Stereoselective Palladium-Catalyzed Approach to Vitamin D Derivatives in Protic Medium.

We describe an efficient convergent synthesis of vitamin D metabolites and analogues. The synthetic strategy relies on a tandem Pd-catalyzed A-ring closure and Suzuki-Miyaura coupling to the CD-side chain component to set directly the vitamin D triene system under protic conditions. This strategy enables rapid access to vitamin D and 3-epi-vitamin D metabolites and analogues modified at the side chain for biological evaluation and structural and metabolic studies.