Recently we have demonstrated that the carbonyl reduction in the enantiomerically pure (R)-β-keto sulfoxide system proceeds highly diastereoselectively to give diastereomeric β-hydroxy sulfoxides, (R,R_S)- or (S,R_S)-form based on the reducing agent employed. These β-hydroxy sulfoxides are synthetically useful intermediates for the preparation of enantiomerically pure hydroxy compounds because of the ready elaboration of the residual functionalities. In order to further extend its synthetic utility, we have undertaken the asymmetric synthesis of some natural products using polyisoprene compounds having chiral β-ketosulfoxide functionality. Additionally we will show that virtually complete asymmetric protonation of prochiral lithium enolates can be attained using chiral β-hydroxy sulfoxides as a chiral proton source. 1. Asymmetric Synthesis of Enantiomerically Pure JH II and JH III. Concise syntheses of enantiomerically pure JH III and JH II have been accomplished by the highly stereoselective reduction reaction of readily available chiral α,α-dialkyl β-keto sulfoxides (6) and (11), respectively. 2. New Asymmetric Polyene Cyclization via Episulfonium Ion. Starting from β-keto sulfoxide (13), both enantiomers of (16a) and (16b) were obtained by the similar sequence as above. 16a undergoes efficient cyclization with TfOH in CH_2Cl_2 to give the enantiomerically pure drimane-type compound (17a) in 75% yield via an episulfonium cation intermediate. 3. Asymmetric Synthesis of Cembranolide System. Vinyl sulfoxide (23), derived from (21), reacted with dichloroketene to afford the γ-tolylthio-γ-lactone (25) which was transformed into the 14-membered compound (26) by treating with LDA via an intramolecular Aldol-type condensation reaction. 4. Asymmetric Protonation of Prochiral Lithium Enolates using Chiral β-Hydroxysulfoxides.
