Novel Concurrent Synthesis of Side-Chain Analogues of Vitamins D2 and D3: 24,24-Dihomo-25-hydroxycholecalciferol and (22E)-22-Dehydro-24,24-dihomo-25-hydroxycholecalciferol

A novel method for the preparation of side-chain extended analogues of vitamins D is described. Both 24,24-dihomo- and (22E)-22-dehydro-24,24-dihomo-25-hydroxycholecalciferols were efficiently prepared from the same intermediates, i.e., the phenyltriazolinedione adduct of previtamin D with a C-22 aldehyde group and a side-chain alkyl sulfone. The key steps in this synthesis involve the Julia coupling of the vitamin D synthon with the side-chain sulfone followed by Barton radical deoxygenation of the C-22 alcohol or dehydroxydesulfonylation of the respective β-hydroxysulfone. All four β-hydroxysulfones of the Julia reaction were separated and characterized for the first time. The absolute configurations at C-22 and C-23 in these compounds were tentatively assigned by high-field proton magnetic resonance. The synthetic method allows a highly efficient concurrent preparation of analogues with a modified side chain attached to the vitamin D nucleus via both single and double bonds.