In the Jacobsen-Katsuki

One of the most significant developmental advances in the Jacobsen-Katsuki epoxidation reaction was the discovery that certain additives can have a profound and often beneficial effect on the reaction. Katsuki first discovered that iV-oxides were particularly beneficial additives. Since then it has become clear that the addition of iV-oxides such as 4-phenylpyridine-iV-oxide (4-PPNO) often increases catalyst turnovers, improves enantioselectivity, diastereoselectivity, and epoxides yields. Other additives that have been found to be especially beneficial under certain conditions are imidazole and cinchona alkaloid derived salts vide infra). 

Cavaiio, L., Jacobsen, H. Radicai intermediates in the Jacobsen-Katsuki epoxidation. Angew. Chem., Int. Ed. Engl. 2000, 39, 589-592. 

FIGURE 1.28 Likely mechanism of the isomerization in the Jacobsen-Katsuki epoxidation of c/s-stilbene. 

Effect of Spin Changes on the Disastereoselectivity in Mn(salen)-Catalyzed Epoxidation." /. Am. Chem. Soc., 121,5083 (1999). Cavallo, L., and Jacobsen, H. "Radical Intermediates in the Jacobsen-Katsuki Epoxidation." Angem Chem. Int. Ed. Eng., 39,589 (2000). 

The Jacobsen-Katsuki epoxidation reaction is an efficient and highly selective method for the preparation of a wide variety of structurally and electronically diverse chiral epoxides from olefins. The reaction involves the use of a catalytic amount of a chiral Mn(III)salen complex 1 (salen refers to ligands composed of the N,N -ethylenebis(salicylideneaminato) core), a stoichiometric amount of a terminal oxidant, and the substrate olefin 2 in the appropriate solvent (Scheme 1.4.1). The reaction protocol is straightforward and does not require any special handling techniques. 

During the early development of the Jacobsen-Katsuki epoxidation reaetion, it was elear that trans-disubstituted olefins were very poor substrates (slow reaetion rates, low enantioseleetivity) eompared to cis-disubstituted olefins. The side-on approaeh model originally proposed by Groves for porphyrin epoxidation systems was used to rationalize the differenees observed in the epoxidation of the cis and trans-disubstituted elasses (Seheme 1.4.7). ... 

The Jacobsen-Katsuki epoxidation reaction has found wide synthetic utility in both academia and industrial settings. As described previously, the majority of olefin classes, when conjugated, undergo Mn(salen)-catalyzed epoxidation in good enantioselectivity. In this section, more specific synthetic utilities are presented. 

The first application of the Jacobsen-Katsuki epoxidation reaction to kinetic resolution of prochiral olefins was nicely displayed in the total synthesis of (+)-teretifolione B by Jacobsen in 1995. 

The Best results are obtained with cA-alkenes however, the epoxidation of tri-and tetra-substituted double bonds is also possible. Because of its versatility, the Jacobsen-Katsuki epoxidation is an important method in asymmetric synthesis. 

Ordinary alkenes (without an allylic OH group) have been enantioselectively epoxidized with sodium hypochlorite (commercial bleach) and an optically active manganese-complex catalyst. Variations of this oxidation use a manganese-salen complex with various oxidizing agents, in what is called the Jacobsen-Katsuki... 

Jonsson, S., Odille Fabrice, G.J., Norrby, P.-O. and Warnmark, K. (2006) Modulation of the reactivity, stability and substrate- and enantioselectivity of an epoxidation catalyst by noncovalent dynamic attachment of a receptor functionality - aspects on the mechanism of the Jacobsen-Katsuki epoxidation applied to a supramolecular system. Org. Biomol. Chem., 4, 1927-1948 Jonsson, S., Odille Fabrice, G.J., Norrby, P.-O. and Warnmark, K. (2005) A dynamic supramolecular system exhibiting substrate selectivity in the catalytic epoxidation of olefins. Chem. Commun., 549-551. 

The Jacobsen-Katsuki Schiff base Mn complexes (6a and 6b) are the most advanced catalysts for enantioselective epoxidation of double bonds. With the typical reactants, cis disubstituted and trisubstituted aromatic olefins, ee values up to 98% are achieved, even if the total number of turnovers is quite limited. In Jacobsen s complex 6a, particularly the bulky /-butyl substituents at positions 3 and 5 of the aromatic ring are crucial in directing the reactant and obtaining high ee values (86). 

High-valent oxo-complexes, isolated or in situ-generated, interact most often with electron-rich n -systems 1 or suitable C-H bonds with low bond dissociation energy (BDE) in substrates 3 (Fig. 2). These reactions may occur concerted via transition states 1A or 3A leading to epoxides 2 or alcohols 4. On the other hand, a number of epoxidation reactions, such as the Jacobsen-Katsuki epoxidation, is known to proceed by a stepwise pathway via transition state IB to radical intermediate 1C [39]. Similarly, hydrocarbon oxidation to 4 can proceed by a hydrogen abstraction/S ... 

