The Catalytic Asymmetric Addition Of 3-Vinylindoles To Isatin Imines

Isatin Imines is one of the most important units for the synthesis of3-substituted-3-aminooxindole compounds which are found in natural products and biologically active compounds.The catalytic asymmetric nucleophilic addition of a nucleophile to an isatin imine is one of the most straightforward strategies for obtaining3-substituted 3-aminooxindole derivatives,however,isatin imines have not yet been used in catalytic asymmetric alkenylation reactions.Recently we found that 3-vinylindole is a good nucleophile which can react smoothly with aldimine,arylformyl formaldehyde and3-indole methanol.In this paper,3-vinylindoles were used as nucleophiles to react with isatin imines to construct structurally diverse 3-alkenyl-3-aminooxindole compounds which can be readily converted to a structurally complex chiral indole without loss of enantioselectivity.On the basis of the absolute configuration established from single-crystal analysis of 3-alkenyl-3-amino oxindole compound,and the mechanism of the classic chiral bis(oxazoline)-copper(II)complex catalyzed asymmetric reactions,we deduced a possible chirality-induced mechanism for this reaction.In the first chapter of the paper,the methods of synthesizing 3-substituted3-aminooxindole compounds from isatin imine via Mannich reaction,Friedel–Crafts reaction,Morita–Baylis–Hillman reaction,Henry reaction,and Strecker reaction have been reviewed,we have also listed some methods for the synthesis of 3-substituted3-aminooxindole compounds from other substances and carried out a systematic summary.At the same time,3-vinylindoles as electrophiles,dienes and dienophiles,especially as nucleophiles in the reactions have also been described.In the second chapter of the paper,we have described the design ideas,the selection of template,the selection of catalysts and other catalytic conditions of the reaction.We have also described the expansions of substrate’s application ranges and the derivations ofcatalytic products.Under the optimal reaction conditions,we have synthesized a series of3-alkenyl-3-aminooxindole compounds with up to 99% yield,97% enantioselectivity,and99:1 diastereoselectivities.This work has provided a new synthetic route of 3-substituted-3-aminooxindole compounds.In the third chapter of the paper,we have provided the detailed description of the experimental processes,and the characterization data of new compounds.