Nickel-Catalyzed Selective C-N Bond Functionalization

The C-N bond is one of the most abundant chemical bonds widely existing in many organic molecules and biomacromolecules.The high C-N bond dissociation energy has made them the most prevalent and unreactive classes of organic compounds in synthetic organic chemistry.Therefore,the C-N bond cleavage will remain a great challenge and will attract much attention in the future.Transition-metal-catalyzed cleavage of C-N single bonds has become a hot area,because it provides either an excellent nitrogen source or an admirable carbon source from readily available and simple N-containing compounds to construct useful molecules.Much progress has been made on the selectively chemical functionalization via inert bonds activation in our group.Based on references and experiments studies,the attention of my doctoral dissertation has been focused on C-N bonds activition with exceptional functional group tolerance,high effciency,and excellent chemoselectivity.The main results of our research are direct borylation of quaternary-N bonds,decarbonylative borylation of amides and decarbonylative elimination of aliphatic amides as follows:Part ?:By developing a mild Ni-catalyzed system,a method for direct borylation of sp~2 and sp~3 C-N bonds has been established.The key to this highly efficient C-N bond borylative cleavage depends on the appropriate choice of the nickel catalyst Ni(COD)2,ICy·HCl as a ligand,and 2-ethoxyethanol as the cosolvent.This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for gram-scale synthesis and late-stage C-N borylation of complex compounds.In view of the widespread-NMe2 group and its precursors in chemicals,this method offers a meaningful tool to enable them as valuable building blocks.Due to these advantages,this reaction should be of high synthetic value.Part ?:A nickel/N-heterocyclic carbene catalytic system has been established for decarbonylative borylation of amides with B2nep2 by C-N bond activation.This transformation shows good functional-group compatibility and can serve as apowerful synthetic tool for late-stage borylation of amide groups in complex compounds.In view of the widespread occurrence of the amide group and the precursor carboxylic acid group in chemicals,this method offers ameaningful tool to enable their use as valuable building blocks.More importantly,a key intermediate,the structure of an acyl nickel complex was first confirmed by X-ray analysis.Furthermore,the decarbonylative process was also observed.These findings confirm the key mechanistic features of the acyl C-N bond activation process.Part ?:Amide and olefins are important synthetic intermediates with complementary reactivity which play an indispensible role in the construction of natural products,pharmaceuticals and artificial materials.Converting the normally highly stable aliphatic amides into olefins directly is a challenging task.Here we demonstrate that a Ni/NHC-catalytic system has been established for decarbonylative elimination of aliphatic amides to generate various olefins via C-N and C-C bond cleavage.This study not only overcomes the acyl C-N bond activation in aliphatic amides,but also encompasses distinct chemical advances on a new type of elimination reaction called retro-hydroamidocarbonylation.This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for late-stage olefination of amide groups in complex compounds.