Alkenes Jacobsen-Katsuki epoxidation

Non-functionalized alkenes 6, with an isolated carbon-carbon double bond lacking an additional coordination site, can be epoxidized with high enantiomeric excess by applying the Jacobsen-Katsuki epoxidation procedure using optically active manganese(iii) complexes ... 

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. 

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... 

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... 

Chiral Mn salen complexes have been prepared by replacing ethylenediatnine with a chiral diamine such as 1,2-cyclohexanediamine, and these complexes show very high enantioselectivity in the epoxidation of alkenes, especially cyclic ones. The Mn-catalyzed asymmetric epoxidation of alkenes is known as the Jacobsen or Jacobsen-Katsuki epoxidation. 

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... 

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). 

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. 

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. 

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. 

For ffie past several decades, several chemocatalysts and biocatalysts have been used for ffie epoxidation of nonfunctionalized aliphatic alkenes. The Katsuki-Jacobsen epoxidation, which is catalyzed by chiral Mn(III)-salen with NaOCl/PhIO as an oxidant, achieves good yields and high stereoselectivities (84-94%ee) for ffie epoxidation of ds-alkenes [21]. The Shi epoxidation, which is catalyzed by ffie fructose-derived ketone and oxone, has been successfully used in ffie epoxidation of frans-alkenes, yielding ffie corresponding oxides with 93-98% ee [74]. However, for nonfunctionalized terminal aliphatic alkenes, chemocatalysts typically display low stereoselectivity [7]. 

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. 

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. 

Conjugated dienes can be epoxidized to provide vinylepoxides. Cyclic substrates react with Katsuki s catalyst to give vinylepoxides with high ees and moderate yields [17], whereas Jacobsen s catalyst gives good yields but moderate enantiose-lectivities [18]. Acyclic substrates were found to isomerize upon epoxidation (Z, )-conjugated dienes reacted selectively at the (Z)-alkene to give trans-vinylepoxides (Scheme 9.4a) [19]. This feature was utilized in the formal synthesis of leuko-triene A4 methyl ester (Scheme 9.4b) [19]. 

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>. 

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. 

Although the Sharpless catalyst was extremely useful and efficient for allylic alcohols, the results with ordinary alkenes were very poor. Therefore the search for catalysts that would be enantioselective for non-alcoholic substrates continued. In 1990, the groups of Jacobsen and Katsuki reported on the enantioselective epoxidation of simple alkenes both using catalysts based on chiral manganese salen complexes [8,9], Since then the use of chiral salen complexes has been explored in a large number of reactions, which all utilise the Lewis acid character or the capacity of oxene, nitrene, or carbene transfer of the salen complexes (for a review see [10]). 

In the same year (1990) that Jacobsen reported his asymmetric epoxidation, a group led by Tsutomu Katsuki at the University of Kyushu in Japan reported a closely related asymmetric epoxidation. The chiral catalyst is also a salen and the metal manganese. The oxidant is iodosobenzene (Phl=0) but this method works best for E-alkenes. It is no coincidence that Katsuki and Jacobsen both worked for Sharpless. It is not unusual for similar discoveries to be made independently in different parts of the world, the Katsuki manganese salen complex... 

Both chemical and enzymatic synthetic methods for the asymmetric oxidation of the carbon-carbon double bond have been developed [46], but the area of carbon-carbon double bond oxidations has been shaped by the breakthrough discovery of asymmetric epoxidation of allylic alcohols with the Katsuki-Sharpless method [47]. Catalytic asymmetric synthesis of epoxides from alkenes by Jacobsen... 

From the work of Jacobsen and Katsuki, it is known that chiral manganese salen complexes are excellent catalysts for the asymmetric epoxidation of alkenes... 

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