SuFEx Activation with Ca(NTf₂)₂: A Unified Strategy to Access Sulfamides, Sulfamates, and Sulfonamides from S(VI) Fluorides

Abstract

A method to activate sulfamoyl fluorides, fluorosulfates, and sulfonyl fluorides with calcium triflimide and DABCO for SuFEx with amines is described. The reaction was applied to a diverse set of sulfamides, sulfamates, and sulfonamides at room temperature under mild conditions. Additionally, we highlight this transformation to parallel medicinal chemistry to generate a broad array of nitrogen-based S(VI) compounds.

The Emerging Applications of Sulfur(VI) Fluorides in Catalysis

“… 48 They proposed that calcium triflimide coordinates either to the oxygens of the sulfonyl fluoride or the fluorine atom to increase the electrophilicity at sulfur. In 2020, Ball and am Ende 49 ( Scheme 11 b) and Grygorenko 50 ( Scheme 11 c) further extended the use of Ca(NTf 2 ) 2 to other S(VI) fluorides, including sulfamoyl fluorides (R = NR 3 R 4 ), fluorosulfates (R = OAr), and sulfonyl fluorides (R = alkyl or aryl). Notably in the second-generation Ball and am Ende Ca(NTf 2 ) 2 system, the introduction of 1,4-diazabicyclo[2.2.2]octane (DABCO) allowed for room-temperature sulfur-fluoride exchange reactions with amines, even with the significantly more stable sulfamoyl fluorides and fluorosulfates.…”

Complementary Base Lowers the Barrier in SuFEx Click Chemistry for Primary Amine Nucleophiles

“… 10 , 23 Overall, it is observed that strong bases and H 2 F – can act as catalysts for the reaction but the exact role is unclear up to now. 10 , 19 , 24 , 25 …”

Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines

“…[5] After extensive screening of the reaction conditions, we found substitution of the S VI À F with amines could be achieved on water (Table 4). [26,27] The functional group compatibility was excellent on both sides of the substrates, such as the carboxylic acid (9-1), heterocycles (9-2), alcohols (9-2, 9-6), olefins , and the cyano groups (9-10). Aniline (9-6) and hydrazine derivatives (9-9) also afforded the desired ligation with high efficiency.…”