Aerobic Oxidative Coupling Reaction Involving Ketone And Amine

During several decades of development,the transition metal catalyzed coupling reaction has become one of the most effective methods for construction of carbon-carbon bonds or carbon-heteroatom bonds.A series of name reactions are constantly emerging:Heck coupling reaction,Negishi coupling reaction,Suzuki coupling reaction,Still coupling reaction,Sonogashira coupling reaction,Ullman coupling reaction,etc.which have been applied to chemical industries and medicine widely.Three scientists from America and Japan:Richard F.Heck,Ei-ichi Negishi and Akira Suzuki were awarded the Nobel Prize in chemistry to honor their contributions to this field in 2010.Recently,as the scientists turn their attention to more sustainable and environmentally friendly synthetic strategies,aerobic oxidative coupling reaction has been developed.Dioxygen is considered as an ideal oxidant due to its easily available,inexpensive,environmentally friendly and highly atom-efficient oxidative characters,so more and more attraction is obtained from academic and industry.On the other hand,nitrogen-containing heterocyclic compounds are widely existing in nature,and have been widely applied in various area.As we all know,ketone and amine can react by condensation dehydration and active the ?-C-H bond of carbonyl,which will be beneficial to synthesize the nitrogen-containing heterocyclic compounds by the construction of C-N bonds and C-C bonds under the transition-metal or transition-metal-free.This thesis briefly reviewed the dioxygen and aerobic oxidative reaction firstly,then presented the recent progress of aerobic oxidative coupling reaction involving or not involving ketone and amine.The content of this thesis mainly focused on the synthesis of 3-azabicyclo[3.1.0]hexanes,pyrazines,pyridines,quinolines and amides under transition-metal or transition-metal-free.More details are as following:1.A novel twice palladation of carbonyl ?-Csp3-H bonds was demonstrated toward the synthesis of 3-azabicyclo[3.1.0]hex-2-ene.Pd(OAc)2 was used as the catalyst,and molecular oxygen was used as the sole oxidant,the reaction condition was mild and simple.The preliminary mechanistic studies by in situ IR revealed that the second C-H palladation or reductive elimination might be slow step.2.Copper-catalyzed aerobic oxidative C-H/N-H coupling between simple ketone and diamine was developed toward the synthesis of a variety of pyrazines.Various substituted ketones were compatible for this transformation.Preliminary mechanistic investigations indicated that radical species were involved.XAFS experiments elucidated that the Cu(II)species coordinated by two N atoms and two O atoms was a reactive one for this aerobic oxidative coupling reaction.DFT calculations suggested that the intramolecular coupling of cationic radical was thermodynamically favourable in this transformation.3.A dioxygen induced C-N bond activation of primary alkyl amines was demonstrated toward the synthesis of pyridines and quinolines.The transition-metal free conditions with O2 as the sole oxidant make this transformation very attractive.Notably,the substrate applicability of different kinds of ketones is greatly broadened for this transformation.4.A copper-catalyzed aerobic C-C bond cleavage/C-N bond formation reaction between simple ketone and amine was developed toward the synthesis of amides,which were useful synthetic intermediates in organic synthesis and important skeletons of biologically active molecules.Notably,the reaction conditions were very mild,and preliminary mechanistic investigations indicated that molecular oxygen might be involved in C-C bond cleavage process.