Modular approach to non-aromatic and aromatic pyrroles through gold-catalyzed [3 + 2] cycloaddition of 2H-azirines and ynamides

Abstract

The developed modular approach to hard-to-reach non-aromatic 3H- and 2H-pyrroles is based on the integration of 2H-azirines and ynamides. Gold-catalyzed [3 + 2] cycloaddition of 2,2-disubstituted 2H-azirines and ynamides constitutes a high-yielding route to 5-amino-3H-pyrroles. This reaction proceeds under mild conditions (HAuCl₄ 5 mol%, DCM, rt) and demonstrates high functional group tolerance (more than 30 examples; yields up to 98%). As a further branch of the proposed synthetic route, we also elaborated a smooth acid-promoted 1,5-shift-based isomerization of the obtained 5-amino-3H-pyrroles to fully substituted 5-amino-2H-pyrroles (18 examples; yields up to 86%). Furthermore, if 2-substituted 2H-azirine-2-carboxylic acid is employed for the cycloaddition with ynamide, a subsequent decarboxylation leads to an aromatic 2-amino-1H-pyrrole scaffold.