Sulfondiimidamides as new functional groups for synthetic and medicinal chemistry

Due to their three-dimensional structure, chemical and metabolic stability, polarity, and hydrogen-bonding ability, sulfonamides occupy a privileged position among the functional groups used to design bioactive molecules. The mono aza variants, sulfonimidamides, a functional group known since the 1930s, possess an extra nitrogen atom, which delivers an additional point of diversity and introduces chirality at sulfur. However, the double aza analogs, sulfondiimidamides, are elusive molecules with severely limited accessibility. We show that sulfondiimidamides are viable molecules and that by using an unsymmetrical sulfurdiimide as a linchpin, in combination with organometallic reagents and amines, that their three-component assembly is possible. Variation of the substrates, and the controlled manipulation of nitrogen functionality, allows a broad range of substituents to be introduced at all three nitrogen atoms and at carbon.