted phenyl. In certain embodiments, R.sup.7 is methyl; and R.sup.8 is phenyl. In certain embodiments, R.sup.8 is optionally substituted alkyl; and R.sup.7 is optionally substituted aryl. In certain embodiments, R.sup.8 is optionally substituted alkyl; and R.sup.7 is optionally substituted phenyl. In certain embodiments, R.sup.8 is C.sub.1-6 alkyl; and R.sup.7 is optionally substituted aryl. In certain embodiments, R.sup.8 is C.sub.1-6 alkyl; and R.sup.7 is optionally substituted phenyl. In certain embodiments, R.sup.8 is methyl; and R.sup.7 is phenyl.

(104) In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted alkyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted alkyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is C.sub.1-6 alkyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is methyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is ethyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is propyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is butyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted alkenyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted alkenyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is C.sub.1-6 alkenyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is vinyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is allyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is 4-butenyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted alkynyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted alkynyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is C.sub.1-6 alkynyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is ethynyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted aryl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted aryl. In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted phenyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted phenyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted heteroaryl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted heteroaryl. In certain embodiments, R.sup.7 is H; and R.sup.8 is substituted pyridyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is unsubstituted pyridyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is OR.sup.e. In certain embodiments, R.sup.7 is H; and R.sup.8 is O-aryl. In certain embodiments, R.sup.7 is H; and R.sup.8 is OPh. In certain embodiments, R.sup.7 is H; and R.sup.8 is OC.sub.1-6 alkyl. In certain embodiments, R.sup.7 is H; and R.sup.8 is OH. In certain embodiments, R.sup.7 is H; and R.sup.8 is N(R.sup.e).sub.2. In certain embodiments, R.sup.7 is H; and R.sup.8 is N(C.sub.1-6 alkyl).sub.2. In certain embodiments, R.sup.7 is H; and R.sup.8 is NH.sub.2. In certain embodiments, R.sup.7 is H; and R.sup.8 is C(O)OR.sup.e. In certain embodiments, R.sup.7 is H; and R.sup.8 is C(O)OMe. In certain embodiments, R.sup.7 is H; and R.sup.8 is C(O)OEt.

(105) In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted alkyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted alkyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is C.sub.1-6 alkyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is methyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is ethyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is propyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is butyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted alkenyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted alkenyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is C.sub.1-6 alkenyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is vinyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is allyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is 4-butenyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted alkynyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted alkynyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is C.sub.1-6 alkynyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is ethynyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted aryl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted aryl. In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted phenyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted phenyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted heteroaryl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted heteroaryl. In certain embodiments, R.sup.8 is H; and R.sup.7 is substituted pyridyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is unsubstituted pyridyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is OR.sup.e. In certain embodiments, R.sup.8 is H; and R.sup.7 is O-aryl. In certain embodiments, R.sup.8 is H; and R.sup.7 is OPh. In certain embodiments, R.sup.8 is H; and R.sup.7 is OC.sub.1-4 alkyl. In certain embodiments, R.sup.8 is H; and R.sup.7 is OH. In certain embodiments, R.sup.8 is H; and R.sup.7 is N(R.sup.e).sub.2. In certain embodiments, R.sup.8 is H; and R.sup.7 is N(C.sub.1-6 alkyl).sub.2. In certain embodiments, R.sup.8 is H; and R.sup.7 is NH.sub.2. In certain embodiments, R.sup.8 is H; and R.sup.7 is C(O)OR.sup.e. In certain embodiments, R.sup.8 is H; and R.sup.7 is C(O)OMe. In certain embodiments, R.sup.8 is H; and R.sup.7 is C(O)OEt.

(106) In certain embodiments, R.sup.7 and R.sup.8 are each H.

(107) In certain embodiments, R.sup.9 and R.sup.10 are each independently selected from the group consisting of substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, and unsubstituted alkynyl. In certain embodiments, R.sup.9 and R.sup.10 are each independently selected from the group consisting of substituted alkyl and unsubstituted alkyl. In certain embodiments, R.sup.9 and R.sup.10 are each C.sub.1-6 alkyl. In certain embodiments, R.sup.9 and R.sup.10 are each methyl. In certain embodiments, R.sup.9 and R.sup.10 are each independently selected from the group consisting of methyl, ethyl, propyl, and butyl.

(108) In certain embodiments, R.sup.9 is optionally substituted alkyl; and R.sup.10 is optionally substituted aryl. In certain embodiments, R.sup.9 is optionally substituted alkyl; and R.sup.1 is optionally substituted phenyl. In certain embodiments, R.sup.9 is C.sub.1-4 alkyl; and R.sup.10 is optionally substituted aryl. In certain embodiments, R.sup.9 is C.sub.1-6 alkyl; and R.sup.10 is optionally substituted phenyl. In certain embodiments, R.sup.9 is methyl; and R.sup.10 is phenyl. In certain embodiments, R.sup.10 is optionally substituted alkyl; and R.sup.9 is optionally substituted aryl. In certain embodiments, R.sup.10 is optionally substituted alkyl; and R.sup.9 is optionally substituted phenyl. In certain embodiments, R.sup.10 is C.sub.1-6 alkyl; and R.sup.9 is optionally substituted aryl. In certain embodiments, R.sup.10 is C.sub.1-6 alkyl; and R.sup.9 is optionally substituted phenyl. In certain embodiments, R.sup.10 is methyl; and R.sup.9 is phenyl.

