An asymmetric synthesis of a 1α,25-dihydroxyvitamin D3 A-ring synthon

Abstract

An efficient asymmetric synthesis of the A-ring of 1α,25-dihydroxyvitamin D 3 from α-bromoacrolein is described. The key steps of the synthesis are the Evans type syn-selective asymmetric aldol reaction of bromoacrolein with the boron enolate of 3-chloroacetyl-4(S)-isopropyl oxazolidinone and ring closure by Heck type reaction of a vinyl bromide onto an α,β-unsaturated ester in the exo-mode. Graphic The synthesis of 1 is achieved in high yield by intramolecular Heck reaction of 2 which in turn was prepared from α-bromoacrolein via the Evans aldol 3 .