[240810-64-4] · C23H12F34O · (MW 950.29)
(reagent used to protect hydroxyl groups and aniline nitrogens; protected substrates are rendered fluorous-soluble and can be purified by fluorous liquid-liquid or solid phase extraction techniques; after cleavage fluorous label can be recycled)
Physical Data: mp 36-38 °C.
Solubility: soluble in tetrahydrofuran, diethyl ether, FC-72; insoluble in H2O.
Analysis of Reagent Purity: 1H and 13C NMR, IR, elemental analysis.
Handling, Storage, and Precautions: reagent is best stored under a nitrogen atmosphere in a dry environment.
Preparative Methods: the fluorous vinyl ether is prepared1 by a two-step reaction sequence involving Grignard reagent formation from commercially available 1H,1H,2H,2H-heptadecafluorodecyl iodide by sonication with magnesium powder and condensation with ethyl formate to give an intermediate secondary alcohol (
Protection of alcohols as fluorous alkoxy ethyl acetals (AE) proceeds under mildly acidic conditions.1 Treatment of an ethereal solution of a primary alcohol and three equiv of fluorous vinyl ether with 5 mol % of 10-camphorsulfonic acid (CSA) for 3 h at room temperature provides the fluorous acetal in good yields (
Although a three-fold excess of the fluorous vinyl ether is necessary for optimal yields, the majority of the unreacted vinyl ether is recoverable after the protection reaction via chromatography on SiO2. The fluorous acetals are stable to basic and nucleophilic reaction conditions.1
A single example of N-protection of an aromatic amine has been reported, although the yield is low (
Removal of fluorous acetals proceeds under mildly acidic conditions (
The fluorous AE and the fluorous THP3 are the only readily recyclable fluorous protecting groups.4
The techniques of fluorous liquid-liquid extraction and fluorous solid-phase extraction can be used to purify the fluorous AE-protected substrates after reactions.2 Due to the high fluorine content of the acetal, fluorous liquid-liquid extraction procedures need not be limited to acetonitrile as the organic solvent; diethyl ether, ethyl acetate, or dichloromethane may also be used. Solid phase extraction using fluorous reverse phase silica gel (FRP SiO2)5 is a purification option for large or highly polar substrates.6 The fluorous AE has higher fluorine content than the fluorous THP3 and the BPFOS7 protecting groups, but lower fluorine content than most tris(perfluoroalkyl) silyl ethers.2,8 The fluorous AE has been applied to a selective purification of a mixture of alcohols.9 Protection of a mixture of six alcohols resulting from addition of six different nucleophiles to a single aldehyde followed by extraction of the fluorous acetals with FC-72/acetonitrile was selective for the six fluorous AE-protected compounds (
University of Pittsburgh, Pittsburgh, Pennsylvania, USA