Jacobsen Epoxidation Catalyst

Scheme 8.28. Formally group-selection insertion of oxygen into enantiotopic C-H bonds, (a) An asymmetric Kharasch reaction [124], The catalyst is similar to that shown in Scheme 8.12, except that each oxazoline bears two methyl substituents at C-5. (b) Kinetic resolution of dihydronaphthalenes [125]. The reaction uses a Jacobsen epoxidation catalyst (Scheme 8.6, type A).

Dihydronaphthalene is often used as a model olefin in the study of epoxidation catalysts, and very often gives product epoxides in unusually high ee s. In 1994, Jacobsen discovered in his study on the epoxidation of 1,2-dihydronaphthalene that the ee of the epoxide increases at the expense of the minor enantiomeric epoxide.Further investigation led to the finding that certain epoxides, especially cyclic aromatically conjugated epoxides, undergo kinetic resolution via benzylic hydroxylation up to a krei of 28 (Scheme 1.4.9). 

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]. 

Fueled by the success of the Mn (salen) catalysts, new forays have been launched into the realm of hybrid catalyst systems. For example, the Mn-picolinamide-salicylidene complexes (i.e., 13) represent novel oxidation-resistant catalysts which exhibit higher turnover rates than the corresponding Jacobsen-type catalysts. These hybrids are particularly well-suited to the low-cost-but relatively aggressive-oxidant systems, such as bleach. In fact, the epoxidation of trans-P-methylstyrene (14) in the presence of 5 mol% of catalyst 13 and an excess of sodium hypochlorite proceeds with an ee of 53%. Understanding of the mechanistic aspects of these catalysts is complicated by their lack of C2 symmetry. For example, it is not yet clear whether the 5-membered or 6-membered metallocycle plays the decisive role in enantioselectivity however, in any event, the active form is believed to be a manganese 0x0 complex <96TL2725>. 

Chiral and achiral Jacobsen s catalysts exhibit similar diatereomeric excesses during the diastereoselective epoxidation of R-(+)-limonene using in situ prepared oxidizing agents. Therefore, the chiral center of the substrate appears to govern the chiral induction. In contrast, the chirality of the Jacobsen s catalyst appears to be responsible for the chiral induction when commercially available oxidants were used. 

Later, Jacobsen and co-worker (31) reported the use of a parallel approach for the discovery of new epoxidation catalysts. With a focus on catalyst activity, a three-phase approach was taken. Four different linkers to the polystyrene support... 

Figure 14.20. Jacobsen s catalyst in enantioselective ring opening of epoxide...

Soluble polymer-bound catalysts for epoxidation reactions have also been explored, with a complete study into the nature of the polymeric backbone performed by Janda [70]. Chiral (salen)-Mn complexes were appended to MeO-PEG, NCPS, Jan-daJeF and Merrifield resin via a glutarate spacer. It was found that for the Jacobsen epoxidation of ds-/ -mefhylstyrene, the enantioselectivities for each polymer-supported catalyst were comparable (86-90%) to commercially available Jacobsen catalyst (88%). Both soluble polymer-supported catalysts could be used twice before a decline in yield and enantioselectivity was observed. However, neither soluble polymer support proved as suitable as the insoluble JandaJel-supported (salen)-Mn complex for the epoxidation because residual impurities during precipitation and leaching of Mn from the complex, resulted in lowered yields. 

To overcome this issue Kureshy et al. [55, 56] reported dimeric form of Jacobsen s catalysts 3, 4. They used the concept of solubility modification by altering the molecular weight of the catalyst so that in a post catalytic work-up procedure the catalyst is precipitated, filtered and used for subsequent catalytic runs. The complexes 3, 4 (0.2 mol % of Co(lll)-salen unit) (Figure 2) were effectively used for HKR of racemic epoxides, e.g., styrene oxide, epichlorohydrin, 1,2-epoxypropane, 1,2-epoxyhexane, 1,2-epoxyoctane, and 1,2-epoxydodecane to achieve corresponding epoxides and 1,2-diols in high optical purity and isolated yields. In this process, once the catalytic reaction is complete the product epoxides were collected by reduced pressure distillation. Addition of diethylether to the residue precipitated the catalyst which was removed by filtration. However, the recovered catalyst was required to be reactivated by its treatment with acetic acid in air. The catalysts were reused 4 times with complete retention of its performance. 

