Synthesis of Sulfonyl Fluorides from Sulfonamides

Abstract

A simple and practical synthesis of sulfonyl fluorides from sulfonamides is reported. The method capitalizes on the formation of the sulfonyl chloride by virtue of the reaction of Pyry-BF 4 and MgCl 2 , and subsequent in situ conversion to the The synthesis of complex organic molecules bearing sulfonyl fluorides in their structure has gained tremendous momentum due to their successful activity in the field of chemical biology. [1,2] Due to its unique chemical properties, several sulfonyl fluorides have been utilized as warheads in chemical biology to target amino acid residues and act as activity-based probes (Figure 1). [3] Numerous synthetic approaches to sulfonyl fluorides are available in the literature, starting from a myriad of different starting materials. [4] Early syntheses can be found from the sulfonyl hydrazide, [5] thiosulfonate, [6] sulfonyl chloride, [2,7] sulfonic acids, [8] sulfonate salts [9] among others (Figure 2A). [10] However, most of these traditional methods are restricted in terms of functional group compatibility and synthetic steps are required to obtain the starting materials. In more recent approaches, Willis and Bagley [11] and Ball [12] independently addressed these issues and reported elegant Pd-catalyzed strategies for the syn-[a]

Multicomponent reaction–derived covalent inhibitor space

“…The potential of electrophile (-fragment) screening as a practical and efficient tool for covalent-ligand discovery is well described ( 25 ). Few generalized approaches toward covalent libraries have been described while the need for biological screening of electrophiles is increasing ( 24 , 25 , 57 , 58 ). The strategic formation of covalent bonds between small molecules and proteins has many other underappreciated applications as enabling platforms for drug discovery ( 59 ).…”

A Unified Strategy for Arylsulfur(VI) Fluorides from Aryl Halides: Access to Ar‐SOF3 Compounds

“…For example, synthesis of aryl sulfonyl fluorides has mainly relied on the anion exchange from the parent arylsulfonyl chlorides [5a, 11] . Recent examples also disclosed the possibility of obtaining sulfonyl fluorides from the corresponding thiophenols (Ar‐SH), [12] aryl halides (Ar‐X) [13] or arylsulfonamides (Ar‐SO 2 NH 2 ) [14] . Access to aryl sulfonimidoyl fluorides is currently possible by halogen exchange from sulfonimidoyl chlorides, [15] oxidation of sulfinamide salts [16] or aryl lithium addition to S(O)(NR)F 2 [6b] .…”

“…[5a, 11] Recent examples also disclosed the possibility of obtaining sulfonyl fluorides from the corresponding thiophenols (Ar-SH), [12] aryl halides (Ar-X) [13] or arylsulfonamides (Ar-SO 2 NH 2 ). [14] Access to aryl sulfonimidoyl fluorides is currently possible by halogen exchange from sulfonimidoyl chlorides, [15] oxidation of sulfinamide salts [16] or aryl lithium addition to S(O)(NR)F 2 . [6b] Finally, state-of-the-art synthesis of Ar-SF 4 Cl mainly relies on the oxidation of the corresponding aryl disulfides.…”

Primary Sulfonamide Synthesis Using the Sulfinylamine Reagent N-Sulfinyl-O-(tert-butyl)hydroxylamine, t-BuONSO

“… 13 The Cornella laboratory has recently reported methods for the conversion of primary sulfonamides to the corresponding sulfonyl chlorides and fluorides by activation with pyrylium salts. 14 There are also examples of their use as directing groups 15 for C–H functionalization. 16 In the past few years, some notable functionalizations which expand the utility of primary sulfonamides have also appeared.…”