Amphiphilic Polyfluorinated Amino Ethers from Cyclic Sulfamidates

Abstract

Regioselective ring opening of cyclic sulfamidates was achieved by means of nucleophilic polyfluorinated alkoxides to access achiral and chiral β- and γ-ORF amines and α-amino esters. Subsequent transformations provide free amines ready for incorporation into bioactive substances through amide bond formation or nucleophilic aromatic substitution.

Monofluoromethylation of Cyclic Sulfamidates and Sulfates with α‐Fluorocarbanions of Fluorobis(phenylsulfonyl)methane and Ethyl 2‐Fluoroacetoacetate

“…The combined organic layers were washed with brine, dried over MgSO 4 and concentrated under vacuum to yield the crude expected product, which was purified by column chromatography (eluent: cyclohexane/EtOAc). Characterization data of sulfamidates 1 a – s are in agreement with literature data [7c,10–11] …”

“…Characterization data of sulfamidates 1 a-s are in agreement with literature data. [7c, [10][11] General procedure for the synthesis of cyclic sulfates: A procedure by E.M. Carreira and co-workers was followed. [19] 1,2-Diol or 1,3-diol (50 mmol, 1.0 equiv) was dissolved in CH 2 Cl 2 (30 mL) and the solution was cooled to 0 °C.…”

“…The nucleophilic trifluoromethylation was demonstrated on simple 1,2 cyclic sulfates by reduction of trifluoromethyl iodide by tetrakis(dimethylamino)ethylene (TDAE) [9] . Chalcogen‐containing fluorinated motifs that are the OR F group [10] and SCF 3 [11] also illustrated the versatility of the cyclic sulfamidate scaffold. In order to fill a gap in this nucleophilic reagent set, we tackled the challenge of monofluoromethylation (Scheme 1b).…”