New Highly Stereoselective Synthesis of (E)-Droloxifene via Selective Protection of 3,4′-Dihydroxybenzophenone and McMurry Reaction

A new, highly stereoselective synthesis of (E)-droloxifene is reported. Deprotection of 3,4′-dimethoxybenzophenone and selective pivaloylation of the 3′-phenolic position gave 4-hydroxy-3′-(trimethylacetoxy)benzophenone. A McMurry reaction between the preceding benzophenone and propiophenone gave the (E)-olefin as a major product (14:1 E/Z ratio in crude reaction), which was then alkylated with 2-dimethylaminoethyl chloride and deprotected to yield (E)-droloxifene with a >100:1 E/Z ratio (5 steps, 13%). Attempts to use this strategy as a suitable stereoselective method to obtain (Z)-droloxifene were not successful.