Preparation of α-amino acids via Ni-catalyzed reductive vinylation and arylation of α-pivaloyloxy glycine

This work emphasizes easy access to alpha-vinyl and aryl amino acids via Ni-catalyzed cross-electrophile coupling of bench-stable N-carbonyl-protected alpha-pivaloyloxy glycine with vinyl/aryl halides and triflates. The protocol permits the synthesis of alpha-amino acids bearing hindered branched vinyl groups, which remains a challenge using the current methods. On the basis of experimental and DFT studies, simultaneous addition of glycine alpha-carbon (Gly) radicals to Ni(0) and Ar-Ni(ii) may occur, with the former being more favored where oxidative addition of a C(sp(2)) electrophile to the resultant Gly-Ni(i) intermediate gives a key Gly-Ni(iii)-Ar intermediate. The auxiliary chelation of the N-carbonyl oxygen to the Ni center appears to be crucial to stabilize the Gly-Ni(i) intermediate.

Automated summary

This work demonstrates the synthesis of alpha-vinyl and aryl amino acids via Ni-catalyzed cross-electrophile coupling, with experimental and DFT studies showing simultaneous addition of glycine alpha-carbon radicals to Ni(0) and Ar-Ni(ii). The auxiliary chelation of the N-carbonyl oxygen to the Ni center is crucial for stabilizing the Gly-Ni(i) intermediate.