In practice in the literature of the past 20 years the important results with ruthenium in epoxidation are those where ruthenium was demonstrated to afford epoxides with molecular oxygen as the terminal oxidant. Some examples are presented (see later). Also ruthenium complexes, because of their rich chemistry, are promising candidates for the asymmetric epoxidation of alkenes. The state of the art in the epoxidation of nonfunctionalized alkenes is namely still governed by the Jacobsen-Katsuki Mn-based system, which requires oxidants such as NaOCl and PhIO [43,44]. Most examples in ruthenium-catalysed asymmetric epoxidation known until now still require the use of expensive oxidants, such as bulky amine oxides (see later). 

Epoxides are a very versatile class of compounds and the interest in catalytic epoxidation reactions is very high.70,71 They are the key raw materials in the syntheses of a wide variety of chemicals. A number of compounds have been shown to be catalytically active, but the regular laboratory reagents for epoxidations are generally methyl trioxorhenium(VII)72-81 and the Jacobsen-Katsuki-catalysts82-94 which can even introduce chirality. They are also theoretically well investigated95-106 and are described below. 

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. 

This past year s literature has shown extraordinary activity in this realm. Perhaps the most firmly entrenched methodology for the preparation of chiral epoxides is the metallosalen mediated epoxidation of unfunctionalized alkenes (the Jacobsen-Katsuki epoxidation), which has been recently reviewed <03SL281 >. It is widely accepted that this reaction proceeds through an 0X0 intermediate, and that the observed enantioselectivities depend upon the electronic stability of this species. For example, Jacobsen found empirically that electron-donating substituents in the 5 and 5 positions of catalyst 1 gave better enantioselectivities <91JA6703>. More recent... 

Kinetic resolution in the catalytic conversion of racemic chloro propanols to optically active epoxides has been achieved by use of a chiral Co(salen) type complex in combination with K2CO3. Although enantioselectivity was modest (< 35 % ee), this first use in asymmetric epoxide formation of the chiral ligand system that was later brought to fame through the Jacobsen-Katsuki asymmetric epoxidation is noteworthy [56,57]. When applied to the prochiral l,3-dichloro-2-propanol, asymmetric induction of up to ca. 60 % ee was achieved (Sch. 8) [58]. 

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... 

An important preparative methodology which has developed rapidly over the last few years is the (salenjMn mediated epoxidation of alkenes (the Jacobsen-Katsuki epoxidation). While the practical utility of this protocol is indisputable, the mechanistic imderpinnings have been the matter of some debate. Adding to this ongoing dialectic is a result from a recently published DFT study, which suggests the salen ligand itself is involved in the transition state of the... 

A similar (salen)manganese(III) catalyst was used by Katsuki for asymmetric sulfide oxidations [35]. Chiral complex 20 bears additional asymmetric carbons in the salicylidene part of the salen. In this system, hydrogen peroxide, which was the preferred oxidant in the Jacobsen procedure, turned out to be inefficient. Instead, iodosylbenzene was chosen, and in the presence of only 1 mol % of catalyst several aryl alkyl sulfides were oxidized in acceptable yields having enantiomeric excesses in the range of 8% to 90%. As in the Jacobsen-KatsuJd-epoxida-tion, the presence of additives such as pyridine N-oxide has a beneficial effect on chemical and optical yields. In addition, such co-ligands suppress the overoxidation of sulfoxides to the corresponding sulfones so that a sulfoxide sulfone ratio of 47 1 can be achieved. Consequentely, as shown for the case of thioanisole. 

J. Am. Chem. Soc. 1996, 118, 35-42 b) The controversy about the mechanism of the Jacobsen-Katsuki epoxidation has recently been highlighted, while this manuscript was in print T. Linker, Angew. Chem. 1997, 109, 2150-2151 Angew. Chem. Int. Ed. Engl. 1997, 36, 2060-2062. 

Asymmetric epoxidation of ds-substituted conjugated alkenes can be achieved efficiently using the Jacobsen-Katsuki conditions (see Section 5.2, Scheme 5.66). For the enantiomer 9, use the (5,5)-(salen)Mn(III)Cl catalyst and NaOCl in CH2CI2 at 4 °C in the presence of an additive such as pyridine A-oxide. 

Other references related to the Jacobsen-Katsuki epoxidation are cited in literature. ... 

Many attempts were undertaken to produce chiral epoxides for chemical syntheses. This can be achieved by the use of chiral catalysts. The first applicable and relatively simple procedure of chemical chiral epoxidations was described by Katsuki and Sharpless [2], later called the Katsuki-Sharpless epoxidation. In this reaction, allyl alcohols are epoxi-dized in the presence of tartrate esters, e.g., (—)-diethyl tartrate. This allows the production of either (/ )- or (S)-epoxides depending on the selection of (R)- or (5)-tartrate ester as chir additive. However, the reaction is limited to ally lie alcohols and is somewhat sensitive to steric hindrances. In the meantime, a number of different catalysts have been developed for the epoxidation of cw-alkenes. The Jacobsen-Katsuki reaction allows the epoxidation of fran5-alkenes and terminal olefins [3]. All of these approaches, however, are limited to the epoxidation of activated double bonds like allylic alcohols or require expensive catalysts, and usually the regiospecificity of these reactions is not sufficient for practical applications. Furthermore, the chiral catalysts, although usually they can be recycled, are often very exj nsive. 

---