Epoxidation unfunctionalized

Binaphthol- and biphenyl-derived ketones (9 and 10) were reported by Song and coworkers in 1997 to epoxidize unfunctionalized alkenes in up to 59% ee (Fig. 3, Table 1, entries 9, 10) [37, 38]. Ketones 9 and 10 were intended to have a rigid conformation and a stereogenic center close to the reacting carbonyl group. The reactivity of ketones 9 and 10 is lower than that of 8, presumably due to the weaker electron-withdrawing ability of the ether compared to the ester. In the same year, Adam and coworkers reported ketones 11 and 12 to be epoxidation catalysts for several trans- and trisubstituted alkenes (Table 1, entries 11,12). Up to 81% ee was obtained for phenylstilbene oxide (Table 1, entry 25) [39]. 

The first reports of a reaction of an amine with an aldehyde by Schiff [584] led to the establishment of a large class of ligands called Schiff bases. Among the most important of the Schiff bases are the tetradentate salen ligands (N,N -bis(salicy-laldehydo)ethylenediamine), which were studied extensively by Kochi and coworkers, who observed their high potential in chemoselective catalytic epoxidation reactions [585]. The best known method to epoxidize unfunctionalized olefins enantioselectively is the Jacobsen-Katsuki epoxidation reported independently by these researchers in 1990 [220,221]. In this method [515,586-589], optically active Mn salen) compounds are used as catalysts, with usually PhlO or NaOCl as the terminal oxygen sources, and with a O=Mn (salen) species as the active [590,591] oxidant [586-594]. Despite the undisputed synthetic value of this method, the mechanism by which the reaction occurs is still the subject of considerable research [514,586,591]. The subject has been covered in a recent extensive review [595], which also discusses the less-studied Cr (salen) complexes, which can display different, and thus useful selectivity [596]. Computational and H NMR studies have related observed epoxide enantioselectivities... 

In 1990, Jacobsen and subsequently Katsuki independently communicated that chiral Mn(III)salen complexes are effective catalysts for the enantioselective epoxidation of unfunctionalized olefins. For the first time, high enantioselectivities were attainable for the epoxidation of unfunctionalized olefins using a readily available and inexpensive chiral catalyst. In addition, the reaction was one of the first transition metal-catalyzed... 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

Ten years after Sharpless s discovery of the asymmetric epoxidation of allylic alcohols, Jacobsen and Katsuki independently reported asymmetric epoxidations of unfunctionalized olefins by use of chiral Mn-salen catalysts such as 9 (Scheme 9.3) [14, 15]. The reaction works best on (Z)-disubstituted alkenes, although several tri-and tetrasubstituted olefins have been successfully epoxidized [16]. The reaction often requires ligand optimization for each substrate for high enantioselectivity to be achieved. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

Metalated epoxides are a special class of a-alkoxy organometallic reagent. Unstabilized oxiranyl anions, however, tend to undergo a-elimination. On the other hand, attempts to metalate simple unfunctionalized epoxides may lead to nucleophilic ring opening. The anion-stabilizing capability of a trimethylsilyl substituent overcomes these problems. Epoxysilanes 22 were... 

Other metals can also be used as a catalytic species. For example, Feringa and coworkers <96TET3521> have reported on the epoxidation of unfunctionalized alkenes using dinuclear nickel(II) catalysts (i.e., 16). These slightly distorted square planar complexes show activity in biphasic systems with either sodium hypochlorite or t-butyl hydroperoxide as a terminal oxidant. No enantioselectivity is observed under these conditions, supporting the idea that radical processes are operative. In the case of hypochlorite, Feringa proposed the intermediacy of hypochlorite radical as the active species, which is generated in a catalytic cycle (Scheme 1). 

Several catalysts that can effect enantioselective epoxidation of unfunctionalized alkenes have been developed, most notably manganese complexes of diimines derived from salicylaldehyde and chiral diamines (salens).62... 

Attempts have been made to exploit the intrinsic C2 symmetry of the phenolate-based dinickel core in enantioselective catalytic reactions. Therefore, enantiomerically pure C2-symmetric ligands such as (736a) and the corresponding dinickel systems (736b) have been prepared ( Equation (27)),1890 and (736b) was tested in the epoxidation of unfunctionalized alkenes with sodium hypochlorite as the oxidant. The catalytic reaction was found to be highly pH dependent with an optimum at a pH of 9. While the complex is catalytically active, significant enantioselectivity was not achieved. 

