Discovery of Annulating Reagents Enabling the One-Step and Highly Stereoselective Synthesis of Cyclopentyl and Cyclohexyl Cores

Org Lett. 2021 Jan 1;23(1):60-65. doi: 10.1021/acs.orglett.0c03695. Epub 2020 Dec 22.

Abstract

The use of the unprecedented annulating reagents methyl N-(tert-butylsulfinyl)-4-chlorobutanimidate and methyl N-(tert-butylsulfinyl)-5-bromopentanimidate enables the diastereoselective preparation of 5- and 6-membered carbocycles bearing three contiguous stereocenters. These synthons undergo cycloaddition with a variety of Michael acceptors to form cyclopentane/cyclohexane rings with excellent stereochemical control, generating only one of the eight possible diastereomers. This novel methodology has enabled the highly enantioselective and high yielding synthesis of novel chemotypes of pharmacological relevance.