Remote Stereocontrolled Asymmetric 1,6/1,4-addition Cascade Reactions Catalyzed By Chiral Primary Amine Catalyst

In the field of asymmetric organocatalysis,cascade reaction is one of the most important strategies to build complex polycyclic framework.Based on vinylogous imine cations activation mode,in this paper,a remote stereocontrolled asymmetric 1,6-addition/1,4-addition cascade reaction catalyzed by chiral primary amine catalyst was disclosed to construct chiral thio-(oxa-)spirocycle compounds.Firstly,the asymmetric 1,6/1,4-addition cascade reactions of 2-indolinethiones to cyclic dienones were developed,in which the functionalization of remote reaction site through LUMO-lowering effect was successfully realized.This method was equally applicable to the structural and electronic variations of both 2-indolinethiones and six-membered cyclic dienones,affording variety of complex spirocompounds with good yields,excellent enantioselectivities and moderate diastereoselectivities(50-78%yield,80->99%ee,3:1-5:1 dr).Moreover,the dienone possessing dimethyl substituent at the β’ site and γ’ site of cyclohexanone ring successfully converted to the corresponding cycloadduct as a single diastereoisomer with 78%yield.All in all,a facile and effective method to construct chiral thio-spirocycle scaffold was provided.Next,the similar asymmetric cascade reactions of 4-Hydroxyl Coumarin and cyclic dienones were accomplished employing chiral primary amine catalyst derived from cinchona alkaloid,obtaining oxa-spiro[cyclohexane-1,2’-pyrano[3,2-c]chromen]framework with good yields(30-71%yield).The scope of the reaction could be expanded to five-membered cyclic dienone with middle enantioselectivity(55%ee).Although,the reactions of cyclic dienones possessing alkyl substituent didn’t occur,this reaction also provided a novel method to synthesize chiral chromen derivatives through remote control.