Synthesis of Hexahydropyrrolo-isoquinolines by 1,3-Dipolar cycloaddition of tetrahydroisoquinolines and cinnamaldehydes

A new method is described for the synthesis of hexahydropyrrolo-isoquinolines through the 1,3-dipolar cycloaddition of cinnamaldehydes with azomethine ylides generated from cinnamaldehydes and tetrahydroisoquinolines. The carbonyl CO groups of cinnamaldehydes serve as the precursor for the generation of azomethine ylides and the CC double bonds of cinnamaldehyde act as the dipolarophiles in the cycloaddition. The key features are easily available substrates, good functional group tolerance and mild reaction conditions. The relative configurations of products are confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed. A gram-scale experiment and some chemical transformations were conducted to show the synthetic utility of this approach. Finally, a plausible mechanism was proposed to clarify the formation of products with different configurations.