Efficient Synthesis of 1α-Fluoro A-Ring Phosphine Oxide, a Useful Building Block for Vitamin D Analogues, from (<i>S</i>)<i>-</i>Carvone via a Highly Selective Palladium-Catalyzed Isomerization of Dieneoxide to Dieneol

Abstract

The 1alpha-fluoro A-ring phosphine oxide 1, a useful building block for fluorinated vitamin D analogues, was synthesized from (S)-carvone in 13 synthetic steps, and only five isolations, in 22% overall yield. In the key synthetic step, a highly selective palladium-catalyzed isomerization of dieneoxide 18 to dieneol 20 was achieved using an appropriately selected fluorinated alcohol as a catalytic proton source.