Stereoselective Palladium-Catalyzed Approach to Vitamin D₃ Derivatives in Protic Medium

Abstract We describe an efficient convergent synthesis of vitamin D 3 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 3 and 3‐epi‐vitamin D 3 metabolites and analogues modified at the side chain for biological evaluation and structural and metabolic studies.