Microwave-induced 1,3-dipolar intramolecular cycloadditions of N-substituted oximes, nitrones, and azomethine ylides for the chiral synthesis of functionalized nitrogen heterocycles

摘要

The nitrone cycloaddition reaction with olefins, particularlynan intramolecular nitrone cycloaddition reaction (INC), hasnexperienced impressive growth, and finds broad applicationsnin organic synthesis due to the production of their productnisoxazolidines, which have a labile N–O bond which is easilynconverted into various functionalized groups. These sequencesnhave been utilized as a key step for the synthesis of highly functionalizednpyrrolidines and piperidines which have been appliednto the synthesis of biologically active natural products.1 However,nit is known that a disadvantageous factor of the reactionnis that the cycloaddition only takes place at high temperaturenand after long reaction times.2 In the past decade, microwavenirradiation has been widely used in organic synthesis.3 However,nso far, only a limited number of microwave-assisted 1,3-dipolarnintermolecular cycloaddition reactions of nitrilimines andnnitrile oxides giving cycloadducts in moderate yields have beennreported.4 Recently, we have investigated the possibility of intramolecularnnitrone cycloaddition reaction under microwavenirradiation. In this paper, we report our research efforts onnthe intramolecular cycloaddition reactions of oximes, nitrones,nand azomethine ylides derived from -serine methyl esternon the surface of silica gel without a solvent under microwavenirradiation, which result in the chiral preparation ofnfunctionalized tricyclic isoxazolidines fused with a pyrrolidinenor piperidine ring.