Stereoselective Construction of Less-Accessible Acyclic α,α-Disubstituted β-Ketiminonitriles via Electrophilic Cyanation of β,β-Disubstituted Enesulfinamides

Org Lett. 2024 May 24;26(20):4371-4376. doi: 10.1021/acs.orglett.4c01409. Epub 2024 May 16.

Abstract

The metalloenamines, formed by NH-deprotonation of β,β-disubstituted enesulfinamides, can undergo reactions with commercially available electrophilic cyanating reagents such as tosyl cyanide (TsCN) or 3-oxo-1,2-benziodoxole-1(3H)-carbonitrile (CBX). Through the utilization of appropriate stereoisomers of enesulfinamides, this method enables the selective synthesis of any of the four stereoisomers of α,α-disubstituted β-sulfinylimino nitriles, which feature acyclic quaternary stereocenters and are typically more challenging to synthesize. These compounds can then undergo stereoselective nucleophilic addition, leading to the creation of valuable enantioenriched multisubstituted β-amino carbonyl surrogates with a high degree of structural diversity.