Oxalic amide ligands, and uses thereof in copper-catalyzed coupling reaction of aryl halides

Abstract

The present invention provides oxalic amide ligands and uses thereof in copper-catalyzed coupling reaction of aryl halides. Specifically, the present invention provides a use of a compound represented by formula I, wherein definitions of each group are described in the specification. The compound represented by formula I can be used as a ligand in copper-catalyzed coupling reaction of aryl halides for the formation of CN, CO and CS bonds. ##STR00001##

Claims

1. A method of a coupling reaction of an aryl halide, comprising performing the coupling reaction in the presence of copper as a catalyst, and a ligand of following of formula (I): ##STR00502## wherein R is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure; R.sub.a is (a) OR; wherein R is substituted or unsubstituted C1-C6 alkyl; or (b) N(R).sub.2; wherein each R is independently selected from the group consisting of H, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group is a monocyclic, polycyclic, spiro or bridged ring structure; R.sub.b is selected from the group consisting of H, and C1-C6 alkyl; or R.sub.b and R, together with adjacent nitrogen atom, form a substituted or unsubstituted 3- to 20-membered heteroaryl, or substituted or unsubstituted 3- to 20-membered heterocyclic group; the term substituted means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl-alkoxy (alkyl-OOC), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl/aryl-NHC(O)), COOH, nitro, cyano, hydroxy, amino, and amino substituted by one or two C1-C6 alkyl; and wherein the aryl halide is selected from the group consisting of aryl chloride, aryl bromide, aryl iodide, and a combination thereof.

2. The method of claim 1, wherein R is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzyl, substituted or unsubstituted quinolinyl, substituted or unsubstituted ##STR00503## substituted or unsubstituted adamantyl, substituted or unsubstituted C1-C6 alkyl, and substituted or unsubstituted ##STR00504## or R and R.sub.b, together with adjacent nitrogen atom, form a substituted or unsubstituted group selected from the group consisting of ##STR00505##

3. The method of claim 1, wherein R is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzyl, C1-C4alkyl, pyridyl, and adamantyl; R.sub.a is (a) OR; wherein R is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl; or (b) N(R).sub.2; wherein each R is independently selected from the group consisting of H, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure.

4. The method of claim 1, wherein, in the coupling reaction, the molar ratio of the ligand to the aryl halide is 1-50:100; and/or the molar ratio of the ligand to the copper catalyst is 1-5:1.

5. The method of claim 1, wherein the coupling reaction is characterized as: ##STR00506## in which ##STR00507## is reacted with a coupling reagent in an inert solvent to produce a compound of ##STR00508## wherein X is selected from the group consisting of N, O, and S; Y is selected from the group consisting of Cl, Br, and I; ##STR00509## is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, amino unsubstituted or substituted by one or two C1-C6 alkyl or C2-C10 acyl (alkyl-CO), hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, 3- to 20-membered heteroaryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acyl-alkoxy (alkyl-OOC), C2-C10 acylamino (alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido; wherein two hydrogen atoms on two adjacent carbon atoms of the aryl is substituted by (CH.sub.2).sub.n (n is 1, 2, 3, 4, 5 or 6); the coupling reagent is selected from the group consisting of ammonium hydroxide, ammonia, ammonium salts (preferably ammonium chloride, ammonium carbonate, ammonium sulfate, ammonium hydrogenphosphate, or the combinations thereof)/hydroxide solution (preferably potassium hydroxide solution), (having 2 to 19 carbon atoms and may be a saturated, partially unsaturated or aromatic ring), R.sub.cC(O)NHR.sub.2, R.sub.1SO.sub.2M (preferably, M is sodium, potassium), sodium azide, NHR.sub.1R.sub.2, R.sub.1OH, R.sub.1SH, and hydroxide (preferably lithium hydroxide, or a mixture of potassium phosphate, potassium carbonate, cesium carbonate and water); each of R.sub.1, R.sub.2, and R.sub.c is independently selected from the group consisting of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkenyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, substituted or unsubstituted C1-C5 alkyl-C3-C20 cycloalkyl, substituted or unsubstituted 3- to 20-membered heterocyclic group, and substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heterocyclic group; or R.sub.1 and R.sub.2, together with adjacent nitrogen atom, form a substituted or unsubstituted 3- to 20-membered heterocyclic group, or substituted or unsubstituted 3- to 20-membered heteroaryl; or R.sub.c and R.sub.2, together with adjacent C(O)NH, form a substituted or unsubstituted 3- to 20-membered heterocyclic group, or substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O, and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure; the term substituted means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, cyano, oxo (i.e. two hydrogen atoms on the same carbon atom of the group are substituted by O), C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl-alkoxy (alkyl-OOC), C2-C10 acyl (alkyl-CO), C2-C10 acylamino (alkyl/aryl-NHC(O)), COOH, nitro, hydroxy, amino, amino substituted by one or two C1-C6 alkyl, and C1-C6 alkyl-S.

6. The method of claim 1, wherein the coupling reaction is performed at a temperature of 50-180 C.

7. The method of claim 1 wherein the coupling reaction includes a following reaction (1), (2), (3), (4), (5), (6), (7) or (8): (1) carrying out a reaction of ##STR00510## with NHR.sub.1R.sub.2 in an inert solvent to produce ##STR00511## (2) carrying out a reaction of ##STR00512## with ammonia source in an inert solvent to produce ##STR00513## and wherein the ammonia source is selected from the group consisting of ammonia, ammonium hydroxide, ammonium chloride, ammonium carbonate, ammonium bicarbonate, ammonium sulfate, ammonium nitrate, ammonium phosphate, diammonium hydrogen phosphate, sodium azide, preferably ammonia, ammonium hydroxide, ammonium chloride and diammonium hydrogen phosphate; (3) carrying out a reaction of ##STR00514## with R.sub.1OH in an inert solvent to produce ##STR00515## (4) carrying out a reaction of ##STR00516## with R.sub.1SH in an inert solvent to produce ##STR00517## (5) carrying out a reaction of ##STR00518## with in an inert solvent to produce ##STR00519## wherein is a substituted or unsubstituted 3- to 20-membered ring containing N atom, and the 3- to 20-membered ring is saturated, unsaturated or aromatic; (6) carrying out a reaction of ##STR00520## with ##STR00521## in an inert solvent to produce ##STR00522## wherein R.sub.c is selected from the group consisting of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group is a monocyclic, polycyclic, spiro or bridged ring structure; or R.sub.c and R.sub.2, together with adjacent C(O)NH, form a substituted or unsubstituted 3- to 20-membered heterocyclic group, or substituted or unsubstituted 3- to 20-membered heteroaryl; the term substituted means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), and COOH; (7) carrying out a reaction of ##STR00523## with R.sub.1SO.sub.2M in an inert solvent to produce ##STR00524## wherein the definition of each group is described as above; (8) carrying out a reaction of ##STR00525## with hydroxide or OH.sup. hydrolyzed from a base in an inert solvent to produce ##STR00526##

8. The method of claim 4, wherein the molar ratio of the ligand to the aryl halide is 5-20:100.

9. The method of claim 4, wherein the molar ratio of the ligand to the copper catalyst is 1-2:1.

10. The method of claim 6, wherein the coupling reaction is carried out at a temperature ranging from 100-130 C.

11. The method of claim 7, wherein the reaction (1), (2), (3), (4), (5), (6), (7) or (8) is carried out at a temperature ranging from 100-130 C.

12. A catalyst system for an aryl coupling reaction, which comprises: a copper catalyst, a ligand, a base, and an organic solvent; wherein the copper catalyst is selected from the group consisting of CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, Cu(acac).sub.2, and the combinations thereof; and preferably is CuI, Cu.sub.2O, or Cu(acac).sub.2; the base is selected from the group consisting of potassium carbonate, cesium carbonate, potassium phosphate, sodium bicarbonate, potassium bicarbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, tetrabutyl ammonium hydroxide, and/or a hydrate of the base, and the combinations thereof; and preferably is potassium phosphate, cesium carbonate, orlithium hydroxide; the solvent is selected from the group consisting of DMSO, DMF, DMA, NMP, acetonitrile, isopropanol, 1,4-dioxane, tetrahydrofuran, toluene, tert-butanol, and the combinations thereof; and preferably is DMSO and/or DMF and/or DMSO/H.sub.2O; the ligand is of formula (I): ##STR00527## wherein R is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure; R.sub.a is selected from (a) or (b): (a) OR; wherein R is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl; or (b) N(R).sub.2; wherein each R is independently selected from the group consisting of H, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure (preferably, N(R).sub.2 is NHR); R.sub.b is selected from the group consisting of H, and C1-C6 alkyl; or R.sub.b and R, together with adjacent nitrogen atom, form a substituted or unsubstituted 3- to 20-membered heteroaryl, or substituted or unsubstituted 3- to 20-membered heterocyclic group; the term substituted means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl-alkoxy (alkyl-OOC), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl/aryl-NHC(O)), COOH, nitro, hydroxy, amino, and amino substituted by one or two C1-C6 alkyl.

13. A process for preparation of a compound of formula (I): ##STR00528## wherein R is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S: the cycloalkyl or heterocyclic group may be is a monocyclic, polycyclic, spiro or bridged ring structure; R.sub.a is (a) OR; wherein R is selected from the group consisting of Me and Et; or (b) N(R).sub.2; wherein each R is independently selected from the group consisting of H, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S: the cycloalkyl or heterocyclic group is a monocyclic, polycyclic, spiro or bridged ring structure; R.sub.b is selected from the group consisting of H, and C1-C6 alkyl; or R.sub.b and R, together with adjacent nitrogen atom, form a substituted or unsubstituted 3- to 20-membered heteroaryl, or substituted or unsubstituted 3- to 20-membered heterocyclic group; and when R.sub.a is selected from (a) and R is H, R is naphthyl substituted by methyl; the term substituted means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl-alkoxy (alkyl-OOC), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl/aryl-NHC(O)), COOH, nitro, cyano, hydroxy, amino, and amino substituted by one or two C1-C6 alkvl; wherein the process is carried out by a method selected from the group consisting of process (i), process (ii) and process (II); wherein: process (i) comprises a step of: ##STR00529## in which RNHR.sub.b is reacted with ##STR00530## in an inert solvent to produce the compound of formula (I); process (ii) comprises a step of: ##STR00531## in which RNH.sub.2 is reacted with ##STR00532## in an inert solvent to produce the compound of formula (I); and process (II) comprises a step of: ##STR00533## in which RNH.sub.2 is reacted with oxalyl chloride in an inert solvent to produce the compound of formula (I).

Description

DETAIL DESCRIPTION OF THE INVENTION

(1) After a long-term and intensive study, the inventors have provided a class of oxalate (mono, bis) amide ligands suitable for copper-catalyzed coupling reaction of aryl chloride. A suitable catalytic system composed of such ligands and copper reagent, base and solvent can be used for copper-catalyzed coupling reaction of aryl halides, and especially, can effectively promote coupling of copper-catalyzed aryl chloride with various nucleophiles, to generate CN, CO, CS bonds and synthesize many useful small molecules, while such coupling is difficult to occur under the normal condition. Mild reaction conditions and wide reaction scope make this method have good prospect in industrial application.

Terms

(2) As used herein, the term halogen refers to fluorine, chlorine, bromine, or iodine.

(3) The term halo means that one or more hydrogen atoms on a group are substituted by halogen.

(4) The term alkyl refers to a straight or branched alkyl. When alkyl has a precedent carbon atom number limitation (e.g., C1-C6), the alkyl group contains 1-6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or the like.

(5) The term cycloalkyl refers to a saturated or partially saturated monocyclic, bicyclic or tricyclic (fused, bridged or spiro) ring system. The cycloalkyl may have 3 to 20 carbon atoms. When the cycloalkyl has a precedent carbon atom number limitation (e.g., C3-C20), the cycloalkyl contains 3 to 20 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, or the like. The cycloalkyl may be a monocyclic, polycyclic, spiro or bridged ring.

(6) As used herein, the term alkoxy refers to an alkyl (e.g., O-alkyl, wherein alkyl is defined as above) attached through an oxygen atom, such as, but not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, or the like. When the alkoxy has a precedent carbon atom number limitation (e.g., C1-C6), the cycloalkyl contains 1-6 carbon atoms.

(7) The term aryl refers to a monocyclic, bicyclic, or fused aromatic hydrocarbon group, and the aryl may be substituted or unsubstituted. When an aryl has a precedent carbon atom number limitation (e.g., C6-C20), the aryl contains 6-20 carbon atoms. Examples of aryl include but are not limited to, phenyl, biphenyl, naphthyl, or the like (each carbon atom may be optionally substituted).

(8) The term heteroaryl refers to a monocyclic, bicyclic, or fused aromatic group that includes at least one heteroatom selected from N, O, or S. The heteroaryl can be a 3- to 20-membered aromatic ring group which has 1-5 heteroatoms each independently selected from N, O or S. Examples of heteoaryl include, but are not limited to, pyridine, pyrimidine, pyrrole, indazole, indole, furan, benzofuran, thiophene, or the like.

(9) The term heterocyclic group refers to a monocyclic or fused ring, which is a saturated or partially saturated substituent comprising at least one same or different heteroatom selected from N, O or S. The heterocyclic group may be a 3- to 20-membered heterocyclic group having 1 to 5 heteroatoms each independently selected from N, O or S. Examples of the heterocyclic group include, but are not limited to, a nitrogen heterocyclic group, an oxygen heterocyclic group, a sulfur heterocyclic group, a nitrogen and oxygen heterocyclic group and so on.

(10) The term ester group refers to a group having the structure of alkyl-OOO, wherein alkyl is defined as above.

(11) The term acyl refers to a group having the structure of alkyl-CO, wherein alkyl is defined as above.

(12) The term acylamino refers to a group having the structure of alkyl-NHC(O) or aryl-NHC(O), wherein alkyl and aryl are defined above.

(13) Ligand

(14) Unless otherwise specified, the term ligand used herein refers to a ligand used in a copper catalyzed coupling reaction of aryl chloride.

(15) The ligand useful in the present invention has the structure shown in the foregoing formula (I), and the preferred ligand has a structure selected from the following group (each group is defined as above):

(16) The first class of ligand: oxalic monoamide mono-methyl/ethyl ester

(17) ##STR00036##

(18) wherein the definition of each group is described as above, and preferably, R is phenyl, substituted phenyl, naphthyl, pyridyl, benzyl, substituted benzyl, adamantyl etc.

(19) More preferred oxalic monoamide mono-methyl/ethyl ester ligands have the structures as shown in Table 1 below:

(20) TABLE-US-00001 TABLE 1 oxalic monoamide mono-methyl/ethyl ester ligand L-I-1 L-I-2 L-I-3 0 L-I-4 L-I-5 L-I-6 L-I-7 L-I-8 L-I-9 L-I-10 L-I-11 L-I-12 L-I-13 0 L-I-14 L-I-15 L-I-16 L-I-17 L-I-18 L-I-19 L-I-20 L-I-21 L-I-22 L-I-23 0 L-I-24 L-I-25 L-I-26 L-I-27 L-I-28 L-I-29 L-I-30 L-I-31 L-I-32 L-I-33 0 L-I-34 L-I-35 L-I-36 L-I-37 L-I-38 L-I-39

(21) The second class of ligand: Oxalic Diamide

(22) ##STR00076##

(23) wherein the definition of each group is described as above, and preferably, R is phenyl, substituted phenyl, naphthyl, anthryl, benzyl, substituted benzyl, C1-C4 alkyl, pyridyl, adamantyl etc.; and R is phenyl, substituted phenyl, naphthyl, benzyl, substituted benzyl, C1-C4 alkyl, pyridyl, adamantyl etc. (R may be equal to or not equal to R).

(24) More preferred oxalic diamide ligands have the structures as shown in Table 2 below:

(25) TABLE-US-00002 TABLE 2 Oxalic Diamide L-II-1 L-II-2 L-II-3 0 L-II-4 L-II-5 L-II-6 L-II-7 L-II-8 L-II-9 L-II-10 L-II-11 L-II-12 L-II-13 0 L-II-14 L-II-15 L-II-16 L-II-17 L-II-18 L-II-19 L-II-20 L-II-21 L-II-22 L-II-23 00 L-II-24 01 L-II-25 02 L-II-26 03 L-II-27 04 L-II-28 05 L-II-29 06 L-II-30 07 L-II-31 08 L-II-32 09 L-II-33 0 L-II-34 L-II-35 L-II-36 L-II-37 L-II-38 L-II-39 L-II-40 L-II-41 L-II-42 L-II-43 0 L-II-44 L-II-45 L-II-46 L-II-47 L-II-48 L-II-49 L-II-50 L-II-51 L-II-52 L-II-53 0 L-II-54 L-II-55 L-II-56 L-II-57 L-II-58 L-II-59 L-II-60 L-II-61 L-II-62 L-II-63 0 L-II-64 L-II-65 L-II-66 L-II-67 L-II-68 L-II-69 L-II-70 L-II-71 L-II-72 L-II-73 0 L-II-74 L-II-75 L-II-76 L-II-77 L-II-78 L-II-79 L-II-80 L-II-81 L-II-82 L-II-83 0 L-II-84 L-II-85 L-II-86 L-II-87 L-II-88 L-II-89 L-II-90 L-II-91 L-II-92 L-II-93 0 L-II-94 L-II-95 L-II-96 L-II-97 L-II-98 L-II-99

(26) Each of the above ligands can be obtained commercially or can be prepared by the preferred method provided in the present invention.

(27) It should be understood that the coupling reaction of aryl bromide and aryl iodide can occur more easily than that of aryl chloride under the same condition because the bond energies of CBr and CI bonds are lower than that of the CCl bond. Thus, in addition to the coupling reaction of aryl chloride, the above ligands are also applicable to the coupling reactions of aryl bromide and aryl iodide which are conventional in the art.

(28) Copper-Catalyzed Coupling Reaction of Aryl Chloride

(29) The present invention also provides a method for copper catalyzed coupling reaction of aryl chloride, which comprises carrying out the above reactions using a compound of formula (I) as described hereinabove as a ligand.

(30) Generally, due to the high reactivity of aryl iodides and aryl bromides, the corresponding coupling reactions proceed well under the catalysis of transition metals such as palladium, copper and nickel. Aryl chlorides are cheaper and more readily available, and have more application prospects compared with aryl bromides (iodides). However, high energy of CCl bond makes the coupling reaction of aryl chlorides difficult to react under the conventional catalytic conditions of aryl bromides and aryl iodides.

(31) The ligands and reaction conditions can be optimized for different reactants within the scope of the present disclosure so as to choose the most suitable ligand types and reaction conditions (e.g., temperature, solvent, reactant ratio, reaction time, etc.). The above optimization is within the skill of one in the art after reading the disclosure of the present application.

(32) Several of the most preferred copper-catalyzed coupling reactions of aryl chloride are as follows:

(33) 1. Copper-Catalyzed CN Coupling Reaction of Aryl Chloride Promoted by oxalic (Mono, bis) Amide Ligand

(34) In CN coupling reaction, the selection of coupling reagent is not particularly limited, and may be the corresponding primary or secondary amines, or other ammonia sources such as ammonia, ammonium hydroxide or ammonium salt, sodium azide, N-containing heteroaromatic ring, etc. The specific reaction process is as follows:

(35) In cases where the coupling reagent is a primary or secondary amine, the reaction is represented by the formula:

(36) ##STR00176##

(37) wherein the definition of each group is described as above,

(38) ##STR00177##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acylamino (alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(39) R.sub.1, R.sub.2 are each independently selected from the group consisting of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group, or R.sub.1 and R.sub.2 together with the adjacent nitrogen atom to form a 3- to 20-membered ring (such as substituted or unsubstituted pyrrole, indole, azoles, benzoxazole and aromatic heterocycles), or R.sub.1 is R.sub.cC(O), wherein R.sub.c is selected from: H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, or substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure;

(40) the substitution means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acylamino (alkyl-NHC(O), aryl-NHC(O)), and COOH.

(41) In the above reaction process, the copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably CuI.

(42) The ligand is not specifically limited, and may be any one of the above ligands. It preferably is L-I-25, L-I-27, L-II-7, L-II-9, L-II-31, L-II-38, or L-II-64, and most preferably L-II-31, L-II-38 or L-II-64.

(43) The preferred base may be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, preferably potassium phosphate, or cesium carbonate, and most preferably is potassium phosphate.

(44) The solvent may be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably is DMSO, or DMF, and most preferably DMSO.

(45) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(46) In cases where the coupling reagents are other ammonia sources, the reaction is as follows:

(47) ##STR00178##

(48) wherein the definition of each group is described as above,

(49) ##STR00179##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO, aryl-NHC(O)), C2-C10 acylamino (alkyl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(50) the ammonia source is selected from the group consisting of ammonia, ammonium hydroxide, ammonium chloride, ammonium carbonate, ammonium bicarbonate, ammonium sulfate, ammonium nitrate, ammonium phosphate, diammonium hydrogen phosphate, sodium azide, preferably ammonia, ammonium hydroxide, ammonium chloride and diammonium hydrogen phosphate.

(51) the copper catalyst may be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably CuI.

(52) The ligand 1 (Ligand) can be any one of the above, and preferably L-I-27, L-II-9, L-II-38, L-II-64, L-II-71, L-II-72, and most preferably L-II-38 or L-II-71.

(53) The base may be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, or potassium bicarbonate, and preferably cesium carbonate, or potassium phosphate, and most preferably potassium phosphate.

(54) The solvent may be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably DMSO, DMF, and most preferably DMSO.

(55) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(56) In a preferred embodiment of the present invention, the coupling reaction of aryl chloride with the N-containing aromatic heterocycles is represented by the following formula:

(57) ##STR00180##

(58) wherein the definition of each group is described as above,

(59) ##STR00181##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acylamino (alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(60) is a substituted or unsubstituted 3- to 20-membered ring containing nitrogen atoms, the 3- to 20-membered ring can be saturated or unsaturated (preferably selected from the group consisting of pyrrole, indole, azoles, benzoxazole as well as the corresponding aromatic heterocycles with substituents);

(61) In the above reaction process, the copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably Cu.sub.2O.

(62) The ligand is not specifically limited, and may be any one of the above ligands, and preferably L-II-82.

(63) The preferred base may be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, or potassium bicarbonate, and preferably potassium phosphate, cesium carbonate, and most preferably potassium phosphate.

(64) The solvent can be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably DMSO, DMF, and most preferably DMSO.

(65) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(66) In a preferred embodiment of the present invention, the coupling reaction of aryl chloride with amide is represented by the following formula:

(67) ##STR00182##

(68) wherein the definition of each group is described as above,

(69) ##STR00183##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acylamino (alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(70) each of 12, and R.sub.2 is independently selected from the group consisting of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O or S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure;

(71) or R.sub.c and R.sub.2 together with adjacent C(O)NH, form a substituted or unsubstituted C3-C20 cycloalkyl, or substituted or unsubstituted 3- to 20-membered heterocyclic group;

(72) the substitution means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), and COOH.

(73) In the above reaction process, the copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably Cu.sub.2O.

(74) The ligand is not specifically limited, and may be any one of the above ligands, and preferably L-II-83, L-II-90.

(75) The preferred base may be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, or potassium bicarbonate, and preferably potassium phosphate, or cesium carbonate, and most preferably potassium phosphate.

(76) The solvent can be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably DMSO, or DMF, and most preferably DMSO.

(77) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(78) 2. Copper-Catalyzed CO Coupling Reaction of Aryl Chloride Promoted by Oxalic (Mono, Bis) Amide Ligand

(79) ##STR00184##

(80) wherein the definition of each group is described as above,

(81) ##STR00185##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, or substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(82) R.sub.1 is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure;

(83) the substitution means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), COOH, CN, MeS, sulfuryl, and sulfonamido.

(84) The copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably CuI.

(85) The ligand is any one of 1, and preferably L-II-34.

(86) The base can be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, or potassium bicarbonate, and preferably potassium phosphate.

