Metal-Free Direct Access to N-Sulfonyl Amidines from Sulfonamides and Secondary Amines Involving Tandem C-N Bond Formations

We report a mild and efficient metal-free one-pot procedure for the synthesis of N-sulfonyl amidines via the direct reaction of sulfonamides with secondary amines without using any additives. A wide range of substrates with variety of functional groups is well tolerated under the reaction conditions. Preliminary mechanistic studies indicate that the secondary amine plays a dual role as a C1 source of the amidine group and an aminating agent. Synthetic utility of this method is shown in the late-stage functionalization of drug molecules on the gram scale.

Automated summary

A mild and efficient metal-free one-pot procedure for the synthesis of N-sulfonyl amidines via the direct reaction of sulfonamides with secondary amines without using any additives was reported. The reaction conditions tolerate a wide range of substrates with various functional groups. Preliminary mechanistic studies suggest that the secondary amine serves as both a C1 source of the amidine group and an aminating agent. The synthetic utility of this method was demonstrated in the late-stage functionalization of drug molecules at the gram scale.