Application of homochiral lithium amide base chemistry to a thiane oxide system

Abstract

Treatment of the thiane oxide 6 with a homochiral lithium amide (HCLA) base 7, followed by electrophilic quench of the so-formed sulfoxide carbanion with Me3SiCl, Mel or ButCO2Et, gives the optically active products (+)-8, (+)-11 and (+)-12, respectively, in 55–60% enantiomeric excess (ee). The reaction of 6 with the HCLA base 9 can be carried out in the presence of Me3SiCl (in situ quench conditions), in which case a silylation–in situ kinetic resolution process occurs, furnishing (–)-8 in low chemical yield, in up to 69% ee. Further transformations of thiane oxides (+)-8 and (+)-11 involving reduction or removal of the ring sulfur atom were conducted, in order to establish the absolute configuration of the products. Highly stereoselective reduction of the keto sulfoxide (+)-12 was also carried out, leading ultimately to an epoxide product 20via opening of the thiane ring.