(109) In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted alkyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted alkyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is C.sub.1-6 alkyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is methyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is ethyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is propyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is butyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted alkenyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted alkenyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is C.sub.1-6 alkenyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is vinyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is allyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is 4-butenyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted alkynyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted alkynyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is C.sub.1-6 alkynyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is ethynyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted aryl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted aryl. In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted phenyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted phenyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted heteroaryl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted heteroaryl. In certain embodiments, R.sup.9 is H; and R.sup.10 is substituted pyridyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is unsubstituted pyridyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is OR.sup.e. In certain embodiments, R.sup.9 is H; and R.sup.10 is O-aryl. In certain embodiments, R.sup.9 is H; and R.sup.10 is OPh. In certain embodiments, R.sup.9 is H; and R.sup.10 is OC.sub.1-6 alkyl. In certain embodiments, R.sup.9 is H; and R.sup.10 is OH. In certain embodiments, R.sup.9 is H; and R.sup.10 is N(R.sup.e).sub.2. In certain embodiments, R.sup.9 is H; and R.sup.10 is N(C.sub.1-6 alkyl).sub.2. In certain embodiments, R.sup.9 is H; and R.sup.10 is NH.sub.2. In certain embodiments, R.sup.9 is H; and R.sup.10 is C(O)OR.sup.e. In certain embodiments, R.sup.9 is H; and R.sup.10 is C(O)OMe. In certain embodiments, R.sup.9 is H; and R.sup.10 is C(O)OEt.

(110) In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted alkyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted alkyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is C.sub.1-6 alkyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is methyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is ethyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is propyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is butyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted alkenyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted alkenyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is C.sub.1-6 alkenyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is vinyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is allyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is 4-butenyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted alkynyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted alkynyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is C.sub.1-6 alkynyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is ethynyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted aryl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted aryl. In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted phenyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted phenyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted heteroaryl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted heteroaryl. In certain embodiments, R.sup.10 is H; and R.sup.9 is substituted pyridyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is unsubstituted pyridyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is OR.sup.e. In certain embodiments, R.sup.10 is H; and R.sup.9 is O-aryl. In certain embodiments, R.sup.10 is H; and R.sup.9 is OPh. In certain embodiments, R.sup.10 is H; and R.sup.9 is OC.sub.1-6 alkyl. In certain embodiments, R.sup.10 is H; and R.sup.9 is OH. In certain embodiments, R.sup.10 is H; and R.sup.9 is N(R.sup.e).sub.2. In certain embodiments, R.sup.10 is H; and R.sup.9 is N(C.sub.1-6 alkyl).sub.2. In certain embodiments, R.sup.10 is H; and R.sup.9 is NH.sub.2. In certain embodiments, R.sup.10 is H; and R.sup.9 is C(O)OR.sup.e. In certain embodiments, R.sup.10 is H; and R.sup.9 is C(O)OMe. In certain embodiments, R.sup.10 is H; and R.sup.9 is C(O)OEt.

(111) In certain embodiments, R.sup.9 and R.sup.10 are each H.

(112) In certain embodiments, R.sup.7, R.sup.8, R.sup.9, and R.sup.10 are each H.

(113) Compounds of Formula (G) include a ligand Y bound to the Fe.sup.II atom. Y may be any ligand capable of binding to the Fe.sup.II atom to form a coordination complex. In certain embodiments, Y is a compound including one or more electron donating moieties. In certain embodiments, Y a compound including one or more heteroatoms. In certain embodiments, Y is a solvent. In certain embodiments, Y is N(R.sup.f).sub.3. In certain embodiments, Y is NEt.sub.3. In certain embodiments, Y is (i-Pr).sub.2NEt. In certain embodiments, Y is R.sup.fOR.sup.f. In certain embodiments, Y is R.sup.fOR.sup.f; and each occurrence of R.sup.f is independently optionally substituted alkyl. In certain embodiments, Y is R.sup.fOR.sup.f; and each occurrence of R.sup.f is independently C.sub.1-6 alkyl. In certain embodiments, Y is diethyl ether. In certain embodiments, Y is methyl t-butyl ether. In certain embodiments, Y is R.sup.fSR.sup.f. In certain embodiments, Y is dimethyl sulfide. In certain embodiments, Y is diethyl sulfide. In certain embodiments, Y is substituted heterocyclyl. In certain embodiments, Y is unsubstituted heterocyclyl. In certain embodiments, Y is substituted tetrahydrofuran. In certain embodiments, Y is 2-methyltetrahydrofuran. In certain embodiments, Y is unsubstituted tetrahydrofuran. In certain embodiments, Y is substituted tetrahydropyran. In certain embodiments, Y is unsubstituted tetrahydropyran. In certain embodiments, Y is substituted heteroaryl. In certain embodiments, Y is unsubstituted heteroaryl. In certain embodiments, Y is substituted pyridine. In certain embodiments, Y is 2,6-lutidine. In certain embodiments, Y is unsubstituted pyridine.

(114) In certain embodiments, R.sup.f is substituted alkyl. In certain embodiments, R.sup.f is unsubstituted alkyl. In certain embodiments, R.sup.f is C.sub.1-6 alkyl. In certain embodiments, R.sup.f is methyl. In certain embodiments, R.sup.f is ethyl. In certain embodiments, R.sup.f is propyl. In certain embodiments, R.sup.f is butyl. In certain embodiments, R.sup.f is Ad. In certain embodiments, R.sup.f is substituted alkenyl. In certain embodiments, R.sup.f is unsubstituted alkenyl. In certain embodiments, R.sup.f is vinyl. In certain embodiments, R.sup.f is substituted alkynyl. In certain embodiments, R.sup.f is unsubstituted alkynyl. In certain embodiments, R.sup.f is ethynyl. In certain embodiments, R.sup.f is substituted carbocyclyl. In certain embodiments, R.sup.f is unsubstituted carbocyclyl. In certain embodiments, R.sup.f is cyclopropyl. In certain embodiments, R.sup.f is cyclobutyl. In certain embodiments, R.sup.f is cyclopentyl. In certain embodiments, R.sup.f is cyclohexyl. In certain embodiments, R.sup.f is cycloheptyl. In certain embodiments, R.sup.f is substituted heterocyclyl. In certain embodiments, R.sup.f is unsubstituted heterocyclyl. In certain embodiments, R.sup.f is substituted aryl. In certain embodiments, R.sup.f is unsubstituted aryl. In certain embodiments, R.sup.f is substituted phenyl. In certain embodiments, R.sup.f is unsubstituted phenyl. In certain embodiments, R.sup.f is substituted heteroaryl. In certain embodiments, R.sup.f is unsubstituted heteroaryl. In certain embodiments, R.sup.f is substituted pyridyl. In certain embodiments, R.sup.f is unsubstituted pyridyl.

