Cycloaddition Of Enals Research Articles

N‐Heterocyclic Carbene Catalyzed [3+2] Cycloaddition of Enals with β,γ ‐Unsaturated α ‐Ketimino Esters for the Synthesis of Multisubstituted Cyclopentanone

AbstractA convenient strategy of N‐heterocyclic carbene catalyzed [3+2] cycloaddition of enals with β,γ‐unsaturated α‐ketimino esters is developed. This effective protocol features mild reaction conditions and broad substrate scope, which enables the rapid assembly of various benzoxazinone derived cyclopentanone scaffolds in good to high yields with excellent diastereoselectivities.magnified image

Two-Step Synthesis of α,β-Unsaturated γ-Amino Acid Esters via N-Heterocyclic Carbene Catalyzed [4+2] Cycloaddition of Enals and Nitroso Compounds

An efficient strategy for the synthesis of various of α,β-unsaturated γ-amino acid esters has been established employing N-heterocyclic carbene catalyzed [4+2] cycloadditions of β-methyl enals and aromatic nitroso compounds to afford 1,2-oxazin-6-ones in good yields. A subsequent acid-catalyzed esterification under ring opening yields the γ-amino enoates in good yields.

N-Heterocyclic Carbene Catalyzed [3+2] Cycloaddition of Enals with Masked Cinnamates for the Asymmetric One-Pot Synthesis of Adipic Acid Derivatives.

A novel short entry to 3,4-disubstituted adipic acids has been developed by employing an asymmetric NHC-catalyzed [3+2] cycloaddition of enals with masked cinnammates in moderate to good yields and high stereoselectivities. The synthetic utility of the protocol was demonstrated by the basic conversion of the masked cyclopentanone intermediates to 3S,4S-disubstituted adipic acid precursors of pharmaceutically important gababutins.

ChemInform Abstract: N‐Heterocyclic Carbene‐Catalyzed Umpolung Formal [3 + 3] Cycloaddition of Enals with Isatogens: Access to Fused Indolin‐3‐ones with a Tetrasubstituted Carbon Stereocenter.

A novel synthetic method to access fused indolin-3-ones with a tetrasubstituted carbon stereocenter has been developed via NHC-catalyzed umpolung formal [3+3] cycloaddtion of enals with isatogens. This methodology could be also applied for the quick construction of the 6-5-5 tricyclic pyrrolo[1,2-a]indole skeleton which is frequently found as a core structure of many indole alkaloids.

N‐Heterocyclic Carbene‐Catalyzed Umpolung Formal [3+3] Cycloaddition of Enals with Isatogens: Access to Fused Indolin‐3‐ones with a Tetrasubstituted Carbon Stereocenter

AbstractA novel synthetic method to access fused indolin‐3‐ones with a tetrasubstituted carbon stereocenter has been developed via NHC‐catalyzed umpolung formal [3+3] cycloaddtion of enals with isatogens. This methodology could be also applied for the quick construction of the 6‐5‐5 tricyclic pyrrolo[1,2‐a]indole skeleton which is frequently found as a core structure of many indole alkaloids.magnified image

DFT Study on the Mechanisms and Stereoselectivities of the [4 + 2] Cycloadditions of Enals and Chalcones Catalyzed by N-Heterocyclic Carbene

The possible reaction mechanisms of stereoselective [4 + 2] cycloaddition of enals and chalcones catalyzed by N-heterocyclic carbene (NHC) have been investigated using density functional theory (DFT). The calculated results indicate that the most favorable reaction channel occurs through five steps. The first step is the nucleophilic attack on the enal by NHC. Then, there are two consecutive acid (AcOH)-assisted proton-transfer steps. Subsequently, the fourth step is the [4 + 2] cycloaddition process associated with the formation of two chiral centers, followed by dissociation of NHC and product. Our computational results demonstrate that the [4 + 2] cycloaddition is the rate-determining and stereoselectivity-determining step. The energy barrier for the SS configurational channel (17.62 kcal/mol) is the lowest one, indicating the SS configurational product should be the main product, which is in agreement with experiment. Moreover, the role of NHC catalyst in the [4 + 2] cycloaddition of enal and chalcone was explored by the analysis of global reactivity indexes. This work should be helpful for realizing the significant roles of catalyst NHC and the additive AcOH and thus provide valuable insights on the rational design of potential catalyst for this kind of reactions.

ChemInform Abstract: Controlled β‐Protonation and [4 + 2] Cycloaddition of Enals and Chalcones via N‐Heterocyclic Carbene/Acid Catalysis: Toward Substrate Independent Reaction Control.

