Cycloaddition Of Ketenes Research Articles

Asymmetric Synthesis of the DEFG Rings of Solanoeclepin A.

Starting from ( R)-seudenol, an asymmetric synthesis of the DEFG rings of solanoeclepin A has been developed. The key transformations include the substrate-controlled asymmetric Staudinger ketene cycloaddition and the intramolecular aldol reaction leading to the tricyclo[5.2.1.01,6]decane core of solanoeclepin A in 10 steps in the longest reaction sequence.

DFT Study of Stereoselective Ketene-imine Cycloadditions, Evaluation of Possible Solvent Effects with IEF-PCM

The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a facile method for the synthesis of biologically important β-lactam derivatives. In this paper two previously reported stereoselective reactions were investigated with computational methods. Our computations support experimental data that a chiral imine, derived from d-glyceraldehyde reacting with ketenes, yields almost exclusively one out of the possible four diastereomers. The reaction proceeds stepwise, first addition of the imine to the ketene yields an intermediate, then the product is formed in a conrotatory electrocyclization. Results indicate that the electrostatic repulsion of the chiral auxiliary group is the main factor of the stereoselectivity, but solvent and substituent effects are not negligible. Calculations were performed at M06-2X/6-31+G** level of theory combined with IEF-PCM solvation, in common solvents such as toluene, THF, dichloromethane, acetonitrile and water. These results provide useful insight for the development of new chiral auxiliaries and optimizing reaction parameters.

A theoretical study on NHC-catalysed enantioselective cycloaddition of ketenes and 3-aroylcoumarins: mechanism and enantioselectivity.

NHC-catalysed enantioselective cycloaddition of ketenes to 3-aroylcoumarins to yield dihydrocoumarin-fused dihydropyranones has been investigated using DFT methods at the B3LYP/6-31G* and MPWB1K/6-311G** computational levels. Two plausible mechanisms have been studied: the "ketene-first" mechanism A and the "coumarin-first" mechanism B. An analysis of the activation Gibbs free energies involved in the two competitive pathways makes it possible to rule out the pathway associated with the "coumarin-first" mechanism B. The first step of the "ketene-first" mechanism A is the formation of zwitterionic intermediate IN1-Zvia a nucleophilic attack of NHC 1 on ketene 2. A [4 + 2] cycloaddition through the nucleophilic attack of enolate IN1-Z on the conjugated double bond of the benzoyl group of coumarin 3, viaTS3-SS-a2 or TS3-RR-a2, yields IN3. Finally, the extrusion of the catalyst through TS5 leads to the final products, either 4-SS or 4-RR. Enantioselectivity observed in the experimental results is determined in the transition states TS3-SS-a2/TS3-RR-a2. In this pathway, the intramolecular hydrogen-bonding between the hydroxyl group of the IN1-Z adduct and the carbonyl oxygen of the original ketene group directs the final stereochemistry throughout the entire process.

Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and Staudinger Cycloadditions.

The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans-β-sultams. In other cases, the above sulfa-Staudinger cycloadditions give rise to trans-β-sultams exclusively. Further mechanistic rationalization discloses that the ortho-nitro effect is attributed to its strong electron-withdrawing inductive effect. Similarly, the ortho-nitro effect also exists in Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current research provides further insights into the diastereoselective control in sulfa-Staudinger and Staudinger cycloadditions.

Synthesis of some novel indeno[1,2-b]quinoxalin spiro-β-lactam conjugates

This article reports the synthesis of some new spiro-β-lactams bearing an indeno[1,2-b]quinoxaline ring system, prepared by a [2 + 2] cycloaddition of ketenes with imines derived from 11-H-indeno[1,2-b]quinoxalin-11-one. The structures of newly synthesized spiro-β-lactams 2a–i and 3a-i were characterized by FT-IR, 1H NMR, 13C NMR, mass spectrometry and elemental analyses. The relative stereochemistry of spiro-β-lactams 2a and 3a was determined unequivocally by X-ray crystallographic studies.

Evidence for an umpolung type of [2+2] cycloaddition of 2-carbamoyl ketenes

2-Carbamoyl ketenes react as nucleophiles with iminium salts and the process leads to the formation of alkylidene malonamides.

ChemInform Abstract: Alkaloid‐Catalyzed Enantioselective [3 + 2] Cycloaddition of Ketenes and Azomethine Imines.

AbstractAn asymmetric formal cycloaddition of in situ generated ketenes and azomethine imines provides bicyclic pyrazolidinones in good to excellent yields with good to excellent diastereoselectivity and excellent enantioselectivity.

ChemInform Abstract: Thermal [2 + 2]‐Cycloaddition of Ketenes with Chiral Enol Ethers: Route to Densely Substituted Cyclobutanones.

AbstractAn unprecedented [2 + 2] cycloaddition of in situ generated ketenes with 1‐(2,4,6‐triisopropylphenyl)ethyl substituted enol ethers provides a synthesis of cyclobutanones with good to excellent diastereoselectivity.

ChemInform Abstract: Lewis Acid‐Promoted [2 + 2] Cycloadditions of Alkenes with Aryl Ketenes.

A method for the [2 + 2] cycloaddition of aryl ketenes and alkenes is presented. The process involves the in situ generation of a ketene in the presence of a Lewis acid. The utility of products is demonstrated towards the synthesis of a common scaffold found in several natural product families.

