Catalyzed Diels-Alder Reaction Research Articles

Enantioselective Artificial Metalloenzymes by Creation of a Novel Active Site at the Protein Dimer Interface

A game of two halves: Artificial metalloenzymes are generated by forming a novel active site on the dimer interface of the transcription factor LmrR. Two copper centers are incorporated by binding to ligands in each half of the dimer. With this system up to 97 % ee was obtained in the benchmark CuII catalyzed Diels–Alder reaction (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Enantioselective Catalytic Diels–Alder Reactions with Enones As Dienophiles

The aqua complexes (SM,RC)-[(η5-C5Me5)M(PROPHOS)(H2O)][SbF6]2 [PROPHOS = (R)-propane-1,2-diylbis(diphenylphosphane); M = Rh (1), Ir (2)] are active catalysts for the asymmetric Diels–Alder reaction between ketones and dienes. At low temperatures, enantioselectivities of up to 89% ee are achieved. The intermediate Lewis acid–dienophile complexes (SM,RC)-[(η5-C5Me5)M(PROPHOS)(MVK)][SbF6]2 (MVK = methyl vinyl ketone; M = Rh (3), Ir (4)) and (SIr,RC)-[(η5-C5Me5)Ir(PROPHOS)(EVK)][SbF6]2 (EVK = ethyl vinyl ketone (5)) have been isolated and characterized by analytical and spectroscopic means, including the determination of the crystal structure of the iridium complexes 4 and 5 by X-ray diffractometric methods. Structural parameters indicate that the dispositions of the coordinated dienophiles are controlled by the CH/π attractive interactions established between a phenyl group of the PROPHOS ligand and the α-vinyl proton of the ketones. Proton NMR parameters indicate that these interactions are maintained in so...

ChemInform Abstract: Intramolecular Gold(III)‐Catalyzed Diels—Alder Reaction of 1‐(2‐Furyl)‐hex‐1‐en‐5‐yn‐3‐ol Derivatives: A Short and Generalized Route for the Synthesis of Hydroxyphenanthrene Derivatives.

AbstractAldehydes of type (I) and (IV) bearing an adjacent furyl substituent are transformed to the corresponding allylic and propargylic alcohols by In‐promoted reaction.

N-Heterocyclic Carbene (NHC)-Catalyzed Highly Diastereo- and Enantioselective Oxo-Diels–Alder Reactions for Synthesis of Fused Pyrano[2,3-b]indoles

A chiral N-heterocyclic carbene (NHC)-catalyzed Diels-Alder reaction of 2-oxoindolin-3-ylidenes and α-chloroaldehydes was developed for the synthesis of fused pyrano[2,3-b]indoles in good to excellent yields (up to 99%) with high cis-diastereoselectivities (>99:1 dr) and enantioselectivities (up to >99% ee).

Intramolecular gold(III) catalysed Diels–Alder reaction of 1-(2-furyl)-hex-1-en-5-yn-3-ol derivatives: a short and generalised route for the synthesis of hydroxyphenanthrene derivatives

Gold(III) catalysed intramolecular Diels–Alder reaction of various 1-(2-furyl)-hex-1-en-5-yn-3-ol derivatives has been studied to synthesise hydroxyphenanthrenes and other polynuclear aromatic hydroxyl compounds. The required precursors were synthesised by indium mediated propargylation of suitable β-furyl-α,β-unsaturated aldehydes.

The Correlation of Lewis Acidities of Silyl Triflates with Reaction Rates of Catalyzed Diels–Alder Reactions

AbstractThe Lewis acidity of various silyl triflates was quantified by utilizing [D5]pyridine as a 2H NMR spectroscopy probe. The chemical shifts of the 2H NMR signals for pyridine–silyl adducts are reported. The rate constants of silyl triflate catalyzed Diels–Alder reactions were determined by using UV/Vis spectroscopy. A correlation of the magnitude of the 2H NMR chemical shifts with the rate constants for most silyl triflates investigated was observed, but Me3SiOTf exhibits a surprisingly large deviation. Control experiments indicate that proton catalysis of the Diels–Alder reaction can be excluded.

