Synthesis and highly selective Diels-Alder cycloadditions of the new dienes N-substituted 2,3,5,6-tetrahydrobenzoxazol-2-ones

The synthesis of the new dienes N-substituted 2,3,4,5-tetrahydrobenzoxazol-2-ones 8a-8c is described, through a one-step convergent process from 1,2-cyclohexanedione (7a) and the corresponding isocyanates 2a-2c. The presence of electron-donor substituents in the aryl ring of the isocyanate gave rise to the exclusive formation of the captodative olefins 10. Diene 8a proved to be reactive and stereoselective in Diels-Alder additions with a cyclic olefin. The reaction with acetylenic dienophiles yielded the 2,3-dihydrobenzoxazol-2-ones 21 and 24, as the products of sequential [4+2] cycloaddition and retro-Diels-Alder reactions. Methyl vinyl ketone (22) underwent regio- and stereoselective tandem Diels-Alder and Michael additions to give propellane 29a. Evidence of an endo π-pyramidalization of the central double bond of adduct 19 would rationalize the exo stereoselection in the formation of 29a. The regioselectivity in these reactions has been rationalized in terms of FMO theory by ab initio calculations.     

Reactions of acceptor substituted thiophene-1,1-dioxides with cyclopentadiene: control of selectivity by substitution

Diels-Alder reactions of thiophene-1,1-dioxides with strong electron withdrawing groups (EWG) were studied experimentally and theoretically. Thiophene-1,1-dioxides with two strong EWG behave as dienophiles and regio- and stereoselectively react with cyclopentadiene to give [2+4] cycloadducts 2a-c, which are derivatives of benzothiophene. In contrast, thiophene-1,1-dioxides with one EWG behave as dienes in the inverse electron demand Diels-Alder reaction yielding dihydro-1H-indenes derivatives. Cope [3,3]-sigmatropic rearrangement of adducts 2a-c was also demonstrated. MP2 calculations successfully rationalize the contrasting regioselectivities of these cycloaddition reactions.     

Imino Diels-Alder reaction of boronates: A new route to 3,4-dihydroquinolines

The synthesis of a series of 3,4-dihydroquinolines (3b-e, 3h and 3i) by Imino Diels-Alder reactions involving sulfolene and boronates 2a-j derived from Schiff bases is described. The reactions are regioselective leading to 4-substituted dihydroquinolines with a cis relative stereochemistry between the phenyl group on the boron atom and the vinyl substituent at position 4, as established by X-ray diffraction analyses of 3b, 3e, 3h and 3i.Boronates 2 containing substituents meta to the imino fragment lead to 4-ethenyl-dihydroquinolines while para substituted derivatives are more reactive and lead to 4-cyclohexenylquinolines 4 formed by a second Diels-Alder reaction with excess of butadiene. The results show that boronates derived from Schiff bases are electron deficient species that react with sulfolene providing a new route to 3,4-dihydroquinolines. Moreover, polarization of the imine bond activates these system toward cycloaddition.     

Synthesis of (±)-kuwanon V and (±)-dorsterone methyl ethers via Diels-Alder reaction

The mulberry Diels-Alder adducts, the pentamethyl ethers of kuwanon V 1a and dorsterone 2a were synthesised via a biomimetic intermolecular [4+2] cycloaddition reaction between a highly electron-rich dienophile and a Lewis acid sensitive diene derived from chalcone. Cycloaddition under thermal conditions afforded 1a and 2a (in 3:2 ratio). Cycloaddition catalysed by AgOTf/Bu₄NBH₄ gave higher yields of the adducts.     

