Enantioselective Oxidation Reactions

The asymmetric epoxidation of an allylic alcohol 1 to yield a 2,3-epoxy alcohol 2 with high enantiomeric excess, has been developed by Sharpless and Katsuki. This enantioselective reaction is carried out in the presence of tetraisopropoxyti-tanium and an enantiomerically pure dialkyl tartrate—e.g. (-1-)- or (-)-diethyl tartrate (DET)—using tcrt-butyl hydroperoxide as the oxidizing agent. 

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

As each BVMO is limited in substrate specificity, it is crucial to have a large collection of these oxidative biocatalysts available. Except for expanding the scope of possible reactions, a large toolbox of BVMOs would also increase the chance of being able to perform any wanted specific chemo-, regio- and/or enantioselective reaction. This contrasts with the present situation as only a relatively small number of BVMOs can be exploited for biocatalytic purposes. Therefore, it is still crucial to discover or engineer BVMOs with novel biocatalytic properties. 

Subsequent ion exchange of the metal cation with the quaternary ammonium ion catalyst provides a lipophilic ion pair (step 2), which either reacts with the requisite alkyl electrophile at the interface (step 3) or is partitioned into the electrophile-containing organic phase, whereupon alkylation occurs and the catalyst is reconstituted. Enantioselective PTC has found apphcation in a vast number of chemical transformations, including alkylations, conjugate additions, aldol reactions, oxidations, reductions, and C-X bond formations." ... 

SCHEME 129. Yields and enantiomeric excesses of the enantioselective aUyUc oxidation (Kha-rasch-Sosnovsky reaction) of cyclohexene using different chiral ligands... 

Control of reaction selectivities with external reagents has been quite difficult. Unsolved problems remaining in the held of nitrile oxide cycloadditions are (a) Nitrile oxide cycloadditions to 1,2-disubstituted alkenes are sluggish, the dipoles undergoing facile dimerization to furoxans in most cases (b) the reactions of nitrile oxides with 1,2-disubstituted alkenes nonregioselective (c) stereo- and regiocontrol of this reaction by use of external reagents are not yet well developed and (d) there are few examples of catalysis by Lewis acids known, as is true for catalyzed enantioselective reactions. 

It is true that highly enantioselective reactions are possible with proline in the asymmetric a-amination of aldehydes by azodicarboxylates and in a-oxidation with nitrosobenzene. However, good rather than excellent yields and enantioselectivities are more common in intermolecular Michael and aldol reactions. Moreover, the high catalyst loadings required for proline-catalyzed aldol reactions (up to 30%), and low TOFs (from hours to days to achieve a good conversion, even at a high catalyst... 

Further efforts to design chiral ligands led to the highly enantioselective oxidation of rranj-/3-methylstyrene (99% ee), mms-stilbene (97% ee), styrene (90%) rrans-3-heptene (90% ee), and dimethyl fumarate (93% ee) (87b-f). Although this reaction is a reliable synthetic method, the metal s cost and toxicity necessitate its use as a catalyst. In 1988, Sharpless found that the desired enantioselective reaction can be achieved... 

Cyclohexanone and cyclopentanone monooxygenases have been used in the microbial BV oxidation of prochiral bicycloketones. A significant difference in behaviour of [3.3.0] and [4.3.0] substrates has been analysed by high-level DFT calculations.345 Al-BINOL complexes catalyse the enantioselective BV oxidation of cyclobutanones to give the corresponding y-butyrolactones in up to 84% ee.346 Advances in the enantioselective metal-catalysed reaction have been reviewed, especially for lactone preparation.347... 

A simplified catalytic cycle shows the formation of an Mn(V)-oxo complex. L could be a counterion or an amine JV-oxide ligand, the addition of which has a slight beneficial effect on enantioselectivity, reaction rate and product yield ... 

The TB ( + )-l adduct of methyltrioxorhenium [(+ )-Re03CH3], characterized by its crystal structural and spectroscopic data, was reported by Herrmann et al. The catalytic properties of this complex were tested in the epoxidation of olefins and the oxidation of sulfides. However, no enantioselective reactions of the pro-chiral olefins and sulfides were observed (97JOM(538)203). 

Ketones can be converted to dioxiranes by Oxone (2KHSO5 KHSO4 K2SO4) under shghtly alkaline conditions (pH 7-8) (400). The dioxirane of 1,1,1-trifluoroacetone is a powerful yet selective oxidant under mild conditions, typically at temperatures below 313 K (10). Exemplary reactions are stereospecific olefin epoxidation and hydroxylation of tertiary C-H groups, or ketonization of CH2 groups. With chiral ketones, even enantioselective reactions are possible (401). Although the reactions are often performed in excess ketone, it is actually possible to use the ketone in a catalytic fashion, for example, for 1,1,1-trifluoroacetone (Scheme 5). 

The most intriguing work in the field of asymmetric oxidative aryl coupling has been directed towards finding catalytic enantioselective reactions. The main goal in these studies has been the synthesis of chiral binaphthyl units as an improvement over stoichiometric chiral reagent enantioselective syntheses. 

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