(87) The solvent can be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably DMSO.

(88) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(89) 3. Copper-Catalyzed CS Coupling Reaction of Aryl Chloride Promoted by Oxalic (Mono, Bis) Amide Ligand

(90) ##STR00186##

(91) wherein the definitinn of each group is described as above,

(92) ##STR00187##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino(alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(93) R.sub.1 is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure;

(94) the substitution means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino(alkyl-NHC(O), aryl-NHC(O)), COOH, CN, MeS, sulfuryl, and sulfonamido.

(95) The copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, and Cu(acac).sub.2, and preferably CuI.

(96) The ligand is any one of 1, and preferably L-II-34.

(97) The base can be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, or potassium bicarbonate, and preferably potassium phosphate.

(98) The solvent can be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably DMSO.

(99) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(100) 4. Copper-Catalyzed CS Coupling Reaction of Aryl Chloride Promoted by Oxalic (Mono, Bis) Amide Ligand

(101) ##STR00188##

(102) wherein the definition of each group is described as above,

(103) ##STR00189##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino(alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(104) R.sub.1 is selected from the group consisting of substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted 3- to 20-membered heteroaryl, substituted or unsubstituted C7-C25 alkyl-aryl, substituted or unsubstituted C1-C5 alkyl-3- to 20-membered heteroaryl, substituted or unsubstituted C3-C20 cycloalkyl, and substituted or unsubstituted 3- to 20-membered heterocyclic group; wherein the heteroaryl or heterocyclic group has 1 to 5 heteroatoms selected from the group consisting of N, O and S; the cycloalkyl or heterocyclic group may be a monocyclic, polycyclic, spiro or bridged ring structure;

(105) the substitution means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), COOH, CN, MeS, sulfuryl, and sulfonamido.

(106) The copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably CuI.

(107) The ligand is any one of 1, preferably L-II-3, L-II-37.

(108) The base can be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, or potassium bicarbonate, and preferably potassium phosphate.

(109) The solvent can be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, or 1,4-dioxane, and preferably DMSO.

(110) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(111) 5. Copper-Catalyzed CO Coupling Reaction of Aryl Chloride Promoted by Oxalic (Mono, Bis) Amide Ligand

(112) ##STR00190##

(113) wherein the definition of each group is described as above,

(114) ##STR00191##
is selected from the group consisting of substituted or unsubstituted C6-C20 aryl, and substituted or unsubstituted 3- to 20-membered heteroaryl; wherein the substitution means that one or more hydrogen atoms on the aryl is substituted by a substituent selected from the group consisting of halogen, nitro, cyano, substituted or unsubstituted amino, hydroxy, unsubstituted or halogenated C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-COO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), COOH, hydroxy-C1-C10 alkylene, MeS, sulfuryl, and sulfonamido;

(115) the substitution means that one or more hydrogen atoms on the group is substituted by a substituent selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryl-oxy, C2-C10 ester group (alkyl-OOO), C2-C10 acyl (alkyl-CO), C2-C10 acyl amino (alkyl-NHC(O), aryl-NHC(O)), COOH, CN, MeS, sulfuryl, and sulfonamido.

(116) The copper catalyst can be CuI, CuBr, CuCl, CuTc, Cu(OAc).sub.2, CuSO.sub.4, Cu.sub.2O, CuBr.sub.2, CuCl.sub.2, CuO, CuSCN, CuCN, or Cu(acac).sub.2, and preferably Cu(acac).sub.2.

(117) The ligand is any one of 1, and preferably L-II-65, or L-II-93.

(118) The base can be potassium carbonate, cesium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, lithium hydroxide, sodium hydroxide, tetrabutyl ammonium hydroxide, and/or a hydrate of the base, and preferably lithium hydroxide.

(119) The solvent can be DMSO, DMF, DMA, NMP, acetonitrile, tert-butanol, isopropanol, THF, 1,4-dioxane, tert-butanol, and/or a mixture of one or more of the foregoing solvents and water, preferably DMSO/H.sub.2O.

(120) The reaction temperature is at 50-180 C., and preferably 100-130 C.

(121) Compared with the Prior Art, the Main Advantages of the Present Invention Include:

(122) 1. It provides a class of catalytic systems capable of carrying out copper-catalyzed coupling reaction of aryl chloride with high efficiency. The catalytic system can make the coupling reaction of aryl chloride proceed successfully which is difficult to be carried out in common coupling conditions for aryl bromide and aryl iodide. Further, the coupling reaction has good compatibility with substrates and wide scope of application.

(123) 2. Compared with the coupling reaction method of aryl chloride in the prior art, the method of the present invention uses the copper catalytic system which is of lower cost. Moreover, the ligand has a simple structure, can be easily prepared, has a low catalytic loading, thus making the reaction more economical.

(124) 3. The aryl chlorides used in the catalytic system of the present invention have lower cost and wider sources than other aryl halides, and have good prospect in large-scale application.

(125) The present invention will be further illustrated below with reference to the specific examples. It should be understood that these examples are only to illustrate the invention but not to limit the disclosure of the invention. The experimental methods without specific conditions in the following embodiments are generally carried out according to conventional conditions, or in accordance with the conditions recommended by the manufacturer. Unless indicated otherwise, parts and percentage are calculated by weight.

Example 1. Synthesis of Ligands (L-I-27, L-II-9, L-II-31 as Examples)

(126) Process i:

(127) ##STR00192##

(128) 2,4,6-Trimethoxyaniline (30 mmol) and triethylamine (36 mmol) were dissolved in 150 mL of tetrahydrofuran, and the concentration of 2,4,6-trimethoxyaniline was 0.2 mol/L. The mixture was cooled in an ice-water bath, and stirred. Then oxalyl chloride monomethyl ester (33 mmol) was added dropwise, the system became cloudy and triethylamine hydrochloride was produced. After the addition was completed, ice water bath was removed, and mixture was naturally restored to room temperature, and stirring was continued for 1 to 2 hours until 2,4,6-trimethoxyaniline was completely consumed (monitored by TLC).

(129) Then the reaction mixture was filtered and triethylamine hydrochloride was removed. The filter cake was rinsed with a small amount of tetrahydrofuran (Do not flush with ethyl acetate, otherwise triethylamine hydrochloride will be dissolved). After the filtrate was concentrated, the residue was purified by silica gel chromatography using petroleum ether:ethyl acetate=5:1 as eluent to give a light yellow solid (7.48 g, 93% yield).

(130) Oxalyl chloride monomethyl ester was replaced by oxalyl chloride monoethyl ester when oxalic monoamide monoethyl ester was prepared.

(131) .sup.1H NMR (400 MHz, CDCl.sub.3) 8.12 (s, 1H), 6.16 (s, 2H), 3.94 (s, 3H), 3.81 (s, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.49, 160.64, 156.07, 154.55, 105.72, 91.18, 56.10, 55.66, 53.73; HRMS (ESI) calcd. for C.sub.12H.sub.16NO.sub.6 (M+H).sup.+: 270.0972, Found: 270.0973.

(132) Process ii:

(133) ##STR00193##

(134) The oxalate monomethyl ester (10 mmol) obtained above was dissolved in 10 mL of THF, and the substrate concentration was 1.0 mol/L. 1.3 mL of benzylamine (12 mmol) was then added. The mixture was heated to 70-80 C. and stirred until the raw materials disappeared (monitored by TLC after 1 hr). The heater was removed and the mixture in reaction flask was stood to cool to room temperature in the air, and then frozen in refrigerator. The product was precipitated out as a white solid. Then the mixture was filtered under reduced pressure with filter paper, dried in an infrared oven, and dried with an oil pump to produce a white solid (2.94 g, 86% yield).

(135) Benzylamine was replaced by other aliphatic amines (such as methylamine solution, diethylamine, etc.) to afford other amides.

(136) .sup.1H NMR (400 MHz, CDCl.sub.3) 3.80 (s, 6H), 3.81 (s, 3H), 4.53 (d, J=6.4 Hz, 2H), 6.16 (s, 2H), 7.30-7.38 (m, 5H), 7.79 (br s, 1H), 8.51 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.40, 159.95, 158.24, 156.03, 136.92, 128.80, 128.03, 127.83, 105.69, 90.96, 55.96, 55.53, 43.86; HRMS (ESI) calcd. for C.sub.18H.sub.21N.sub.2O.sub.5 (M+H).sup.+: 345.1445, Found: 345.1444.

(137) Process II:

(138) ##STR00194##

(139) 2-Phenoxyaniline (30 mmol) and triethylamine (31.5 mmol) were dissolved in 100 mL of tetrahydrofuran, and the concentration of 2-phenoxyaniline was 0.3 mol/L. The mixture was cooled in an ice-water bath, and stirred. Then oxalyl chloride (15.8 mmol) was added dropwise. The system turned to turbid and triethylamide hydrochloride was formed. The ice-water bath was then removed and the mixture was warmed to room temperature in the air, and continuously stirred for 2 hours until 2-phenoxyaniline was completely consumed (monitored by TLC). Then the stirring was stopped for post process.

(140) The stirring bar was removed by a magnetic bar, and tetrahydrofuran was removed by evaporation under reduced pressure. 50 mL of distilled water was added to the resultant residue. The solid on the flask wall was scraped off and immersed into distilled water, and stirred to form slurry. Et.sub.3N.HCl was completely dissolved in water while the oxalic diamide was left undissolved. Then the slurry was filtered under reduced pressure, and the solid on filter paper was washed with cold diethyl ether. The residue was removed and dried in an infrared oven, and then dried with an oil pump to afford a white solid (5.45 g, 86% yield).

(141) .sup.1H NMR (400 MHz, CDCl.sub.3) 9.96 (s, 2H), 8.46 (dd, J=8.0, 1.7 Hz, 2H), 7.43-7.30 (m, 4H), 7.22-7.01 (m, 10H), 6.89 (dd, J=8.0, 1.5 Hz, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 157.36, 156.06, 146.73, 129.97, 127.97, 125.40, 124.18, 123.75, 120.49, 119.02, 117.60; HRMS (ESI) calcd. for C.sub.26H.sub.21N.sub.2O.sub.4 (M+H).sup.+: 425.1496, Found: 425.1492.

(142) Synthesis of Other Ligands (New Compounds):

