Epoxidation chiral alkenes, stereoselectivity

These reagents may be considered to be one of the elusive aza-analogues of peroxyacids, and there are significant mechanistic similarities between the Rees-Atkinson reaction and the Bartlett epoxidation. Chiral Q-reagents have been used to effect highly stereoselective aziridination of alkenes (Scheme 4.13) [1],... 

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 . ... 

Many oxo-metal complexes efficiently epoxidize alkenes. Stereoselectivity in these epoxidations is most often achieved by precoordination of functional groups in the substrates. If the metallic centers are embedded in a chiral environment that allows stereoselectivity to rely solely on nonbonded interactions, enantioselective epoxidation may be extended to nonfunctionalized alkenes16. 

In addition to the 1,3-ally lie strain concept, Houk has employed a model for 7t-facial stereoselection of electrophilic additions to chiral alkenes, such as hydroboration, epoxidation, and dihydroxylation, with similar predictive success. ... 

Stereoselective epoxidation of alkenes, desymmetrization of maso-TV-sulfonylaziri-dines, Baeyer-Villiger oxidation of cyclobutanones, Diels-Alder reactions of 1,2-dihydropyridines, and polymerization of lactides using metal complexes of chiral binaphthyl Schiff-base ligands 03CCR(242)97. 

The development of solid-supported chiral oxidants is a challenging area that has yielded interesting results in the development of a chiral supported dioxiran precursor. The preparation of non-racemic epoxides has been extensively studied in recent years since they are important building blocks in stereoselective synthesis. A supported dioxirane precursor based on a-fluorotropinones was shown to promote the epoxidation of alkenes [28, 29]. The reactant was anchored on meso-porous MCM-41 and amorphous silicas. It has shown comparable activity to its homogenous counterpart and good stability on recycling. The enantiomerically enriched version efficiently promotes the enanhoselective epoxidation of alkenes, with ee values up to 80% (Scheme 4.4). 

The first example of the immobilization of a chiral ketone to promote the enan-tioselective epoxidation of alkenes with Oxone has been reported by Sartori and coworkers [322]. They anchored a-fhiorotropinone on KG-60 silica, MCM-41 and a Merrifield resin. The catalysts were tested for the epoxidation of 1-phenylcyclo-hexene but the polymer-supported fhiorotropinone 121 showed a low activity and selectivity. The catalyst immobilized on inorganic supports promoted the stereoselective epoxidation of alkenes with ee values up to 80% and could be reused with the same performance for three runs. 

For the enantioselective preparations of chiral synthons, the most interesting oxidations are the hydroxylations of unactivated saturated carbons or carbon-carbon double bonds in alkene and arene systems, together with the oxidative transformations of various chemical functions. Of special interest is the enzymatic generation of enantiopure epoxides. This can be achieved by epoxidation of double bonds with cytochrome P450 mono-oxygenases, w-hydroxylases, or biotransformation with whole micro-organisms. Alternative approaches include the microbial reduction of a-haloketones, or the use of haloperoxi-dases and halohydrine epoxidases [128]. The enantioselective hydrolysis of several types of epoxides can be achieved with epoxide hydrolases (a relatively new class of enzymes). These enzymes give access to enantiopure epoxides and chiral diols by enantioselective hydrolysis of racemic epoxides or by stereoselective hydrolysis of meso-epoxides [128,129]. 

A new stereoselective epoxidation catalyst based on a novel chiral sulfonato-salen manganese(III) complex intercalated in Zn/Al LDH was used successfully by Bhattacharjee et al. [125]. The catalyst gave high conversion, selectivity, and enantiomeric excess in the oxidation of (i )-limonene using elevated pressures of molecular oxygen. Details of the catalytic activities with other alkenes using both molecular oxygen and other oxidants have also been reported [126]. 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

The Jacobsen-Katsuki-catalysts (Fig. 13) have recently received much attention as the most widely used alkene epoxidation catalysts. An example of Jacobsen s manganese-salen catalyst is shown in Fig. 13. They promote the stereoselective conversion of prochiral olefins to chiral epoxides with enantiomeric excesses regularly better than 90% and sometimes exceeding 98%.82,89,92,93,128 The oxidation state of the metal changes during the catalytic cycle as shown in Scheme 8. 

The confomiational preferences and stereoselective reactions of a number of macrocyclic systems have been studied. The stereochemical results have been explained on the basis of the model of local conformer control. The epoxidation of a macrocyclic alkene containing the substitution pattern (21) provides a single epoxide having the stereochemistry (22). A macrocycle containing a l,S-diene system adepts the local confoimation (23) that is iree of torsional strain epoxidation of (23) from the less hindered side fiimishes the syn-diepoxide (24). The MCPBA epoxidations of the unsaturated macrocyclic lactones (25) and (2Q are stereoselective (equations 9 and 10). In the epoxidation of (26) six new chiral centres are introduced the reaction product is a 20 1 1 mixture of triepoxides. The tiiepoxide (27) is closely related to the C(9)-C(23) segment of monensin B. 

Earlier in the chapter we discussed how to make single diastereoisomers by stereospecific additions to double bonds of fixed geometry. But if the alkene also contains a chiral centre there will be a stereoselective aspect to its reactions too its faces will be diastereotopic, and there will be two possible outcomes even if the reaction is fully stereospecific. Here is an example where the reaction is an epoxidation. 

Diaminocyclohexane [(R,R)- and ( S, S)-enantiomer] forms an imine (SCHIFF base) with 2,5-di-/ rr-butylsalicylaldehyde, which gives a chiral Mn(III) (salen) complex with Mn(II)acetate and oxygen. In contrast to the Sharpless-Katsuki protocol (p 20), this complex effects the stereoselective oxygen transfer (from oxidants, e.g. monopersulfate or NMO) to unfunctionalized alkenes (Jacobsen epoxidation [1], extended by Katsuki [2]) giving rise to enantiomeric oxiranes with 90-98% ee. 

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