Micellar-driven substrate selectivity in Cr(salen)Cl catalytic Diels–Alder reaction in water

A 3.5 increase in catalytic activity was observed in the Cr(III) (salen)Cl 3 catalyzed Diels–Alder reaction between cyclopentadiene 1 with the longer trans-2-decenal 2g compared to the shorter trans-2-butenal 2a dienophile under aqueous micellar conditions, while in chloroform the two substrates react with comparable activities.

Application of Electron-Withdrawing Coordinatively Unsaturated η6-Arene β-Diketiminato–Ruthenium Complexes in Lewis Acid Catalyzed Diels–Alder Reactions

Utilizing the aza-Wittig reaction involving the ylid 3,5-(CF3)2C6H3NPPh3 and 1,1,1,5,5,5-hexafluoro-2,4-pentanedione, a highly fluorinated and electron-withdrawing β-diketiminate was obtained. Using strong bases, nBuLi, Ag2O, or TlOEt, the corresponding β-diketiminato-Li, -Ag, or -Tl chelated complexes were prepared. Subsequent in situ transmetalation with (Ru(η6-C6H6)Cl2)2 or (Ru(η6-p-cymene)Cl2)2 afforded the half-sandwich chloro-substituted Ru(II) β-diketimino complexes in high yield. The synthesis of the Lewis acidic catalysts featuring a vacant coordination site at the metal center was accomplished using [Na]BArF (BArF = tetrakis[3,5-bis(trifluoromethyl)phenyl]boron). These complexes are active for the Lewis acid catalyzed Diels–Alder reaction between α,β-unsaturated aldehydes, that is, methacrolein, acrolein, and dienes, that is, cyclopentadiene and 2,3-dimethyl-1,3-butadiene, with conversions in the range of 66–98% under mild conditions. Whereas the herein described catalysts generally promote exo ...

Asymmetric Catalysis of Diels–Alder Reactions with in Situ Generated Heterocyclic ortho-Quinodimethanes

The Diels-Alder reaction is probably the most powerful technology in the synthetic repertoire for single-step constructions of complex chiral molecules. The synthetic power of this fundamental pericyclic transformation has greatly increased with the emergence of asymmetric catalytic variants, and research aimed at further expanding its potential is still exciting and fascinating the chemical community. Here, we document the first asymmetric catalytic Diels-Alder reaction of in situ generated heterocyclic ortho-quinodimethanes (oQDMs), reactive diene species that have never before succumbed to a catalytic approach. Asymmetric aminocatalysis, that uses chiral amines as catalysts, is the enabling strategy to induce the transient generation of indole-, pyrrole- or furan-based oQDMs from simple starting materials, while directing the pericyclic reactions with nitroolefins and methyleneindolinones toward a highly stereoselective pathway. The approach provides straightforward access to polycyclic heteroaromatic compounds, which would be difficult to synthesize by other catalytic methods, and should open new synthetic pathways to complex chiral molecules using nontraditional disconnections.

Lewis Acid Catalyzed Reactions of Chiral Imidazolidinones and Oxazolidinones: Insights on the Role of the Catalyst

The mechanism proposed by Evans to justify the selectivity obtained in Lewis acid catalyzed Diels-Alder reactions of cyclopentadiene with acyloxazolidinones has been generalized and used in the rationalization of selectivities obtained in many other systems. However, we recently proposed an alternative mechanism, on the basis of open-chain mono- and bicomplexes, that avoids the need for chelates and explains the selectivity obtained by Evans. In this manuscript we apply our proposal to the catalyzed conjugated addition of amines to acylimidazolidinones, reported by Cardillo, and we clearly show that aluminum chelates are not involved in the reaction, as they induce no selectivity, while Cardillo observed high experimental selectivities. Our data equally show that bicomplexes with carbonyl parallel orientation, proposed by Cardillo to justify the experimental selectivity with nonchelating Lewis acids, indeed induce the opposite selectivity and have also to be dismissed. On the other hand, our mechanistic proposal allows for the full rationalization of the data obtained by Cardillo with aluminum, boron, or zinc Lewis acids and supports our previous proposal on DA cycloadditions of dienes to Evans chiral auxiliary derivatives.

