Asymmetric oxidative transformations

Figure 20.10 Selected examples of other enzymes for asymmetric oxidative transformations.

H. B. Kagan, Asymmetric Oxidation Mediated by Organometallic Species, in W. Bartmann and K. B. Sharpless, eds., Stereochemistry of Organic and Bioorganic Transformations, p. 31, Verlag Chemie, Weinheim, 1987. 

Asymmetric oxidation of formaldehyde dithioacetals with aqueous NaI04 was realized by Ogura et al. in the presence of a catalytic amount of BSA (0.005-0.02 mol equiv.) [96]. Under conditions the authors used, the starting sulfide was virtually insoluble in water (pH 9.2), and the best results were obtained at low concentrations of BSA. This result clearly indicates that the BSA/sulfide ratio is not the controlling factor of enantioselectivity. With this protocol, p-Tol-S-CH2-S-p-Tol could be transformed into monosulfoxide with 60% ee. The same protocol gave isopropyl phenyl sulfoxide with 60% ee. 

Permanganese is a common oxidative reagent, the application of which to the asymmetric oxidative cyclization of 1,5-dienes has been reported by Brown (Scheme 3.14). The addition of acetic acid is quite important for the reaction to proceed, and highly functionalized tetrahydrofurans are obtained in a range of 58 to 75% ee, in diastereoselective manner [35]. Another oxidative transformation using KMn04 with a chiral ammonium salt has been investigated. Scheme 3.15 illustrates the asymmetric dihydroxylation of electron-deficient olefins to chiral diols in the... 

The 1,2-diols formed by the asymmetric oxidation can be used as substrates in a wide variety of transformations. Conversion of the hydroxy groups to p-toluenesulfonates then allows nucleophilic displacement by azide at both centers with inversion of configuration (Scheme 9.22).161... 

The procedure with an excess of DET gives better results in the asymmetric oxidation of 1,3-dithiolane (Table 9). This latter finding has been elegantly applied by the same group to the resolution of racemic ketones, through their transformation into 1,3-dithiolanes, asymmetric monosulfoxidation followed by diastereomeric separation, and regeneration of the parent ketone.56... 

Foumeron, J.D., Ardielas, A. and Furstoss, R. (1989) Microbial transformations. 12. Regiospedfic and asymmetric oxidation of the remote double bond of geraniol. 

Preparative Methods racemic l,l -bi-2,2 -naphthol (BINOL) is most conveniently prepared by the oxidative coupling reaction of 2-naphthol in the presence of transition metal complexes (eq 1). The resolution of racemic BINOL with cinchonine may be performed via the cyclic phosphate (eq 2). An alternative procedure to provide directly optically active BINOL is the oxidative coupling of 2-naphthol catalyzed by Cu salt in the presence of chiral amines (eq 3). The best procedure uses (+)-amphetamine as the chiral ligand and provides BINOL in 98% yield and 96% ee. Above 25 °C the Cu /(+)-amphetamine/(5)-BINOL complex precipitates, while the more soluble Cu /(+)-amphetamine/(I )-BINOL complex is slowly transformed into the former complex. 9,9 -Biphenanthrene-10,10 -diol has also been prepared in 86% yield and with 98% ee by a similar asymmetric oxidative coupling of 9-phenanthrol in the presence of (I )- 1,2-diphenylethylamine. ... 

Major interest has been expressed in the synthesis of chiral sulfoxides since the early 1980s, when it was discovered that chiral sulfoxides are efficient chiral auxiliaries that are able to bring about important asymmetric transformations [22]. Sulfoxides are also constituents of important drugs (e.g., omeprazole (Losec , Priso-lec )) [23]. There is a plethora of routes of access to enantioenriched sulfoxides, and many involve metal-catalyzed asymmetric oxidations [24]. Examples of ruthenium metal-based syntheses of sulfoxides are scarce, presumably due to the tendency of sulfur atoms to bind irreversibly to a ruthenium center. Schenk et al. reported a dia-stereoselective oxidation of Lewis acidic Ru-coordinated thioethers with dimethyl-dioxirane (DMD) (Scheme 10.16) [25[. Coordination of the prochiral thioether to the metal is followed by diastereoselective oxygen transfer from DMD in high yield. The... 

