Regioselective 1,2-dearomatization of functionalized azines by organolanthanide catalysts

Abstract

A 1,2-regioselective organolanthanide-catalyzed azine dearomatization process using pinacolborane is disclosed.

Claims

1. A method for dearomatizing an aromatic azine ring compound, said method comprising treating an azine ring compound comprising at least one nitrogen atom with at least one main-group element hydride in the presence of an organolathanide catalyst to afford a 1,2-dearomatized azine.

2. The method according to claim 1, wherein the 1,2-dearomatized azine is regioselective.

3. The method according to claim 2, wherein the regioselective 1,2-dearomatized azine is a regioselective 1,2-dihydropyridine.

4. A method according to claim 1, wherein the at least one main-group element hydride is pinacolborane.

5. A method according to claim 1, wherein the organolanthanide catalyst has a formula of (L).sub.xLn-H, wherein L is an ancillary ligand selected from a group consisting of Cp, Cp* and CGC, Cp; Ln is a lanthanide element; X is an integer selected from a group consisting of 1 and 2; and H is hydrogen.

6. A method according to claim 5, wherein the lanthanide element is selected from a group consisting of Sc, Y, La, Sm, Nd, Yb and Lu.

7. A method according to claim 1, wherein the azine is a substituted with one or more subsituents.

8. A method according to claim 7, wherein the one or more substituents are independently selected from a group consisting of halogen, CF.sub.3, OMe, (2S)-1-methyl-2-pyrrolidinyl, 1-piperidinyl, phenyl, vinyl, SnMe.sub.3, Bpin and fused ring systems and combinations thereof.

9. A method according to claim 1, wherein the azine is pyridine.

10. A method according to claim 1, wherein the azine and the at least one main-group element hydride are present in equimolar quantity.

11. A method according to claim 10, wherein the catalyst is present in less than equimolar quantity relative to the azine and the at least one main-group element hydride.

12. A method according to claim 11, wherein the catalyst is present in about 1% stoichiometric quantity relative to the azine and the at least one main-group element hydride.

13. A method according to claim 1, wherein the treating of the azine with at least one main-group element hydride in the presence of an organolathanide catalyst is performed in a solvent comprising benzene.

14. A method according to claim 3, wherein the regioselective 1,2-dihydropyridine is selected from a group consisting of: 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-fluoro-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,5-methyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methoxy-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroquinoline; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroisoquinoline; 1,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydropyrazine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-iodo-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methoxy-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-piperidino-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-vinyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-trimethylstannyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-chloro-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-chloro-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-bromo-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-bromo-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-iodo-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-iodo-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-phenyl-1,2-dihydropyridine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-phenyl-1,2-dihydropylidine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine; and 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine (3s).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 depicts the importance of saturated six-membered nitrogenous heterocycles and recent progress toward their synthesis; in particular a) selected examples of natural products and drugs containing dearomatized pyridines and azines; b) synthetic utility of 1,2-dihydropyridines; c) recent advances in metal-catalyzed dearomatization of pyridines with pinacolborane; d) example of organolanthanide-catalyzed alkene hydroboration; and e) scheme of the organolanthanide-catalyzed azine 1,2-dearomatization of the present invention.

(2) FIG. 2 is a plausible elementary reaction sequence for catalytic pyridine dearomatization; in particular a) bridge-cleaving reaction of 1 with pyridine to yield hydrido pyridine complexes which subsequently undergo intramolecular CN insertion (equations 1 and 2); b) LaN/HB -bond metathesis to release the dearomatized product and regenerate the hydrido pyridine complex; c) possible competitive inhibition by HBpin; d) reaction of 1 and HBpin to yield zwitterionic deactivation product 4; and e) ORTEP plot of the molecular structure of zwitterion 4.

(3) FIG. 3 depicts DFT-derived energetics of the catalytic pyridine dearomatization reaction coordinate; in particular a) energetic profile for transformations of precatalyst 1 in the presence of pyridine and HBpin: active catalyst generation, inhibition, and deactivation; b) energetic profile of the catalytic cycle for the Cp.sub.2*La-catalyzed pyridine dearomatization along with the off-cycle active catalyst inhibition process.

(4) FIG. 4 is a mechanistic summary of catalytic pyridine dearomatization according to the invention.

(5) FIG. 5 shows DFT computed versus experimental organolanthanide-catalyzed turnover frequencies for functionalized pyridines; in particular a) trends as a function of pyridine substituents; b) correlation between experimental TOFs and positive Mulliken Orbital Overlap Population (MOOP) contributions due to halogen-CH.sub.2 bonding interactions in the turnoverand regioselectivitydetermining TS3 structures for a series of 3-halogen-substituted pyridines.

(6) FIG. 6 a) is a plot of [catalyst].sub.0 vs. reaction rate (M/min); b) van't Hoff plot for reaction rate law order in [catalyst].sub.0; c) plot of [pyridine] vs. rate (M/min); d) van't Hoff plot for reaction rate law order in [pyridine]; e) Plot of [HBpin] vs. rate(M/min); f) van't Hoff plot for reaction rate law order in [HBpin].

(7) FIG. 7 a) is an Erying plot (equation 11) and b) is an Arrhenius plot (equation 12) with the line as the least-squares fit to the data points.

(8) FIG. 8 is a .sup.1H NMR spectrum of 3c in C.sub.6D.sub.12.

(9) FIG. 9 is a .sup.1H NMR spectrum of 3c in C.sub.6D.sub.12, wherein P=product; I. S.=internal standard; and S=solvent.

(10) FIG. 10 is a .sup.1H NMR spectrum of 3e in C.sub.6D.sub.12, wherein P=product; I. S.=internal standard; and S=solvent.

(11) FIG. 11 is a .sup.1H NMR spectrum of 3j in C.sub.6D.sub.12, wherein P=product; and S=solvent.

(12) FIG. 12 is a .sup.1H NMR spectrum of 3i in C.sub.6D.sub.12, wherein P=product; I. S.=internal standard; and S=solvent.

(13) FIG. 13 is a .sup.1H NMR spectrum of 3g in C.sub.6D.sub.12, wherein P=product; I. S.=internal standard; and S=solvent.

(14) FIG. 14 is a .sup.1H NMR spectrum of 3h in C.sub.6D.sub.12, wherein P=product; I. S.=internal standard; and S=solvent.

(15) FIG. 15 is a .sup.1H NMR spectrum of 3l in C.sub.6D.sub.12, wherein P1=3-chloro-1,2-dihydropyridine; P2=5-chloro-1,2-dihydropyridine; C=catalyst; and S=solvent.

(16) FIG. 16 is a .sup.1H NMR spectrum of 3m in C.sub.6D.sub.12, wherein P1=3-bromo-1,2-dihydropyridine; P2=5-bromo-1,2-dihydropyridine; and S=solvent.

(17) FIG. 17 is a .sup.1H NMR spectrum of 3n in C.sub.6D.sub.12, wherein P1=3-iodo-1,2-dihydropyridine; P2=5-iodo-1,2-dihydropyridine; and S=solvent.

(18) FIG. 18 is a .sup.1H NMR spectrum of 3q in C.sub.6D.sub.12, wherein P1=3-phenyl-1,2-dihydropyridine; P2=5-phenyl-1,2-dihydropyridine; S=solvent.

(19) FIG. 19 is a .sup.1H NMR spectrum of 3s in C.sub.6D.sub.12, wherein P1=3-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine; P2=5-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine; S=solvent.

(20) FIG. 20 is a .sup.1H NMR stack spectra plot of a) pyridine, b) HBpin, and c) pyridine+HBpin in C.sub.6D.sub.12, wherein #=unknown impurity in commercial HBpin.

(21) FIG. 21 is an expansion ( 8.706.80 ppm) of the .sup.1H NMR stack spectra plot of a) pyridine and b) pyridine+HBpin in C.sub.6D.sub.12.

(22) FIG. 22 is an expansion ( 4.50-3.00 ppm) of the .sup.1H NMR stack spectra plot of a) HBpin and b) pyridine+HBpin in C.sub.6D.sub.12.

(23) FIG. 23 is a .sup.1H NMR spectrum of the stoichiometric reaction between [Cp*.sub.2LaH].sub.2, pyridine and HBpin in C.sub.6D.sub.12, wherein Product=1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3a).

(24) FIG. 24 is a .sup.1H NMR stack spectra plot of a) [Cp*.sub.2LaH].sub.2, b) pyridine+HBpin, and c) [Cp*.sub.2LaH].sub.2+pyridine+HBpin in C.sub.6D.sub.12, wherein Product=1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3a) and #=unidentified impurity.

(25) FIG. 25 is an expansion ( 2.05-1.83 ppm) of .sup.1H NMR stack spectra plot of a) the Cp* region of [Cp*.sub.2LaH].sub.2, and b) [Cp*.sub.2LaH].sub.2+pyridine+HBpin in C.sub.6D.sub.12.

(26) FIG. 26 is an expansion ( 4.33-3.00 ppm) of .sup.1H NMR stack spectra plot of a) HBpin and b) [Cp*.sub.2LaH].sub.2+pyridine+HBpin in C.sub.6D.sub.12, wherein Product=1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3a) and *=unidentified impurity.

(27) FIG. 27 is an expansion ( 9.006.80 ppm) of .sup.1H NMR stack spectra plot of a) pyridine, and b) [Cp*.sub.2LaH].sub.2+pyridine+HBpin in C.sub.6D.sub.12.

(28) FIG. 28 is an expansion ( 10.60-9.80 ppm) of .sup.1H NMR stack spectra plot of a) [Cp*.sub.2LaH].sub.2 and b) [Cp*.sub.2LaH].sub.2+pyridine+HBpin in C.sub.6D.sub.12.

(29) FIG. 29 is an expansion ( 2.05-1.83 ppm) of .sup.1H NMR stack spectra plot of a) [Cp*.sub.2LaH].sub.2; b) stoichiometric reaction between [Cp*.sub.2LaH].sub.2, pyridine, and HBpin; c) catalytic reaction between pyridine and HBpin in the presence of 1 mol % [Cp*.sub.2LaH].sub.2 after 5 minutes; d) after 180 minutes; and e) after 1440 min in C.sub.6D.sub.12, wherein #=unidentified byproducts.