Heterogeneous Asymmetric Epoxidation of Olefins over Jacobsen s Catalyst Immobilized in Inorganic Porous Materials... 

In the present work, the Jacobsen s catalyst was immobilized inside highly dealuminated zeolites X and Y, containing mesopores completely surrounded by micropores, and in Al-MCM-41 via ion exchange. Moreover, the complex was immobilized on modified silica MCM-41 via the metal center and through the salen ligand, respectively. cis-Ethyl cinnamate, (-)-a-pinene, styrene, and 1,2-dihydronaphtalene were used as test molecules for asymmetric epoxidation with NaOCl, m-CPBA (m-chloroperoxybenzoic acid), and dimethyldioxirane (DMD) generated in situ as the oxygen sources. 

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 Epoxidation allows the enantioselective formation of epoxides from various -substituted olefins by using a chiral Mn-salen catalyst and a stoichiometric oxidant such as bleach. 

Regardless of the mechanism, the chiral (salen)Mn-mediated epoxidation of unfunctionalized alkenes represents a methodology with constantly expanding generality. Very mild and neutral conditions can be achieved, as illustrated by Adam s epoxidation of chromene derivatives 12 using Jacobsen-type catalysts and dimethyldioxirane as a terminal oxidant [95TL3669]. Similarly, periodates can be employed as the stoichiometric oxidant in the epoxidation of cis- and tram-olefins [95TL319],... 

Many other projects in the past dealt with the immobilization of the famous chelating salen ligand or salen metal complexes, respectively—the Mnm salen Schiff base complex is also known as Jacobsen s catalyst, and it is used, among others, in asymmetric epoxidation of olefinstttt—mainly onto the surface of MCM-41 and SBA-15. 

Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis-amino-indanol for the synthesis of Crixivan, This process is very much the cornerstone of the whole synthesis. During the development of the first laboratory route into a route usable on a very large scale, many methods were tried and the final choice fell on this relatively new type of asymmetric epoxidation. The Sharpless asymmetric epoxidation works only for allylic alcohols (Chapter 45) and so is no good here. The Sharpless asymmetric dihydroxylation works less well on ris-alkenes than on trans-alkenes, The Jacobsen epoxidation works best on cis-alkenes. The catalyst is the Mn(III) complex easily made from a chiral diamine and an aromatic salicylaldehyde (a 2-hydroxybenzaldehyde). 

Jacobs et al has also reported immobilisation of Jacobsen s catalyst in a polydimethylsiloxane (PDMS) membrane for the epoxidation of terminal alkene (Scheme 6b).53 In the case of styrene epoxidation using NaOCl, styrene oxide was obtained with nearly the same activity and enantioselectivity (52 %) than in homogeneous conditions. Interestingly, the catalytic membranes are easily regenerable. 

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. 

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

Another recent example by Peukert and Jacobsen (199) took advantage of the first polymer supported Jacobsen s catalyst 8.53 (Fig. 8.31) comparable with the soluble catalyst in asymmetric epoxidation and its full characterization (200, 201). The supported catalyst, prepared from the activated carbonate of hydroxymethyl PS and from a soluble phenolic catalyst (201), was used to catalyze the opening of racemic alkyl epoxides (Mi, Fig. 8.31) with substituted phenols and yielded the 50-member aryloxy alcohol library L15 with good enantiomeric purity (average >90%, never below 80% e.e.). 8.53 was also used to produce the chiral intermediate monomer set M3 (Fig. 8.31) which was used to make two 50-member chiral libraries L16 (1,4-diary-loxy 2-propanols) and L17 (3-aryloxy-2-hydroxy propanamines) with excellent enantiomeric excess following the straightforward synthetic schemes reported in Fig. 8.31. 

Meunier has reviewed recent advances in asynunetric oxidation. Jacobsen s asymmetric epoxidation catalysts are some of the most successful. These use Mn(III) in a chiral salen hgand with NaOCl as primary oxidant. The intermediacy of Mn(V) 0x0 species has been proposed as the active species formed after O atom transfer from the hypochlorite. Enantiomeric excesses of 97-98% are seen in the epoxide product on a consistent basis across a wide variety of alkene substrates. 

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