Theoretical Insights into the Enantioselectivity and Mechanism of Diels–Alder Reactions Involving Chiral Cationic Oxazaborolidinium Catalyst

Abstract The chiral oxazaborolidinium ion catalyzed Diels–Alder reaction between 2-methyl-1,3-butadiene and 2,3-dimethyl-1,4-benzoquinone was studied by means of density functional theory (DFT) at the B3LYP/6-31G(d) level of theory. Different DFT-based theoretical approaches including the reaction force, the natural population analysis of the charge transfer, the topological analysis of the electron localization function (ELF), and the global and local reactivity indices were applied to investigate and rationalize the mechanism and the endo/exo selectivity of this reaction. The changes in the physical and chemical properties of the reacting molecules along the intrinsic reaction coordinate (IRC) were also monitored to shed light on the mechanistic details. The analysis of the studied Diels–Alder reaction within the framework of DFT revealed and explained the preference of the endo path to the exo channel, and pointed out a concerted but highly asynchronous reaction mechanism.

Selectivities in Chiral Lewis Acid Catalyzed Diels–Alder Reactions of Acetylenic Ketones: Explanation for Differences of Selectivities between Acylic and Cyclic Dienes

Huey Lewis (acid) and the News: Crystallographic and computational studies on the cationic-oxazaborolidine-catalyzed Diels–Alder reaction of acetylenic ketones indicated that the reaction proceeds through a favored syn, exo transition state. These results provide a basis for understanding why acyclic dienes give higher enantioselectivities than cyclic dienes. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Brønsted acid catalyzed Diels–Alder reactions of 2-vinylindoles and 3-nitrocoumarins: an expedient synthesis of coumarin-fused tetrahydrocarbazoles

A Brønsted acid catalyzed Diels–Alder reaction of 2-vinylindoles and 3-nitrocoumarins has been described. The methodology allows a rapid and expedient synthesis of a variety of coumarin-fused polycyclic indoles in good yields (up to 82%) with high diastereoselectivities (up to >19:1).

Synthesis of 2-Trifluoromethyl Quinoline by the Reaction of Fluorinated Imine with Alkyne Catalyzed by Indium(III) Triflate

Preparation of 2-trifluoromethyl-4-aryl quinolines from a variety of readily available alkynes and N-aryl trifluoroethylimine has been achieved via indium(III) triflate catalyzed Diels-Alder reactions.

ChemInform Abstract: Catalysis of Diels-Alder Reactions by Metalloporphyrins.

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ChemInform Abstract: Diels-Alder Reactions Catalyzed by Zeolites.

Abstract Various Zeolite catalysed Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with less reactive dienophiles were studied. Exclusive endoselectivity was obtained with Ce-Y zeolite + anhydrous ZnBr2 for cyclopentadiene as well as cyclohexadiene Diels-Alder reactions.

ChemInform Abstract: (S)-(+)-Carvone as Chiral Starting Material. Part 2. Lewis Acid Catalyzed Diels-Alder Reactions of (S)-(+)-Carvone with Silyloxy Dienes. Total Synthesis of (+)-α-Cyperone.

ChemInform Abstract: (S)-(+)-Carvone as Chiral Starting Material. Part 2. Lewis Acid Catalyzed Diels-Alder Reactions of (S)-(+)-Carvone with Silyloxy Dienes. Total Synthesis of (+)-α-Cyperone.

ChemInform Abstract: A Stereoselective Synthesis of 2,6-Dideoxy-6,6,6-trifluoro-arabino-hexoses via an Asymmetric Diels-Alder Strategy.

