Generation of Sulfamoyl Radical for the Modular Synthesis of Sulfonamides
Haiping Lv, Xinzhou Chen, Xuemei Zhang, Søren Kramer, Zhong Lian
Abstract
Efficient synthesis of sulfonamides has long been pursued by chemists due to their frequent occurrence in pharmaceuticals, especially in anti-inflammatory medicines. The traditional assembly from sulfonyl chlorides and amines, as well as the recently developed one-step synthesis of sulfonamides involving sulfur dioxide, still faces challenges such as poor substrate compatibility and/or stringent reaction conditions. Herein, we present a strategy for the in situ generation of sulfamoyl radicals for the one-step modular synthesis of both alkenyl and alkyl sulfonamides with wide substrate applicability (>100 examples), mild reaction conditions, and easily accessible starting materials. This method is successfully applied to the late-stage modification of drug molecules (23 examples), the one-step synthesis of the drug molecule naratriptan, and the 15 N-labeling of sulfonamides.