(30) FIG. 30 is an expansion ( 6.50-3.45 ppm) of .sup.1H NMR stack spectra plot of catalytic reaction of a) [Cp*.sub.2LaH].sub.2+Pyridine and b) (Cp*.sub.2LaH].sub.2+Pyridine) +HBpin after 5 minutes in C.sub.6D.sub.12, wherein P=1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3a), I=1,2-organolanthanum-dihydropyridine complex, and #=unidentified byproducts.

(31) FIG. 31 is an expansion ( 9.50-3.25 ppm) of .sup.1H NMR stack spectra plot of stoichiometric reaction of a) [Cp*.sub.2LaH].sub.2+pyridine; b) ([Cp*.sub.2LaH].sub.2+pyridine)+HBpin; and c) pyridine in C.sub.6D.sub.12, wherein #=unidentified byproduct.

(32) FIG. 32 is a .sup.1H NMR spectrum of 4 in C.sub.6D.sub.6.

(33) FIG. 33 is a .sup.13C NMR spectrum of 4 in C.sub.6D.sub.6.

(34) FIG. 34 is a .sup.1H-.sup.13C HSQC NMR spectrum of 4 in C.sub.6D.sub.6.

(35) FIG. 35 is an expansion (2.200.90 ppm) of .sup.1H NMR stack spectra plot of a) [Cp*.sub.2LaH].sub.2; b) soluble fraction of [Cp*.sub.2LaH].sub.2+2HBpin; and c) insoluble fraction of [Cp*.sub.2LaH].sub.2+2HBpin in C.sub.6D.sub.12, wherein #=unknown compound.

(36) FIG. 36 is a .sup.1H NMR spectrum of the attempted reaction between 4-I-pyridine and HBpin using [RhCl(cod)].sub.2/PCy.sub.3 catalytic system in C.sub.6D.sub.6 after 24 hours at 50 C.

(37) FIG. 37 is a .sup.1H NMR spectrum of reaction between 10 equivalents of pyridine and 1 equivalent of HBpin using [RhCl(cod)].sub.2/PCy.sub.3 catalytic system in C.sub.6D.sub.6 after 16 hours at 50 C.

(38) FIG. 38 is a) an energetic profile for transformations of the precatalyst 1 in the presence of pyridine and HBpin reactants: active catalyst generation, inhibition, and deactivation; b) an energetic profile of the catalytic cycle for the La-catalyzed pyridine dearomatization along with the off-cycle active catalyst inhibition process.

(39) FIGS. 39A-U provides Cartesian Coordinates for all computed structures.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

(40) The invention relates to a method for the organolanthanide-catalyzed 1,2-hydroboration of an azine ring with a main-group element hydride. In an embodiment, the main-group element hydride is pinacolborane (HBpin), the method comprising treating the azine with HBpin in the presence of an organolanthanide catalyst to afford a 1,2-dihydropyridines.

(41) It is appreciated that main-group element hydrides other than or in combination with HBpin can be employed with the methods disclosed herein. By main-group element hydride is meant a compound of the formula H-ER.sub.n, wherein H is hydrogen; E is a main-group element from Groups 1-2 and 13-18 (other than hydrogen), R is linear or together with E is cyclic, and consists of one or more groups selected from a group consisting of H, O, NH (or N substituted with a group other than H), C substituted with two or three H or at each instance independently with another group, wherein n=1-4, and wherein the one or more independent groups depends on the value of n and/or whether R is linear or cyclic. Preferred main-group elements are selected from a group consisting of B, Si, Sn and Ge. As discussed above, the main-group element hydride is preferably pinacolborane. By pinacolborane or (HBpin) is meant 4,4,5,5-tetramethyl-1,3,2-dioxaborolane. The formula of HBpin is depicted below.

(42) ##STR00001##

(43) The organolanthanide catalyst has a formula of (L).sub.xLn-H, wherein L is an ancillary ligand, such as, for example, Cp, Cp*, CGC, Cp, and the like; Ln is a lanthanide element, and preferably selected from a group consisting of Sc, Y, La, Sm, Nd, Yb and Lu; X is an integer, and preferably 1 or 2; and H is hydrogen.

(44) The following abbreviations/structures can be used interchangeably herein:

(45) CGC-Me.sub.2SiCpNCMe.sub.3.

(46) Me-Methyl.

(47) Cp-

(48) ##STR00002##
(C.sub.5Me.sub.4).

(49) Cp*-

(50) ##STR00003##
(C.sub.5Me.sub.5).

(51) By azine ring as provided herein is meant a cyclic organic compound having a ring including one or more nitrogen atoms. Preferably, the cyclic organic compound is six-membered or and contains one or more nitrogen atoms in the ring, such as, for example, pyridine; or the cyclic organic compound is a fused six-membered ring system of two or more rings and contains one or more nitrogen atoms in the ring, such as, for example, quinoline. The azine ring can be unsubstituted or substituted with one or more substituents.

(52) In an embodiment, optimization of reaction parameters, including catalyst concentration, substrate ratio, and reaction temperature, reveal that clean 1,2-regiospecific pyridine hydroboration as well as overall optimal catalytic performance [turnover frequency (TOF), turnover number (TON), and conversion] is achieved, preferably with equimolar quantities of HBpin and pyridine and less than equimolar quantities of catalyst, for example, 1% catalyst 1 at 35 C. in cyclohexane (Table 1, entry 3). Similar reaction efficiency is achieved when the solvent comprises (or consists essentially of) benzene (entry 4). It is noted that excess pyridine is unnecessary to reach high conversions, and no regioisomeric N-boryl-1,4-dihydropyridine is detected during the reaction course, even at 100 C. for 48 hours (Arrowsmith, M. et al., Organometallics 30, 5556-5559 (2011); Oshima, K. et al., J. Am. Chem. Soc. 134, 3699-3702 (2012); and Gountchev, T. I. et al., Organometallics 18, 2896-2905 (1999), all of which are incorporated herein by reference).

(53) TABLE-US-00001 TABLE 1 La-catalyzed 1,2-hydroboration of pyridine with pinacolborane (HBpin)..sup.a Temperature Yield Time Entry ( C.) (%).sup.b (h) TOF (h.sup.1).sup.c 1.sup.d 25 0 48 2 25 90 70 6.6 0.1 3 35 87 11 17.0 0.6 4.sup.e 35 77 7.5 16.5 1.6 5 45 72 5 46.9 1.2 6 55 68 2.5 99.4 2.5 .sup.aReaction conditions: pyridine (0.25 mmol), HBpin (0.25 mmol), [Cp*.sub.2LaH].sub.2 (2.5 10.sup.3 mmol), Ph.sub.3SiMe (5.43 10.sup.2 mmol) in 1.25 mL of C.sub.6D.sub.12. Each entry performed in triplicate. .sup.bBy .sup.1H NMR analysis with Ph.sub.3SiMe as internal standard. .sup.cTurnover frequency, TOF = [product] [catalyst].sup.1 h.sup.1 .sup.dNo La catalyst. .sup.eC.sub.6D.sub.6 as the solvent.

(54) The hydroboration scope is explored with a series of substituted pyridines and related six-membered heterocycles using equimolar HBpin and 1% catalyst 1 at 35 C. (Table 2). It is found that a wide range of azines possessing both strongly electron-donating and -withdrawing groups undergo a highly efficient 1,2-regiospecific hydroboration to afford the corresponding dearomatized products in moderate-to-excellent yields and with moderate-to-high turnover frequencies (TOFs). Both electronic and steric factors are found to exercise significant influence on the hydroboration rates. That steric encumbrance plays a significant role is evidenced by the lack of 1,2-hydroboration activity for 2-substituted pyridines (vide infra) and is consistent with trends for other organolanthanide/actinide- and group-4-catalyzed hydroelementation processes (Reznichenko, A. L. et al., Top. Organomet. Chem. 43, 51-114 (2013), incorporated herein by reference).

(55) A variety of functional groups such as CF.sub.3, OMe, (2S)-1-methyl-2-pyrrolidinyl (nicotine), 1-piperidinyl, phenyl, vinyl, SnMe.sub.3, and Bpin groups, as well as halogens (F, Cl, Br, and I) are all compatible with this organolanthanide-catalyzed process (Table 2), thus offering the possibility of further selective functionalization of the dearomatized products. Halogenated dihydropyridines, especially iodo- and bromo-substituted molecules, are challenging syntheses using the existing precious metal-catalyzed methodologies due to competing C-halogen bond oxidative addition to Rh(I) (see Oshima et al.). Furthermore, the reported Mg(II)-catalyzed dearomatization is incompatible with coordinating substituents (e.g., Me.sub.2N, OMe) (see Arrowsmith et al.). In contrast, these functionalities are completely tolerated under the present catalytic conditions. The hydroboration of 4-substituted pyridines proceeds smoothly to furnish the corresponding dearomatized products in high yields. Reactions with pyridines having electron-withdrawing groups at C4 position exhibit increased initial rates (CF.sub.3>I>H) and require shorter reaction times to reach completion (<1 h), whereas the presence of electron-donating groups leads to falling TOFs in the order: Ph>OMe>Me>NR.sub.2 (Table 2). In addition, catalytic hydroboration of various meta-functionalized pyridines affords N-boryl-3-substituted-1,2-dihydropyridines with good-to-excellent regioselectivities, with the H atom delivered preferentially to the more hindered C2 position. Also, hydroboration of benzofused azines, including quinoline and isoquinoline, proceeds rapidly (<1 h) to afford the corresponding 1,2-dearomatized derivatives in good yields. Finally, the reaction of pyrazine with 1.0 equivalent of HBpin results in selective formation of a N,N-diboryl-1,2,3,4-tetrahydropyrazine along with 0.5 equivalent of unreacted pyrazine, with no mono-hydroboration product observed. When two equivalents of HBpin are used, the reaction proceeds at the same initial rate (TOF) to produce the doubly hydroborated product in 92% yield (Oshima, K. et al. II, Chem. Commun. 48, 8571-8573 (2012), incorporated herein by reference). Furthermore, the La-catalyzed dearomatization is successfully scaled up without significant loss in efficiency as indicated in entry 3 of Table 2 (compound 3c), wherein the 1,2-dearomatized product is isolated by simple filtration in 87% yield.

