Hexafluoroisopropyl Sulfamate

[637772-38-4] C3H3F6NO3S (MW 247.11) InChI = 1S/C3H3F6NO3S/c4-2(5,6)1(3(7,8)9)13-14(10,11)12/h1H,(H2,10,11,12) InChIKey = MIEKENGUIASFSB-UHFFFAOYSA-N (a sulfamoylation reagent for the synthesis of sulfamates and sulfamides from alcohols and amines; a nitrogen source for N-atom transfer in CH insertions and aziridinations) Alternative Names: HFIPS; HfsNH2; 1,1,1,3,3,3-hexafluoro-2-propyl sulfamate. Physical Data: white solid; mp 52–55 °C.1 1H NMR (CDCl3): δ 5.18 (sept, 3JHF = 5.6 Hz, 1H), 5.18–5.09 (brs, 2H). 13C NMR (CDCl3): δ 120.1 (qq, 1JCF = 283 Hz, 3JCF = 3.7 Hz, 2C), 73.5 (sept, 2JCF = 35.3 Hz). 19F NMR (CDCl3): δ −73.67.1 Solubility: soluble in EtOAc, Et2O, THF, DMF, MeCN, and acetone; moderately soluble in CH2Cl2 and CDCl3; and poorly soluble in hexanes. HFIPS is also soluble in DMSO, MeOH, and EtOH, but the long-term stability of the reagent in these solvents has not been determined. Analysis of Reagent Purity: 1H NMR, 13C NMR, and/or 19F NMR. HFIPS has also been characterized by X-ray crystallographic analysis (CCDC 2059516).1 Preparative Methods: HFIPS is synthesized using a two-step, one-pot procedure from chlorosulfonyl isocyanate (CSI)2 and hexafluoroisopropanol (HFIP) (eq 1). The slow addition of formic acid to a solution of CSI in acetonitrile, which generates sulfamoyl chloride in situ, is followed by the slow addition of a solution of HFIP in dimethylacetamide (DMA) without additional base (Caution: Strong evolution of CO and CO2 gas upon addition; potential runaway kinetics in certain solvents on larger scales).3–5 High yields for HFIPS have been reported (83–100%) using a large excess CSI (3–4 equiv) relative to HFIP,6–11 but a more reliable and atom-economical procedure using only a modest excess of CSI (1.3 equiv) has been published (74%, 32-g scale).1 Note that DMA and NMP are superior solvents to DMF for this reaction, and that, using an additional amine base is detrimental.3,4 The reaction is quenched with a slow addition of water, and HFIPS is extracted with Et2O. After washing the ethereal extracts with water and brine, the removal of residual DMA is aided considerably by washing with aqueous LiCl (10% w/v). (1) Purification: HFIPS is isolated in high purity following an aqueous workup but can also be purified using flash chromatography (EtOAc/Hex) on silica gel if desired. It should be noted, however, that HFIPS can be difficult to visualize by TLC since it is resistant to most common TLC stains, but its presence can be inferred by negative staining with iodine.11 Handling, Storage, Precautions: Stable for extended periods at room temperature, but storage at lower temperatures is likely beneficial; less stable when stored with water or DMA impurities.

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