The observation of zwitterions in the thermal reaction of ketenes with carbon-nitrogen double bonds

Pacansky, J.; Chang, J. S.; Brown, Daniel W.; Schwarz, W.

doi:10.1021/jo00132a065

Cited by 69 publications

(18 citation statements)

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“…In these cases, the aromaticity of the heterocycles precluded the evolution of these zwitterions to the -lactam products. However, when electron-withdrawing groups are present in the imidazole ring, new IR bands observed at 1770 cm -1 were attributed 21 to the formation of -lactams 3c (Scheme The zwitterionic intermediates INTd and INTf depicted in Scheme 4 formed the corresponding -lactams 3c,d. The formation of the -lactam ring should take place via conrotatory electrocyclization of the zwitterionic intermediate (Scheme 5).…”

Section: Mechanism Of the Reaction Between Imines And Ketenes: Concermentioning

confidence: 99%

The Mechanism of the Ketene−Imine (Staudinger) Reaction in Its Centennial: Still an Unsolved Problem?

2008

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[Reaction: see text]. Although Staudinger reported the reaction between ketenes and imines 100 years ago (1907), this process is still the most general and useful method for the synthesis of beta-lactams and their derivatives. This reaction is a [2 + 2] thermal cycloaddition in which two chiral centers may be generated in one preparative step. Staudinger reactions involving alpha,beta-unsaturated imines or ketenes have issues concerning the [2 + 2] or [4 + 2] periselectivity of the reaction. This Account discusses how the main factors that determine the regiochemical and stereochemical outcomes of this reaction were elucidated with computational and experimental data. This fruitful interplay between theory and experiment has revealed that the [2 + 2] cycloaddition is actually a two-step process. The first step is a nucleophilic addition of the nitrogen atom of the imine on the sp-hybridized carbon atom of the ketene. This attack forms a zwitterionic intermediate that evolves toward the final beta-lactam cycloadduct. The second step can be viewed as a four-electron conrotatory electrocyclization that is subject to torquoelectronic effects. When alpha,beta-unsaturated imines are used, the zwitterionic intermediates yield either the corresponding 4-vinyl-beta-lactams or the alternative 3,4-dihydropyridin-2(1 H)-ones. In this latter case, the cyclization step consists of a thermal disrotatory electrocyclization. In the context of stereoselectivity, it is usually assumed that the first step takes place through the less hindered side of the ketene. The cis-trans selectivity of the reaction depends on the geometry of the imine. As the general rule, ( E)-imines form cis-beta-lactams whereas ( Z)-imines yield trans-beta-lactams. Most of the experimental results point to the two-step model. The asymmetric torquoselectivity of the conrotatory ring closure of the second step accounts for the stereochemical discrimination in the reaction of chiral ketenes or chiral imines. Nevertheless, recent studies have revealed that isomerization paths in the imine or in the zwitterion may determine the stereochemistry of the reaction. Thus, if the rotation about the N1-C4 bond of the zwitterion intermediate is faster than the cyclization, the formation of trans-beta-lactams from ( E)-imines is biased. Alternatively, in some cases, the ( E)-( Z) isomerization of the starting imines prior to the cycloaddition steps also results in the formation of trans-cycloadducts. Although the main variables that govern the outcome of the reaction have been elucidated, there are still several aspects of the reaction yet to be disclosed. Finally, the discovery of the catalytic version of the reaction is a new and formidable mechanistic challenge and will be a nice playground for forthcoming theoretical-experimental discussions.

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Section: Mechanism Of the Reaction Between Imines And Ketenes: Concermentioning

confidence: 99%

The Mechanism of the Ketene−Imine (Staudinger) Reaction in Its Centennial: Still an Unsolved Problem?

