Cycloaddition Of Ketenes Research Articles

Asymmetric N-Heterocyclic Carbene-catalyzed [4+2] Cycloaddition of Ketenes with α-cyanochalcones

报道了氮杂环卡宾催化烯酮与氰基查尔酮的[4+2]不对称环加成反应.通过L-焦谷氨酸衍生的大位阻卡宾催化烯酮与氰基查尔酮反应,以良好的产率、良好的顺反选择性和优良的对映选择性得到相应的手性多取代二氢吡喃酮类化合物.

Changing the regioselectivity and asynchronicity of the possible concerted [2+2] and [4+2] cycloadditions of ketene and halogenated ketenes with cyclopentadiene: a DFT survey

Two concerted Diels–Alder [4+2] and two concerted Staudinger [2+2] reactions between ketene and/or dihaloketenes with cyclopentadiene are examined at B3LYP/6-31+G* level. For the parent ketene, two cycloaddition modes including [2+2] across the CC and [4+2] across the CC bond of ketene are thermodynamically favorable (ΔE=−13.4 and −17.3 kcal/mol, respectively) while the two other including [2+2] across the CO and [4+2] across the CO bond of ketene are endoergic. The corresponding barrier heights change to a lesser amount and ranging from 20.8 to 35.1 kcal/mol. Halogenated ketenes significantly affect both the thermodynamics and kinetics of these reactions in a way that they increase the exoergicity and reduce the barrier heights result in the decrease of regioselectivity. Unsymmetrical bond formations in the structures of TSs indicate that all the reaction modes are concerted and synchronous but halogens increase the asynchronicity due to the electronic effects. Moreover, three transient halogenated cycloadducts obtained through the [4+2] cycloaddition across the CO bond are converted to some new products via a [3,3] sigmatropic rearrangement. The AIM pictures show that in the [4+2] cycloadditions four TS structures represent pericyclic reactions, while all the [2+2] reactions are classified as pseudopericyclic. FMO theory is applied to justify the findings. The reliability of B3LYP results is confirmed through comparison with the HF and MP2 methods.

Chiral Lewis Acid Catalyzed Asymmetric Cycloadditions of Disubstituted Ketenes for the Synthesis of β-Lactones and δ-Lactones

Highly diastereo- and enantioselective [2 + 2]- and [4 + 2]-cycloadditions of disubstituted ketenes were realized by chiral Lewis acid catalysis. A series of arylalkylketenes underwent the reaction smoothly with isatins and β,γ-unsaturated α-ketoesters, providing optically active β-lactones and δ-lactones with vicinal chiral centers in excellent yields (up to 99%) and enantioselectivities (up to 99% ee), as well as exclusively high diastereoselectivities under 0.2-2 mol % catalyst loading.

DFT Investigation on Mechanisms and Stereoselectivities of [2 + 2 + 2] Multimolecular Cycloaddition of Ketenes and Carbon Disulfide Catalyzed by N-Heterocyclic Carbenes

The first theoretical investigation using density functional theory (DFT) methods to study the detailed reaction mechanisms of stereoselective [2 + 2 + 2] multimolecular cycloaddition of ketene (two molecules) and carbon disulfide (CS2, one molecule) which is catalyzed by N-heterocyclic carbene (NHC) is presented in this paper. The calculated results indicate that this reaction occurs through four steps: the complexation of NHC with ketene (channel 1a) rather than with CS2 (channel 1b), addition of CS2 (channel 2b) but not dimerization of ketene (channel 2a), formal [4 + 2] cycloaddition with a second molecule of ketene (channel 3a) rather than intramolecular [2 + 2] cycloaddition (channel 3b), and finally regeneration of NHC. The second step is revealed to be the rate-determining step. Moreover, the stereoselectivities associated with the chiral carbon center and the carbon double bond are predicted to be respectively determined in the second and third steps and respectively R and E configurations dominated, which are in good agreement with the experimental results. Furthermore, the possible mechanisms of the identical [2 + 2 + 2] cycloaddition catalyzed by N,N-dimethylpyridin-4-amine (DMAP) have also been investigated to help understand the ring closure mechanism proceeding in the third step.

