Transamidation of N-Benzyl-N-Boc-amides under Transition Metal-Free and Base-Free Conditions

A new protocol for the transamidation of N-benzyl-N-Boc-amides under transition metal-free and base-free conditions is described. The reaction features high reactivity of N-Boc-imides via direct acyl nucleophilic substitution mechanism, and provides access to a diverse array of substituted amides in good to excellent yields. Notably, the base-free condition preserves enantiopurity with respect to chiral amino-acid-derived nucleophiles, and N-Boc-amides bearing an epimerizable stereocenter. The application of this method is also demonstrated through the synthesis of pro-drugs and antidepressant moclobemide.

Automated summary

The new protocol allows for the transamidation of N-benzyl-N-Boc-amides under transition metal-free and base-free conditions, resulting in a diverse array of substituted amides in good yields. Notably, the reaction preserves enantiopurity with respect to chiral amino-acid-derived nucleophiles. The method has been successfully applied in the synthesis of pro-drugs and the antidepressant moclobemide.