The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognize...The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognized.A challenge arises mainly from the difficult reaction initiation inherent in alkyl halides and the construction of fully substituted chiral C–N bonds from sterically congested tertiary alkyl radicals.Herein,we report a copper-catalyzed asymmetric three-component radical carboamination of acrylamides utilizing an anionic chiral N,N,N-ligand under mild conditions.This ligand was essential for the reaction initiation by enhancing the reducing capability of copper and enabling the enantiocontrol over tertiary alkyl radicals.The substrate scope was broad,covering an array of acrylamides,aryl-and heteroaryl-amines,as well as alkyl halides and sulfonyl chlorides,enabling good functional group tolerance.When combined with the follow-up transformation,this strategy provides a versatile platform for accessing structurally diverse chiralα-tertiary N-arylamine building blocks of interest in organic synthesis.展开更多
Enantioselective radical desymmetrization is a highly effective approach for rapidly creating enantioenriched molecules,introducing dramatically increased structural complexity from readily available prochiral or meso...Enantioselective radical desymmetrization is a highly effective approach for rapidly creating enantioenriched molecules,introducing dramatically increased structural complexity from readily available prochiral or meso compound feedstocks.Two strategic modes have been developed for these reactions,which differ in the nature of the stereo-determining steps.The first category deals primarily with the stereoselective desymmetrization of closed-shell radical precursors or functional reagents,whereas the second category achieves desymmetrization by stereoselectively functionalizing open-shell radical species.This mini-review explores the research progress in this growing field,aiming to elucidate mechanistic scenarios related to stereochemical control.Additionally,it offers insights into the challenges and opportunities that lie ahead for further development.展开更多
基金Financial supports were obtained from the National Natural Science Foundation of China(NSFC,grant nos.22025103,22331006,92256301,22371112,and 22101122)the National Key R&D Program of China(grant nos.2021YFF0701604 and 2021YFF0701704)+5 种基金Guangdong Major Project of Basic and Applied Basic Research,China(grant no.2023B0303000020)Guangdong Basic and Applied Basic Research Foundation,China(grant no.2023A1515140088)Shenzhen Science and Technology Program,China(grant nos.JCYJ20220818100600001,JCYJ202205300115409020,and 20220814231741002)the Shenzhen Key Laboratory of Cross-Coupling Reactions,China(grant no.ZDSYS20220328104200001)Dongguan Key Laboratory of Interdisciplinary Science for Advanced Materials and Large-Scale Scientific Facilities,China(grant no.2023KSYS014)Also,the New Cornerstone Science Foundation through the XPLORER PRIZE is gratefully acknowledged.
文摘The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognized.A challenge arises mainly from the difficult reaction initiation inherent in alkyl halides and the construction of fully substituted chiral C–N bonds from sterically congested tertiary alkyl radicals.Herein,we report a copper-catalyzed asymmetric three-component radical carboamination of acrylamides utilizing an anionic chiral N,N,N-ligand under mild conditions.This ligand was essential for the reaction initiation by enhancing the reducing capability of copper and enabling the enantiocontrol over tertiary alkyl radicals.The substrate scope was broad,covering an array of acrylamides,aryl-and heteroaryl-amines,as well as alkyl halides and sulfonyl chlorides,enabling good functional group tolerance.When combined with the follow-up transformation,this strategy provides a versatile platform for accessing structurally diverse chiralα-tertiary N-arylamine building blocks of interest in organic synthesis.
基金Financial support from the National Natural Science Foundation of China (grant nos.22025103,92256301,21831002,22271133,22101122,and 22201127)the National Key R&D Program of China (grant nos.2021YFF0701604 and 2021YFF0701704)+1 种基金New Cornerstone Science Foundation through the XPLORER PRIZE,Shenzhen Science and Technology Program (grant nos.KQTD20210811090112004 and JCYJ20220818100600001)Shenzhen Key Laboratory of Cross-Coupling Reactions (grant no.ZDSYS20220328104200001).
文摘Enantioselective radical desymmetrization is a highly effective approach for rapidly creating enantioenriched molecules,introducing dramatically increased structural complexity from readily available prochiral or meso compound feedstocks.Two strategic modes have been developed for these reactions,which differ in the nature of the stereo-determining steps.The first category deals primarily with the stereoselective desymmetrization of closed-shell radical precursors or functional reagents,whereas the second category achieves desymmetrization by stereoselectively functionalizing open-shell radical species.This mini-review explores the research progress in this growing field,aiming to elucidate mechanistic scenarios related to stereochemical control.Additionally,it offers insights into the challenges and opportunities that lie ahead for further development.
