A four-step domino Knoevenagel–hetero-Diels–Alder reaction

A new, catalyst-free, domino Knoevenagel–hetero-Diels–Alder elimination oxidation reaction is reported. 5-Aryl-2H,6H-chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol-2-ones are formed in moderate to good yields via reaction of 2-(3-aryl-3-chloro-2-propenyloxy)benzaldehydes with 4-thioxo-1,3-thiazolidin-2-one.     

Synthesis of heterocycles by domino-Knoevenagel–hetero-Diels–Alder reactions

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Diels–Alder Additions to 2,2’-Biaceanthrylene

A series of Diels–Alder reactions between the diene 2,2’-biaceanthrylene and several dienophiles is presented. The diene is a cyclopenta-fused polycyclic aromatic hydrocarbon with anthracene units linked by two cyclopentene rings. Depending on the dienophile, the major product was the result of a single addition (dimethyl acetylenedicarboxylate) or double addition (quinone, benzyne) to the diene. Single crystal X-ray analysis of the quinone-derivative shows a propeller-like structure composed of mixed enantiomers. The synthesis and photophysical properties of these compounds are presented.     

How Lewis Acids Catalyze Diels–Alder Reactions

The Lewis acid(LA)-catalyzed Diels–Alder reaction between isoprene and methyl acrylate was investigated quantum chemically using a combined density functional theory and coupled-cluster theory approach. Computed activation energies systematically decrease as the strength of the LA increases along the series I₂<SnCl₄<TiCl₄<ZnCl₂<BF₃<AlCl₃. Emerging from our activation strain and Kohn–Sham molecular orbital bonding analysis was an unprecedented finding, namely that the LAs accelerate the Diels–Alder reaction by a diminished Pauli repulsion between the π-electron systems of the diene and dienophile. Our results oppose the widely accepted view that LAs catalyze the Diels–Alder reaction by enhancing the donor–acceptor [HOMO_diene–LUMO_dienophile] interaction and constitute a novel physical mechanism for this indispensable textbook organic reaction.     

Asymmetric diastereoselective thia-hetero-Diels–Alder reactions of dithioesters

Asymmetric thia-Diels–Alder reactions involving new dithioesters bearing a chiral auxiliary are described, with diastereoselectivities up to 78%. Double-stereodifferentiating experiments employing chiral substrates in the presence of a chiral Lewis acid catalyst have been also carried out and, in this case, a diastereomeric excess of 90% was reached. The absolute stereochemistry of cycloadducts resulting from dithiooxalates and carbonyloxazolidinone dithioesters was assigned based on an X-ray structure and chemical correlation. In order to rationalize the sense of the chiral induction, stereochemical models for Cu(II)/bis(oxazoline)/dithioester complexes are proposed.     

Aluminosilicate Catalysis of Chalcone Diels–Alder Reactions

Previously unreported Diels–Alder adducts of substituted chalcones with isoprene and myrcene have been formed at more than 0°C by employing a nanoporous aluminosilicate catalyst. This catalyst eliminates problems with diene polymerization that are encountered with many other Lewis acids. The chalcone component has some size restrictions.     

Diels–Alder Reactions of β-Acylacrylic Acids

The Diels–Alder reaction of β-acylacrylic acids with dienes gave good yields and good regio- or stereoselectivity of the corresponding cycloaddition products with the use of Lewis acids.     

Dual Activation of Aromatic Diels–Alder Reactions

The unusually fast Diels–Alder reactions of [5]cyclophanes were analyzed by DFT at the BLYP-D3(BJ)/TZ2P level of theory. The computations were guided by an integrated activation-strain and Kohn–Sham molecular orbital analysis. It is revealed why both [5]metacyclophane and [5]paracyclophane exhibit a significant rate enhancement compared to their planar benzene analogue. The activation strain analyses revealed that the enhanced reactivity originates from 1) predistortion of the aromatic core resulting in a reduced activation strain of the aromatic diene, and/or 2) enhanced interaction with the dienophile through a distortion-controlled lowering of the HOMO–LUMO gap within the diene. Both of these physical mechanisms and thus the rate of Diels–Alder cycloaddition can be tuned through different modes of geometrical distortion (meta versus para bridging) and by heteroatom substitution in the aromatic ring. Judicious choice of the bridge and heteroatom in the aromatic core enables effective tuning of the aromatic Diels–Alder reactivity to achieve activation barriers as low as 2 kcal mol⁻¹, which is an impressive 35 kcal mol⁻¹ lower than that of benzene.     