(115) Shown in FIG. 3 is a proposed mechanism for the intramolecular CH amination reaction of an azide RCH(R)N.sub.3 (e.g., R(CH.sub.2).sub.4N.sub.3), catalyzed by a Fe.sup.IICl(L)-dipyrromethene complex (e.g., 3A), to yield a

(116) ##STR00044##
dipyrromethene complex

(117) ##STR00045##
dipyrromethene complex). First, the Fe.sup.IICl(L)-dipyrromethene complex undergoes a ligand exchange to form radical imido intermediate 4. The intermediate 4 abstracts a hydrogen atom intramolecularly from a CH moiety of intermediate 4 to give rise to intermediate 5. Radical recombination furnishes the CH amination product 6. The net effect of the reaction is the transfer of the nitrene group N: of RCH(R)N: (e.g., R(CH.sub.2).sub.4N:) to the CH of RCH(R)N. The mechanism for a similar reaction using compound 3B as the catalyst instead of 3A is similar to or the same as the mechanism described herein.

(118) The acyclic secondary amines may be synthesized under any suitable conditions described herein.

(119) Synthesis of Protected Cyclic Secondary Amines

(120) The method of preparing a compound of Formula (II-1), or a salt or stereoisomer thereof, which is a coordination complex of a cyclic secondary amine and ferrous compound, may further comprise the step of:

(121) reacting the compound of Formula (II-1), or a salt or stereoisomer thereof, with Boc.sub.2O to provide a compound of Formula (II-2-A), which is a Boc-protected cyclic secondary amine:

(122) ##STR00046##
or a salt or stereoisomer thereof; wherein X, n, R.sup.7, R.sup.8, R.sup.9, and R.sup.10 are as defined herein.

(123) Exemplary compounds of Formula (II-2-A) that can be prepared by the inventive methods include, but are not limited to:

(124) ##STR00047## ##STR00048##
and salts and stereoisomers thereof.

(125) The method of preparing a compound of Formula (II-1), or a salt or stereoisomer thereof, which is a coordination complex of a cyclic secondary amine and ferrous compound, may further comprise the step of:

(126) reacting the compound of Formula (II-1), or a salt or stereoisomer thereof, with Fmoc-OSuc to provide a compound of Formula (II-2-B), which is a Fmoc-protected cyclic secondary amine:

(127) ##STR00049##
or a salt or stereoisomer thereof; wherein X, n, R.sup.7, R.sup.8, R.sup.9, and R.sup.10 are as defined herein.

(128) The protected cyclic secondary amines may be synthesized under any suitable conditions described herein.

(129) Synthesis of Cyclic Secondary Amines

(130) The method of preparing a compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, which is a Boc- or Fmoc-protected cyclic secondary amine, may further comprise the step of:

(131) deprotecting the compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, to provide a cyclic amine of Formula (II-3):

(132) ##STR00050##
or a salt or stereoisomer thereof; wherein X, n, R.sup.7, R.sup.8, R.sup.9, and R.sup.10 are as defined herein.

(133) The step of deprotecting a compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, may also comprise deprotecting the compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, under suitable conditions to remove the protecting group. The step of deprotecting a compound of Formula (II-2-A), or a salt or stereoisomer thereof, may comprise increasing the temperature of the compound of Formula (II-2-A), or a salt or stereoisomer thereof, above room temperature. In certain embodiments, the temperature of the compound of Formula (II-2-A), or a salt or stereoisomer thereof, is increased to at least 100 C. In certain embodiments, the temperature of the compound of Formula (II-2-A), or a salt or stereoisomer thereof, is increased to at least 150 C. In certain embodiments, the temperature of the compound of Formula (II-2-A), or a salt or stereoisomer thereof, is increased to at least 200 C. In certain embodiments, the temperature of the compound of Formula (II-2-A), or a salt or stereoisomer thereof, is increased to at least 250 C.

(134) The suitable conditions in the step of deprotecting a compound of Formula (II-2-A), or a salt or stereoisomer thereof, may be acidic conditions. In certain embodiments, the deprotection step comprises reacting an acidic compound with the compound of Formula (II-2-A), or a salt or stereoisomer thereof, to remove the protecting group. In certain embodiments, the acidic compound is an inorganic acid. In certain embodiments, the inorganic acid is HCl. In certain embodiments, the inorganic acid is HBr. In certain embodiments, the inorganic acid is HI. In certain embodiments, the inorganic acid is HClO.sub.4. In certain embodiments, the inorganic acid is HNO.sub.3. In certain embodiments, the inorganic acid is H.sub.2SO.sub.4. In certain embodiments, the inorganic acid is H.sub.3PO.sub.4. In certain embodiments, the acidic compound is an organic acid. In certain embodiments, the organic acid is trifluoroacetic acid. In certain embodiments, the organic acid is a sulfonic acid. In certain embodiments, the organic acid is methanesulfonic acid. In certain embodiments, the organic acid is trifluoromethanesulfonic acid. In certain embodiments, the organic acid is p-toluenesulfonic acid. In certain embodiments, the organic acid is benzenesulfonatic acid. In certain embodiments, the acidic compound is a trialkylsilyl halide. In certain embodiments, the trialkylsilyl halide is trimethylsilyl chloride. In certain embodiments, the trialkylsilyl halide is trimethylsilyl bromide. In certain embodiments, the trialkylsilyl halide is trimethylsilyl iodide. In certain embodiments, the acidic compound is trimethylsilyl trifluoromethanesulfonate. In certain embodiments, the acidic compound is tetrabutylammonium fluoride. In certain embodiments, the acidic compound is a Lewis acid. In certain embodiments, the Lewis acid is boron trifluoride etherate.