The insoluble polymer-supported Rh complexes were the first immobilized chiral catalysts.174,175 In most cases, however, the immobilization of chiral complexes caused severe reduction of the catalytic activity. Only a few investigations of possible causes have been made. The pore size of the insoluble support and the solvent may play important roles. Polymer-bound chiral Mn(III)Salen complexes were also used for asymmetric epoxidation of unfunctionalized olefins.176,177... 

The protocol developed by Jacobsen and Katsuki for the salen-Mn catalyzed asymmetric epoxidation of unfunctionalized alkenes continues to dominate the field. The mechanism of the oxygen transfer has not yet been fully elucidated, although recent molecular orbital calculations based on density functional theory suggest a radical intermediate (2), whose stability and lifetime dictate the degree of cis/trans isomerization during the epoxidation <00AG(E)589>. 

More subtle arguments have been invoked to rationalize the dichotomous behavior of so-called second-generation Mn-salen catalysts of type 7 toward unfunctionalized and nucleophilic olefins. For example, higher yields and ee s are obtained with the (i ,S)-complex for the epoxidation of indene (8). However, JV-toluenesulfonyl-l,2,3,4-tetrahydropyridine (10) gave better results using the (R,/ -configuration. An analysis of the transition-state enthalpy and entropy terms indicates that the selectivity in the former reaction is enthalpy driven, while the latter result reflects a combination of enthalpy and entropy factors <00TL7053>. 

Oxazolines can be obtained by the Lewis acid catalyzed epoxide ring opening of glycidic esters or amides (e.g., 118) with acetonitrile . Oxazolidines are available from the palladium-catalyzed cycloaddition of vinyl epoxides with imines <00H885> or the samarium-promoted reaction of ketimines (e.g., 120) with unfunctionalized... 

Following the success with the titanium-mediated asymmetric epoxidation reactions of allylic alcohols, work was intensified to seek a similar general method that does not rely on allylic alcohols for substrate recognition. A particularly interesting challenge was the development of catalysts for enantioselective oxidation of unfunctionalized olefins. These alkenes cannot form conformationally restricted chelate complexes, and consequently the differentiation of the enan-tiotropic sides of the substrate is considerably more difficult. 

TABLE 4-18. Epoxidation of Unfunctionalized Olefins Catalyzed by 119 substrate catalyst iodosylbenzene = 1 0.025 1... 

Many efforts have been made to develop salen catalysts for the epoxidation of unfunctionalized olefins, and such work has been well documented.93 Very recently, Ito and Katsuki94 proposed that the ligand of the oxo salen species is not planar, but folded as shown in Figure 4-7 (R/ / H, R2 = H, L = achiral axial ligand). This folded chiral structure amplifies asymmetric induction by the Mn-salen complex. This transition state proposed by Ito and Katsuki is not compatible with the proposal by Palucki et al.95 that the salen ligands of oxo species are planar. 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

The requirement for the presence of an adjacent alcohol group can be regarded as quite a severe limitation to the substrate range undergoing asymmetric epoxidation using the Katsuki-Sharpless method. To overcome this limitation new chiral metal complexes have been discovered which catalyse the epoxidation of nonfunctionalized alkenes. The work of Katsuki and Jacobsen in this area has been extremely important. Their development of chiral manganese (Ill)-salen complexes for asymmetric epoxidation of unfunctionalized olefins has been reviewed1881. 

Chapters 4-6 present an overview and a comparison between the various existing strategies for asymmetric epoxidation of unfunctionalized alkenes, a, (3-unsaturated ketones and allylic alcohols. 

The deoxygenation of simple unfunctionalized epoxides has already been investigated with titanocene [17-20] and samarium [27] reagents. Usually both metal complexes give mixtures of the isomers with low selectivity. Epoxide 7 investigated here is mechanistically more interesting because the... 

The product of this preparation is the most enantioselective catalyst developed to date for asymmetric epoxidation of a broad range of unfunctionalized olefins.6 The procedure includes a highly efficient resolution of trans-1,2-diaminocyclohexane as well as a convenient analytical method for the determination of its enantiomeric purity. This method is general for the analysis of chiral 1,2-diamines. The Duff formylation described in Step B is a highly effective method for the preparation of 3,5-di-tert-... 

In addition to the unfunctionalized alkene epoxides discussed in the previous subsection, various other types of epoxides exist that are also derived from unconjugated alkenes but that share two additional features, i. e., being characterized by the presence of one or more functional group(s) and having biological significance. Thus, the present subsection examines epoxy alcohols, epoxy fatty acids, allylbenzenes 2, 3 -oxides, as well as alkene oxide metabolites of a few selected drugs. 

Jacobsen EN (1993) Asymmetric catalytic epoxidation of unfunctionalized olefins. In Ojimal (ed) Catalytic asymmetric synthesis. VCH, Weinheim,p 159... 

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