DMAP-Catalyzed Direct Conversion of Cbz/Boc-Protected Amines to Amides with Carboxylic Acids as the Acylating Agent

Carbamate-protected amines, such as Cbz and Boc derivatives, are ubiquitous synthetic intermediates that classically require deprotection prior to acylation. We report a 4-dimethylaminopyridine (DMAP)-catalyzed protocol that directly converts these protected amines into amides using carboxylic acids. This method bypasses the traditional deprotection step, operates under mild conditions, and delivers a wide range of amides in moderate-to-excellent yields (up to 85%). Mechanism studies support a pathway involving transient activation of the carbamate via a mixed anhydride-like intermediate. The reaction's broad scope and operational simplicity redefine protected amines as versatile, direct synthons for streamlined amide assembly, overturning the long-held perception that protected amino groups are intrinsically inert toward nucleophilic acyl substitution. This strategy holds particular promise for peptide synthesis, where it could eliminate the repetitive deprotection-acylation cycle that has long been a bottleneck in both solution- and solid-phase peptide assemblies.