2008

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“…The amide enol generated from amination of 2‐pyridylketene is stabilized by a strong intramolecular hydrogen bond to the pyridyl nitrogen . The existence of zwitterions as transients was also reported in the literature . There is little experimental information on the structures of the intermediates formed from highly reactive ketenes (unstable) such as phenylketene.…”

Section: Resultsmentioning

confidence: 97%

“…[18] The existence of zwitterions as transients was also reported in the literature. [29][30][31][32][33] There is little experimental information on the structures of the intermediates formed from highly reactive ketenes (unstable) such as phenylketene. It is difficult to differentiate experimentally between the amide enols and zwitterions; therefore, we carried out the theoretical calculations for the amide enols, zwitterions, and the final products (amides) in gas phase and in acetonitrile by using Tomasi's Polarized Continuum Model (PCM).…”

Section: Resultsmentioning

confidence: 99%

Amination of phenylketenes. Substituent effect on amine‐catalyzed tautomerization of amide enol

Badal

Zhang

Kobayashi

et al. 2013

J of Physical Organic Chem

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The transient intermediates with infrared bands at 1676-1680 cm À1 observed for reaction of substituted phenylketenes with diethylamine in acetonitrile were suggested to be the amide enols rather than the zwitterions on the basis of the theoretical calculations. A single broad band at 1674 cm À1 observed for reaction with the primary amines was attributed to overlap of two bands of the intermediate (amide enol) and the final product (amide). The substituent effect for the second-order rate constants of diethylamine-catalyzed tautomerization of the amide enol intermediates to give the amides was analyzed successfully by the Yukawa-Tsuno equation, giving a ρ value of 0.63 and an r À value of 1.31. The r À value larger than unity for pK a of phenols indicates that the negative charge formed at an oxygen atom of the amide enol at the transition state is significantly delocalized into the aromatic π-system through the ethenyl group. This r À value was considered to reflect an intrinsic property of β-phenylenolate skeleton. A remarkably small ρ value attributes to the cyclic transition structure where the negative charge disperses in a six-member ring.

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“…In the second rate‐determining step, the intermediate undergoes an electrocyclic conrotatory ring‐closure to give the final product, the β‐lactam. The existence of zwitterionic intermediates was proved experimentally in the thermal reaction of ketenes with imidazoles by using IR spectroscopy at low temperature 9. Some ab initio studies, however, predict that the mechanism for the reaction between formaldimine and ketene takes place by a concerted mechanism 10.…”

Section: Introductionmentioning

confidence: 99%

Application of the Octacarbonyldicobalt‐Catalyzed Carbonylation of Ethyl Diazoacetate for the One‐Pot Synthesis of N‐tert‐Butyl‐trans‐α‐ethoxycarbonyl‐β‐phenyl‐β‐lactam

et al. 2009

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Keywords: Cobalt / Carbene ligands / Carbonyl ligands / C-C coupling / Lactams / Density functional calculations N-tert-Butyl-trans-α-ethoxycarbonyl-β-phenyl-β-lactam has been prepared in 95 % yield (GC) by the octacarbonyldicobalt-catalyzed carbonylation of ethyl diazoacetate in dichloromethane in the presence of N-tert-butylbenzaldimine at 10°C and 75 bar pressure of carbon monoxide. The key step of the reaction is the catalytic formation of the highly reactive (ethoxycarbonyl)ketene from both of the intermediary complexes [Co 2 (CO) 7 (CHCO 2 Et)] and [Co 2 (CO) 6 (CHCO 2 Et) 2 ], which is in situ scavenged by the imine in a [2+2] cycload-

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The observation of zwitterions in the thermal reaction of ketenes with carbon-nitrogen double bonds

Cited by 69 publications

References 0 publications

The Mechanism of the Ketene−Imine (Staudinger) Reaction in Its Centennial: Still an Unsolved Problem?

The Mechanism of the Ketene−Imine (Staudinger) Reaction in Its Centennial: Still an Unsolved Problem?

Amination of phenylketenes. Substituent effect on amine‐catalyzed tautomerization of amide enol

Application of the Octacarbonyldicobalt‐Catalyzed Carbonylation of Ethyl Diazoacetate for the One‐Pot Synthesis of N‐tert‐Butyl‐trans‐α‐ethoxycarbonyl‐β‐phenyl‐β‐lactam

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