Divergent synthesis of pyrrole carboxamides from pyrrole carboxaldehyde and formamides/amines via oxidative amidation involving pyrrole acyl radicals

Abstract

A non-traditional approach for the synthesis of pyrrole carboxamides from pyrrole carboxaldehyde and formamides or amines with catalytic amounts of nBu₄NI and TBHP as oxidants is reported herein. The method is operationally simple providing straightforward access to primary, secondary, and tertiary pyrrole carboxamides in good to excellent yields utilizing inexpensive reagents under mild conditions. Unlike traditional amidations that involve ionic reactions, a mechanistic study of our current method unveils the involvement of 2- or 3-pyrrole acyl radicals that are otherwise rarely postulated. The applicability of the current method is further demonstrated in the synthesis of a drug-like compound, i.e., an optically pure carboetomidate amide.