(143) TABLE-US-00003 ligand (new compound) Characterization Data .sup.1H NMR (400 MHz, CDCl.sub.3) 9.17 (s, 1H), 8.33 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.64-7.57 (m, 1H), 7.57-7.51 (m, 1H), 6.84 (d, J = 8.5 Hz, 1H), 4.03 (s, 3H), 4.02 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.94, 154.52, 154.30, 127.90, 127.45, 126.00, 125.80, 123.59, 123.09, 121.20, 120.26, 103.41, 55.85, 54.19; HRMS (ESI) calcd. for C.sub.14H.sub.14NO.sub.4 (M + H).sup.+: 260.0923, found: 260.0917. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.27 (s, 1H), 7.19 (t, J = 8.4 Hz, 1H), 6.57 (d, J = 8.5 Hz, 2H), 3.91 (s, 3H), 3.80 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.20, 155.07, 153.99, 128.45, 112.35, 104.31, 55.97, 53.62: LC-MS (ESI, m/z): 240.1 (M + H).sup.+. .sup.1H NMR (400 MHz, d6-DMSO) 10.51 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.62 (s, 2H), 7.52-7.34 (m, 13H), 3.65 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.73, 155.01, 141.44, 141.02 (2C), 140.00, 139.16 (2C), 129.01 (2C), 128.91 (2C), 128.75 (4C), 128.62 (4C), 127.95 (2C), 127.88 (2C), 127.36 (2C), 53.75: HRMS-ESI: m/z calcd for C.sub.27H.sub.22O.sub.3N (M + H).sup.+: 408.1594, found: 408.1592. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.81 (s, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.54-7.50 (m, 1H), 7.49-7.45 (m, 1H), 7.39 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 2.43 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.27, 154.93, 133.07, 132.55, 129.64, 128.65, 128.15 (2C), 127.85, 126.79, 125.46, 121.73, 53.84. 18.62; HRMS-ESI: m/z calcd for C.sub.14H.sub.14O.sub.3N (M + H).sup.+: 244.0968, found: 244.0968. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.23 (s, 1H), 6.85 (s, 1H), 3.97 (s, 3H), 2.72 (m, 4H), 2.56 (m, 4H), 1.76-1.74 (m, 8H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.53, 154.50, 135.39, 131.40 (4C), 130.10, 53.93, 29.39 (2C), 25.27 (2C), 23.00 (2C), 22.83 (2C); HRMS-ESI: m/z calcd for C.sub.17H.sub.22O.sub.3N (M + H).sup.+: 288.1594, found: 288.1594. 00 .sup.1H NMR (500 MHz, CDCl.sub.3) 1.40 (d, J = 7.5 Hz, 6H), 3.97 (s, 3H), 4.62 (hept, 1H), 6.91-6.70 (m, 2H), 7.07-7.12 (m, 1H), 8.39-8.43 (m, 1H), 9.59 (brs, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.34, 153.18, 146.66, 127.00, 125.13, 120.94, 119.86, 112.84, 71.61, 53.78, 21.99; HRMS-ESI: m/z calcd for C.sub.12H.sub.16NO.sub.4 (M + H).sup.+: 238.1074, found: 238.1079. 01 .sup.1H NMR (400 MHz, CDCl.sub.3) 10.35 (s, 1H), 7.32 (s, 1H), 7.26 (s, 1H), 6.39 (br s, 1H), 3.96 (s, 3H), 2.93-2.90 (m, 3H), 2.24 (s, 3H): .sup.13C NMR (100 MHz, d6-DMSO) 166.24, 160.60, 154.96, 138.21, 134.52, 131.71, 131.58, 130.87, 125.51, 53.27, 26.18, 18.07; HRMS-ESI: m/z calcd for C.sub.12H.sub.14O.sub.4N.sub.2Cl (M + H).sup.+: 285.0637, found: 285.0639. 02 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.51 (m, 2H), 7.38-7.33 (m, 6H), 6.96 (s, 2H), 3.52 (s, 3H): .sup.13C NMR (100 MHz, CDCl.sub.3) 162.46, 161.52, 137.79, 137.23, 135.10, 133.31, 130.93, 129.76, 129.63, 129.42, 129.35, 129.04, 128.71, 128.14, 127.60, 126.93, 52.22: HRMS-ESI: m/z calcd for C.sub.17H.sub.14O.sub.3N (M + H).sup.+: 280.0968, found: 280.0968. 03 .sup.1H NMR (400 MHz, CDCl.sub.3) 4.66 (d, J = 6.0 Hz, 2H), 7.35-7.42 (m, 5H), 7.48-7.58 (m, 4H), 7.92 (br s, 1H), 8.00-8.07 (m, 4H), 8.51 (s, 1H), 9.63 (s, 1H); .sup.13C NMR (100 MHz, d6-DMSO) 160.61, 160.09, 138.75, 131.18, 128.55, 128.38, 127.76, 127.59, 127.01, 126.35, 126.27, 125.59, 123.59, 42.65: HRMS-ESI: m/z calcd for C.sub.23H.sub.19N.sub.2O.sub.2 (M + H).sup.+: 355.1441, found: 355.1446. 04 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.55 (s, 1H), 8.43 (dd, J = 8.2, 0.9 Hz, 1H), 7.88 (s, 1H), 7.56-7.49 (m, 2H), 7.47-7.37 (m, 4H), 7.37- 7.22 (m, 7H), 4.48 (d, J = 6.2 Hz, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 159.75, 157.19, 137.25, 136.66, 133.40, 132.89, 130.37, 129.24, 129.16, 128.81, 128.45, 128.35, 127.88, 127.80, 125.21, 120.24, 43.88; LC-MS (ESI, m/z): 331.0 (M + H).sup.+. 05 .sup.1H NMR (400 MHz, CDCl.sub.3) 1.41 (d, J = 6.0 Hz, 6H), 4.56 (d, J = 6.4 Hz, 2H), 4.62 (hept, 1H), 6.92-6.99 (m, 2H), 7.07-7.12 (m, 1H), 7.30-7.38 (m, 5H), 7.86 (br s, 1H), 8.36 (dd, J = 8.0, 1.6 Hz, 1H), 9.97 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.06, 157.11, 147.12, 136.86, 128.87, 127.90, 127.85. 127.16, 125.07, 120.90, 119.77, 113.04, 71.64, 43.94, 22.11: HRMS-ESI: m/z calcd for C.sub.18H.sub.21N.sub.2O.sub.3 (M + H).sup.+: 313.1547, found: 313.1550. 06 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.91 (s, 1H), 8.43 (dd, J = 7.9, 1.6 Hz, 1H), 7.91 (s, 1H), 7.43-7.26 (m, 7H), 7.19-7.00 (m, 5H), 6.88 (dd, J = 8.0, 1.3 Hz, 1H), 4.53 (d, J = 6.2 Hz, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 159.67, 157.40, 156.07, 146.73, 136.74, 129.94, 128.83, 128.00, 127.89, 127.85, 125.30, 124.13, 123.70, 120.55, 119.00, 117.63, 43.96: LC-MS (ESI, m/z): 347.0 (M + H).sup.+. 07 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.88 (s, 1H), 8.43 (dd, J = 8.0, 1.6 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.43-7.22 (m, 6H), 7.18-6.98 (m, 5H), 6.87 (dd, J = 8.1, 1.4 Hz, 1H), 5.16-4.99 (m, 1H), 1.58 (d, J = 6.9 Hz, 3H): .sup.13C NMR (100 MHz, CDCl.sub.3) 158.83, 157.48, 156.04, 146.70, 141.91, 129.91, 128.80, 128.02, 127.75, 126.14, 125.24, 124.10, 123.67, 120.46, 118.98, 117.58, 49.77, 21.63: LC-MS (ESI, m/z): 383.0 (M + Na).sup.+. 08 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.56 (s, 1H), 8.46 (dd, J = 8.2, 0.7 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.56-7.45 (m, 2H), 7.46-7.20 (m, 10H), 5.06 (dq, J = 14.2, 7.0 Hz, 1H), 1.55 (d, J = 7.0 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.92, 157.35, 141.94, 137.27, 133.46, 132.87, 130.40, 129.24, 129.15, 128.79, 128.45, 128.33, 127.72, 126.11, 125.18, 120.21, 49.64, 21.76: LC-MS (ESI, m/z): 367.0 (M + Na).sup.+. 09 .sup.1H NMR (400 MHz, CDCl.sub.3) 2.94 (d, J = 5.2 Hz, 3H), 3.78 (s, 6H), 3.81 (s, 3H), 6.16 (s, 2H), 7.49 (br s, 1H), 8.48 (s, 1H): .sup.13C NMR (100 MHz, CDCl.sub.3) 160.69, 160.38, 158.36, 156.04, 105.67, 90.94, 55.94, 55.52, 26.21; HRMS (DART) calcd. for C.sub.12H.sub.17N.sub.2O.sub.5 (M + H).sup.+: 269.1132, Found: 269.1131. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (t, J = 6.8 Hz, 3H), 1.28 (t, J = 6.8 Hz, 3H), 3.46 (a, J = 7.2 Hz, 2H), 3.76-3.83 (m, 11H), 6.16 (s, 2H), 8.25 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 162.21, 160.19, 160.09, 155.99, 106.12, 90.93, 55.91, 55.47, 43.31, 41.79, 14.69, 12.54; HRMS-ESI: m/z calcd for C.sub.15H.sub.23N.sub.2O.sub.5 (M + H).sup.+: 311.1601, found: 311.1610. .sup.1H NMR (400 MHz, CDCl.sub.3) 2.94 (d, J = 5.2 Hz, 3H), 6.87-6.90 (m, 1H), 7.03-7.16 (m, 5H), 7.32-7.37 (m, 2H), 7.74 (br s, 1H), 8.41-8.44 (m, 1H), 9.89 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.43, 157.57, 156.16, 146.76, 129.98, 128.11, 125.32, 124.13, 123.75, 120.63, 118.95, 117.80, 26.44; HRMS-ESI: m/z calcd for C.sub.15H.sub.15N.sub.2O.sub.3 (M + H).sup.+: 271.1077, found: 271.1082. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.84 (s, 2H), 7.15 (d, J = 8.2 Hz, 2H), 6.44 (d, J = 2.4 Hz, 2H), 6.42 (d, J = 2.4 Hz, 1H), 6.40 (d, J = 2.4 Hz, 1H), 4.38 (d, J= 6.2 Hz, 4H), 3.82 (s, 6H), 3.79 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.92, 159.66, 158.76, 130.59, 117.72, 104.01, 98.71, 55.54, 55.50, 39.33; HRMS-ESI: m/z calcd for C.sub.20H.sub.25N.sub.2O.sub.6 (M + H).sup.+: 389.1713, found: 389.1707. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.78 (t, J = 6.1 Hz, 2H), 6.50 (s, 4H), 4.42 (d, J = 6.1 Hz, 4H), 3.84 (s, 12H), 3.82 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 159.66, 153.64, 137.82, 132.46, 105.18, 60.98, 56.30, 44.29; HRMS-ESI: m/z calcd for C.sub.22H.sub.29N.sub.2O.sub.8 (M + H).sup.+: 449.1924, found: 449.1915. .sup.1H NMR (400 MHz, CDCl.sub.3) 1.43 (d, J = 6.0 Hz, 12H), 4.63 (hept, 2H), 6.93-7.02 (m, 4H), 7.08-7.14 (m, 2H), 8.42-8.45 (m, 2H), 10.04 (s, 2H): .sup.13C NMR (100 MHz, CDCl.sub.3) 157.46, 147.17, 127.23, 125.13, 120.94, 119.80, 113.12, 71.73, 22.14: HRMS-ESI: m/z calcd for C.sub.20H.sub.25N.sub.2O.sub.4 (M + H).sup.+: 357.1809, found: 357.1813. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.71 (s, 2H), 7.22 (t, J = 8.4 Hz, 2H), 6.61 (d, J = 8.5 Hz, 4H), 3.84 (s, 12H); .sup.13C NMR (100 MHz, CDCl.sub.3) 157.97, 155.18, 128.14, 112.84, 104.29, 56.01; LC-MS (ESI, m/z): 361.0 (M + H).sup.+. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 9.33 (s, 2H), 6.29 (s, 4H), 3.80 (s, 6H), 3.75 (s, 12H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) 159.7, 158.9, 156.3, 106.3, 91.0, 55.7, 55.4; HRMS-ESI: m/z calcd for C.sub.20H.sub.25N.sub.2O.sub.8 (M + H).sup.+: 421.1605, found: 421.1607. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.25 (s, 1H), 7.92 (s, 1H), 7.85-7.82 (m, 2H), 7.78-7.76 (d, J = 8.4 Hz, 1H), 7.54-7.49 (m, 1H), 7.48-7.44 (m, 1H), 7.40-7.33 (m, 6H), 4.60-4.58 (d, J = 6 Hz, 2H), 2.42 (s, 3H): .sup.13C NMR (100 MHz, d6-DMSO) 160.13, 159.69, 138.79, 132.65, 132.25, 130.44, 130.13, 128.64, 128.40 (2C), 127.86, 127.59 (2C), 127.14, 127.04, 126.40, 125.31, 122.91, 42.66, 18.23: HRMS-ESI: m/z calcd for C.sub.20H.sub.19O.sub.2N.sub.2 (M + H).sup.+: 319.1441, found: 319.1440. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.83 (s, 1H), 8.71 (d, J = 9.1 Hz, 1H), 8.29 (dd, J = 9.1, 2.7 Hz, 1H), 8.22 (d, J = 2.7 Hz, 1H), 7.74 (s, 1H), 7.65-7.46 (m, 3H), 7.46-7.38 (m, 2H), 7.38-7.27 (m, 5H), 4.49 (d, J = 6.1 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 158.98, 157.62, 144.04, 139.11, 136.28, 134.93, 133.20, 129.77, 129.50, 128.98, 128.91, 128.09, 127.83, 125.68, 124.12, 119.69, 44.05: HRMS (DART): m/z calcd for C.sub.21H.sub.18O.sub.4N.sub.3 (M + H).sup.+: 376.1292, found: 376.1290. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.50 (s, 1H), 8.37 (dd, J = 8.9, 5.3 Hz, 1H), 8.00 (t, J = 6.1 Hz, 1H), 7.60-7.44 (m, 3H), 7.43-7.22 (m, 7H), 7.15-7.00 (m, 2H), 4.48 (d, J = 6.2 Hz, 2H): .sup.13C NMR (100 MHz, CDCl.sub.3) 159.76, 159.66 (d, J = 245.8 Hz), 157.26, 136.77, 136.36, 135.11 (d, J = 7.5 Hz), 129.67 (d, J = 2.9 Hz), 129.46, 129.03, 128.89, 127.97, 127.86, 122.23 (d, J = 8.2 Hz), 117.17 (d, J = 23.0 Hz), 115.04 (d, J = 22.0 Hz), 43.95; HRMS (ESI): m/z calcd for C.sub.21H.sub.17O.sub.2NaN.sub.2F (M + Na).sup.+: 371.1166, found: 371.1168. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 9.68 (s, 1H), 8.62 (d, J = 8.6 Hz, 1H), 7.75 (s, 1H), 7.66 (dd, J = 8.7, 2.2 Hz, 1H), 7.61-7.54 (m, 3H), 7.53-7.45 (m, 1H), 7.43-7.38 (m, 2H), 7.38-7.27 (m, 4H), 4.48 (d, J = 6.2 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 159.45, 157.63, 136.61, 136.58, 135.98, 133.08, 129.71, 129.21, 129.20, 129.04, 128.17, 127.98, 127.48 (q, J =3.8 Hz), 127.08 (q, J = 32.8 Hz), 125.71 (q, J = 3.7 Hz), 124.05 (q, J = 272.6 Hz), 120.09, 44.14; HRMS (DART): m/z calcd for C.sub.22H.sub.18O.sub.2N.sub.2F.sub.3 (M + H).sup.+: 399.1315, found: 399.1313. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.72 (s, 1H), 8.59-8.57 (d, J = 8.4 Hz, 1H), 8.09-8.07 (dd, J.sub.1 = 1.8 Hz, J.sub.2 = 8.6 Hz, 1H), 8.02-8.01 (d, J = 2 Hz, 1H), 7.78 (s, 1H), 7.58-7.54 (m, 2H), 7.50-7.46 (m, 1H), 7.43-7.41 (m, 2H), 7.36-7.27 (m, 5H), 4.49-4.48 (d, J = 6 Hz, 2H), 2.92 (s, 3H); .sup.13C NMR (100 MHz, d6-DMSO) 165.56, 159.39, 157.84, 138.30, 137.89, 136.50, 133.42, 131.10, 129.44, 129.21 (2C), 128.88 (2C), 128.44, 128.29 (2C), 127.37 (2C), 126.99, 126.11, 121.22, 52.21, 42.72; HRMS-ESI: m/z calcd for C.sub.23H.sub.21O.sub.4N.sub.2 (M + H).sup.+: 389.1496, found: 389.1494. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.46 (s, 1H), 8.30-8.29 (d, J = 6.8 Hz, 1H), 7.81 (s, 1H), 7.53-7.50 (m, 2H), 7.45-7.42 (m, 1H), 7.40-7.38 (m, 1H), 7.35-7.32 (m, 2H), 7.30-7.28 (m, 3H), 7.22-7.20 (d, J = 6.8 Hz, 1H), 7.14 (d, J = 1.2 Hz, 1H), 4.48-4.47 (d, J = 4.8 Hz, 2H), 2.38 (s, 3H); .sup.13C NMR (100 MHz, d6-DMSO) 159.83, 157.88, 138.48, 137.94, 135.09, 134.51, 131.10, 130.81, 128.80 (2C), 128.79 (2C), 128.64, 128.29 (2C), 127.70, 127.36 (2C), 126.96, 122.73,42.63, 20.52; HRMS-ESI: m/z calcd for C.sub.22H.sub.21O.sub.2N.sub.2 (M + H).sup.+: 345.1598, found: 345.1596. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.59 (s, 1H), 8.52 (d, J = 8.5 Hz, 1H), 7.81 (t, J = 6.2 Hz, 1H), 7.69-7.59 (m, 3H), 7.58-7.52 (m, 3H), 7.50-7.41 (m, 5H), 7.39-7.26 (m, 6H), 4.49 (d, J = 6.1 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 159.72, 157.16, 140.09, 138.00, 137.21, 136.61, 133.25, 133.25, 132.68, 129.31, 129.17, 128.97, 128.83, 128.47, 127.91, 127.81, 127.41, 126.97, 126.92, 120.53, 43.91; HRMS (DART): m/z calcd for C.sub.27H.sub.23O.sub.2N.sub.2 (M + H).sup.+: 407.1754, found: 407.1750. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.35 (s, 1H), 8.31-8.29 (d, J = 7.6 Hz, 1H), 7.79 (s, 1H), 7.53-7.50 (m, 2H), 7.46-7.43 (m, 1H), 7.41-7.39 (m, 2H), 7.35-7.32 (m, 2H), 7.31-7.26 (m, 3H), 6.96-6.93 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 7.2 Hz, 1H), 6.87-6.86 (d, J = 2.4 Hz, 1H), 4.48-4.47 (d, J = 4.8 Hz, 2H), 3.83 (s, 3H): .sup.13C NMR (100 MHz, d6-DMSO) 159.88, 158.12, 157.09, 138.51, 138.01, 136.78, 128.73 (2C), 128.65 (2C), 128.27 (2C), 127.74, 127.32 (2C), 126.93, 126.60, 125.27, 115.24, 113.53, 55.37. 42.54; HRMS-ESI: m/z calcd for C.sub.22H.sub.21O.sub.3N.sub.2 (M + H).sup.+: 361.1547. found: 361.1545. .sup.1H NMR (500 MHz, CDCl.sub.3) 9.24 (s, 1H), 8.16 (d, J = 9.1 Hz, 1H), 7.83 (s, 1H), 7.54-7.46 (m, 2H), 7.46-7.37 (m, 3H), 7.36-7.31 (m, 2H), 7.31-7.26 (m, 3H), 6.70 (d, J = 9.2 Hz, 1H), 6.59 (d, J = 3.0 Hz, 1H), 4.47 (d, J = 6.2 Hz, 2H), 3.37 (q, J = 7.1 Hz, 4H), 1.17 (t, J = 7.1 Hz, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 160.34, 156.65, 145.56, 138.58, 136.95, 134.89, 129.25, 129.17, 128.92, 128.19, 127.96, 122.46, 122.28, 113.35, 111.43,44.60, 43.97, 12.74; LC-MS (ESI, m/z): 402.5 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.78 (s, 1H), 7.86 (s, 1H), 7.39-7.32 (m, 5H), 7.82-7.80 (d, J = 8.8 Hz, 2H), 4.55-4.54 (d, J = 6 Hz, 2H), 2.22 (s, 6H); .sup.13C NMR (100 MHz, d6-DMSO) 160.40 (J = 241 Hz, 1C), 159.90, 159.04, 138.70, 137.74 (J = 9 Hz, 2C), 130.46 (J = 2 Hz, 1C), 128.34 (2C), 127.49 (2C), 126.98, 114.02 (J = 22 Hz, 2C), 42.54, 18.05 (2C); HRMS-ESI: m/z calcd for C.sub.17H.sub.18O.sub.2N.sub.2F (M + H).sup.+: 301.1347, found: 301.1347. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.02 (s, 1H), 7.98 (s, 2H), 7.81 (s, 1H), 7.40-7.25 (m, 5H), 4.55 (d, J = 6.1 Hz, 2H), 2.33 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 159.03, 157.68, 146.53, 138.34, 136.68, 136.29, 128.93, 128.10, 127.97, 123.28, 44.11, 18.86: LC-MS (ESI, m/z): 328.0 (M + H).sup.+. .sup.1H NMR (500 MHz, CDCl.sub.3) 8.68 (s, 1H), 7.89 (s, 1H), 7.42-7.29 (m, 5H), 6.46 (s, 2H), 4.55 (d, J = 6.1 Hz, 2H), 2.93 (s, 6H), 2.20 (s, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 160.00, 158.41, 149.99, 136.72, 135.57, 128.83, 128.01, 127.89, 121.59, 112.12, 43.93, 40.60, 18.91; LC-MS (ESI, m/z): 326.0 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.70 (s, 1H), 7.83 (s, 1H), 7.41-7.27 (m, 6H), 6.49 (s, 2H), 4.55 (d, J = 6.1 Hz, 2H), 2.15 (s, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 159.81, 158.66, 155.17, 136.79, 136.72, 129.05, 128.16, 128.15, 125.02, 115.21, 44.16, 18.63; LC-MS (ESI, m/z): 299.4 (M + H).sup.+. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 8.78 (s, 1H), 7.89 (s, 1H), 7.39-7.32 (m, 5H), 7.11 (s, 2H), 4.56-4.54 (d, J = 6 Hz, 2H), 2.23 (s, 6H), 1.30 (s, 9H); .sup.13C NMR (100 MHz, d6-DMSO) 160.09, 158.88, 149.14, 138.76, 134.35 (2C), 131.60, 128.34 (2C), 127.53 (2C), 126.98, 124.63 (2C), 42.56, 34.01, 31.16 (3C), 18.32 (2C); HRMS-ESI: m/z calcd for C.sub.21H.sub.27O.sub.2N.sub.2 (M + H).sup.+: 339.2067, found: 339.2065. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.32 (s, 2H), 7.94-7.92 (d, J = 8.4 Hz, 2H), 7.89-7.87 (d, J = 8.0 Hz, 2H), 7.83-7.81 (d, J = 8.4 Hz, 2H), 7.60-7.56 (m, 2H), 7.52-7.48 (m, 2H), 7.46-7.44 (d, J = 8.4 Hz, 2H), 2.53 (s, 6H); .sup.13C NMR (100 MHz, d6-DMSO) 158.79 (2C), 133.16 (2C), 132.94 (2C), 130.02 (2C), 128.96 (2C), 128.47 (2C), 128.45 (2C), 128.34 (2C), 127.20 (2C), 125.81 (2C), 122.12 (2C), 19.04 (20: HRMS-ESI: m/z calcd for C.sub.24H.sub.21O.sub.2N.sub.2 (M + H).sup.+: 369.1598, found: 369.1597. .sup.1H NMR (400 MHz, CDCl.sub.3) 2.27 (s, 12H), 6.84 (d, J = 8.8 Hz, 4H), 8.77 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 161.62 (d, J = 246.8 Hz), 158.17, 137.42 (d, J = 8.8 Hz), 128.06 (d, J = 3.2 Hz), 114.98 (d, J = 22.1 Hz), 18.60 (d, J = 1.5 Hz); HRMS (DART) calcd. for C.sub.18H.sub.19O.sub.2N.sub.2F.sub.2 (M + H).sup.+: 333.1409, Found: 333.1410. .sup.1H NMR (400 MHz, CDCl.sub.3) 2.34 (s, 12H), 3.92 (s, 6H), 7.82 (s, 4H), 8.92 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 166.63, 157.56, 136.42, 135.10, 129.66, 129.36, 52.21, 18.57: HRMS (DART) calcd. for C.sub.22H.sub.25N.sub.2O.sub.6 (M + H).sup.+: 413.1707, Found: 413.1704. .sup.1H NMR (400 MHz, d6-DMSO) 2.24 (s, 12H), 7.71 (s, 4H), 10.54 (s, 2H), 12.87 (br s, 2H); .sup.13C NMR (100 MHz, d6-DMSO) 167.0, 158.52, 138.44, 135.56, 129.22, 128.74, 18.00; HRMS (DART) calcd. for C.sub.20H.sub.21N.sub.2O.sub.6 (M + H).sup.+: 385.1394, Found: 385.1393. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.94 (s, 2H), 8.03 (s, 4H), 1.59 (s, 12H): LC-MS (ESI, m/z): 387.0 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 1.31 (s, 18H), 2.28 (s, 12H), 7.13 (s, 4H), 8.81 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.27, 150.72, 134.25, 129.72, 125.50, 34.42, 31.36, 18.74; HRMS (DART) calcd. for C.sub.26H.sub.37O.sub.2N.sub.2 (M + H).sup.+: 409.2850, Found: 409.2847. .sup.1H NMR (400 MHz, d6-DMSO) 2.13 (s, 12H), 3.74 (s, 6H), 6.69 (s, 4H), 10.09 (s, 2H); .sup.13C NMR (100 MHz, d6-DMSO) 159.17, 157.68, 136.26, 127.03, 112.87, 55.05, 18.20: HRMS (DART) calcd. for C.sub.20H.sub.25N.sub.2O.sub.4 (M + H).sup.+: 357.1809, Found: 357.1807. .sup.1H NMR (400 MHz, d6-DMSO) 2.06 (s, 12H), 6.50 (s, 4H), 9.25 (s, 2H), 9.96 (s, 2H); .sup.13C NMR (100 MHz, d6-DMSO) 159.25, 155.83, 136.04, 125.49, 114.24, 18.09: HRMS (DART) calcd. for C.sub.18H.sub.21N.sub.2O.sub.4 (M + H).sup.+: 329.1496, Found: 329.1496. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.72 (s, 2H), 6.49 (s, 4H), 2.93 (s, 12H), 2.23 (s, 12H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.80, 149.77, 135.62, 121.99. 112.33, 40.74, 18.89; LC-MS (ESI, m/z): 383.0 (M + H).sup.+. 0 .sup.1H NMR (500 MHz, CDCl.sub.3) 9.73 (s, 2H), 8.63 (d, J = 10 Hz, 2H), 8.30-8.20 (m, 4H), 7.65-7.35 (m, 10H); HRMS (DART) calcd. for C.sub.26H.sub.19N.sub.4O.sub.6 (M + H).sup.+: 483.1299, Found: 483.1295. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.02-7.10 (m, 4H), 7.37-7.40 (m, 4H), 7.46-7.57 (m, 6H), 8.32-8.36 (m, 2H), 9.44 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 159.76 (d, J =246.3 Hz), 157.26, 136.29 (d, J = 1.5 Hz), 135.10 (d, J = 7.8 Hz), 129.55, 129.50 (d, J = 2.9 Hz), 129.08, 129.00, 122.27 (d, J = 8.3 Hz), 117.24 (d, J = 23.1 Hz), 115.11 (d, J = 22.0 Hz); LC-MS (ESI, m/z): 429.3 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.63 (s, 2H), 8.55 (d, J = 8.6 Hz, 2H), 7.66-7.50 (m, 10H), 7.44-7.37 (m, 4H); .sup.13C NMR (125 MHz, CDCl.sub.3) 157.32, 136.25, 135.82, 133.16, 129.77, 129.32, 129.19, 127.51, 126.98 (q, J = 32.6 Hz), 125.69, 123.97 (d, J = 271.4 Hz), 120.19; LC-MS (ESI, m/z): 529.4 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.67 (s, 2H), 8.52-8.50 (d, J = 8.4 Hz, 2H), 8.06-8.03 (dd, J.sub.1 = 2.0 Hz, J.sub.2= 8.4 Hz, 2H), 8.01-8.00 (d, J = 2 Hz, 2H), 7.59-7.54 (m, 4H), 7.53-7.49 (m, 2H), 7.42-7.39 (m, 4H), 3.91 (s, 6H); .sup.13C NMR (100 MHz, d6-DMSO) 166.48 (2C), 157.30 (2C), 137.21 (2C), 136.21 (2C), 132.66 (2C), 131.91 (2C), 130.17 (2C), 129.67 (4C), 129.27 (4C), 129.08 (2C), 126.84 (2C), 119.61 (2C), 52.37 (2C): HRMS-ESI: m/z calcd for C.sub.30H.sub.25O.sub.6N.sub.2 (M + H).sup.+: 509.1707, found: 509.1704. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.47 (s, 2H), 8.25-8.23 (d, J = 8.0 Hz 2H), 7.53-7.50 (m, 4H), 7.46-7.42 (m, 2H), 7.39-7.37 (d, J = 7.6 Hz, 4H), 7.18-7.16 (d, J = 8.4 Hz, 2H), 7.12 (s, 2H), 2.36 (s, 6H); .sup.13C NMR (100 MHz, d6-DMSO) 157.40 (2C), 137.51 (2C), 135.13 (2C), 132.93 (2C), 131.10 (2C), 130.91 (2C), 129.34 (4C), 129.26 (4C), 129.05 (2C), 128.40 (2C), 120.40 (2C), 21.10 (2C); HRMS-ESI: m/z calcd for C.sub.28H.sub.25O.sub.2N.sub.2 (M + H).sup.+: 421.1911, found: 421.1906. .sup.1H NMR (500 MHz, CDCl.sub.3) 9.60 (s, 2H), 8.48 (d, J = 8.5 Hz, 2H), 7.65-7.53 (m, 12H), 7.52-7.40 (m, 10H), 7.38-7.32 (m, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 157.30, 140.07, 138.13, 137.17, 133.25, 132.53, 129.36, 129.20, 128.99, 128.84, 128.53, 127.45, 126.96, 126.94, 120.60; LC-MS (ESI, m/z): 545.3 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.37 (s, 2H), 8.26-8.24 (d, J = 8.8 Hz, 2H), 7.56-7.50 (m, 4H), 7.46-7.43 (m, 2H), 7.40-7.38 (m, 4H), 6.92-6.89 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.8 Hz, 2H), 6.85 (d, J = 3.2 Hz, 2H), 3.82 (s, 6H); .sup.13C NMR (100 MHz, d6-DMSO) 157.31 (2C), 156.90 (2C), 137.38 (2C), 134.69 (2C), 129.37 (4C), 129.18 (4C), 128.58 (2C), 126.73 (2C), 122.14 (2C), 115.82 (2C), 113.57 (2C), 55.68 (2C); HRMS-ESI: m/z calcd for C.sub.28H.sub.25O.sub.4N.sub.2 (M + H).sup.+: 453.1809, found: 453.1805. .sup.1H NMR (500 MHz, CDCl.sub.3) 9.27 (s, 2H), 8.11 (d, J = 9.0 Hz, 2H), 7.64-7.35 (m, 10H), 6.66 (dd, J = 9.0, 3.0 Hz, 2H), 6.57 (d, J = 3.0 Hz, 2H), 3.35 (q, J = 7.0 Hz, 8H), 1.16 (t, J = 7.0 Hz, 12H), .sup.13C NMR (125 MHz, CDCl.sub.3) 157.29, 145.49, 138.63, 134.75, 129.27, 129.16, 128.13, 122.49, 122.40, 113.44, 111.47, 44.59, 12.73. LC-MS (ESI, m/z): 535.3 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 9.53 (s, 2H), 6.97 (d, J = 2.8 Hz, 2H), 6.67 (d, J = 2.4 Hz, 2H), 3.88 (s, 6H), 3.86 (s, 6H), 3.84 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 167.14 (2C), 158.44 (2C), 157.80 (2C), 154.22 (2C), 127.63 (2C), 117.61 (2C), 105.23 (2C), 103.06 (2C), 56.32 (2C), 55.87 (2C), 52.57 (2C); LC-MS (ESI, m/z): 477.5 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.63 (s, 2H), 6.39-6.25 (m, 4H), 3.83 (s, 6H), 3.80 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.12 (J = 12.9 Hz, 2C), 158.48 (J = 247.4 Hz, 2C), 158.05 (2C), 155.71 (J = 7.6 Hz, 2C), 105.46 (J = 15.8 Hz, 2C), 94.97 (J = 2.6 Hz, 2C), 93.73 (J = 24.5 Hz, 2C), 56.21 (2C), 55.87 (2C); LC-MS (ESI, m/z): 397.4 (M + H).sup.+.

(144) The following ligands were prepared according to process II:

(145) TABLE-US-00004 Ligang Structure Characterization Data of Structure 0 .sup.1H NMR (400 MHz, DMSO-d6) 9.27 (t, J = 6.4 Hz, 1H), 6.61 (s, 2H), 4.26 (d, J = 6.4 Hz, 2H), 3.73 (s, 6H), 3.62 (s, 3H),; .sup.13C NMR (101 MHz, DMSO-d6) 160.07, 152.74, 136.48, 134.34, 104.93, 59.98, 55.78, 42.67. ESI-MS m/z 471.3 (M + Na).sup.+; HRMS Calcd. For C.sub.22H.sub.28N.sub.2O.sub.8 (M + Na).sup.+ requires 471.1738; found: 471.1745. .sup.1H NMR (400 MHz, DMSO-d6) 9.25 (t, J = 6.4 Hz, 1H), 6.87-6.80 (m, 2H), 6.74 (dd, J = 8.0, 1.3 Hz, 1H), 5.97 (s, 2H), 4.22 (d, J = 6.5 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 160.01, 147.18, 146.18, 132.60, 120.77, 108.16, 108.00, 100.84, 42.19. ESI-MS m/z 379.2 (M + Na).sup.+; HRMS Calcd. For C.sub.18H.sub.16N.sub.2NaO.sub.6 (M + Na).sup.+ requires 379.0906; found: 379.0901. .sup.1H NMR (400 MHz, DMSO-d6) 9.43 (t, J = 6.4 Hz, 1H), 7.11 (tt, J = 9.4, 2.3 Hz, 1H), 7.05-6.94 (m, 2H), 4.35 (d, J = 6.4 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) (163.60, 163.47, 161.16, 161.02), 160.20, (143.49, 143.40, 143.31), (110.49, 110.43, 110.31, 110.24), (102.64, 102.38, 102.13), 41.78. ESI-MS m/z 339.2 (M H).sup.; HRMS Calcd. For C.sub.16H.sub.11F.sub.4N.sub.2O.sub.2 (MH).sup. requires 339.0762.; found: 339.0767. .sup.1H NMR (400 MHz, DMSO-d6) 9.40 (t, J = 6.1 Hz, 1H), 7.35 (dt, J = 20.3, 10.2 Hz, 2H), 7.12 (s, 1H), 4.31 (d, J = 6.3 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 160.12, (150.47, 150.34, 149.64), (148.03, 147.90, 147.33, 147.21), (136.54, 136.48, 136.45), (124.21, 124.18, 124.15, 124.12), (117.38, 117.21), (116.57, 116.40), 41.52.; ESI-MS m/z 339.1 (M H).sup.; HRMS Calcd. For C.sub.16H.sub.11F.sub.4N.sub.2O.sub.2 (M H).sup. requires 339.0762.; found: 339.0752. .sup.1H NMR (400 MHz, DMSO-d6) 9.22 (t, J = 6.1 Hz, 1H), 7.58-7.53 (m, 1H), 6.38 (dd, J = 3.1, 1.9 Hz, 1H), 6.22 (d, J = 3.2 Hz, 1H), 4.31 (d, J = 6.2 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.86, 151.48, 142.13, 110.50, 107.14, 35.76. ESI-MS m/z 271.1 (M + Na).sup.+; HRMS Calcd. For C.sub.12H.sub.12N.sub.2NaO.sub.4 (M + Na).sup.+ requires 271.0689.; found: 271.0693. .sup.1H NMR (400 MHz, DMSO-d6) 9.42 (t, J = 6.3 Hz, 1H), 7.38 (dd, J = 5.0. 1.3 Hz, 1H), 6.95 (dt, J = 4.9, 2.8 Hz, 2H), 4.47 (d, J = 6.4 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.75, 141.23, 126.66, 125.93, 125.21, 37.37. ESI-MS m/z 302.9 (M + Na).sup.+; HRMS Calcd. For C.sub.12H.sub.12N.sub.2NaO.sub.2S.sub.2 (M + Na).sup.+ requires 303.0232.; found: 303.0233. .sup.1H NMR (400 MHz, DMSO-d6) 10.54 (s, 1H), 8.91 (t, J = 6.1 Hz, 1H), 6.63 (dd, J = 4.2, 2.5 Hz, 1H), 5.89 (dd, J = 5.5, 2.7 Hz, 1H), 5.88-5.84 (m, 1H), 4.27 (d, J = 6.2 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.59, 125.66, 117.23, 107.13, 105.93, 35.72. ESI-MS m/z 269.1 (M + Na).sup.+; HRMS Calcd. For C.sub.12H.sub.14N.sub.4NaO.sub.2 (M + Na).sup.+ requires 269.1009.; found: 269.1002. .sup.1H NMR (400 MHz, DMSO-d6) 9.12 (t, J = 6.1 Hz, 1H), 6.08 (d, J = 2.9 Hz, 1H), 5.96 (d, J = 2.6 Hz, 1H), 4.25 (d, J = 6.2 Hz, 2H), 2.21 (s, 3H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.78, 150.70, 149.64, 108.00, 106.38, 35.77, 13.25. ESI-MS m/z 299.1 (M + Na).sup.+; HRMS Calcd. For C.sub.14H.sub.15N.sub.2O.sub.4 (M + Na).sup.+ requires 275.1037.; found: 275.1032. .sup.1H NMR (400 MHz, DMSO-d6) 9.26 (t, J = 6.3 Hz, 1H), 7.46 (dd, J = 4.9, 3.0 Hz, 1H), 7.28 (d, J = 1.8 Hz, 1H), 7.04 (dd, J = 4.9, 1.0 Hz, 1H), 4.31 (d, J = 6.4 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.95, 139.41, 127.56, 126.28, 122.07, 37.90. ESI-MS m/z 302.9 (M H).sup.; HRMS Calcd. For C.sub.12H.sub.11N.sub.2O.sub.2S.sub.2 (M H).sup. requires 279.0267.; found: 279.0257. .sup.1H NMR (400 MHz, DMSO-d6) 9.00 (t, J = 5.8 Hz, 1H), 6.62 (s, 1H), 5.90 (s, 1H), 5.88-5.84 (m, 1H), 4.27 (d, J = 6.1 Hz, 1H), 3.55 (s, 1H), ESI-MS m/z [M + 1].sup.+ 275.26 0 .sup.1H NMR (400 MHz, DMSO-d6) 9.44 (t, J = 6.0 Hz, 1H), 7.58 (d, J = 7.3 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.30-7.18 (m, 2H), 6.72 (s, 1H), 4.52 (d, J = 6.0 Hz, 2H), ESI-MS m/z 371.1 (M + Na).sup.+; HRMS Calcd. For C.sub.20H.sub.15N.sub.2O.sub.4 (M + Na).sup.+ requires 347.1037.; found: 347.1041. .sup.1H NMR (400 MHz, DMSO-d6) 9.33 (t, J = 6.1 Hz, 1H), 8.54-8.48 (m, 1H), 7.77 (td, J = 7.7, 1.8 Hz, 1H), 7.28 (dd, J = 10.1, 4.9 Hz, 2H), 4.47 (d, J = 6.2 Hz, 2H),; .sup.13C NMR (101 MHz, DMSO-d6) 160.14, 157.37, 148.87, 136.78, 122.26, 121.03, 44.22. ESI-MS m/z 293.1 (M + Na).sup.+; HRMS Calcd. For C.sub.14H.sub.14N.sub.4NaO.sub.2 (M + Na).sup.+ requires 293.1009.; found: 293.1012. .sup.1H NMR (400 MHz, DMSO-d6) 9.42 (s, 2H), 6.86-6.68 (m, 4H); ESI-MS m/z 377.2 (M + H).sup.+. .sup.1H NMR (400 MHz, DMSO-d6) 10.78 (s, 2H), 7.43-7.31 (m, 4H); .sup.13C NMR (100 MHz, DMSO-d6) 161.15 (dt, J = 246, 15.3 Hz, 2C), 158.95 (2C), 158.49 (ddd, J = 249, 15.9, 7.3 Hz, 4C), 110.78 (td, J = 17.2, 5.1 Hz, 2C), 101.65 (td, J = 27.2, 2.9 Hz, 4C); ESI-MS: 349.0 (M + H).sup.+ .sup.1H NMR (400 MHz, DMSO-d6) 10.52 (s, 2H), 6.88 (d, J = 9.6 Hz, 4H), 3.81 (s, 6H); .sup.13C NMR (100 MHz, DMSO-d6) 159.93 (t, J = 13.6 Hz, 2C), 159.30 (2C), 158.89 (dd, J = 246, 8.1 Hz, 4C), 106.33 (t, J = 17.8 Hz, 2C), 99.02 (d, J = 26.7 Hz, 4C), 56.73 (2C); ESI-MS: 395.2 (M + Na).sup.+ .sup.1H NMR (400 MHz, DMSO-d6) 10.36 (s, 2H), 7.36 (s, 4H), 2.16 (s, 12H); .sup.13C NMR (100 MHz, DMSO-d6) 18.16, 120.14, 130.72, 134.23, 138.38, 159.15; ESI-MS: 453.0 (M + H).sup.+ .sup.1H NMR (400 MHz, DMSO-d6) 10.31 (s, 2H), 7.18 (dd, J = 8.1, 6.6 Hz, 2H), 7.12 (d, J = 7.4 Hz, 4H), 2.54 (q, J = 7.6 Hz, 4H), 2.17 (s, 6H), 1.11 (t, J = 7.6 Hz, 6H); .sup.13C NMR (100 MHz, DMSO-d6) 14.84, 18.42, 24.92, 126.65, 127.75, 128.25, 134.24, 135.88, 141.45, 159.85; ESI-MS: 325.3 (M + H).sup.+ .sup.1H NMR (400 MHz, DMSO-d6) 10.78 (s, 2H), 7.50-7.41 (m, 2H), 7.29-7.20 (m, 4H); .sup.13C NMR (100 MHz, DMSO-d6) 158.95 (2C), 158.36 (dd, J = 248, 4.8 Hz, 4C), 129.67 (t, J = 9.9 Hz, 2C), 113.81 (t, J = 16.8 Hz, 2C), 112.54 (dd, J = 18.2, 4.9 Hz, 4C); ESI-MS: 335.1 (M + Na).sup.+ .sup.1H NMR (400 MHz, DMSO-d6) 10.53 (s, 1H), 10.39 (s, 1H), 7.73 (s, 2H), 7.37 (s, 2H), 3.85 (s, 3H), 2.24 (s, 6H), 2.17 (s, 6H): .sup.13C NMR (100 MHz, DMSO-d6) 18.16, 18.47, 52.59, 120.16, 128.56, 129.03, 130.73, 134.21, 136.34, 138.38, 139.38, 159.05, 159.08, 166.47; ESI-MS: 433.1 (M + H).sup.+ H NMR (400 MHz, DMSO-d6) 10.34 (s, 1H), 10.31 (s, 1H), 7.36 (s, 2H), 7.13-7.10 (m, 3H), 2.17 (s, 12H); .sup.13C NMR (100 MHz, DMSO-d6) 18.17, 18.45, 120.10, 127.47, 128.24, 130.71, 134.32, 134.65, 135.57, 138.39, 159.10, 159.39; ESI-MS: 397.2 (M + Na).sup.+ 0 .sup.1H NMR (400 MHz, DMSO-d6) 10.69 (s, 1H), 9.37 (t, J = 6.1 Hz, 1H), 7.95-7.89 (m, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 1.0 Hz, 1H), 7.55-7.43 (m, 3H), 6.43 (dd, J = 3.1, 1.9 Hz, 1H), 6.32 (d, J = 3.0 Hz, 1H), 4.43 (d, J = 6.2 Hz, 2H), 2.31 (s, 3H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.99, 159.46, 151.51, 142.21, 132.62, 132.21, 130.35, 130.07, 128.60, 127.83, 127.11, 126.37, 125.28, 122.85, 110.56, 107.34, 35.91, 18.17. .sup.1H NMR (400 MHz, DMSO-d6) 10.69 (s, 1H), 9.37 (t, J = 6.1 Hz, 1H), 7.95-7.89 (m, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 1.0 Hz, 1H), 7.55-7.43 (m, 3H), 6.43 (dd, J = 3.1, 1.9 Hz, 1H), 6.32 (d, J = 3.0 Hz, 1H), 4.43 (d, J = 6.2 Hz, 2H), 2.31 (s, 3H),; .sup.13C NMR (101 MHz, DMSO-d6) 159.99. 159.46, 151.51, 142.21, 132.62, 132.21, 130.35, 130.07, 128.60, 127.83, 127.11, 126.37, 125.28, 122.85, 110.56, 107.34, 35.91, 18.17.

Example 2 Synthesis of N-benzyl-4-methylaniline by Coupling Reaction of 1-chloro-4-methylbenzene with Benzylamine

(146) ##STR00272##

(147) Copper (I) iodide (0.05 mmol), ligand (0.1 mmol) and potassium phosphate (1.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1-chloro-4-methylbenzene (0.5 mmol), benzylamine (0.75 mmol) and 1 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and the mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography (petroleum ether:ethyl acetate=50:1) to give the product N-benzyl-4-methylaniline (89 mg, yield 91%).

(148) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.34-7.21 (m, 5H), 6.96 (d, J=8.0 Hz, 2H), 6.54 (d, J=8.4 Hz, 2H), 4.28 (s, 2H), 3.88 (br s, 1H), 2.22 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 20.6, 48.8, 113.2, 126.9, 127.3, 127.7, 128.8, 130.0, 139.8, 146.1; HRMS (ESI) calcd. for C.sub.14H.sub.16N (M+H).sup.+: 198.1283, Found: 198.1287.

Example 3 Synthesis of N-benzyl-4-methylaniline by Coupling Reaction of 1-chloro-4-methylbenzene with Benzylamine

(149) The operation of this example is the same as that of Example 2 except that different oxalic amide ligands were used. The results are shown in the following table.

(150) TABLE-US-00005 Ligand Yield/% Ligand Yield/% Ligand Yield/% L-I-1 62 L-II-9 75 L-II-38 92 L-I-2 64 L-II-13 52 L-II-31 86 L-I-7 65 L-II-14 17 L-II-29 66 L-I-23 62 L-II-7 73 L-II-27 45 L-I-22 59 L-II-15 56 L-II-33 82 L-I-24 44 L-II-16 11 L-II-36 73 L-I-27 74 L-II-24 61 L-II-28 17 L-I-9 55 L-II-18 40 L-II-34 57 L-I-8 67 L-II-1 56 L-II-35 21 L-I-25 75 L-II-8 60 L-II-30 65 L-I-31 40 L-II-5 64 L-II-37 76 L-I-32 34 L-II-6 74 L-II-4 81 L-I-36 17 L-II-41 62 L-II-19 40 L-II-20 70 L-II-21 65 L-II-22 25 L-II-23 60 L-I-4 37 L-I-34 20 L-I-39 64 L-II-61 <10 L-II-59 46 L-II-60 10 L-II-58 81 L-II-62 63 L-II-63 76 L-II-66 89 L-II-64 92 L-II-65 44 L-II-67 <10 L-II-69 23 L-II-70 48 L-II-68 61 L-II-72 77 L-II-71 87 L-II-73 88 L-II-74 85

Example 4 Synthesis of N-benzyl-4-methylaniline by Coupling Reaction of 1-chloro-4-methylbenzene with Benzylamine

(151) ##STR00273##

(152) The operation of this example was the same as that of Example 2 except different copper salt as catalyst, base, solvent and temperature were used. The results are shown in the following table.

(153) TABLE-US-00006 Copper Tempera- No. salt X Base Solvent ture/ C. Yield/% 1 CuI 10 K.sub.3PO.sub.4 DMSO 120 92 2 CuBr 10 K.sub.3PO.sub.4 DMSO 120 81 3 CuCl 10 K.sub.3PO.sub.4 DMSO 120 83 4 CuTc 10 K.sub.3PO.sub.4 DMSO 120 43 5 Cu(OAc).sub.2 10 K.sub.3PO.sub.4 DMSO 120 56 6 CuSO.sub.4 10 K.sub.3PO.sub.4 DMSO 120 52 7 CuBr.sub.2 10 K.sub.3PO.sub.4 DMSO 120 49 8 CuCl.sub.2 10 K.sub.3PO.sub.4 DMSO 120 60 9 Cu.sub.2O 10 K.sub.3PO.sub.4 DMSO 120 67 10 CuI 10 K.sub.2CO.sub.3 DMSO 120 48 11 CuI 10 Cs.sub.2CO.sub.3 DMSO 120 61 12 CuI 10 Na.sub.2CO.sub.3 DMSO 120 38 13 CuI 10 KHCO.sub.3 DMSO 120 31 14 CuI 10 NaHCO.sub.3 DMSO 120 29 15 CuI 10 K.sub.3PO.sub.4 DMA 120 79 16 CuI 10 K.sub.3PO.sub.4 DMF 120 86 17 CuI 10 K.sub.3PO.sub.4 NMP 120 62 18 CuI 10 K.sub.3PO.sub.4 MeCN 120 49 19 CuI 10 K.sub.3PO.sub.4 1,4- 120 33 dioxane 20 CuI 10 K.sub.3PO.sub.4 THF 120 30 21 CuI 5 K.sub.3PO.sub.4 DMSO 120 90 22 CuI 2.5 K.sub.3PO.sub.4 DMSO 120 81 23 CuI 1 K.sub.3PO.sub.4 DMSO 120 54 24 CuI 10 K.sub.3PO.sub.4 DMSO 110 63 25 CuI 10 K.sub.3PO.sub.4 DMSO 100 38 26.sup.a CuI 2.5 K.sub.3PO.sub.4 DMSO 120 81 .sup.athe reaction was enlarged to a 5 mmol scale by using L-II-31 as a ligand, while benzylamine was reduced to 1.3 equivalents, CuI was reduced to 2.5 mol %, ligand was reduced to 5 mol %, and potassium phosphate was reduced to 1.0 equivalents. The amount of DMSO was 2 mL, and the reaction time was extended to 41 hours.

Example 5 Synthesis of the Corresponding Aniline Derivatives by the Coupling Reaction of 1-chloro-4-methylbenzene with Various Primary and Secondary Amines

(154) A schematic of this coupling reaction of 1-chloro-4-methylbenzene with various primary and secondary amines of Example 5 is shown in FIG. 3.

(155) Copper iodide (0.05 mmol), ligand L-II-38 (0.05 or 0.1 mmol), potassium phosphate (1.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1-chloro-4-methylbenzene (1.0 mmol), amine (1.5 mmol) and 1 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 or 48 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product N-p-methylphenyl amine.

(156) Different amines were used in this example, including primary, secondary aliphatic amines and aromatic amines. The reaction conditions included A and B. Conditions A were for the more reactive amines and conditions B were for the less reactive amines. The results are shown in the table below.

(157) TABLE-US-00007 Product, Reaction conditions and Yield Characterization data of product .sup.1H NMR (500 MHz, CDCl.sub.3) 7.07 (d, J = 8.1 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 3.42 (br s, 1H), 3.16 (t, J = 7.2 Hz, 2H), 2.33 (s, 3H), 1.68 (p, J = 7.2 Hz, 2H), 1.53-1.34 (m, 6H), 1.00 (t, J = 6.8 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 146.25, 129.60, 126.11, 112.81, 44.31, 31.62, 29.54, 26.82, 22.58, 20.28, 13.98; LC-MS (ESI, m/z): 192.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.00 (d, J = 7.9 Hz, 1H), 6.60 (d, J = 8.4 Hz, 2H), 3.83 (t, J = 5 Hz, 2H), 3.29 (t, J = 5 Hz, 2H), 2.25 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 145.67, 129.68, 127.15, 113.46, 61.02, 46.42, 20.30; LC-MS (ESI, m/z): 152.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.99 (d, J = 8.0 Hz, 2H), 6.56 (d, J = 8.0 Hz, 2H), 4.99 (t, J = 4.5 Hz, 1H), 4.06-3.95 (m, 2H), 3.92-3.80 (m, 2H), 3.25 (t, J = 6.5 Hz, 2H), 2.23 (s, 3H), 2.01 (td, J = 6.5, 4.5 Hz, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 146.00, 129.55, 126.27, 112.90, 103.59, 64.77, 39.45, 32.92, 20.26; HRMS (DART) calcd. for C.sub.12H.sub.18NO.sub.2 (M + H).sup.+: 208.1332, Found: 208.1333. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.27-7.17 (m, 2H), 7.13-7.00 (m, 2H), 7.00 (d, J = 8.1 Hz, 2H), 6.57 (d, J = 8.4 Hz, 2H), 3.60 (br s, 1H), 3.39 (t, J = 7.1 Hz, 2H), 2.95 (td, J = 7.1, 1.1 Hz, 2H), 2.25 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.18 (d, J = 244.8 Hz), 145.50, 130.94 (d, J = 5.0 Hz), 129.66, 127.98 (d, J = 8.1 Hz), 126.41, 126.24 (d, J = 16.0 Hz), 123.96 (d, J = 3.6 Hz), 115.21 (d, J = 22.2 Hz), 112.96, 44.04, 28.99 (d, J = 1.8 Hz), 20.26; HRMS (DART) calcd. for C.sub.15H.sub.17NF (M + H).sup.+: 230.1340, Found: 230.1340. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.36 (dd, J = 1.9. 0.9 Hz, 1H), 7.00 (d, J = 7.8 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 6.32 (dd, J = 3.2, 1.8 Hz, 1H), 6.23 (dd, J = 3.2, 0.9 Hz, 1H), 4.30 (s, 2H), 3.89 (br s, 1H), 2.25 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 152.89, 145.26, 141.70, 129.60, 127.08, 113.24, 110.21, 106.77, 41.63, 20.31; LC-MS (ESI, m/z): 188.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.99 (d, J = 8.3 Hz, 2H), 6.90-6.74 (m, 3H), 6.56 (d, J = 8.3 Hz, 2H), 5.95 (s, 2H), 4.22 (s, 2H), 3.86 (br s, 1H), 2.25 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 147.78, 146.57, 145.74, 133.52, 129.66, 126.68, 120.46, 112.94, 108.18, 107.96, 100.88, 48.34, 20.32; HRMS (DART) calcd. for C.sub.15H.sub.16NO.sub.2 (M + H).sup.+: 242.1176, Found: 242.1175. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.45-7.36 (m, 4H), 7.36-7.29 (m, 1H), 7.01 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H), 4.92 (dd, J = 8.7, 3.8 Hz, 1H), 3.42 (dd, J = 13.1, 3.9 Hz, 1H), 3.28 (dd, J = 13.1, 8.7 Hz, 1H), 2.25 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.48, 142.07, 129.76, 128.52, 127.85, 127.37, 125.83, 113.68, 72.31, 52.19, 20.35; HRMS (ESI) calcd. for C.sub.15H.sub.18NO (M + H).sup.+: 228.1383, Found: 228.1384. .sup.1H NMR (400 MHz, CDCl.sub.3) 1.05-1.48 (m, 8H), 2.02-2.06 (m, 2H), 2.17 (s, 3H), 3.18-3.25 (m, 1H), 3.36 (s, 1H), 6.52 (d, J = 8.2 Hz, 2H), 6.96 (d, J = 8.1 Hz, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 145.22, 129.85, 126.20, 113.59, 52.16, 33.67, 26.11, 25.18, 20.49; LC-MS (ESI, m/z): 190.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.96 (d, J = 7.9 Hz, 2H), 6.52 (d, J = 8.4 Hz, 2H), 3.55 (ddd, J = 10.0, 4.2, 2.0 Hz, 2H), 2.47-2.31 (m, 1H), 2.23 (s, 3H), 1.86- 1.67 (m, 3H), 1.46-1.31 (m, 1H), 1.28-1.16 (m, 1H), 0.97 (s, 3H), 0.93-0.86 (m, 7H); .sup.13C NMR (100 MHz, CDCl.sub.3) 146.75, 129.74, 125.99, 113.28, 58.70, 49.46, 48.17, 45.15, 38.91, 28.36, 27.87, 20.45, 19.97, 18.86, 14.43; HRMS (DART) calcd. for C.sub.17H.sub.26N (M + H).sup.+: 244.2060, Found: 244.2059. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.98 (d, J = 7.8 Hz, 2H), 6.52 (d, J = 8.4 Hz, 2H), 3.51 (br, 1H), 3.22-3.00 (m, 2H), 2.53-2.26 (m, 2H), 2.23 (s, 3H), 2.14-1.80 (m, 5H), 1.69-1.44 (m, 1H), 1.20 (s, 3H), 1.04 (s, 3H), 0.92 (d, J = 9.6 Hz, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 146.39, 129.78, 126.20, 112.95, 50.45, 44.28, 41.57, 41.20, 38.82, 33.54, 28.17, 26.28, 23.45, 20.50, 20.48; HRMS (DART) calcd. for C.sub.17H.sub.26N (M + H).sup.+: 244.2060, Found: 244.2060. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.98 (d, J = 7.7 Hz, 2H), 6.54 (d, J = 7.7 Hz, 2H), 3.77 (ddd, J = 12.3, 6.8, 5.5 Hz, 1H), 3.49 (br, 1H), 2.24 (s, 3H), 2.01 (m, 2H), 1.78-1.67 (m, 2H), 1.66-1.54 (m, 2H), 1.51-1.39 (m, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 145.89, 129.76, 126.19, 113.49, 55.04, 33.68, 24.19, 20.48; LC-MS (ESI, m/z): 176.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.00 (d, J = 7.5 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 4.01 (s, 1H), 3.78-3.34 (m, 4H), 3.21 (m, 1H), 2.24 (s, 3H), 2.17 (m, 1H), 1.88 (s, 1H), 1.46 (s, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) 154.73, 144.68, 129.93, 127.17, 113.50, 79.49, 53.36, 52.65, 52.24, 51.98, 44.24, 43.91, 31.95, 31.32, 28.61, 20.46; HRMS (DART) calcd. for C.sub.16H.sub.25N.sub.2O.sub.2 (M + H).sup.+: 277.1911, Found: 277.1910. (Note: Rotary isomers exists, leading to the higher peak in the is wider peak in the upperfield of .sup.1H NMR spectrum, and the double peak of single carbon atom in the upperfield of 13C NMR spectrum) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.90 (d, J = 7.8 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.23 (ddd, 1H), 2.99 (ddd, 1H), 2.75 (br, 1H), 2.14 (s, 3H), 2.06-1.95 (m, 2H), 1.71-1.65 (m, 1H), 1.64-1.55 (m, 1H), 1.35-1.17 (m, 3H), 1.00-0.85 (m, 1H), 0.82-0.68 (m, 1H). .sup.13C NMR (125 MHz, CDCl.sub.3) 145.52, 129.93, 127.90, 114.91, 77.41, 77.16, 76.91, 74.61, 60.83, 33.23, 31.69, 25.20, 24.42, 20.50; HRMS (DART) calcd. for C.sub.13H.sub.20NO (M + H).sup.+: 206.1539, Found: 206.1539. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.00 (d, J = 7.8 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 4.13-4.03 (m, 1H), 4.00-3.90 (m, 2H), 3.88-3.80 (m, 1H), 3.74-3.66 (m, 1H), 2.30-2.19 (m, 4H), 1.94-1.79 (m, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 144.83, 129.79, 126.89, 113.53, 73.69, 67.05, 54.06, 33.17, 20.36; HRMS (ESI) calcd. for C.sub.11H.sub.16NO (M + H).sup.+: 178.1226, Found: 178.1229. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.00 (d, J = 8.2 Hz, 2H), 6.60 (d, J = 8.4 Hz, 2H), 3.81 (dd, J = 11.0, 5.5 Hz, 1H), 3.38 (t, J = 5.3 Hz, 2H), 2.54-2.43 (m, 1H), 2.24 (s, 3H), 2.03-1.92 (m, 2H), 1.71-1.59 (m, 2H), 1.25 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 173.10, 145.14, 129.76, 127.29, 113.87, 54.46, 41.79, 27.94, 20.89, 20.45; HRMS (DART) calcd. for C.sub.12H.sub.17N.sub.2O (M + H).sup.+: 205.1335, Found: 205.1336. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.89 (d, J = 7.7 Hz, 2H), 6.38 (d, J = 8.4 Hz, 2H), 5.96 (s, 1H), 4.95 (s, 1H), 3.91 (d, J = 10.2 Hz, 1H), 3.26-3.12 (m, 2H), 2.13 (s, 3H), 2.05-1.92 (m, 2H), 1.84-1.66 (m, 2H), 1.46-1.33 (m, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 177.22, 144.06, 129.85, 126.22, 113.03, 55.61, 42.21, 30.91, 29.06, 28.01, 20.40; HRMS (DART) calcd. for C.sub.13H.sub.19N.sub.2O (M + H).sup.+: 219.1492, Found: 219.1491. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.06 (d, J = 8.2 Hz, 2H), 6.52 (d, J = 8.2 Hz, 2H), 3.25 (dd, J = 6.4, 6.4 Hz, 4H), 2.24 (s, 3H), 1.98 (dd, J = 6.4, 6.4 Hz, 4H); .sup.13C NMR (100 MHz, CDCl.sub.3) 146.1, 129.6, 124.4, 111.8, 47.8, 25.4, 20.2; LC-MS (ESI, m/z): 162.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl3) 7.12 (d, J = 5.2 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 5.2 Hz, 1H), 4.26 (s, 2H), 3.57 (t, J = 5.6 Hz, 2H), 2.98 (t, J = 5.6 Hz, 2H), 2.28 (s, 3H); .sup.13C NMR (100 MHz, CDCl3) 148.60, 133.56, 133.36, 129.67, 128.87, 125.09, 122.77, 116.53, 49.44, 48.05, 25.31, 20.38; HRMS (ESI) calcd. for C.sub.14H.sub.16NS (M + H).sup.+: 230.0998, Found: 230.0999. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.24-7.20 (m, 2H), 7.07 (d, J = 8.2 Hz, 2H), 7.01-6.98 (m, 4H), 6.87 (t, J = 7.3 Hz, 1H), 5.58 (br s, 1H), 2.30 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 143.9, 140.2, 130.9, 129.8, 129.3, 120.3, 118.9, 116.8, 20.7; LC-MS (ESI, m/z): 184.3 (M + H).sup.+.