(56) TABLE-US-00002 TABLE 2 Substrate scope for the La-catalyzed 1,2-hydroboration of the indicated azines..sup.a 3b 3c 3d 0 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 0 3o 3p 3q 3r 3s 3t 3u 3v .sup.aReaction conditions: azine (0.25 mmol), HBpin (0.25 mmol), [Cp*.sub.2LaH].sub.2 (1 mol %, 2.5 10.sup.3 mmol), Ph.sub.3SiMe (Inter. Std.; 5.43 10.sup.2 mmol) in 1.25 mL of C.sub.6D.sub.12 at 35 C. Each entry performed in triplicate. Turnover frequencies (TOF (h.sup.1) = [product] [catalyst].sup.1 h.sup.1) by .sup.1H NMR analysis with PH.sub.3SiMe internal standard. Quantities in brackets are NMR yields and corresponding reaction times. Isomer ratios in brackets refer to ratios of regioisomeric 3- and 5-substituted-1,2- dihydropyridines. .sup.bReaction monitored by 1H NMR and halted immediately after all HBpin consumed to minimize 3 g polymerization. .sup.cPerformed in C.sub.6D.sub.6. .sup.dPerformed at 25 C. .sup.eWith 2.0 equiv. HBpin (0.5 mmol).

(57) A qualitative discussion of the experimental observables and the constraints placed on the various mechanistic scenarios is also provided herein, as well as a quantitative DFT (Discrete Fourier Transform)/Energetic Span analysis. In agreement with related literature (Ringelberg, S. N., Bond activation and catalysis with organolanthanides. Ch. 5 (Dissertation, University Library Groningen, Groningen, 2001, incorporated herein by reference), treating a pale yellow solution of 1 with excess pyridine under catalytically relevant conditions effects a rapid color change to orange and affords a Cp*.sub.2La(NC.sub.5H.sub.6)(Py) complex in which one pyridine is dearomatized via LaH 1,2-addition across the pyridine CN unit as identified by in situ .sup.1H NMR spectroscopy (FIG. 2a, S21-32; eqs. 1 and 2) (in FIG. 2, thermal ellipsoids are drawn at the 50% probability level, and H atoms are omitted for clarity, except for the BH.sub.3 group). Subsequent addition of 1.0 equivalent HBpin yields the dearomatized BN product (equation 3). Mechanistically, these observations suggest rapid, stepwise cleavage of the dimeric LaH precatalyst 1 under catalytic reaction conditions to generate mono- and bis-pyridine adducts which then undergo intramolecular CN insertion to create the bound, dearomatized ligand. Subsequent LaN/HB -bond metathesis, driven by strong BN bond formation (see computational study below) then affords the desired product and regenerates the active catalyst (equation 3). The stoichiometric addition of HBpin to 1 results in rapid formation in near-quantitative yields of the unusual and catalytically inert, colorless zwitterionic product 4, which is characterized by standard analytical techniques and x-ray diffraction (FIG. 2e, eq. 5). This reactivity mode of dialkoxyboranes with organo-f-element complexes has not been documented previously (Mnnig, D. et al., J. Organomet. Chem. 275, 169-171 (1984), incorporated herein by reference).

(58) Detailed .sup.1H NMR spectroscopic kinetic studies at 35 C. indicate that the rate law is first-order in La concentration, first-order in pyridine concentration below 0.2 M, approaching zero-order at higher pyridine concentrations, and approximately inverse first-order in HBpin (equation 6). These results suggest that resting state of

(59) $\begin{array}{cc}\frac{d\left[P\right]}{dt}=k_{\mathrm{obs}}\frac{{{\left[\mathrm{La}\right]}^1\left[\mathrm{pyridine}\right]}^x}{{\left[\mathrm{HBpin}\right]}^1};\mathrm{where}x=0-1& \left(6\right)\end{array}$
the catalyst may be a mononuclear Cp*.sub.2LaH(py).sub.n-related species, with turnover-limiting intramolecular CN insertion, implied by zero-order pyridine kinetics at high [pyridine] (Harrison, K. N. et al., J. Am. Chem. Soc. 114, 9220-9221 (1992); Fu, P.-F. et al., J. Am. Chem. Soc. 117, 7157-7168 (1995); and Obora, Y. et al., J. Am. Chem. Soc. 119, 3745-3755 (1997), all incorporated herein by reference). The inverse order in [HBpin] implies kinetic inhibition competing with the turnover-limiting step (e.g., equation 4), while the irreversible formation of complex 4 represents a deactivation pathway (equation 5) (Sevov, C. S. et al., J. Am. Chem. Soc. 134, 11960-11963 (2012) and Muhoro, C. N. et al., J. Am. Chem. Soc. 121, 5033-5046 (1999), both incorporated herein by reference). In addition, the .sup.1H NMR spectroscopy provides no evidence for pyridine-HBpin reactivity/complexation. Kinetic measurements as a function of temperature (Table 1, entries 2-6) and standard Eyring and Arrhenius kinetic analyses provide the activation parameters, H.sup.=15.7(0.5) kcal/mol, S.sup.=27.2(0.3) cal/mol, and E.sub.a=16.3(0.4) kcal/mol, suggesting an organized transition state (large negative S.sup.) characteristic of many d.sup.0,f.sup.n-centered hydroelementations (Hong, S. et al., Acc. Chem. Res. 37, 673-686 (2004) and Amin, S. B. et al., Angew. Chem. Int. Ed. 47, 2006-2025 (2008), both incorporated herein by reference).

(60) Evaluation of several theoretical approaches identified the M06 DFT functional at 6-31G** level of theory as the best-performing DFT method for the present study. To validate the DFT-predicted mechanisms and guide computational efforts, the Energetic Span model recently developed by Kozuch, Shaik, and Martin is employed (with the aid of AUTOF program) (Kozuch, S., WIREs Comput. Mol. Sci. 2, 795-815 (2012) and Kozuch, S. et al., Acc. Chem. Res. 44, 101-110 (2011), both incorporated herein by reference). Here the experimental rate constant expressed as turnover frequency (TOF) is related to the calculated energy profile by the equations 7 and 8, where E is the energetic span

(61) $\begin{array}{cc}\mathrm{TOF}=\frac{k_{B}T}{h}{e}^{-E/\mathrm{RT}}\frac{\left[\mathrm{Reactants}\right]}{\left[\mathrm{Products}\right]}{|}_{\mathrm{from}\mathrm{TDI}\mathrm{to}\mathrm{TDTS}}& \left(7\right)\\ E=\{\begin{array}{cc}{G}_{\mathrm{TDTS}}-G_{\mathrm{TDI}}& \mathrm{if}\mathrm{TDTS}\mathrm{appears}\mathrm{after}\mathrm{TDI}\left(a\right)\\ G_{\mathrm{TDTS}}-G_{\mathrm{TDI}}+G_r& \mathrm{if}\mathrm{TDTS}\mathrm{appears}\mathrm{before}\mathrm{TDI}\left(b\right)\end{array}& \left(8\right)\end{array}$
representing the Gibbs free energy difference between the TOF-determining transition state (TDTS) and TOF-determining intermediate (TDI), if TDTS appears after TDI in the reaction profile (equation 8a). When TDTS is followed by TDI, the reaction energy (G.sub.r) is added to this difference (equation 8b). The assignments of a transition state as the TDTS and an intermediate as the TDI are made in a way that yields the highest energetic span E values possible for a given reaction profile. Among multiple possible reaction mechanisms, the fastest and thus the most feasible reaction pathway has the smallest energetic span E value. Once the TDI and TDTS are defined, equation 7 can be used to evaluate TOF along with the influence of reactant/product concentrations on the overall reaction rate. The concentration dependence is zero-order for all reactants or products entering or exiting catalytic cycle outside the turnover frequency-determining TDI-TDTS region. Therefore, comparison of predicted TOFs and concentration effects between individual DFT scenarios and against the experimental data provides a straightforward tool for validating the feasibility of a DFT-predicted reaction mechanism.

(62) The active catalyst (see equations 1 and 2 above) and its competitive inhibition with HBpin (equation 4) is identified by combining the [Cp*.sub.2LaH].sub.2 precatalyst 1 with multiple pyridine and/or HBpin molecules. It is found that complex 1 undergoes facile activation.sup.i to yield binuclear complexes V and VI via the pathway depicted in FIG. 3a (Wobser, S. D. et al., Organometallics 32, 1317-1327 (2013), incorporated herein by reference). In FIG. 3, all energies are Gibbs free energies in kcal/mol. The barrier-less first pyridine addition is particularly favored in saturating the Cp*.sub.2La coordination sphere, while the second pyridine coordination is less stabilizing since the bridging hydride in V already saturates the other Cp*.sub.2La-center. Finally, the energy required for adduct VI dissociation to produce monomeric VII is balanced by the entropic gain of the dissociation process. The overall 7.6 kcal/mol energetic barrier for the 1.fwdarw.VII process is in accord with the rapid activation observed experimentally. Next, the feasibility of a VII-HBpin interaction as in equation 5 is investigated. DFT exploration of several possibilities indicates a favorable interaction with G=9.1 kcal/mol to form bidentate adduct VIII (TS1: 8.0 kcal/mol activation barrier). Intrigued by the formation of complex 4 (FIG. 2e, equation 5), possible BO bond activation by adduct VIII is examined. Initial rearrangement yields pinacolate IX while addition of a second HBpin affords very stable, experimentally observed zwitterion 4 (G=15.0 kcal/mol versus VII) via kinetically accessible TS2 (25.6 kcal/mol barrier). Zwitterion 4 formation observed in the stoichiometric experiment of FIG. 2e presumably occurs via a similar pathway wherein the pyridine role is played by the second HBpin molecule. It is seen as proposed that Cp*.sub.2LaH(Py) is the active catalyst for the 1,2-hydroboration reaction and is in equilibrium with inhibition product VIII (equation 4), while zwitterion 4 is the final catalyst deactivation product (equation 5). Therefore, the sequence 1.fwdarw.VII .fwdarw.VIII.fwdarw.>4 corresponds to the catalyst activation, inhibition, and deactivation processes of the dearomatization cycle (FIG. 3a).

