Silicon-Mediated Synthesis of Bibenzyl Systems: Synthesis of Ring and Side-Chain Functionalized Hexestrol Derivatives

Article abstract of DOI:10.1021/jo00181a021

Derivatives of hexestrol <(3R*,4S*)-3,4-bis(4-hydroxyphenyl)hexane>, a non-steroidal estrogen, bearing photochemically reactive functional groups or γ-emmitting radionuclides, are useful as affinity labeling agents for the estrogen receptor or as imaging agents for receptor positive breast tumors, respectively.We have developed convenient synthetic routes to two side chain functionalized and aromatic ring functionalized hexestrol derivatives, based on a direct benzylic coupling reaction mediated by allylsilanes or silyl ketene acetals. 1-Dehydrohexestrol and variousaromatic ring substituted 1-dehydrohexestrol derivatives can be prepared by coupling 3-(trimethylsilyl)-1-(4-methoxyphenyl)propene with various reactive benzylic derivatives, and pentestrol derivatives are prepared by the coupling of the silyl ketene acetal derivative of p-methoxyphenyl acetic ester with benzylic derivatives.The R*,S* (erythro) and R*,R* (threo) diastereomers formed in each case can be separated readily by chromatography and recrystallization.This silicon-mediated approach to functionalized hexestrol derivatives provides a convenient route to many compounds of interest as biochemical probes and receptor-based diagnostic reagents.