Heterocyclic synthesis via catalysis of N-heterocyclic carbenes: very classical and very modern chemical species

Abstract After a long history of medical and biochemical investigations of vitamin B1, N-heterocyclic carbenes (NHCs) have recently been used as organocatalysts for a variety of synthetic reactions. This review article highlights the application of NHC-catalyzed reactions including enantioselective reactions to the heterocyclic synthesis. NHC-catalyzed benzoin condensation and Stetter reaction of ether- and amine-linked aldehydes give four- to six-membered oxygen and nitrogen heterocycles. NHC-catalyzed conjugate additions of enals to ketones and imines afford γ-lactones and γ-lactams. When the NHC-catalyzed reaction intermediates of enals are protonated, the reaction of the resulting enols with enones and ene-imines furnish formal hetero-Diels-Alder products. Acyl fluoride and esters can be activated by NHCs, and subsequent aldol and Michael reactions give β-lactones. Oxidation of intermediates derived from enals or the intermediates from ynals provide unsaturated acyl azolium which are transformed into cyclic products via subsequent nucleophilic reactions. NHCs also catalyze [2+2] cycloadditions of ketenes and other heterocumulenes and ring expansion of cyclic aldehydes.

ChemInform Abstract: Enantioselective Cycloaddition Reactions of Ketenes Catalyzed by N‐Heterocyclic Carbenes

AbstractReview: 94 refs.

Enantioselective Cycloaddition Reactions of Ketenes Catalyzed by N-Heterocyclic Carbenes

This account summarizes recent research in our group on the development of N-heterocyclic carbene (NHC) catalyzed cycloaddition reactions of ketenes. The NHCs were found to be efficient catalysts for the enantioselective [2+2]-, [2+2+2]-, [3+2]-, and [4+2]-cycloaddition reactions of ketenes with various electrophiles, such as imines, carbonyl compounds, oxaziridines, oxodienes and azadienes. The NHC-catalyzed [4+2] cycloaddition of α,β-unsaturated acyl chlorides was also investigated. 1 Introduction 2 [2+2] Cycloaddition of Ketenes 2.1 With Carbon–Nitrogen Double Bonds 2.2 With Carbon–Oxygen Double Bonds 2.3 With Oxygen–Nitrogen and Nitrogen–Nitrogen Double Bonds 2.4 With X=Y=Z Bonds 3 [3+2] Cycloaddition of Ketenes 4 [4+2] Cycloaddition of Ketenes 5 [4+2] Annulation of Unsaturated Acyl Chlorides 6 Conclusions and Outlook

ChemInform Abstract: N‐Heterocyclic Carbene‐Catalyzed [4 + 2] Cycloaddition of Ketenes and 3‐Aroylcoumarins: Highly Enantioselective Synthesis of Dihydrocoumarin‐Fused Dihydropyranones.

The N-heterocyclic carbene-catalyzed [4 + 2] cyclization of ketenes and 3-aroylcoumarins has been developed to give the corresponding dihydrocoumarin-fused multisubstituted dihydropyranones in high yield with good diastereoselectivity and high enantioselectivity.

Annuloselectivity in Cycloadditions of Ketenes with Imines: A DFT Study

The annuloselectivity defined as the annulation selectivity between [2 + 2] cycloaddition and two kinds of novel cascade [2 + 2 + 2] cycloadditions (2 ketenes + imine and ketene + 2 imines) in a Staudinger reaction to afford three classes of annulation products has been studied in depth with the density functional theory (DFT) calculations. The computed results indicate that the cascade [2 + 2 + 2] reaction of ketene 4 and ketimine 5 initiates the dimerization of the ketene as the rate-determining step, affording a lactone that further converts to α-acetylketene, followed by the [4 + 2] cycloaddition with imine 5 to furnish a 2,3-dihydro-1,3-oxazin-4-one derivative. That is very competitive to the normal Staudinger reaction. The alternative [2 + 2 + 2] cycloaddition undergoes the hetero-Diels-Alder (HDA) cycloaddition of the zwitterionic intermediates generated from ketenes and conjugated imine 11 with less steric hindrance as a good dienophile to afford 2,3,4,5-tetrahydropyrimidin-6(1H)-ones, which is the most favorable pathway in the case of the Staudinger reaction system. The HDA process is supported and confirmed experimentally by X-ray crystallography via analysis of the stereochemistry of the cycloadducts. The further investigation into the nature of the frontier molecular orbitals accounts well for the origin of the annuloselectivity. The extensive studies on ketenes containing various representative substituents reveal that ketenes with electron-donor and conjugated monosubstituents are inclined to dimerization, preferring the [2 + 2 + 2] cycloaddition of two molecules of ketenes and one molecule of imines, while less steric bulky imines with ketenes are apt to the [2 + 2 + 2] cycloaddition of one molecule of ketenes and two molecules of imines.

