Continuous-Flow Photochemical Nitrile Imine Cycloadditions with Cyclopropenes: Access to Substituted Pyrazoles

Abstract

Herein, we report a general continuous-flow photochemical protocol for the synthesis of highly substituted pyrazoles through the reaction of tetrazoles with cyclopropenes. The methodology combines monochromatic 308 nm UV-B LED irradiation with continuous-flow processing, providing short residence times, operational simplicity, and gram-scale preparation under safe reaction conditions. A broad range of tetrazoles and cyclopropenes were successfully converted into the corresponding pyrazoles, while selected aryl-substituted cyclopropenes afforded isolable bicyclic cycloadducts. The spontaneous conversion of one of these intermediates into the corresponding pyrazole provides experimental support for the proposed cycloaddition/ring opening sequence. Overall, this work extends the synthetic utility of tetrazole-derived nitrile imines and establishes cyclopropenes as versatile dipolarophiles for the preparation of substituted pyrazoles.