Example 6 Synthesis of N-benzylaniline Derivatives by Coupling Reaction of Aryl Chloride with Benzylamine

(158) ##STR00293##

(159) Copper iodide (0.05 mmol), ligand L-II-38 (0.05 mmol) and potassium phosphate (1.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then aryl chloride (1.0 mmol), benzylamine (1.5 mmol) and 1 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product N-benzylaniline derivatives.

(160) This example used different aryl chlorides. The results are given in the following table.

(161) TABLE-US-00008 Product and Yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3) 7.42-7.31 (m, 4H), 7.30-7.26 (m, 1H), 6.78 (d, J = 8.9 Hz, 2H), 6.61 (d, J = 8.9 Hz, 2H), 4.29 (s, 2H), 3.75 (s, 3H); 13C NMR (101 MHz, CDCl.sub.3) 152.2, 142.5, 139.7, 128.6, 127.6, 127.2, 114.9, 114.1, 55.8, 49.2; HRMS (ESI) calcd. for C.sub.14H.sub.16NO (M + H).sup.+: 214.1232, Found: 214.1237. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.39-7.30 (m, 5H), 7.30-7.26 (m, 1H), 7.25- 7.21 (m, 2H), 7.04-6.88 (m, 1H), 6.63-6.55 (m, 2H), 4.31 (s, 2H), 4.02 (s, 1H), 2.13 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 168.26, 145.51, 139.45, 128.76, 128.39, 127.58, 127.37, 122.52, 113.17, 48.66, 24.40: HRMS (ESI) calcd. for C.sub.15H.sub.17N.sub.2O (M + H).sup.+: 241.1341. Found: 241.1337. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.41-7.31 (m, 4H), 7.31-7.27 (m, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 8.4 Hz, 2H), 4.55 (s, 2H), 4.34 (s, 2H), 4.10 (s, 1H): .sup.13C NMR (125 MHz, CDCl.sub.3) 147.99, 139.38, 130.06. 129.00, 128.79, 127.57, 127.40, 112.97, 65.57, 48.43; HRMS (ESI) calcd. for C.sub.14H.sub.16NO (M + H).sup.+: 214.1232, Found: 214.1225. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.41-7.31 (m, 4H), 7.31-7.27 (m, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 8.4 Hz, 2H), 4.55 (s, 2H), 4.34 (s, 2H), 4.10 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 147.99, 139.38, 130.06, 129.00, 128.79, 127.57, 127.40, 112.97, 65.57, 48.43; HRMS (ESI) calcd. for C.sub.13H.sub.13N.sub.2O.sub.2 (M + H).sup.+: 229.0977, Found: 229.0970. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.45-7.39 (m, 2H), 7.39-7.28 (m, 5H), 6.59 (d, J = 8.8 Hz, 2H), 4.61 (s, 1H), 4.38 (d, J = 5.5 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 151.21, 137.92, 133.86, 129.00, 127.84, 127.45, 120.48, 112.54, 99.27, 47.65; HRMS (ESI) calcd. for C.sub.14H.sub.13N.sub.2 (M + H).sup.+: 209.1079, Found: 209.1072. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.45-7.35 (m, 6H), 7.35-7.27 (m, 1H), 6.64 (d, J = 7.8 Hz, 2H), 4.38 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 150.59, 138.58, 128.93, 127.66, 127.50, 126.76 (q, J = 3.8 Hz), 125.09 (q, J = 270.3 Hz), 119.20 (q, J = 32.6 Hz), 112.12, 47.95; HRMS (ESI) calcd. for C.sub.14H.sub.13F.sub.3N (M + H).sup.+: 252.1000, Found: 252.1007. 00 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.82 (d, J = 8.7 Hz, 2H), 7.39-7.33 (m, 4H), 7.32- 7.27 (m, 1H), 6.60 (d, J = 8.7 Hz, 2H), 4.58 (s, 1H), 4.41 (s, 2H), 2.49 (s, 3H): .sup.13C NMR (100 MHz, CDCl.sub.3) 196.2, 152.0, 138.3, 130.8, 129.0, 127.6, 127.4, 127.2, 111.6, 47.7, 26.0; HRMS (ESI) calcd. for C.sub.15H.sub.16NO (M + H).sup.+: 226.1232, Found: 226.1227. 01 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.33 (m, 4H), 7.32-7.27 (m, 1H), 6.95- 6.83 (m, 2H), 6.62-6.52 (m, 2H), 4.30 (s, 2H), 3.94 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 156.02 (d, J = 235.0 Hz), 144.61, 139.37, 128.80, 127.62, 127.44, 115.80 (d, J = 22.4 Hz), 113.77 (d, J = 7.5 Hz), 49.08; HRMS (ESI) calcd. for C.sub.13H.sub.13FN (M + H).sup.+: 202.1032, Found: 202.1037. 02 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.86 (d, J = 8.8 Hz, 2H), 7.40-7.32 (m, 4H), 7.32- 7.27 (m, 1H), 6.59 (d, J = 8.8 Hz, 2H), 4.49 (s, 1H), 4.39 (s, 2H), 3.85 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 167.2, 151.8, 131.7, 131.6, 128.5, 127.5, 118.8, 111.7, 51.5, 47.7; HRMS (ESI) calcd. for C.sub.15H.sub.16NO.sub.2 (M + H).sup.+: 242.1181, Found: 242.1183. 03 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.42-7.32 (m, 4H), 7.32-7.26 (m, 1H), 7.13- 7.06 (m, 1H), 6.33-6.25 (m, 2H), 6.23-6.19 (m, 1H), 4.33 (s, 2H), 4.06 (s, 1H), 3.76 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 160.94, 149.67, 139.44, 130.12, 128.76, 127.64, 127.37, 106.10, 102.80, 98.99, 55.19, 48.45; HRMS (ESI) calcd. for C.sub.14H.sub.16NO (M + H).sup.+: 214.1232, Found: 214.1230. 04 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.59-7.50 (m, 2H), 7.50-7.42 (m, 2H), 7.44- 7.34 (m, 6H), 7.38-7.22 (m, 3H), 6.72 (d, J = 8.5 Hz, 2H), 4.39 (s, 2H), 4.30- 3.71 (m, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 147.61, 141.34, 139.38, 130.68, 128.81, 128.77, 128.09, 127.64, 127.44, 126.43, 126.21, 113.29, 48.50; HRMS (ESI) calcd. for C.sub.19H.sub.18N (M + H).sup.+: 260.1439, Found: 260.1433. 05 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.45-7.32 (m, 4H), 7.32-7.26 (m, 1H), 6.90- 6.78 (m, 2H), 6.74-6.66 (m, 1H), 6.62 (dd, J = 7.8, 1.6 Hz, 1H), 4.65 (s, 1H), 4.37 (s, 2H), 3.87 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 146.88, 139.69, 138.23, 128.68, 127.62, 127.22, 121.38, 116.73, 110.17, 109.49, 55.51, 48.15; HRMS (ESI) calcd. for C.sub.14H.sub.16NO (M + H).sup.+: 214.1232, Found: 214.1228. 06 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.41-7.31 (m, 4H), 7.31-7.26 (m, 1H), 5.90 (t, J = 2.1 Hz, 1H), 5.84 (d, J = 2.1 Hz, 2H), 4.31 (s, 2H), 4.06 (s, 1H), 3.74 (s, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 161.83, 150.20, 139.36, 128.76, 127.66, 127.39, 91.84, 90.02, 55.27, 48.47; HRMS (ESI) calcd. for C.sub.15H.sub.18NO.sub.2 (M + H).sup.+: 244.1338, Found: 244.1330. 07 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.32-7.26 (m, 4H), 7.25-7.18 (m, 1H), 7.17- 7.13 (m, 1H), 6.87 (d, J = 7.7 Hz, 1H), 6.77 (s, 1H), 6.67 (dd, J = 8.2, 2.4 Hz, 1H), 4.27 (s, 2H), 4.15 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 148.2, 138.5, 131.6 (q, J = 31 Hz), 129.6, 128.7, 127.5, 126.3, 122.3, 115.70 (q, J = 1.1 Hz), 113.94 (q, J = 3.9 Hz), 109.08 (q, J = 3.9 Hz), 48.09; HRMS (ESI) calcd. for C.sub.14H.sub.13F.sub.3N (M + H).sup.+: 252.1000, Found: 252.1007. 08 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.42-7.31 (m, 4H), 7.31-7.26 (m, 1H), 6.97 (t, J = 7.9 Hz, 1H), 6.17-6.05 (m, 2H), 5.98 (t, J = 2.2 Hz, 1H), 4.30 (s, 2H), 3.67 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 149.37, 147.52, 139.58, 130.11, 128.60, 127.48, 127.17, 105.07, 104.05, 99.46, 48.28; HRMS (ESI) calcd. for C.sub.13H.sub.15N.sub.2 (M + H).sup.+: 199.1235, Found: 199.1240. 09 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.69 (d, J = 8.1 Hz, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.46-7.41 (m, 2H), 7.41-7.34 (m, 3H), 7.34-7.28 (m, 1H), 7.24-7.18 (m, 1H), 6.93 (dd, J = 8.8, 2.3 Hz, 1H), 6.86 (d, J = 2.3 Hz, 1H), 4.45 (s, 2H), 4.20 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.55, 139.02, 135.13, 128.97, 128.69, 127.67, 127.64, 127.36, 126.33, 126.02, 122.13, 117.90, 104.93, 48.49; HRMS (ESI) calcd. for C.sub.17H.sub.16N (M + H).sup.+: 234.1283, Found: 234.1278. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.76-7.64 (m, 2H), 7.38-7.30 (m, 4H), 7.30- 7.24 (m, 2H), 7.24-7.13 (m, 3H), 6.52 (d, J = 7.4 Hz, 1H), 4.58 (s, 1H), 4.38 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 143.32, 139.21, 134.41, 128.84, 128.82, 127.85, 127.51, 126.73, 125.86, 124.86, 123.49, 120.01, 117.75, 104.86, 48.71; HRMS (ESI) calcd. for C.sub.17H.sub.16N (M + H).sup.+: 234.1283, Found: 234.1280. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.43-7.34 (m, 4H), 7.33-7.27 (m, 1H), 7.15- 7.06 (m, 2H), 6.73-6.66 (m, 1H), 6.63 (dd, J = 8.0, 1.2 Hz, 1H), 4.39 (s, 2H), 3.88 (s, 1H), 2.18 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 146.19, 139.62, 130.20, 128.79, 127.67, 127.38, 127.29, 122.05, 117.30, 110.09, 48.44, 17.70; HRMS (ESI) calcd. for C.sub.14H.sub.16N (M + H).sup.+: 198.1283, Found: 198.1285. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.44-7.40 (m, 1H), 7.40-7.27 (m, 6H), 6.70 (t, J = 7.5 Hz, 1H), 6.64 (d, J = 8.5 Hz, 1H), 5.05 (t, J = 5.7 Hz, 1H), 4.44 (d, J = 5.5 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 150.05, 137.70, 134.26, 132.75, 128.86, 127.64, 127.16, 117.86, 116.86, 111.03, 95.94, 47.48; HRMS (ESI) calcd. for C.sub.14H.sub.13N.sub.2 (M + H).sup.+: 209.1079, Found: 209.1070. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.37-8.03 (m, 2H), 7.40-7.30 (m, 4H), 7.30- 7.26 (m, 1H), 6.60-6.42 (m, 1H), 5.98 (s, 1H), 4.64 (d, J = 5.8 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 162.42, 158.09, 139.20, 128.67, 127.69, 127.30, 110.70, 45.57; HRMS (ESI) calcd. for C.sub.11H.sub.12N.sub.3 (M + H).sup.+: 186.1031, Found: 186.1025. .sup.1H NMR (400 MHz, CDC1.sub.3) 8.07 (d, J = 2.9 Hz, 1H), 8.02-7.90 (m, 1H), 7.35 (d, J = 4.4 Hz, 4H), 7.32-7.26 (m, 1H), 7.11-7.01 (m, 1H), 6.91-6.81 (m, 1H), 4.34 (d, J = 4.8 Hz, 2H), 4.19 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 144.22, 138.82, 138.62, 136.18, 128.79, 127.50, 127.44, 123.81, 118.55, 47.86; HRMS (ESI) calcd. for C.sub.12H.sub.13N.sub.2 (M + H).sup.+: 185.1079, Found: 185.1083. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.39-7.30 (m, 4H), 7.30-7.24 (m, 2H), 6.47 (d, J = 7.3 Hz, 1H), 6.17 (d, J = 8.3 Hz, 1H), 4.93 (s, 1H), 4.46 (d, J = 5.8 Hz, 2H), 2.39 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 158.36, 157.02, 139.23, 137.93, 128.58, 127.33, 127.17, 112.53, 102.86, 46.57, 24.35; HRMS (ESI) calcd. for C.sub.13H.sub.15N.sub.2 (M + H).sup.+: 199.1235, Found: 199.1228. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.43-7.32 (m, 4H), 7.32-7.27 (m, 1H), 7.20- 7.13 (m, 1H), 6.72-6.58 (m, 1H), 6.04-5.94 (m, 1H), 4.28 (s, 2H), 3.98 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 148.58, 139.42, 128.73, 127.85, 127.44, 125.32, 120.01, 96.22, 50.79; HRMS (ESI) calcd. for C.sub.11H.sub.12NS (M + H).sup.+: 190.0690, Found: 190.0695. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.00 (dd, J = 2.8, 1.5 Hz, 1H), 7.89 (d, J = 1.5 Hz, 1H), 7.82 (d, J = 2.8 Hz, 1H), 7.38-7.33 (m, 4H), 7.33-7.27 (m, 1H), 4.96 (s, 1H), 4.56 (d, J = 5.7 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 154.54, 142.12, 138.55, 133.29, 132.22, 128.90, 127.70, 127.69, 45.71; HRMS (ESI) calcd. for C.sub.11H.sub.12N.sub.3 (M + H).sup.+: 186.1031, Found: 186.1037. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.64 (d, J = 8.6 Hz, 1H), 7.47-7.40 (m, 2H), 7.40- 7.34 (m, 3H), 7.34-7.27 (m, 1H), 7.16 (dt, J = 5.5, 1.0 Hz, 1H), 7.05-6.98 (m, 1H), 6.77 (dd, J = 8.6, 2.3 Hz, 1H), 4.40 (s, 2H), 4.09 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.79, 141.09, 139.50, 129.59, 128.78, 127.65, 127.37, 126.99, 123.50, 122.96, 114.04, 105.09, 48.88; HRMS (ESI) calcd. for C.sub.15H.sub.14NS (M + H).sup.+: 240.0847, Found: 240.0842. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.72 (s, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.92 (s, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.69-7.62 (m, 1H), 7.62-7.56 (m, 1H), 7.50- 7.43 (m, 2H), 7.42-7.35 (m, 2H), 7.36-7.30 (m, 1H), 4.53 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 142.56, 138.61, 137.64, 129.15, 128.97, 128.59, 128.20, 127.96, 127.80, 127.08, 126.01, 123.92, 119.30, 48.58; HRMS (ESI) calcd. for C.sub.16H.sub.15N.sub.2 (M + H).sup.+: 235.1235, Found: 235.1229. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 8.61 (dd, J = 4.2, 1.6 Hz, 1H), 7.89 (d, J = 8.9 Hz, 2H), 7.45-7.34 (m, 4H), 7.34-7.28 (m, 1H), 7.25 (dd, J = 8.3, 4.3 Hz, 1H), 7.14 (dd, J = 9.1, 2.6 Hz, 1H), 6.72 (d, J = 2.6 Hz, 1H), 4.44 (d, J = 3.7 Hz, 2H), 4.38 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 146.42, 146.08, 143.44, 138.81, 134.02, 130.46, 130.21, 128.90, 127.67, 127.61, 121.51, 121.41, 103.44, 48.44; HRMS (ESI) calcd. for C.sub.16H.sub.15N.sub.2 (M + H).sup.+: 235.1235, Found: 235.1237. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.31 (m, 4H), 7.31-7.26 (m, 1H), 6.66 (d, J = 8.3 Hz, 1H), 6.27 (d, J = 2.3 Hz, 1H), 6.08 (dd, J = 8.3, 2.4 Hz, 1H), 5.85 (s, 2H), 4.27 (s, 2H), 3.84 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 148.33, 143.94, 139.69, 139.40, 128.62, 127.52, 127.24, 108.63, 104.41, 100.57, 96.00, 49.26; HRMS (ESI) calcd. for C.sub.14H.sub.14NO.sub.2 (M + H).sup.+: 228.1025, Found: 228.1030. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.61 (dt, J = 8.2, 1.1 Hz, 1H), 7.86 (d, J = 2.7 Hz, 1H), 7.61-7.54 (m, 2H), 7.47-7.42 (m, 1H), 7.42-7.33 (m, 5H), 7.32-7.27 (m, 1H), 7.00 (dd, J = 8.7, 2.7 Hz, 1H), 4.45 (s, 2H), 4.32 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3) 180.00, 146.95, 138.75, 137.94, 131.79, 130.30, 129.94, 129.10, 128.86, 127.73, 127.59, 127.02, 126.07, 125.78, 125.39, 120.13, 110.41, 48.33; HRMS (ESI) calcd for C.sub.20H.sub.16NOS (M + H).sup.+ 318.0953, found 318.0952. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.54 (d, J = 8.6 Hz, 1H), 7.43-7.38 (m, 2H), 7.38- 7.31 (m, 2H), 7.30-7.26 (m, 1H), 7.16 (d, J = 2.4 Hz, 1H), 6.73 (dd, J = 8.6, 2.3 Hz, 1H), 2.77 (s, 3H); HRMS (ESI) calcd for C.sub.15H.sub.15N.sub.2S (M + H).sup.+ 255.0956, found 255.0952. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.31 (m, 4H), 7.30-7.26 (m, 1H), 6.84 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 4.30 (s, 2H), 3.88-3.83 (m, 4H), 3.06-2.98 (m, 4H); .sup.13C NMR (126 MHz, CDCl.sub.3) 143.71, 142.91, 139.78, 128.67, 127.63, 127.25, 118.47, 114.00, 67.20, 51.34, 49.10; HRMS (ESI) calcd for C.sub.17H.sub.21N.sub.2O (M + H).sup.+ 269.1654, found 269.1650. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.98 (d, J = 8.0 Hz, 1H), 7.94-7.89 (m, 2H), 7.84 (d, J = 8.0 Hz, 1H), 7.46-7.41 (m, 1H), 7.40-7.35 (m, 4H), 7.34-7.28 (m, 2H), 6.73-6.66 (m, 2H), 4.45 (s, 1H), 4.42 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 168.77, 154.44, 150.52, 138.67, 134.68, 129.25, 128.90, 127.63, 127.56, 126.14, 124.44, 123.06, 122.50, 121.50, 112.71, 47.96; HRMS (ESI) calcd for C.sub.20H.sub.17N.sub.2S (M + H).sup.+ 317.1112, found 317.1108.

Example 7 Synthesis of Substituted Aromatic Amines (Different Arylchlorides and Different Amines)

(162) ##STR00326##

(163) Copper iodide (0.05 mmol), ligand L-II-38 (0.05 mmol) and potassium phosphate (1.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then aryl chloride (1.0 mmol), amine (1.5 mmol) and 1 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product substituted aromatic amines.

(164) Different aryl chlorides and different amines were used in this example. The results are given in the following table.

