Synthesis of Phostones via the Palladium-Catalyzed Ring Opening of Epoxy Vinyl Phosphonates

The
reaction of epoxy aldehydes with tetraethyl methylenediphosphonate
gave γ,δ-epoxy vinyl phosphonates. The palladium-catalyzed
addition of primary alcohols gave the monoprotected diols as single
diastereoisomers. The trans- and cis-epoxides lead to opposite (syn and anti) diastereoisomers of the addition products. The alkene of the vinyl
phosphonates was subjected to hydrogenation, and the resulting saturated
phosphonates underwent base-catalyzed cyclization to give phostones
with a very high diastereoselectivity in the formation of the new
chiral center at the phosphorus atom.