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. (C) 2000 Elsevier Science Ltd. All rights reserved.