Oxiranes kinetics

The several kinetic rates are a consequence of Reactions 2-5 The first two represent monomeric additions the third describes all rates by which two polymeric molecules smaller than j form a molecule of size j. The molecule A AC contains a carboxylic anion the second molecule P. supplies aS oxirane and, in general, is any polymeric molecule of iSze j-n. 

Scheme 8.26. Kinetic resolution of cyclic vinyl oxiranes 44.

The above-mentioned facts have important consequences on the stereochemical outcome of the kinetic resolution of asymmetrically substituted epoxides. In the majority of kinetic resolutions of esters (e.g. by ester hydrolysis and synthesis using lipases, esterases and proteases) the absolute configuration at the stereogenic centre(s) always remains the same throughout the reaction. In contrast, the enzymatic hydrolysis of epoxides may take place via attack on either carbon of the oxirane ring (Scheme 7) and it is the structure of the substrate and of the enzyme involved which determine the regioselec-tivity of the attack [53, 58-611. As a consequence, the absolute configuration of both the product and substrate from a kinetic resolution of a racemic... 

Theoretical evidence [Hartree-Fock (RHF) calculations and density functional theory] has been obtained for a concerted mechanism of oxirane cleavage and A-ring formation in oxidosqualene cyclization. A common concerted mechanistic pathway has been demonstrated for the acid-catalysed cyclization of 5,6-unsaturated oxiranes in chemical and enzymic systems. For example, the conversion of (24) into (26) proceeds via (25) and not via a discrete carbocation (27). Kinetic studies and other evidence are presented for various systems. 

Kirkovsky, L.I., Lermontov, S.A., Zavorin, S.T, Sukhozhenko, I.I., Zavelsky, V.I., Their, R., and Bolt, H.M. Hydrolysisofgen-otoxic methyl-substituted oxiranes experimental kinetic and semiempirical stidies. Environ. Toxicol. Chem., 17(11) 2141-2147, 1998. 

The -deprotonation reaction was initially considered as the normal mode of oxirane isomerization in basic media with a-deprotonation appearing as an alternative pathway when the principal process was slowed. Recent studies based on kinetic studies, calculations and labeling experiments, along with advances in the determination of the organolithium... 

Based on this feature, aggregation states of transition-state structures for base-promoted isomerization of oxiranes have been established by kinetic studies of LDA-mediated isomerizations of selected oxiranes in nonpolar media in the presence of variable concentrations of coordinating solvents (ligands). Results reported provide the idealized rate law V = [ligand]" [base] [oxtrane] for a-deprotonation and v = fc[ligand]°[base] / [oxirane]... 

The growing interest in enantioselective isomerization of meso oxiranes to allylic alcohols arises from the ready availabihty of starting materials and the synthetic value of the homochiral products. First apphed to simple meso cycloalkene oxides, this methodology has been successfully exteuded to fuuctioualized meso oxiranes, and even to the kinetic resolution of racemic oxiranes, demonstrating its potential in accessing highly advanced synthons. 

By contrast with the enantioselective deprotonation of meso oxiranes, there is only a limited number of reports on the kinetic resolution of unsymmetrically substituted oxiranes. This reaction involves the preferential recognition of one of the two enantiomers of a racemic mixture by a chiral reagent to provide both the starting material and the product in enantioenriched form . Several HCLA bases developed for enantioselective deprotonation have been tested as chiral reagent in stoichiometric or catalytic amount for the kinetic resolution of cyclic and linear oxiranes. 

With regard to the general behavior of oxiranes, studies on kinetic resolution of alkyl or alkoxy substituted linear oxiranes mediated by 0.5 to 0.75 equivalent of HCLA base 53 have shown better enantiomeric discrimination for cis (Table 9, entries 1 and 4) rather than trans or terminal oxiranes (Table 9, entries 2, 3 and 5). 

Reactivity of oxiranes with organolithium reagents TABLE 9. Kinetic resolution of racemic oxiranes using HCLA 53... 

