Comparison of the Electrophilic Reactivities of <i>N</i>‐Acylpyridinium Ions and Other Acylating Agents

Nigst, Tobias A.; Mayr, Herbert

doi:10.1002/ejoc.201201540

Cited by 7 publications

(4 citation statements)

References 65 publications

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“…Such participation has been noted in carbocationic oxygen structures; therefore, a similar interaction in this system is reasonable. , This betaine is then rapidly and irreversibly oxidized by 1b to an N-acylpyridinium species, a highly reactive acylating agent. This species is commonly cited as the key intermediate in nucleophilic acyl substitution reactions. − Such a mechanistic path involving oxoammonium salts has not, to the best of our knowledge, been proposed elsewhere in the literature.…”

Section: Resultsmentioning

confidence: 99%

Oxoammonium Salt Oxidations of Alcohols in the Presence of Pyridine Bases

et al. 2014

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Oxoammonium salt oxidations (using 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) of alcohols containing a β-oxygen atom in the presence of pyridine yield dimeric esters, while in the presence of 2,6-lutidine the product is a simple aldehyde. The formation of a betaine between pyridine and an aldehyde is presented to explain this disparity in reactivity. The betaine is oxidized by the oxoammonium salt to give an N-acylpyridinium ion that serves as an acylating agent for ester formation. Steric effects deter the formation of such a betaine with 2,6-disubstituted pyridines. A series of alcohols containing a β-oxygen substituent were oxidized to aldehydes in the presence of 2,6-lutidine, and a short study of the relative reactivity of various alcohols is given. An overall mechanism for oxoammonium cation oxidations is suggested, premised on nucleophilic additions to the oxygen atom of the positively charged nitrogen-oxygen double bond. Possible mechanisms for both dimeric oxidations and simple oxidations are given.

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Section: Resultsmentioning

confidence: 99%

Oxoammonium Salt Oxidations of Alcohols in the Presence of Pyridine Bases

et al. 2014

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“…These latter intermediates are reacted in the second model reaction with benzylamine 8 . The kinetics of both model reactions were followed by UV/Vis spectrophotometry under first‐order conditions by monitoring the absorbances of the N ‐benzoylpyridinium chlorides 7a – h as described previously 5b,5c. For all reactions, monoexponential increases or decays of the absorbances of 7a – h were observed and the first‐order rate constants k obs were obtained by least‐squares fitting of the exponential function A = A 0 (1 – e – k (obs) t ) + C or A = A 0 e – k (obs) t + C to the time‐dependent absorbances.…”

Section: Resultsmentioning

confidence: 99%

Inductive Effects through Alkyl Groups – How Long is Long Enough?

Tandon¹,

Nigst²,

Zipse³

2013

Eur J Org Chem

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“…Amines 2 – 7 employed in this study cover a relatively small range of nucleophilicity in water (12.99< N <14.28), which corresponds to a reactivity difference of only a factor of 20 towards a certain electrophile (if differences in s N are neglected). Because anilines attack at C3, whereas aliphatic amines attack at C1, the rate constants for nucleophilic attack at 1 are additionally influenced to a different extent by anomeric effects …”

Section: Resultsmentioning

confidence: 99%

Kinetic and Theoretical Studies of Beta‐Lactone Reactivity—A Quantitative Scale for Biological Application

et al. 2015

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Natural products comprise a rich source for bioactive molecules with medicinal relevance. Many of these contain electrophilic scaffolds that bind conserved enzyme active sites covalently. Prominent examples include beta‐lactams and beta‐lactones, which specifically acylate serine residues in diverse peptidases. Although these scaffolds appear similar, their bioactivities and corresponding protein targets vary. To quantify and dissect these differences in bioactivities, the kinetics of the reactions of beta‐butyrolactone with a set of reference amines in buffered aqueous solution at 37 °C have been analyzed. Different product ratios of C1 versus C3 attack on the beta‐butyrolactone have been observed, depending on the aliphatic or aromatic nature of the standard amine used. Quantum mechanics/molecular mechanics (QM/MM) calculations reveal that a H3O+ molecule has a crucial role in stabilizing C3 attack by aniline, through coordination of the lactone ring oxygen. In agreement with their weak proteome reactivity, monocyclic beta‐lactams did not react with the set of standard nucleophiles studied herein. Bicyclic beta‐lactams, however, exhibited a lower activation barrier, and thus, reacted with standard nucleophiles. This study represents a starting point for semiquantitative reactivity scales for natural products, which, in analogy to chemical reactivity scales, will provide predictions for electrophilic modifications in biological systems.

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Comparison of the Electrophilic Reactivities of N‐Acylpyridinium Ions and Other Acylating Agents

Cited by 7 publications

References 65 publications

Oxoammonium Salt Oxidations of Alcohols in the Presence of Pyridine Bases

Oxoammonium Salt Oxidations of Alcohols in the Presence of Pyridine Bases

Inductive Effects through Alkyl Groups – How Long is Long Enough?

Kinetic and Theoretical Studies of Beta‐Lactone Reactivity—A Quantitative Scale for Biological Application

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