One Pot Synthesis Of Cyclopropane Derivatives By A Combination Of Wittig Olefination And Sulfur Ylide Cyclopropanation

A new method have been developed to synthesize cyclopropane derivatives starting froman aldehyde via a two-step-in-one-pot route, i.e. Wittig olefination via stabilized phosphoniumylide to form an α,β-unsaturated carbonyl compound followed by sulfur ylidecyclopropantion to afford1,2,3-trisubstituted cyclopropanes. The phosphonium ylide andsulfur ylide were in situ generated from phosphonium salt Ph3P+CH2COPh (Br-) andsulfonium salt forming from tetrahydrothiophene and α-bromoacetophenone by treating witha base, respectively. When using Cs2CO3as base and CH3CN/water (8/2, v/v) as solvent, themajor product of cyclopropanes was obtained as a cis-isomer (cis is referred to two benzoylgroups) in38-99%yields and with the cis-stereoselectivity up to97%; when using DBU asbase and methanol as solvent, the major product of cyclopropanes was obtained as atrans-isomer in30-99%yields and with the trans-stereoselectivity up to99%. For aldehydeswith an electron-withdrawing group and some aldehydes with an electron-donating group, themajor isomer of cyclopropane products could gradually precipitate from the reaction mixture.After reaction, therefore，this isomer could be isolated as a pure product in44-79%yields bysimply filtering by suction.This one-pot protocol is simple and performed at room temperature to affordcyclopropanes in high yields and with high stereoselectivites, so it provides a facile route toaccess1,2,3-trisubstituted cyclopropanes.In the course of studying the above reaction, a novel reaction was unexpectedly found,which could produce alkylthio-substituted cyclopropane derivatives. By using saturatedNaHCO3as base and solvent, the reaction of an aldehyde with a sulfonium salt fromtetrahydrothiophene and α-bromoacetophenone could provide an alkylthio-substitutedcyclopropane. Although the reaction yield was low, the operation was simple and the startingmaterial is cheap and easily available. By further exploring and studying this reaction, anew method to synthesize alkylthio-substituted cyclopropane derivatives may be developed.