Hydrolysis of epoxide

A complementary method one that gives anti hydroxylation of alkenes by way of the hydrolysis of epoxides will be described m Section 16 13... 

Epoxides are cleaved by treatment with acid just as other ethers are, but under much milder conditions because of ring strain. As we saw in Section 7.8, dilute aqueous acid at room temperature is sufficient to cause the hydrolysis of epoxides to 1,2-diols, also called vicinal glycols. (The word vicinal means "adjacent/ and a glycol is a diol.) The epoxide cleavage takes place by SK2-like backside attack of a nucleophile on the protonated epoxide, giving a trans- 1,2-dio) as product. 

Figure 5.25 Enantioconvergent hydrolysis of epoxides (35) to the corresponding diols (36) using mung bean epoxide hydrolase.

An enantioconvergent transformation leads to a single enantiomeric product from a racemate [51]. Each enantiomer is transformed via independent pathways by the same catalyst or by two different catalysts (Figure 6.6). For example, the hydrolysis of epoxides may proceed with high regio- and stereoselectivity vdth inversion or retention of configuration. Several enantioconvergent transformations of epoxides are reported in the last section of this chapter. 

The hydrolysis of epoxides is a eonvenient method for the preparation of vic-diols. The reaction is catalyzed by acids or bases (see discussion of the mechanism on p. 462). Among acid catalysts the reagent of choice is perchloric acid, since side... 

Hydrolysis of epoxides Coupling of alcohols Hydroxylation of alkenes... 

Figure 5 Time-resolved IR thermographic imaging of the enantioselective hydrolysis of epoxide (48c) catalyzed by >S,//-(50a-c) after (a) 0, (b) 2.5, (c) 4, (d) 5, (e) 7, (g) 8, (h) 15, and (i) 32 min. In (f) the same images is shown as in (e), except that the temperature window ranges over 10 K. The bar on the far right of each image is the temperature/colour key of the temperature window used (°C).SS...

Hydrolysis of epoxides and arene oxides Hydrolysis of amides and esters Hydrolysis of glycosides... 

As with several other functional groups considered earlier, epoxides are most commonly found in alkaloid metabolites rather than the original compound. These epoxides may arise via oxidation of alkenes or aromatic hydrocarbons. Epoxide hydrolase catalyzes hydrolysis of epoxides to the more hydrophilic diol. As seen in Scheme 6, this is usually a stereospecific reaction that always yields a... 

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... 

Scheme 7. Hydrolysis of epoxides proceeding with retention or inversion of configuration...

One of the first applications of the microbial hydrolysis of epoxides for the synthesis of a bioactive compound is based on the resolution of a 2,3-disub-stituted oxirane having a cis-configuration (Scheme 14). Thus, by using an enzyme preparation derived from Pseudomonas sp., the (91 ,10S)-enantiomer was hydrolyzed in a frans-specific fashion (i.e. via inversion of configuration at C-10) yielding the 9R,10R)-threo-diol. The remaining (9S,101 )-epoxide was converted into (-1-)-dispar lure, the sex pheromone of the gypsy moth in >95% ee [101]. 

Kim, G. J. Park D. W. (2000) The catalytie aetivity of new ehiral salen complexes immobilized on MCM-41 in the asymmetrie hydrolysis of epoxides to diols., Catalysis Today 63 537-547. 

A simple example of a ring-opening substitution reaction is the acid-catalysed hydrolysis of epoxides. In the example shown, protonation of the epoxide oxygen improves the leaving group, and an Sn2 reaction may then proceed using water as the nucleophile. Three-membered rings must of necessity... 

The first two reported studies concern the epoxide hydrolase from Aspergillus niger (ANEH) 95,96). The enzyme had previously been purified to homogeneity, the gene cloned and expressed in E. coli, and the catalytic hydrolysis of epoxides optimized to high substrate concentrations. Initial attempts were made to enhance the enantioselectivity of the ANEH-catalyzed hydrolytic kinetic resolution of glycidyl phenyl ether (rac-33). The WT leads to an E value of only 4.6 in favor of (5)-34 96). 

Some interesting work has been published dealing with the metal ion-promoted hydrolysis of epoxides. Hanzlik and Michaely499 first observed that in the presence of copper(II) the hydration of 2-pyridyloxirane (153) is accelerated by a factor of 1.8 x 104 and its reaction with Cl-, Br and MeO becomes 100% regiospecific for /3-attack. The magnitude of the catalytic effect decreases in the order Cun> Con>Zn11 Mn". The pH rate profile for the copper(II)-catalyzed reaction is a bell-shaped curve with a maximum at ca. pH 5. 

The hydrolysis of epoxides can occur through neutral, acid-, or base- mediated reactions. Because the add and neutral processes generally dominate over the range of environmental pH, the base-mediated reaction often can be ignored. The products of hydrolysis are usually the corresponding diol and sometimes rearranged products (Equation (12)). 

It is interesting to note that acyloxyepoxides can be converted to a-hydroxyke-tones with retention or inversion of configuration at C-a, depending on the reaction conditions chosen. As shown in Scheme 10.5, hydrolysis of epoxide 20a leads... 

In Water In Section 8-13 we saw that acid-catalyzed hydrolysis of epoxides gives glycols with anti stereochemistry. The mechanism of this hydrolysis involves protonation of oxygen (forming a good leaving group), followed by Sn2 attack by water. Anti stereochemistry results from the back-side attack of water on the proto-nated epoxide. 

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