(165) TABLE-US-00009 Product and Yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3) 6.92-6.83 (m, 2H), 6.56-6.50 (m, 2H), 3.73 (p, J = 6.1 Hz, 1H), 3.49 (s, 1H), 2.08-1.94 (m, 2H), 1.79-1.57 (m, 4H), 1.51-1.39 (m, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 155.73 (d, J = 234.2 Hz), 144.55 (d, J = 1.8 Hz), 115.68 (d, J = 22.3 Hz), 114.08 (d, J = 7.2 Hz), 55.41, 33.67, 24.21 HRMS (ESI) calcd for C.sub.11H.sub.15FN (M + H).sup.+ 180.1189, found 180.1183 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.16 (d, J = 8.5 Hz, 2H), 6.59 (d, J = 8.5 Hz, 2H), 4.97 (t, J = 4.5 Hz, 1H), 4.52 (s, 2H), 4.02-3.93 (m, 2H), 3.91-3.81 (m, 2H), 3.26 (t, J = 6.5 Hz, 2H), 2.00 (td, J = 6.5, 4.5 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 148.17, 129.80, 128.90, 112.91, 103.76, 65.45, 65.02, 65.02, 39.36, 33.01; HRMS (ESI) calcd for C.sub.12H.sub.18NO.sub.3 (M + H).sup.+ 224.1287, found 224.1285. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.82-6.74 (m, 2H), 6.62-6.55 (m, 2H), 4.97 (td, J = 1.7, 0.9 Hz, 1H), 4.89 (m, 1H), 3.75 (s, 3H), 3.65 (s, 2H), 1.79 (dd, J = 1.5, 0.9 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 152.15, 143.25, 142.65, 114.97, 114.19, 110.97, 55.93, 51.00, 20.64; HRMS (ESI) calcd for C.sub.11H.sub.16NO (M + H).sup.+ 178.1232, found 178.1228. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.44 (d, J = 8.9 Hz, 2H), 6.49 (d, J = 8.9 Hz, 2H), 3.36-3.27 (m, 4H), 2.10-1.97 (m, 4H); .sup.13C NMR (125 MHz, CDCl.sub.3) 150.14, 133.57, 121.13, 111.57, 96.70, 47.61, 25.54; HRMS (ESI) calcd for C.sub.11H.sub.13N.sub.2 (M + H).sup.+ 173.1079, found 173.1077. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.37 (dd, J = 1.9, 0.9 Hz, 1H), 6.32 (dd, J = 3.2, 1.9 Hz, 1H), 6.27-6.22 (m, 1H), 5.92 (t, J = 2.1 Hz, 1H), 5.87 (d, J = 2.1 Hz, 2H), 4.29 (s, 2H), 4.06 (s, 1H), 3.75 (s, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 161.80, 152.66, 149.69, 142.05, 110.48, 107.17, 92.15, 90.45, 55.28, 41.53; HRMS (ESI) calcd for C.sub.13H.sub.16NO.sub.3 (M + H).sup.+ 234.1130, found 234.1127. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.66 (d, J = 8.3 Hz, 1H), 6.29 (d, J = 2.3 Hz, 1H), 6.10 (dd, J = 8.3, 2.3 Hz, 1H), 5.86 (s, 2H), 3.81 (t, J = 5.2 Hz, 2H), 3.23 (t, J = 5.2 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 148.36, 143.79, 140.03, 108.60, 104.98, 100.63, 96.51, 61.25, 47.15; HRMS (ESI) calcd for C.sub.9H.sub.12NO.sub.3 (M + H).sup.+ 182.0817, found 182.0814. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.58 (dd, J = 4.2, 1.7 Hz, 1H), 7.91-7.87 (m, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.23 (dd, J = 8.3, 4.2 Hz, 1H), 7.05 (dd, J = 9.0, 2.6 Hz, 1H), 6.68 (d, J = 2.6 Hz, 1H), 3.44-3.31 (m, 1H), 2.20-2.05 (m, 2H), 1.85-1.74 (m, 2H), 1.73-1.63 (m, 1H), 1.50-1.35 (m, 2H), 1.32- 1.16 (m, 4H); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.98, 145.36, 143.05, 133.74, 130.40, 130.37, 121.74, 121.44, 103.25, 51.86, 33.30, 26.03, 25.11; HRMS (ESI) calcd for C.sub.15H.sub.19N.sub.2 (M + H).sup.+ 227.1548, found 227.1546. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.62 (d, J = 8.6 Hz, 1H), 7.36 (d, J = 5.4 Hz, 1H), 7.17 (dd, J = 5.4, 0.8 Hz, 1H), 6.98 (d, J = 2.3 Hz, 1H), 6.73 (dd, J = 8.7, 2.3 Hz, 1H), 3.63 (s, 1H), 3.16 (t, J = 7.1 Hz, 2H), 1.72-1.61 (m, 2H), 1.49- 1.39 (m, 2H), 1.38-1.30 (m, 4H), 0.97-0.86 (m, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 146.18, 141.18, 129.25, 126.88, 123.47, 122.89, 114.15, 104.93, 44.72, 31.82, 29.64, 27.06, 22.79, 14.20; HRMS (ESI) calcd for C.sub.14H.sub.20NS (M + H).sup.+ 234.1316, found 234.1315.

Example 8 Synthesis of (4-aminophenyl)methanol

(166) ##STR00335##

(167) Chlorobenzyl alcohol (0.5 mmol), ammonia source (0.75 mmol), copper salt catalyst (0.05 mmol), ligand (0.05 mmol) and base (0.5 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 0.5 mL of solvent was added. The reaction mixture was stirred well at 110 C. for 12 hours. After cooling, the mixture was filtered through silica gel and celite. The filtrate was concentrated and purified by column chromatography to give the product (4-aminophenyl) methanol (light yellow solid).

(168) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.11 (d, J=8.3 Hz, 2H), 6.62 (d, J=8.3 Hz, 2H), 4.49 (s, 2H), 3.22 (br s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 145.9, 131.0, 128.7, 115.1, 65.1; LC-MS (ESI, m/z): 124.1 (M+H).sup.+.

(169) In this example, different ammonia sources, copper salt catalysts, ligands, bases and solvents were used. The results are given in the following table.

(170) TABLE-US-00010 ammonia copper sol- No. source salt ligand base vent Yield/% 1 NH.sub.3H.sub.2O CuI L-II-4 K.sub.3PO.sub.4 DMSO 33 2 NH.sub.3H.sub.2O CuI L-II-37 K.sub.3PO.sub.4 DMSO 62 3 NH.sub.3H.sub.2O CuI L-II-41 K.sub.3PO.sub.4 DMSO 31 4 NH.sub.3H.sub.2O CuI L-II-2 K.sub.3PO.sub.4 DMSO 25 5 NH.sub.3H.sub.2O CuI L-II-42 K.sub.3PO.sub.4 DMSO 30 6 NH.sub.3H.sub.2O CuI L-II-8 K.sub.3PO.sub.4 DMSO <10 7 NH.sub.3H.sub.2O CuI L-II-38 K.sub.3PO.sub.4 DMSO 90 8 NH.sub.3H.sub.2O CuI L-II-31 K.sub.3PO.sub.4 DMSO 68 9 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 DMSO 82 10 NH.sub.3H.sub.2O CuI L-II-27 K.sub.3PO.sub.4 DMSO 14 11 NH.sub.3H.sub.2O CuI L-II-29 K.sub.3PO.sub.4 DMSO 42 12 NH.sub.3H.sub.2O CuI L-II-30 K.sub.3PO.sub.4 DMSO 78 13 NH.sub.3H.sub.2O CuI L-II-28 K.sub.3PO.sub.4 DMSO 23 14 NH.sub.3H.sub.2O CuI L-II-36 K.sub.3PO.sub.4 DMSO 49 15 NH.sub.4Cl + KOH CuI L-II-1 K.sub.3PO.sub.4 DMSO 32 16 NH.sub.4Cl + KOH CuI L-II-3 K.sub.3PO.sub.4 DMSO 44 17 NH.sub.4Cl + KOH CuI L-II-4 K.sub.3PO.sub.4 DMSO 63 18 NH.sub.4Cl + KOH CuI L-II-5 K.sub.3PO.sub.4 DMSO 40 19 NH.sub.4Cl + KOH CuI L-II-6 K.sub.3PO.sub.4 DMSO 35 20 NH.sub.4Cl + KOH CuI L-II-7 K.sub.3PO.sub.4 DMSO 33 21 NH.sub.4Cl + KOH CuI L-II-9 K.sub.3PO.sub.4 DMSO 33 22 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 DMF 56 23 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 DMA 58 24 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 NMP 42 25 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 MeCN 16 26 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 1,4- <10 dioxane 27 NH.sub.3H.sub.2O CuI L-II-34 K.sub.3PO.sub.4 THF <10 28 NH.sub.4Cl + KOH CuI L-II-34 K.sub.3PO.sub.4 DMSO 67 29 (NH.sub.4).sub.2CO.sub.3 + CuI L-II-34 K.sub.3PO.sub.4 DMSO 39 KOH 30 (NH.sub.4).sub.2SO.sub.4 + CuI L-II-34 K.sub.3PO.sub.4 DMSO 59 KOH 31 (NH.sub.4).sub.2HPO.sub.4 + CuI L-II-34 K.sub.3PO.sub.4 DMSO 70 KOH 32 NH.sub.3 (gas, CuI L-II-34 K.sub.3PO.sub.4 DMSO 77 5 atm) 33 NaN.sub.3 CuI L-II-38 K.sub.3PO.sub.4 DMSO 43 34 NH.sub.3H.sub.2O CuI L-II-34 K.sub.2CO.sub.3 DMSO 51 35 NH.sub.3H.sub.2O CuI L-II-34 Na.sub.2CO.sub.3 DMSO 17 36 NH.sub.3H.sub.2O CuI L-II-34 Cs.sub.2CO.sub.3 DMSO 90 37 NH.sub.3H.sub.2O CuBr L-II-34 K.sub.3PO.sub.4 DMSO 71 38 NH.sub.3H.sub.2O CuCl L-II-34 K.sub.3PO.sub.4 DMSO 73 39 NH.sub.3H.sub.2O Cu.sub.2O L-II-34 K.sub.3PO.sub.4 DMSO 51 40 NH.sub.3H.sub.2O Cu(OAc).sub.2 L-II-34 K.sub.3PO.sub.4 DMSO 43 41 NH.sub.3H.sub.2O CuTc L-II-34 K.sub.3PO.sub.4 DMSO 24 42.sup.a NH.sub.3H.sub.2O CuI L-II-38 K.sub.3PO.sub.4 DMSO 68 43.sup.a NH.sub.3H.sub.2O CuI L-II-64 K.sub.3PO.sub.4 DMSO 69 44.sup.a NH.sub.3H.sub.2O CuI L-II-58 K.sub.3PO.sub.4 DMSO 44 45.sup.a NH.sub.3H.sub.2O CuI L-II-37 K.sub.3PO.sub.4 DMSO 77 46.sup.a NH.sub.3H.sub.2O CuI L-II-71 K.sub.3PO.sub.4 DMSO 87 47.sup.a NH.sub.3H.sub.2O CuI L-II-73 K.sub.3PO.sub.4 DMSO 84 .sup.a2.0 eq ammonium hydroxide (1.0 mmol) was used as ammonia source, and the reaction temperature was 105 C.

Example 9 Synthesis of Aromatic Amines

(171) Copper iodide (0.05 mmol), ligand L-II-71 (0.05 or 0.1 mmol), potassium phosphate (1.1 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then aryl chloride (1.0 mmol), 1 mL of DMSO and ammonium hydroxide (2.0 mmol) were added. The reaction mixture was well stirred at 110 C. or 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product aromatic amines.

(172) In this example, different aryl chlorides were used, and the reaction conditions were C and D. Condition C were for the more reactive aryl chlorides and condition D were for the relatively less reactive aryl chlorides. The results are shown in the table below. A schematic of this reaction of the synthesis of aromatic amines using copper iodide, potassium phosphate, aryl chloride, and ammonium hydroxide is shown in FIG. 4.

(173) TABLE-US-00011 Product, Reaction Conditions and Yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3) 6.84-6.75 (m, 2H), 6.63-6.55 (m, 2H), 3.51 (s, 2H), 1.28 (s, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) 147.05, 142.38, 125.34, 115.39, 77.71, 28.68.; LC-MS (ESI, m/z): 166.2 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.50 (dd, J = 8.5, 0.6 Hz, 1H), 6.92 (t, J = 1.3 Hz, 1H), 6.89 (dd, J = 2.3, 0.6 Hz, 1H), 6.69 (dd, J = 8.5, 2.3 Hz, 1H), 3.60 (br, 1H), 2.26 (d, J = 1.3 Hz, 3H).; .sup.13C NMR (100 MHz, CDCl.sub.3) 143.35, 140.78, 131.17, 130.53, 123.10, 122.19, 114.54, 106.62, 13.80; HRMS (ESI) calcd. for C.sub.9H.sub.10NS (M + H).sup.+: 164.0528. Found: 164.0532. .sup.1H NMR (400 MHz, CDCl.sub.3) 5.93 (t, J = 2.1 Hz, 1H), 5.87 (d, J = 2.1 Hz, 2H), 3.74 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.59, 148.53, 93.63, 90.77, 55.02; LC-MS (ESI, m/z): 154.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.87 (d, J = 8.3 Hz, 1H), 7.56 (d, J = 8.6 Hz, 1H), 7.15 (d, J = 2.3 Hz, 1H), 7.02 (d, J = 8.2 Hz, 1H), 6.91 (dd, J = 8.6, 2.3 Hz, 1H), 4.04 (br s, 2H), 2.67 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.95, 149.34, 148.01, 135.91, 128.53, 120.22, 118.34, 117.62, 108.34, 25.04; HRMS (ESI) calcd. for C.sub.10H.sub.11N.sub.2 (M + H).sup.+: 159.0917, Found: 159.0919. 0 .sup.1H NMR (500 MHz, CDCl.sub.3) 7.95 (d, J = 8.4 Hz, 1H), 7.29-7.21 (m, 2H), 7.11 (dd, J = 8.1, 1.3 Hz, 1H), 6.90 (dd, J = 7.5, 1.2 Hz, 1H), 4.95 (s, 2H), 2.71 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 156.10, 143.44, 137.85, 136.04, 126.89, 126.31, 122.11, 115.84, 110.10, 25.22; LC-MS (ESI, m/z): 159.1 (M + H).sup.+. .sup.1H NMR (500 MHz, CDCl.sub.3) 8.74 (s, 1H), 8.03 (s, 1H), 7.95-7.87 (m, 1H), 7.84-7.75 (m, 1H), 7.71-7.62 (m, 1H), 7.62-7.53 (m, 1H), 4.11 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 142.97, 137.12, 128.96, 128.63, 127.99, 127.73, 127.03, 126.05, 120.12; LC-MS (ESI, m/z): 145.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.65 (dd, J = 4.2, 1.6 Hz, 1H), 7.94-7.86 (m, 2H), 7.27 (dd, J = 8.2, 4.3 Hz, 1H), 7.16 (dd, J = 8.9, 2.6 Hz, 1H), 6.90 (d, J = 2.7 Hz, 1H), 3.96 (s, 2H).; .sup.13C NMR (100 MHz, CDCl.sub.3) 146.50, 144.85, 143.14, 133.75, 130.19, 129.74, 121.60, 121.29, 107.20; LC-MS (ESI, m/z): 145.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.62 (d, J = 8.1 Hz, 1H), 6.29 (d, J = 2.3 Hz, 1H), 6.13 (dd, J = 8.1, 2.3 Hz, 1H), 5.86 (s, 2H), 3.45 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 148.18, 141.46, 140.30, 108.58, 106.89, 100.65, 98.08; LC-MS (ESI, m/z): 138.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 5.45 (s, 1H), 4.68 (br s, 2H), 3.90 (s, 3H), 3.89 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 171.94, 165.80, 165.18, 80.40, 54.08, 53.40; LC-MS (ESI, m/z): 156.1 (M + H).sup.+. .sup.1H NMR (500 MHz, CDCl.sub.3) 8.66 (d, J = 2.0 Hz, 1H), 8.55 (d, J = 1.9 Hz, 1H), 7.88 (d, J = 8.9 Hz, 1H), 7.19 (dd, J = 9.0, 2.6 Hz, 1H), 7.14 (d, J = 2.5 Hz, 1H), 4.23 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 148.27, 145.09, 144.97, 141.02, 138.09, 130.47, 122.23, 107.93; LC-MS (ESI, m/z): 146.1 (M + H).sup.+. .sup.1H NMR (500 MHz, d6-DMSO) 8.17-8.10 (m, 1H), 7.50 (br s, 1H), 7.19 (d, J = 1.4 Hz, 1H), 6.42-6.36 (m, 2H), 5.65 (br s, 2H); .sup.13C NMR (125 MHz, d6-DMSO) 147.05, 146.47, 131.18, 126.71, 110.36, 106.49, 92.25; LC-MS (ESI, m/z): 134.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.79 (dd, J = 8.3, 1.4 Hz, 1H), 7.67 (dd, J = 8.3, 1.2 Hz, 1H), 7.56 (d, J = 1.5 Hz, 0H), 7.35-7.23 (m, 1H), 6.59 (s, 1H), 4.94 (br s, 2H), 2.58 (d, J = 1.0 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 155.88, 148.30, 142.39, 130.38, 123.91, 123.22, 122.70, 122.58, 112.40, 18.80; LC-MS (ESI, m/z): 159.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.16 (d, J = 8.0 Hz, 2 H), 6.60 (d, J = 8.0 Hz, 2 H), 3.49 (br s, 2 H), 1.27 (s, 9 H); .sup.13C NMR (100 MHz, CDCl.sub.3) 143.9, 141.3, 126.1, 115.0, 33.9, 31.6; LC-MS (ESI, m/z): 150.2 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.25 (d, J = 7.1 Hz, 1H), 6.96 (d, J = 2.8 Hz, 1H), 6.73 (dd, J = 8.6, 2.7 Hz, 1H), 3.84 (br s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.26, 132.18, 128.81 (q, J = 31.0 Hz), 122.98 (q, J = 273.1 Hz), 120.34 (q, J = 1.9 Hz), 118.80, 113.76 (q, J = 5.6 Hz); LC-MS (ESI, m/z): 195.9 (M + H).sup.+. 0 .sup.1H NMR (500 MHz, CDCl.sub.3) 6.32 (t, J = 2.0 Hz, 1H), 6.28 (t, J = 1.9 Hz, 1H), 6.09 (t, J = 2.1 Hz, 1H), 3.73 (s, 3H), 3.63 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 161.28, 148.47, 135.41, 108.05, 104.53, 99.41, 55.39; LC-MS (ESI, m/z): 158.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.18 (d, J = 8.5 Hz, 2H), 6.63 (d, J = 8.5 Hz, 2H), 3.53 (s, 2H), 2.41 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 145.17, 131.02, 125.65, 115.74, 18.77; LC-MS (ESI, m/z): 140.1 (M + H).sup.+. .sup.1H NMR (500 MHz, CDCl.sub.3) 8.35-8.14 (m, 2H), 7.14 (t, J = 2.4 Hz, 1H), 3.91 (br s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 143.06, 139.95, 135.29 (q, J = 4.4 Hz), 127.62, 127.03 (q, J = 32.6 Hz), 124.91, 122.20, 119.49, 117.48 (g, J = 3.7 Hz); LC-MS (ESI, m/z): 163.0 (M + H).sup.+. .sup.1H NMR (400 MHz, DMSO-d6-d6-d.sub.6) 8.44 (dd, J = 8.2, 1.1 Hz, 1H), 7.80-7.74 (m, 1H), 7.74-7.67 (m, 1H), 7.66 (d, J = 2.6 Hz, 1H), 7.55- 7.46 (m, 2H), 7.09 (dd, J = 8.6, 2.6 Hz, 1H), 5.67 (s, 2H); .sup.13C NMR (126 MHz, DMSO-d.sub.6) 178.69, 148.06, 137.17, 132.11, 129.38, 129.02, 127.92, 127.05, 126.33, 125.87, 122.07, 121.20, 110.90; LC-MS (ESI, m/z): 228.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.07-5.98 (m, 3H), 3.75 (s, 2H), 3.74 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 164.69 (d, J = 241.8 Hz), 161.83 (d, J = 13.5 Hz), 148.70 (d, J = 13.4 Hz), 96.68 (d, J = 2.4 Hz), 95.05 (d, J = 25.2 Hz), 91.96 (d, J = 25.7 Hz), 55.46; LC-MS (ESI, m/z): 141.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.63 (dd, J = 9.8, 8.3 Hz, 1H), 6.42 (dd, J = 12.3, 2.5 Hz, 1H), 6.33 (ddd, J = 8.3, 2.5, 1.0 Hz, 1H), 3.35 (s, 4H); .sup.13C NMR (125 MHz, CDCl.sub.3) 152.59 (d, J = 238.0 Hz), 139.39 (d, J = 9.4 Hz), 126.04 (d, J = 13.5 Hz), 118.56 (d, J = 4.8 Hz), 111.56 (d, J = 3.2 Hz), 103.63 (d, J = 22.3 Hz); LC-MS (ESI, m/z): 127.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 6.83-6.76 (m, 2H), 6.70-6.63 (m, 2H), 3.89-3.81 (m, 4H), 3.43 (s, 2H), 3.08-2.95 (m, 4H); .sup.13C NMR (125 MHz, CDCl.sub.3) 144.57, 140.44, 118.33, 116.36, 67.22, 51.25; LC-MS (ESI, m/z): 179.3 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.15-7.06 (m, 2H), 6.94-6.86 (m, 2H), 6.69-6.60 (m, 2H), 6.27-6.18 (m, 2H), 3.60 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 144.65, 133.04, 122.49, 119.81, 115.78, 109.56; LC-MS (ESI, m/z): 159.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.99 (d, J = 8.1 Hz, 1H), 7.93-7.87 (m, 2H), 7.85 (d, J = 7.9 Hz, 1H), 7.48-7.41 (m, 1H), 7.36-7.29 (m, 1H), 6.77-6.71 (m, 2H), 4.00 (s, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 168.65, 154.39, 149.36, 134.73, 129.29, 126.20, 124.59, 124.11, 122.63, 121.55, 114.92; LC-MS (ESI, m/z): 227.2 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.21 (d, J = 8.8 Hz, 1 H), 6.92 (d, J = 2.0 Hz, 1 H), 6.61 (dd, J = 8.4 Hz, J = 2.0 Hz, 1 H), 3.77 (s, 2 H), 2.55 (s, 3 H); .sup.13C NMR (125 MHz, CDCl.sub.3) 164.3, 144.8, 143.6, 142.4, 112.8, 110.2, 104.7, 14.5; LC-MS (ESI, m/z): 149.1 (M + H).sup.+. 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 6.76-6.68 (m, 4H), 3.33 (br s, 4H); .sup.13C NMR (100 MHz, CDCl.sub.3) 134.8, 120.3, 116.7; LC-MS (ESI, m/z): 109.2 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 4.40 (br s, 2H), 6.60 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.8 Hz, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 99.7, 114.3, 120.2, 133.6, 150.5; LC-MS (ESI, m/z): 119.1 (M + H).sup.+. 86%, 20 mmol scale, CuI (2.5 mol %) and L-II-38 (5 mol %) were used, NH.sub.3 (gas, 5 atm) was used as ammonia source, K.sub.3PO.sub.4 (1.1 eq) was used as base, DMSO (8 mL) was used as solvent, the reaction was carried out in an autoclave at 120 C. for 25 hours.

Example 10 Synthesis of 1-methyl-4-phenoxybenzene

(174) ##STR00363##

(175) Phenol (1.5 mmol), copper iodide (0.1 mmol), ligand L-II-31 (0.1 mmol) and potassium phosphate (1.5 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1-chloro-4-methylbenzene (1.0 mmol) and 1 mL of DMSO were added. The reaction mixture was well stirred at 120 C. for 14 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtrated through silica gel and kieselguhr. The filtrate was concentrated and purified by column chromatography to give the product 1-methyl-4-phenoxybenzene (0.1105 g, yield 60%).

(176) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.31 (m, 2H), 7.21-7.15 (m, 2H), 7.14-7.08 (m, 1H), 7.06-7.01 (m, 2H), 7.00-6.93 (m, 2H), 2.38 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.02, 154.91, 133.06, 130.45, 129.83, 122.98, 119.32, 118.53, 20.89

Example 11 Synthesis of 1-methyl-4-phenoxybenzene

(177) ##STR00364##

(178) The operation of this example was the same as that of Example 10 except that different ligands, copper salt catalysts, bases, solvents and temperature were used. The results are shown in the following table.