Examples for and have been observed under certain experimental conditions for reactive and/or strained chiral oxiranes which were separated by complexation gas chromatography (Figure 21)133. The first eluted peak was diminished in the separation of racemic 2-methyl-3-phenylo.xirane. In this case two enantioselective processes are mediated by the chiral metal chelate, i.e., chromatographic resolution and kinetic resolution (in favor of the first eluted enantiomer). Since two enantioselective processes are involved, the elution profile will be the same svhen the chirality of the metal chelate is inverted. 

With chiral racemic oxiranes one enantiomer reacts faster than the other the degree of kinetic resolution is very high for L-valine/alanine-based dialkoxydihydropyrazines. For example, in the reaction of one equivalent of (2.S )-2,5-dihydro-2-isopropyl-3,6-dimethoxy-5-methyl-pyrazine (1, R1 = CH3) with two equivalents of fW-(//,/ )-2,3-dimethyloxirane (R2,R4 = CH3 R = H) virtually only the (2//,3/ )-oxirane enantiomer reacts with the lithiated dihydropyrazine to give exclusively the (l /, 2/, 2 / )-configuratcd adduct i.e., (2/ ,5S)-2,5-dihydro-5-isopropyl-3,6-dimethoxy-2-[(l/ ,2/ )-2-(2-methoxyethoxymethoxy)-l-methylpropyl]-2-methylpyrazine, entry 7. Likewise, kinetic resolution (intramolecular) occurs upon reaction with rac-7-oxabicy-clo[4.1.0]heptane (entry 8). 

From the kinetics of the oxirane polymerization initiated hy alcoholate (l6) and hy fluorenyl potassium (27) and as fluorenyl and dihydronaphthalene mono anion (28) have approximately the same basicity, the ka2 over kpr0p ratio may be estimated to 20. Therefore, the length of the two growing polyether chains must be largely independent on the nature of the initiating site. 

In concomitance with the displacement observed by i.r., an evolution of the catalytic activity has been observed while studying the liquid-phase epoxidation of cyclohexene in the presence of (EGDA)- Mo(VI), freshly prepared or after four months of conditioning at room temperature under inert atmosphere. As usual, the appearance of epoxide was followed by gas chromatographic analyses or by direct titration of oxirane oxygen and the disappearance of hydroperoxide was monitored by iodometric titration. In figure we report concentration-time for typical runs in ethylbenzene at 80°C obtained with the experimental procedure already described (ref. 9). It may be seen that with a freshly prepared catalyst an induction period is observed which lowers the initial catalytic activity. Our modified Michaelis-Menten type model equation (ref. 9) cannot adequately fit the kinetic curves obtained due to the absence of kinetic parameters which account for the apparent initial induction period (see Figure). 

In a recent theoretical study [MP2, B3LYP, CCSD(T)]112 the inversion at the oxygen of the (9-methylated oxirane cation 39 was calculated to be 15.7 kcal mol-1, which agrees well with the experimentally determined value for cation 38. Cation 39 is kinetically stable because a high-energy barrier (35.3 kcal mol-1) separates it from the ring-opened, significantly more stable isomeric oxonium ions (Scheme 4.5). In... 

A mixture of epoxides 483 obtained on oxidation of 482 with dimethyldioxirane, when exposed to ferric chloride provided, as the kinetically controlled product, the a-aldehyde 484, which without purification was reduced to the a-alcohol 485. The exclusive formation of 484 is believed to occur via the benzyl cation 486, generated by Lewis-acid opening of the oxirane ring, suffering a stereospecific kinetic 1,2-hydride shift The amino alcohol 487 obtained after sequential removal of O-benzyl and N-tosyl groups from 485, on treatment with triphenylphosphine and iodine in the presence of imidazole furnished the tetracyclic base 488, which was oxidised to the ketone 489. Trapping of the kinetically generated enolate of 489 as the silylether, followed by palladium diacetate oxidation yielded the enone 490. The derived... 

Decomposition of Caro s acid is catalysed by acetone.324 A kinetic study in aqueous alkaline medium indicates simple second-order kinetics. Nucleophilic addition of S052- to the carbonyl carbon leads to oxirane by reaction with another SOs2- to give... 

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