Epoxides acidic activation

Titanium-IV compounds with their Lewis acid activity may catalyze an interfering rearrangement of the starting allylic alcohol or the epoxy alcohol formed. In order to avoid such side-reactions, the epoxidation is usually carried out at room temperature or below. 

The Feltzin mechanism 73) takes account of the presence of proton donors at the beginning of copolymerization. However, initiation probably proceeds in two ways 74) and depends on the type of the proton donor and its concentration in the copolymerization mixture. If HA in Eq. (45) is alcohol, phenol or moisture, initiation occurs according to Eq. (46), i.e. through interaction with the anhydride yielding an ammonium salt of the monoester. The formation of monoesters as primary active centres accounts here for the lower cocatalytic effect of phenols as compared with alcohols. If the proton donor is a carboxylic acid, activation of the tertiary amine (Eq. (63)) is followed by reaction with the epoxide according to Eq. (76)74. ... 

Other enzymes associated with xenobiotic metabolism are also altered by dietary protein levels. Epoxide hydratase can hydrolyze various epoxides and appears to be important in decreasing their toxicity and carcinogenicity, although it is involved in the metabolic activation of certain carcinogens. Low dietary protein depresses epoxide hydratase activity in our dietary model (8). This may indicate both a decreased ability to detoxify epoxides and a decrease in metabolic activation of specific carcinogens, such as benzo(a)pyrene. Woodcock and Wood (19) have reported that dietary protein deficiency increases the activity of uridine diphosphate glucuronic acid (UDP6) transferase activity. This indicates that... 

In addition to the above hydrolysis reactions, dinuclear approach to providing joint Lewis acid activation and nucleophile activation has been applied to other organic reactions (Figure 6.14) including stereoselective ring-opening of epoxides (18) [65, 66], stereoselective aldol condensation (19) [67, 68], and stereoselective reduction (20) reactions [69]. 

Methyl esters prepared from undecylenic acid and containing an episulfide group were tested as inhibitors of JH III epoxide hydrolase activity to evaluate its biological role in insects <2005MI140>. 

The mechanistic aspects of this Lewis acid promoted reaction have been examined by low temperature NMR studies, and reaction of the lithium alkynides with the Lewis acid activated epoxides is indicated. The order of the addition of the reagents does not affect the product yields provided that the reaction is carried out at -78 C addition of BF3-OEt2 to a mixture of an epoxide and an alkynide or addition of an epoxide to a mixture of an alkynide and BF3-OEt2 are both possible. The transmetalation between RLi and BF3 which produces unreactive organoboron compounds is shown to be very slow at this temperature. - ... 

In each case, note that the attack of the nucleophile is from the opposite side to the bridging oxygen atom, and so the resultant addition of the two hydroxyl units is anti. Under basic conditions, the nucleophile is a hydroxide anion, and the resultant anion gains a proton from the solvent. Under acidic conditions, the epoxide is activated by protonation of the epoxide oxygen. This in turn makes the epoxide carbons more electrophilic and so more susceptible to attack by a nucleophile, namely in this case a water molecule. After the nucleophilic attack, the resultant adduct loses a proton to the solvent, and so yields the desired product. Overall, there has been an anti-addition of the symmetrical molecule H202. 

Intramolecular vinylation of Lewis acid-activated carbon electrophiles with vinylsilanes is very valuable for construction of carbocycles and oxygen- or nitrogen-containing heterocycles [4]. In contrast, fhere are few reports of intermolecular vinylation [525]. Schaumann et al. recently reported TiCl4-promoted vinylation of epoxides wifh l,3-bis(trimethylsilyl)-l-propene (Scheme 10.200) [526]. 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

Acidic activation of the epoxide can be achieved either by Brpnsted-acidic catalysis via addition of a proton to the epoxide oxygen or by Lewis-acidic catalysis via coordination of the epoxide oxygen to a multivalent cation. In basic catalysis one of the epoxide carbons is attacked by a nucleophile. Only acid-catalyzed ringopening leads to an intermediate carbocation (3) which can easily result in the mi-... 

Comparison of proposed ensembles for (c) asymmetric epoxidation and (d) Lewis-acid activation of epoxides for nucleophilic attack. 

Preparations of purified phenobarbital-induced cytochrome P-450 (P-450 PB-Bj and P-450 LMj from rat and rabbit liver, respectively [377,399]), metabolised arachidonic acid by epoxidation of each of the four double bonds [397]. Using such preparations with negligible epoxide hydrolase activity, the four epoxides could be isolated [397,400]. The monooxygenase metabolism of arachidonic acid is summarised in Fig. 10. In the presence of soluble or microsomal epoxide hydrolase, the corresponding 1,2-diols are rapidly formed. Liver and renal cortical microsomes may further metabohse the 1,2-diols by wl- and w2-oxidation to yield a family of tri hydroxy compounds and other metabolites, with polarity similar to those of many prostaglandins [396,401]. 

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