Transition Metal-catalyzed Direct C-H Bond Activation/Coupling Cyclization

N-heterocylcles are ubiquitous in natural products,drug molecules and functional materials.Therefore,developing an efficient and green synthetic method for constructing these compounds always highly remains desirable.Among the various methods,transition metal-catalyzed C-H bond activation strategy has emerged as one of the most powerful tools due to high atom and step economy.However,although this strategy can site-selectively introduce specific functional groups into the target molecules,removal of the directing groups generally suffers from tedious chemical transformation.Hence,designing versatile directing group-containing molecules,in which the directing group could assist the metal to activate specific C-H bond,and also the directing group could further trap the introduced functional groups via coupling cyclization,this strategy would open up a new area of C-H bond functionalization.In this thesis,we reported nitrogen-based functional groups assisted C-H bond activation/annulation reaction for constructing versatile N-heterocylcles.Firstly,by introducing the aminocarbonyl group into the 1-position of the indoles,we systemically investigated Rh(III)-catalyzed [4+2] annulations of N-amidoindoles with ?-acyl diazo compounds.This transformation provides a novel approach to produce polysubstituted 2H-pyrimido[1,6-a]indol-1-ones via aminocarbonyl group assisted regioselective C(2)-H alkenylation/cyclization.In this transformation,the aminocarbonyl group could not only assist Rh(III)-catalyzed indole C(2)-H functionalization,but also act as a nucleophile to trap the carbonyl group of diazo compounds,and then underwent intramolecular [4+2] cyclization reaction to furnish target products.Both H/D exchange and kinetic studies indicated that the indol C(2)-H bond-breaking was possibly involved in the rate-limiting step of this transformation.Subsequently,in view that the imine/enamine-isomerization could improve the reactivity of ?-imino Csp3-H bond,we made a series of N-(2-pyridyl)-ketoimines and invested Rh(III)-catalyzed [3+2] cascade cyclization of N-(2-pyridyl)-ketoimines with ?-acyl diazocarbonyl compounds.This transformation offered an efficient access to synthetically versatile polysubstituted N-(2-pyridyl)pyrroles in good to excellent yield with a broad range of functional group tolerance(such as methyl,halogen,acetal and heteroaryl groups).It’s worth pointing out that this method could also selectively introduce the phosphonyl and sulfonyl groups into the 3-position of the pyrroles compounds.The corresponding control experiments indicated that imine-enamine tautomerization could efficiently occur and enable the ?-imino Csp3-H bond activation with the assistance of the [Cp*RhCl2]2 catalysts.In recent year,developing inexpensive earth-abundant transition metals as alternative catalysts is attracting increasing attention in the field of C-H functionalization.On the basis of our previous works,we further investigated that Co(III)-catalyzed coupling cyclization of N-nitrosoanilines with ?-acyl diazocarbonyl compounds to assemble structurally diverse and sterically hindered indolones via a C-H bonds activation/[3+2] annulation process.The preliminary H/D exchange and kinetic isotope effect experiments indicated this novel transformation involves the formation of cobalt-ketene complexes,which derived from a C-H bond activiation/carbonyl rearrangement process.This novel carbonyl rearrangement reaction will offer new approach to develop new type of organic reactions.Lastly,on the basis of the [4+2] and [3+2] coupling cyclization initiated by transition metal-catalyzed C-H bonds carbenoid functionalization,we further realized a Co(III)-catalyzed [4+1] cyclization of 2-arylpyridines with aldehydes.In which pyridine-directed Csp2-H addition to aldehydes occurred to form alcohols via carbonyl insertion process by employing Co(III)catalyst,and then Co(III)catalysts continued to act as a Lewis acid catalyst to activate the C-O bond of hydroxymethylene group,and led to the intramolecular SN2 nucleophilic cyclization.Moreover,this reaction are not only limited to 2-arylpyridines,2-alkenylpyridines could also smoothly undergo a [4+1] cycloaddition to furnish structurally diverse indolizines.