The Application Of Asymmetric Michael Reaction In The Construction Of Chiral γ-Disubstituted Butenolide

Butenolide units that feature a five-membered γ-lactone with unsaturation at α,β-carbon atoms occur in a wide range of natural products and biologically active compounds.This ubiquitous nature of butenolides has attracted considerable attention regarding the development of a synthetic methodology for optically active butenolide-containing compounds.Previously,the study mostly focused on using 2-trimethylsilyl-furan as precursor to synthesis optically active butenolide,but this method usually produceed undesired co-generation of silicon-derived by-products.Therefore,based on atomic economy and efficiency considerations,chemists began to look for a more efficient way.So the direct use of unactivated butenolides as pronucleophiles has become the most economical method,but the majority of these jobs still remained in the synthesis of y-monosubstituted chiral butenolide compounds.Although there are some impressive contributions to buildγ,γ-disubstituted butenolides in the past few years,further use of γ-monosubstituted butenolides to be rendered direct asymmetric transformations to y,γ-disubstituted butenolides is still a dark side in this area of research.To our best knowledge,there has no report about using lower active Michael acceptor,imidazole modified α,β-unsaturated ketones,to build y,y-disubstituted butenolides.In this thesis,we have developed a catalytic system using a bifunctional thiourea as catalyst that enable the efficient direct asymmetric vinylogous conjugate additions of γ-monosubstituted butenolides to imidazole modified a,P-unsaturated ketones under mild conditions.By this asymmetric Michael reaction,we build a series of functionalized γ,γ-disubstituted butenolides in good yields(43-99%yield),enantioselectivity(72-98%ee),and most of these compounds have good diastereoselectivity(up to>20:1 d.r.).It also has a widely rage of application in substrates.We firmly believe that this method can provide a new route to the study of the synthesis of chiral drugs and natural products that containing butenolide skeleton.