Studies On Transition Metal Catalyzed Functionalization Of Diazo Compounds

Metal carbenes are a family of important active synthetic intermediates,which have been widely used to construct C–C and C–X bonds,and prepare various multi-functionalized molecules.To control the selectivity of metal carbenes participated reactions,especially the enantioselectivity,has always been the challenge and focus of the field,which relies on the development of novel synthetic methodologies and catalytic systems with high efficiency and selectivity.In this thesis,we have successfully achieved transition-metal-catalyzed selective multi-functionalization of diazo compounds and their equivalents triazoles by optimizing the catalytic system and designing suitable substrates.In Chapter 1,a historical development of metal carbenes and their applications in organic synthesis was reviewed.The recent advances in metal carbene involved transition-metal-catalyzed asymmetric synthesis reactions using diazo compounds and triazoles as carbene precursors was thoroughly discussed,including cyclopropanations,X–H bond insertions,ylide formations and cross-coupling reactions,etc.In Chapter 2,a novel rhodium-catalyzed dearomative N-alkylation reactions of O-substituted 2-pyridones was developed involving the pyridinium ylide formation and sequential 1,4-acyl migratory rearrangement from O to C.What was further found is that asymmetric transformation can be accomplished using a chiral dirhodium complex catalyst Rh₂（S-TCPTTL）₄,affording optically pure products in moderate to good yields with excellent enantioselectivities（up to 99%ee）.DFT calculations indicate that the chirality is transferred from axial chirality to the central stereogenic center.In Chapter 3,in order to further develop reliable and efficient synthetic protocols for N-substituted 2-pyridones,the controllable 1,4-and 1,6-migratory rearrangements between 2-oxypyridines and N-sulfonyl-1,2,3-triazoles via regulating the substrate structure and catalyst were established.We found that in presence of Rh₂（OPiv）₄ as the catalyst,O-carboxylic ester pyridines can undergo 1,4-migration of the carboxylic ester group from O to C to give the N-alkylated 2-pyridones with a newly formed tetrasubstituted carbon center,whereas the use of O-acyl pyridines with Rh₂（esp）₂ catalyst resulted in the formation of N-alkenylated products via 1,6-acyl migration from O to N.In addition,the reaction of pyridotriazoles with 2-oxypyridines afforded the 1,4-migration products in high efficiency.In Chapter 4,An enantioselective tandem cross-coupling/alkynylogous Aldol reaction between diazoacetates and 2-propargylbenzaldehydes using Cu（tfacac）₂/chiral bisoxazolines as the catalytic system has been developed,and chiral exocyclicα-allenols bearing both central and axial chirality were produced in moderate to good yields（30-92%）with excellent enantio-and diastereoselectivity（up to 97%ee,up to 19:1 dr）.Distinct from the reported asymmetric Cu（I）-catalysis,this protocol features the first example of Cu（II）-catalyzed asymmetric cross-coupling of terminal alkynes with diazo compounds.In Chapter 5,Based on the cooperative catalysis of an achiral gold complex and a chiral phosphoric acid,the first enantioselective C-H functionalization of anisole derivatives with diazo compounds has been realized,providing a novel protocol for the direct asymmetric synthesis of chiralα,α-diaryl acetates in moderate to good yields with high enantioselectivities（up to 96%）.The detailed mechanism of this C-H functionalization and the origin of the enantiocontrol was disclosed by theoretical calculations.