Highly versatile synthesis of nitrogen-containing compounds by means of nitrobenzenesulfonamides

Summarized in this article are the syntheses of nitrogen-containing compounds by means of nitrobenzenesulfonamides (Ns-amides), which serve both as protecting and activating groups. Ns-Amides, readily prepared from primary amines, were converted to the N,N-disubstituted sulfonamides by conventional alkylation or Mitsunobu conditions. The Ns group was readily removed with soft nucleophiles via Meisenheimer complexes to give the corresponding secondary amines. The major advantage of this method is that both alkylation and deprotection proceed under mild conditions. Furthermore, Ns-amides allow efficient synthesis of a variety of diamines and protected primary amines. When treated with NsCl, symmetrical diamines gave mono-nosylated diamines selectively. Using these diamines as starting material, natural polyamine toxins were synthesized in short steps and in high yields. In the case of HO-416 b and Agel-489, Ns group was removed while the substrates were on a solid support, thus allowing an efficient isolation of these highly polar compounds. Lipogrammistin-A was synthesized using Ns-assisted macrocyclization as a key step.