Asymmetric Friedel-Crafts Alkylation/Cyclization Of 3-Aminophenol Derivatives

The Friedel-Crafts reaction is a powerful chemical method for the construction of new C-C bonds,and it has been widely applied for derivatize aromatics and heteroaromatics.Because 3-aminophenols are pivotal building blocks for quinolinone alkaloids or carbazole alkaloids,and also used as precursors for dyes.The enantioselective Friedel-Crafts reaction of 3-aminophenols has attracted long-term attention.However,due to the interaction between the basic amino group and chiral Lewis acid catalysts,resulting in the deactivation of the latter;and the stronger nucleophilicity of the 3-aminophenols N-H bond,probably facilitating the N-H functionalization of N-monosubstituted 3-aminophenols.So the employment of 3-aminophenols in catalytic asymmetric Friedel-Crafts alkylations,remain a challenging topic.This research work presented the enantioselective Friedel-Crafts alkylation/cyclization tandem reaction of 3-aminophenols with α,α-dicyanoolefins,which has been performed successfully using a chiral dinuclear zinc catalyst.Through the screening and optimization of reaction conditions,various α,α-dicyanoolefins and 3-aminophenols can be well tolerated in this catalytic system,leading to a range of chiral 2-amino-4H-chromenes in 98%yield and up to 99%ee.Using X-ray single crystal diffraction analysis,the absolute configuration of the product was determined.The reaction mechanism was preliminarily verified by the intermolecular KIE experiment.The gram-scale reaction and further derivatization to active compound analogues exhibited the potential utility of our method.