The Diels-Alder Reaction of Dienes Derived from Substituted 3-(Phenyl-Thio)-3-Sulfolenes

Substituted 3-(phenylthio)-3-sulfolenes (3) and (4) are good precursors for 2-(phenylthio)-1,3-butadienes (5) and (6). The Diels-Alder reaction of the dienes derived from (3) and (4) with various dienophiles was studied. It was found that heating of sulfolenes (3) with methyl propiolate and N-phenylmaleimide afforded the Diels-Alder adducts of (5) directly and with complete regio- and stereospecificity. The same reaction with methyl vinyl ketone gave a mixture of endo and exo addition products. If sulfolenes (3) were first converted to the dienes (5) using lithium aluminum hydride and then reacted with methyl vinyl ketone in the presence of anhydrous zinc chloride, the stereoselectivity could be improved. Sulfolenes (4) also underwent cycloreversion/cycloaddition with methyl acrylate, methyl vinyl ketone, and N-phenylmaleimide, but gave mostly the double bond-isomerized cycloaddition products. The regiochemistry of cycloaddition was delicately dependent on the dienophiles used.     

New Dienophiles: 1-Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

The preparations of 1-acetylvinyl arenecarboxylates H₂C=C(COCH₃)OCOR with R = phenyl, p-nitrophenyl, 2,4-dinitrophenyl, α- and β-naphthyl are described (3) . The Diels-Alder reactivity of these dienophiles toward cyclopentadiene is evaluated and compared with that of methyl vinylketone, 3-trimethylsilyloxy-, 3-ethoxy- and 3-acetoxy-3-buten-2-ones. The stereoselectivity of the cycloadditions of these dienophiles with 2,3,5,6-tetramethylidene-7-oxanorbornane (1) and 5,8-dimethoxy-1,4-epoxy-2,3-dimethylidene-1,2,3,4-tetrahydroanthracene (2) is studied. In principle, the dienophiles 3 allow direct functionalization of the position C(9) of the A-ring of daunomycinone analogs by Diels-Alder additions to exocyclic dienes such as 1 and 2 .     

Diels-Alder reaction in protic ionic liquids

Protic imidazolium ionic liquids have been tested as reaction media in the Diels-Alder reaction between cyclopentadiene and two dienophiles (dimethyl maleate and methyl acrylate). Good conversions and endo/exo selectivities were achieved. The activation of the dienophile by hydrogen bonding with protic imidazolium ILs was demonstrated.     

Catalytic Asymmetric Inverse‐Electron‐Demand Oxa‐Diels–Alder Reaction of In Situ Generated ortho‐Quinone Methides with 3‐Methyl‐2‐Vinylindoles

The first catalytic asymmetric inverse‐electron‐demand (IED) oxa‐Diels–Alder reaction of ortho‐quinone methides, generated in situ from ortho‐hydroxybenzyl alcohols, has been established. By selecting 3‐methyl‐2‐vinylindoles as a class of competent dienophiles, this approach provides an efficient strategy to construct an enantioenriched chroman framework with three adjacent stereogenic centers in high yields and excellent stereoselectivities (up to 99 % yield, >95:5 d.r., 99.5:0.5 e.r.). The utilization of ortho‐hydroxybenzyl alcohols as precursors of dienes and 3‐methyl‐2‐vinylindoles as dienophiles, as well as the hydrogen‐bonding activation mode of the substrates met the challenges of a catalytic asymmetric IED oxa‐Diels–Alder reaction.     

Chemie der Cumalinsäurederivate. I. Synthese und Diels-Alder-Reaktionen von 1-Arylamino-2-methoxycarbonylbutadienen

The nucleophilic attack of substituted anilines at position 6 of methyl coumalate (1) opens the α-pyrone ring to form 4-arylamino-3-(methoxycarbonyl)butadien-1-carboxylic acid 2 (Scheme 1). The latter are easily decarboxylated at room temperature in polar aprotic solvents to 1-arylamino-2-(methoxycarbonyl)butadiene 4 which smoothly undergo regio- and stereospecific Diels-Alder reactions with different dienophiles.     

