Heteroaryl 2‐Sulfonamide Synthesis by SN2 Reaction–Oxidation Cascade

Heteroaryl 2‐sulfonamides are an important structural moiety in drug discovery. However, reports of the efficient synthesis of these scaffolds are rare. Herein we disclose new reaction conditions to synthesize heteroaryl 2‐sulfonamides from disulfanes and amines through an SN2‐oxidation cascade. The approach is compatible with a wide variety of heteroaryl and amine substrates and can be conducted on a gram scale. A potential Werner Syndrome Protein (WRN) small molecule inhibitor H3B‐968 was also synthesized by this method. An efficient SN2‐oxidation cascade reaction for synthesizing heteroaryl 2‐sulfonamides from disulfanes and amines is described. The methodology has broad scope, affording heteroaryl 2‐sulfonamides in moderate to good yields, and was applied to the synthesis of H3B‐968, a potential Werner Syndrome Protein (WRN) small molecule inhibitor.