Sustainable Diels–Alder syntheses in imidazolium ionic liquids

An effective and simple protocol for the Diels–Alder reactions catalyzed and mediated by ionic liquid in conjunction with Lewis acid was studied. Diels–Alder adduct of the reaction of 1,4-benzoquinone with isoprene and 2,3-dimethyl-1,3-butadiene was obtained in good to excellent yields within the time span of 5.00–4.00 min under microwave irradiation. Due to the excellent activity of 2,3-dimethyl-1,3-butadiene as a diene, its efficiency was further analyzed by performing against four different dienophiles under various reaction conditions. The ionic liquid, 3-methyl-1-octyl-imidazolium tetrachloroaluminate mixed with Lewis acids, could be recycled and reused for consecutive cycles. The recovered ionic liquid in conjunction with Lewis acid displayed almost similar activity without any significant loss. This system is an essential upgrade and related to the reactions consuming common organic solvents at high temperatures and longer duration. Diels–Alder reactions under solventless conditions have also been investigated for the aforesaid reactions.     

Dynamics of Diels–Alder reactions involving 2-trialkylsilyloxyfurans

Increasing the size of the silyl group on 2-trialkylsilyloxyfurans reduces the rate of Diels–Alder reactions with maleic acid derivatives. While the exo-adduct resulted from the reaction between 2-silyloxyfurans and maleic anhydride, endo-adducts resulted from the reactions with maleate esters. Analysis of transition state structures for the cycloaddition, calculated at the B3LYP/6-31G1 level of theory, revealed significant stretch-mode asynchronicity in the forming bonds, with selectivity arising from steric interactions that affect torsional strain about the shorter of the forming bonds.     

Ruthenium carbenes as catalysts in stereoselective ene–yne metathesis/Diels–Alder and ene–yne metathesis/Diels–Alder/cross coupling multicomponent reactions

An ene–yne cross metathesis of silyl substituted alkynes and alkenes followed by a Diels–Alder reaction of the metathesis product 2-silyl-1,3-dienes has been developed. The dienes thus prepared in situ were shown to participate in highly diastereoselective Diels–Alder reactions. In one case the silicon substituted Diels–Alder cycloadduct was subsequently used without isolation and purification in a Hiyama cross coupling reaction. The cross coupling reactions enable these silicon dienes to be used as synthons for a variety of other dienes.     

Diels–Alder reactions of five-membered heterocycles containing one heteroatom

Diels–Alder reactions of five-membered heterocycles containing one heteroatom with an N-arylmaleimide were studied. Cycloaddition of 2,5-dimethylfuran (4) with 2-(4-methylphenyl)maleimide (3) in toluene at 60 °C gave bicyclic adduct 5. Cycloadditions of 3 with 2,5-dimethylthiophene (11) and 1,2,5-trimethylpyrrole (14) were also studied. Interestingly, the bicyclic compound 5 cleanly rearranged, with loss of water, when treated with p-toluenesulfonic acid in toluene at 80 °C to give 4,7-dimethyl-2-p-tolylisoindoline-1,3-dione (6).     

Tandem intramolecular Diels–Alder/retro-Diels–Alder cycloaddition of 2H-chromen-2-one as dienes with the expulsion of CO_2

To study the intramolecular Diels-Alder cycloadditon of 2H-chromen-2-one as a diene, a series of chiral N-allyl-N-benzylamides that contain a 2H-chromen-2-one moiety were designed for the synthesis of benzo[f]isoindol-1-ones via an intramolecular Diels-Alder and a subsequent retro-Diels-Alder cycloaddition with the expulsion of CO₂. Both the yield (80%-89%) and absolute stereocontrol of the tandem reaction were high when an electron-withdrawing group was attached to the dienophile. The double bond in the styrene substructure remained in the products could be further derivatized by dihydroxylation.     