AbstractIn the title reaction acid co‐catalysts are used to achieve selective homoenolate β‐protonation and controlled access to previously unobservable enolate products (III) and (VI).

Controlled β-protonation and [4+2] cycloaddition of enals and chalconesvia N-heterocyclic carbene/acid catalysis: toward substrate independent reaction control

A substrate-independent selective generation of enolates over homoenolate equivalents in NHC-catalyzed reactions of enals and chalcones is disclosed. Acid co-catalysts play vital roles in control of the reaction pathways, allowing for individual access to diverse products from identical substrates.

ChemInform Abstract: Cooperative Dienamine/Hydrogen‐Bonding Catalysis: Enantioselective Formal [2 + 2] Cycloaddition of Enals with Nitroalkenes.

AbstractThe title synthesis is the first example of a cascade reaction involving the dienamine/iminium manifold.

Organocatalytic [2+2] Cycloaddition of Enals and Nitroalkenes

Organocatalytic [2+2] Cycloaddition of Enals and Nitroalkenes

ChemInform Abstract: Complete 2,5‐Diastereocontrol in the Organocatalytic Enantioselective [3 + 2] Cycloaddition of Enals with Azomethine Ylides Derived from α‐Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocenters.

AbstractThe title cycloaddition reaction provides access towards pyrrolidines (III) with four stereocenters, one of them being a quaternary stereocenter, in excellent diastereo‐ and high enantioselectivities.

Cooperative Dienamine/Hydrogen‐Bonding Catalysis: Enantioselective Formal [2+2] Cycloaddition of Enals with Nitroalkenes

Two can play this game: The title reaction is catalyzed by a chiral secondary amine in the presence of an achiral thiourea for the enantio- and diastereoselective synthesis of highly functionalized cyclobutanes (see scheme; TMS=trimethylsilyl). Mechanistically, two consecutive Michael reactions proceed through an unprecedented combination of an dienamine/iminium activation mode.

Cooperative Dienamine/Hydrogen‐Bonding Catalysis: Enantioselective Formal [2+2] Cycloaddition of Enals with Nitroalkenes

Doppeltes Spiel: Die enantio- und diastereoselektive Titelreaktion wird durch ein chirales sekundäres Amin in Gegenwart eines achiralen Thioharnstoffs katalysiert und liefert hoch funktionalisierte Cyclobutane (siehe Schema). Dabei laufen nacheinander zwei Michael-Reaktionen über eine ungewöhnliche Kombination aus Dienamin- und Iminium-Aktivierung ab.

Complete 2,5‐Diastereocontrol in the Organocatalytic Enantioselective [3+2] Cycloaddition of Enals with Azomethine Ylides Derived from α‐Iminocyanoacetates: Asymmetric Synthesis of Pyrrolidines with Four Stereocentres

AbstractRacemic α‐iminocyanoacetates have been used as azomethine ylide precursors in the catalytic enantioselective [3+2] cycloaddition with α,β‐unsaturated aldehydes catalyzed by (S)‐α,α‐diphenylprolinol leading to the fully stereocontrolled formation of pyrrolidine cycloadducts with four stereocentres, one of them being a quaternary one. The reaction proceeded with excellent yields, endo‐selectivities and enantioselectivities. Remarkably, complete 2,5‐diastereoselection has also been achieved under the optimized reaction conditions, which has been explained in terms of the participation of intramolecular H‐bonding interaction which contributes to stabilize one determined geometry for the in situ generated azomethine ylide.

Highly Stereoselective Formal [3 + 3] Cycloaddition of Enals and Azomethine Imines Catalyzed by N‐Heterocyclic Carbenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Highly stereoselective formal [3 + 3] cycloaddition of enals and azomethine imines catalyzed by N-heterocyclic carbenes.

N-Heterocyclic carbenes derived from N-mesityl benzimidazolium salts are effective catalysts for generating homoenolate species from α,β-unsaturated aldehydes. The nucleophilic intermediate adds to azomethine imines, and the resulting activated carbonyl unit undergoes an intramolecular acylation event. This formal [3 + 3] cycloaddition between α,β-unsaturated aldehydes and azomethine imines catalyzed by NHC has been developed to give substituted pyridazinones in good to excellent yields with high diastereoselectivity (>20:1). The NHC-catalyzed reaction accommodates aromatic and alkyl α,β-unsaturated aldehydes and various aromatic azomethine imines. The pyridazinones can undergo selective six-membered ring opening upon addition of alcohols or amines to give esters and amides.