Decarboxylative Amidation of Aryl/Heteroarylacetic Acids via Activated Esters through Traceless α-Functionalized Benzylic Radicals

Unlike conventional amide synthesis, a decarboxylative amidation of aryl/heteroarylacetic acids by reaction with NHS and tert-butyl nitrite has been reported to afford both aliphatic and (hetero)aromatic amides in satisfactory yields. Mechanistic studies revealed a previously unexplored pathway for the formation of an activated ester through the generation and subsequent reactions of traceless alpha-functionalized benzylic radicals, which upon subsequent one-pot reaction with amines form the amides. A gram-scale synthesis of Moclobemide indicates the practical applicability.

Automated summary

A decarboxylative amidation of aryl/heteroarylacetic acids by reaction with NHS and tert-butyl nitrite has been reported, which offers a convenient method for the synthesis of aliphatic and (hetero)aromatic amides. Mechanistic studies reveal a previously unexplored pathway involving traceless alpha-functionalized benzylic radicals for the formation of activated ester, followed by one-pot reaction with amines to form amides. The gram-scale synthesis of Moclobemide demonstrates the practical applicability of this method.