Alkene epoxidation diastereoselectivity

Table 1. Diastereoselectivities of Alkene Epoxidations Used for Parametriza-tion of an MM2 Force Field...

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. 

The stereochemical outcome of Q [WZnM2(ZnW9034)2] [M = Zn(II), Mn(II), Ru(III), Fe(III)]-cafalyzed H2O2 epoxidation of various allylic alcohols with the OH group attached to a chiral center is controlled by allylic strain effects [23,24]. Thus, allylic alcohols with only 1,2-allylic strain were foimd to afford erythro-epoxides with excellent diastereoselectivity (Fig. 16.4, alkene A). In contrast, threo-epoxides predominate strongly in case of 1,3-allylic strain (alkene B). Diastereoselectivity drops to very low values in the absence of allylic strain (alkene C) or when both 1,2- and 1,3-allylic strain are present in the substrate (alkene D). 

As previously noted, optically active trans-epoxides are not easily available through the (salen)Mn-catalyzed epoxidation of rrans-olefins. However, a modification in the conditions for cis-alkene epoxidation can provide access to trans-epoxides [94JA6937]. Addition of an cinchona alkaloid derivative such as 18 promotes a remarkable crossover in diastereoselectivity, such that the trans-epoxide 17 can be prepared in 90% de from cis-B-methylstyrene (16). It is not yet clear whether these chiral quaternary ammonium salts fundamentally change the nature of the manganese-based oxidant, or rather somehow prolong the lifetime of the radical intermediate, allowing rotation before collapse. 

Chiral Auxiliary-hased Epoxidation of Substituted Alkenes. High diastereoselectivities were found for the m-CPBA or dimethyldioxirane epoxidation of chiral oxazolidine-substituted alkenes bearing a strongly basic urea group (eq 29). However, in most cases, the diastereoselectivities were superior with dimethyldioxirane. 

Rh2(OAc)4 catalyses Mukaiyama epoxidation of alkenes in acetone in the presence of 2 and i-PrCHO in good yields. Mono-epoxidation products for neryl and geranyl acetate are obtained in 65% and 74% yield, respectively, on decreasing the amount of aldehyde. Conditions for regioselective epoxidation and mono-epoxidation of terpenes have been established. The epoxidation diastereoselectivity increases with increasing steric bulk around the CHO group of the aldehyde. The oxidation is initiated by the O2 entrapped in Rh(II) complex. " ... 

Epoxidation of conjugated dienes can be regioselective when one double bond is more electron-rich than the other otherwise mixtures of mono- and diepoxides will be obtained. When the alkene contains an adjacent stereocenter, the epoxidation can be diastereoselective [2]. Hydroxy groups can function as directing groups, causing the epoxidation to take place syn to the alcohol [2, 3]. 

Unlike the catalytic epoxidation or aziridination reactions of simple alkenes, where enantiocontrol is the only stereochemical differentiation, synthetically effective intermolecular cyclopropanation requires both diastereocontrol and enantiocontrol. High diastereoselectivity for the trans-isomer can be achieved with the use of bulky diazoacetates such as BDA" 187 or DCM97 188. 

However, styrene and cyclohexene gave complex product mixtures, and 1-octene did not react under the same reaction conditions. Thus, the activity of this catalyst is intrinsically low. Jacobs and co-workers [159,160] applied Veturello s catalyst [PO WCKOj ]3- (tethered on a commercial nitrate-form resin with alkylammonium cations) to the epoxidation of allylic alcohols and terpenes. The regio- and diastereoselectivity of the parent homogeneous catalysts were preserved in the supported catalyst. For bulky alkenes, the reactivity of the POM catalyst was superior to that of Ti-based catalysts with large pore sizes such as Ti-p and Ti-MCM-48. The catalytic activity of the recycled catalyst was completely maintained after several cycles and the filtrate was catalytically inactive, indicating that the observed catalysis is truly heterogeneous in nature. 

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 . ... 

Silylation followed by selenium dioxide oxidation converted 13 into 14. Epoxidation of the derived TES ether proceeded by addition of oxygen to the more open face of the alkene, leading to 15. Ozonolysis followed by diastereoselective one-carbon homologation provided 17. This set the stage for intramolecular epoxide opening by the carboxylate, to give 2, in which all of the stereogenic centers of tetrodotoxin have been established. 

Jacobsen and co-workers have found that catalytic amounts of chiral quaternary ammonium salts, such as 6i, promote a dramatic reversal in the diastereoselectivity of (salen)Mn-catalyzed epoxidation of cis-alkenes, resulting in a highly enantioselective catalytic route to trans-epoxides (Scheme 10.14) [72]. 

A similar cyclisation of an alkene derived from geranyl acetate 24 by dihydroxylation and formation of the epoxide 26 leads to a substituted cyclohexane 28. The Lewis acid ZrCU is used to open the epoxide and the alkene attacks intramolecularly 27 to give eventually the ryn-compound 28 with both substituents equatorial. The alignment of the alkene and the epoxide in a chair conformation 27a is responsible for the diastereoselectivity Note the regioselectivity the less substituted end of the alkene attacks the more substituted end of the epoxide 27. These are just two examples of the very many ordinary ionic reactions that can be used to make six-membered rings. 

The conversion of an alkene to a halohydrin can also be considered as an epoxidation because this can be achieved by a simple ring closure.184 Although no reagent is yet available to perform an asymmetric conversion of an isolated alkene to a halohydrin, the reaction can be controlled through diastereoselection. One such case is the halolactonization of y,8-unsaturated carboxylic acids, N,N-dialkylamides.185189... 

To explain the observed selectivities, a similar model was proposed as for the epoxidation reactions (see Section 10.2.1.10) [96]. In this model, the ylide conformation is controlled as before, and the alkene selectively attacks one face in an analogous manner to the aldehyde in the epoxidation reactions. It was noted that in this case betaine formation was non-reversible so the diastereoselectivity is controlled by non-bonding interactions during the betaine-formation step [79]. 

We started this section with a diastereoselective epoxidation of an alkene. The alkene was this one, and it has a substituent cis to the stereo genic centre. We can therefore expect it to have one important conformation, with H eclipsing the double bond. When a reagent—m-CPBA here—attacks this conformation, it will approach the less hindered face, and the outcome is shown. 

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