Synthesis of Highly Stereodefined Tetrasubstituted Acyclic All-Carbon Olefins via a Syn-Elimination Approach

• DOI: 10.1021/acs.orglett.7b03141
• Publication Date: 2017-11-08T16:10:51Z
• Authors: Ngiap-Kie Lim; Patrick Weiss; Beryl X. Li; Christina H. McCu...; Stephanie R. Hare; Bronwyn L. Bensema; Teresa A. Palazzo; Dean J. Tantillo; Haiming Zhang; Francis Gosselin
• Keywords: 01 natural sciences; 0104 chemical sciences

An efficient synthesis of stereodefined tetrasubstituted acyclic all-carbon olefins has been developed via a bis(2,6-xylyl)phosphate formation of stereoenriched tertiary alcohols, followed by in situ syn-elimination of the corresponding phosphates under mild conditions. This chemistry tolerates a wide variety of electronically and sterically diverse substrates and generates the desired tetrasubstituted olefins in high yields and stereoselectivities (>95:5) in most cases. This stereocontrolled olefin synthesis has been applied to the synthesis of anticancer drug tamoxifen in three steps from commercially available 1,2-diphenylbutan-1-one in 97:3 stereoselectivity and 78% overall yield.