[4+2] Cycloaddition reactions of 4-sulfur-substituted 2-pyridones with electron-deficient dienophiles

[4+2] Cycloaddition reactions of 4-(phenylthio)-1-tosyl-2-pyridone (6a) and 4-(phenylsulfonyl)-1-tosyl-2-pyridone (6b) with electron-deficient dienophiles 7 (N-methylmaleimide, N-phenylmaleimide, and methyl acrylate) gave new isoquinuclidine products 8-10. The N-tosyl group of 6a and 6b was also efficiently converted to N-alkyl derivatives 6c-f, which showed different stereoselectivity toward reactions with dienophiles 7. Several other dienophiles 15 (dimethyl acetylenedicarboxylate, methyl vinyl ketone, ethyl vinyl ether, and methyl methacrylate) were found not to react with 6a or 6b, but led to the formation of tosyl migration products 4-(phenylthio)-O-tosyl-pyridinol (16a) and 4-(phenylsulfonyl)-O-tosyl-2-pyridinol (16b), respectively. The reactivity, regioselectivity, and stereoselectivity of the cycloaddition reactions were also compared with semi-empirical calculations.     

Simple and New Method for the Synthesis of β-Acetamido Ketones on a Solid Surface

Diels–Alder reactions of 3-vinylindoles were carried out with methyl acrylate and N-phenylmaleimide as dienophiles under microwave conditions to furnish unreported tetrahydrocarbazoles regio- and stereoselectively in good yields. Further dehydrogenation resulted in new substituted carbazoles.     

Chiral thiophene dioxides and thiophene S,N-ylides as dienes for asymmetric diels-aldlr application

2-Menthyltrihalothiophene S,S-dioxides are efficient asymmetric dienes in Diels-Alder reactions with dienophiles to give regio- and stereoisomerically pure adducts. Thus styrene, allyl alcohol, methyl acrylate and acrylamide give solely one adduct while flat dienophiles such as indene and acenaphthylene give two diastereomers. Analogous 1- and 3- chirally substituted thiophenes are of little value in generating pure single adducts. Further transformations of the above adducts into useful enantiomerically pure compounds is briefly discussed.     

Preparation of vinylogous 2-sulfonylindolines by the palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones and their further transformation to indoles and carbazoles.

The palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones provides a convenient route to vinylogous 2-sulfonylindolines 3. The reaction proceeds in DMF/water in the presence of potassium carbonate and catalytic palladium(II) acetate and is compatible with both electron-donating and -withdrawing substituents in the para position of the aniline, and with an alkyl substituent at C-2 of the dienyl sulfone. The indolines underwent oxidation with DDQ to afford the corresponding indoles 4. The latter were then employed as dienes in Diels-Alder reactions with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate, or methyl acrylate. In the case of the latter two dienophiles, the cycloadditions were highly regioselective, affording the corresponding 1,3-products (with respect to the relative positions of the sulfone and ester groups), exclusively. The cycloadducts from acetylenic dienophiles were converted to the corresponding carbazoles by elimination of the sulfone moiety with DBU, and that from methyl acrylate was subjected to reductive desulfonylation and oxidation to the corresponding carbazole with DDQ. The method thus provides access to carbazoles with various substituents at the 3-, 4-, and 6-positions.     

A rationalization of the solvent effect on the Diels-Alder reaction in ionic liquids using multiparameter linear solvation energy relationships

The Diels-Alder reaction between cyclopentadiene and three dienophiles (acrolein, methyl acrylate and acrylonitrile) having different hydrogen bond acceptor abilities has been carried out in several ionic liquids and molecular solvents in order to obtain information about the factors affecting reactivity and selectivity. The solvent effects on these reactions are examined using multiparameter linear solvation energy relationships. The collected data provide evidence that the solvent effects are a function of both the solvent and the solute. For a solvent effect to be seen, the solute must have a complimentary character; selectivities and rates are determined by the solvent hydrogen bond donation ability (alpha) in the reactions of acrolein and methyl acrylate, but not of acrylonitrile.     