Diels-Alder cycloaddition of 2-azadienes to methyl 2-(2,6-dichlorophenyl)-2H-azirine-3-carboxylate in the synthesis of methyl 4-oxo-1,3-diazabicyclo[4.1.0]heptane-6-carboxylates

A number of fused 4-oxo-1,3-diazabicyclo[4.1.0]heptane-6-carboxylates, a new type of compound, have been obtained by Diels-Alder cycloaddition between nucleophilic 2-azadienes and an electrophilic 2H-azirine. The reactions are completely endo- and regioselective, the azirine being added by its less hindered face to the diene. There are two isomers 7 and 8 formed from dienes 1 due either to isomerization of the cycloadducts 7 and 8 or by isomerization of the CN bond of the diene during the reaction. The isomer 10 is formed from diene 2e, and a single diastereoisomer structure 4a-i is formed from dienes 11. Some pyrimidones 8a, 7c/8c, 7e, 10, 11d have been hydrolyzed leading to functionalised aziridines 12, 13 and 15.     

Imino Diels-Alder reaction of boronates. Preparation and characterization of new 3,4-dihydroquinoline and 1,2,3,6-tetrahydropyridine derivatives

The preparation of 3,4-dihydroquinolines (2a-d and 3a,b,d), as well as 1,2,3,6-tetrahydropyridines (4a-e) by imino Diels-Alder reaction of boronates (1a-e) with 2,3-dimethylbutadiene is reported. Boronates (1a-d) containing substituents meta and para relative to the imino fragment lead to diastereomeric mixtures of 4-methyl-4-ethenyl-3,4-dihydroquinolines (2, 3) and tetrahydropyridines (4). In contrast, the presence of an electron withdrawing substituent at the para position (1e), favors the iminodienophile behavior giving 4,5-dimethyl-1,2,3,6-tetrahydropyridine (4e) as the main product. The results show that boronates derived from Schiff bases are electron deficient species which can act either as dienophiles or dienes in the reaction with 2,3-dimethylbutadiene to give 3,4-dihydroquinolines and 1,2,3,6-tetrahydropyridines. All products were characterized by NMR and X-ray diffraction analysis of 2b, 2d, 3d and 4c allowed to assign the relative configuration of the newly formed stereogenic centers.     

Diels-Alder reactions of masked o-benzoquinones with acrylonitrile

Regioselective Diels-Alder reactions of masked o-benzoquinones (MOBs) 2a-i derived from the corresponding 2-methoxyphenols 1a-i with acrylonitrile leading to highly functionalized bicyclo[2.2.2]octenone derivatives in high yields are described.     

Highly efficient synthesis of extended triptycenes via Diels-Alder cycloaddition in water under microwave radiation

Microwave-irradiated Diels-Alder reactions of anthracene and endoxides (6a-g) in water afforded the cycloadducts (8a-g) with high efficiencies. The extended triptycenes (2a-g) were readily obtained by dehydration of 8a-g in a mixture of AcOH and Ac₂O with good overall yields.     

Synthesis of substituted pyrano[3,2-c]pyridines via Diels-Alder reaction of 3-methylenepyridin-4-one

On heating, the di-Boc-pyridin-4-one derivative 7 gave an unstable 3-methylenepyridin-4-one intermediate 3, which underwent a rearomatising Diels-Alder cycloaddition with activated alkenes to give substituted pyrano[3,2-c]pyridines in moderate yields.     

Domino routes to substituted benzoindolizines: tandem reorganization of 1,3-dipolar cycloadducts of nitrones with allenic esters/ketones and alternative cycloaddition-palladium catalyzed cyclization pathway

Reactions of C-(4-oxo-4H[1]benzopyran-3-yl)-N-phenyl nitrones (7) with allenic esters (8a-c) and allenic ketones (18a-d) furnish benzoindolizines (9a-k, 19a-d) in good yields. The formation of benzoindolizines is postulated to involve regioselective addition of 1,3-dipole to C2-C3 π bond of allenic esters/ketones followed by domino transformation of the cycloadducts, which involve an intramolecular aza Diels-Alder reaction in the intermediate C. DFT calculations of various parameters for diene and dienophile components in the proposed intermediate C have revealed that conformational constraints imposed by the alkyl groups (R=Me, Et) favor intramolecular aza-Diels-Alder cycloaddition. An alternative domino route to benzoindolizines (9a,d,g) involving sequential one-pot cycloaddition of azadienes (22a-c) with silyl-enol ether (23) followed by palladium(0)-catalyzed Heck coupling reaction has also been developed. Both these approaches represent novel domino routes for the synthesis of benzoindolizines.     

