Chiral epoxidizing agent preparation

Chiral and achiral Jacobsen s catalysts exhibit similar diatereomeric excesses during the diastereoselective epoxidation of R-(+)-limonene using in situ prepared oxidizing agents. Therefore, the chiral center of the substrate appears to govern the chiral induction. In contrast, the chirality of the Jacobsen s catalyst appears to be responsible for the chiral induction when commercially available oxidants were used. 

Although the chiral ketoiminatomanganese(lll) complexes were reported to catalyze the asymmetric aerobic alkene epoxidations, an aldehyde such as pivalaldehyde is required as a sacrihcial reducing agent. Groves reported that the dioxo(porphyrinato)ruthenium complexes 31, prepared with m-chloroperoxyben-zoic acid, catalyzed the aerobic epoxidation without any reductant. " On the basis of these reports, Che synthesized the optically active D4-porphyrin 35 and applied it to the truly aerobic enantioselective epoxidation of alkenes catalyzed by the chiral frani-dioxo (D4-porphyrinato)ruthenium(Vl) complex. The dioxoruthenium complex catalyzed the enantioselective aerobic epoxidation of alkenes with moderate to good enantiomeric excess without any reductant. In the toluene solvent, the turnovers for the epoxidation of T-(3-methylstyrene reached 20 and the ee of the epoxide was increased to 73% ee. 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

Besides Pseudomonas oleovorans numerous bacteria have been shown to epox-idize alkenes [1167, 1168]. As shown in Scheme 2.155, the optical purity of epoxides depends on the strain used, although the absolute configuration is usually R) [1169]. This concept has been recently applied to the synthesis of chiral alkyl and aryl gycidyl ethers [ 1170,1171], The latter are of interest for the preparation of enantiopure 3-substituted l-alkylamino-2-propanols, which are widely used as p-adrenergic receptor-blocking agents [1172],... 

In addition to the enantioselective synthesis of oxiranes through the use of electrophilic oxidants as described above, there have also been significant advances in the development of nucleophilic oxidation catalysts for the epoxi-dation of electron-deficient substrates. Shibasaki has reported an effective chiral catalyst system readily prepared from equimolar amounts of BINOL (102), Ph3As = 0, and La(Oi-Pr)3 (Scheme 9.12) [101]. Use of 1-5 mol % of the chiral lanthanide catalyst permits the epoxidation of a,/3-unsaturated ketones. The method has also been extended to include a,/funsaturated imi-dazolides as substrates to provide convenient access to chiral carboxylic acids [102]. As an example, asymmetric epoxidation of enone 101 proceeded in excellent selectivity and yield (96% ee, 94%) [103], The resulting epoxide 103 was subsequently converted into (-i-)-decursin (104), a potent cytotoxic agent associated with protein kinase C activation. 

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