Diels-Alder reactions of 2-azadienes derived from cysteine and serine methyl esters and aldehydes

The Diels-Alder reactions of N-benzylidenedehydroalanine methyl ester 1a with but-3-en-2-one and with other electron deficient dienophiles have been found to give new dihydro- and tetrahydropyridines. The cycloaddition reactions are regioselective but not stereoselective. Cycloaddition reactions between 1a and enamines have also been observed. The [4 + 2] cycloaddition reactions of other N-arylidenedehydroalanine methyl esters are also reported. Two new types of azadiene were prepared, namely N-(benzoylmethylene)dehydroalanine methyl ester 1e and N-(ethoxycarbonylmethylene)dehydroalanine methyl ester 1f. Their reactions with N-cyclohexen-1-ylpyrrolidine and with N-cyclopenten-1-ylpyrrolidine have led to the isolation of the dihydropyridine and pyridine esters.     

Diels-Alder reactions of N-acyl-2-alkyl(aryl)-5-vinyl-2,3-dihydro-4-pyridones

Readily available N-acyl-5-vinyl-2,3-dihydro-4-pyridones undergo Diels-Alder cyclization with various dienophiles to afford novel octahydroquinolines containing synthetically useful functionality. With dihydropyridone 5 and cis-disubstituted dienophiles, the resulting cycloadducts were obtained as single diastereomers in good to excellent yield. The corresponding reaction of 5 with methyl acrylate, acrylonitrile, and phenyl vinyl sulfone showed modest preference for the endo adducts. The effect of the dihydropyridone C-2 and C-4 substituents on the degree of diastereofacial control was examined. By using this methodology, the core decahydroquinoline skeleton of gephyrotoxin was prepared in a stereocontrolled fashion. Interesting reactivity was observed with certain dienophiles leading to ring-opening of the initially formed cycloadducts. This tandem reaction provides a route to uniquely substituted beta-aminoketones, alcohols, and unnatural amino acids.     

Complete pi-facial diastereoselectivity in Diels-Alder reactions of dissymmetric 2,4-cyclohexadienones

[reaction: see text] The studies in the Diels-Alder reactions of 5-methoxy-masked o-benzoquinone (1a, R = OMe) and simple dissymmetric 2,4-cyclohexadienones 1b-e with methyl vinyl ketone, styrene, and benzyl vinyl ether are described. The dienones 1b-e reacted with dienophiles to form syn adducts (dienophile approach is syn to allylic methoxy group) exclusively.     

Highly stereoselective hydroxy-directed Diels-Alder reaction

The successful stereocontrol of the Diels-Alder reaction of semicyclic dienes possessing a secondary and tertiary allylic magnesium alkoxide alcohol functionality and activated dienophiles such as methyl acrylate, methacrolein, acrolein, and N-phenylmaleimide is described.     

Reactivity of 4-Hydroxy-2-pyrones in the Diels-Alder Reactions

Biphenylcarboxylic acid derivatives, and some tetracyclic bridge cycloadducts have been prepared by Diels-Alder reactions of acetylenic and olefinic dienophiles with 4-hydrpxy-6-phenyl-2H-pyran-2-one and its methyl ether derivative.     

Synthesis and thermal polymerization of perylene bisimide containing benzocyclobutene groups

Fourfold benzocyclobutene-functionalized perylene bisimide（PBI 4） has been synthesized and its structure was characterized by FTIR,MS and NMR.PBI 4 can react either with itself,or the appropriate dienophiles to form the corresponding products under appropriate temperature.The polymer film obtained from the reaction of PBI 4 with methyl vinyl silicone rubber possessed excellent film forming properties including flatness.The optical properties of PBI 4 and polymer film obtained from the reaction of PBI 4 and methyl vinyl silicone rubber have been determined by UV/vis and fluorescence spectroscopy.     

