Unified Approach to Benzo[d]thiazol-2-yl-Sulfonamides

In this paper, we report a unified approach to N-substituted and N,N-disubstituted benzothiazole (BT) sulfonamides. Our approach to BT-sulfonamides starts from simple commercially available building blocks (benzo[d]thiazole-2-thiol and primary and secondary amines) that are connected via (a) a S oxidation/S-N coupling approach, (b) a S-N coupling/S-oxidation sequence, or via (c) a S-oxidation/S-F bond formation/SuFEx approach. The labile N-H bond in N-monoalkylated BT-sulfonamides (pK(a) (BTSO2N(H)Bn) = 3.34 +/- 0.05) further allowed us to develop a simple weak base-promoted N-alkylation method and a stereoselective microwave-promoted Fukuyama-Mitsunobu reaction. N-Alkyl-N-aryl BT-sulfonamides were accessed with the help of the Chan-Lam coupling reaction. Developed methods were further used in stereo and chemoselective transformations of podophyllotoxin and several amino alcohols.

Automated summary

This paper presents a unified method for synthesizing N-substituted and N,N-disubstituted benzothiazole (BT) sulfonamides, starting from commercially available building blocks and utilizing various reaction sequences. The labile N-H bond in N-monoalkylated BT-sulfonamides facilitated the development of simple alkylation methods and stereoselective reactions. These methods were applied to the transformation of podophyllotoxin and several amino alcohols.