Concise synthesis of chiral tricyclic γ-lactams via synergistic isothiourea/Ir catalyzed asymmetric [3 + 2] annulation.

ABSTRACT: Accessing trans-fused N-fused tricyclic frameworks with multiple contiguous stereocenters remains a major challenge in synthesis. We report a synergistic isothiourea/Ir-catalyzed [3 + 2] annulation of arylacetic acid esters with azabenzonorbornadienes, providing trans-fused tricyclic γ-lactams with three contiguous tertiary stereocenters in high regio-, enantio-, and diastereoselectivity. The method tolerates diverse arylacetates, heterocycles, and pharmaceutically relevant carboxylates, and is amenable to gram-scale synthesis. Mechanistic studies support a cooperative cycle involving C1-ammonium enolate formation and enantioselective S_N2' attack on the Ir-activated azabenzonorbornadiene. Downstream functionalizations, including epoxidation, hydrogenation, and amino alcohol form

SUBMITTER: Xiao G 

PROVIDER: S-EPMC12816648 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature