Trapped acylation

N-Carbobenzoxy-L-alanine-/>-nitrophenyl ester is a specific substrate for elastase in which the rate-limiting step is deacylation, that is, hydrolysis of the acyl-enzyme intermediate. In 70% methanol over a reasonable temperature range the energy of activation of the turnover reaction, that is, deacylation, is 15.4 kcal mol. In the pH 6-7 region in this cryoprotective solvent, the turnover reacdon can be made negligibly slow at temperatures of -50 C or below. Under such conditions/i-nitro-phenol is released concurrent to acyl enzyme formation in a 1 1 stoichiometry with active enzyme in the presence of excess substrate. In other words, even at low temperatures, the acylation rate is much faster than deacylation and the acyl enzyme will accumulate on the enzyme. The rate of acyl-enzyme formation can be monitored by following the rate of p-nitrophenol release, and thus the concentration of trapped acyl enzyme may be determined. This calculadon has been carried out and... 

Conditions have been defined for the preparation of acylsilanes by trapping acyl anions, formed from alkyl-lithium reagents and carbon monoxide, at low temperature with trimethylsilyl chloride. Acylsilanes have found use as hindered aldehydes, improving selectivity in the addition of ambident nucleophiles. ... 

Alkyl- and arylmercury(II) halides are used for the ketone formation[402]. When active methylene compounds. such as /f-keto esters or malonates are used instead of alcohols, acylated / -keto esters and malonates 546 are produced, For this reaction, dppf is a good ligand[403]. The intramolecular version of the reaction proceeds by trapping the acylpalladium intermediate with eno-late to give five- and six-membered rings smoothly. Formation of 547 by intramolecular trapping with malonate is an example[404]. 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

Dihydropyrroles (2-pyrrolines 231) are in tautomeric equilibrium with the corresponding 1-pyrrolines (232) the latter readily form trimers of type (233). The trimer dissociates in boiling THF to 1-pyrroline (232) trimerization is relatively slow at -78 °C and the monomer can be trapped by reaction with acylating reagents to give (V-acyl-2-pyrrolines (81JOC4791). 

However, the thermolysis of diacylfuroxans (429) yielded two types of nitrile Af-oxides. An uncrowded diacylfuroxan such as (429a) rearranged to the a- acyloximino nitrile A-oxide (430) the diacylfuroxan with bulky substituents such as in (429b) gave rise to the half molecule acyl nitrile Af-oxide (431). Both types of nitrile Af-oxides (431) and (430) have been trapped with DMAD and hexafluoro-2-butyne to give isoxazoles in good yield. These reactions are shown in Scheme 97. 

V-Acylation of oxaziridine (54) is of more importance, yielding 2-acyloxaziridines which were unaccessible otherwise until recently. Oxaziridines (54) derived from cyclohexanone, butanone or benzaldehyde are acylated readily by acetic anhydride, acid chlorides or isocyanates. Oxaziridines from aliphatic aldehydes, too unstable to be isolated, may be trapped in situ by benzoylation (67CB2593). 

The submitters have shown that these reactions proceed by dehydro-chlorination of the acid chloride to the ketene, which is then trapped by reaction with the phosphorane. The resulting betaine decomposes to the allenic ester via an oxaphosphetane. In contrast, the reaction of acid chlorides with 2 equivalents of phosphoranes involves initial acylation of the phosphorane followed by proton elimination from the phosphonium salt. ... 

Bischler-Napieralski reactions of N-acyl tryptamine derivatives 16 are believed to proceed via a related mechanism involving the initial formation of intermediate spiroindolenines (17) that rearrange to the observed 2-carboline products (18). The presence of these intermediates has been inferred by the observation of dimerized products that are presumably formed by the intermolecular trapping of the spiroindolenine by unreacted indole present in the reaction mixture." ... 

