Asymmetric Synthesis of Bioactive Fluorinated Sulfonyl-Cyclobutene Derivatives via P(III)/P(V) Redox Catalysis

An efficient tandem Michael addition/intramolecular Wittig olefination has been developed for the enantioselective synthesis of fluorinated sulfonyl cyclobutenes. The reactions were performed in the presence of a catalytic amount of a chiral phosphine and phenylsilane to <i>in situ</i> reduce the corresponding phosphine oxide, leading to a variety of functionalized cyclobutenes isolated with up to 90% ee. After different postfunctionalizations, preliminary biological evaluations of these new molecules of interest revealed significant cytotoxicity against leukemia K562 cells.