(63) The mechanism of the pyridine dearomatization is probed by DFT and Energetic Span techniques. Scenarios considering only Cp*.sub.2LaH(Py).sub.n complexes with n=1 results in energetic profiles with relatively large energetic spans (E>25 kcal/mol), implying very slow processes. In contrast, coordination of a second pyridine to the Cp*.sub.2La center in VII to yield XI is found to be isoergonic and barrier-less, arguing for rapid equilibration between these two structures (FIG. 3b). Furthermore, the calculations indicate that it is the n=2 species XI that is the immediate precursor to the 1,2-dearomatization product in a low-energy span with one pyridine remaining coordinated to Cp*.sub.2La through the entire catalytic cycle (FIG. 3b). As proposed above, starting from XI, the pyridine dearomatization occurs via intramolecular hydride transfer (1,2-addition/CN insertion) to produce a stabilized Cp*.sub.2La-1,2-dihydropyridine intermediate XII (G=2.4 kcal/mol). This dearomatization step proceeds via four-center transition state TS3 in a concerted process (7.8 kcal/mol barrier) (Perrin, L. et al., Inorg Chem, 53, 6261-6373 (2014)). The relatively high TS3 energy is in accord with the experimental sluggishness of equation 2 (vide supra). Subsequent re-coordination of HBpin to XII yields isoenergetic intermediate XIII in which the HBpin BH coordinates to the Cp*.sub.2La-center. Next, XIII undergoes rapid, concerted LaN . . . HB -bond metathesis to form stable product complex XIV (G=8.3 kcal/mol) via four-centered transition state TS4 (1.3 kcal/mol barrier) as above (equation 3). Finally, dissociation of XIV requires G=5.1 kcal/mol to release product 3a and regenerate the active catalyst VII. It is noted that coordination of the second, bystander pyridine significantly lowers the barriers (by >8 kcal/mol) for both the 1,2-addition/CN insertion and the -bond metathesis steps versus analogous processes involving only single-pyridine catalysts (n=1).

(64) In parallel with the productive catalytic cycle (FIG. 3b, right), the off-cycle pathway (FIG. 3b, left) involves the aforementioned HBpin coordination to the active catalyst VII (8.0 kcal/mol free energy barrier) to generate a stable complex VIII (G=9.1 kcal/mol). The barrier for this step at TS1 is comparable to that for the 1,2-addition/CN insertion via TS3. Applying the Energetic Span model to the extended catalytic cycle outlined in FIG. 3b identifies complex VIII as the TDI and two energetically similar transition states TS1 and TS3 as the TDTSs (i.e., TDTS1 and TDTS2, respectively). Thus, the Energy Span E evaluated from the profile in FIG. 3b is 17.0 kcal/mol, and states TDI, TDTS1, and TDTS2 control the overall reaction kinetics via eqs. 7 and 8. Further examination shows that only HBpin exits the catalytic cycle between the TDI and TDTS1, while a pyridine molecule enters the catalytic cycle between TDI and TDTS2. In this way, the pyridine: HBpin concentration ratio dictates the TOF control exerted by TDTS1 (TS1) and TDTS2 (TS3). Specifically, at high pyridine concentrations the reaction rate is determined by TDTS1, with no pyridine entering the cycle in the TOF-determining TDI-TDTS1 zone, and thus the kinetic rate law becomes zero-order in pyridine (see equation 7). In contrast, both TDTS1 (TS1) and TDTS2 (TS3) influence the TOF at lower pyridine concentrations. The fraction of TOF control that is due to TDTS2 increases commensurate with the fall in pyridine concentration. Therefore, the rate law is expected to be first-order in pyridine concentration at low pyridine concentrations, zero-order at higher pyridine concentrations, and inverse first-order in HBpin concentration according to the equation 7, since HBpin is released in the TOF-determining zone. It is noted that these results are in excellent agreement with experiment and fully support the DFT-predicted mechanism. In addition, bond enthalpy estimations (H.sub.r) for the dearomatization reaction predict net exothermicity of 18 kcal/mol, which correlates well with the DFT computed H.sub.r.sup.DFT=17 kcal/mol. From FIG. 3, it is also evident that the overall reaction is driven by the energy released during the -bond metathesis step and strong BN bond formation (XIII.fwdarw.XIV, G=8.3 kcal/mol). Finally, extended Energetic Span calculations of nonstandard Gibbs energies(G.sup.) for the reaction profile in FIG. 3 using the AUTOF program identify reversible and irreversible reaction steps. Specifically, intermediates having virtually identical nonstandard Gibbs energies exist in quasi-equilibrium. Thus, inhibition product VIII, active catalyst VII, and bis-pyridine complex XI are in equilibrium, and the same applies to the pairs of intermediates XII XIII and XIV VII. However, the pyridine dearomatization (XI.fwdarw.XII, G.sup.=8.61 kcal/mol) and the -bond metathesis (XIII.fwdarw.XIV, G.sup.=1.42 kcal/mol) steps are irreversible. In summary, the experimental and DFT mechanistic data are in good agreement and implicate active catalyst generation and 1,2 LaH bond addition to the pyridine CN unsaturation as turnover-limiting (McSkimming, A. et al., Chem. Soc. Rev. 42, 5439-5488 (2013); Diaconescu, P. L., Acc. Chem. Res. 43, 1352-1363 (2010), both incorporated herein by reference).

(65) Kinetic isotope effect (ME) measurements are performed to further probe the above mechanistic proposal. Comparison of the hydroboration reaction rates for pyridine versus pyridine-d.sub.5 in the pseudo-first-order regime yield an inverse secondary KIE k.sub.H/k.sub.D=0.440.04, in accord with TOF-limiting 1,2-addition to the CN functionality (e.g., TDTS2) rather than CH scission. TDI structure VIII is one of the most energetically stable intermediates on the energetic profile, and hypothetically, could selectively be generated when no excesses of both pyridine and HBpin are present. In addition, evaluation of the catalytic species concentrations with the Extended Energetic Span model suggests that VIII represents 95% of all La species involved in the reaction. To test this hypothesis, studies of stoichiometric reactions between La-catalyst 1 and 1.0:1.0 pyridine: HBpin mixtures by in situ .sup.1H NMR spectroscopy reveal disappearance of the LaH and BH signals, displacement of the pyridine and Cp* signals, and emergence of a new multiplet corresponding to a La(-H).sub.2B functionality, consistent with structure VIII. Under these stoichiometric reaction conditions at 10 C., complex VIII undergoes decomposition release of the 1,2-dihydropyridine product. Furthermore, .sup.1H NMR monitoring of the catalytic dearomatization reaction confirms the presence of complex VIII, validating its catalytic relevance. However, attempts to detect complex VIII after sequential additions to La-complex 1 of pyridine and then HBpin or vice versa indicate that the amounts are below the detection limits, further supporting the fidelity of this model. A summary of the proposed reaction mechanism including key findings from the Energetic Span model study is outlined in FIG. 4. Referring to FIG. 4, precatalyst activation, productive catalytic cycle, and off-cycle processes with the most relevant intermediates are depicted. The Energetic Span model affords mechanistic details, explains the observed rate law and reactivity trends, and guides experiments to locate the catalyst resting state and turnover-limiting transition states. In addition, the proposed mechanistic scenario is very different from the oxidative addition/reductive elimination sequence postulated for Rh-catalyzed processes. These differences stem from the appreciable lanthanide electrophilicity, non-dissociable supporting ligation, large ionic radii, resistance to two-electron reductive elimination, and very high kinetic lability (Jantunen, K. C. et al., J. Am. Chem. Soc. 128, 6322-6323 (2006); Edelmann, F T., Coord. Chem. Rev. 261, 73-155 (2014); and Minasian, S. G. et al., Chem. Eur. J. 17, 12234-12245 (2011), all of which are incorporated herein by reference).

(66) The present 3-functionalized pyridine 1,2-hydroboration (Table 2, entries 3k-o, 3q-s) of the invention is regioselective and intriguingly affords dearomatized products in which hydride is preferably delivered to the most hindered position. Similar regioselectivity was observed previously with Rh catalysts, however no explanation is provided. Hence, reactivities of several 3- and 4-substituted pyridines are investigated, as well as the unusual reactivity preference of the former by DFT/Energetic Span methodology. For the 4-substituted pyridines, calculations included iodo-, phenyl-, and trifluoromethyl-substituted pyridines, while entire halogen series (F, Cl, Br, I) is examined for 3-substituted substrates. Computed TOFs are obtained from equation 7 but neglecting the concentrations term and using the energetic span E values from DFT. To simplify the DFT calculations, only TDI and TDTS2 energies (e.g., substituted analogs of TS3 and complex VIII; FIG. 3) are computed, with all other intermediates and transition states omitted. Even with such pragmatic approximations, linear correlations between experimental and computed TOF values are found for the 3- and 4-substituted pyridine series (FIG. 5a). Differences in slope between 3- and 4-substituted series are provisionally attributed to two distinct substituent effects. For the 4-substituted pyridines, the TOF trends track the substituent electron-withdrawing ability (Ph<I<CF.sub.3). For the 3-functionalized substrates, inductive effects alone do not explain the experimental trends. Thus, a Mulliken Orbital Overlap Population (MOOP) analysis of the frontier orbitals (i.e., HOMO) of the TDTS2 structures is carried out to probe possible bonding (e.g., positive MOOP contribution), anti-bonding (negative), and nonbonding (zero) interactions (Glassey, W. V. et al., J. Chem. Phys. 113, 1698-1704 (2000), incorporated herein by reference). A through-bond interaction between the halogen and vicinal CH.sub.2 group is evident for all TS3 (TDTS2) structures that lead to the 3-halo-1,2-dihydropyridine products (FIG. 5b). Furthermore, this interaction falls in the order I>Br>Cl>F, exactly reproducing the experimental TOF trend. Note however that a nonbonding interaction (zero MOOP value) is also located for the TS3 structures leading to the 5-halo-1,2-dihydropyridine regioisomers. That such products are not observed likely reflects the appreciable halogen-emerging CH.sub.2 distances. Thus, these observations argue that halogen-CH.sub.2 bonding interactions in the turnover- and regioselectivity-determining transition states (TS3, TDTS2) strongly influence the regioselectivity of 3-substituted pyridine dearomatization.

