Copper catalyzed amine arylation

Figure 2.17 A cross-section of results for the copper-catalyzed amine arylation reported by Kwong and Buchwald [73]. The isolated yields (in parenthesis) shown were the average of two experiments.

Elimination-addition reactions of aryl halides with alkali-metal amides are discussed in Section 14-6C high-temperature copper-catalyzed amination, also effective, usually does not lead to rearrangement. 

Kang, S.-K., Lee, S.-H., Lee, D. Copper-catalyzed N-arylation of amines with hypervalent iodonium salts. Synlett 2000, 1022-1024. 

SCHEME 14. Mechanism of copper-catalyzed amination of aryl halides... 

The intramolecular amine-halogen copper-promoted indohzation was applied to the synthesis of more-complex indoles (Scheme , equations 1 ) [58-61]. Other examples in this category of copper-catalyzed amination are syntheses of the carbazole alkaloids murrayaquinone-A and ( )-bis-murrayaquinone-A [62], 3-aryl p-carbolin-l-ones [63, 64], carbazoles from donble C-N cyclization [65], pyrrolo[2,3-c]... 

The usefulness of ancillary ligands L66-L78 to promote the copper-catalyzed N-arylation of aryl halides with aliphatic amines has been demonstrated (Schemes 20.20 and 20.21) [46,47]. In absence of the ligands, the coupling of aryl halides with alkyl amines requires higher ternperamre [48]. 

Kang and coworkers developed a number of metal-catalyzed arylations with diaryliodonium salts under mUd reaction conditions at the turn of the century, including the Pd-catalyzed arylation of secondary amines at room temperature and the Cu-catalyzed arylation of amines, anilines, amides, imidazoles, and triazoles at room temperature to 50 °C [98, 99]. The copper-catalyzed N-arylation of indoles, on the other hand, required heating to 150 °C in DMF [100], and makes an interesting comparison with the recently developed C-arylation of the same substrates (see Sect. 4.2.2). 

There have been other important developments from a green chemistry perspective, for example those by Li ef al. on the copper-catalyzed Af-arylation of imidazole and pyrrole with aliphatic amines... 

Figure 2.19 A cross-section of results for the copper-catalyzed amination of aryl halides with nitriles to give amides and benzoxazoles via in situ hydrolysis, by Xiang et al. [89].

Scheme 2.21 The aryl triolborate reagents developed by Yamamoto and Miyaura [108] and used for the copper-catalyzed N-arylation of amines.

SCHEME 3.101 Copper-catalyzed N-arylation of lf/-pyrazolo[3,4-i>]pyridin-3-amine [103],... 

This chapter covers more specifically the copper-catalyzed C(aryl)-N bond formation via the coupling of aryl halides with nitrogen nucleophiles such as N-heterocycles, amines, anilines, amides, ammonia, azides, hydroxylamines, nitrite salts or phosphonic amides. The C(aryl)-N bond formation as a result of the coupling between these nucleophiles and arylboronic acids (the Chan-Lam reaction) will be also presented. It is worth noting that this chapter mainly focuses on the most significant results and important breakthroughs in this field. 

Scheme 20 Copper-catalyzed amination of ortho-functionalized aryl halides using NaNa as amino source...

The copper-catalyzed amination developed by Buchwald is an effective method for catalytic coupling of aryl boronic acids with amines [61]. Yudin has recently shown that N-arylation of aziridines is possible under modification of Buchwald s method and is successful with a range of functionalized aryl boronic acids (Scheme 3.41) [62]. 

Some other examples of metal-catalyzed substitutions are given in Scheme 11.10. Entries 1 to 3 are copper-catalyzed reactions. Entry 1 is an example of arylation of imidazole. Both dibenzylideneacetone and 1,10-phenanthroline were included as ligands and Cs2C03 was used as the base. Entry 2 is an example of amination by a primary amine. The ligand used in this case was (V,(V-diethyl sal icyl amide. These conditions proved effective for a variety of primary amines and aryl bromides with both ERG and EWG substituents. Entry 3 is an example of more classical conditions. The target structure is a phosphodiesterase inhibitor of a type used in treatment of asthma. Copper powder was used as the catalyst. 

Many other kinds of nucleophiles can be arylated by copper-catalyzed substitution.132 Among the reactive nucleophiles are carboxylate ions,133 alkoxide ions,134 amines,135... 

The utility of the method was demonstrated with a variety of electron-rich and electron-poor aryl aldehydes, but the method was not suitable for aliphatic aldehydes. No racemization was observed in the copper-catalyzed oxidative amidation reaction when an optically active amine, (S)-valine methyl ester, was employed. 

Waterlot, C., D. Couturier, and B. Rigo. 2000. Montmorillonite-palladium-copper catalyzed cross-coupling of methyl acrylate with aryl amines. Tetrahedron Lett. 41 317-319. 

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