Synthesis of Quaternary Spirooxindole 2H‐Azirines under Batch and Continuous Flow Condition and Metal Assisted Umpolung Reactivity for the Ring‐Opening Reaction

Abstract

An efficient and new approach for the synthesis of spirooxindole 2H ‐azirines via intramolecular oxidative cyclization of 3‐(amino(phenyl)methylene)‐indolin‐2‐one derivatives in the presence of I 2 and Cs 2 CO 3 under batch/continuous flow is described. This method is mild and facile to synthesize a variety of spirooxindole 2H ‐azirines derivatives in gram‐scale. Furthermore, we have synthesized spiroaziridine derivatives from spirooxindole 2H ‐azirines derivatives via addition of grignard reagent. In addition, we discloses an metal assisted attack of Grignard nucleophile at N ‐centre rather than C‐ of the spirooxindole 2H ‐azirines, which concurrently underwent ring opening of transient aziridines to afford N ‐substituted Z ‐3‐(aminophenyl)indolin‐2‐one. A plausible mechanism for azirination and ring‐opening reaction is also presented.