Hexafluoroisopropyl Sulfamate: A Useful Reagent for the Synthesis of Sulfamates and Sulfamides

Abstract

Sulfamates and sulfamides are most often synthesized from alcohols and amines with sulfamoyl chloride, which is an unstable reagent. We have identified hexafluoroisopropyl sulfamate (HFIPS) as a bench-stable solid that reacts readily with a wide variety of alcohols, amines, phenols, and anilines under mild reaction conditions. The sole byproduct of the reaction is hexafluoroisopropanol (HFIP) and reaction products can often be isolated in high purity after an aqueous workup (optional) and removal of solvents by evaporation.

Catalyst-Controlled, Site-Selective Sulfamoylation of Carbohydrate Derivatives

“…Masked sulfamates can also be accessed using N -acylated sulfamoyl chlorides 3 , which are generated from alcohols and chlorosulfonyl isocyanate (ClSO 2 NCO). Sulfamate esters that react with alcohols via group transfer have also been investigated, including electron-deficient aryl sulfamate 4a and fluorinated congener 4b …”

“…Selective sulfamoylation of a primary hydroxyl (OH) group in the presence of a secondary OH has been achieved in several studies; conditions that have been used for this purpose include ClSO 2 NH 2 at low temperature, reagent 4a (catalytic N -methylimidazole, THF, 0 °C or room temperature), and reagent 2b (acetonitrile/dichloromethane, room temperature) . Chemoselective sulfamoylations, in particular, O -sulfamoylations of adenosine derivatives having a free NH 2 group, have also been reported. , In contrast, site-selective sulfamoylation of secondary OH groups remains an unsolved problem, despite the potential it offers for exploring structurally novel nucleoside analogs or carbohydrate derivatives. , In recent years, catalyst control has emerged as a broadly applicable approach for site-selective manipulation of polyfunctional compounds, including carbohydrates . Research in our laboratory has focused on the use of organoboron catalysts to activate diol groups toward reactions with a variety of electrophilic species .…”

“…Sulfamate esters that react with alcohols via group transfer have also been investigated, including electron-deficient aryl sulfamate 4a 10 and fluorinated congener 4b. 11 The prospect of achieving late-stage introduction of a sulfamoyl group to a functionalized compound has motivated the exploration of site-selective sulfamoylations. Selective sulfamoylation of a primary hydroxyl (OH) group in the presence of a secondary OH has been achieved in several studies; conditions that have been used for this purpose include ClSO 2 NH 2 at low temperature, 12 reagent 4a (catalytic N-methylimidazole, THF, 0 °C or room temperature), 10 and reagent 2b (acetonitrile/dichloromethane, room temperature).…”

“…9b Chemoselective sulfamoylations, in particular, Osulfamoylations of adenosine derivatives having a free NH 2 group, have also been reported. 11,13 In contrast, site-selective sulfamoylation of secondary OH groups remains an unsolved problem, despite the potential it offers for exploring structurally novel nucleoside analogs 14 or carbohydrate derivatives. 12,15 In recent years, catalyst control has emerged as a broadly applicable approach for site-selective manipulation of polyfunctional compounds, including carbohydrates.…”

Annulation Cascade of Sulfamate-Derived Cyclic Imines with Glycine Aldimino Esters: Synthesis of 1,3-Benzoxazepine Scaffolds

“…These observations indicate a mixed organic base system is critical for this process. The efficacy of bases can be rationalized by the extent of their interaction with HNSO 2 generated during the course of the reaction (Scheme ), and it is minimal for bulky bases as suggested by Johnson and Magolan groups, although our attempts to characterize the end product stemming from HNSO 2 was unsuccessful. The reaction yield was also not improved when the reaction medium was changed from DCM to 1,2-dichloroethane (DCE), CH 3 CN, or THF (entries 12–14).…”