Enantioselective Reductive Cyclization of Alkynyl-Tethered Cyclohexadienones Catalyzed by Rhodium Complexes

Org Lett. 2024 Jul 12;26(27):5614-5619. doi: 10.1021/acs.orglett.4c01276. Epub 2024 Jul 2.

Abstract

Although various types of asymmetric cyclization reactions of 1,6-enynes have been established, simple asymmetric reductive cyclization remains underdeveloped. In this study, the enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones (1,6-enynes) has been developed via a chiral pincer rhodium catalyst, affording cis-hydrobenzofurans and cis-hydroindoles with high enantioselectivities (90-99% ee). Furthermore, several synthetic applications and preliminary inhibitory activity studies against SARS-CoV-2 3CLpro are presented.