Further studies on the synthesis of 24(S),25-epoxycholesterol. A new, efficient preparation of desmosterol

Efforts to improve the synthesis of 24(S),25-epoxycholesterol from stigmasterol have included identification of 6α-hydroxy-i-steroid (I) (R1 = OH, R2 = αOH) as a byproduct from the ozonolysis of steroid (II) and an attempt to effect conversion of sulfone I (R1 = SO2Ph, R2 = βOMe) (III) to diol (IV) via Payne rearrangement and nucleophilic trapping of (S)-2-hydroxymethyl-3,3-dimethylepoxide, which led instead to (V) (R3 = α or β OH) (97% yield). A more efficient synthesis of 24(S),25-epoxycholesterol was achieved via coupling of cuprate I (R1 = CuCNLi, R2 = βOMe) (VI) with allylic acetate H2C=CHCMe2OAc to give 73% of I (R1 = CH2CH=CMe2, R2 = βOMe) (VII), in the most efficient conversion yet of a C22 intermediate to desmosterol or its acetate.