Jacobsen-Katsuki catalysts

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. 

Fig. 13 Jacobsen-Katsuki-catalyst with a cyclohexane backbone.

Scheme 9 Proposed pathways for the epoxidation by Jacobsen-Katsuki-catalysts.

The use of fluorous chiral manganese salene (Jacobsen-Katsuki) catalysts (29, 30) [30] in combination with different oxidants enables enantioselective epoxidation of olefins [31] in high yields and with moderate to high enantiomeric excess (Scheme 3.12). 

Scheme 3.12 Enantioselective epoxidation of olefins /ith fluorous Jacobsen-Katsuki catalysts 29 and 30 (obove) [31a], and the synthesis of these catalysts (below) (D-100 consists mainly of n-perfluorooctane, b. p. 100°C, and is commercially available from Ausimont).

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). 

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]. 

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. 

There are several remarkable features of these immobilized salens, notably the fact that the dendritic branches do not appear to decrease the catalytic activity with respect to the complexes in solution. Moreover, the reactions with dendritic catalysts incorporated in polystyrene gave products of essentially the same enantiopurity as those observed in homogeneous solution, with the dendritically substituted or with the original Jacobsen-Katsuki complexes. Some of the Mn-loaded beads were stored for a year without loss of activity. Especially, the biphenyl- and acetylene-linked salen polymers gave Mn complexes of excellent performance, which after ten catalytic rims showed no loss of enantioselectivity or degree of conversion. 

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). 

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... 

Equation 12.16 is an example of the Sharpless-Katsuki asymmetric epoxi-dation of allylic alcohols, which is catalyzed by a Ti complex bound to a chiral tartrate ligand.38 A Mn-salen39 complex serves as catalyst for asymmetric epoxi-dation (Jacobsen-Katsuki reaction) of a wide variety of unfunctionalized alkenes, shown in equation 12.17.40 0s04 complexed with chiral alkaloids, such as quinine derivatives (equation 12.18), catalyzes asymmetric 1,2-dihydroxylation of alkenes (known as the Sharpless asymmetric dihydroxylation).41 The key step of all these transformations is the transfer of metal-bound oxygen, either as a single atom or as a pair, to one face of the alkene. 

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 alternative approach for the epoxidation of simple olefins has been developed by Pietikainen and co-workers and Katsuki and co-workers by using the Jacobsen-type catalysts (Fig. 23) and in situ addition of imidazole or N-methylimidazole (122,129). The highest cc-values obtained were 60 % for... 

The rate of Jacobsen-Katsuki epoxidation can be enhanced in the presence of additives such as pyridine A-oxide or related aromatic A-oxides. For example, in a synthesis of the potassium channel activator BRL-55834, only 0.1 mol% of the (5,5)-(salen)Mn(III)Cl catalyst 58 was required for efficient epoxidation of the chromene 62 in the presence of 0.1 mol% isoquinoline A-oxide (5.68). In the... 

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. 

Many interesting reports on the epoxidation of alkcnes have appeared in the literature, particularly involving asymmetric methods. In this regard, the chiral salen catalysts (1 and 2) developed by Jacobsen and Katsuki <01C()C663> find frequent use, and convenient methods for their industrial preparation continue to be reported. For example, Jacobsen s catalyst (1, Rl = R2 = <-Bu X = Q) is now available in 75% overall yield from commercially available starting materials <01SC2913>. 

Metal complexes of enantiomericaUy pure N,N -ethylenebis(salicylideneaminato) (salen) complexes in combination with stoichiometric oxidants currently provide the most selective method for the catalytic asymmetric epoxidation of unfunctionalised alkenes. The use of C2-symmetric salen complexes of manganese(lll) were reported independently in 1990 by Jacobsen and coworkers and Katsuki and coworkers. The first generation catalysts are represented by the general structure (4.33). The complex with R = Bu is known as Jacobsen s catalyst. All of the first generation catalysts are composed of a enantiopure diamine core and possess large substituents at the 3/3 and 5/5 positions. Subsequently Katsuki and coworkers developed second generation catalysts such as (4.34) with axially chiral groups at the 3/3 positions. 

Whilst the Sharpless epoxidation with titanium catalysts and the Jacobsen-Katsuki epoxidation with manganese(salen) complexes are at the forefront of enantioselec-tive epoxidation with metal catalysts, there are alternative systems available. Ruthenium pyridinebisoxazoline (PYBOX) complexes have been independently reported, using either phenyliodinium diacetate or sodium periodate as... 

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