Synthesis of 2,2′-bipyridyl derivatives using aza Diels-Alder methodology

Amidrazone 1 and the tricarbonyl derivatives 2a-c gave the triazines 3a-c, respectively, which reacted with 2,5-norbornadiene 4 in boiling ethanol yielding the corresponding novel 2,2′-bipyridines 5a-c in good yield. Triazine 6 gave the 2,2′-bipyridyl derivative 7 (65%) with compound 4 in 1,2-dichlorobenzene at 140°C.     

Solid-state photocycloaddition of 6,6′-dimethyl-4,4′-[bis(methylenoxy)phenylene]-di-2-pyrones with benzophenone

Photocycloaddition reactions of 6,6′-dimethyl-4,4′-[bis(methylenoxy)phenylene]-di-2-pyrones (4a-c) with benzophenone (2a) by mixing in the solid state (solid solution) afforded the corresponding oxetane derivatives (5a-c; 1:2 adducts) with high site- and regioselectivity across the C5-C6 and C5′-C6′ double bonds in 4 via the triplet excited state of benzophenone. The oxetane formation proceeded more effectively in the solid state than in solution. The reaction mechanism was inferred by MO methods to be initiated by electrostatic interaction between the C6 position of 4a-c and the carbonyl oxygen of 2a in their ground states. The solid-state interaction may be enhanced by the electron density at the carbonyl oxygen of the triplet 2a. The transition state (TS) analysis of the [2+2] cycloaddition reactions also suggested some triplet complexes and high regioselectivity. The hydrogen-bonding interaction between 2a and 4a-c and the triplet reaction mechanism were also explained by the IR analyses and the quenching experiments, respectively.     

Intramolecular Diels-Alder reaction of 2-diphenylphosphinyl-5-(propargyloxymethyl)furans followed by nucleophilic 1,2-rearrangement of the phosphinyl group

The base-catalyzed intramolecular Diels-Alder reactions of 2-diphenylphosphinyl-5-(propargyloxymethyl)furans 2a-e gave the tetrahydrofuran ring annulated o-diphenylphosphinophenols 3a-e in 70-80% yields, a novel reaction involving an intramolecular Diels-Alder reaction of furan diene with allenyl ether dienophile followed by a nucleophilic 1,2-rearrangement of the diphenylphosphinyl group.     

A tandem decarboxylation and inverse electron-demand Diels-Alder reaction of amino-thiophenecarboxylic acids with 1,3,5-triazines

The scope of 1,3,5-triazine inverse electron-demand Diels-Alder (IDA) reactions was expanded to include aminothiophenecarboxylic acids as latent dienophiles. A series of 2-amino-3-thiophenecarboxylic acids (1a-d) and a 3-amino-2-thiophenecarboxylic acid (5) were introduced as productive dienophiles in IDA reactions with various 1,3,5-triazines (2a-e). This method is useful for the one-step synthesis of both thieno[2,3-d]pyrimidines and thieno[3,2-d]pyrimidines, which should complement existing methods.     

Chiral pyridine imidazolines from C1-symmetric diamines: Synthesis, arene ruthenium complexes and application as asymmetric catalysis for Diels-Alder reactions

Condensation of mono N-substituted chiral ethylenediamines and pyridine-2-methoxyimidate gives new chiral pyridine imidazolines (1a-c). These react with [RuCl₂(mes)]₂ (mes = 1,3,5-trimethyl benzene) in the presence of NaSbF₆ to give complexes [RuCl(L)(mes)][SbF₆] (5a-c) which after treatment with AgSbF₆ are enantioselective catalysts for the Diels-Alder reaction of methacrolein and cyclopentadiene. The imidazoline catalysts are less selective than the corresponding oxazoline ones. Compounds 1a, 5b and 5c have been characterised by X-ray crystallography.     

