Katsuki-Jacobsen epoxidation

Katsuki, T. In Catalytic Asymmetric Synthesis 2 ed. Ojima, I., ed. Wiley-VCH New York, 2000, 287. (Review). 

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 

While generation of a Mn(V)oxo salen intermediate 8 as the active chiral oxidant is widely accepted, how the subsequent C-C bond forming events occur is the subject of some debate. The observation of frans-epoxide products from cw-olefins, as well as the observation that conjugated olefins work best support a stepwise intermediate in which a conjugated radical or cation intermediate is generated. The radical intermediate 9 is most favored based on better Hammett correlations obtained with o vs. o . In addition, it was recently demonstrated that ring opening of vinyl cyclopropane substrates produced products that can only be derived from radical intermediates and not cationic intermediates.  

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). 

Entry Substrate Catalyst Conditions ee cis/trans Reference 

Initial studies on the Jacobsen-Katsuki epoxidation reaction identified conjugated eyelie and acyelic cw-disubstituted olefins as the class of olefins best suited for the epoxidation reaetion. Indeed a large variety of c/s-disubstituted olefins have been found to undergo epoxidation with a high degree of enantioselectivity. 2,2 -Dimethylehromene derivatives are especially good substrates for the epoxidation reaetion. Table 1.4.1 lists a variety of examples with their corresponding reference. 

The mechanism of the J-K epoxidation is not fully understood, but most likely a manganese(V)-specles Is the reactive intermediate, which Is formed upon the oxidation of the Mn(lll)-salen complex. The enantioselectivity Is explained by either a top-on approach (Jacobsen) or by a side-on approach (Katsuki) of the olefin. The three major mechanistic pathways are shown below. The radical intermediate accounts for the formation of mixed epoxides when conjugated olefins are used as substrates. 

The synthesis of the tetrasubstituted dihydroquinoline portion of siomycin Di, which belongs to the thiostrepton family of peptide antibiotics, was achieved in the laboratory of K. Hashimoto. The Jacobsen epoxidation was utilized to introduce the epoxide enantioselectively at the C7-C8 position. The olefin was treated with 5 mol% of Jacobsen s manganese(lll)-salen complex (R =f-Bu) and 4% aqueous NaOCI solution in dichloromethane. To enhance the catalyst turnover, 50 mol% of 4-phenylpyridine-A/-oxide was added to the reaction mixture. The desired epoxide was obtained in 43% yield and with 91% ee. 

The short asymmetric synthesis of the CBI accomplished by D.L. Boger and co-workers.  

The catalytic asymmetric synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine was developed by J. Lee et al. using an intramolecular epoxide opening 5-exo-tet) followed by ring expansion. The acyclic c/s-epoxide substrate was prepared in good yield and in greater than 94% ee by the Jacobsen epoxidation from the corresponding (Z)-alkene.  

Lynch and co-workers reported the asymmetric total synthesis of the PDE IV inhibitor CDP840 in which they utilized the Jacobsen epoxidation to introduce the only stereocenter of the target. The triaryl (Z)-olefin substrate was epoxidized with significantly higher enantiomeric excess than the triaryl ( )-olefin. This finding was interpreted with Jacobsen s skewed side-on approach model. 

Oxygen transfer via radical intermediate (tran -epoxide)  

Jacobsen, E. N. Wu, M. H. in Comprehensive Asymmetric Catalysis, Jacobsen, E. N. Pfaltz, A. Yamamoto, H. Eds. Springer New York 1999, Chapter 18.2. (Review). Katsuki, T. In Catalytic Asymmetric Synthesis 2 edn. Ojima, L, Ed. Wiley-VCH New York, 2000, 287. (Review). 

Palucki, M. Jacobsen-Katsuki epoxidation In Name Reactions in Heterocyclic Chemistry, Li, J. J. Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2005, 29—43. (Review). 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 132, Springer-Verlag Berlin Heidelberg 2009 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 141, Springer International Publishing Switzerland 2014 

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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. 

Jacobsen-Katsuki epoxidation reaction in total synthesis Scheme 1.4.11... 

The Jacobsen-Katsuki epoxidation reaction has been widely used for the preparation of a variety of structurally diverse complex molecules by both academia and the pharmaceutical industry. Summarized below are a few examples. 

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. 

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 potential of a catalytic process for use on a large scale can be a good indication of its efficiency. During recent decades there has been an increasing tendency to apply asymmetric catalytic processes in industry [1], The asymmetric Noyori hydrogenation [2] and the Sharpless and Jacobsen-Katsuki epoxidation [3] are representative examples of impressive developments in this field [1]. 

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 ... 

T. Linker, The Jacobsen-Katsuki epoxidation and its controversial mechanism, Angew. Chem. 1997, 109,2150-2152 Angew. Chem. Int. Ed. Engl. 1997, 36, 2060-2062. 

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... 

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