Epoxidation, stereochemistry

J. W. Keller, C. Heidelberger, F. A. Beland, R. G. Harvey, Hydrolysis of syn- and anti-Benzo[a]pyrene Diol Epoxides Stereochemistry, Kinetics, and the Effect of an Intramolecular Hydrogen Bond on the Rate of. vyn-Diol Epoxide Solvolysis ,./. Am. Chem. Soc. 1976, 98, 8276 - 8277. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in trans-epoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)g.65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

The pinacolic rearrangement of acyclic a-silyloxy epoxides presents an attractive procedure for the stereocontrolled preparation of aldol-type products under extremely mild conditions33 35. Treatment of epoxides with an appropriate Lewis acid catalyst results in a [1,2] shift with net inversion of epoxide stereochemistry to afford highly functionalized /J-hydroxy ketones. 

Epoxide stereochemistry and helicity around the 3,4 bond. Conformation of the substrate in the transition state. 

Jhh and " Jhh couplings have been measured by Katrizky et al for re-gioisomeric 3-[2- or 5-anilino-2-(alkylamino)phenyl]propanoic acids, 2H-1,4-benzothioazin-3(4/f)-ones and 2,3-dihydro-l,5-benzothiazepin-4(5if)-ones, by Suri et for a series of pyrido[l,2-a]pyrimidine derivatives, and by Laatsch and co-workers for helquinoline, a new tetrahydroquinoline antibiotic isolated from Janibacter limosus. The configuration around the double bonds and the epoxide stereochemistry of oximidine III, a new antitumor antibiotic against transformed cells from Pseudomonas sp., has been established on the basis of Vhh by Hayakawa et... 

In contrast to the previous methods involving reductive coupling of two 71-components, a method involving participation of the sigma bond of an epoxide has been demonstrated. Treatment of a monosubstituted epoxide and alkyne with EtaB in the presence of a nickel catalyst generated from Ni(cod)2 and PBus affords homoallylic alcohols from reductive coupling (Scheme 3-67). The process proceeds with retention of epoxide stereochemistry, and intramolecular versions are endoselective. These aspects can be explained by initial oxidative addition of Ni(0) to... 

Aromatic amines are converted into carbamate esters on treatment with an alcohol and CO (1 atm) in the presence of 0 , CuClo, and catalytic amounts of PdCl2 (Scheme 64). Vinyl epoxides react with CO2 in the presence of a palladium(O) catalyst, generated in situ from Pd(0H. )., P(0Pr )T, and BuLi, to give the corres-ponding vinyl carbamates (Scheme 65). The epoxide stereochemistry is retained and this methodology corresponds overall to a cis-dihydroxylatlon process. 

A hindered Hthium amide such as lithium 2,2,6,6-tetramethylpiperidide (LTMP) has proved to be effective in triggering a direct intramolecular cyclopropanation of the unsaturated terminal epoxide 31 to the tricycHc alcohol 32 (2010JOC2157). This strategy has been used successfully in a concise synthesis of (—)-cubelol (33) from (—)-menthone. Similarly, the naturally occurring (—)-10-epicubelol (34) can be prepared from (+)-menthone. Interestingly, whatever is the stereochemistry of the tethered alkene, the facial selectivity of cyclopropanation is controlled solely by the epoxide stereochemistry (Scheme 8). 

It is relatively straightforward to predict the stereochemistry and rates of these reactions. The more electron rich the double bond, the faster it will react with the peracid. Also, sterics are the primary factor directing the epoxidation stereochemistry. The least hindered face of a double bond is predominately epoxidized. The reaction is typically 100% stereospecific, with trans-olefins giving trans-epoxides and cis-olefins giving cis-epoxides. 

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. 

Studies were conducted examining the influence of the epoxide stereochemistry on the asymmetric induction of the reaction. Investigating the stereochemical outcome of the reaction with monosubstituted matched and mismatched epoxides, Myers et al. concluded that the facial selectivity... 

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