N-heterocyclic carbene-catalyzed [4 + 2] cycloaddition of ketenes and 3-aroylcoumarins: highly enantioselective synthesis of dihydrocoumarin-fused dihydropyranones

The N-heterocyclic carbene-catalyzed [4 + 2] cyclization of ketenes and 3-aroylcoumarins has been developed to give the corresponding dihydrocoumarin-fused multisubstituted dihydropyranones in high yield with good diastereoselectivity and high enantioselectivity.

Theoretical Investigations toward the [4 + 2] Cycloaddition of Ketenes with N-Benzoyldiazenes Catalyzed by N-Heterocyclic Carbenes: Mechanism and Enantioselectivity

Density functional theory (DFT) calculations have been performed to provide the first detailed computational study on the mechanism and enantioselectivity for the [4 + 2] cycloaddition reaction of ketenes with N-benzoyldiazenes catalyzed by N-heterocyclic carbenes (NHCs). Two possible mechanisms have been studied: first is the "ketene-first" mechanism (mechanism A), and second is the novel "diazene-first" mechanism (mechanism B). The calculated results reveal that mechanism B is more favorable than mechanism A because it is not only of lower energy barrier but also more consistent with the provided general experimental procedure (Huang, X.-L.; He, L.; Shao, P.-L.; Ye, S. Angew. Chem., Int. Ed.2009, 48, 192-195). The enantioselectivity-determining step is demonstrated to present during the first process of cycloaddition, and the main product configuration is verified to agree with the experimental ee values very well. This study should be of some worth on forecasting how different substituent groups of catalysts and/or reactants affect the enantioselectivity of products. The obtained novel mechanistic insights should be valuable for not only rational design of more efficient NHC catalysts but also understanding the general reaction mechanism of [4 + 2] cycloaddition of ketenes.

Beyond Frontier Molecular Orbital Theory: A Systematic Electron Transfer Model (ETM) for Polar Bimolecular Organic Reactions

Polar bimolecular reactions often begin as charge-transfer complexes and may proceed with a high degree of electron transfer character. Frontier molecular orbital (FMO) theory is predicated in part on this concept. We have developed an electron transfer model (ETM) in which we systematically transfer one electron between reactants and then use density functional methods to model the resultant radical or radical ion intermediates. Sites of higher reactivity are revealed by a composite spin density map (SDM) of odd electron character on the electron density surface, assuming that a new two-electron bond would occur preferentially at these sites. ETM correctly predicts regio- and stereoselectivity for a broad array of reactions, including Diels-Alder, dipolar and ketene cycloadditions, Birch reduction, many types of nucleophilic additions, and electrophilic addition to aromatic rings and polyenes. Conformational analysis of radical ions is often necessary to predict reaction stereochemistry. The electronic and geometric changes due to one-electron oxidation or reduction parallel the reaction coordinate for electrophilic or nucleophilic addition, respectively. The effect is more dramatic for one-electron reduction.

Mechanistic Investigation of the Ring Opening in the Staudinger Cycloaddition Involving Ketenes with Electron‐Withdrawing Substituents

AbstractThe cycloaddition of ketenes and imines (Staudinger cycloaddition) is a general method for the synthesis of various β‐lactams. However, reactions of imines and ketenes with electron‐withdrawing substituents produce α,β‐unsaturated alkenamides, ring‐opening products of the intermediates generated from imines and the ketenes, even as sole products, besides the desired β‐lactams. The mechanism of the formation of α,β‐unsaturated alkenamides was investigated. The results indicate that the α,β‐unsaturated alkenamides are generated via a base‐induced CC bond isomerization followed by electrocyclic ring opening of the formed azacyclobutenes (=1,2‐dihydroazetes; cf. Scheme 3).

