Study on Single Electron Oxidation-mediated C?H Functionalization of Arylamines

Author:Zhao He

Supervisor:zhang zuo


Degree Year:2019





Arylamines are important skeletal structures of numerous natural products,pharmaceuticals and functional materials.Direct C-H functionalization of arylamines constitutes one of highly valuable research topics.Transition metal catalysis has been repeatedly proven to be a powerful tool in the construction of complex molecules via direct C-H functionalization,especially for those free radical coupling reactions with high atom and step economy,which has become an effective new manner toward the formation of chemicalbonds.Via single electron oxidation-mediated direct C-H functionalization of aromatic amines under transition metal catalysis,this thesis describes the synthesis of a series of arylamine derivatives with novel structures and unique properties.Except for the first chaper describing the background of the research,the main contents of the thesis are as follows:(1)In chapter 2,a copper-catalysed dehydrogenative?-C(sp3)-H amination of tetrahydroquinolines with O-benzoyl hydroxylamines is demonstrated,the syntheis proceeds with the merits of operational simplicity,good functional tolerance,mild conditions,the use of O2 as the oxidant and no need for installation of directing groups.Some of the products had better inhibitory effect on candida albicans.(2)In chapter 3,a cobalt-catalyzed site-selective functionalization of aniline derivatives with hexafluoroisopropanol is presented,which enables the synthesis of a wide array of fluoroalkylated anilines,a class of highly valuable building blocks for further preparation of fluorinated functional products,is reported.The developed transformation proceeds with operational simplicity,use of earth-abundant metal catalyst,broad substrate scope,good functional group tolerance,and mild reaction conditions.For the first time,the finding of an efficient cobalt/O-benzoyloxy-piperidine catalyst system is the key to lead to the developed chemistry,which offers the potential for further design of radical-induced coupling reactions.(3)Under the conditions of aerobic copper catalysis,chapter 4 describes a diverse synthesis of functional quinoxalines via tandem dual C-H aminations of tetrahydroquinoxalines with both primary and secondary aryl and alkylamines.The catalytic transformation proceeds with the striking features of mild conditions,short reaction time,good substrate and functional group compatibility,the use of naturally abundant[Cu]/O2catalyst system,excellent chemoselectivity and atom-efficiency,and no need for pre-installation of specific aminating agents and directing groups.The work presented supplements the field on selective oxidative C-H amination between two different redox active amines,and offers the potential for further design of cross-coupling reactions of electron-rich systems.(4)In chaper 5,we show a novel method in the synthesis of functional quinoxalines via direct C-H amination and sulfonation of the tetrahydroquinoxalines.Through radical/radical coupling of tetrahydroquinoxalines with amines or sodium benzenesulfonic acids in Cu/O2system.The transformation is characterized by operational simplicity,mild conditions,good substrate suitability and functional group compatibility,no need for directing groups and pre-installation substrates.Mechanistic investigations support that the amination and sulfonylation of C(sp2)-H of tetrahydroquinoxoline were initiated by single electron oxidation,which offers an effective way toward the enrichment of quinoxoline derivatives.(5)Finally,a novel copper-catalyzed dehycrogenative annulation reaction of tetrahydroquinoxalines and 2-naphthol derivatives is shown.The desired products,quinoxaline-fused furans,are generated via cross C-C bond coupling followed by C-O bond formation.The reaction proceeds with the merits of operational simplicity,the use of molecular oxygen as the oxidant,easily accessible raw materials,no need for pre-installation of directing groups and addition of additives,which offers a new potential platform for the discovery of functional products including the biologically active moleclules.