Copper-catalyzed amination

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. 

SCHEME 12. Potential mechanisms for copper-catalyzed amination reactions with low-valent organometallic reagents... 

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

The copper-catalyzed amination of bromopyridine 29 was reported by workers at Merck on route to the synthesis of muscarinic (M3) antagonist 31 <01TL3251>. Interestingly, an uncatalyzed amination of 3-nitropyridines has also been reported <01JCS(P1)376>. Other metal mediated processes have been used to access pyridines with important biological activity as well <0lJOC605x01TL6811>. 

General procedure for the copper-catalyzed amination offunctionalized diarylzinc reagents. N-(2-Nitrophenyl)-dibenzylamin ... 

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]... 

In 2008, Li et al. reported a copper-catalyzed amine-alkyne-alkyne addition reaction as an efficient method for the synthesis of Y,5-alkynyl-p-amino acid derivatives 102 (Scheme 3.52) [137]. In this case, the first step of the reaction is proposed to be the hydroamination of the electron-deficient alkyne 100, which plays the role of the aldehyde component. Subsequent reaction of the resultant intermediate XXX with alkyne 101 would afford intermediate XXXI, which would be then protonated to give an iminium intermediate XXXII. Finally, an intramolecular transfer of the alkyne moiety to the iminium ion would yield the 7,8-alkynyl-p-amino ester 102 and regenerate the catalyst. The reaction was later extended using chiral prolinol derivatives as the amine component, which afforded the corresponding Y,5-alkynyl-p-amino acid derivatives with excellent diaste-reoselectivities (up to >99 1) [138]. 

L. Zhou, H.-F. Jiang, C.-J. Li, Adv. Synth. Catal. 2008, 350, 2226-2230. Efficient synthesis of y,8-alkynyl- 3-amino acid derivatives by a new copper-catalyzed amine-alkyne-alkyne addition reaction. 

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.

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].

Lefevre G, Franc G, Adamo C, Jutand A, Ciofini I (2012) Influence of the formation of the halogen bond ArX.N on the mechanism of diketonate ligated copper-catalyzed amination of aromatic halides. Organometallics 31 914—920... 

Scheme 5.130 Enantioselective copper-catalyzed amination of silicon enolates 526, 529, and 531 with azoimide 527 proposed catalytic cycle.

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]. 

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