Studies On The Catalytic Activation Of Sp~3 C-H Bond Of N-heteroarylmethanes And Its Applications

N-heteroarylmethanes are an important class of N-containing compounds which have been widely applied in material chemistry,pharmaceutical chemistry,natural products chemistry and organic synthesis as a basic unit.Transition metal-catalyzed direct C-H bond activation is one of the most straightforward and economic strategies to construct novel C-C and C-Z bonds in the modern organic chemistry.This dissertation mainly concerns about the functionalization of Csp3-H bond at methyl group of V-heteroarylmethans.The detailed research contents and results are exhibited as below:1.Bronsted acid-catalyzed highly efficient deuteration at the methyl group of N-heteroarylmethanesWe prepared a series of deuterated compounds with high ratios of deuterium incorporation through readily-available Br(?)nsted acid-catalyzed deuteration at methyl group of N-heteroarylmethanes with D2O.This reaction presented the qualities of high efficiency,high selectivity,high economy and exhibited good functional tolerance with wide substrate scope.Diversified methyl substituted N-heteroaryls like pyridines,quinolines,indoles etc.showed good reactivity.This new transformation can be applicable to some bioactive pharmaceutical molecules(Tropicamide and papaverine)and be performed in a large scale(500 mmol)with easy purification through extracting,dehydration and further evaporated the solvent obtaining the analytic pure product showing good potential of industrial application.2.Copper-catalyzed oxidative esterification of N-heteroarylmethanes with alcoholsA series of N-heteroaryl esters had been synthesized via aerobic oxidative dehydrogenation-coupling catalyzed by copper catalyst.This transformation showed good functional group tolerance with wide substrate scope.The electronic withdrawing and electronic donating substituents of N-heteroarylmethanes exhibited good reactivity.Various substrates including both aliphatic and aromatic alcohols,primary and secondary alcohols were applicable to this transformation,producing the corresponding heteroaromatic esters in good to excellent yields.This protocol could achieve the sp3C-H bond and O-H bond functionalization utilizing the green and safe oxidant oxygen as the sole oxidant.3.Transition-metal free catalyzed ortho-oxidative carbonylation of Phenols with N-HeteroarylmethanesWe realized the transition-metal free direct oxidative ortho-acylation of phenols with N-heteroarylmethanes utilizing green and safe oxygen as the sole oxidant via the Iodine-catalyzed.This transformation proceeded via a sp C-H and sp2C-H dual activation process,regio-selectively producing the corresponding(2-hydroxyphenyl)arylmethanones in moderate to good yields.The hydroxyl group plays a bifunctional role in the oxidative acylation:activating the sp2C-h substrate,capturing the intermediates generated from coupling partner via hydrogen bonds and thus ensuring the site-selectivity.This method exhibited high atom-economic and step-economic conducted under a mild reaction condition with broad substrate scope.Of which provided a fresh protocol in the preparation of medicinal molecules,natural product synthesis and organic chemistry.4.Transition-metal free catalyzed para-oxidative carbonylation of anilines with N-HeteroarylmethanesWe have disclosed an aerobic oxidative para-acylation of unprotected anilines with N-heteroarylmethanes under a mild metal-free reaction condition via sp3C-H and sp2C-7 dual activation applying the green and safe oxygen as the sole oxidant.The reaction proceeded in a facile I2/DMSO/O2 catalytic system,regio-selectively producing the corresponding(4-aminophenyl)arylmethanones in good to excellent yields without substrate pre-activation and the loading of peroxide.The high site-selectivity,broad functional-group-compatibility,scale-up experiment,and easy derivation of products through transformation of free amino group clearly demonstrated the potential synthetic value of this new reaction and the steric hindrance of the free amino group might be the key issue to the regio-selectivity.