(135) The suitable conditions in the step of deprotecting a compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, may be nucleophilic conditions. In certain embodiments, the deprotection step comprises reacting an nucleophilic compound with the compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, to remove the protecting group. In certain embodiments, the suitable conditions in the deprotection step comprise use of a nucleophilic compound. In certain embodiments, the nucleophilic compound is alkyl lithium. In certain embodiments, the nucleophilic compound is LiMe. In certain embodiments, the nucleophilic compound is n-BuLi. In certain embodiments, the nucleophilic compound is sec-BuLi. In certain embodiments, the nucleophilic compound is t-BuLi. In certain embodiments, the nucleophilic compound is aryl lithium. In certain embodiments, the nucleophilic compound is LiPh. In certain embodiments, the nucleophilic compound is a Grignard reagent. In certain embodiments, the nucleophilic compound is MeMgCl, MeMgBr, or MeMgI. In certain embodiments, the nucleophilic compound is EtMgCl, EtMgBr, or EtMgI. In certain embodiments, the nucleophilic compound is PhMgCl, PhMgBr, or PhMgI. In certain embodiments, the nucleophilic compound is TMSMgCl or TMSMgBr. In certain embodiments, the nucleophilic compound is ammonia. In certain embodiments, the nucleophilic compound is ammonium hydroxide. In certain embodiments, the nucleophilic compound is a primary amine. In certain embodiments, the nucleophilic compound is methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, n-pentylamine, n-hexylamine, cyclohexylamine, ethanolamine (i.e., 2-aminoethanol), Tris (i.e., 2-amino-2-hydroxymethyl-propane-1,3-diol), ethylenediamine, triethylenediamine, or aniline. In certain embodiments, the nucleophilic compound is a secondary amine. In certain embodiments, the nucleophilic compound is dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, ethylisopropylamine, dicyclohexylamine, methylethanolamine, pyrrolidine, piperidine, morpholine, piperazine, or 1,4-bis-(3-aminopropyl)piperazine. In certain embodiments, the nucleophilic compound is a tertiary amine. In certain embodiments, the nucleophilic compound is trimethylamine, triethylamine, diisopropylethylamine (DIPEA), tri-n-butylamine, 4-dimethylaminopyridine (DMAP), or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

(136) The suitable conditions in the step of deprotecting a compound of Formula (II-2-B), or a salt or stereoisomer thereof, may be basic conditions. In certain embodiments, the deprotection step comprises reacting an basic compound with the compound of Formula (II-2-B), or a salt or stereoisomer thereof, to remove the protecting group. In certain embodiments, the suitable conditions in the deprotection step comprise use of a basic compound. In certain embodiments, the basic compound is alkyl lithium. In certain embodiments, the basic compound is LiMe. In certain embodiments, the basic compound is n-BuLi. In certain embodiments, the basic compound is sec-BuLi. In certain embodiments, the basic compound is t-BuLi. In certain embodiments, the basic compound is aryl lithium. In certain embodiments, the basic compound is LiPh. In certain embodiments, the basic compound is a Grignard reagent. In certain embodiments, the basic compound is MeMgCl, MeMgBr, or MeMgI. In certain embodiments, the basic compound is EtMgCl, EtMgBr, or EtMgI. In certain embodiments, the basic compound is PhMgCl, PhMgBr, or PhMgI. In certain embodiments, the basic compound is TMSMgCl or TMSMgBr. In certain embodiments, the basic compound is ammonia. In certain embodiments, the basic compound is ammonium hydroxide. In certain embodiments, the basic compound is a primary amine. In certain embodiments, the basic compound is methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, n-pentylamine, n-hexylamine, cyclohexylamine, ethanolamine (i.e., 2-aminoethanol), Tris (i.e., 2-amino-2-hydroxymethyl-propane-1,3-diol), ethylenediamine, triethylenediamine, or aniline. In certain embodiments, the basic compound is a secondary amine. In certain embodiments, the basic compound is dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, ethylisopropylamine, dicyclohexylamine, methylethanolamine, pyrrolidine, piperidine, morpholine, piperazine, or 1,4-bis-(3-aminopropyl)piperazine. In certain embodiments, the basic compound is a tertiary amine. In certain embodiments, the basic compound is trimethylamine, triethylamine, diisopropylethylamine (DIPEA), tri-n-butylamine, 4-dimethylaminopyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), pyridine, or 2,6-lutidine.

(137) The suitable conditions in the step of deprotecting a compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, may be reductive conditions. In certain embodiments, the deprotection step comprises reacting an reductive compound with the compound of Formula (II-2-A) or (II-2-B), or a salt or stereoisomer thereof, to remove the protecting group. In certain embodiments, the suitable conditions in the deprotection step comprise use of a reductive compound. In certain embodiments, the reductive compound is a mixture of zinc and HCl. In certain embodiments, the reductive compound is LiAlH.sub.4. In certain embodiments, the reductive compound is a mixture of rhodium and hydrogen. In certain embodiments, the reductive compound is a mixture of sodium and ammonia.

