Origins and applications of stereoselective sulfenate anion alkylation reactions

Abstract

Selected sulfenate anions can be alkylated with diastereoselectivities near 9:1 when there is appropriately positioned carbon chirality in the sulfenate structure or in the alkylation electrophile. Both protocols represent a conceptually different approach to β-amino sulfoxides. When vinylic β-amino sulfoxides are cyclized, thiomorpholine S-oxides result, and substrate control over the stereochemistry of alkyl substituents was found. This finding facilitates the synthesis of cis and trans dialkylpyrrolidines, known ant venom alkaloids. A computational model is demonstrated to account for some of the diastereoselection results. The importance of intramolecular interactions of sulfenate constituent atoms with pendent substituents is established.

Graphical Abstract

Keywords:

• Sulfenate anion
• stereoselection
• computations
• pyrrolidines
• alkylation

Acknowledgements

The authors with to thank the following agencies for funding for the chemistry reported herein: Natural Sciences and Engineering Research Council (NSERC) of Canada; Petroleum Research Fund administered by the ACS; Shared Hierarchical Academic Research Computing Network (SHARCNET: www.sharcnet.ca); Compute/Calcul Canada.