EXAMPLES OF THE INVENTION

(67) Materials and Methods. Due to the air and moisture sensitivity of organolanthanide complex 1, all manipulations of air-sensitive materials are carried out with rigorous exclusion of O.sub.2 and moisture in flame- or oven-dried Schlenk-type glassware on either a dual-manifold Schlenk line, interfaced to a high-vacuum manifold (10.sup.6 Torr), or in a N.sub.2-filled MBraun glovebox with a high-capacity recirculator (<1 ppm O.sub.2). Argon (Airgas) is purified by passage through a MnO column to remove O.sub.2 and a column of Davison 4A molecular sieves to remove water immediately before use. Cyclohexane-d.sub.12 (Cambridge Isotope Laboratories, 99+ atom % D) for NMR reactions and kinetic measurements is stored over Na/K alloy in vacuo and vacuum transferred before use. Pyridines are purchased from Sigma-Aldrich, TCI America, or Acros Organics, distilled from CaH.sub.2, and stored under inert atmosphere in a glovebox. Liquid substrates and substrate solutions are degassed by freeze-pump-thaw methods. Solid substrates are purified by sublimation under high vacuum and are stored in a glovebox. Pinacolborane (HBpin) is purchased from TCI America, distilled, and stored at 35 C. in a glovebox. The triphenylmethylsilane internal integration standard for kinetic NMR studies is purchased from Strem, sublimed under high-vacuum, and stored in the glove box. The precatalyst [Cp*.sub.2LaH].sub.2 (1) is prepared as reported in the literature (Jeske, G. et al., J. Am. Chem. Soc. 107, 8091-8103 (1985), incorporated herein by reference). The following compounds are previously reported: 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3a) (see Arrowsmith et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)-1,2-dihydropyridine (3b) (see Oshima et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1,2-dihydropyridine (3d) (see Arrowsmith et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyl-1,2-dihydropyridine (3f) (see Arrowsmith et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-fluoro-1,2-dihydropyridine (3k) (see Oshima et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methyl-1,2-dihydropyridine (3o) (see Arrowsmith et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methoxy-1,2-dihydropyridine (3r) (see Oshima et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroquinoline (3t) (see Arrowsmith et al.), 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroisoquinoline (3u) (see Arrowsmith et al.), 1,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydropyrazine (3v) (see Oshima II).

(68) Physical and Analytical Measurements. NMR spectra are recorded on Agilent HCN600 (DDR2, FT, 500 MHz, .sup.1H; 125 MHz, .sup.13C), Agilent F500 (DDR2, FT, 500 MHz, .sup.1H; 125 MHz, .sup.13C; 160 MHz, .sup.11B, 376 MHz, .sup.19F), Varian UNITYInova-500 (FT, 500 MHz, .sup.1H; 125 MHz, .sup.13C), Agilent Au400 (DDR2, FT, 400 MHz, .sup.1H; 100 MHz, .sup.13C; 128 MHz, .sup.11B), or Bruker Avance III 500 (direct cryoprobe, 500 MHz, .sup.1H; 125, .sup.13C) instruments. Chemical shifts for .sup.1H and .sup.13C spectra are referenced using internal solvent resonances and are reported relative to tetramethylsilane (TMS). BF.sub.3.OEt.sub.2 is used as an external reference for .sup.11B NMR spectra. NMR experiments on air-sensitive samples are conducted in Teflon-valve-sealed sample tubes (J. Young). High-resolution mass spectra (HRMS) are acquired on an Agilent 6210 LC-TOF (ESI, APCI, APPI) mass spectrometer with acetonitrile as the solvent in the positive ion mode.

(69) Procedure for Typical NMR-Scale Catalytic Reactions. In a glove box, 100 L of a solution of the catalyst 1 (C.sub.6D.sub.12, 0.025 M, 2.5 mol) and 150 L of C.sub.6D.sub.12 are added to a J. Young NMR tube. Triphenylmethylsilane (15.0 mg, 54 mol) is weighed out in a 4 mL vial that is then closed with a cap equipped with s septum. Next, 500 L of a solution of pyridine (C.sub.6D.sub.12, 0.5 M, 250 mol) and 500 L of a solution of HBpin (C.sub.6D.sub.12, 0.5 M, 250 mol) are added to the vial, thoroughly mixed, and subsequently transferred to the J. Young NMR tube. The tube is sealed immediately, quickly removed from the glove box, and placed into a dry ice/acetone bath, where it is maintained at 78 C. until just before the NMR experiment. At this point, it is thawed, shaken, and immediately placed in the pre-heated and temperature-calibrated by an ethylene glycol standard (0.3 C.) probe of the NMR spectrometer. Single pulse .sup.1H NMR spectra are taken at regular intervals. Substrate and/or product concentrations are determined relative to the intensity of the internal standard resonance plotted versus time.

(70) Kinetic Analysis. Kinetic analysis of the NMR-scale reactions described above is carried out by collecting multiple (>30) data points early in the reaction before the substrate concentrations are appreciably depleted (Ansyln, E. V. et al., Modern Physical Organic Chemistry. (University Science, 2006); Espenson, J. H., Chemical Kinetics and Reaction Mechanisms. 2nd edn, (McGraw-Hill, Inc, 2002); and Pilling, M. J. & Seakins, P. W. Reaction Kinetics. (Oxford University Press, 1995), all of which are incorporated herein by reference). Under these conditions, the reaction is approximated as pseudo-zero-order with respect to the substrate concentrations. A long pulse delay is used during data acquisition to avoid saturation. The kinetic data are usually obtained from intensity changes in the dearomatized 1,2-dihydropyridine--H integral or the substrate pyridine--H resonance integral over 3 or more half-lives. The product concentration is measured from the area of the dearomatized 1,2-dihydropyridine--H peak, A.sub.s, standardized to A.sub.1, the methyl peak area of the Ph.sub.3SiMe internal standard. Data are fit by least-squares analysis (R.sup.2>0.98) according to equation 9, where t is time and [product] is the concentration of product at time t. The turnover frequency (TOF, h.sup.1) is calculated from the least-squares determined slope (m) according to equation 10 where [catalyst].sub.0 is the initial concentration of the catalyst 1. A 0.025 M stock solution of 1 is prepared in the glove box by dissolving 0.205 g (0.25 mmol) of 1 in 10 mL of C.sub.6D.sub.12. The mixture is stirred until 1 is completely dissolved. The solution is stored in a sealed storage tube at 0 C. prior to use).
[product]=mt(9)

(71) $\begin{array}{cc}\mathrm{TOF}\left(h^{-1}\right)=\frac{m}{{\left[\mathrm{catalyst}\right]}_0}& \left(10\right)\end{array}$

(72) Referring to FIG. 6, FIG. 6a is a plot of [catalyst].sub.0 vs. reaction rate (M/min). FIG. 6b is a van't Hoff plot for reaction rate law order in [catalyst].sub.0. FIG. 6c is a plot of [pyridine] vs. rate (M/min) FIG. 6d is a van't Hoff plot for reaction rate law order in [pyridine]. FIG. 6e is a plot of [HBpin] vs. rate(M/min) FIG. 6f is a van't Hoff plot for reaction rate law order in [HBpin]. 25% [HBpin] point is excluded from the van't Hoff plot due to the very fast reaction (27% conversion after 3 min).

(73) Activation Parameters. Eyring and Arrhenius plots for the reaction between pyridine and HBpin are plotted according to equation 11 and 12 respectively, where k is calculated by the least-square slope (m) according to equation 9. An Erying plot (equation 11) and an Arrhenius plot (equation 12) is provided in FIGS. 7a and 7b, respectively.

(74) $\begin{array}{cc}\ln \left(\frac{k}{T}\right)=-\frac{H^{*}}{\mathrm{RT}}\left[\frac{I^{*}}{R}-\ln \left(\frac{h}{k_b}\right)\right]& \left(11\right)\\ \ln \left(k\right)=-\frac{E_a}{\mathrm{RT}}+\ln A& \left(12\right)\end{array}$
glove box, and stirred at 35 C. for 2 hours in an oil bath. Then, the volatiles are removed in vacuo and the solid redissolved in pentane (15 mL). The solution is then cannula filtered into a pre-weighed Schlenk flask and evaporated, yielding 0.72 g (87% yield) of 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3c) that is pure by .sup.1H NMR (see FIG. 8).

(75) Spectroscopic Characterization of 1,2-Dihydropyridines.

(76) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3a): .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.72 (d, J=7.4 Hz, 1H), 5.79 (m, 1H), 5.10 (m, 1H), 4.17 (d, J=4.1 Hz, 2H), 1.01 (s, 12H) ppm.

(77) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)-1,2-dihydropyridine 3b): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.45 (d, J=7.5 Hz, 1H), 5.53 (s, 1H), 5.04 (d, J=7.5 Hz, 1H), 4.04 (s, 2H), 1.19 (s, 12H) ppm.

(78) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1,2-dihydropyridine (3d): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =7.34-7.03 (m, 5H), 6.50 (d, J=7.3 Hz, 1H), 5.32 (m, 2H), 4.09 (s, 2H), 1.18 (s, 12H) ppm.

(79) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methyl-1,2-dihydropyridine (3f): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.29 (d, J=7.4 Hz, 1H), 4.83 (s, 1H), 4.78 (d, J=7.4 Hz, 1H), 3.89 (s, 2H), 1.59 (s, 3H) 1.18 (s, 12H) ppm.

(80) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-fluoro-1,2-dihydropyridine (3k): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.07 (d, J=7.2 Hz, 1H), 5.23 (dd, J=11.4 Hz, J=6.2 Hz, 1H), 4.69 (d, J=5.9 Hz, 1H), 4.10 (s, 2H), 1.19 (s, 12H).

