Full functionalization of the imidazole scaffold by selective metalation and sulfoxide/magnesium exchange

Abstract

A simple, flexible, and straightforward method for the functionalization of all the positions of the imidazole heterocycle through regioselective arylations, allylations, acylations, and additions to aldehydes is disclosed. Starting from the readily available key imidazole 1, highly functionalized imidazole derivatives have been synthesized in a regioselective manner from directed metalations and a sulfoxide/magnesium exchange. Moreover, the selective N3-alkylation followed by deprotection of N1 (trans-N-alkylation) allows the regioselective N-alkylation of complex imidazoles.

Keywords: imidazole; magnesium; metalation; sulfoxides; zinc.