Stereoselective olefin formation from the dehydration of 1-(p-alkoxyphenyl)-1,2-diphenylbutan-1-ols: application to the synthesis of tamoxifen

Abstract

Acid-catalysed dehydration of either diastereoisomer of a 1-(p-alkoxyphenyl)-1,2-diphenylbutan-1-ol gives mainly the Z isomer of the but-1-ene via a common carbenium ion intermediate that can be regenerated by protonation of the (Z)- or (E)-butene with fluorosulphonic acid. Highly stereoselective syn eliminations were achieved by treatment of the butan-1-ols with base and carbon disulphide but dehydrations using N,N,N-triethylammonio-N′-methoxycarbonylsulphamidate proceeded mainly via a carbenium ion. Aspects of the stereoselectivity of the reactions are discussed. The methods can be applied to give simple stereoselective syntheses of the anti-cancer drug tamoxifen.