Novel synthetic approach to 1α,25 -dihydroxyvitamin D3and analogues

A mild and stereoconvergent synthesis of 1α25-dihydroxyvitamin D 3 (calcitriol, la) is described. The key step is a cascade process consisting of two consecutive transformations: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflate 4 followed by a Negishi cross-coupling reaction with alkenyl zinc 3. This approach is of interest for the rapid synthesis of a variety of new vitamin D 3 analogues of therapeutic potential, especially those modified at the triene and ring-A. The mildness of the method also allows the preparation of thermal sensitive vitamin D 3 analogues.