Prochiral alkenes, epoxidation

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

The enantioselective epoxidation of prochiral alkenes with an aldehyde dioxirane was achieved by Bez and Zhao . ... 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

Asymmetric epoxidation of a prochiral alkene is an appealing process because two stereogenic centers are established in the course of the reaction. Often, the starting alkene is inexpensive. There have been several interesting recent advances in the asymmetric nucleophilic epoxidation. 

The rate constants for oxidation of a series of cycloalkenes with ozone have been determined using a relative rate method. The effect of methyl substitution on the oxidation of cycloalkenes and formation of secondary organic aerosols has been analysed.155 Butadiene, styrene, cyclohexene, allyl acetate, methyl methacrylate, and allyl alcohol were epoxidized in a gas-phase reaction with ozone in the absence of a catalyst. With the exception of allyl alcohol, the yield of the corresponding epoxide ranged from 88 to 97%.156 Kinetic control of distereoselection in ozonolytic lactonization has been (g) reported in the reaction of prochiral alkenes.157... 

In epoxidation reactions allyl alcohol can act as a prochiral alkene. Enantio-merically pure glycidol isomers (see Table 1.1) may be used to make S-propanolol 9.61, a drug for heart disease and hypertension. The mechanistic details of the epoxidation reaction with V5+ and Mo6+ complexes as catalysts were discussed in Section 8.6. The basic mechanism of epoxidation reaction, the transfer of an oxygen atom from f-butyl hydroperoxide to the alkene functionality, remains the same. 

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. 

Catalytic oxidahon reachons were among the earliest explored applicahons of the FBS concept because of the chemical and thermal stabihty of perfluorocarbons, the convenient partihon of the final polar products into the organic phase, and the possible increased lifetime of the catalysts confined in the fluorous phase [4—6]. The first example of enantioselechve catalysis under FBS condihons, reported in 1998, also dealt with an oxidation process, namely the epoxidahon of prochiral alkenes [26]. Mn(III)-complexes of salen hgands 2 and 3 were found to catalyze the asymmetric epoxidation of indene in a two-phase system CH2Cl2/perfluoroc-tane at 20 °C under an atmospheric pressure of oxygen in the presence of pivalal-dehyde (Scheme 5.1). 

Three different chiral biphenyl iminium salts have been prepared and tested as asymmetric catalysts for epoxidation of prochiral alkenes with oxone in MeCN-H20 in the presence of a base. The complexes (74) and (75) have electron-withdrawing 3,3 -substitutents on the terminal phenyl units but salt (75) lacks the t-butyl and methoxy groups at the central biphenyl unit. The salt (76) bears no t-butyl or methoxy groups or electron-withdrawing substitutents at a biphenyl unit. The catalytic reactivity of these complexes in terms of the yield and ee of the epoxidized product is in the following order (76) > (75) > (74). This suggests that substitution on the biphenyl unit introduces steric bulk which is damaging for catalytic activity and enantioselectivity. ... 

Chiral epoxides can be prepared (a) by a stereoselective oxidation of prochiral alkenes (e.g. by Sharpless and Jacobsen epoxidation), or (b) by an enantioselective aUcylidenation of prochiral oxo componnds with ylides, carbenes, or through the Darzens reaction. 

Epoxides are interesting starting materials for further derivatisation. In most instances the reaction will lead to the formation of mixtures of enantiomers (that is when the alkenes are prochiral, or when the faces are enantiotopic). Four important reactions should be mentioned in this context ... 

The haem peroxidases are a superfamily of enzymes which oxidise a broad range of structurally diverse substrates by using hydroperoxides as oxidants. For example, chloroperoxidase catalyses the regioselective and stereoselective haloge-nation of glycals, the enantioselective epoxidation of distributed alkenes and the stereoselective sulfoxidation of prochiral thioethers by racemic arylethyl hydroperoxides [62]. The latter reaction ends in (i )-sulfoxides, (S)-hydroperoxides and the corresponding (R)-alcohol, all In optically active forms. 

Wistuba, D., Nowotny, H.P., Trager, O. Schurig, V. (1989) Cytochrome P-450 catalyzed asymmetric epoxidation of simple prochiral and chiral aliphatic alkenes. Species dependence and effect of enzyme induction on enantioselective oxirane formation. Chirality, 1, 127-136... 

Asymmetric epoxidation The catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades. The non-racemic epoxides are prepared either by enantioselective oxidation of a prochiral carbon-carbon double bond or by enantioselective alkylidenation of a prochiral C=0 bond (e.g. via a ylide, carbene or the Darzen reaction). The Sharpless asymmetric epoxidation (SAE) requires allylic alcohols. The Jacobsen epoxidation (using manganese-salen complex and NaOCl) works well with ds-alkenes and dioxirane method is good for some trans-alkenes (see Chapter 1, section 1.5.3). 

Alcohols can be obtained from many other classes of compounds such as alkyl halides, amines, al-kenes, epoxides and carbonyl compounds. The addition of nucleophiles to carbonyl compounds is a versatile and convenient methc for the the preparation of alcohols. Regioselective oxirane ring opening of epoxides by nucleophiles is another important route for the synthesis of alcohols. However, stereospe-cific oxirane ring formation is prerequisite to the use of epoxides in organic synthesis. The chemistry of epoxides has been extensively studied in this decade and the development of the diastereoselective oxidations of alkenic alcohols makes epoxy alcohols with definite configurations readily available. Recently developed asymmetric epoxidation of prochiral allylic alcohols allows the enantioselective synthesis of 2,3-epoxy alcohols. 

In addition to the fact that the reagent s ingredients are commercially available, the reaction is promiscuous and proceeds in good chemical yield with excellent enantiomeric excesses. The reaction, however, does suffer when bulky substituents are cis to the hydroxymethyl functionality (R in Figure 1). For prochiral alcohols, the absolute stereochemistry of the transformation is predictable, whereas for a chiral alcohol, the diastereofacial selectivity of the reagent is often sufficient to override those preferences inherent in the substrate. When the chiral atom is in the -p-position of the allyl alcohol (R ), then the epoxidation can be controlled to access either diastereoface of the alkene. In contrast, when the chirality is at either the a- or Z-P-positions (R or R ), the process is likely to give selective access of the reagent from only one of the two diastereotopic faces [6,12]. Many examples of substrates for the epoxidation protocol are known [1,13,14]. 

---