Acyl azides can undergo photolytic cleavage and rearrangement upon irradiation at room temperature or below. In that case acyl nitrenes 8 have been identified by trapping reactions and might be reactive intermediates in the photo Curtius rearrangement. However there is also evidence that the formation of isocyanates upon irradiation proceeds by a concerted reaction as in the case of the thermal procedure, and that the acyl nitrenes are formed by an alternative and competing pathway " ... 

Besides protonation, the dianion can be trapped by methylation. silylation and acylation, always leading to the corresponding 1,4-dihydro derivative very cleanly at low temperature. 

As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

As to the question of intra- or intermolecularity of the rearrangement there are three opinions, one which states that the reaction is completely intermolecular148, another supports a concurrent intra- and intermolecular mechanism149, whilst a third claims that the reaction is completely intramolecular150. Evidence for the intermolecular mechanism is based on trapping experiments such as the reaction of meta-tolyl acetate (CVIII) in the presence of we/a-chlorobenzoyl chloride (CIX) when the acylation product (CX) is formed rather than the products of... 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

If k2 > kj, the glycosyl-enzyme intermediate will accumulate, and may be trapped by the rapid denaturation of the enzyme in the presence of (saturating) amounts of substrate. With -glucoside Aj from Asp. wentii and 4-nitrophenyl [ C]-2-deoxy-) -D-irra />jo-hexopyranoside, it was possible to identify the intermediate as a glycosyl ester (acylal) of 2-deoxy-D-arabino-hexose bound to the same aspartate residue that had previously been labeled with the active-site-directed inhibitor conduritol B epoxide and with D-glucal." This constituted an important proof that the carboxylate reacting with the epoxide is directly involved in catalysis. 

This enolate can then react with a plethora of electrophiles, setting a new stereocenter by a diastereoface-selective reaction. The simplest electrophile to trap enolate 71 is H" ", which can, for example, originate from methanol [89] or diphenyl acetaldehyde (as a readily enolizable aldehyde) [90] leading to the acy-lated catalyst species (Fig. 38). The free catalyst is regenerated by acyl-group transfer to methanol(ate) or the aldehyde-derived enolate, producing methyl or enolesters 72/73 in good yields and enantioselectivities. 

Hydroxyenones have also been used in catalytic amide formation, although 1,2,4-triazole is required as a co-catalyst. Assumed protonation of the Breslow intermediate and tautomerisation generates an acylazolium intermediate, which is trapped by triazole, releasing the NHC and generating the acyltriazole 60 that is the active acylating agent for the amine (Scheme 12.11) [16]. 

In Entry 13, the dioxinone ring undergoes thermal decomposition to an acyl ketene that is trapped by the solvent methanol. The resulting (3-keto-y,8-enoate ester then undergoes stereoselective cyclization. The stereoselectivity is controlled by the preference for pseudoequatorial conformations of the C(6) and C(9) substituents. 

The main synthetic application of the Wolff rearrangement is for the one-carbon homologation of carboxylic acids.242 In this procedure, a diazomethyl ketone is synthesized from an acyl chloride. The rearrangement is then carried out in a nucleophilic solvent that traps the ketene to form a carboxylic acid (in water) or an ester (in alcohols). Silver oxide is often used as a catalyst, since it seems to promote the rearrangement over carbene formation.243... 

All these 3,4-dihydro-2H-1 -benzopyran-2-ones 17 and 18 are substrates of class A and class C (3-lactamases. They are thus the first 8-lactones that are hydrolyzed by [3-lactamases. The kcat values for these substrates are generally smaller than those of the analogous acyclic phenaceturates suggesting that the tethered leaving group obstructs the attack of water on the acyl-enzyme. Despite the apparent advantage of the long-lived acyl-enzymes, the irreversible inhibition by the functionalized compounds is no better than that of acyclic molecules 16. Thus, even the tethered QM cannot efficiently trap a second nucleophile at the [3-lactamase active site, at least as placed as dictated by the structure of compounds 18.70... 

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