Epoxide chiral

In cases where Noyori s reagent (see p. 102f.) and other enantioselective reducing agents are not successful, (+)- or (—)-chlorodiisopinocampheylborane (Ipc BCl) may help. This reagent reduces prochiral aryl and tert-alkyl ketones with exceptionally high enantiomeric excesses (J. Chandrasekharan, 1985 H.C. Brown, 1986). The initially formed boron moiety is usually removed hy precipitation with diethanolamine. Ipc2BCl has, for example, been applied to synthesize polymer-supported chiral epoxides with 90% e.e. from Merrifield resins (T. Antonsson, 1989). 

Stuckey, D.C., Rosjidi, M., Leak, D.J., The downstream separation of chiral epoxides using colloidal liquid aphrons (CLAs), "Separations for Biotechnology III" ed. D.L. Pyle, pp.440-446, SCI Publishing, 1994. 

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. 

Fritsch-Bobbitt imine 34 was prepared by reacting amine 33 with chiral epoxide 32. 

The second system studied was the separation of the chiral epoxide enantiomers (la,2,7,7a-tetrahydro-3-methoxynaphth-(2,3b)-oxirane Sandoz Pharma) used as an intermediate in the enantioselective synthesis of optically active drugs. The SMB has been used to carry out this chiral separation [27, 34, 35]. The separation can be performed using microcrystalline cellulose triacetate as stationary phase with an average particle diameter greater than 45 )tm. The eluent used was pure methanol. A... 

The competitive adsorption isotherms were determined experimentally for the separation of chiral epoxide enantiomers at 25 °C by the adsorption-desorption method [37]. A mass balance allows the knowledge of the concentration of each component retained in the particle, q, in equilibrium with the feed concentration, < In fact includes both the adsorbed phase concentration and the concentration in the fluid inside pores. This overall retained concentration is used to be consistent with the models presented for the SMB simulations based on homogeneous particles. The bed porosity was taken as = 0.4 since the total porosity was measured as Ej = 0.67 and the particle porosity of microcrystalline cellulose triacetate is p = 0.45 [38]. This procedure provides one point of the adsorption isotherm for each component (Cp q. The determination of the complete isotherm will require a set of experiments using different feed concentrations. To support the measured isotherms, a dynamic method of frontal chromatography is implemented based on the analysis of the response curves to a step change in feed concentration (adsorption) followed by the desorption of the column with pure eluent. It is well known that often the selectivity factor decreases with the increase of the concentration of chiral species and therefore the linear -i- Langmuir competitive isotherm was used ... 

Nieoud R. M., Euehs G., Adam P, Bailly M., Kusters E., Antia E, Reuille R., Sehmid E. (1993) Preparative Seale Enantioseparation of a Chiral Epoxide Comparison of Liquid Chromatography and Simulated Moving Bed Adsorption Teehnology, Chirality 5 267-271. 

Kusters E., Gerber G., Antia E. D. (1995) Enantioseparation of a Chiral Epoxide by SMB Chromatography using Chiraleel-OD, Chromatographia 40 387-393. 

Finally, the necessity arose for the synthesis of pentulose 21, labeled with, 3C on the central carbons, C-2 and C-3, for an independent biosynthetic study, which is reported in Section III.5.27 The doubly labeled ester 34 (Scheme 14) is readily available by a Wittig- Homer condensation of benzyloxyacetaldehyde with commercially available triethylphosphono-(l,2-l3C2)acetate. Chirality was introduced by the reduction of ester 34 to the allylic alcohol, which produced the chiral epoxide 35 by the Sharpless epoxidation procedure. This was converted into the tetrose 36, and thence, into the protected pentulose 37 by the usual sequence of Grignard reaction and oxidation. 

Chiral epoxides and their corresponding vicinal diols are very important intermediates in asymmetric synthesis [163]. Chiral nonracemic epoxides can be obtained through asymmetric epoxidation using either chemical catalysts [164] or enzymes [165-167]. Biocatalytic epoxidations require sophisticated techniques and have thus far found limited application. An alternative approach is the asymmetric hydrolysis of racemic or meso-epoxides using transition-metal catalysts [168] or biocatalysts [169-174]. Epoxide hydrolases (EHs) (EC 3.3.2.3) catalyze the conversion of epoxides to their corresponding vicinal diols. EHs are cofactor-independent enzymes that are almost ubiquitous in nature. They are usually employed as whole cells or crude... 

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. 

Gong, P.-F. and Xu, J.-H. (2005) Bio-resolution of a chiral epoxide using whole cells of Bacillus megaterium ECU1001 in a biphasic system. Enzyme and Microbial Technology, 36, 252-257. 

It is possible to prepare either enantiomer of a chiral epoxide in high enantiomeric excess ... 

Moreover, using the cobalt catalyst S,S-(50c) it was possible to perform substrate screening45 so that the chiral epoxides (48a-c) could be studied in parallel.55 It was found that //-(48a) is the most reactive substrate followed by //-(48c) and //-(48b). The relative reactivity of //-(48b) and //-(48c) corresponds to that reported in the literature for laboratory scale reactions,83 whereas the reaction... 

Several recent articles describe the ring-opening of chiral epoxides under microwave irradiation conditions (see also Scheme 6.103). In the context of the preparation of novel /32-adrenoceptor agonists related to formoterol and salmeterol, Fairhurst and a team from Novartis have described the synthesis of chiral ethanolamines by solvent-free microwave-assisted ring-opening of a suitable chiral epoxide precursor with secondary benzylated amines (Scheme 6.129) [262]. At 110 °C, the reaction occurred... 

Finally, chiral epoxides can be prepared from a,p-unsaturated carbonyl compounds through an entirely different approach, in which the epoxide oxygen is derived from the carbonyl moiety. For example, trans-aryl-vinyl epoxides 52 can be synthesized from conjugated aldehydes 50 and chiral sulfonium salts 51, with excellent ee s. The protocol is especially effective for substrates which bear a p-mcthoxy group on the aryl substituent <00TL7309>. 

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