APPLICATION OF HOMOCHIRAL LITHIUM AMIDE BASE CHEMISTRY TO A THIANE OXIDE SYSTEM

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, (+)-ll 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 (+)-ll 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 20 via opening of the thiane ring.