Studies Of Some New Reactions For Construction Of Aza-quaternary Carbon

The aza-quaternary carbon chiral centers have more crowded structure,more rigid spatial structure and more diverse molecular structures,they are widely found in active natural products and drug molecules.Developing efficient methods to construct the azaquaternary carbon chiral centers has important academic significance and potential application value in the total synthesis of natural products and the development of new drugs.In this paper,we focus on the C3-amino-substituted spirocyclic oxindoles and ?-quaternary amino acids which are two dominant skeletons containing aza-quaternary carbon chiral centers to carry out research work,the detailed research works are as follows:1)By tertiary amine hydrogen bond donor bifunctional catalysis,the first highly enantioselective asymmetric 6? electrocyclization of the ketimines derived from isatins was developed.The corresponding C3-amino-substituted spirocyclic oxindoles were obtained in up to 95% yield and 99% ee.The hydrogen bond donor on the chiral thiourea catalyst plays an important role for carrying out the reaction smoothly by the control experiments.Subsequently,a one-pot sequential triple relay catalytic reaction was developed to construct C3-amino-substituted spirocyclic oxindoles from the simple nitro-compounds,this reaction avoided the separation and purification of intermediates and reduced the use of solvents and waste emissions.Then,the chiral C3-aminosubstituted bispirocyclic oxindoles also were achieved by this reaction.On this basis,the asymmetric ene reaction of the ketimines derived from isatins was studied preliminarily.2)Using cheap and readily available acid catalysts,the azidations of tertiary alcohols such as 3-hydroxyoxindoles,?-hydroxy esters and ?-hydroxy ketones were achieved.Thus,a large number of ?-quaternary amino acids derivatives were synthesized efficiently.Then,the kinetic resolution of 3-azido-substituted oxindole was carried out.At present,the triazole product and recycled raw material were obtained in 67% and 50% ee,respectively.Finally,the asymmetric azidation of ?-hydroxy ester was studied preliminarily,and a series of chiral phosphoric acid catalysts have been tried,but the results are not satisfactory.3)Using tetramethylguanidine as catalyst,the addition reactions of nitrones derived from isatins with electrophilic reagents such as aldehydes,ketones and imines were developed firstly.The nitrone products with carbon chain extension could be obtained in up to 95% yield.The reaction has broad substrates,mild reaction conditions and simple reaction operations.The asymmetric version was also investigated.Using the chiral guanidine derived from cinchona as the chiral superbase catalyst,the corresponding chiral product could be achieved with 40% ee.