(179) TABLE-US-00012 Temperature/ Ligand Copper salt Base Solvent C. Yield/% L-II-31 CuI K.sub.3PO.sub.4 DMSO 120 60 L-II-31 CuBr K.sub.3PO.sub.4 DMSO 120 57 L-II-31 CuCl K.sub.3PO.sub.4 DMSO 120 55 L-II-31 CuTc K.sub.3PO.sub.4 DMSO 120 50 L-II-31 Cu(OAc).sub.2 K.sub.3PO.sub.4 DMSO 120 43 L-II-31 CuSO4 K.sub.3PO.sub.4 DMSO 120 49 L-II-31 CuBr.sub.2 K.sub.3PO.sub.4 DMSO 120 52 L-II-31 CuCl.sub.2 K.sub.3PO.sub.4 DMSO 120 56 L-II-31 Cu.sub.2O K.sub.3PO.sub.4 DMSO 120 53 L-II-31 CuI K.sub.2CO.sub.3 DMSO 120 15 L-II-31 CuI Cs.sub.2CO.sub.3 DMSO 120 49 L-II-31 CuI K.sub.3PO.sub.4 NMP 120 44 L-II-31 CuI K.sub.3PO.sub.4 DMF 120 33 L-II-31 CuI K.sub.3PO.sub.4 MeCN 120 41 L-II-31 CuI K.sub.3PO.sub.4 1,4-dioxane 120 37 L-II-31 CuI K.sub.3PO.sub.4 .sup.tBuOH 120 18 L-II-38 CuI K.sub.3PO.sub.4 DMSO 120 20 L-II-33 CuI K.sub.3PO.sub.4 DMSO 120 20 L-II-36 CuI K.sub.3PO.sub.4 DMSO 120 45 L-II-29 CuI K.sub.3PO.sub.4 DMSO 120 44 L-II-32 CuI K.sub.3PO.sub.4 DMSO 120 57 L-II-35 CuI K.sub.3PO.sub.4 DMSO 120 46 L-II-26 CuI K.sub.3PO.sub.4 DMSO 120 30 L-II-40 CuI K.sub.3PO.sub.4 DMSO 120 54 L-II-27 CuI K.sub.3PO.sub.4 DMSO 120 58 L-II-37 CuI K.sub.3PO.sub.4 DMSO 120 66 L-II-5 CuI K.sub.3PO.sub.4 DMSO 120 50 L-II-7 CuI K.sub.3PO.sub.4 DMSO 120 51 L-II-43 CuI K.sub.3PO.sub.4 DMSO 120 39 L-II-9 CuI K.sub.3PO.sub.4 DMSO 120 41 L-II-18 CuI K.sub.3PO.sub.4 DMSO 120 23 L-II-20 CuI K.sub.3PO.sub.4 DMSO 120 26 L-II-21 CuI K.sub.3PO.sub.4 DMSO 120 43 L-II-30 CuI K.sub.3PO.sub.4 DMSO 120 74 L-II-34 CuI K.sub.3PO.sub.4 DMSO 120 73 L-II-4 CuI K.sub.3PO.sub.4 DMSO 120 70 L-II-34 CuI K.sub.3PO.sub.4 DMSO 110 57 L-II-34 CuI K.sub.3PO.sub.4 DMSO 110 40 L-II-47 CuI K.sub.3PO.sub.4 DMSO 120 90

Example 12 Synthesize of Diaryl Ether Via Reaction of 1-chloro-4-methylbenzene with Phenol

(180) ##STR00365##

(181) Phenol (1.2 mmol), copper iodide (0.05 mmol), ligand L-II-34 (0.1 mmol) and potassium phosphate (2.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1-chloro-4-methylbenzene (1.0 mmol) and 1 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtrated through silica gel and kieselguhr. The filtrate was concentrated and purified by column chromatography to give the product diaryl ether. The results obtained are shown in the following table.

(182) TABLE-US-00013 Phenol product and yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.31 (m, 2H), 7.21- 7.15 (m, 2H), 7.14-7.08 (m, 1H), 7.06-7.01 (m, 2H), 7.00- 6.93 (m, 2H), 2.38 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.02, 154.91, 133.06, 130.45, 129.83, 122.98, 119.32, 118.53, 20.89; GC-MS (EI, m/z): 184.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.28-7.24 (m, 2H), 7.14 (d, J = 8.8 Hz, 2H), 6.96-6.88 (m, 4H), 2.47 (s, 3H), 2.34 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 154.0, 153.4, 132.5, 131.5, 129.3, 128.5, 117.7, 116.9, 21.5, 15.3; GC-MS (EI, m/z): 230.3 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.81-7.84 (2H, m), 7.68 (1H, d, J = 8.0 Hz, 7.38-7.47 (2H, m), 7.26 (2H, t, J = 3.6 Hz), 7.18 (2H, d, J = 8.0 Hz), 6.99 (2H, d, J = 8.4 Hz), 2.38 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.7, 154.7, 134.4, 133.1, 130.3, 130.0, 129.8, 127.7, 127.1, 126.5, 124.5, 119.8, 119.3, 113.3, 20.8; GC-MS (EI, m/z): 234.2 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.28-7.35 (m, 2H), 7.08-7.14 (m, 2H), 6.88-6.93 (m, 4H), 2.31 (s, 3H), 1.32 (s, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.35, 155.08, 145.69, 132.62, 130.22, 126.51, 118.95, 118.65, 117.95, 115.96, 34.32, 31.58, 20.77; GC-MS (EI, m/z): 234.2 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.14 (2H, d, J = 8.3 Hz), 7.00 (2H, d, J = 9.1 Hz), 6.91 (4H, m), 3.83 (3H, s), 2.36 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 156.0, 155.6, 150.7, 132.0, 130.0, 120.2, 117.7, 114.7, 55.6, 20.5; GC-MS (EI, m/z): 214.2 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 2.30 (s, 6 H), 6.88 (d, J = 8.4 Hz, 4H), 7.1 (d, J = 8.4 Hz, 4H); .sup.13C NMR (100 MHz, CDCl.sub.3) 20.8, 118.7, 130.3, 132.5, 155.5; GC-MS (EI, m/z): 198.2 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 2.18 (s, 6H), 2.24 (s, 3H), 6.52 (s, 2H), 6.62 (s, 1H), 6.81 (d, J = 7.6 Hz, 2H), 7.03 (d, J = 7.6 Hz, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 20.8, 21.4, 116.2, 119.2, 124.7, 130.3, 132.7, 139.5, 155, 157.9; GC-MS (EI, m/z): 212.2 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 2.34 (s, 3H), 3.88 (s, 3H), 6.90 (m, 4H), 6.94 (m, 1H), 7.13 (m, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.7, 151.4, 145.9, 132.3, 130.3, 124.5, 121.2, 117.7, 112.9, 56.2, 20.9; GC-MS (EI, m/z): 214.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 2.34 (s, 3 H), 6.88 (d, J = 7.6 Hz, 2H), 6.94-6.97 (m, 2H), 7.15 (d, J = 8.6 Hz, 2H), 7.35 (t, J = 8.0 Hz, 1 H), 7.45-7.54 (m, 2H), 7.58 (d, J = 8.2 Hz, 1H), 7.84-7.87 (m, 1H), 8.22-8.25 (m, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 20.7, 112.6, 118.8, 122.1, 122.9, 125.8, 125.8, 126.5, 126.7, 127.7, 130.3, 132.8, 134.9, 153.6, 155.3; GC-MS (EI, m/z): 234.3 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 2.24 (s, 3 H), 2.29 (s, 3H), 6.80 (d, J = 8.4 Hz, 2H); 6.85 (d, J = 8.0 Hz, 1H), 7.01 (t, J = 7.2 Hz, 1H), 7.05-7.15 (m, 3H), 7.21 (d, J = 7.6 Hz, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 16.3, 20.7, 117.6, 199.3, 123.7, 127.2, 129.8, 130.2, 131.5, 132, 155.1, 155.7; GC-MS (EI, m/z): 198.2 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.14 (d, 2H, J = 8.1 Hz), 7.07-6.92 (m, 4H), 6.89 (d, 2H, J = 8.2 Hz), 2.35 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.6 (d, J = 241.0 Hz), 155.3, 153.5, 132.9, 130.3, 120.0 (d, J = 8.2 Hz), 118.6, 116.2 (d, J = 23.3 Hz), 20.7; GC-MS (EI, m/z): 202.2 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 2.37 (s, 3H), 2.57 (s, 3H), 6.95-6.98 (m, 4H), 7.18-7.21 (d, J = 8.26 Hz, 2H), 7.91-7.94 (d, J = 8.72, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 20.8, 26.4, 116.8, 120.2, 130.5, 131.6, 134.3, 153.0, 162.4, 196.7; GC-MS (EI, m/z): 226.2 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 2.37 (3H, s), 6.91-6.95 (2H, m), 7.16-7.22 (4H, m), 7.31-7.41 (2H, m); .sup.13C NMR (100 MHz, CDCl.sub.3) 157.7, 154.0, 131.5, 129.1, 128.7, 125.3, 123.2, 121.1, 118.7, 117.2, 112.3, 21.1; GC-MS (EI, m/z): 209.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 8.39 (s, 1H), 8.33 (d, J = 2.3 Hz, 1H), 7.26-7.22 (m, 2H), 7.17 (d, J = 8.3 Hz, 2H), 6.98- 6.90 (m, 2H), 2.35 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.7, 152.2, 141.1, 139.5, 134.3, 130.1, 124.1, 121.0, 119.5, 20.9; LC-MS (ESI, m/z): 186.2 (M + H).sup.+.

Example 13 Synthesis of Diaryl Ether and Aryl Alkyl Ether Via Coupling Reaction of Aryl Chloride and R1OH

(183) ##STR00394##

(184) Aryl halide substrate (1.0 mmol), phenol (1.2 mmol), copper iodide (0.05 mmol), ligand L-II-34 (0.1 mmol), and potassium phosphate (2.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1 mL of DMSO was added. The reaction mixture was well stirred at 120 C. for 30 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtrated through silica gel and kieselguhr. The filtrate was concentrated and purified by column chromatography to give the product diaryl ether. The results obtained are shown in the following table.

(185) TABLE-US-00014 aryl halide and phenol product and yield Characterization data of the product .sup.1H NMR (400 MHz, CDCl.sub.3) 3.83 (s, 3H), 6.94 (m, 4H), 7.01 (m, 2H), 7.58 (m, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 55.9, 105.4, 115.5, 117.3, 119.2, 122.1, 134.3, 148.1, 157.3, 162.8; GC-MS (EI, m/z): 225.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.90 (2H, d, J = 8.8 Hz), 7.00 (2H, d, J = 9.0 Hz), 6.92-6.88 (4H, m), 3.80 (3H, s), 2.55 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 196.6, 162.9, 156.6, 148.4, 131.3, 130.5, 121.6, 116.3, 115.0, 55.6, 26.3; GC-MS (EI, m/z): 242.1 (M.sup.+). 00 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.80 (2H, d, J = 9.0 Hz), 7.66 (1H, d, J = 8.0 Hz), 7.42 (2H, m), 7.26 (1H, m), 7.18 (1H, m), 7.06 (2H, d, J = 8.9 Hz), 6.92 (2H, d, J = 9.0 Hz); .sup.13C NMR (100 MHz, CDCl.sub.3) 156.4, 156.0, 140.0, 134.3, 129.7, 127.6, 126.9, 126.4, 124.3, 121.0, 119.3, 114.9, 112.2, 55.6; GC-MS (EI, m/z): 250.1 (M.sup.+). 01 02 .sup.1H NMR (400 MHz, CDCl.sub.3) 6.91-6.81 (8H, m), 3.85 (4H, m), 3.77 (3H, s), 3.08 (4H, m); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.3, 151.6, 151.3, 147.1, 119.6, 119.1, 117.3, 114.6, 66.9, 55.6, 50.2; LC-MS (ESI, m/z): 286.1 (M + H).sup.+. 03 04 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.69 (1H, s), 7.43-7.45 (2H, d, J = 8.8), 7.13-7.14 (2H, d, J = 8.2), 6.94-6.95 (2H, d, J = 8.8), 6.89-6.91 (2H, d, J = 8.4), 2.34 (3H, s), 2.17 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 168.8, 155.2, 154.4, 135.9, 133.3, 133.0, 130.5, 129.0, 122.1, 119.2, 118.9, 24.6, 20.9; LC-MS (ESI, m/z): 242.1 (M + H).sup.+. 05 06 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.56 (d, J = 8.6 Hz, 2H), 7.29-7.25 (m, 1H), 7.04-6.99 (m, 1H), 7.03 (d, J = 8.7 Hz, 2H), 6.87-6.84 (m, 2H), 2.36 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.7, 155.7, 140.4, 129.8, 127.0, 125.3, 124.6, 122.9, 120.6, 117.9, 117.0, 21.4; GC-MS (EI, m/z): 252.1 (M.sup.+). 07 08 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.38-7.31 (m, 2H), 7.15- 7.09 (m, 1H), 7.07-7.02 (m, 2H), 6.23 (t, J = 2.2 Hz, 1H), 6.18 (d, J = 2.2 Hz, 2H), 3.75 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.72, 159.37, 156.82, 129.85, 123.63, 119.37, 97.38, 95.58, 55.54; GC-MS (EI, m/z): 230.1 (M.sup.+). 09 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.01-6.95 (m, 2H), 6.92- 6.86 (m, 2H), 6.70 (s, 1H), 6.58 (s, 2H), 3.82 (s, 3H), 2.28 (s, 6H); .sup.13C NMR (126 MHz, CDCl.sub.3) 158.61, 155.87, 150.42, 139.57, 124.33, 120.93, 115.44, 114.91, 55.77, 21.46; GC-MS (EI, m/z): 228.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.37-7.30 (m, 2H), 7.10 (t, J = 8.0 Hz, 2H), 7.06-7.01 (m, 2H), 6.46-6.38 (m, 2H), 6.34 (t, J = 2.2 Hz, 1H), 3.45 (s, 2H); .sup.13C NMR (126 MHz, CDCl.sub.3) 158.54, 157.24, 148.06, 130.45, 129.75, 123.26, 119.20, 110.20, 109.01, 105.64, 114.91, 55.77, 21.46; LC-MS (ESI, m/z): 186.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 2.27 (3H, s), 6.58 (2H, s), 6.73 (1H, s), 6.9-7.1 (4H, m); .sup.13C NMR (100 MHz, CDCl.sub.3) 21.7, 116.4, 116.6 (d, J = 23 Hz), 120.9 (d, J = 8.6 Hz), 120.9, 125.3, 140.0, 153.5 (d, J = 2.6 Hz), 158.0, 159.1 (d, J = 241 Hz); GC-MS (EI, m/z): 216.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31 (d, J = 8.6 Hz, 2H), 7.14 (d, J = 8.6 Hz, 2H), 7.00-6.94 (m, 2H), 6.94-6.88 (m, 2H), 4.65 (s, 2H), 2.34 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 155.9, 154.0, 134.3, 131.5, 128.7, 128.0, 121.9, 117.1, 21.3; HRMS-ESI: m/z calcd for C.sub.14H.sub.15O.sub.2 (M + H).sup.+: 215.1072, found: 215.1069. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.33-7.29 (m, 2H), 7.06 (t, J = 7.3 Hz, 1H), 6.96 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 2.3 Hz, 1H), 6.50 (dd, J = 2.3 Hz, J = 8.4 Hz, 1H), 5.97 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.63, 151.81, 148.80, 144.19, 130.09, 123.15, 118.25, 112.39, 108.71, 102.62, 101.94; GC-MS (EI, m/z): 214.1 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 8.60-8.13 (m, 2H), 7.25- 7.21 (m, 2H), 7.16 (d, J = 8.2 Hz, 2H), 6.92 (d, J = 8.5 Hz, 2H), 2.34 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 153.91, 143.98, 141.08, 133.93, 130.60, 130.47, 124.88, 124.12, 119.25, 20.83; HRMS-ESI: m/z calcd for C.sub.12H.sub.12NO (M + H).sup.+: 186.0919, found: 186.0916. .sup.1H NMR (500 MHz, CDCl.sub.3) 8.81 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.98 (dd, J = 8.3, 1.5 Hz, 1H), 7.48 (dd, J = 9.2, 2.7 Hz, 1H), 7.34 (dd, J = 8.3, 4.2 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 7.16 (d, J = 2.7 Hz, 1H), 7.00 (d, J = 8.5 Hz, 2H), 2.37 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 156.23, 153.99, 148.80, 144.96, 135.10, 133.78, 131.23, 130.47, 129.12, 122.99, 121.45, 119.75, 112.00, 20.78; LC-MS (ESI, m/z): 235.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.81 (d, J = 8.7 Hz, 1H), 7.47 (d, J = 5.5 Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.24 (dd, J = 5.5, 0.8 Hz, 1H), 7.16 (d, J = 8.5 Hz, 2H), 7.11 (dd, J = 8.7, 2.4 Hz, 1H), 6.95 (d, J = 8.5 Hz, 2H), 2.36 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 155.51, 155.31, 140.88, 134.53, 132.83, 130.37, 128.03, 123.77, 123.51, 118.88, 117.26, 112.56, 20.84; HRMS-EI: m/z calcd for C.sub.15H.sub.12OS (M.sup.+): 240.0603, found: 240.0609. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.43 (1H, d, J = 1.1), 8.25 (1H, d, J = 2.7), 8.11 (1H, dd, J = 2.7, 1.1), 7.24 (2H, d, J = 8.5), 7.07 (2H, d, J = 8.5), 2.39 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.5, 150.7, 141.1, 138.3, 135.8, 135.1, 130.3, 121.1, 20.9; HRMS-ESI: m/z calcd for C.sub.11H.sub.11N.sub.2O (M + H).sup.+: 187.0871, found: 187.0875.

Example 14 Synthesis of 4,4-dimethyldiphenylsulfide

(186) ##STR00427##

(187) 4-methylthiophenol (1.5 mmol), copper iodide (0.1 mmol), ligand L-II-34 (0.1 mmol) and potassium phosphate (1.5 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1-chloro-4-methylbenzene (1.0 mmol) and 1 mL of DMSO were added. The reaction mixture was well stirred at 120 C. for 14 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtrated through silica gel and kieselguhr. The filtrate was concentrated and purified by column chromatography to give the product 4,4-dimethyldiphenylsulfide (36.4 mg, yield 17%).

(188) .sup.1H NMR (400 MHz, CDCl.sub.3) 2.32 (s, 6H), 7.10 (d, J=7.8 Hz, 2H), 7.22-7.25 (m, 4H); .sup.13C NMR (100 MHz, CDCl.sub.3) 21.2, 130.0, 131.2, 132.8, 137.0.

Example 15 Synthesis of Aromatic Amines by Reaction of Aryl Bromides/Iodides and Amines

(189) ##STR00428##

(190) Aryl bromide/iodide substrates (1.0 mmol), amine (1.2 mmol), copper iodide (0.05 mmol), ligand L-II-38 (0.05 mmol) and potassium phosphate (1.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1 mL of DMSO was added. The reaction mixture was well stirred at 20-70 C. for 5-10 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtrated through silica gel and kieselguhr. The filtrate was concentrated and purified by column chromatography to give the product aromatic amines. The results obtained are shown in the following table.

(191) TABLE-US-00015 Temperature Substrate, Product and Yield and Time Characterization data of product 0 70 C., 6 h 70 C., 6 h 1H NMR (400 MHz, CDCl.sub.3) 7.42-7.31 (m, 4H), 7.27 (t, J = 6.8 Hz, 1H), 7.17 (t, J = 7.8 Hz, 2H), 6.71 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 8.1 Hz, 2H), 4.32 (s, 2H), 4.02 (br s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 148.26, 139.54, 129.38, 128.75, 127.62, 127.34, 117.66, 112.94, 48.41; HRMS-ESI: m/z calcd for C.sub.13H.sub.14N (M + H).sup.+: 184.1121, found: 184.1124. 24 C., 6 h 70 C., 10 h .sup.1H NMR (400 MHz, CDCl.sub.3) 7.17 (t, J = 7.8 Hz, 2H), 6.73 (t, J = 7.4 Hz, 1H), 6.65 (d, J = 8.0 Hz, 2H), 3.85 (d, J = 5.4 Hz, 1H), 2.13-2.14 (m, 1H), 1.06 (q, J = 3.6 Hz, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 176.3, 147.3, 129.3, 118.2, 113.6, 62.3, 19.2, 18.3; HRMS-ESI: m/z calcd for C.sub.11H.sub.16NO.sub.2 (M + H).sup.+: 194.1182, found: 194.1173. 70 C., 5 h .sup.1H NMR (500 MHz, CDCl.sub.3) 6.78 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.20-3.15 (m, 2H), 2.06 (d, J = 10.2 Hz, 2H), 1.79-1.75 (m, 2H), 1.67-1.65 (m, 1H), 1.40-1.32 (m, 2H), 1.26-1.21 (m, 1H), 1.17-1.09 (m. 2H): .sup.13C NMR (125 MHz, CDCl.sub.3) 152.1, 141.8, 115.1, 115.0, 56.0, 53.0, 33.8, 26.2, 25.3; HRMS-ESI: m/z calcd for C.sub.13H.sub.20NO (M + H).sup.+: 206.1539, found: 206.1543. 50 C., 10 h .sup.1H NMR (400 MHz, CDCl.sub.3) 7.50-7.40 (m, 4H), 7.39-7.31 (m, 1H), 7.23-7.13 (m, 2H), 6.65-6.54 (m, 2H), 4.34 (s, 2H), 3.97 (br s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 146.67, 138.97, 129.09, 128.74, 127.45, 127.40, 122.06, 113.99, 48.32; HRMS-ESI: m/z calcd for C.sub.13H.sub.13ClN (M + H).sup.+: 218.0731, found: 218.0735.

Example 16 Synthesis of Diaryl Ethers Via Reaction of Aryl Bromides with phenols

(192) ##STR00435##

(193) Aryl halide substrate (1.0 mmol), phenol (1.2 mmol), copper iodide (0.05 mmol), ligand L-II-37 (0.05 mmol), potassium phosphate (2.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 1 mL of DMSO was added. The reaction mixture was well stirred at 80 C. for 12 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtrated through silica gel and kieselguhr. The filtrate was concentrated and purified by column chromatography to give the product diaryl ether. The results obtained are shown in the following table.