A novel approach toward the synthesis of strigolactones through intramolecular [2+2] cycloaddition of ketenes and ketene-iminiums to olefins. Application to the asymmetric synthesis of GR-24

An intramolecular [2+2] cycloaddition of ketenes and ketene-iminium was developed for the preparation of GR-24, a synthetic analogue of the family of strigolactone plant hormones. Excellent levels of regioselectivity and of chiral induction were obtained using a bulky chiral amine for the formation of the cyclobutanone and a subsequent regioselective Baeyer–Villiger afforded the tricyclic lactone core of (+)-GR-24.

Synthesis of β-lactams with π electron-withdrawing substituents

β-Lactams are crucial structural feature of β-lactam antibiotics and important intermediates in synthetic and pharmaceutical chemistry. Synthetic methods for β-lactams with π electron-withdrawing substituents, such as formyl (carbaldehyde), acyl, imino, carboxylic acids, carboxylates, carboxamides, cyano (carbonitriles), and nitro groups, on their 3- and/or 4-position(s) are presented in this review. The methods are divided mainly into intramolecular cyclizations, cycloaddition, and other methods, for example, Ugi-type reaction of β-keto acids, amines, and isonitriles, and modification of β-lactam derivatives. Cyclizations include cyclization of haloacetamidoacetates(malonates), intramolecular carbene insertion of α-diazoalkanamides, ring-opening cyclization of α,β-epoxyalkanamidoacetates, oxidative coupling of 3-oxoalkanamidoacetates, oxidative cyclization of N-p-hydroxyphenyl β-oxoalkanamides, intramolecular cyclization of aspartic acid derivatives or β-hydroxyalkanamides, and radical cyclization of N-vinyl β-oxoalkanamides. Cycloadditions incorporate Staudinger cycloaddition of ketenes and imines, cycloaddition of nitrones and alkynes, cycloaddition of nitrones and alkylidenecycopropanes and subsequent acidic rearrangement, and condensation of imines and enolates (ethers) of esters. The scope, limitation, and stereoselectivity are also discussed for some methods. Most of the β-lactam derivatives are key intermediates or precursors for preparation of β-lactam antibiotics and their analogs.

Temperature-Independent Stereoselectivity in Intramolecular Cycloaddition of Ketene Generated from Diazoester in Solution and in Vapor Phase: How Entropy Term Governs the Selectivity

Abstract The intramolecular [2 + 2] cycloaddition between alkene and ketene linked with 2,4-pentanediol tether was performed in a wide range of temperature, −60 to +400 °C. When the ketene was generated by photolysis at the diazoester in a pentane solution, the cycloadduct obtained was of 90–98% de depending on the structure of the olefinic part as well as the structure of the tether. Notably, each substrate showed practically constant selectivity in a temperature range of −60 to +130 °C. The thermolysis in vapor phase above 250 °C also gave the same cycloadducts; the de values of the kinetic products are similar to those obtained by photolysis. The observed temperature-independent stereoselectivity should be controlled by the entropy term, which is also investigated by ab initio calculations in the framework of density functional theory.

ChemInform Abstract: NHC‐Catalyzed Enantioselective [2 + 2] and [2 + 2 + 2] Cycloadditions of Ketenes with Isothiocyanates.

AbstractThe [2 + 2]‐cycloaddition reaction of the aromatic isothiocyanate (III) with ketenes proceeds at room temperature with formation of 4‐thioxo‐2‐azetidinones.

BINAPHANE-Catalyzed Asymmetric Synthesis of trans-β-Lactams from Disubstituted Ketenes and N-Tosyl Arylimines

The development of a BINAPHANE-catalyzed formal [2 + 2]-cycloaddition of disubstituted ketenes and inexpensive N-tosyl arylimines that provides access to a variety of highly substituted β-lactams (16 examples) is described. The BINAPHANE catalytic system displays moderate to excellent enantioselectivity (up to 98% ee) and high diastereoselectivity in most cases, favoring formation of the trans-diastereomer (13 examples with dr ≥ 90:10).

ChemInform Abstract: N‐Heterocyclic Carbene Catalysis: Enantioselective Formal [2 + 2] Cycloaddition of Ketenes and N‐Sulfinylanilines.

AbstractThe use of PGT and IOT as chiral catalysts allows the highly enantioselective synthesis of both enantiomers (III).

NHC-Catalyzed Enantioselective [2 + 2] and [2 + 2 + 2] Cycloadditions of Ketenes with Isothiocyanates

The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N-aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 °C favors the [2 + 2 + 2] cycloaddition.