Development of New Synthetic Methods for Heterocycles Utilizing 1,3-Dipoles

Toward the preparation of heterocycles using 1,3-dipoles, the approaches have been generally limited to concerted 1,3-dipolar cycloaddition. A strategy consisted of a stepwise addition to 1,3-dipoles followed by cyclizaion could be an alternative pathway to synthesize of heterocycles. We have been interested in nucleophilic addition reactions to nitrones. In pursuing them, synthesis of heterocycles based on a new strategy of stepwise nucleophilic addition-cyclization and related transformations consisted of [1,3]-sigmatropic rearrangement was developed. A novel [5+1] cycloaddition reaction of C,N-cyclic-N'-acyl azomethine imines as 1,5-dipoles, 1,3-dipoles with extended conjugation, with isocyanides was explored. A [3+1+1] cycloaddition of azomethine ylides generated from aziridines in situ with isocyanides was also realized by the use of Lewis-acid catalyst. Furthermore, unprecedented ring enlargement reaction of the azomethine imines with sulfonium ylide was developed.