(138) The suitable conditions in the step of deprotecting a compound of Formula (II-2-B), or a salt or stereoisomer thereof, may be oxidative conditions. In certain embodiments, the deprotection step comprises reacting an oxidative compound with the compound of Formula (II-2-B), or a salt or stereoisomer thereof, to remove the protecting group. In certain embodiments, the oxidative compound is a mixture of CrO.sub.3 and pyridine.

(139) In certain embodiments, the compound of Formula (II-3) is of Formula (II-4):

(140) ##STR00051##
or a stereoisomer thereof, wherein V is an anionic counterion. All anionic counterions described herein are contemplated as being within the scope of the invention. In certain embodiments, the anionic counterion is F.sup., Cl.sup., Br.sup., or I.sup.. In certain embodiments, the anionic counterion is ClO.sub.4.sup.. In certain embodiments, the anionic counterion is NO.sub.3.sup.. In certain embodiments, the anionic counterion is HSO.sub.4.sup.. In certain embodiments, the anionic counterion is H.sub.2PO.sub.4.sup.. In certain embodiments, the anionic counterion is a sulfonate ion. In certain embodiments, the anionic counterion is a methansulfonate, trifluoromethanesulfonate, p-toluenesulfonate, or benzenesulfonate ion. In certain embodiments, the anionic counterion is BF.sub.4.sup..

(141) A compound of Formula (II-4), or a stereoisomer thereof, may be further reacted by contacting with a base to provide a compound of Formula (II-3), or a stereoisomer thereof. In certain embodiments, the base is an inorganic base. In certain embodiments, the inorganic base is ammonia. In certain embodiments, the inorganic base is ammonium carbonate. In certain embodiments, the inorganic base is ammonium hydroxide. In certain embodiments, the inorganic base is an alkali metal carbonate. In certain embodiments, the inorganic base is Li.sub.2CO.sub.3, Na.sub.2CO.sub.3, K.sub.2CO.sub.3, Rb.sub.2CO.sub.3, or Cs.sub.2CO.sub.3. In certain embodiments, the inorganic base is an alkali metal bicarbonate. In certain embodiments, the inorganic base is LiHCO.sub.3, NaHCO.sub.3, KHCO.sub.3, RbHCO.sub.3, or CsHCO.sub.3. In certain embodiments, the inorganic base is an alkali metal hydroxide. In certain embodiments, the inorganic base is LiOH, NaOH, KOH, RbOH, or CsOH. In certain embodiments, the inorganic base is an alkaline earth metal carbonate. In certain embodiments, the inorganic base is BeCO.sub.3, MgCO.sub.3, CaCO.sub.3, SrCO.sub.3, or BaCO.sub.3. In certain embodiments, the inorganic base is an alkaline earth metal bicarbonate. In certain embodiments, the inorganic base is Be(HCO.sub.3).sub.2, Mg(HCO.sub.3).sub.2, Ca(HCO.sub.3).sub.2, Sr(HCO.sub.3).sub.2, or Ba(HCO.sub.3).sub.2. In certain embodiments, the inorganic base is an alkaline earth metal hydroxide. In certain embodiments, the inorganic base is Be(OH).sub.2, Mg(OH).sub.2, Ca(OH).sub.2, Sr(OH).sub.2, or Ba(OH).sub.2. In certain embodiments, the base is an organic base. In certain embodiments, the organic base is an aliphatic amine. In certain embodiments, the organic base is an aromatic amine. In certain embodiments, the organic base is a primary amine. In certain embodiments, the organic base is a secondary amine. In certain embodiments, the organic base is a tertiary amine. In certain embodiments, the organic base is triethylamine, DIPEA, or DBU. In certain embodiments, the organic base is substituted pyridine. In certain embodiments, the organic base is 2,6-lutidine or DMAP. In certain embodiments, the organic base is unsubstituted pyridine.

(142) A compound of Formula (II-3), or a stereoisomer thereof, may be further reacted with an acid to provide a salt of compound of Formula (II-3), or a stereoisomer thereof. The acid is as described herein.

(143) The cyclic secondary amines may be synthesized under any suitable conditions described herein.

(144) The compounds synthesized by the inventive methods may be screened for a wide range of biological activities, e.g., for anti-proliferative, anti-microbial, anti-arrhythmic, anti-hypertensive, anti-neurodegenerative, and/or anti-diabetic activities. The compounds prepared by the inventive methods, or salts or stereoisomers thereof, may be administered to a subject to treat and/or prevent a disease (e.g., a proliferative disease, infectious disease, inflammatory disease, autoimmune disease, cardiovascular disease, gastrointestinal disease, neurodegenerative disease, or metabolic disease) in the subject.

EXAMPLES

(145) In order that the invention described herein may be more fully understood, the following examples are set forth. These examples are for illustrative purposes only and are not to be construed as limiting this invention in any manner.

(146) Preparation of the Iron-Based Catalysts

(147) The iron-based catalysts described herein that are useful in the inventive methods (e.g., a ferrous compound of Formula (B) or (G), or a salt thereof, such as compounds 3A and 3B) may be synthesized according to reported processes, such as ones described in King et al., J. Am. Chem. Soc. 133, 4917 (2011), which is incorporated herein by reference.

(148) Preparation of Acyclic Secondary Amines

(149) Acyclic secondary amines (e.g., compounds 25A-25D) may be synthesized according to the general method shown in Scheme 4 through a reaction of an azide (e.g., R.sup.AN.sub.3) with an substituted or unsubstituted, branched or unbranched, cyclic or acyclic olefin (e.g., compounds 26A-26C) catalyzed by a compound of Formula (B) or (G) (e.g., compound 3, 3A, or 3B). Any suitable conditions may be employed. For example, compounds 25A-25D may be prepared at about 25 C., about 60 C., about 100 C., or about 120 C. for about 6 hours, about 12 hours, or about 24 hours, using benzene as the solvent or no solvent (i.e., neat). When 1 equiv. of R.sup.AN.sub.3 and 1 or more equiv. of the olefin are used, the loading of compound 3 may be about 10% (i.e., 0.1 equiv.) or about 20% (i.e., 0.2 equiv.). The reactions may be conducted under an atmosphere of nitrogen or argon. Compounds 25A-25D may be purified and characterized using methods known in the art (e.g., flash chromatography).

