Concerted acyl transfer

Sn2 and related concerted reactions (concerted phosphoryl transfer, concerted acyl transfer) have proven difficult to treat by NBT. The difficulty here is that... 

For acyl transfer, phosphoryl transfer, and sulfonyl transfer, the primary kind of evidence in favor of concerted mechanisms for some reactions is a linear Bronsted plot of log k versus for a range of nucleophiles, spanning p/ir/ = - p r s = 0, coupled... 

T.P. Curran et al., Structure-Reactivity Studies on the Equilibrium Reaction Between Phenolate Ions and 2-Aryloxazolin-5-ones Data Consistent with a Concerted Acyl-Group Transfer Mechanism, J. Am. Chem. Soc., 1980,102, 6828. 

In non-polar solvents and at high concentration, a concerted mechanism is hypothesized [13]. This mechanism involves a tri-molecular reaction among the isocyanide, the carboxylic acid, and the carbonyl in a sequence of nucleophilic additions. The transition state (below) is depicted as a 5-memhered ring with partial covalent or double bonding. The second step of the Passerini reaction is an acyl transfer to the neighboring hydroxyl group, 2. There is support for this proposed... 

Evidence has been accumulated for the existence of a tetrahedral intermediate and a concerted proton transfer mechanism from Ser-195 to His-57 and from His-57 to Asp-102 during the hydrolysis of p-nitroanilide peptide substrates catalyzed by a serine protease from Myxobacter 495 named a-lytic protease. It possesses only one histidine residue (82,83). The rate-limiting step of the hydrolysis is the decomposition of the tetrahedral intermediate to acyl-enzyme and p-nitroaniline. The experimental results support the view that the two proton transfers which occur during this step take place in a concerted, not stepwise, maimer. 

Figure 3. Mitochondrial fatty acid oxidation. Long-chain fatty acids are converted to their CoA-esters as described in the text, and their fatty-acyl-groups transferred to CoA in the matrix by the concerted action of CPT 1, the acylcarnitine/carnitine exchange carrier and CPT (A) as described in the text. Medium-chain and short-chain fatty acids (Cg or less) diffuse directly into the matrix where they are converted to their acyl-CoA esters by a acyl-CoA synthase. The mechanism of p-oxidation is shown below (B). Each cycle of P-oxidation removes -CH2-CH2- as an acetyl unit until the fatty acids are completely converted to acetyl-CoA. The enzymes catalyzing each stage of P-oxidation have different but overlapping specificities. In muscle mitochondria, most acetyl-CoA is oxidized to CO2 and H2O by the citrate cycle (Figure 4) some is converted to acylcamitine by carnitine acetyltransferase (associated with the inner face of the inner membrane) and exported from the matrix. Some acetyl-CoA (if in excess) is hydrolyzed to acetate and CoASH by acetyl-CoA hydrolase in the matrix. Enzymes ...

Concerted mechanisms are possible for acyl, phosphoryl, and sulfonyl transfer. By thinking about the stepwise limits for each possible concerted process, one can, even with quite crude calculations, make some judgment about the feasibility of the concerted process. This area of chemistry is as yet unsettled and will see some changes in what is now generally accepted. 

A cis-coordinating ligand is apparently required to bind and activate MeOH so that a methoxy group is transferred to the polyketone chain and a hydride remains on palladium. Two mechanisms are possible for this reaction (i) nucleophilic attack by the oxygen at the acyl carbonyl with concerted formation of Pd-H (ii) formation of a Pd(acyl) (methoxy) complex and H, followed by reductive elimination and subsequent proton attack on a Pd center. No experimental evidence favoring either mechanism in ethene/CO copolymerisation has been provided so far. 

The detailed mechanism of the formation of acyl cations is not yet clear. It seems certain that the leaving group is a neutral water or alcohol molecule, and thus that a proton transfer is involved. It is not possible at this time, however. to distinguish between a pre-equilibrium formation of the tautomeric form protonated on the alkyl-oxygen, which would then cleave in the ratedetermining step (route A)14 28 and the similar mechanism in which the proton transfer and cleavage reactions are concerted (route B)14. 

Several detailed reaction paths have been proposed for the addition process (117). The most powerful acylating agent present is the proton-ated lactam (XXIX), p. 437, and the strongest nucleophile is the neutral amine group so that the fastest addition should be reaction (92). Since the equilibrium (91) results in a low concentration of lactam cations and neutral amine groups, most amine groups are present as ammonium ions or undissociated salt (—COONH3—). Therefore, a two-step or concerted mechanism could also be operative in which the iVI-protonation of the lactam by an ammonium ion is accompanied or followed by acylation of the amine and intramolecular proton transfer [220], viz. 

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