Highly Enantioselective Construction of the Polycyclic Piperazin-2-ones via NHC-Catalyzed [12 + 2] Cycloadditions

Org Lett. 2023 Nov 3;25(43):7917-7922. doi: 10.1021/acs.orglett.3c03171. Epub 2023 Oct 24.

Abstract

NHC-catalyzed diastereoselective and enantioselective [12 + 2] higher-order cycloadditions of 5H-benzo[a]-pyrrolizine-3-carbaldehydes with cyclic sulfonic imines are described. Various optically pure polycyclic piperazin-2-ones were successfully constructed under mild reaction conditions with excellent diastereoselectivities and enantioselectivities. The generated chiral polycyclic piperazin-2-ones could be transformed to planar-chiral nine-membered cyclic amides via squaramide-catalyzed asymmetric ring-expansion reactions.