Computational Insights Into The Chemoselctivities In Transition-Metal Calalyzed Carbene And Nitrene Transfer Reactions

Transition-metal catalyzed carbene and nitrene transfer reactions continue to attract significant research attention in organic synthesis.Transition metal carbene species have been a hot field in contemporary organic synthesis due to the easy access,versatile reactivities and attractive transformations.Many effective carbene precursors have been developed,such as diazo compounds,cyclopropenes,triazoles,hydrazones,enynyl ketones,propargylic esters,allenes etc.The transition-metal catalyzed carbenes could undergo a variety of synthetically attractive transformations,such as C-H functionalization,cyclopropanation,cycloaddition,cascade reactions,cross coupling reactions,and others.Analogously,the formed key nitrenes are usually capable of initiating various types of synthetically significant transformations,such as C-H amination,aziridination,cycloaddition,and cascade reactions,which can efficiently synthesize the synthetically useful N－containing compounds.Transition metal catalyzed nitrene transfer reactions are increasingly being applied to the construction of carbon-nitrogen bonded compounds.The mechanisms and the origins of chemoselectivities in the Rh2(Ⅱ)-catalyzed N－aryl nitrene and analogous Rh2(Ⅱ)/Cu(Ⅰ)-catalyzed aryl carbene involved reactions were investigated by DFT calculations.For the reaction of Rh2(Ⅱ)-catalyzed ortho-alkenyl substituted aryl azides to produce 3H-indoles,after the formation of the crucial Rh2(Ⅱ)-N-arylnitrene intermediate,calculation results suggest that it is favorable for the triplet Rh2(Ⅱ)-N-arylnitrene to undergo intramolecular nitrene addition to the alkenyl moiety followed by the migration of ester group could proceed to afford the final 3H-indole derivative product.For the mechanism of Rh2(Ⅱ)-catalyzed analogous aryl-substituted carbene transfer reaction,computational results show that it is more advantageous for the key Rh2(Ⅱ)-arylcarbene to trigger intramolecular allyl sp3 C-H insertion thereby forming the 1H-indene derivative in a concerted manner.In addition,for the Cu(I)-catalyzed carbene transfer reaction with the same substrate,after the formation of the key Cu(Ⅰ)-carbenoid intermediate,the nucleophilic attack of oxygen of carbonyl group to carbene moiety is found to be the most favorable pathway,yielding an epoxide intermediate through cyclization.The subsequent stepwise ring opening of the three-membered ring and methyl migration would afford the final a-alkoxy 2H-naphthalenone product.As a safe and efficient carbene precursor,1,2,3-triazole could afford the a-imino metal carbene intermediate through the extrusion of nitrogen by transition-metal catalysis,which is different with the traditional carbenes generated from diazo compounds.Due to the presence of both electrophilic and nucleophilic characters in the formed metal-azavinyl carbene intermediates,diverse reactions with unsaturated bonds have been reported in the literature,including nitrile,alkyne,allene,isocyanate and aldehyde.Computational studies were carried out to investigate the mechanisms and the origins of chemoselectivities for intramolecular reaction of Rh2(Ⅱ)-catalyzed 1,2,3-triazole and diazo compounds.For the N-sulfonyl-1,2,3-triazole,the calculation results show that it is easier to trigger intramolecular[3+2]cycloaddition reaction.For the reaction of N-sulfonyl-1,2,3-triazole with a carbonyl group at the α-position,computational results show that it is favorable to undergo the intramolecular cyclization reaction to obtain a ylide intermediate,the subsequent migration of the proton could proceed to afford the final product.For the mechanism of Rh2(Ⅱ)-catalyzed analogous diazo substrate,the[2+1]cycloaddition is found to be the most favorable pathway to yield the cyclopropane intermediate.Afterwards,ring expansion can follow to give the 1,3,5-cycloheptatriene derivative.In addition,we performed mechanistic studies of Rh2(Ⅱ)-catalyzed reaction of analogous diazo substrate with a carbonyl group at theα-position,the sp2 C-H functionalization would take place to generate the final product.