(150) ##STR00052##

(151) For example, a wide range of acyclic secondary amines may be prepared by a method similar to the following procedure. Under an inert N.sub.2 atmosphere, 1-azidoadamantane (60.9 mg, 0.28 mmol, 10 equiv.) was added to a stirring solution of compound 3B (20 mg, 0.028 mmol, 1 equiv.) in 1 mL of an olefin (e.g., styrene) in a 20 mL scintillation vial. The resultant inky, dark red solution was stirred for 12 hours at 25 C. The mixture was purified by flash chromatography using a short pipette of triethylamine-treated silica gel eluted with 10:1 hexanes:EtOAc to yield a brightly colored solution. Volatiles were removed under reduced pressure to yield the acyclic secondary amine product. The yields were determined by .sup.1H NMR via integration against ferrocene, averaging over three runs for each substrate.

(152) Alternatively, the following procedure may be used to make acyclic secondary amines, especially, allylic acyclic secondary amines. Under an inert N.sub.2 atmosphere, 1-azidoadamantane (30.5 mg, 0.14 mmol, 5 equiv., or 60.9 mg, 0.28 mmol, 10 equiv.) was added to a stirring solution of compound 3B (20 mg, 0.028 mmol, 1 equiv.) in 2 mL of an olefin in a 20 mL scintillation vial. The resultant inky, dark red solution was stirred for 12 hours at the indicated temperature. The mixture was concentrated and purified by flash chromatography eluted with 9:1 DCM:methanol to yield a yellow solution. Volatiles were removed under reduced pressure to yield the allylic amine product. The yields were determined by .sup.1H NMR via integration against ferrocene.

(153) Yields of exemplary acyclic secondary amines synthesized using the inventive methods are shown in Table 5.

(154) TABLE-US-00002 TABLE 5 Synthesis of acyclic amines 25. 3B Temperature 26 Loading (mol %) ( C.) 25 Yield E/Z ratio 10 100 49 20 20 10 25 60 100 35 51 53 20 10 25 100 26 38 Only E isomer observed 0 20 10 25 100 12 29 20 20 10 25 60 100 10 38 39 10 100 14 10 100 17 20 20 10 10 25 60 100 120 23 50 48 25 5:1 E:Z 6:1 E:Z 6:1 E:Z 3:1 E:Z 0 20 10 60 100 68 49 7:1 E:Z 5:1 E:Z 20 10 60 100 71 57 5:1 E:Z 4:1 E:Z 10 60 17
Preparation of Protected Cyclic Secondary Amines

(155) Boc- or Fmoc-protected cyclic secondary amines may be synthesized according to the general method shown in Scheme 5.

(156) ##STR00076##

(157) For example, a variety of substituted aliphatic azides (e.g., 1-azido-5-hexene) were subjected to compound 3A. Exposure of 1-azido-5-hexene to compound 3A at room temperature in benzene quickly consumed the azide, as ascertained by the disappearance of the azide stretch in the IR spectrum and afforded a new paramagnetically shifted .sup.1H NMR spectrum. Crystallization was induced by slow diffusion of a hexanes solution of the product at 23 C. to yield crystals in which 2-vinylpyrrolidine was bound to the iron-based complex to give compound 8 (Scheme 6 and FIG. 5A). Similarly, treatment of 1-azido-4-phenylbutane with 3A afforded the cyclized product 2-phenylpyrrolidine as an iron-bound adduct 9 (FIG. 5B). In addition to allylic and benzylic CH bonds, less reactive tertiary CH bonds could similarly be functionalized. The reaction of 1-azido-5-methylpentane and 3A under standard conditions gave the 2,2-dimethylpyrrolidine iron-bound product. Gratifyingly, even secondary aliphatic CH bonds could be functionalized through this method. Addition of 1-azidohexane to 3A resulted in the rapid consumption of the azide to afford a single product, which was determined to be the 2-ethylpyrrolidine complex 10 (FIG. 5C). In an attempt to activate the primary CH bond of an aliphatic azide substrate, 1-azidobutane was exposed to 3A. However, the only products observed in this transformation were linear n-butylamine and n-butylimine. To eliminate the potential for imine formation, through a process involving intermolecular CH bond activation or -hydride elimination, the gem-dimethyl substrate 2-azido-2-methylpentane was prepared and subjected to 3A at room temperature for 6 h to afford the cyclized 2,2-dimethylpyrrolidine complex 11 (FIG. 5D) in quantitative yield. The presence of the two -Me substituents may facilitate the CH bond functionalization/cyclization process through the Thorpe-Ingold effect (Beesley et al., J. Chem. Soc., Trans., 107, 1080 (1915)).

(158) ##STR00077## ##STR00078##

(159) ##STR00079##

(160) With a reliable protocol for the stoichiometric CH functionalization/cyclization of aliphatic azides in hand, attempts to render the reaction catalytic were undertaken (5-10 equiv. of azide per 1 equiv. of compound 3A or 3B). Unfortunately, examination of the cyclization reaction under catalytic conditions did not markedly increase the yield of the resultant free heterocyclic product. The lack of catalyst turnover may be attributed to product inhibition, in which a tight Lewis-acid/base pair between the dipyrromethene-iron and the heterocyclic nitrogen atom is formed. This hypothesis is supported by the ease with which crystals of the corresponding dipyrromethene-iron complexes were obtained (FIGS. 4 and 5).