(81) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methyl-1,2-dihydropyridine (3o): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.17 (d, J=7.4 Hz, 1H), 5.43 (s, 1H), 4.80 (t, J=6.5 Hz, 1H), 3.89 (s, 2H), 1.58 (s, 3H), 1.19 (s, 12H).

(82) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,5-methyl-1,2-dihydropyridine (3p): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.97 (s, 1H), 5.35 (s, 1H), 3.79 (s, 2H), 1.60 (s, 3H), 1.58 (s, 3H), 1.17 (s, 12H) ppm.

(83) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-methoxy-1,2-dihydropyridine (3r): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.02 (d, J=7.2 Hz, 1H), 4.85 (t, J=6.7 Hz, 1H), 4.74 (d, J=6.1 Hz, 1H), 3.91 (s, 1H), 3.73 (s, 2H), 3.46 (s, 3H), 1.18 (s, 12H) ppm.

(84) (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroquinoline (3t): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.92-6.70 (m, 4H), 6.25 (d, J=9.5 Hz, 1H), 5.68 (m, 1H), 4.01 (s, 2H), 1.17 (s, 12H) ppm.

(85) (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroisoquinoline (3u): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.97-6.76 (m, 4H), 6.49 (s, 1H), 5.50 (s, 1H), 4.35 (s, 2H), 1.18 (s, 12H) ppm.

(86) 1,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydropyrazine (3v): .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =5.59 (s, 2H), 3.24 (s, 4H), 1.15 (s, 24H) ppm.

(87) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-iodo-1,2-dihydropyridine (3c). 1H NMR (600 MHz, C.sub.6D.sub.12): =6.18 (d, J=7.5 Hz, 1H), 5.57 (s, 1H), 5.15 (d, J=7.5 Hz, 1H), 3.92 (d, J=4.5 Hz, 2H), 1.18 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): 6=134.1, 122.1, 111.7, 88.9, 83.7, 45.5, 25.0 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): 6=23.2 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.11H.sub.17BINO.sub.2: 333.04. found: 334.134 (M-H.sup.+) (FIG. 9).

(88) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-methoxy-1,2-dihydropyridine (3e). .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.3 (d, J=7.75 Hz, 1H), 4.81 (dd, J.sup.1=7.75 Hz, J.sup.2=1.95 Hz, 1H), 4.02 (s, 3H), 3.38 (s, 3H), 1.18 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): 6=134.7, 109.7, 102.2, 83.3, 82.2, 53.7, 42.8, 25.0 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): 6=23.6 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.12H.sub.20BNO.sub.3: 237.11. found: 238.149 (M-H) (FIG. 10).

(89) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-piperidino-1,2-dihydropyridine (3j). .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.34 (d, J=7.8 Hz, 1H), 4.89 (dd, .sup.1J=7.8 Hz, .sup.2J=2.25 Hz, 1H), 4.14 (q, 1H), 3.93 (d, .sup.1J=4.2 Hz, 2H), 2.70 (m, 4H), 1.54 (m, 4H), 1.68 (s, 2H), 1.17 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.6): =145.6, 132.7, 102.2, 89.2, 82.1, 49.7, 42.1, 26.5, 24.6, 24.1 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.6): =23.5 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.16H.sub.27BN.sub.2O.sub.2 290.22. found: 291.223 (M-H) (FIG. 11).

(90) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridine (3i). .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.74 (d, J=7.3 Hz, 1H), 6.31 (t, J=4.4 Hz, 1H), 5.81 (d, J=7.3 Hz, 1H), 4.16 (d, J=4.4 Hz, 2H), 1.04 (s, 12H), 0.99 (d, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.6): =131.1, 128.8, 128.0, 106.1, 82.9, 82.7, 42.6, 24.5, 24.3 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.6): =28.4, 23.6 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.17H.sub.29B.sub.2NO.sub.4 333.23. found: 334.221 (M-H.sup.+) (FIG. 12).

(91) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-vinyl-1,2-dihydropyridine (3g). .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =. 6.39 (d, J=7.0 Hz, 1H), 6.11 (dd, J=9.2 Hz, J=4.9 Hz, 1H), 5.22 (d, J=7.0 Hz, 1H), 5.1 (m, 2H), 4.85 (d, J=9.2 Hz, 1H), 4.01 (s, 2H), 1.18 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): =150.9, 136.0, 120.7, 117.4, 111.0, 100.2, 83.1, 43.1, 25.3 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): =28.2 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.13H.sub.20BNO.sub.2 233.16. found: 234.144 (M-H.sup.+) (FIG. 13).

(92) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-trimethylstannyl-1,2-dihydropyridine (3h). .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.31 (d, J=7.1 Hz, 1H), 5.29 (t, J=4.2 Hz, 1H), 5.09 (d, J=7.1 Hz, 1H), 3.85 (d, J=4.2 Hz, 2H), 1.19 (s, 12H), 0.10 (s, 9H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): =148.6, 130.4, 122.2, 108.0, 82.2, 42.0, 24.1, 11.2 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): =34.1 ppm. .sup.119Sn NMR (128 MHz, C.sub.6D.sub.12): =32.4 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.14H.sub.26BNO.sub.2Sn, 371.11. found: 372.100 (M-H.sup.+) (FIG. 14).

(93) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-chloro-1,2-dihydropyridine and 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-chloro-1,2-dihydropyridine (3l). 3-chloro-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.24 (d, J=7.3 Hz, 1H), 5.76 (m, 1H), 4.78 (dd, J=7.3 Hz, J=6.1 Hz 1H), 4.11 (d, J=1.4 Hz, 2H), 1.19 (s, 12H) ppm. 5-chloro-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.41 (s, 1H), 5.72 (m, 1H), 5.15 (m, 1H), 3.88 (dd, J=4.3 Hz, J=1.7 Hz 2H), 1.18 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): =150.5, 148.7, 131.2, 130.6, 121.8, 120.7, 116.6, 101.9, 84.3, 84.2, 49.4, 42.7, 25.6, 25.5 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): =23.7 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.11H.sub.17BClNO.sub.2 241.52. found: 242.099 (M-H.sup.+) (FIG. 15).

(94) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-bromo-1,2-dihydropyridine and 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-bromo-1,2-dihydropyridine (3m). 3-bromo-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.30 (d, J=7.26 Hz, 1H), 5.98 (m, 1H), 4.74 (dd, J=7.26 Hz, J=1.4 Hz, 1H), 4.20 (d, J=1.4 Hz, 2H), 1.19 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.6): =132.6, 124.2, 114.9, 103.8, 83.1, 42.5, 24.7. 5-bromo-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.52 (s, 1H), 5.78 (m, 1H), 5.11 (m, 1H), 3.90 (m, 2H), 1.18 (s, 12H). .sup.13C NMR (125 MHz, C.sub.6D.sub.6): =132.7, 131.2, 128.8, 125.4, 116.0, 102.0, 97.3, 83.7, 50.5, 41.8, 25.0 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.6): =23.6 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.11H.sub.17BBrNO.sub.2 285.05. found: 286.11 (M-H.sup.+) (FIG. 16).

(95) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-iodo-1,2-dihydropyridine and 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-iodo-1,2-dihydropyridine (3n). 3-iodo-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.38 (d, J=5.9 Hz, 1H), 6.27 (d, J=7.2 Hz 1H), 4.70 (dd, J=7.2 Hz, J=5.9 Hz 1H), 4.20 (d, J=1.4 Hz, 2H), 1.19 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): =133.0, 131.1, 102.5, 82.8, 78.7, 52.8, 24.1 ppm. 5-iodo-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =6.66 (s, 1H), 5.84 (m, 1H), 5.03 (m, 1H), 3.92 (dd, J=4.3 Hz, J=1.7 Hz, 2H), 1.18 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): =137.5, 131.0, 115.3, 78.7, 62.7, 40.4, 24.0 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): =23.5 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.11H.sub.17BINO.sub.2 333.04. found: 334.0321 (M-H.sup.+) (FIG. 17).

(96) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-phenyl-1,2-dihydropyridine and 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-phenyl-1,2-dihydropyridine (3q). 3-phenyl-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =7.27-7.02 (m, 5H), (m, 5H), 6.43 (d, J=7.2 Hz, 1H), 6.19 (d, J=6.4 Hz, 1H), 5.10 (t, J=7.2 Hz, 1H), 4.35 (d, J=1.1 Hz, 2H), 1.19 (s, 12H) ppm. 5-phenyl-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.12): =7.27-7.02 (m, 5H), 6.68 (s, 1H), 6.24 (m, 1H), 5.31 (m, 1H), 3.99 (m, 2H), 1.19 (s, 12H) ppm. .sup.13C NMR (125 MHz, C.sub.6D.sub.12): =140.5, 132.9, 129.3, 127.3, 125.5, 125.4, 125.3, 121.0, 116.3, 104.6, 84.0, 45.4, 25.7 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): =23.8 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.17H.sub.22BNO.sub.2 283.17. found: 284.166 (M-H.sup.+) (FIG. 18).

(97) 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine and 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine (3s). 3-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.26 (d, J=7.1 Hz, 1H), 5.64 (d, J=4.5 Hz, 1H), 4.89 (t, J=5.2 Hz, 1H), 3.98 (d, J=15.0 Hz, 1H), 3.81 (d, J=15.0 Hz, 1H), 2.99 (t, J=6.35 Hz, 1H), 2.50 (t, J=6.35 Hz, 1H), 2.11 (s, 3H), 2.03 (m, 1H), 1.72 (m, 4H), 1.18 (s, 12H) ppm. 5-[(2S)-1-methyl-2-pyrrolidinyl-1,2-dihydropyridine: .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =6.20 (s, 1H), 5.92 (d, J=9.6 Hz, 1H), 5.19 (m, 1H), 3.21 (m, 1H), 3.08 (m, 1H), remaining protons overlap with the major product. .sup.13C NMR (125 MHz, C.sub.6D.sub.6): =131.8, 128.3, 121.0, 103.2, 83.0, 72.4, 57.3, 42.1, 40.4, 30.8, 25.1, 23.4. .sup.13C NMR (125 MHz, C.sub.6D.sub.6): =129.7, 124.4, 116.5, 115.8, 82.9, 69.7, 57.2, 43.4, 40.2, 32.3, 25.0, 23.0. .sup.11B NMR (128 MHz, C.sub.6D.sub.6): =23.6 ppm. HRMS (LC-TOF, positive mode, CH.sub.2Cl.sub.2/CH.sub.3CN): m/z calcd for C.sub.16H.sub.27BN.sub.2O.sub.2 290.21. found: 291.210 (M-H.sup.+) (FIG. 19).

