Rhodium(iii)-catalyzed diverse [4 + 1] annulation of arenes with 1,3-enynes via sp3/sp2 C–H activation and 1,4-rhodium migration

Abstract

Nitrogen-rich heterocyclic compounds have a profound impact on human health. Despite the numerous synthetic methods, diversified, step-economic, and general synthesis of heterocycles remains limited. C–H bond functionalization catalyzed by rhodium(III) cyclopentadienyls has proven to be a powerful strategy in the synthesis of diversified heterocycles. Herein we describe rhodium(III)-catalyzed sp² and sp³ C–H activation-oxidative annulations between aromatic substrates and 1,3-enynes, where alkenyl-to-allyl 1,4-rhodium(III) migration enabled the generation of electrophilic rhodium(III) π-allyls via remote C–H functionalization. Subsequent nucleophilic trapping of these species by various sp²-hybridized N-nucleophiles delivered three classes (external salts, inner salts, and neutral azacycles) of five-membered azacycles bearing a tetrasubstituted saturated carbon center, as a result of [4 + 1] annulation with the alkyne being a one-carbon synthon. All the reactions proceeded under relatively mild conditions with broad substrate scope, high efficiency, and excellent regioselectivity. The synthetic applications of this protocol have also been demonstrated, and experimental studies have been performed to support the proposed mechanism.