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

We describe an efficient convergent synthesis of vitamin D3 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 D3 and 3‐epi‐vitamin D3 metabolites and analogues modified at the side chain for biological evaluation and structural and metabolic studies. Even better than the real thing? An efficient convergent synthesis of vitamin D3 metabolites and analogues is described (see scheme). This strategy enables rapid access to vitamin D3 and 3‐epi‐vitamin D3 metabolites and analogues modified at the side chain for biological evaluation and structural and metabolic studies.