Highly Enantioselective Diels–Alder Reaction Catalyzed by Chiral Imidazolidinone

New chiral imidazolidinone with an indole group was synthesized and used to catalyze the Diels–Alder reaction of α,β-unsaturated aldehyde with diene. High enantiomeric excesses and good yields were obtained. The reaction media were also surveyed. The best result in terms of enantioselectivity was achieved using acrolein and 2,3-dimethylbutdiene (up to 95% ee) in CH₃OH/H₂O.     

Synthesis of Chiral Bis-Thiazolines and Asymmetric Diels–Alder Reactions

Abstract

New chiral ligands, bis-thiazoline derivatives (sulfur analogues of known oxazolines) were prepared from chiral bis-(N-acylamino alcohols) with Lawesson's reagent. Bis-thiazolines thus obtained proved to be useful chiral ligands for metal in asymmetric Diels–Alder reaction.     

Water-soluble graphene dispersion functionalized by Diels–Alder cycloaddition reaction

Water-soluble graphene dispersions were fabricated by the exfoliation of graphite functionalized with furfuryl alcohol by Diels–Alder cycloaddition reaction. The pristine graphite was firstly heat-treated in N-methyl-2-pyrrolidone (NMP) before it was functionalized with furfuryl alcohol, and then, the increased interlayer spacing is propitious for furfuryl alcohol to enter into the lattice and react with graphite. High-resolution transmission electron microscopy and Raman spectroscopy indicate that the functional graphene is a high-quality product without any significant defects, and atomic force microscopy shows that the functional graphene consists of single to few layers graphene. Moreover, the grafting ratio onto graphene is up to 1.52 mmol/g. Therefore, the method provides a feasible route to produce functional graphene.     

Asymmetric Diels–Alder addition of cyclopentadiene to chiral naphthoquinones

Diels–Alder reactions of 1,4-naphthoquinones bearing a chiral auxiliary at C-2, with cyclopentadiene under Lewis acid conditions afforded the corresponding Diels–Alder adducts. High levels of diastereomeric excess were obtained using (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide and trans-2-phenylcyclohexanol as auxiliaries. Moderate asymmetric induction was achieved using Oppolzer's camphorsultam and (R)-(+)-4-benzyl-2-oxazolidinone as auxiliaries. X-Ray crystallographic analysis of the pantolactone adduct enabled determination of the stereochemistry of all adducts obtained.     

Synthesis of isoindolinones via inverse-electron demand Diels–Alder cycloadditions

A new synthetic method has been developed for the synthesis of 2,4,5-substituted isoindolinones by means of intramolecular inverse-electron demand Diels–Alder cycloaddition reactions of substituted pyridazines. By taking advantage of the inherent reactivity of an intermediate chloropyridazine, a diverse set of analogues were prepared from common reagents and intermediates.     

Enantioselective Diels–Alder reactions with left-handed G-quadruplex DNA-based catalysts

Since the discovery of left-handed G-quadruplex (L-G4) structure formed by natural DNA, there has been a growing interest in its potential functions. This study utilised it to catalyse enantioselective Diels-Alder reactions, considering its different optical rotation compared to an ordinary G4. It was determined that when L-G4 was used with a combination of copper(II) ions, there was a good enantioselectivity (?52% ee) without further addition of ligands. When further consideration was given by adding G4 ligands, G4 was further stabilised, even obtaining a better enantioselectivity (up to ?80% ee). Moreover, when using ligands that have regulatory effects on G4, the ee value can be adjusted. In this work, a minimal left-handed G4 was reported. A follow-up study was also conducted, which recovers that the minimal left-handed G4 remains its catalytic effect and enantioselectivity, but is not so effective as the former case. This indicates that a complete G4 structure is relatively conducive to chiral catalysis.     

Asymmetric Diels–Alder reactions of optically active oxazolidinone-derived vinylsulfonamides

Chiral vinylsulfonamides bearing an oxazolidin-2-one moiety derived from (R)-2-phenylglycinol and (1R,2S)-norephedrine have been employed as dienophiles in asymmetric Diels–Alder reactions at normal pressure affording d.e.s of up to 99% when EtAlCl₂ or Et₂AlCl were employed as Lewis acids. Theoretical calculations justify the observed enantio- and diastereoselectivity.