Efficient synthesis of 1alpha-fluoro A-ring phosphine oxide, a useful building block for vitamin D analogues, from (S)-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.