Alkoxide leaving group

Tire mechanism of the Claisen condensation is similar to that of the aldol condensation and involves the nucleophilic addition of an ester enolate ion to the carbonyl group of a second ester molecule. The only difference between the aldol condensation of an aldeiwde or ketone and the Claisen condensation of an ester involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is protonated to give an alcohol product—exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution product—exactly the behavior previously seen for esters (Section 21.6). The mechanism of the Claisen condensation reaction is shown in Figure 23.5. 

The nature of the reaction catalyzed by PLC i( in which phosphatidylcholine is split into diacylglycerol and phosphorylcholine (Fig. 11) requires two proton transfer steps The first is the deprotonation of an active site water to generate the attacking hydroxide nucleophile, and the second is the protonation of the alkoxide leaving group. Although analyses of the X-ray structures of PLCSc and... 

Zr L = a bidentate hydroxypyranonate or hydroxypyridinonate ligand and X is a halide or alkoxide leaving group (264,265). Replacement of chloride by thiocyanate, pyrazine, or water (in acetonitrile solution) in 3-hydroxy-4-pyranonate or 3-hydroxy-4-pyr-idinonate tin(IV) complexes in all cases follows a two-term rate law of the type... 

A typical role for the histidine imidazole ring is shown below, in the enzyme mechanism for a general base-catalysed hydrolysis of an ester. The imidazole nitrogen acts as a base to remove a proton from water, generating hydroxide that attacks the carbonyl. Subsequently, the alkoxide leaving group is reprotonated by the imidazolium... 

In examining the mechanism leading to the nucleophile-mediated conversion of an ester to a ketone, initial addition of a nucleophile to the carbonyl results in formation of a hemi-acetal intermediate. Subsequent collapse of the hemiacetal intermediate liberates a ketone and an alkoxide leaving group. This mechanistic sequence, illustrated in Scheme 7.19... 

Normal, acyclic esters are different their alkoxide leaving groups can leave, and the result is a different sort of reaction, which you will meet in the next chapter. 

In a competition experiment between chiral N-sulfinyl oxazolidinone and Andersen s menthyl sulfinate ester, it has been shown that the former is at least two orders of magnitude more reactive than the latter. This finding is being used to avoid some of the problems involved in sulfinate esters, related to the nature of the alkoxide leaving group in the nucleophilic substitution. 

This first product is a kind of tetrahedral intermediate and eliminates the alkoxide leaving group, - u may object that is more stable than 0 but the Al-O bond is stronger than the Al-S bond cd that decides which group leaves. 

The model studies imply mechanistic paths in the enzyme that would accommodate much of the rate enhancement and are consistent with the observations above. These are displayed in Scheme 14. The phosphate ester binds to both Zn ions, which activates the P center to attack by the coordinated deprotonated serine nucleophile. Binding the serine hydroxyl to the metal ion enhances its deprotonation and gives an efficient intramolecular nucleophile, as we have seen from model studies. Such a process would also be assisted by an enzyme base to remove the proton intramolecularly and protonation of the alkoxide leaving group by an enzyme acid would be helpful. In addition, inversion of configuration would ensue at the P center. A coordinated water at the second Zn + ion could then be deprotonated to function as the intramolecular nucleophile which eliminates the serine alkoxide ion. Both aspects would be assisted by an enzyme base and acid, respectively. The stereochemistry of the processes would lead to inversion and therefore to net retention overall consistent with the expectation from the experiments by Jones et al. (89). 

Metal species have often proved to be essential components in many DNA and RNA cleavage systems. Effective metal ion-centred catalytic systems for the hydrolysis of phospho-diester bonds have been proposed which employ metal ions both to deliver a hydroxide ion in a direct in-line displacement and to complex the incipient alkoxide leaving group. This type... 

In the associative model (Fig. 4.3) a nucleophile attacks the phosphate centre to produce an unstable five coordinate oxy-phosphorane species in the rate-limiting step. The oxyphosphorane then decays, losing an alkoxide leaving group. Unlike the dissociative pathway, the rate of reaction in the associative pathway is dependent on the... 

Somewhat between diastereoselective and enantioselective approaches is the Cram s synthesis involving the oxazolines with chiral alkoxide leaving groups [26]. In this manner, bromine in oxazoline 596 was substituted with sodium alkoxides, derived from readily available natural alcohols such as menthol (597), fenchyl alcohol (598), bomeol (599), quinine (600), and quinidine (601) to give the respective chiral oxazolines 602-606, Scheme 10. The Meyers reaction of oxazolines 602-606 and 1-naphthylmagnesium bromide (608) was effected at low temperatures (-42 °C) affording the expected biaryl 609 with respective chiral induction. 

The most difficult step in the catalytic cycle is the first an oxidative insertion of the palladium catalyst a into the C—O bond of the carboxylic ester 3c, leading to the acyl complex b. This was unprecedented even for activated esters, and is increasingly endothermic with increasing basicity of the alkoxide leaving group. In analogy to the de Vries process, an... 

Cu-catalysed substitution of allyl ethers (alkoxide leaving group). Very similar synthetically useful reactions are exhibited by a-ethylenic acetals and ortho-esters. ... 

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