Stereoselectivity in Diels-Alder reactions of diene-substituted N-alkoxycarbonyl-1,2-dihydropyridines

Diene substituent effects on the regiochemical and stereochemical outcomes of uncatalyzed Diels-Alder reactions of N-alkoxycarbonyl-1,2-dihydropyridines with both styrene and methyl vinyl ketone (MVK) were studied. Alkyl substitution on the diene in all cases examined resulted in a kinetic preference for 7-endo isomers (7-phenyl 51-96% exo and 7-acetyl 54-96% exo). For both dienophiles, the highest stereoselectivities (>or=89% endo) were observed with 5-methyl or 6-methyl substituents in the dihydropyridine. Theoretical calculations of the energies of gas phase endo and exo transition states at the RHF/3-21G(*) predict that total entropy, DeltaStotal, considerations favor endo cycloadducts for both dienophiles with DHP, while total energy considerations, DeltaEo, favor endo cycloadducts for styrene and exo cycloadducts for MVK. At this level, favored endo-phenyl isomers are correctly predicted for styrene reactions, but the calculation of 7-acetyl exo or endo isomer dominance is diene-substituent-dependent for MVK reactions. The preference for endo addition of MVK to the parent, 5-methyl, and 6-methyl-DHPs was successfully predicted by calculations at the B3LYP/6-31G* theory level.     

Stereoselective Synthesis of 4,5‐Diethylidene‐Oxazolidinones as New Dienes in Diels‐Alder Reactions

The N‐substituted isomeric (4Z,5Z)‐ and (4E,5Z)‐4,5‐diethylideneoxazolidin‐2‐ones 5 and 6 were synthesized, the latter being favored during the one‐step process from the α‐diketone 1c and different isocyanates. The steric interaction between the N‐substituent and the Me group attached to the exocyclic diene moiety plays a decisive role in controlling the observed stereoselectivity, as suggested by the calculated free energies of the two isomers. Both dienes undergo efficient additions to symmetric dienophiles in thermal Diels‐Alder reactions to yield the adducts 11 and 13 , respectively. These molecules displayed interesting C−H⋅⋅⋅π, and C−H⋅⋅⋅X (X=O, Cl) interactions according to their X‐ray crystal structures. Isomers 6 suffered highly stereo‐ and regioselective additions with nonsymmetrical dienophiles such as methyl vinyl ketone or methyl propiolate. Steric interactions, promoted by the inward‐pointing Me group in 6 , seem to explain such selectivity. These results have also been rationalized by ab initio calculations in terms of the FMO theory.     

Synthesis and diels-alder reactions of e-1-trimethylsilylbuta-1,3-diene

A novel synthesis of E-1-trimethylsilylbuta-1,3-diene (1) has been achieved, and its Diels-Alder reactions with maleic anhydride, diethyl maleate, dimethyl fumarate, methyl propiolate, acrolein and acrylonitrile have been investigated. The structures of the products were studied to determine the stereoselectivity and regioselectivity of the reactions of this diene. In all cases with monosubstituted dienophiles the silyldiene 1 afforded the 1,3-disubstituted isomer (meta isomer) as the predominate regioisomer.     

Enchainements heteroatomiques et leurs produits de cyclisation—III : Réactions de Diels-Alder entre vinylogues de thioamides et diénophiles acryliques fonctionnels linéaires et cycliques. Propriétés chimiques des 2H-thiopyrannes liées aux substituants en position 2 et 3

The thioamide vinylogues (2-aminovinyl thioketones) react as heterodienes with open-chain and cyclic dienophiles to give substituted 4-amino-3,4-dihydro-2H-thiopyrans, or substituted 2H-thiopyrans and substituted 7 - methyl - 7,7a - dihydro - 5H - thiopyranno[2,3 - c] - 5 - furanones respectively, in good agreement with calculated perturbation energy of second order.