(98) .sup.1H NMR Spectra of Pyridine and HBpin. FIG. 20 shows the .sup.1H NMR spectra of pyridine, HBpin, and their equimolar mixture in cyclohexane-d.sub.12. It can be seen that no new resonances are formed or shifted at 35 C. in cyclohexane-d.sub.12, indicating that there is no complex formation between pyridine and HBpin, as well as that the dearomatization reaction does not occur in the absence of the catalyst. FIG. 21 shows the expansion ( 8.70-6.80 ppm) of the .sup.1H NMR stack spectra plot of pyridine a), and pyridine+HBpin b) in C.sub.6D.sub.12. FIG. 22 shows the expansion ( 4.50-3.00 ppm) of the .sup.1H NMR stack spectra plot of HBpin a) and pyridine+HBpin b) in C.sub.6D.sub.12.

(99) NMR Monitored Stoichiometric Reaction of [Cp*.sub.2LaH].sub.2 with Pyridine and HBpin. [Cp*.sub.2LaH].sub.2 (1) (3.08 mg, 3.7510.sup.3 mmol) is weighed into J. Young NMR tube, dissolved in 500 L C.sub.6D.sub.12 and frozen at 30 C. Stock solutions of pyridine (98 L, 6.7610.sup.3 mmol) and HBpin (98 L, 6.7610.sup.3 mmol) are mixed together in a small septum-capped vial and then quickly transferred to the frozen solution of 1. The tube is capped immediately and frozen at 78 C. Then, it is slowly warmed in a 10 C. ice bath, quickly mixed, and frozen at 78 C. immediately after mixing. The tube is then warmed to 10 C. in a temperature regulated VT NMR machine and the ensuing reaction monitored by .sup.1H NMR.

(100) The signals in the .sup.1H NMR spectra of the La-complex 1/pyridine/HBpin mixture are noticeably shifted from those of the starting materials (FIGS. 23 and 24). The pyridine peaks are shifted downfield (FIG. 25), indicating a decrease in the overall electron density on pyridine associated with coordination to the lanthanum center. The HB quartet peak of HBpin is broadened and shifted upfield (FIG. 26), along with the concomitant disappearance of the LaH signal of 1 (FIG. 27). In addition, the integral of new BH peak at 3.4 ppm corresponds to two magnetically equivalent H atoms, suggesting that the hydrides of the former La-complex 1 and HBpin become bridging between B- and La-centers in VIII. The Cp* peaks of the lanthanum catalyst also shift upfield, suggesting an increase in electron density on lanthanum center (FIG. 28). Therefore, the observed .sup.1H NMR shifts support formation of the intermediate VIII. However, this complex is quite labile and undergoes decomposition within 30 minutes at 10 C. releasing the 1,2-hydroboration product 3a.

(101) NMR Observation of Intermediate VIII Under Catalytic Reaction Conditions. At an early stage of the catalytic reaction, it is possible to observe the formation of compound VIII in the .sup.1H NMR spectrum at 1.86 ppm (FIG. 29c). This signal decreases gradually in intensity and a new peak at 1.98 ppm emerges as the reaction progresses (FIG. 29c versus 29d). Considering a parallel increase in concentration of the final product 3a, this latter signal can be assigned to the complex XIV, in which the generated product weakly coordinates to the lanthanum metal center of the active catalyst. Therefore, both VIII and XIV can be considered as the catalyst resting state intermediates at a later stage of the reaction. Expectedly, with further accumulation of the product 3a closer to the end of the reaction, complex 14 becomes the dominant turnover-determining intermediate and the peak at 1.86 ppm (complex VIII) almost completely disappears (FIG. 29e).

(102) NMR Monitored Reaction of [Cp*.sub.2LaH].sub.2 with Pyridine. [Cp*.sub.2LaH].sub.2 (1) (3.08 mg, 3.7510.sup.3 mmol) is weighed into J. Young NMR tube, dissolved in 500 L C.sub.6D.sub.12 and frozen at 30 C. Stock solution of pyridine (98 L, 6.7610.sup.3 mmol) is quickly transferred to the frozen solution of 1. The tube is capped immediately and frozen at 78 C. Then, it is slowly warmed in a 10 C. ice bath, quickly mixed, and frozen at 78 C. immediately after mixing. The tube is then warmed to 25 C. in a temperature regulated VT NMR spectrometer and monitored by .sup.1H NMR.

(103) The signals in the .sup.1H NMR spectra of the La-complex 1/pyridine mixture are noticeably shifted from those of the starting material. The pyridine peaks are shifted downfield (FIG. 31), indicating a decrease in the overall electron density on pyridine associated with coordination to the lanthanum center. However, after addition of an equimolar HBpin stock solution (98 L, 6.7610.sup.3 mmol) no appreciable formation of 1,2-hydroboration product 3a is observed.

(104) Reaction of [Cp*.sub.2LaH].sub.2 with HBpin. Excess Reaction: HBpin (0.352 mL, 2.43.Math.10Y.sup.3 mol) is added to a solution of [Cp*.sub.2LaH].sub.2 (0.2 g, 2.43.Math.10.sup.4 mol) in dry C.sub.6H.sub.12 (20 mL). The resulting colorless solution is stirred for 3 hours at room temperature. The volatiles are next removed in vacuo and the residue is recrystallized from pentane to give bis-pentamethyl-cyclopentadiene-2-boratetrihydrobutoxy-2,3-dimethyl-3-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxy]lanthanum (4) as a white powder (0.155 g, Yield 96%). Colorless crystals of 4 suitable for X-ray studies are obtained from pentane solution at 40 C. Anal. Calcd for C.sub.32H.sub.57B.sub.2LaO.sub.4 (M=666.30): C, 57.63; H, 8.62. Found: C, 57.61; H, 8.60. .sup.1H NMR (500 MHz, C.sub.6D.sub.6): =2.77-2.38 (br m, BH.sub.3, 3H), 2.18 (s, Cp*, 30H), 1.30 (s, 2Me, 6H), 1.25 (s, 2Me, 6H), 1.02 (s, Bpin, 12H) ppm. .sup.13C NMR (126 MHz, C.sub.6D.sub.6): =120.30, 89.35, 84.84, 81.91, 25.06, 24.64, 23.22, 12.43 ppm. .sup.11B NMR (128 MHz, C.sub.6D.sub.12): =22.3 (OBpin), 14.4 (OBH.sub.3.sup.) ppm.

(105) Stoichiometric Reaction: HBpin (0.070 mL, 4.86.Math.10.sup.4 mol) is added to a solution of [Cp*.sub.2LaH].sub.2 (0.2 g, 2.43.Math.10.sup.4 mol) in dry C.sub.6H.sub.12 (20 mL). The resulting colorless solution is stirred for 3 hours at room temperature. The solid, corresponding to complex 4, is collected by filtration, washed with cyclohexane, and dried under vacuum. The volatiles are next removed in vacuo and the residue is analyzed by .sup.1H NMR, which confirm the presence of unreacted starting material [Cp*.sub.2LaH].sub.2 and unknown compound (FIG. 35).

(106) Attempted catalytic hydroboration of 4-iodopyridine using [RhCl(cod)].sub.2/PCy.sub.3. In the glovebox, [RhCl(cod)].sub.2 (1.0 mg, 2 mol), PCy.sub.3 ligand (1.12 mg, 4 mol), and triphenylmethylsilane (54.9 mg, 0.2 mmol) are weighed into a screw-capped vial. Then, 1.5 mL of C.sub.6D.sub.6, 4-iodopyridine (410.0 mg, 2 mmol), and HBpin (26.0 mg, 0.2 mmol) are added to the vial. The resulting mixture is sealed, removed from the glove box, and stirred at 50 C. After about 1 hour, the colorless solution turned green and a black precipitate formed. After 24 hours, the mixture is analyzed by .sup.1H NMR and no conversion is detected (FIG. 36).

(107) In contrast, when pyridine is used under the same reaction conditions ([RhCl(cod)].sub.2 (1.0 mg, 2 mol), PCy.sub.3 ligand (1.12 mg, 4 mol), triphenylmethylsilane (54.9 mg, 0.2 mmol), pyridine (158.0 mg, 2 mmol), HBpin (26.0 mg, 0.2 mmol), in 0.2 mL of C.sub.6D.sub.6), complete conversion is observed after 16 hours at 50 C. (FIG. 37).

(108) X-ray Data Collection, Structure Solution, and Refinement.

(109) Single crystals of C.sub.32H.sub.57B.sub.2LaO.sub.4 (4) are recrystallized from pentane, mounted in inert oil, and transferred to the cold gas stream of a Bruker Kappa APEX CCD area detector equipped with a MoKa sealed tube with graphite. Crystallographic and experimental details of the structure are determined. The crystal is maintained at 100.01 K during data collection. An empirical correction for absorption is made (Sheldrick, G. M. SADABS; Bruker Analytical X-ray Systems, Madison, Wis., 2008). wR2(int) is 0.0656 before and 0.0543 after correction. The ratio of minimum to maximum transmission is 0.8993. The /2 correction factor is 0.0015. Using Olex2 (Dolomanov, O. V. et al., J. Appl. Crystallogr. 42, 339-341 (2009), incorporated herein by reference), the structure is solved with the XS (Sheldrick, G. M., Acta Crystallogr. A 64, 112-122 (2008), incorporated by reference) structure solution program using Patterson Method and refined with the ShelXL refinement package (SHELXTL PC: An Integrated System for Solving, Refining, and Displaying Crystal Structures from Diffraction Data v. Version 6.014 (Bruker AXS, Madison, Wis., 2000) using full-matrix least-squares procedures (based on F.sub.o.sup.2) first with isotropic thermal parameters and then with anisotropic thermal parameters in the last cycles of refinement for all non-hydrogen atoms. All hydrogen atoms are located from the residual electron density and freely refined. CCDC 996116 contains the supplementary crystallographic data. These data is obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data request/cif.

