Conjugate nucleophiles

Conjugate Nucleophilic Addition to ,jB-Unsaturated Aldehydes and Ketones... 

Conjugate Nucleophilic Addition to a, /3-Unsaturated Aldehydes and Ketones 727... 

The mechanism of the reaction is thought to involve conjugate nucleophilic addition of the diorganocopper anion, R2C1F, to the enone to give a... 

The following transformation involves a conjugate nucleophilic addition reaction (Section 19.13) followed by an intramolecular nucleophilic acyl substitution reaction (Section 21.2). Show the mechanism. 

Conjugate nucleophilic addition of water to the double bond gives a /3-hydroxyacyl CoA. 

Step 2 of Figure 29.12 Isomerization Citrate, a prochiral tertiary alcohol, is next converted into its isomer, (2, 35)-isocitrate, a chiral secondary alcohol. The isomerization occurs in two steps, both of which are catalyzed by the same aconitase enzyme. The initial step is an ElcB dehydration of a /3-hydroxy acid to give cfs-aconitate, the same sort of reaction that occurs in step 9 of glycolysis (Figure 29.7). The second step is a conjugate nucleophilic addition of water to the C=C bond (Section 19.13). The dehydration of citrate takes place specifically on the pro-R arm—the one derived from oxaloacetate—rather than on the pro-S arm derived from acetyl CoA. 

Steps 7-8 of Figure 29.12 Hydration and Oxidation The final two steps in the citric acid cycle are the conjugate nucleophilic addition of water to fumarate to yield (S)-malate (L-malate) and the oxidation of (S)-malate by NAD+ to give oxaloacetate. The addition is cataiyzed by fumarase and is mechanistically similar to the addition of water to ris-aconitate in step 2. The reaction occurs through an enolate-ion intermediate, which is protonated on the side opposite the OH, leading to a net anti addition. 

Vinyl monomers with electron-withdrawing substituents (EWG) can be polymerized by basic (anionic) catalysts. The chain-carrying step is conjugate nucleophilic addition of an anion to the unsaturated monomer (Section 19.13). 

Conjugate Nucleophilic Addition to cn/3-Llnsaturated Aldehydes and Ketones 725... 

With amino thiols, the amino group can serve as the second nucleophile to induce further conjugate nucleophilic attack to form heterocyclic compounds 614 [273, 274],... 

Examples of such molecules include conjugated nucleophiles such as the enolate anion. Such nucleophiles have potentially two attacking atoms (in the case of the enolate anion, the oxygen or the a-carbon) reaction conditions affect which will be the more prevalent species. Other examples include the cyanide (CN ) and the nitrite (NO2 ) ions. 

The value of AH is large for reactions at the carbon atom (AH 40 kcal./mole), and hence this determines the reactivity at both saturated and unsaturated carbon atoms. (K 1 and K ->- 1 respectively). The contribution of K A H is much smaller for the reaction at phosphorus, hence the first term determines the relative reactivity in reaction (d), (particularly in the non-polar solvents used in such reactions). These examples are sufficient to illustrate the inadequacy of the SHAB rule when conjugated nucleophiles are considered. 

Electrophilic attack will be favoured by metals in low oxidation states, with few or no competitive Tc-acceptor ligands. In such situations, retrodonation from the metal loads the alkene with excessive electron density which is attractive to an external electrophile. As in the case of nucleophilic attack, it may not always be clear, however, whether electrophilic attack has occurred directly at the alkene, or alternatively at the metal centre followed by insertion of the alkene into the metal-electrophile bond (Figure 6.8). This is a real possibility, since the factors that activate the alkene to electrophilic attack are also factors that render the metal centre potentially nucleophilic. Furthermore, the electrophilic conversion of an alkene to a P-functionalized alkyl deprives the metal centre of 2YE this may make it prone to P-M-E(H) elimination (unless blocked by coordination of the conjugate nucleophile), obscuring the mechanistic detail (Figure 2.25). 

In some cases. Phase I metabolites may not be detected, owing to their instability or high chemical reactivity. The latter type are often electrophilic substances, called reactive intermediates, which frequently react non-enzymically as well as enzymically with conjugating nucleophiles to produce a Phase II metabolite. A common example of this type is the oxidative biotransformation of an aromatic ring and conjugation of the resulting arene oxide (epoxide) with the tripeptide glutathione. Detection of metabolites derived from this pathway often points to the formation of precursor reactive electrophilic Phase I metabolites, whose existence is nonetheless only inferred. 

STEPS 7-8 Regeneration of oxaloacetate. Catalyzed by the enzyme fumarase, conjugate nucleophilic addition of water to fumarate yields L-malate in a reaction similar to that of step 2 in the fatty acid jS-oxidation pathway. Oxidation with NAD then gives oxaloacetate in a step catalyzed by malate dehydrogenase, and the citric acid cycle has returned to its starting point, ready to revolve again. 

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