Solution-Phase Parallel Wittig Olefination:  Synthesis of Substituted 1,2-Diarylethanes

Abstract

An efficient strategy for solution-phase parallel synthesis of substituted 1,2-diarylethanes is described. A stilbene library was initially generated by Wittig olefination utilizing amino-labeled phosphines. The stilbene analogues were obtained in high yields and excellent purities after solid-phase extraction. Subsequent reduction of the stilbene libraries simultaneously unmasked functional groups by deprotection, facilitating orthogonal synthesis and further diversification into sublibraries. The libraries from libraries were obtained in good yields and purities using parallel solution-phase alkylation and acylation methodologies. Screening of the sublibraries revealed selective 5-HT2A inverse agonists with IC-50 values between 10 and 100 nM.