Alkaloid-Catalyzed Enantioselective [3 + 2] Cycloaddition of Ketenes and Azomethine Imines.

A new asymmetric synthesis of bicyclic pyrazolidinones through an alkaloid-catalyzed formal [3 + 2] cycloaddition of in situ generated ketenes and azomethine imines is described. The products were formed in good to excellent yields (52-99% for 17 examples), with good to excellent diastereoselectivity (dr 5:1 to 27:1 for 11 examples), and with excellent enantioselectivity in all cases (≥96% ee). This method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.

Theoretical investigations towards the [4+2] cycloaddition of ketenes with 1-azadienes catalyzed by N-heterocyclic carbenes: mechanism and stereoselectivity

This present work reported a detailed DFT study to the reaction mechanism and stereoselectivities of the NHC-catalyzed [4+2] cycloaddition of ketenes with 1-azadienes. The calculated results reveal that the ‘ketene-first’ mechanism is more energetically favorable than the ‘azadiene-first’ one, and the cycloaddition step is demonstrated to be both the rate- and stereoselectivity-determining step. The Gibbs free energy barrier to afford the product in SS configuration is lower than those in other configurations, which is well consistent with the experimental results. Analyses to the distortion–interaction energies of two key species and the components of the free energy barriers of the step in which the stereocenters generate were conducted, and it was concluded that stereoseletivities of the reaction should originate from differences of enthalpy barriers via the four transition state isomers, rather than the distinctions of barriers stemming from entropy penalties.

Thermal [2 + 2]-Cycloaddition of Ketenes with Chiral Enol Ethers: Route to Densely Substituted Cyclobutanones.

Access to chiral polysubstituted cyclobutanones by [2 + 2]-cycloaddition of ketenes with chiral acyclic enol ethers is reported. A wide variety of easily accessible di- and monosubstituted ketenes were found to react with a very high degree of stereoselectivity with chiral, Stericol derived, acyclic enol ethers. This combination of simple reagents provides straightforward entry to highly substituted enantioenriched cyclobutanones.

A Theoretical Study on the Reaction Mechanisms and Stereoselectivities of NHC-Catalyzed [2 + 2] Cycloaddition of Ketene with C=N Double Bond of Isothiocyanate

A Theoretical Study on the Reaction Mechanisms and Stereoselectivities of NHC-Catalyzed [2 + 2] Cycloaddition of Ketene with C=N Double Bond of Isothiocyanate

Insights into the NHC-Catalyzed Formal [2 + 2 + 2] Cycloaddition of Ketenes with C=S Double Bond of Isothiocyanate

Insights into the NHC-Catalyzed Formal [2 + 2 + 2] Cycloaddition of Ketenes with C=S Double Bond of Isothiocyanate

Lewis acid-promoted [2 + 2] cycloadditions of alkenes with aryl ketenes.

A method for the [2 + 2] cycloaddition of aryl ketenes and alkenes is presented. The process involves the in situ generation of a ketene in the presence of a Lewis acid. The utility of products is demonstrated towards the synthesis of a common scaffold found in several natural product families.

First ketene cycloaddition approach to (±)-junionone

Junionone is the first monocyclic cyclobutane monoterpenoid isolated from a plant. Of the existing four syntheses of this compound, none employs a ketene cycloaddition to construct the four-membered ring. Herein, we report the first total synthesis of junionone that features a ketene cycloaddition for the synthesis of this compound, starting from the commercially available 1,5-hexadiene.

ChemInform Abstract: Kinetic Resolution in the [2 + 2] Cycloaddition of Ketenes: An Experimental and Theoretical Study.

AbstractThe procedure uses the high difference in reactivity and thus allows the access to pure (E) alkenes, often difficult or impossible to isolate from the mixtures or expensive in trade.

Probing the Diastereoselectivity of Staudinger Reactions Catalyzed by N-Heterocyclic Carbenes.

The reaction of ethylphenylketene with 1,3-dimesitylimidazol-2-ylidene (IMes) or 1,3-dimesitylimidazolin-2-ylidene (SIMes) afforded the corresponding azolium enolates in high yields. The two zwitterions were fully characterized by various analytical techniques. Their thermal stabilities were monitored by thermogravimetric analysis and the molecular structure of SIMes⋅EtPhCCO was determined by means of X-ray crystallography. A mechanism was proposed to account for the trans-diastereoselectivity observed in the [2+2] cycloaddition of ketenes and N-protected imines catalyzed by N-heterocyclic carbenes and an extensive catalytic screening was performed to test its validity. The steric bulk of the NHC catalyst markedly affected the cis/trans ratio of the model β-lactam product. The nature of the solvent used to carry out the Staudinger reaction also significantly influenced its diastereoselectivity. Conversely, the nature of the substituent on the N-sulfonated imine reagent and the reaction temperature were less critical parameters.

Frontispiece: Kinetic Resolution in the [2+2] Cycloaddition of Ketenes: An Experimental and Theoretical Study

Frontispiece: Kinetic Resolution in the [2+2] Cycloaddition of Ketenes: An Experimental and Theoretical Study

Kinetic resolution in the [2+2] cycloaddition of ketenes: an experimental and theoretical study.

The kinetic resolution of Z and E olefins by [2+2] cycloaddition with ketenes allows the isolation of pure E olefin, as well as the synthesis of pure cis-cyclobutanones, starting from Z/E mixtures. A computational rationale for this kinetic difference is reported. The obtained difference of energy of activation matches with the experimental results.