Stereocontrolled Total Synthesis of 1a,25-Dihydroxyergocalciferol

A stereocontrolled total synthesis of the vitamin D2metabolite 1a,25-dihydroxyergocalciferol (1), which involves a coupling of the previously described A ring synthon 2 with the appropriately functionalized C-D moiety 3, is described. In the key step, stereochemical control is achieved by taking advantage of the thermal reversibility of a [3+ 2]-cyc1oaddition of methyl 0,~-dimethylacrylate and the C-D C-23 nitrone 4 to effect conversion to the C-24S isoxazolidinecarboxylic acid methyl ester Sa, which is readily transformed by reduction followed by elimination of the nitrone function into the necessary C-D precursor