Hydrolysis of enol esters

Hydrolysis of Enol Esters. Enzyme-mediated enantioface-differentiating hydrolysis of enol esters is an original method for generating optically active a-substituted ketones (84—86). If the protonation of a double bond occurs from one side with the simultaneous elimination of the acyl group (Fig. 3), then the optically active ketone should be produced. Indeed, the incubation of l-acetoxy-2-methylcyclohexene [1196-73-2] (68) with Pichia... 

The acid-catalyzed hydrolysis of enol esters (RCOOCR =CR) can take place either by the normal Aac2 mechanism or by a mechanism involving initial protonation on the double-bond carbon, similar to the mechanism for the hydrolysis of enol ethers given in 10-6, ° depending on reaction conditions. In either case, the products are the carboxylic acid RCOOH and the aldehyde or ketone R2" CHCOR. ... 

Hydrolysis of gem-dihalides 0-4 Hydrolysis of enol esters of inorganic acids... 

Hydrolysis of enol esters 0-83 Reduction of acyl halides 0-84 Reduction of carboxylic acids, esters, or anhydrides 0-85 Reduction of amides 0-95 Alkylation and hydrolysis of imines, alkylation of aldehydes 0-97 Alkylation and hydrolysis of dithi-anes... 

Hydrolysis of enol esters 0-76 Reduction of halo ketones 0-78 Reduction of hydroxy ketones 0-82 Reduction of diazo ketones or nitro ketones... 

One of the first enantiofacially selective processes catalyzed by an antibody involved the hydrolysis of enol esters [15]. Hapten 4 was used to elicit antibodies for the hydrolysis of enol ester 5 (Scheme 2). This reaction proceeds via a putative enolate intermediate 6 and the key asymmetric induction step involves antibody-catalyzed enantiofacial protonation of one of the prochiral faces of 6. Antibody 27B5 catalyzes the hydrolysis of the enol ester 5 with a turnover number k apO.Ol min corresponding to an enhancement ratio (ER), k j/non-cata-lyzed rate (kuncat) provides an optically enriched mixture of the R-ke-tone product 7 (42% ee). Although the asymmetric induction is lower than that achievable by natural enzymes for certain substrates [ 16], it was a successful demonstration, at entry level, for catalytic antibodies and asymmetric induction. 

Tokunaga and coworkers reported the enantioselective hydrolysis of enol esters (111) in the presence of catalyst 8b under phase-transfer conditions with aqueous KOH. The proposed mechanism of this reaction has the protonation of the ammonium-enolate ionic complex as the enantioselective step. Their achievement of the first nonbiomimetic asymmetric hydrolysis of esters catalysed by organocatalysts with high catalytic efficiency in buffer-free conditions has considerable potential to replace enzymatic resolutions in industrial processes (Scheme 16.41). ... 

The acylation of enamino ketones can take place on oxygen or on carbon. While reaction at nitrogen is a possibility, the N-acylated products are themselves acylating agents, and further reaction normally takes place. The first reported acylation of enamino ketones (72) was that of 129, prepared by acylation of the enamine (113), which was shown to have undergone O acylation because on mild hydrolysis the enol ester (130) could be isolated. A similar reaction took place with other aliphatic acid chlorides (80) and with dibasic acid chlorides [e.g., with succinyl chloride to give 118 above]. 

Hydrolysis of enol ethers, acetals, or ortho esters... 

The very important type of reaction known as enolization is catalyzed by both acids and bases. Also, the hydrolysis of an ester,... 

This is another exampie of substrate-level phosphorylation, but differs from the earlier example that involved hydrolysis of a mixed anhydride. Here, we have merely the hydrolysis of an ester, and thus a much lower release of energy. In fact, with 1,3-diphosphoglycerate, we specifically noted the difference in reactivity between the anhydride and ester groups. So how can this reaction lead to ATP synthesis The answer lies in the stability of the hydrolysis product, enolpyruvic acid. Once formed, this enol is rapidly isomerized to its keto tautomer, pyruvic acid, with the equilibrium heavily favouring the keto tautomer (see Section 10.1). The driving force for the substrate-level phosphorylation reaction is actually the position of equilibrium in the subsequent tautomerization. 

In this case, we formulate the Claisen reaction between two ester molecules as enolate anion formation, nucleophilic attack, then loss of the leaving group. Now reverse it. Use hydroxide as the nucleophile to attack the ketone carbonyl, then expel the enolate anion as the leaving group. All that remains is protonation of the enolate anion, and base hydrolysis of its ester function. 

The mechanistic steps can be deduced by inspection of structures and conditions. Enolate anion formation from diethyl malonate under basic conditions is indicated, and that this must attack the epoxide in an Sn2 reaction is implicated by the addition of the malonate moiety and disappearance of the epoxide. The subsequent ring formation follows logically from the addition anion, and is analogous to base hydrolysis of an ester. Ester hydrolysis followed by decarboxylation of the P-keto acid is then implicated by the acidic conditions and structural relationships. 

Hydrolysis of alkyl halides 0-4 Hydrolysis of inorganic esters 0-6 Hydrolysis of enol ethers, acetals, or ortho esters... 

Hydrolysis of both ester groups is followed, by decarboxylation of one of them to give the enol of the final product. 

A less common approach to the synthesis of phosphinates is the reaction of electrophilic phosphonates with carbon nucleophiles such as Grignard reagents or lithium enolates. For example, the phosphinic acid analogue 71 of the amino acid statine was synthesized by displacement of tert-butyl lithioacetate on a 5-phenyl phosphonothioate 70 (Scheme 23)d104l The racemic diastereomers of the 5-phenyl phosphonothioate were obtained in pure form, and the displacement of the phenylsulfanyl moiety was found to be stereospecific, although the stereocenter at phosphorus would later be lost on hydrolysis of the ester. A similar displacement reaction has been described using the p h osp h on och I ori d ate.1711... 

Hydrolysis of F.not Esters. En/yme-mcdiaied enaniiofacc-diffcrentia-ting hydrolysis ol enol esters is an original method for generating optically active cr-suhsiitutcd ketones. 

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