Installation of -SO2F groups onto primary amides.

Jing Liu,Shi-Meng Wang,Hua-Li Qin,Njud S Alharbi

doi:10.3762/bjoc.15.186

Abstract

A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics.

Highlights

Sulfur(VI) fluoride exchange (SuFEx) is a new class of click chemistry developed by Sharpless and co-workers in 2014, for creating molecular connections based on the unique stability–reactivity pattern of the S(VI)–F bond with reliability and efficiency, which has been widely applied in organic synthesis, chemical biology and drug discovery [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
We speculate that the tautomerism of amides [43] may occur in the reaction process and the tautomer 3e could react with Na2SO4 to generate 4e, which indicated that N–H connected with two electron-withdrawing groups can behave as an acid to donate a proton for chemical transformations
We have developed a novel method for N-fluorosulfonylation of amides. This simple, convenient, and mild protocol provides a portal to a class of novel sulfonyl fluorides for SuFEx click chemistry with great potential to be applied in the development of covalent inhibitors

Summary

Introduction

Sulfur(VI) fluoride exchange (SuFEx) is a new class of click chemistry developed by Sharpless and co-workers in 2014, for creating molecular connections based on the unique stability–reactivity pattern of the S(VI)–F bond with reliability and efficiency, which has been widely applied in organic synthesis, chemical biology and drug discovery [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. The reactions of aliphatic or aromatic amines with SO2F2 or the fluorosulfurylimidazolium salt have been achieved for assembly of N-sulfonyl fluorides [1,30], which have served as important active precursors for the development of noncovalent inhibitors (Scheme 1, (1)) [1,30,31]. The installation of sulfonyl fluoride (SO2F) onto nitrogen atoms of amides has not been achieved, which, if accomplished, would provide a very important class of sulfonyl fluorides, namely, N-fluorosulfonyl amides, for the development of potential covalent inhibitors [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24].

Results

Conclusion