Sulfonyl radical-triggered two/three-component tandem bicyclization of CN-containing 1,6-enynes under transition metal- and base-free conditions

Abstract

Radical tandem bicyclization provides a novel approach for the preparation of complex polycyclic compounds in synthetic chemistry. Herein, we first described a tandem radical bicyclization reaction of CN-containing 1,6-enynes with sulfonyl hydrazides by using tert-butyl hydroperoxide (TBHP) as the oxidant under metal- and base-free conditions. To expand the synthetic utility of our protocol, we then proposed a more practical three-component reaction of 1,6-enynes, aryldiazoniums and Na₂S₂O₅ without any additives, generating the sulfonyl radical via the rapid insertion of sulfur dioxide (SO₂) using cheap and non-toxic Na₂S₂O₅. These two protocols feature several merits including transition metal- and base-free conditions, step- and atom-economical reaction modes, remarkably broad substrate scope, and capability of scaling up to the gram scale.