Epoxides asymmetric fluorination

It should be noted that the related imine-oxaziridine couple E-F finds application in asymmetric sulfoxidation, which is discussed in Section 10.3. Similarly, chiral oxoammonium ions G enable catalytic stereoselective oxidation of alcohols and thus, e.g., kinetic resolution of racemates. Processes of this type are discussed in Section 10.4. Whereas perhydrates, e.g. of fluorinated ketones, have several applications in oxidation catalysis [5], e.g. for the preparation of epoxides from olefins, it seems that no application of chiral perhydrates in asymmetric synthesis has yet been found. Metal-free oxidation catalysis - achiral or chiral - has, nevertheless, become a very potent method in organic synthesis, and the field is developing rapidly [6]. 

Bruns and Haufe have described the first examples of a transition metal complex mediated asymmetric ring opening (ARO) of both meso- and racemic epoxides via formal hydro-fluorination [23]. Initial attempts with chiral Euln complexes led to very low asymmetric induction. Opening of cyclohexene oxide 30 with potassium hydrogendifluoride in the presence of 18-crown-6 and a stoichiometric amount of Jacobsens chiral chromium salen complex 29 [24a] finally yielded two products 31 and 32 in a 89 11 ratio and 92% combined yield, the desired product 31 being formed with 55% ee. Limiting 29 to a catalytic amount of 10 mol% led to an increase in the ratio of 31, however, with the enantiomeric excess dropping to 11% (Scheme 5). 

Haufe, G. Bruns, S. Runge, M. Enantioselective ring-opening of epoxides by HF-reagents. Asymmetric synthesis of fluoro lactones. J. Fluorine Chem. 2001, 772(1), 55-61. 

The application of fluorinated media seems to be a flourishing new area in homogeneous catalysis (103). However, until now enantioselective catalytic reactions in this alternative solvent are very rare. Chiral perfluoroalkylated SALEN-manganese complexes have been used for asymmetric epoxidation (104). 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

Denmark and co-workers used 7-membered C -symmetric carbocyclic biaryl ketones 362 for the asymmetric epoxidation of fraris-olelins [247]. Ketone 362c was found to be more active than ketones 359 (Table 7.25). At the same time the structurally related fluorinated binaphthyl ketones 363 of similar catalytic profile were reported by Behar et al. in 2002 [248]. 

In 2000, Solladie-Cavallo synthesized fluorinated ketones 408 from (+)-dihydrocarvone and investigated them in the asymmetric epoxidation of different fran -stilbenes and silyl enol ethers (Fig. 7.20) [285-287]. Later she reported rigid fran -decalones 409 which gave up to 70% ee (409a) and 20% ee (409b) in the epoxidation of ran -P-methylstyrene (Fig. 7.20) [288]. 

In 2000, SoUadie-Cavallo et al. reported the asymmetric epoxidation of p-methylcinnamate with fluorocyclohexanones 408 [286]. Higher conversion and ee s were achieved with 408a than with 408b. Presumably, the axial fluorine is a more efficient electron withdrawing substituent than equatorial fluorine (Table 7.28). 

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