(161) To overcome this problem, the cyclization reaction was performed in the presence of an in situ protection reagent, which would reduce the nucleophilicity of the product cyclic amines while avoiding the generation of byproducts that might retard or prevent catalysis. Accordingly, treatment of a solution of 1-azido-4-phenylbutane and 9-fluorenylmethyl N-succinimidyl carbonate (Fmoc-OSuc) in benzene at room temperature with a stoichiometric amount of compound 3A for 12 h afforded the Fmoc-protected 2-phenylpyrrolidine in 98% yield. Similarly, addition of an equivalent of compound 3A to a solution of 1-azido-4-phenylbutane and di-t-butyl dicarbonate (Boc.sub.2O) under similar reaction conditions afforded the 1-butyloxycarbonyl (Boc) protected product 1-Boc-2-phenylpyrrolidine in 93% yield. As catalyst loading was decreased, it was discovered that the N-hydroxysuccinimide byproduct of Fmoc-protection led to catalyst decomposition through ligand protonation and limited the reaction to a single turnover. Fortunately, the byproducts of protection with Boc.sub.2O (i.e., t-BuOH and CO.sub.2) did not inhibit catalyst turnover, permitting the cyclic amines to be synthesized with catalytic amounts of compound 3B (chosen to eliminate benzylic CH bonds from catalyst meso-aryl substituent).

(162) Application of catalytic quantities of compound 3B to the established in situ protection protocol for CH functionalization/cyclization was investigated (Table 2). Exposure of azides 13 containing allylic, benzylic, or tertiary CH bonds to compound 3B (10 mol %) provided the corresponding Boc-protected pyrrolidine 14 in good yield (57-64%, entries 1-3). Next, catalytic functionalization of a secondary CH bond was also possible, affording 1-Boc-2-ethylpyrrolidine in modest yield (27%, entry 4). Even, a primary CH bond in 2-azido-2-methylpentane could be functionalized to give 1-Boc-2,2-dimethylpyrrolidine in 17% yield (entry 6). The substrate scope was then expanded to include hetero-atom containing functional groups. Exposure of ethyl-5-azidopentanoate to compound 3B under standard catalytic conditions only resulted in linear primary amine and imine products (entry 7). Again, blocking the -position of the azide 13 with gem-dimethyl substituents led to productive cyclization (entry 8). Introduction of heteroatoms between the reactive functionalities allowed for the formation of 1-Boc-2-phenyloxazolidine in 47% yield (entry 9).

(163) TABLE-US-00003 TABLE 2 Amination reactions of azides 13 catalyzed by compound 3B yielding pyrrolidines 14. 0 Yield Entry 13 14 (%).sup.a 1 64 2 57 3 60 4 27 5 0 0 6 17 (7).sup.b 7 0 8 11.sup.b 9 47.sup.b .sup.aYield determined by .sup.1H NMR using ferrocene or trimethoxybenzene as the internal standard. .sup.b20 mol% loading of compound 3B.

(164) The scope of CH functionalization/cyclization was further explored in substrates accessible via cuprate-assisted epoxide opening (Drouin et al., Tetrahedron 36, 1195 (1980)) followed by azide formation (Table 3). The use of epoxides 15 and alkyl halides (which may be transformed into Grignard reagents 16) permits virtually any substitution pattern to be programmed into the ensuing heterocyclic product. After Li.sub.2[CuCl.sub.4] promoted epoxide opening, the resultant primary or secondary alcohols were tosylated and displaced with sodium azide to provide the desired cyclization precursor 17. Alternatively, tertiary and benzylic alcohols were directly converted to the corresponding azide (e.g., compound 18) by exposure to trimethylsilylazide and boron trifluoride diethyl etherate (Mukaiyama et al., Heterocycles 80, 63 (2010)). Allylic, tertiary and secondary CH bond substrates available through either reaction sequence underwent facile CH functionalization/cyclization to give protected (e.g., protected with Boc) cyclic amines 19 (entries 1-9, 58-98% yield). Notably, this method provides access to an all-carbon spiro-center (entry 7, 67%). Functionalization of primary CH bonds may require a higher loading of the catalyst (e.g., compound 3A or 3B) than a catalytic amount (entry 10). For example, a stoichiometric reaction similar to the reaction in Table 3, entry 10, except that Fmoc-OSuc was used instead of Boc.sub.2O and that 1 equiv. of compound 3B was employed, gave rise to

(165) ##STR00099##
in 78% yield. Interestingly, use of (R)-2-phenyl-5-azidopentane (95% enantiomeric excess (ee)) in the catalytic transformation resulted in (S)-2-methyl-2-phenylpyrrolidine with retention of configuration (entry 5, 75%, 93% ee). A similar reaction using stoichiometric quantities of compound 3A gave the corresponding (S)-2-methyl-2-phenylpyrrolidine iron-bound adduct 20 whose absolute stereochemistry was verified by X-ray diffraction (FIG. 6).

(166) TABLE-US-00004 TABLE 3 Synthesis of 1,2,3,4-substituted pyrrolidines 19. 00 Yield Entry 15 16 17 or 18 19.sup.a (%).sup.b dr.sup.c 1 01 02 03 04 60 3.9:1 2 05 06 07 66 1.5:1 3 08 09 0 70 4 98 5 75 6 0 84 1.1:1 7 67 8 73 2.1:1 9 0 58 5.5:1.5:1:0.08 10 14 .sup.aPyrrolidines 19 are racemic unless otherwise noted. .sup.bYields are representative of cyclization reactions only and are determined by .sup.1H NMR using ferrocene or trimethoxybenzene as the internal standard. .sup.cThe term dr refers to diastereomeric ratio.

