Double bonds epoxidation

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

Steric hindrance can cause polymerization to predominate even if (5) is an aldehyde. With increasing bulk of substituents on one side of a double bond, epoxidation can compete with ozonolysis. 

As with an isolated double bond, epoxide formation in an aromatic ring, i.e., arene oxide formation, can occur mechanistically either by a concerted addition of oxene to form the arene oxide in a single step, pathway 1, or by a stepwise process, pathway 2 (Fig. 4.78). The stepwise process, pathway 2, would involve the initial addition of enzyme-bound Fe03+ to a specific carbon to form a tetrahedral intermediate, electron transfer from the aryl group to heme to form a carbonium ion adjacent to the oxygen adduct followed by... 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

Carbon-carbon double bonds epoxidation, 362-472 nucleophilic addition cychzation, 230, 233, 238-45... 

If bifunctional or potentially bifunctional (e.g., containing a double bond) epoxides are absolutely essential, separate the epoxides (or the epoxide and the double bond) by more than six carbon atoms. 

Carbon-carbon Imnd oxidation is beyond die scope of this work, but is a consequence of initial hydroxylation followed by further metabolism involving other enzyme systems. Many examples of alcohol dehydrogenation and double bond epoxidation have been published previously, and these will not be considered fordier here. 

As shown in Section 4.5.1.3.2.2.1., epoxidation of the exocyclic conjugated double bond in terpenes usually leads to a mixture of diastereomeric epoxides. The situation changes when one moves to terpenes with endocyclic conjugated double bonds. Epoxidation of this class of compounds has been thoroughly studied35 40-42, and it has been shown that such epoxidation, under Weitz-Scheffer conditions, is stereospecific, resulting in the formation of a single epoxide 1-89 and 942. 

J Deprotection was concomitant to C-C double-bond reduction. b Double-bond epoxidation. 

The oxidahon of olefins with aqueous hydrogen peroxide in methanol can produce several products, by different reachon paths double bond epoxidation, allylic H-abstraction, epoxide solvolysis, alcohol and glycol oxidation (Scheme 18.6). Normally, oxide catalysts of Group IV-Vl metals are poorly selechve, because of their acidic properhes, the inhibition they are subject to in aqueous media and homo-lytic side reachons with hydrogen peroxide. The only excephon concerns the epoxidahon of a,(3-unsaturated alcohols and acids, which are able to bind on the... 

A number of excellent reviews with comprehensive coverage on the literature of biooxidations have appeared in journals and books l 8). In this chapter we will only try to highlight some of these biotransformation reactions, in particular hydroxyla-tion of non-activated carbon atoms and double-bond epoxidation reactions. 

It should be noted that the same cytochrome P450 enzyme is able to achieve reactions as different as double-bond epoxidation or heteroatom demethylation. Thus it appears clear that the chemo-, regio- and stereoselectivity of the reaction is a function of the nature and the fit of the substrate, or, more properly, of its transition state with the protein, rather than being governed by enzyme reaction specificity. 

S. Shaik (2002). What factors affect the regiose-lectivity of oxidation by cytochrome P450 A DFT study of allylic hydroxylation and double bond epoxidation in a model reaction. J. Am. Chem. Soc. 124, 11809-11826. 

Figure 9.18 Relative contribution of CYP3A4-catalyzed double bond epoxidation to drug metabolism. For carbamazepine, this represents the major metabolic route, while for tamoxifen CYP3A4-catalyzed epoxidation of the alkene is negligible and the enzyme instead Y-demethylates it.

Formally, this type of transformation can be illustrated by the known syntheses of 4,5-dihydro-oxepin from bicyclo[2.2.0]hex-2-ene <71JA6102, 76JOC2028> including double-bond epoxidation and rearrangement of the intermediate tricycle (Scheme 15). 

A traditional way to epoxidize a,p-unsaturated carbonyl compounds in aqueous meda is the Michael reaction with alkaline hydroperoxides [Ij. Baeyer-Villiger oxidation is a concomitant reaction, making double-bond epoxidation a delicate procedure. 

A general synthesis of terminal acetylenes (278) has been developed by Ikegami et al, whereby the vinylstannane derivatives (277), prepared from the aldehydes (276), are treated with lead tetra-acetate. The method will tolerate a wide range of sensitive functionality, such as double bonds, epoxides, and silyl and THP ethers. 

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