Synthesis of Optically Active Carboxylic Acids and Amines with Asymmetric Favorskii Rearrangement

Abstract

The optically active α-chloro α-sulfonyl ketones were easily synthesized in a four-step conversion from optically active 4-tolyl alkyl sulfoxide in good overall yield. Treatment of the ketones with NaH and BnNH₂ gives β-sulfonyl amides via asymmetric Favorskii rearrangement. The sulfonyl group of β-sulfonyl amides was reduced to afford optically active α-alkyl amides. The amides were converted to acetoxypivalimides, and then the imides were hydrolyzed to yield (+)-, (–)-2-ethylhexanoic acid without epimerization. The process to (+)-, (–)-2-ethylhexylamine will be presented.

Scheme 1