(110) Computational Details. Geometry optimizations of all reactants, products, intermediates and transition states are carried out along the entire catalytic cycle. Calculations are performed adopting the M06 hybrid meta-GGA functional. The effective core potential of Hay and Wadt (LANL2DZ) and the relative basis set were used for the lanthanum and iodine atoms (Yang, S. H. et al., Organometallics 25, 1144-1150 (2006); Yang, S. H. et al., Macromolecules 37, 5741-5751 (2004), both incorporated herein by reference). The standard all-electron 6-31G** basis is used for all remaining atoms (Rassolov, V. A. et al., J. Chem. Phys. 109, 1223-1229 (1998), incorporated herein by reference). Molecular geometry optimization of stationary points is carried out without symmetry constraints and used analytical gradient techniques. The transition states are searched with the distinguished reaction coordinate procedure along the emerging bonds. In particular, the hydride transfer step during the insertion of pyridine into the LaH bond is monitored along the emerging CH bond, the subsequent -bond metathesis step induced by the incoming HBpin molecule is monitored along the emerging NB bond, and the formation of structure VIII is monitored along the emerging BH bond. Frequency analysis is performed to obtain thermochemical information about the reaction pathways at 298 K using the harmonic approximation. All calculations are performed using the G09 code (Gaussian 09, Revision D.01, Frisch, M. J. et al. Gaussian, Inc., Wallingford Conn., 2009) on Linux cluster systems.

(111) The energetic span model is an effective mathematical framework that allows a straightforward interpretation and global kinetic evaluation of computationally predicted catalytic reaction mechanisms (Kozuch, S. et al., Acc. Chem. Res. 44, 101-110 (2010)). According to this model, the experimental rate constant presented as turnover frequency (TOF) is related to the calculated energy profile by the equations 7 and 8 as depicted above, where E is the energetic span that represents the Gibbs free energy difference between the turnover frequency-determining transition state (TDTS) and turnover frequency-determining intermediate (TDI), if the TDTS appears after the TDI in a reaction profile (equation 14a). When TDTS is followed by TDI, the reaction energy (G.sub.r) is added to this difference (equation 14b). The assignments of a transition state as the TDTS and an intermediate as the TDI are made in a way that these transition state(s) and intermediate(s) yield the highest energetic span E values possible for a given reaction profile (see Kozuch). Following the strategy outlined above, all of the DFT-computed mechanisms for the present transformations are evaluated using the energetic span methodology with regard to TOFs and reactant concentration effects.

(112) E and G Profiles and E, H, G of the Processes in FIG. 3. Referring to FIG. 38, a) is an energetic profile for transformations of the precatalyst 1 in the presence of pyridine and HBpin reactants: active catalyst generation, inhibition, and deactivation, while b) is an energetic profile of the catalytic cycle for the La-catalyzed pyridine dearomatization along with the off-cycle active catalyst inhibition process. In FIG. 38, all energies are in kcal/mol.

(113) For the conversion of active catalyst VII into dipyridine adduct XI, coordination of the second pyridine is highly stabilizing in terms of potential energy (E=15.9 kcal/mol), however entropic factors related to the bimolecular association increase the Gibbs free energy. The stabilizing interaction between XII and HBpin to give XIII is confirmed by the elongation of the BH bond compared to the free HBpin (=0.013 ). The entropic factors again neutralize the coordination energy gain (E=15.1 kcal/mol).

(114) TABLE-US-00003 TABLE 5 Potential energy (E), enthalpy (H) and Gibbs free energy (G) values (kcal/mol) for the pyridine dearomatization catalytic cycle in FIGS. 3 and 41. E, H, G, Species kcal/mol kcal/mol kcal/mol VIII 29.7 25.7 9.1 TS1 10.8 9.0 8.0 VII 0.0 0.0 0.0 XI 15.9 13.7 0.6 TS3 9.8 8.4 7.8 XII 21.8 17.1 1.8 XIII 36.9 30.6 2.3 TS4 35.7 30.1 1.0 XIV 48.9 42.1 10.6 VII 19.3 17.0 5.5

(115) TDI/TDTS Energy Values for the Dearomatization of Substituted Pyridines

(116) TABLE-US-00004 TABLE 6 Free energy values of the TDI and TDTS2 states for the dearomatization/hydroboration reaction of substituted pyridines. G VIII (TDI), G TS3 (TDTS2), E, Substrate kcal/mol kcal/mol kcal/mol pyridine (2a) 9.1 7.8 16.9 4-substituted 4-CF.sub.3-pyridine (2b) 10.1 4.4 14.5 4-Ph-pyridine (2d) 11.7 5.2 16.9 4-I-pyridine (2c) 9.0 5.7 14.7 3-substituted 3-F-pyridine (2k) 7.8 7.5 15.3 3-Cl-pyridine (2l) 12.1 2.6 14.7 3-Br-pyridine (2m) 10.5 4.4 14.9 3-I-pyridine (2n) 10.9 3.3 14.2

(117) It is noted that the accurate calculation of absolute TOF values is difficult, since even a small inaccuracy in TDTS/TDI energies leads to an exponential error in TOF estimations. However, because of error compensation, relative TOF values for a series of analogous substrates can be quantitatively useful.

(118) Cartesian Coordinates for all Computed Structures. Cartesian coordinates for all computed structures as provided herein is found in FIG. 39.

(119) Thermochemistry Estimations of the La-Catalyzed Pyridine Hydroboration Reaction

(120) TABLE-US-00005 TABLE 7 Thermochemistry analysis of the La-catalyzed pyridine 1,2-hydroboration reaction.* Bonds Breaking Bonds Forming Step 1 HLaPyridine.sup.b 9.1 kcal/mol H.sub.Coordination = 9.1 kcal/mol Step 2 LaH.sup.a 54.2 kcal/mol LaN(CH.sub.2)CHCH.sup.a 45.0 kcal/mol CHCNCH (C sp.sup.2) 153.0 kcal/mol CH.sub.2CN(La)C (C sp.sup.3) 68.0 kcal/mol CCNCH(H) 80.0 kcal/mol H.sub.Insertion = (54.2 +153.0) (45.0 + 68.0 + 80) + 14.2 kcal/mol Step 3 LaN(CH.sub.2)CHCH.sup.a 45.0 kcal/mol LaH.sup.a 54.2 kcal/mol RO.sub.2BH 78.9 kcal/mol RO.sub.2BNCH.sub.2 92.7 kcal/mol H.sub.Protonolysis = (45.0 + 78.9) (54.2 + 92.7) 23.9 kcal/mol .sup.aWith Ln/An adjustments. .sup.bEstimated from the sum of Ln-phenyl and Ln-thf coordination bond disruption enthalpies. *H. Y. Afeefy, J. F. Liebman, and S. E. Stein, Neutral Thermochemical Data in NIST Chemistry WebBook, NIST Standard Reference Database Number 69, Eds. P. J. Linstrom and W. G. Mallard, National Institute of Standards and Technology, Gaithersburg MD, 20899, http://webbook.nist.gov, (retrieved Jun. 4, 2014); Wobser, S. D. et al., Organometallics 32, 1317-1327 (2013); Blanksby, S. J., Acc. Chem Res 36, 255-263 (2003); Marks, T. J. Bonding Energetics in Organometallic Compounds. Vol. 428 1-18 (ACS Symposium Series 1990); Nolan, S. P. et al., J. Am. Chem. Soc. 111, 7844-7853 (1989); Griller, D. et al., Theochem.-J. Mol Struc. 40, 125-131 (1988); Bruno, J. W. et al., J. Am. Chem. Soc. 108, 7275-7280 (1986); Bruno, J. W. et al., J. Am. Chem. Soc. 105, 6824-6832 (1983); and Mcmillen, D. F. & Golden, D. M. Hydrocarbon Bond-Dissociation Energies. Annu. Rev. Phys. Chem. 33, 493-352 (1982), all incorporated herein by reference.

CONCLUSIONS

(121) N-boryl-1,2-dihydroazine products 3 are highly air- and moisture-sensitive and decompose rapidly when exposed to the conditions describe above. Hydroboration of pyridine with HBpin catalyzed by [RhCl(cod)].sub.2/phosphine ligand provides mixtures of 1,2- and 1,4-dihydropyridine, and the regioselectivity is ligand-dependent. The magnesium-catalyzed hydroboration generally proceeds with lower degrees of selectivity often favoring the formation of 1,4-isomeric products. Under the conditions in Table 2, the reaction is not compatible with substrates bearing acidic (i.e., CO.sub.2H, OH) and highly electrophilic CHO groups, most likely due to catalyst decomposition. The dearomatization reactions of 3-bromopyridine (2m) at 10 or 60 C. do not exhibit appreciable differences in isomer ratios 3m:3m relative to that performed at 35 C.

(122) In conclusion, a highly efficient 1,2-regioselective dearomatization of a diverse set of azines with pinacolborane using an earth-abundant organolanthanide catalyst is provided. The process employs equimolar amounts of reagents, displays good functional group compatibility, and enables the regiospecific preparation of a wide range of 1,2-dihydropyridines. The dearomatized products are prominent motifs in many naturally occurring and pharmacologically active compounds and serve as useful intermediates in the synthesis of valuable nitrogen-containing molecules. Particularly noteworthy is the ability of the present catalytic system to address shortcomings of existing pyridine dearomatization methods, especially the reliance on precious transition metal catalysts. Mechanistic studies reveal an experimental rate law with a variable dependence on pyridine concentration and an unusual inverse first-order dependence on pinacolborane concentration. DFT calculations with an Energetic Span evaluation suggest a turnover-determining Cp*.sub.2LaH(pyridine)(pinacolborane) resting state and identify two turnover-determining transition statesdissociation of pinacolborane from the Cp*.sub.2LaH(pyridine) active catalyst and 1,2-addition of the LaH bond to the pyridine CN unsaturation. These results are in excellent agreement with the experimental kinetics and reactivity trends, and are further supported by in situ stoichiometric spectroscopic experiments.