A Regioselective [3 + 2] Cycloaddition of Alkynols and Ketones To Access Diverse 1,3-Dioxolane Scaffolds

J Org Chem. 2024 Jan 5;89(1):719-724. doi: 10.1021/acs.joc.3c01820. Epub 2023 Dec 27.

Abstract

This study presents a stepwise exoselective [3 + 2] cycloaddition reaction of alkynols with ketones, leading to the synthesis of 4-methylene-1,3-dioxolane derivatives. Remarkably, without any Thorpe-Ingold induced effect, the cyclization reaction was demonstrated with complete regio- and chemoselectivity, which was solely promoted by cesium carbonate. A wide range of unactivated ketones are viable under these mild reaction conditions, and both primary and tertiary alkynols are compatible with these cyclization reactions. We have prepared a diverse array of highly dense exomethylene 1,3-dioxolane rings demonstrating a remarkable tolerance for various functional groups.