Exploiting Configurational Lability in Aza‐Sulfur Compounds for the Organocatalytic Enantioselective Synthesis of Sulfonimidamides

Abstract

Methods for establishing the absolute configuration of sulfur-stereogenic aza-sulfur derivatives are scarce, often relying on cumbersome protocols and a limited pool of enantioenriched starting materials. We have addressed this by exploiting, for the first time, a feature of sulfonimidamides in which it is possible for tautomeric structures to also be enantiomeric. Such sulfonimidamides can readily generate prochiral ions, which we have exploited in an enantioselective alkylation process. Selectivity is achieved using a readily prepared bis-quaternized phase-transfer catalyst. The overall process establishes the capability of configurationally labile aza-sulfur species to be used in asymmetric catalysis. Scheme 1. a) Examples of aza-sulfur compounds, including sulfonimidamides. b) Proposed enantioselective synthesis of aza-sulfur compounds by exploiting configurational lability.

Enantioselective Sulfonimidamide Acylation via a Cinchona Alkaloid-Catalyzed Desymmetrization: Scope, Data Science, and Mechanistic Investigation

“…Willis and co-workers have reported an enantioselective alkylation of protected sulfonimidamides using cinchona alkaloid-derived phase-transfer catalysts. 9 Additionally, we have recently disclosed an enantioselective Pd-catalyzed arylcarbonylation of sulfonimidamides with aryl and heteroaryl iodides (Figure 1B). 10 This reaction leveraged the rapid tautomerization of the imido and amido nitrogen atoms on unprotected sulfonimidamide starting materials, which provided a unique opportunity to desymmetrize the prochiral nitrogen atoms via dynamic kinetic resolution.…”