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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.… Click to show full abstract

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 α-functionalized benzylic radicals, which upon subsequent one-pot reaction with amines form the amides. A gram-scale synthesis of Moclobemide indicates the practical applicability.

Keywords: functionalized benzylic; heteroarylacetic acids; decarboxylative amidation; amidation aryl; aryl heteroarylacetic; traceless functionalized

Journal Title: Organic letters
Year Published: 2023

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