One-pot synthesis of spiro-3,4-dihydro-2H-pyrroles through tandem nucleophilic cyclisation reaction

A very simple and convenient one-pot synthesis of spiro-3,4-dihydro-2H-pyrrole has been developed while synthesising the 2,2,5-trisubstituted pyrrolidines. Initially, the Meldrum's acid has been treated with alpha,beta-unsaturated ketones in presence of anhydrous carbonate base and phase transfer catalyst benzyltriethylammonium chloride in acetonitrile to afford the Michael adduct which is readily converted to the corresponding oxime using standard conditions. The crude oxime is treated directly with p-toluenesulfonyl chloride and in presence of excess organic base results in tandem nucleophilic cyclisation product spirobicyclic as spiro-3,4-dihydro-2H-pyrrole directly, instead the tosyloxime as product.

Automated summary

A simple and convenient one-pot synthesis method has been developed for the preparation of spiro-3,4-dihydro-2H-pyrrole, while synthesizing 2,2,5-trisubstituted pyrrolidines.