Electronically Matching C-H Alkylation Strategies for the Synthesis of alpha-Heteroaryl Acetic Acid Derivatives

Abstract

A strategy in which complementary species are paired for the preparation of alpha-heteroaryl esters and amides from heteroarenes was developed. Readily available alpha-haloacetates and alpha-acetamides provided the requisite acetate and acetamide groups via three distinctive reactive species, namely nucleophilic carbanions, alkylpalladium complexes, and photoredox-generated electrophilic radicals. Based on their electronic properties, these intermediates were matched with various five-membered heteroarenes, such as pyrazoles, imidazoles, thiophenes, furans, pyrroles, and indoles. These flexible protocols offer easy access to alpha-heteroaryl acetic acid derivatives and expand the scope of heteroarenes that can be utilized for C-H alkylation.