Easy Access to Aliphatic Sulfonamides using Sulfamoyl Chlorides Under Visible Light Activation

Abstract

Sulfonamides are prevalent motifs in marketed drugs and natural products. Their synthesis represents a great interest to the pharmaceutical industry, due to their unique biological properties. Recently, several methods for the synthesis of aryl sulfonamides have been developed, but little effort has focused on developing one-step methodologies to access sulfonamides flanked by two alkyl groups. This protocol describes a practical and facile method for the net hydrosulfamoylation of electron-deficient alkenes using sulfamoyl chlorides as radical precursors under blue-light activation. This practical and cost-effective methodology is performed in the presence of the metal-free photocatalyst Eosin Y and uses light as a clean and traceless energy source. The procedure is scalable, displays a broad functional group tolerance, and can be applied for late-stage functionalization. All reagents used in this protocol are commercially available. Simple reaction set-up, the absence of work-up and easy purification, demonstrate the convenience of this protocol. The reaction is best applied to electron-deficient alkenes. INTRODUCTION:Over the recent decades, sulfonamides featured in a broad range of biologically active molecules and are common motifs in pharmaceuticals and agrochemicals 1,2 . Initially employed for antibacterial purposes 3,4 , the application of this motif in drug discovery has been extended 1 2 3 4 5 7 8 9

Photocatalysis in the Life Science Industry

“…In 2020, Janssen and Gouverneur disclosed two independent methodologies for the formal hydrosulfamoylation (Scheme ) , and hydrosulfonylation (Scheme ) of alkenes and alkynes. The hydrosulfamoylation reaction proceeds via a silicon radical mediated chlorine atom abstraction to generate the sulfur radical (Scheme ).…”

“…The hydrosulfamoylation reaction proceeds via a silicon radical mediated chlorine atom abstraction to generate the sulfur radical (Scheme ). , This distinct strategy avoids the challenging single electron reduction of S–Cl groups to liberate S -centered radicals. The sulfamoyl radical then adds to the olefin via a Giese-type reaction giving the product, following HAT from the silane.…”