The anion of an aldehyde dithioacetal 5-oxide is well known to add to a,3-unsaturated carbonyl compounds. " Conjugate addition of formaldehyde di-p-tolyl dithioacetal 5-oxide (114) to open-chain and cyclic enones is achieved by using HMPA as a polar cosolvent in THF (-78 C)." The lithio derivative of (5)-(114) was found to add to 2-cyclopentenone with asymmetric induction. Transformation of the dithioacetal part into a formyl group gives 3-formylcyclopentanone in 39% enantiomeric excess (equation 28)." Interestingly, highly asymmetric induction is observed in the conjugate addition of the... 

Polymers Il-m have been transformed by asymmetric oxidation into chiral poly(ester 0-sulfoxide)s V-m. These modified polymers present a cholesteric mesophase of limited persistence. Their optical activity and stability are also discussed. 

Asymmetric oxidations have followed the usual development pathway in which face selectivity was observed through the use of chiral auxiliaries and templates. The breakthrough came with the Sharpless asymmetric epoxidation method, which, although stoichiometric, allowed for a wide range of substrates and the stereochemistry of the product to be controlled in a predictable manner [1]. The need for a catalytic reaction was very apparent, but this was developed and now the Sharpless epoxidation is a viable process al scale, although subject to the usual economic problems of a cost-effective route to the substrate (see later) [2]. The Sharpless epoxidation has now been joined by other methods and a wide range of products are now available. The pow er of these oxidations is augmented by the synthetic utility of the resultant epoxides or diols that can be used for further transformations, especially those that use a substitution reaction (see Chapter 7) [1]. 

Another way to improve the yield of such transformations is to combine a chemical asymmetric oxidation and a biocatalytic approach. This has been illustrated on 2-methyl-epoxyheptane as shown in Fig. 22. Thus, a 33% overall yield of the corresponding (S)-epoxide was obtained with an ee of 97% [149]. It is to be emphasized that, in this particular case the best corresponding chemical method for obtaining this epoxide, i. e. the Sharpless asymmetric dihydroxylation, only led to an ee of 71 %. 

A total synthesis of LTB has been reported by Corey et al. as outlined in Scheme 3.16. By using the Sharpless asymmetric oxidation, the enantiomer of the epoxy alcohol in Scheme 3.11 was obtained, from which the corresponding aldehyde was then prepared. The epoxy olefin was transformed to the desired Wittig salt 39, which was condensed with the homologated aldehyde 40, giving a modest yield of the desired (8Z)-isomer. Again, the benzoyloxy aldehyde... 

In summary, we have presented a variety of metal-based catalysts which are able to mediate the asymmetric oxidations of sulfides to the corresponding sulfoxides and sulfimides. Although very different approaches relying on distinct metal complexes are known, there is still a demand for an appropriate system which would allow the transformation of any sulfide to occur with high enantioselec-tivity. Especially the rational design of chiral complexes able to selectively oxidize substrates, in particular, those compounds other than aryl methyl sulfides is still a major challenge. 

The characteristic features of the Kobayashi approach (Scheme 50) are the construction of the Cig alkenyl-furan by a Cf + Cn + C4 sequence, the Sharpless asymmetric dihydroxylation of the olefinic C=C bond, and the oxidative transformation, efficiently and under mild conditions, of the substituted furan ring into a 4-oxobut-2-enoic-acid moiety, which is diastereoselec-tively reduced by Zn(BH4)2. 

This asymmetric oxidation of sulfides has been achieved successfully using bio-transformations. However, a detailed discussion of these reactions is beyond the scope of the present book. A number of enatiomerically pure transition metal complexes in combination with terminal oxidants have been used to effect the asymmetric oxidations of sulfides to sulfoxides. ... 

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