On-water pyrrolidine-mediated domino synthesis of 2-iminoisatins

The on-water reaction between 2-(sulfonylamino)-benzaldehydes, isocyanides and pyrrolidine is able to afford a library of poorly synthetically accessible 2-iminoisatins. The pyrrolidine exhibits for the first time the unique role of promoting a triple domino process, i.e. the formation of an N-alkyl-2,3-diaminoindole, the sulfonamide heterolytic N–S bond cleavage, and the hydrolysis of the resulting iminium ion, with the loss of p-toluenesulfinic acid. RP HPLC-DAD and UHPLC-HRMS real-time monitoring of the reaction provided experimental data that support the reaction mechanism. The use of water as a solvent under ultrasound catalysis and the convergent nature of this approach allow, for the first time, a green and sustainable synthesis of 2-iminoisatins.