Epoxidation with Metal salen Complexes

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. 

A variety of catalysts with differing aromatic substituents and ethylenediamine cores have been prepared and tested, but few perform better than Jacobsen s catalyst. These catalysts are not general for all alkene substrates and the best results have been achieved using cis-alkenes, trisubstituted alkenes and some tetrasubstituted derivatives. Especially high ees have been obtained with conjugated alkenes, in particular chromenes and P-substituted styrenes while trans-olefins and terminal olefins are poor substrates for this process. 

The details of the manganese(salen) catalysed epoxidation remain a topic of some debate. It has been established that the epoxidation proceeds via formation of an 0X0 Mn(V) complex by reaction of the Mn(lll) complex with the oxidant. However, a number of other oxidising species have also been 

Rgure 4.4 Mechanistic pathways for the Mn(salen)-catalysed epoxidations 

Most frequently, iodosylbenzene (PhlO) or sodium hypochlorite (NaOCl) are used as the stoichiometric oxidant, althoi alternative reagents have been used, including hydrogen peroxide, periodate,dimethyldioxirane, and an mCPBA/N-methylmorpholine-N-oxide combination which allows the use of a lower temperature and provides higher enantioselectivities.  

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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... 

Several research groups reported that various ILs could be effective cocatalysts in the copolymerization of CO2 and epoxides with metal salen or metal porphyrin complexes [126-130]. In some cases, it was shown that the activities of theses metal complexes were drastically enhanced by the co-presence of IL, although they had no or a very low activity for the coplymerization in the absence of IL. 

The second example demonstrated immobilization via ship in a bottle , ionic, metal center, and covalent bonding approaches of the metal-salen complexes. Zeolites X and Y were highly dealuminated by a succession of different dealumi-nation methods, generating mesopores completely surrounded by micropores. This method made it possible to form cavities suitable to accommodate bulky metal complexes. The catalytic activity of transition metal complexes entrapped in these new materials (e.g, Mn-S, V-S, Co-S, Co-Sl) was investigated in stereoselective epoxidation of (-)-a-pinene using 02/pivalic aldehyde as the oxidant. The results obtained with the entrapped organometallic complex were comparable with those of the homogeneous complex. 

The third investigation track demonstrated the immobilization of metal-salen complexes in mesoporous materials and their use in the hydrolytic kinetic resolution of meso and terminal epoxides. The best results were obtained over cobalt-Ja-cobsen catalysts. The catalytic activity of the (S,S)-Co(II)-Jacobsen complex immobilized on Al-MCM-41 was comparable with that of the homogeneous counterpart. Several other immobilization methods are still under investigation. 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

Initial successes with these ligands came independently from the groups of Jacobsen and Katsuki in the asymmetric epoxidation of unfimctionalized olefins. Since these seminal works in 1990, metal salen complexes have become workhorse in asymmetric catalysis, finding applications in a wide variety of reactions. In Figure 1 is illustrated a variety of metal salen complexes. Scheme 1 lists some of the transformations in which they have been used, demonstrating the broad utility of these complexes. 

To illustrate the utility of the metal salen complexes, several reactions are outlined in Scheme 1. They include the asymmetric epoxidation of unfimctionalized cw-disubstituted and trisubstituted olefins, which are promoted by (salen)Mn complexes." In the case of trani-disubstituted olefins, the simple (salen)Mn complexes do not exhibit the same levels of enantioselectivity as they do with the cis- and trisubstituted derivatives. Promising alternatives include more elaborate (salen)Mn complexes based on the binaphthyl imit, (salen)Cr complexes,and (salen)Ru-based catalysts. Catalysts based on (salen)Co moiety have exhibited amazing levels of selectivity in the hydrolytic kinetic resolution (HKR) of terminal epoxides. The HKR allows access to terminal epoxides and diols with very high enantioselectivities. 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

Figure 1 Structures of some metal salen complexes (a) epoxidation catalysts, (b) proposed structure in the asymmetric addition of alkyl groups to alpha ketoesters with a bifunctional catalyst, and (c) oligomeric bifunctional salen catalyst for the hydrolytic catalytic resolution... 

A number of other transition metal(salen) complexes have been investigated. A ruthenium(salen)-catalysed asymmetric epoxidation of wide scope has been developed by Katsuki that proceeds under irradiation with visible light. Trans-and terminal olefins are epoxidised with good ee but the selectivities obtained with ds-substrates are not as good as those achieved using Mn(salen) complexes. The use of palladium(salen) complexes as epoxidation catalysts has also been explored, but relatively poor selectivities have been obtained to date. ... 

Indirect electrochemical oxidative carbonylation with a palladium catalyst converts alkynes, carbon monoxide and methanol to substituted dimethyl maleate esters (81). Indirect electrochemical oxidation of dienes can be accomplished with the palladium-hydroquinone system (82). Olefins, ketones and alkylaromatics have been oxidized electrochemically using a Ru(IV) oxidant (83, 84). Indirect electrooxidation of alkylbenzenes can be carried out with cobalt, iron, cerium or manganese ions as the mediator (85). Metalloporphyrins and metal salen complexes have been used as mediators for the oxidation of alkanes and alkenes by oxygen (86-90). Reduction of oxygen and the metalloporphyrin generates an oxoporphyrin that converts an alkene into an epoxide. 

Supercritical CO2 is a non-polar, aprotic solvent and promotes radical mechanisms in oxidation reactions, similar to liquid-phase oxidation. Thus, wall effects might occur as known, e.g. from olefin epoxidation with 02 or H202 which may decrease epoxide selectivities. The literature covers the synthesis of fine chemicals by oxidation either without catalysts (alkene epoxidation, cycloalkane oxidation, " Baeyer-Villiger oxidation of aldehydes and ketones to esters ), or with homogeneous metal complex catalysts (epoxidation with porphyrins, salenes or carbonyls ). Also, the homogeneously catalysed oxidation of typical bulk chemicals like cyclohexane (with acetaldehyde as the sacrificial agent ), toluene (with O2, Co +/NaBr ) or the Wacker oxidation of 1-octene or styrene has been demonstrated. 

C.-X. Miao, J.-Q. Wang, Y. Wu, Y. Du, L.-N. He, Bifunctional metal-salen complexes as efficient catalysts for the fixation of CO2 with epoxides under solvent-free conditions, ChemSusChem 1 (2008) 236-241. 

Although the enantioselective intermolecular addition of aliphatic alcohols to meso-epoxides with (salen)metal systems has not been reported, intramolecular asymmetric ring-opening of meso-epoxy alcohols has been demonstrated. By use of monomeric cobalt acetate catalyst 8, several complex cyclic and bicydic products can be accessed in highly enantioenriched form from the readily available meso-epoxy alcohols (Scheme 7.17) [32]. 

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