An iminophosphorane-based approach for the synthesis of spiropyrrolidine–imidazole derivatives

A method based on the reaction of an E-phosphazide, an intermediate in the Staüdinger reaction between triphenylphosphine and an azide, with heterocumulenes allows the one-pot, two-component synthesis of a number of pyrrole–imidazole derivatives. The procedure, which involves sequential treatment of the appropriate α-azido ester with triphenylphosphine and isocyanate leads to the hydantoin product after aqueous work-up. The cyclization conditions can also be adapted for the synthesis of thiohydantoins by using isothiocyanates. These hybrids pyrrole–thiohydantoins undergo a novel oxidative spirocyclization by action of DDQ to give a tricyclic derivative (pyrrole–pyrrolidine–imidazole), which displays an interesting cytotoxic activity.