The enantioselective syntheses of each enantiomer of ethyl 2,6-dideoxy-6,6,6-trifluoro-β-arabino-hexopyranoside (3) and of 2,6-dideoxy-6,6,6-trifluoro-arabino-hexose (4) are described. The key step in the approach is the inverse electron demand Lewis acid catalysed Diels–Alder reaction of the heterodiene (E)-1,1,1-trifluoro-4-[(1R)-1- phenylethoxy]but-3-en-2-one (5) and either ethyl vinyl ether (7a) or benzyl vinyl ether (7b). The titanium(IV) chloride catalysed cycloadditions at low temperature displayed high endo-selectivity and modest diastereofacial selectivity. Hydroboration of the mixture of the cis-cycloadducts (8a) afforded the separable diastereoisomers (9a) and (10a). Hydrogenolysis of (9a) gave ethyl 2,6-dideoxy-6,6,6-trifluoro-β-L-arabino-hexopyranoside (+)-(3), and of (10a) gave the corresponding D-glycoside (−)-(3). Similarly, hydroboration of the cis-cycloadducts (8b) gave the protected benzyl glycosides (9b) and (10b). Hydrogenolysis of each gave 2,6-dideoxy-6,6,6-trifluoro-L-arabino-hexopyranose (−)-(4) and the corresponding D-sugar (+)-(4) respectively. The absolute configurations of fluorinated carbohydrates (+)- and (−)-(3) were determined by comparison of their molar rotations with those of the parent glycosides. These assignments were confirmed by an X-ray crystallographic structure determination of the glycoside (9a).

(1R)-(+)-Camphor and Acetone Derived α′-Hydroxy Enones in Asymmetric Diels−Alder Reaction: Catalytic Activation by Lewis and Brønsted Acids, Substrate Scope, Applications in Syntheses, and Mechanistic Studies

The Diels-Alder reaction constitutes one of the most powerful and convergent C-C bond-forming transformations and continues to be the privileged route to access cyclohexene substructures, which are widespread within natural products and bioactive constituents. Over the recent years, asymmetric catalytic Diels-Alder methodologies have experienced a tremendous advance, but still inherently difficult diene-dienophile combinations prevail, such as those involving dienes less reactive than cyclopentadiene or dienophiles like beta-substituted acrylates and equivalents. Here the main features of alpha'-hydroxy enones as reaction partners of the Diels-Alder reaction are shown, with especial focus on their potentials and limitations in solving the above difficult cases. Alpha'-hydroxy enones are able to bind reversibly to both Lewis acids and Brønsted acids, forming 1,4-coordinated species that are shown to efficiently engage in these inherently difficult Diels-Alder reactions. On these bases, a convenient control of the reaction stereocontrol can be achieved using a camphor-derived chiral alpha'-hydroxy enone model (substrate-controlled asymmetric induction) and either Lewis acid or Brønsted acid catalysis. Complementing this approach, highly enantio- and diastereoselective Diels-Alder reactions can also be carried out by using simple achiral alpha'-hydroxy enones in combination with Evans' chiral Cu(II)-BOX complexes (catalyst-controlled asymmetric induction). Of importance, alpha'-hydroxy enones showed improved reactivity profiles and levels of stereoselectivity (endo/exo and facial selectivity) as compared with other prototypical dienophiles in the reactions involving dienes less reactive than cyclopentadiene. A rationale of some of these results is provided based on both kinetic experiments and quantum calculations. Thus, kinetic measurements of Brønsted acid promoted Diels-Alder reactions of alpha'-hydroxy enones show a first-order rate with respect to both enone and Brønsted acid promoter. Quantum calculations also support this trend and provide a rational explanation of the observed stereochemical outcome of the reactions. Finally, these fundamental studies are complemented with applications in natural products synthesis. More specifically, a nonracemic synthesis of (-)-nicolaioidesin C is described wherein a Brønsted acid catalyzed Diels-Alder reaction involving a alpha'-hydroxy enone substrate is the key step toward the hitherto challenging trisubstituted cyclohexene subunit.

(η6-Arene) ruthenium(ii) complexes and metallo-papain hybrid as Lewis acid catalysts of Diels–Alder reaction in water

Covalent embedding of a (eta(6)-arene) ruthenium(II) complex into the protein papain gives rise to a metalloenzyme displaying a catalytic efficiency for a Lewis acid-mediated catalysed Diels-Alder reaction enhanced by two orders of magnitude in water.