Diels-Alder reactions of pyrrolo[3,4-b]porphyrins

In the presence of excess dimethylacetylene dicarboxylate (DMAD), nickel(II) pyrrolo[3,4-b]porphyrins undergo both Diels-Alder cycloaddition and Michael addition in toluene to give two bis-adducts, identified as compounds 4 and 5; the reaction can be accelerated by the addition of Lewis or Brønsted-Lowry acids. Refluxing the reaction mixture in 1,2,4-trichlorobenzene (220 °C) leads to a nickel(II) monobenzoporphyrin 2 as the main product. The structure of compound 4 was confirmed by X-ray crystallography.     

Sequential homo-coupling Diels-Alder/retro Diels-Alder reaction of 5,5′-bi-1,2,4-triazine-containing thiamacrocycles as a new route to thiacrown ethers incorporating a 2,2′-bipyridine subunit

A new route to thiacrown ethers 5a-d and 6a-d incorporating a 2,2′-bipyridine subunit is elaborated using, (1) homo-coupling of 1,2,4-triazine sulfides 3a-d tethered to poly(ethylene glycol) chains with potassium cyanide and (2) Diels-Alder/retro Diels-Alder reaction with norbornadiene or 1-pyrrolidino-1-cyclopentene as the key steps.     

Cyclization in situ of enose-/ynose-nitrilimines: an expedient approach to the synthesis of chiral glycopyrazoles and pyrazolonucleosides

Intramolecular [3+2] nitrilimine cycloaddition reactions on carbohydrate-derived substrates proceed in a regioselective fashion, affording structurally novel chiral glycopyrazoles (4-6 and 10a-c) in good yields. The products can be subsequently transformed to bicyclic pyrazoles (viz. 11 from 4) or nucleoside analogues (viz. 12 from 4).     

Microwave-assisted reactions of nitroheterocycles with dienes. Diels-Alder and tandem hetero Diels-Alder/[3,3] sigmatropic shift

Diels-Alder cycloaddition of 3-nitro-1-(p-toluenesulfonyl)indole 1 with dienes 2-6 under microwave irradiation in solvent-free conditions gave carbazole derivatives after elimination of the nitro group and in situ aromatization. While 3-nitro-1-(p-toluenesulfonyl)pyrrole 11 afforded indole derivatives, 4-nitro-1-(p-toluenesulfonyl)pyrazole 13 with cyclohexadiene 2 did not afford the expected cycloadduct but instead gave 1-cyclohexen-2-ylpyrazole 16. This process occurred by hydrolysis of the 1-(p-toluenesulfonyl) group, protonation of the diene and nucleophilic addition of the pyrazolate ion, as elucidated by computational studies. Reaction of nitroindole 1 with cyclohexadiene 2 afforded exclusively the endo stereoisomer (10endo) in a tandem hetero Diels-Alder/[3,3] sigmatropic shift, as determined by computational calculations.     

[60]Fullerene adducts with 9-substituted anthracenes: mechanochemical preparation and retro Diels-Alder reaction

Three 9-substituted anthracene derivatives, that is, 9-hydroxymethylanthracene (2), 9-methoxymethylanthracene (3) and bis(9-anthrylmethyl) adipate (6), were chosen as the model compounds to evaluate the reactivity in their Diels-Alder reactions with [60]fullerene and in retro Diels-Alder reactions of the formed cycloadducts. Corresponding adducts 4, 5 and 7 were prepared in high yields under solvent-free conditions using high-speed vibration milling technique. In order to determine thermal stabilities of adducts 4, 5 and 7, their dissociations in the temperature range of 40-65 °C were investigated. Fitting the dissociation rates and temperatures to the Arrhenius equation gives the activation energies of 25.8, 21.8 and 24.9 kcal/mol for compounds 4, 5 and 7, respectively.