Stereodivergent Synthesis of N-Heterocycles by Catalyst-Controlled, Activity-Directed Tandem Annulation of Diazo Compounds with Amino Alkynes

Abstract

A stereodivergent synthesis of five-membered N-heterocycles, such as 2,3-dihydropyrroles, and 2-methylene and 3-methylene pyrrolidines, has been developed through a tandem annulation of amino alkynes with diazo compounds and involves the trapping of in situ formed intermediates. Mechanistic investigations indicate that the copper-catalyzed tandem annulations proceed by allenoate formation and subsequent intramolecular hydroamination. In contrast, the rhodium-catalyzed protocol features a carbenoid insertion into the NH bond and subsequent Conia-ene cyclization.

Keywords: copper; cyclizations; diazo compounds; homogeneous catalysis; rhodium.