Transition Metal-Catalyzed Cyclization Of Propargylic Pyridines

Indolizines are significant nitrogen-fused heterocycles featured by an N-bridgedhead bicyclic ring system,which are found in natural products and biologically active compounds.It is of great significance to create convenient and fast methods to construct indolizines.In recent years,chemists have been attracted by the transition-metal-catalyzed cyclization of alkynyl-pyridine derivatives,which is rapid and efficient to synthesize indolizines with a wide substrate scope.In this dissertation,we first synthesized a designed substrate 2-?2-enynyl?pyridines and investigated its tandem cyclization,developing the regioselective addition reactions with nucleophiles and[3+4]cycloaddtiion reactions with nitrones,respectively.1.Efficient access to 1,3-disubstituted indolizines via Cu-catalyzed cyclization of 2-?2-enynyl?pyridines with nucleophiles through simultaneous formation of a C-N bond and a remote carbon-nucleophile bond.The reaction proceeded efficiently with 5 mol%CuI as catalyst and1.0 equiv Et₃N as base,providing the target indolizines in excellent yield?up to 99%?.1,3-Dicarbonyl compound,indoles,amides,alcohol,and even water were used as nucleophiles in this reaction.In addition,the reaction employ by indole as nucleophile achieves the preliminary result in the asymmetric catalysis with 33%ee under the catalysis of a chiral silver phosphate complex.2.Gold-catalyzed intermolecular[3+4]cycloaddition of 2-?1-alkynyl cyclopropyl?pyridines with nitrones was developed,which afforded seven membered heterocycles indolizines in excellent yields and high diastereoselectivity.In all of this study,83 new compounds were synthesized and confirmed by ¹H NMR,¹³C NMR,and HRMS analysis.