Copper-catalyzed Ring-opening C(sp~3)-N Coupling Of Cycloketone Oxime Esters:access To 1°,2° And 3° Alkyl Amines

Alkyl amines are one of the most important type of organic compounds,which are frequently engaged motifs in natural products and bioactive pharmaceutical molecules.Therefore,the synthesis of alkyl amines has attracted much attention all over the world.The most common method to construct these compounds relies on direct substitution of alkyl electrophiles with nitrogen nucleophiles.However,such processes suffer from some limitations including deactivation of nitrogen nucleophiles under acidic conditions in S_N1 reactions;being difficult or even impossible for bulky secondary and tertiary alkyl electrophiles in S_N2 reactions;and concomitant elimination or overalkylation.A renaissance was stimulated in exploring effective protocols towards their facile preparation over the past few years,such as reductive amination,C(sp~3)-H amination and olefin hydroamination.Recently,transition metal-catalyzed alkylation of nitrogen nucleophiles with alkyl electrophiles has been a promising solution to directly forge C(sp~3)-N bonds.Despite its success,this method poses two distinct challenges simultaneously:?-hydride elimination from metal alkyl intermediates and the difficulty in C(sp~3)-N reductive elimination.Recent advances have demonstrated that the generation of alkyl carbon radicals containing a cyano group from C-C bond cleavage of cycloketone oxime derivatives could be achieved by transition metal catalysis or photoredox catalysis via a SET process.This strategy has implemented the construction of C(sp~3)-C and C(sp~3)-Y(Y=O,S,Se,Te,N3 or B)bonds.In this work,a novel copper-catalyzed C(sp~3)-N coupling of cycloketone oxime esters with nitrogen nucleophiles has been realized.All of the N-aryl/alkyl anilines,anilines and benzophenone imine could be employed as the nitrogen nucleophiles by 1 or 2 steps for the efficient assembly of a variety of 1°,2°and 3° alkyl anilines.These cyano-containing alkyl amines have proven to be important synthetic frameworks in various chemical transformations.This article is mainly divided into the following two parts:The first part is a brief introduction towards the synthesis of alkyl amines and the ring-opening reactions of cycloketone oxime esters.The second part focuses on the introduction of the research background,optimization of experimental conditions and experimental results.This protocol features wide functional group compatibility and broad substrate scope.The resultant cyano containing alkyl amines can be used for a variety of chemical transformations.