Feng Liu; Hua Wang; Suhua Li; Grant A. L. Bare; Xuemin Chen; Chu Wang; John E. Moses; Peng Wu; K. Barry Sharpless
Angew. Chem. Int. Ed. Engl., 2019, 58(24), 8029-8033
https://doi.org/10.1002/anie.201902489

Abstract

We report here the development of a suite of biocompatible SuFEx transformations from the SOF4-derived iminosulfur oxydifluoride-hub in aqueous buffer conditions. Thes biocompatible SuFEx reactions of iminosulfur oxydifluorides (R-N=SOF2) with primary amines give sulfamides (8 examples, up to 98%), while the reaction with secondary amines furnish sulfuramidimidoyl fluoride products (8 examples, up to 97%). Likewise, under mild buffered conditions, phenols react with the iminosulfur oxydifluorides (Ar-N=SOF2) to produce sulfurofluoridoimidates (13 examples, up to 99%), which can themselves be further modified by nucleophiles. These transformations open the potential for asymmetric and trisubstituted linkages projecting from the sulfur(VI) center, including versatile S-N and S-O connectivity (9 examples, up to 94%). Finally, the SuFEx bioconjugation of iminosulfur oxydifluorides to amine-tagged single-stranded DNA and to BSA protein demonstrate the potential of SOF4 derived SuFEx click chemistry in biological applications.