The first convergent synthesis of 1 α,24( R)-dihydroxyvitamin D 3via diastereoselective isopropylation and alkylative enyne cyclization

Abstract

An efficient covergent synthesis of 1 α,24( R)-dihydroxyvitamin D 3 ( 1) has been achieved using the palladium-catalyzed alkylative enyne cyclization reaction. This is the first example of the convergent coupling procedure to synthesize 1 α,24( R)-dihydroxyvitamin D 3 ( 1). The CD-ring synthons were successfully obtained via the diastereoselective addition of diisopropylzinc to CD-ring 24-aldehyde precursors in the presence of a chiral β-amino alcohol with high diastereoselectivities.