Stereoselective Cyclopropanation of Multisubstituted Enesulfinamides: Asymmetric Construction of α-Tertiary Cyclopropylamine Derivatives Containing β-Quaternary Stereocenters

Abstract

Enesulfinamides with α,β,β-trisubstitution undergo a Simmons−Smith reaction to yield multisubstituted cyclopropylamine derivatives with high stereocontrol. The resulting α-tertiary cyclopropylamine derivatives, which feature β-quaternary stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl), are seldom achieved by using conventional methods. By adjusting the stereochemistry of the carbon−carbon double bond and/or sulfinyl group within the enesulfinamides, it is feasible to selectively produce four stereoisomers of the cyclopropylamines, each with different absolute configurations at the αand β-carbons.

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

“…We have developed methods for highly stereoselective formation of either geometric isomers of aza-enolates bearing two similar β-subsitutions (β-position relative to the nitrogen atom in the aza-enolates) . These aza-enolates, also known as β,β-disubstituted enesulfinamides, contain a chiral tert -butanesulfinyl group that can provide excellent stereocontrol in subsequent reactions of these nucleophilic species . We envisioned that these species could be intercepted by suitable electrophilic cyanating reagents to construct β-ketiminonitriles with acyclic quaternary α-stereocenters, which are challenging to construct with high stereoselectivity using conventional cyanation processes (Scheme c).…”