EPOXIDATION, ENANTIOSELECTIVE

The mesoporous character of MCM-41 overcomes the size limitations imposed by the use of zeolites and it is possible to prepare the complex by refluxing the chiral ligand in the presence of Mn +-exchanged Al-MCM-41 [34-36]. However, this method only gives 10% of Mn in the form of the complex, as shown by elemental analysis, and good results are only possible due to the very low catalytic activity of the uncomplexed Mn sites. The immobihzed catalyst was used in the epoxidation of (Z)-stilbene with iodosylbenzene and this led to a mixture of cis (meso) and trans (chiral) epoxides. Enantioselectivity in the trans epoxides was up to 70%, which is close to the value obtained in solution (78% ee). However, this value was much lower when (E)-stilbene was used (25% ee). As occurred with other immobilized catalysts, reuse of the catalyst led to a significant loss in activity and, to a greater extent, in enantioselectivity. 

Davies and Reider (1996) have given some details of the HIV protease inhibitor CRDCIVAN (INDINAVIR) for which (lS,2R)-c -amino indanol is required. Indene is epoxidized enantioselectively, using the lacobsen strategy (SS-salen Mn catalyst, aqueous NaOH and PiNO), to (lS,2/ )-indene oxide in a two-phase system, in which the OH concentration is controlled. Indene oxide was subjected to the Ritter reaction with MeCN, in the presence of oleum, and subsequent hydrolysis and crystallization in the presence of tartaric acid gives the desired amino indanol. 

Discrepancies in the enantioselectivity reported for the same lithium amide and reaction conditions may be due to different enantiomeric purity of the lithium amides (Table 6, entries 1 -3,4-6 and 7-9 and Table 7, entries 3-5) . Interestingly, for the elimination of the cw-epoxides enantioselectivity is higher in benzene than in tetrahydrofuran (Table 6, entries 1 and 3.12 and 13 and 14 and 15) whereas for that of the trans-epoxide the situation is reversed (Tabic 7, entries 2 and 6). The enantioselectivity of the elimination of the /rans-epoxide can be raised significantly through addition of DBU (Table 7, entries 6 and 7). 

Epoxide is an important intermediate for various bioactive compounds, so the demand for the chiral epoxide is increasing. Epoxide hydrolase can hydrolyze epoxide enantioselectively (Figure 20).21 For example, Aspergillus niger was used for the hydrolysis of carvone epoxide (Figure 20(a)).2 11 In the reaction of styrene oxide, the... 

Tetrasubstituted olefins are particularly difficult to epoxidize enantioselectively with (salen)Mn catalysts. Nevertheless, Jacobsen has reported moderate to high enantioselectivi-ties with certain tetrasubstituted olefins by careful selection of reaction parameters. Curiously enough, the more bulky catalysts appear to be the most effective for these substrates, as... 

Transition-metal-catalysed epoxidations work only on allylic alcohols, so there is one limitation to the method, but otherwise there are few restrictions on what can be epoxidized enantioselectively. When this reaction was discovered in 1981 it was by far the best asymmetric reaction known. Because of its importance, a lot of work went into discovering exactly how the reaction worked, and the scheme below shows what is believed to be the active complex, formed from two titanium atoms bridged by two tartrate ligands (shown in gold). Each titanium atom retains two of its isopropoxide ligands, and is coordinated to one of the carbonyl groups of the tartrate ligand. The reaction works best if the titanium and tartrate are left to stir for a while so that these dimers can form cleanly. 

Peroxidases are ubiquitous, and many are b-type heme proteins. Several good reviews summarize years of peroxidase research and describe peroxidase applications [57 -61]. Some of the reactions catalyzed by peroxidases are listed in Tab. 10.2 and include oxidation of aromatic and heteroatom compounds, epoxidation, enantioselective reduction of racemic hydroperoxides, free radical oligomerizations and polymerizations of electron-rich aromatics, and the oxidative degradation of lignin [58, 60],... 

SHARPLESS Asymmetne Epoxidation Enantioselective epoxidation of ailyi alcotiois by means of Manbm altoxide. ( ) or () diethyl lartarate (OET) and t butyl hydroperoxide (TBHP)... 

Ordinary alkenes (without an allylic OH group) do not give optically active alcohols by the Sharpless protocol because binding to the catalyst is necessary for enantioselectivity. Simples alkenes can be epoxidized enantioselectively with sodium hypochlorite (NaOCl, commercial bleach) and an optically active manganese-complex catalyst. An important variation of this oxidation uses a manganese-salen complex with various oxidizing agents, in what is called... 

Oxidations catalyzed by monooxygenases Oxygenations of C-H and C=C bonds forming alcohols, epoxides enantioselective Baeyer-Villiger oxidations of ketones to chiral lactones and of sulfides to chiral sulfoxides nuclear and side-chain hydroxylation of aromatic compounds. 

Another method, where a different reduction methodology is employed, can be used to generate secondary and tertiary allylic alcohols from primary ones, and when this method is used in combination with Sharpless asymmetric epoxidation enantioselectivity may even be achieved (Scheme 11). ... 

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. 

Jacobsen-Katsuki epoxidation Enantioselective epoxidation of unfunctionalized alkyl-and aryl-substituted olefins. 222... 

Dimethyl-2//-chromenes have been epoxidized enantioselectively with DMD in the presence of chiral Mn(III)salen catalysts <95TL3669>. 

Epoxide hydrolases Resolution of aryl and substituted alicyclic epoxides. Enantioselective catalyst... 

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... 

BimetaUic chiral cobalt salen catalysts containing transition-metal salts have also been demonstrated by Kim et al. [190] to be remarkably efficient and highly enantioselective in hydrolytic KRs of various epoxides. Enantioselectivity of up to 99% ee for the recovered epoxides combined with very high catalytic activity could be reached. Another means for fixing or linking two or more Co(salen) units in dose proximity to decrease the catalyst requirements by making the reaction of... 

Introduction to Ethers Nomenclature of Ethers Structure and Properties of Ethers Crown Ethers Preparation of Ethers Reactions of Ethers Nomenclature of Epoxides Preparation of Epoxides Enantioselective Epoxidation Ring-Opening Reactions of Epoxides Thiols and Sulfides... 

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