Efficient Asymmetric Synthesis of an A‐Ring Synthon for Pd‐Catalyzed Preparation of 1α‐Hydroxyvitamin D Metabolites and Analogs

The secondary parallel hypercalcemic effects associated with the treatment of several hyperproliferative diseases natural hormone 1α,25-dihydroxyvitamin D3 (calcitriol) and/or known active vitamin D metabolites and analogs, demand development efficient rapid methods for preparation receptor (VDR) ligands as new selective non-calcemic agonists. Here we describe an adaptable multigram-scale synthetic sequence to access A-ring synthon useful precursor triene system 1α-hydroxylated derivatives via Pd-catalyzed carbocyclization/Suzuki–Miyaura cross-coupling reactions in a protic medium. key step is asymmetric Lewis acid-promoted carbonyl-ene reaction chiral glyosylate ester establish 1α-hydroxyl group its derivatives.