Diastereoselectivity dioxirane epoxidation

Highly diastereoselective dioxirane epoxidations have been widely employed in organic synthesis. For example, in the total synthesis of epothilone B, an important antitumor agent , the required epoxide was obtained in good yield and diastereoselectivity by DMD oxidation (equation 7) . ... 

As already mentioned, the dioxirane epoxidation of an alkene is a stereoselective process, which proceeds with complete retention of the original substrate configuration. The dioxirane epoxidation of chiral alkenes leads to diastereomeric epoxides, for which the diastereoselectivity depends on the alkene and on the dioxirane structure. A comparative study on the diastereoselectivity for the electrophihc epoxidants DMD versus mCPBA has revealed that DMD exhibits consistently a higher diastereoselectivity than mCPBA however, the difference is usually small. An exception is 3-hydroxycyclohexene, which displays a high cis selectivity for mCPBA, but is unselective for DMD . ... 

The results of the dioxirane epoxidation of some 3-alkyl-substituted cyclohexenes and of 2-menthene indicate that the diastereoselectivity control is subject to the steric interactions of the dioxirane with the substituents of the substrate, while the size of the dioxirane substituents has only a minimal effect . In the favored transition structure, the alkyl groups of the dioxirane cannot interact effectively with the substituents at the stereogenic center of the chiral alkene . ... 

Adam, W., Mitchell, C. M., Saha-Moeller, C. R. Regio- and Diastereoselective Catalytic Epoxidation of Acyclic Ailylic Alcohols with Methyltrioxorhenium A Mechanistic Comparison with Metal (Peroxy and Peroxo Complexes) and Nonmetal (Peracids and Dioxirane) Oxidants. J. Org. Chem. 1999, 64, 3699-3707. 

This synthesis is shown in Scheme 13.59. Two enantiomerically pure starting materials were brought together by a Wittig reaction in Step C. The aldol addition in Step D was diastereoselective for the anti configuration, but gave a 1 1 mixture with the 6S, 1R-diastereomer. The stereoisomers were separated after Step E-2. The macrolactonization (Step E-4) was accomplished by a mixed anhydride (see Section 3.4.1). The final epoxidation was done using 3-methyl-3-trifluoromethyl dioxirane. 

In the epoxidation of acyclic allylic alcohols (Scheme 6), the diastereoselectivity depends significantly on the substitution pattern of the substrate. The control of the threo selectivity is subject to the hydroxyl-group directivity, in which conformational preference on account of the steric interactions and the hydrogen bonding between the dioxirane oxygen atoms and the hydroxy functionality of the allylic substrate steer the favored 7r-facial... 

The chemoselectivity, regioselectivity, diastereoselectivity, and enantioselectivity of heteroatom oxidations, epoxidations and CH insertions by dioxiranes have been reviewed.26 The selective ring-opening reactions of epoxides at high pressures have been reviewed (in Japanese).27... 

Cyclodextrins have been covalently modified for catalytic oxidation, such as compounds 57, 62-65 (Schemes 3.14 to 3.16) [44, 45]. Enantioselective epoxidation of styrene derivatives, and carene using 20-100 mol% of the CD-ketoester 57 has been achieved. The inclusion-complex formation was confirmed by aH NMR titration experiments, confirming the 1 1 substrate catalyst stoichiometry under the reaction conditions. In the oxidation of carene, NOE and ROESY experiments showed different behavior according to the size of the R group (Scheme 13.14). Evidence was found for the formation of inclusion complexes with compounds 58 and 59. On the other hand, compounds 60 and 61 proved to interact with the catalyst via a tail inclusion vide infra). The increased diastereoselectivity observed with compounds 58 and 59 might be explained by a closer proximity to the covalently linked dioxirane. 

The epoxidation reactions of a series of m-3,4-disubstituted-(CH2X)-cyclobutenes 6-11 with DMDO and MCPBA have been investigated by Freccero et a/. <1999X11309>. A remarkable ry -diastereoselectivity in the formation of the epoxide has been observed for substrates bearing electron-withdrawing substituents. Transition structures for epoxidations of 3,4-dimethylcyclobutene 6 and 3,4-bis(mesyloxymethyl)-l-cyclobutene 11 with dioxirane and peroxy-formic acid have been located with the B3LYP/6-31G method (Table 1). 

Denmark et al. reported a general protocol for the catalytic epoxidation of alkenes by in r// -generated reactive dioxiranes capable of epoxidizing a variety of alkenes under biphasic conditions <1995JOC1391>. The epoxide diastereoselectivity (Scheme 4) showed pronounced dependence on the solvent used since the ratio of diastereo-mers, as well as the distribution between epoxide and enone products, is dependent on the solvent <1995TL2437, 1999TL8023>. Selected examples are given in Table 2. 

Steric and field effects in the diastereoselective epoxidation of substituted cyclohexenes by dioxiranes were investigated, revealing that the diastereoselectivity is determined by the steric and field effects of both dioxiranes and olefins <1999JOG1635>. The reaction of 2,7-dimethyloxepin 92 with DMDO lb and TFDO Ic has been reported together with detailed H NMR study of the reaction and the possible evidence of intermediate 2,3-epoxyoxepin 93 <1998STC223>. 

Yang, D. Jiao, G.-S. Yip, Y-C. Wong, M.-K., Diastereoselective Epoxidation of Cyclohexene Derivatives by Dioxiranes Generated in Situ. Importance of Steric and Field Effects. /. Org. Chem. 1999, 64,1635. 

Ketone-catalyzed asymmetric and diastereoselective epoxidation of olefins by use of dioxiranes generated in situ from chiral ketones and oxone (2KFfS05 KH-S04 K2S04) 04ACR497. 

The in situ procedure as proposed by Sonnet et al. (18) is much more attractive for synthetic applications. With the use of only a moderate excess of monopersulfate (C=C KHSO5 = l 2-2.4), they achieved an 80% yield for the epoxidation of oleic acid methyl ester and 81-96% for the epoxidation of various plant oils. It is a twophase reaction with a crown-ether as phase-transfer catalyst yet a considerable amount of inorganic waste (six times the weight of the product) is produced. In a recent work (21), the phase-transfer catalyst was replaced by acetonitrile as a polar solvent. In summary, epoxidation by dioxiranes is a promising new method for oleo-chemistry, especially because it also works in combination with metal catalysts to influence diastereoselectivity (22) an enantioselective epoxidation with sugardioxiranes has also been reported (23). 

Staurosporine 196 has been prepared from 6-0-triisoprylsilyl-L-gIucaI 194 by Danishefsky and co-workers, via the oxazoUdinone epoxide 195. The key epoxide stereochemistry was established by diastereoselective epoxidation using dimethyl-dioxirane (Scheme 38). The enantiomer of staurosporine was also prepared by the same synthetic route but commencing with the D-sugar. These syntheses corrected the prior assignment of absolute configuration of the natural product. 

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