ABSTRACT
A mild and stereoconvergent synthesis of 1alpha,25-dihydroxyvitamin D(3) (calcitriol, 1a) 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.
Subject(s)
Vitamin D/analogs & derivatives , Molecular Structure , Vitamin D/chemical synthesis , Vitamin D/chemistryABSTRACT
[reaction: see text] A mild palladium-catalyzed cascade has been used for the synthesis of the hormone 1alpha,25-dihydroxyvitamin D3 (calcitriol, 1a) and its analogues 1b and 1c. This one-pot process involves two consecutive transformations at room temperature: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflates followed by a Negishi cross-coupling reaction with an alkenyl zinc. This novel strategy opens new possibilities for the preparation of a variety of new vitamin D analogues of therapeutic potential, particularly with modifications at the triene and/or ring-A.
