Organocatalytic Atropo- And E/Z-selective Michael Addition Reaction Of Ynones With ?-Amido Sulfones As Sulfone-type Nucleophile

The direct asymmetric Michael reaction is one of the most powerful and fundamental tools for forming new carbon-carbon or carbon-heteroatom bonds and homochiral carbon center simultaneously.In most cases,the nucleophilic reagent reacts with the sp~2 carbon of an electron-deficient substrate and converts it into a sp~3 carbon to generate a new chiral carbon center.Considerable effort has been made and many catalytic systems have been developed,including metal-and organocatalysis.In sharp contrast,scarce attention has been paid to the Michael addition of appropriate nucleophiles to acceptor-substituted triple bond,because the addition of a nucleophile changes the hybridation from Csp to Csp~2,and only E/Z mixtures without chirality can be obtained.However,if the rotation of the single bond between the generated substituted alkene and an aromatic ring was restricted,the enantiomers of axially styrene will exist.The development of methods for the enantioselective synthesis of these axially chiral styrenes is an important task in organic chemistry and it remains a daunting challenge in modern organic synthesis.The lack of reported literature and the difficulty in controlling the E/Z geometry and enantioselectivity of axially styrene have led to the insufficiency of this research field.Despite these progresses,a practical E/Z-selective and enantioselective synthetic route allowing various substitution patterns is still highly desirable.We herein developed the first direct organocatalytic asymmetric Michael reaction of ynones with?-amido sulfones using a multiple hydrogen-bonding N-squaramide catalyst,and obtained axially chiral styrenes with excellent stereoselectivity even at a high temperature.This catalyst system can control the E/Z isomers and the configuration of the new asymmetric axial.The synthetic method provides a facile and convenient tactic to construct axially chiral styrene in organic synthesis.Such structural motifs are important precursors for further transformations into biologically active compounds and synthetic useful intermediates and may have potential applications in asymmetric synthesis as olefin ligands or organocatalysts.