Enantioselective synthesis of a key 'A-ring' intermediate for the preparation of 1 alpha-fluoro vitamin D-3 analogues

摘要

1 alpha-Fluoro A-ring dienol 2, a useful building block for the preparation of fluorinated vitamin D-3 analogues, was synthesized in eight steps from 4-{[tert-butyldimethylsilyl]oxy}-cyclohexanone. The most distinctive synthetic development to emerge from this new synthesis is an unprecedented substrate-controlled diastereoselective fluorodesilylation of an advanced dienylsilane intermediate. This is the first enantioselective route to compound 2 relying on the use of an electrophilic fluorinating reagent.