(194) TABLE-US-00016 aryl bromide and phenol product and yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3) 3.83 (s, 3H), 6.94 (m, 4H), 7.01 (m, 2H), 7.58 (m, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 55.9, 105.4, 115.5, 117.3, 119.2, 122.1, 134.3, 148.1, 157.3, 162.8; GC-MS (EI, m/z): 225.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.90 (2H, d, J = 8.8 Hz), 7.00 (2H, d, J = 9.0 Hz), 6.92-6.88 (4H, m), 3.80 (3H, s), 2.55 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 196.6, 162.9, 156.6, 148.4, 131.3, 130.5, 121.6, 116.3, 115.0, 55.6, 26.3; GC-MS (EI, m/z): 242.1 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.80 (2H, d, J = 9.0 Hz), 7.66 (1H, d, J = 8.0 Hz), 7.42 (2H, m), 7.26 (1H, m), 7.18 (1H, m), 7.06 (2H, d, J = 8.9 Hz), 6.92 (2H, d, J = 9.0 Hz); .sup.13C NMR (100 MHz, CDCl.sub.3) 156.4, 156.0, 140.0, 134.3, 129.7, 127.6, 126.9, 126.4, 124.3, 121.0, 119.3, 114.9, 112.2, 55.6; GC-MS (EI, m/z): 250.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 2.35 (s, 3H), 6.88 (m, 2H), 6.93 (d, J = 7.5 Hz, 1H), 7.06 (m, 2H), 7.23 (m, 1H), 7.35 (m, 1H), 7.43 (m, 2H), 7.58 (m, 4H); .sup.13C NMR (100 MHz, CDCl.sub.3) 157.1, 156.0, 134.0, 138.1, 133.9, 129.2, 128.7, 128.3, 127.9, 127.6, 122.3, 118.0, 116.3, 115.7, 21.3; GC-MS (EI, m/z): 260.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.30 (s, 2H), 7.08-7.14 (m, 2H), 6.88-6.93 (m, 4H), 2.31 (s, 3H,), 1.32 (s, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.35, 155.08, 145.69, 132.62, 130.22, 126.51, 118.95, 118.65, 117.95, 115.96, 34.32, 31.58, 20.77; GC-MS (EI, m/z): 240.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 6.91-6.81 (8H, m), 3.85 (4H, m), 3.77 (3H, s), 3.08 (4H, m); .sup.13C NMR (100 MHz, CDCl.sub.3) 155.3, 151.6, 151.3, 147.1, 119.6, 119.1, 117.3, 114.6, 66.9, 55.6, 50.2; LC-MS (ESI, m/z): 286.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.56 (d, J = 8.6 Hz, 2H), 7.29-7.25 (m, 1H), 7.04-6.99 (m, 1H), 7.03 (d, J = 8.7 Hz, 2H), 6.87-6.84 (m, 2H), 2.36 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.7, 155.7, 140.4, 129.8, 127.0, 125.3, 124.6, 122.9, 120.6, 117.9, 117.0, 21.4; GC-MS (EI, m/z): 252.1 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 7.38-7.31 (m, 2H), 7.15- 7.09 (m, 1H), 7.07-7.02 (m, 2H), 6.23 (t, J = 2.2 Hz, 1H), 6.18 (d, J = 2.2 Hz, 2H), 3.75 (s, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) 161.72, 159.37, 156.82, 129.85, 123.63, 119.37, 97.38, 95.58, 55.54; GC-MS (EI, m/z): 230.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.01-6.95 (m, 2H), 6.92-6.86 (m, 2H), 6.70 (s, 1H), 6.58 (s, 2H), 3.82 (s, 3H), 2.28 (s, 6H); .sup.13C NMR (126 MHz, CDCl.sub.3) 158.61, 155.87, 150.42, 139.57, 124.33, 120.93, 115.44, 114.91, 55.77, 21.46; GC-MS (EI, m/z): 228.1 (M.sup.+). .sup.1H NMR (400 MHz, CDCl.sub.3) 7.37-7.30 (m, 2H), 7.10 (t, J = 8.0 Hz, 2H), 7.06-7.01 (m, 2H), 6.46-6.38 (m, 2H), 6.34 (t, J = 2.2 Hz, 1H), 3.45 (s, 2H); .sup.13C NMR (126 MHz, CDCl.sub.3) 158.54, 157.24, 148.06, 130.45, 129.75, 123.26, 119.20, 110.20, 109.01, 105.64, 114.91, 55.77, 21.46; LC-MS (ESI, m/z): 186.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.31 (d, J = 8.6 Hz, 2H), 7.14 (d, J = 8.6 Hz, 2H), 7.00-6.94 (m, 2H), 6.94-6.88 (m, 2H), 4.65 (s, 2H), 2.34 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 155.9, 154.0, 134.3, 131.5, 128.7, 128.0, 121.9, 117.1, 21.3; HRMS-ESI: m/z calcd for C.sub.14H.sub.15O.sub.2 (M + H).sup.+: 215.1072, found: 215.1069. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.33-7.29 (m, 2H), 7.06 (t, J = 7.3 Hz, 1H), 6.96 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 2.3 Hz, 1H), 6.50 (dd, J = 2.3 Hz, J = 8.4 Hz, 1H), 5.97 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) 158.63, 151.81, 148.80, 144.19, 130.09, 123.15, 118.25, 112.39, 108.71, 102.62, 101.94; GC-MS (EI, m/z): 214.1 (M.sup.+). 0 .sup.1H NMR (400 MHz, CDCl.sub.3) 8.60-8.13 (m, 2H), 7.25- 7.21 (m, 2H), 7.16 (d, J = 8.2 Hz, 2H), 6.92 (d, J = 8.5 Hz, 2H), 2.34 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 153.91, 143.98, 141.08, 133.93, 130.60, 130.47, 124.88, 124.12, 119.25, 20.83; HRMS-ESI: m/z calcd for C.sub.12H.sub.12NO (M + H).sup.+: 186.0919, found: 186.0916. .sup.1H NMR (500 MHz, CDCl.sub.3) 8.81 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.98 (dd, J = 8.3, 1.5 Hz, 1H), 7.48 (dd, J = 9.2, 2.7 Hz, 1H), 7.34 (dd, J = 8.3, 4.2 Hz, 1H), 7.20 (d, J = 8.2 Hz, 2H), 7.16 (d, J = 2.7 Hz, 1H), 7.00 (d, J = 8.5 Hz, 2H), 2.37 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 156.23, 153.99, 148.80, 144.96, 135.10, 133.78, 131.23, 130.47, 129.12, 122.99, 121.45, 119.75, 112.00, 20.78; LC-MS (ESI, m/z): 235.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.81 (d, J = 8.7 Hz, 1H), 7.47 (d, J = 5.5 Hz, 1H), 7.39 (d, J = 2.4 Hz, 1H), 7.24 (dd, J = 5.5, 0.8 Hz, 1H), 7.16 (d, J = 8.5 Hz, 2H), 7.11 (dd, J = 8.7, 2.4 Hz, 1H), 6.95 (d, J = 8.5 Hz, 2H), 2.36 (s, 3H); .sup.13C NMR (126 MHz, CDCl.sub.3) 155.51, 155.31, 140.88, 134.53, 132.83, 130.37, 128.03, 123.77, 123.51, 118.88, 117.26, 112.56, 20.84; HRMS-EI: m/z calcd for C.sub.15H.sub.12OS (M.sup.+): 240.0603, found: 240.0609. .sup.1H NMR (400 MHz, CDCl.sub.3) 8.43 (1H, d, J = 1.1), 8.25 (1H, d, J = 2.7), 8.11 (1H, dd, J = 2.7, 1.1), 7.24 (2H, d, J = 8.5), 7.07 (2H, d, J = 8.5), 2.39 (3H, s); .sup.13C NMR (100 MHz, CDCl.sub.3) 160.5, 150.7, 141.1, 138.3, 135.8, 135.1, 130.3, 121.1, 20.9; HRMS-ESI: m/z calcd for C.sub.11H.sub.11N.sub.2O (M + H).sup.+: 187.0871, found: 187.0875.

Example 17 Synthesis of N-4-methoxyphenylpyrrole Via Coupling Reaction of 4-chloroanisole with Pyrrole

(195) ##STR00468##

(196) Cuprous oxide (0.1 mmol), ligand (0.1 mmol), potassium phosphate (2.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then 4-chloroanisole (1.0 mmol), pyrrole (1.3 mmol) and 0.5 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography (petroleum ether:ethyl acetate=50:1) to give the product N-4-methoxyphenylpyrrole (88 mg, 51% yield).

(197) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.29-7.33 (m, 2H), 6.98-7.01 (m, 2H), 6.90-6.96 (m, 2H), 6.32 (t, J=2.0 Hz, 2H), 3.83 (s, 3H). GC-MS (EI): m/z=173 [M].sup.+.

Example 18 Synthesis of N-4-methoxyphenylpyrrole Via Coupling Reaction of 4-chloroanisole with Pyrrole

(198) The operation of this example was the same as that of Example 17 except different oxalamide ligands was used. The results of the supplemental experiment are shown in the following table.

(199) TABLE-US-00017 Ligand Yield/% Ligand Yield/% Ligand Yield/% L-II-82 51 L-II-83 42 L-II-84 25 L-II-85 48 L-II-86 23 L-II-87 18 L-II-88 36 L-II-89 17 L-II-21 32 L-II-79 28 L-II-80 33 L-II-81 30 L-II-98 22 L-II-99 36

Example 19 Synthesis of N-aryl Heterocycles

(200) Cuprous oxide (0.1 mmol), ligand (0.1 mmol), potassium phosphate (2.0 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (three times), and then 4-chloroanisole (1.0 mmol), nitrogen heteroaryl compound (1.3 mmol) and 0.5 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product N-aryl heterocycles.

(201) Different N-heteroaromatic rings were used in this example. The results are given in the following table.

(202) ##STR00469##

(203) TABLE-US-00018 Product and Yield Characterization data of product 0 .sup.1H NMR (400 MHz, CDCl.sub.3) : 7.72 (d, J = 7.5 Hz, 1H), 7.49-7.41 (m, 3H), 7.30 (d, J = 3.3 Hz, 1H), 7.26-7.15 (m, 2H), 7.06-7.03 (m, 2H), 6.68 (d, J = 3.0 Hz, 1H), 3.89 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) : 158.2, 136.3, 132.8, 128.9, 128.3, 125.9, 122.1, 120.9, 120.0, 114.7, 110.3, 102.8, 55.6. HRMS (ESI) Calcd for C.sub.15H.sub.13NO (M + H+): 223.0997, found 223.1002. .sup.1H NMR (300 MHz, CDCl.sub.3) : 8.14 (d, J = 7.8 Hz, 2H), 7.47-7.42 (m, 2H), 7.39-7.36 (m, 2H), 7.33-7.20 (m, 4H), 7.12-7.07 (m, 2H), 3.90 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) : 158.8, 141.3, 130.2, 128.5, 125.8, 123.0, 120.2, 119.6, 115.0, 109.6, 55.6. HRMS (ESI) Calcd for C.sub.19H.sub.15NO (M + H+): 273.1154, found 273.1157. .sup.1H NMR (400 MHz, CDCl.sub.3, ppm): 7.81 (d, J = 3.2 Hz, 1H), 7.69 (d, J = 1.6 Hz, 1H), 7.59-7.55 (m, 2H), 6.98-6.93 (m, 2H), 6.42 (t, J = 2.4 Hz, 1H), 3.83 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3, ppm): 158.2, 140.6, 134.0, 126.8, 119.9, 114.5, 107.2, 55.6. HRMS (ESI) Calcd for C.sub.10H.sub.10N.sub.2O (M + H+): 174.0793, found 174.0792. .sup.1H NMR (400 MHz, CDCl.sub.3) : 7.77 (s, 1H), 7.33-7.28 (m, 2H), 7.20 (d, J = 6.6 Hz, 2H), 7.03-6.97 (m, 2H), 3.85 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) : 158.8, 135.8, 130.7, 130.0, 123.2, 118.7, 114.8, 55.6. HRMS (ESI) Calcd for C.sub.10H.sub.10N.sub.2O (M + H+): 174.0793, found 174.0796.

Example 20 Synthesis of N-(4-methoxyphenyl)benzamide Via Coupling Reaction of 4-chloroanisole with Benzamide

(204) ##STR00474##

(205) Cuprous oxide (0.1 mmol), ligand L-II-83 (0.1 mmol), potassium phosphate (1.5 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (three times), and then 4-chloroanisole (1.0 mmol), benzamide (1.3 mmol) and 0.5 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography (petroleum ether:ethyl acetate=2:1) to give the product N-(4-methoxyphenyl)benzamide (127 mg, 56% yield).

(206) .sup.1H NMR (400 MHz, CDCl.sub.3): 7.85 (d, J=7.2 Hz, 3H), 7.55-7.51 (m, 3H), 7.46 (t, J=7.6 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 3.81 (s, 3H). LC-MS (ESI, m/z): 228.1 (M+H).sup.+.

Example 21 Synthesis of N-(4-methoxyphenyl)benzamide Via Coupling Reaction of 4-chloroanisole with Benzamide

(207) The operation of this example was the same as that of Example 20 except that different oxalic diamide ligands were used. The results of the experiment are shown in the following table.

(208) TABLE-US-00019 Ligand Yield/% Ligand Yield/% Ligand Yield/% L-II-82 53 L-II-83 56 L-II-84 15 L-II-85 30 L-II-86 20 L-II-87 32 L-II-88 37 L-II-89 35 L-II-21 20 L-II-79 25 L-II-80 28 L-II-81 38 L-II-90 60 L-II-90 75 (The reaction time was extended to 36 hours)

Example 22 Synthesis of N-(4-methoxyphenyl)benzamide Via Coupling Reaction of 4-chloroanisole with Benzamide

(209) ##STR00475##

(210) The operation of this example was the same as that of Example 20 except that different copper salt catalysts, bases, solvents and temperatures were used. The results obtained are shown in the following table.

(211) TABLE-US-00020 Entry Copper salt Base Solvent Temperature/ C. Yield/% 1 CuI K.sub.3PO.sub.4 DMSO 120 40 2 CuBr K.sub.3PO.sub.4 DMSO 120 45 3 CuCl K.sub.3PO.sub.4 DMSO 120 41 4 CuTc K.sub.3PO.sub.4 DMSO 120 38 5 Cu(OAc).sub.2 K.sub.3PO.sub.4 DMSO 120 37 6 Cu.sub.2O K.sub.3PO.sub.4 DMSO 120 56 7 CuBr.sub.2 K.sub.3PO.sub.4 DMSO 120 29 8 Cu.sub.2O K.sub.3PO.sub.4 DMSO 120 28 9 Cu.sub.2O K.sub.3PO.sub.4 DMSO 120 39 11 Cu.sub.2O K.sub.3PO.sub.4 DMF 120 28 12 Cu.sub.2O K.sub.3PO.sub.4 MeCN 120 42 13 Cu.sub.2O K.sub.3PO.sub.4 DMSO 130 58 14 Cu.sub.2O K.sub.3PO.sub.4 DMSO 140 55

Example 23 Synthesis of N-aryl Benzamides

(212) Cuprous oxide (0.1 mmol), ligand (0.1 mmol) and potassium phosphate (1.5 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (three times), and then 1-chloro-4-(methoxyl)benzene (1.0 mmol), amide (1.3 mmol) and 0.5 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give N-aryl benzamide.

(213) In this example, different chlorobenzenes and amides were used. The results are given in the following table.

(214) ##STR00476##

(215) TABLE-US-00021 Product and Yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3): 7.81 (br s, 1H), 7.37 (d, J = 9.0 Hz, 2H), 6.81 (d, J = 9.0 Hz, 2H), 3.76 (s, 3H), 2.10 (s, 3H). LC-MS (ESI, m/z): 165.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3): d = 7.28 (d, J = 7.6 Hz, 2H), 7.20-7.15 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 6.72 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 3.44 ppm (s, 3H); LC-MS (ESI, m/z): 242.1 (M + H).sup.+. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.50 (d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H), 3.85-3.80 (m, 5H,), 2.60 (t, 2H, J = 8.0 Hz, J = 8.0 Hz), 2.20-2.14 (m, 2H); LC-MS (ESI, m/z): 192.1 (M + H).sup.+. 0 .sup.1H NMR (400 MHz, CDCl.sub.3): 7.96 (br s, 1H), 7.84 (d, J = 7.2 Hz, 2H), 7.54-7.49 (m, 3H), 7.46-7.41 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H); LC-MS (ESI, m/z): 211.1 (M + H).sup.+.

Example 24 Coupling of 4-chloroanisole with Sodium Alkylsulfinate or Sodium Arylsulfinate

(216) ##STR00481##

(217) Sodium methanesulfinate (0.6 mmol), copper iodide (0.05 mmol), ligand (0.1 mmol) and potassium phosphate (1.5 mmol) were added into a 10 mL of Schlenk tube. The tube was evacuated and backfilled with argon (three times), and then 4-chloroanisole (0.5 mmol) and 1 mL of DMSO were added. The reaction mixture was stirred well at 120 C. for 24 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtered through silica gel and celite column. The filtrate was concentrated and purified by column chromatography to give the product.

(218) 1-methoxy-4-(methylsulfonyl)benzene: .sup.1H NMR (400 MHz, CDCl.sub.3) 3.05 (s, 3H), 3.90 (s, 3H), 7.04 (dd, J=7.5, 2.1 Hz, 2H), 7.88 (dd, J=7.5, 2.1 Hz, 2H); ELMS (m/z) 186 (M+)

(219) 1-methoxy-4-(phenylsulfonyl)benzene: .sup.1H NMR (400 MHz, CDCl.sub.3) 3.84 (s, 3H), 6.96 (m, 2H), 7.51 (m, 3H), 7.90 (m, 4H); ELMS (m/z) 248 (M+).

(220) The results obtained by using different ligands are listed in the following table.

(221) TABLE-US-00022 Ligand Yield/% Ligand Yield/% Ligand Yield/% PhSO.sub.2Na L-I-16 20 L-II-3 30 L-II-5 15 L-II-7 10 L-II-18 16 L-II-19 20 L-II-44 5 L-II-47 8 L-II-53 15 CH.sub.3SO.sub.2Na L-II-31 17 L-II-37 24

Example 25 Synthesis of 4-methoxyphenol by Copper-Catalyzed Reaction of 4-chloroanisole

(222) ##STR00482##

(223) Copper acetylacetonate (Cu(acac).sub.2) (0.025 mmol), ligand L-II-93 (0.025 mmol), lithium hydroxide monohydrate (1.05 mmol) were added into a 10 mL of Schlenk tube. The tube was evacuated and backfilled with argon (three times), and then 4-chloroanisole (0.5 mmol), 0.8 mL of DMSO and 0.2 mL of H.sub.2O were added successively under argon. The reaction mixture was stirred well at 130 C. for 24 hours. After cooling, 2 mL of hydrochloric acid (1 mol/L), water and ethyl acetate were added and separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography (dichloromethane:methanol=60:1) to give the product 4-methoxyphenol (46 mg, 74% yield).

(224) .sup.1H NMR (400 MHz, CDCl.sub.3) 6.79-6.61 (m, 4H), 4.96 (br s, 1H), 3.69 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 55.9, 114.9, 116.1, 149.6, 153.7; ESI-MS: 125.1 (M+H).sup.+

Example 26 Synthesis of 4-methoxyphenol by Copper-Catalyzed Reaction of 4-chloroanisole

(225) The operation of this example was the same as that of Example 25 except that different oxalic diamide ligands were used. The results obtained are shown in the following table.

(226) TABLE-US-00023 Ligand Yield/% Ligand Yield/% Ligand Yield/% L-II-30 25 L-II-34 19 L-II-35 4 L-II-58 21 L-II-59 5 L-II-60 6 L-II-62 23 L-II-64 27 L-II-65 64 L-II-91 2 L-II-92 8 L-II-93 74 L-II-94 9 L-II-95 2 L-II-96 37 L-II-97 41

Example 27 Synthesis of 4-methoxyphenol by Copper-Catalyzed Reaction of 4-chloroanisole

(227) The operation of this example was the same as that of Example 25. L-II-93 was chosen as the ligand, and different copper catalysts, bases, solvents were used. The results are shown in the following table.

(228) TABLE-US-00024 Concen- Copper tration/ Yield/ Entry salt Base Solvent/mL mol/L % 1 Cu(acac).sub.2 K.sub.3PO.sub.4 DMSO/H.sub.2O = 0.5/0.5 0.5 24 2 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.5/0.5 0.5 32.5 3 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.75/0.25 0.5 56 4 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 75 5 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.85/0.15 0.5 62 6 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.9/0.1 0.5 58 7 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.95/0.05 0.5 58 8 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 1/0 0.5 0 9 Cu.sub.2S LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 0 10 Cu.sub.2O LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 75 11 CuSCN LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 16 12 CuCN LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 38 13 CuBr LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 71 14 CuCl LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 71 15 CuI LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 74 16 Cu(OAc).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 49 17 CuO LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 76 18 CuCl.sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 74 19 CuBr.sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 80 20 CuTc LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 0.5 73 21 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 1 83 22 Cu(acac).sub.2 LiOHH.sub.2O DMA/H.sub.2O = 0.8/0.2 1 9 23 Cu(acac).sub.2 LiOHH.sub.2O DMF/H.sub.2O = 0.8/0.2 1 10 24 Cu(acac).sub.2 LiOHH.sub.2O DMSO/t-BuOH/H.sub.2O = 1 28 0.5/0.5/0.1 25 Cu(acac).sub.2 LiOHH.sub.2O DMSO/H.sub.2O = 0.8/0.2 1.5 80

Example 28 Synthesis of Substituted Phenol Via Copper-Catalyzed Reaction of Aryl

(229) ##STR00483##

(230) Copper acetylacetonate (Cu(acac).sub.2) (0.025 mmol), ligand L-II-93 (0.025 mmol) and lithium hydroxide monohydrate (1.05 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (three times), and then aryl chloride (0.5 mmol), 0.8 mL of DMSO and 0.2 mL of H.sub.2 were added successively under argon. The reaction mixture was stirred well at 130 C. for 24 hours. After cooling, 2 mL of hydrochloric acid (1 mol/L), water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product substituted phenol.

(231) TABLE-US-00025 Product and Yield Characterization data of product .sup.1H NMR (400 MHz, CDCl.sub.3) 7.03 (d, J = 8.1 Hz, 2H), 6.73 (d, J = 8.4 Hz, 2H), 4.93 (br s, 1H), 2.27 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 20.5, 115.1, 130.0, 130.1, 153.3; ESI-MS: 109.1 (M + H).sup.+ .sup.1H NMR (400 MHz, CDCl.sub.3) 7.56-7.48 (m, 2H), 7.34 (t, J = 7.8 Hz, 1H), 7.10 (ddd, J = 8.1, 2.5, 0.9 Hz, 1H), 6.43 (br s, 1H), 2.60 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) 26.8, 114.8, 121.0, 121.1, 130.0, 138.3, 156.5, 199.6; ESI-MS: 137.1 (M + H).sup.+ .sup.1H NMR (400 MHz, CDCl.sub.3) 8.22-8.14 (m, 1H), 7.83-7.76 (m, 1H), 7.50-7.45 (m, 2H), 7.43 (d, J = 8.3 Hz, 1H), 7.29 (t, J = 7.8 Hz 1H), 6.79 (dd, J = 7.4, 0.6 Hz, 1H), 5.63 (br s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 108.7, 120.7, 121.6, 124.4, 125.3, 125.9, 126.5, 127.7, 134.8, 151.5; ESI-MS: 145.1 (M + H).sup.+ .sup.1H NMR (400 MHz, CDCl.sub.3) 6.94-6.86 (m, 2H), 6.80-6.73 (m, 2H), 5.90 (br s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3) 157.38 (d, J = 36.4 Hz), 151.30 (d, J = 2.2 Hz), 116.35 (d, J = 8.1 Hz), 116.07 (d, J = 23.3 Hz); ESI-MS: 111.0 (M H).sup.

Example 28 Synthesis of Substituted Phenol Via Copper-Catalyzed Reaction of Aryl Iodide/Bromide

(232) ##STR00488##

(233) Copper acetylacetonate (Cu(acac).sub.2) (0.1 mmol), ligand L-II-65 (0.1 mmol) and lithium hydroxide monohydrate (4.2 mmol) were added into a 10 mL of Schlenk tube. The tube was evacuated and backfilled with argon (three times), and then 4-iodoanisole or 4-bromoanisole (2 mmol), 1.6 mL of DMSO and 0.4 ml of H.sub.2O were added successively under argon. The reaction mixture was stirred well at 80 C. for 12 hours. After cooling, 6 mL of hydrochloric acid (1 mol/L), water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product p-methoxy phenol (for 4-iodoanisole: yield 95%, for 4-bromoanisole: yield 93%).

Example 29 Coupling Reaction of 4-bromoanisole with Benzylamine

(234) ##STR00489##

(235) Copper catalyst (0.01 mmol), ligand (0.01 mmol) and base (1.5 mmol) were added into a 10 mL of Schlenk tube. The tube was evacuated and backfilled with argon (three times), and then 4-bromoanisole (1.0 mmol), benzylamine (1.5 mmol) and 1 mL of solvent were added. The reaction mixture was stirred well at 80 C. for 12 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product N-(4-methoxy)phenylbenzylamine.

(236) The results obtained are shown in the following table.

(237) TABLE-US-00026 Copper Tempera- No. catalyst Ligand Base Solvent ture/ C. Yield/% 1 CuI L-II-94 K.sub.3PO.sub.4 DMSO 80 45 2 CuI L-II-94 KOH DMSO 80 76 3 CuI L-II-94 NaOH DMSO 80 96 4 CuI L-II-94 NaOAc DMSO 80 94 5 Cu.sub.2O L-II-93 KOH DMSO 80 98 6 Cu.sub.2O L-II-93 NaOH DMSO 80 97 7 Cu.sub.2O L-I-16 KOH tBuOH 80 98 8* Cu.sub.2O L-I-16 NaOH tBuOH 70 94 *Reaction at 70 C. for 24 hours.

Example 30 Coupling Reaction of 4-bromoanisole with Other N-nucleophiles

(238) ##STR00490##

(239) Copper catalyst (0.1 mmol), ligand (0.1 mmol) and potassium phosphate (2.0 mmol) were added into a 10 mL of Schlenk tube. The tube was evacuated and backfilled with argon (three times), and then aryl bromide (1.0 mmol), 1 mL of DMSO and coupling reagent (2.0 mmol) were added. The reaction mixture was stirred well at 90 C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the corresponding coupling products. The experimental results are as follows:

(240) TABLE-US-00027 N-nucleophiles Copper catalyst Ligand Product and Yield NH.sub.3H.sub.2O CuI L-II-71 Cu.sub.2O L-II-82 Cu.sub.2O L-II-82 Cu.sub.2O L-II-82 Cu.sub.2O L-II-90 00 Cu.sub.2O L-II-90 01

(241) All publications mentioned herein are incorporated by reference as if each individual document is cited as a reference in the present application. It should also be understood that, after reading the above contents of the present invention, those skilled in the art can make various changes or modifications, equivalents of which falls in the scope of claims as defined in the appended claims.