(167) The potential of the inventive methods to generate cyclic amines of various ring sizes was also explored. It was expected that a vinyl directing group could be employed to encourage the site-selective functionalization of the allylic CH bond within the acyclic precursor. Treatment of 1-azido-6-heptene and Boc.sub.2O (1 equiv.) with compound 3B (1 equiv.) at room temperature generated the 6-membered 1-Boc-2-vinylpiperidine (entry 1, Table 4) as the exclusive reaction product. Unfortunately, use of the vinyl activating group to target 7-membered azepane products led to exclusive formation of the corresponding pyrrolidine (entry 4). In contrast, a phenyl activating group was not effective in favoring the formation of a 6-membered ring product. Addition of compound 3B to 1-azido-5-phenyl-pentane under standard conditions resulted in a 1:0.85 mixture of both 1-Boc-2-phenylpiperidine and 1-Boc-2-benzylpyrrolidine (entry 2). Similarly, the use of a tertiary CH bond to favor 6-membered ring formation in the case of 1-azido-5-methylhexane resulted in a mixture of piperidine and pyrrolidine products (entry 3). An attempt was made to block the potential for pyrrolidine formation; exposure of 2-azido-2,5,5-trimethylhexane and Fmoc-OSuc to compound 3B resulted in both the anticipated 1-Fmoc-2,2,5,5-tetramethylpiperidine and the unexpected 1-Fmoc-2,2-dimethyl-4-tert-butylazetidine (entry 5). Alternatively, use of compound 3A and omission of Fmoc-OSuc allowed for the characterization of the corresponding iron-bound adducts by X-ray analysis (FIGS. 7B and 7C).

(168) TABLE-US-00005 TABLE 4 Synthesis of cyclic amines 24 of various ring sizes. Entry Azide 23 Product(s) 24 Conv. (%).sup.a,b 1 45 2 0 82 3 52 (1.0:0.9) 4 47 (1.0:1.5) 5 47 (1.0:1.5) .sup.aYields are determined by .sup.1H NMR using ferrocene or trimethoxybenzene as the internal standard. .sup.bRatios are deteremined by integration of GC/MS peaks.

(169) As illustrated in FIG. 3, it is hypothesize that the CH bond functionalization/cyclization reaction occurs via a three-step process involving: (1) oxidation of the Fe.sup.II catalyst (e.g., compound 3A) to an Fe.sup.III imido radical (e.g., compound 4) by the alkyl azide substrate; (2) intramolecular H-atom abstraction to generate an alkyl radical and an Fe.sup.III amide (e.g., compound 5) (path Ia); and (3) radical recombination to form the observed cyclic amine product (e.g., compound 6) (path Ib). Alternatively, a direct CH bond insertion by the Fe.sup.III imido radical intermediate cannot be excluded (path II). Both mechanisms require that the substrate CH bond be brought into close proximity to the reactive Fe-imido radical. Based on previous findings, the imido radical likely resides in the plane defined by the iron and the dipyrrin ligand, flanked by large pyrrolide adamantyl substituents. Such a conformation requires that the CH bond substrate approach the imido radical opposite the chloride ligand. It is expected that once this orientation is obtained, CH bond functionalization is rapid. This hypothesis is supported by the retention of stereochemical information during the cyclization of (R)-2-phenyl-5-azidopentane. Additionally, cyclization of 1-azido-4-deutero-4-phenylbutane (Scheme 7) provides an intramolecular kinetic isotope effect (KIE) of 5.3 at 25 C. and 5.1(2) at 65 C. This value is similar to the KIE observed in the hydroxylation of 1,3-dideuteroadamantane catalyzed by tetramesitylporphyrin iron with oxone [k.sub.H/k.sub.D=4.1(2)](Sorokin et al., J. Am. Chem. Soc. 115, 7293 (1993)). Finally, addition of the radical clock substrate (2-(4-azidobutyl)cyclopropyl)benzene to compound 3B exclusively furnishes the pyrrolidine product 1-Boc-2-(2-phenylcyclopropyl)pyrrolidine with the cyclopropyl unit intact (Scheme 8). The non-unity intramolecular kinetic isotope effect suggests a stepwise mechanism for benzylic substrates (FIG. 3, Path I (i.e., Ia and Ib)), which is consistent with previously reported intermolecular amination reaction (King et al., J. Am. Chem. Soc. 133, 4917 (2011)). The stereospecificity of the cyclization and the preservation of the cyclopropyl unit in the radical clock experiment suggest that if a stepwise mechanism is operative, the radical intermediate following H-atom abstraction is short-lived [recombination rate>1011 s.sup.1 (Newcomb et al., Acc. Chem. Res. 33, 449 (2000))]. Alternatively, the reaction mechanism may change to a direct insertion mechanism (FIG. 3, path II) when stronger substrate CH bonds are functionalized.

(170) ##STR00148##

(171) ##STR00149##

(172) The results described herein have demonstrated the oxidative potency of the transiently formed, high-spin iron imido radical for the functionalization of both activated and unactivated aliphatic CH bond substrates. This iron-mediated cyclization of linear azides provides facile entry into complex acyclic and cyclic amines from readily available substrates that cannot be achieved by azide photolysis (Barton et al., J. Chem. Soc. 2444 (1965)) or via classic Hoffmann-Lffler-Freytag methodologies (Hoffman, Berichte 18, 105 (1885)). It is expected that the methods of the invention can be extended to produce a wide variety of acyclic and cyclic amines (e.g., saturated cyclic amines). The oxidative amination of aliphatic CH bonds over more electron-rich CH bonds (olefins and aromatics) is made possible by the unique electronic structure of the putative iron-stabilized imido radical intermediate.

EQUIVALENTS AND SCOPE

(173) In the claims articles such as a, an, and the may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include or between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

(174) Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is/are referred to as comprising particular elements and/or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms comprising and containing are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

(175) This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.

(176) Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.