Epoxide hydrolysis, selective

G. Bellucci, C. Chiappe, A. Cordoni, F. Marioni, The Rabbit Liver Microsomal Biotransformation of 1,1-Dialkylethylenes Enantioface Selection of Epoxidation and Enantioselectivity of Epoxide Hydrolysis , Chirality 1994, 6, 207 - 212. 

The epoxidation proceeds via substrate control to yield the a-epoxide 41 selectively. The C-nucleophile 42 that results from deprotonation of 27 opens the epoxide from above through an attack at C-8, and the resulting alcoholate 43 cyclizes upon reacting with the electrophilic carbon to form the five-membered ring, which becomes the hemiacetal 28 after hydrolysis. 

Another strategy for the achievement of an enantioconvergent process was set up using the combination of bio- and chemo-catalysis[107, 109, 121> 122). For instance, 2,2-disubstituted epoxides were selectively resolved by lyophilized whole cells of Nocardia sp. The biohydrolysis proceeds via attack at the less substituted C-atom with excellent regioselectivity thus leading to retention of configuration at the stereogenic center. On the other hand, acid-catalyzed hydrolysis of such epoxides usually proceeds at the more substituted oxirane carbon with inversion. Careful... 

Later on, Dohi et al. [8] developed an L-selective epoxidation/hydrolysis sequence on a glycoheptopyranose intermediate. 

Osmium tetroxide reacts with alkenes in a two-step process to give the corresponding vicinal diols in a stereospecihcally syn manner. The process therefore complements the epoxidation-hydrolysis seqnence described in the previons section, which proceeds with anti selectivity. 

Another synthesis was reported in 2005 by Genisson etal. who constmcted the six-membered indohzidine skeleton via RCM starting from the epoxide 206 (Scheme 2.46). Selective epoxide hydrolysis, followed by alkylation with the triflate of 3-butenol, led to the diolefin 207 in 72%. Subsequent RCM ([Ru]-II [5-10 mol%], toluene, 70 °C) afforded the tetrahydropyridine 208 in 66% yield. Completion of the synthesis enclosed hydrogenolysis followed by ring closure to afford the targeted alkaloid (—)-lentiginosine (209) [71]. 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

The zirconium alkoxides Zr(OR)4 are reported as inactive for the epoxidation of olefins under the conditions recommended with the titanium analogs. When synthesized by reaction of Zr(CH2CMe3)4 with silica, followed by hydrolysis or calcination, a solid as active as the related Ti-based catalyst is obtained. The low selectivity for the formation of the epoxide is related to the fact that the same Zr centers catalyze both the formation and the decomposition of the epoxide.46... 

The results of the olefin oxidation catalyzed by 19, 57, and 59-62 are summarized in Tables VI-VIII. Table VI shows that linear terminal olefins are selectively oxidized to 2-ketones, whereas cyclic olefins (cyclohexene and norbomene) are selectively oxidized to epoxides. Cyclopentene shows exceptional behavior, it is oxidized exclusively to cyclopentanone without any production of epoxypentane. This exception would be brought about by the more restrained and planar pen-tene ring, compared with other larger cyclic nonplanar olefins in Table VI, but the exact reason is not yet known. Linear inner olefin, 2-octene, is oxidized to both 2- and 3-octanones. 2-Methyl-2-butene is oxidized to 3-methyl-2-butanone, while ethyl vinyl ether is oxidized to acetaldehyde and ethyl alcohol. These products were identified by NMR, but could not be quantitatively determined because of the existence of overlapping small peaks in the GC chart. The last reaction corresponds to oxidative hydrolysis of ethyl vinyl ether. Those olefins having bulky (a-methylstyrene, j8-methylstyrene, and allylbenzene) or electon-withdrawing substituents (1-bromo-l-propene, 1-chloro-l-pro-pene, fumalonitrile, acrylonitrile, and methylacrylate) are not oxidized. 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

Reaction in organic solvent can sometimes provide superior selectivity to that observed in aqueous solution. For example, Keeling et al recently produced enantioenriched a-trifluoromethyl-a-tosyloxymethyl epoxide, a key intermediate in the synthetic route to a series of nonsteroidal glucocorticoid receptor agonist drug candidates, through the enan-tioselective acylation of a prochiral triol using the hpase from Burkholderia cepacia in vinyl butyrate and TBME (Scheme 1.59). In contrast, attempts to access the opposite enantiomer by desymmetrization of the 1,3-diester by lipase-catalysed hydrolysis resulted in rapid hydrolysis to triol under a variety of conditions. 

A broad spectrum of chemical reactions can be catalyzed by enzymes Hydrolysis, esterification, isomerization, addition and elimination, alkylation and dealkylation, halogenation and dehalogenation, and oxidation and reduction. The last reactions are catalyzed by redox enzymes, which are classified as oxidoreductases and divided into four categories according to the oxidant they utilize and the reactions they catalyze 1) dehydrogenases (reductases), 2) oxidases, 3) oxygenases (mono- and dioxygenases), and 4) peroxidases. The latter enzymes have received extensive attention in the last years as bio catalysts for synthetic applications. Peroxidases catalyze the oxidation of aromatic compounds, oxidation of heteroatom compounds, epoxidation, and the enantio-selective reduction of racemic hydroperoxides. In this article, a short overview... 

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