[32751-01-2]  · C3H2F6O3  · 2-Hydroperoxyhexafluoro-2-propanol  · (MW 200.05)

(oxidizing agent capable of Baeyer-Villiger oxidation;1 selective alkene epoxidation;2 conversion of aldehydes to carboxylic acids;3 N-, S-, Se-oxidation;4 strong parallels in structure and function to biologically active flavin oxidants5-7)

Alternate Name: HPHP.

Physical Data: liquid at rt.

Solubility: sol CH2Cl2.

Preparative Method: prepared by the reaction of hexafluoroacetone (HFA)8 with either 30% or 90% Hydrogen Peroxide by the following representative procedure. A 250 mL roundbottomed flask is fitted with Claisen adapter, pressure-equalizing, graduated addition funnel, dry ice condenser, and CaCl2 drying tube. Anhydrous HFA (14 mL, 0.12 mol) is collected in the addition funnel and the roundbottom is charged with CH2Cl2 (100 mL) and 90% H2O2 (3.0 mL, 0.11 mol), and then cooled to -60 °C. After dropwise addition of HFA, the mixture is allowed to warm to rt and a clear, homogeneous solution results which can be titrated (NaI, Na2S2O3, ca. 0.7 M) and stored conveniently at -5 °C. Under these conditions, the reagent is stable for at least 2 months.

Handling, Storage, and Precautions: slowly decomposes at rt to form CO2, O2, CF3OOH and other products. Hexafluoroacetone is a highly toxic, nonflammable gas and should only be handled in a fume hood. Concentrated solutions of hydrogen peroxide must be handled with care.

Baeyer-Villiger Oxidation.

The oxidation of ketones to esters or lactones, usually performed with peroxycarboxylic acids, can be readily accomplished using HPHP in CH2Cl2 at reflux (4-5 h).1 Nonaromatic ketones are cleanly oxidized to the corresponding esters (Table 1) while the oxidation of aromatic ketones is accompanied by tar formation, probably due to electrophilic aromatic substitution. Notably, mesitylene affords mesitol. Aniline is converted to nitrobenzene, but pentafluoroaniline gives only decafluoroazobenzene in low yield.

Selective Epoxidations.

With its close similarity to peroxyimidic, -carbamic, and -carboxylic acids, solutions of HPHP in methylene chloride or 1,2-dichloroethane transform unhindered alkenes to epoxides at rt or reflux.2 Oxidations can be carried out either using stoichiometric quantities of oxidant, or in a two-phase mixture of substrate, solvent, catalytic hexafluoroacetone, and excess H2O2. Epoxidation of allylic alcohols or acetates occurs with high syn stereoselectivity. The alkenes shown in Table 2 gave the corresponding epoxides (yield and stereochemistry indicated parenthetically). A similar process was subsequently reported to occur with hexachloroacetone.9

Oxidation of Aldehydes to Carboxylic Acids.

HPHP is also synthetically useful as a nucleophilic reagent for the conversion of aldehydes to carboxylic acids in the presence of other functional groups (Table 3).3 Unlike most chromium and manganese reagents, HPHP does not oxidize alcohols, and it provides a useful, nonmetal-based alternative to Silver(II) Oxide. Like epoxidations, aldehyde oxidations can be performed with H2O2 and a catalytic quantity of HPHP in a two-phase CH2Cl2-Na2CO3 system. The aldehydes shown in Table 3 can be converted to the corresponding carboxylic acids.

Oxidation of Amines to Amine Oxides and Sulfides to Sulfoxides and Sulfones.

As shown in Table 4, HPHP oxidizes tertiary amines to N-oxides in 60-95% yield, and can also transform sulfides to sulfoxides (1 equiv HPHP) or to sulfones (2 equiv).4 Competitive amine-versus-sulfide experiments indicate that sulfur oxidation is faster. Conversion of diallyl sulfide to diallyl sulfoxide illustrates the additional selectivity which can be expected. Rates are fastest in CH2Cl2 and diminish considerably in hydrogen-bonding solvents.

1. Chambers, R. D.; Clark, M. TL 1970, 2741.
2. Heggs, R. P.; Ganem, B. JACS 1979, 101, 2484.
3. Ganem, B.; Heggs, R. P.; Biloski, A. J.; Schwartz, D. R. TL 1980, 21, 685.
4. Ganem, B.; Biloski, A. J.; Heggs, R. P. TL 1980, 21, 689.
5. Wessiak, A.; Bruice, T. C. JACS 1981, 103, 6996.
6. Ball, S.; Bruice, T. C. JACS 1980, 102, 6498.
7. Kemal, C.; Chan, T. W.; Bruice, T. C. PNA 1977, 74, 405.
8. Dupont Product Information Bulletin SD-7R, April, 1980.
9. Stark, C. J. TL 1981, 22, 2089.

Bruce Ganem

Cornell University, Ithaca, NY, USA

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