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

• Published in: Angewandte Chemie Vol. 133; no. 49; pp. 25884 - 25891
• Main Authors: Tilby, Michael J., Dewez, Damien F., Hall, Adrian, Martínez Lamenca, Carolina, Willis, Michael C.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.12.2021
• Subjects: Absolute configuration; Alkylation; Catalysis; Catalysts; Chemistry; cinchona alkaloid; Enantiomers; enantioselective catalysis; Lability; phase-transfer catalysis; Selectivity; sulfonimidamides; Sulfur; Sulfur compounds
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202109160

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. The unusual stereochemical feature of certain sulfonimidamides, in which tautomeric forms are also enantiomeric, has been exploited to develop a catalytic enantioselective synthesis of alkylated sulfonimidamides. The reactions proceed through a prochiral anionic intermediate to deliver enantiomerically enriched products. A double‐alkylated, cinchona alkaloid‐derived catalyst is used as a phase‐transfer catalyst.