Selective synthesis of multiply substituted 7-norbornenone derivatives or Diels-Alder cycloadducts from 1,2,3,4-tetrasubstituted 1,3-butadienes and maleic anhydride with or without Lewis acids

Reactions of 1,2,3,4-tetrasubstituted 1,3-butadienes with maleic anhydride and other dienophiles were investigated with or without addition of Lewis acid. When the silylated 1,3-butadienes, such as 1,4-bis(trimethylsilyl)-1,3-butadienes or 1-trimethylsilyl-1,3-butadienes, were treated with maleic anhydride in the presence of 2 equiv of AlCl₃, multi-substituted 7-norbornenones of well-defined exo,exo-disubstituted patterns were produced by an unprecedented and synthetically useful tandem process. Although some tetrasubstituted 1,3-butadienes could react directly with maleic anhydride under relative harsh conditions to afford Diels-Alder cycloadducts, the reactions, in the presence of 1 equiv of AlCl₃, afforded the corresponding cycloadducts in higher yields under mild conditions. These results showed that the size and substitution pattern of substituents on the butadienyl skeleton played a very important role in the reactivity of butadienes as a partner for the Diels-Alder reaction and Lewis acid could promote and/or realize the process of a Diels-Alder reaction.     

Dipolar cycloadditions of imidazoline 3-oxides with N-arylmaleimides. Synthesis and diethylamine induced ring-opening of exo and endo hexahydro-7-oxa-2,5,6a-triaza-cyclopenta[a]pentalene-1,3-diones

1,4-Diarylimidazoline 3-oxides react with N-arylmaleimides in benzene to give predominantly the corresponding endo adducts. Chiral imidazoline 3-oxides react diastereospecifically (cis configuration of the tetrahydroimidazo ring) and diastereoselectively to give cis-endo adducts. The effects of substituents on the aromatic ring of the maleimide was investigated. The presence of electron-withdrawing or releasing groups have minor effect on the total yields but more pronounced is the effect on the ratio of exo and endo diastereomers. The adducts undergo an interesting and unprecedented ring-opening in the presence of secondary amines to give deoxygenated 3-imidazoline 3-oxides instead of the expected double cis elimination products. Tertiary amines did not induce any reaction.     

Integrity of alkene stereochemistry in the Diels—Alder reaction

The Diels—Alder reaction of hexachlorocyclopentadiene and α-methylstyrene produces both exo-phenyl and endo-phenyl adducts, with the latter in preponderance. A deuterium label at the β position of the alkene provides a probe for determining whether the vicinal stereochemical relationship between groups on the alkene is retained in the adducts. From the alkene labeled 77.6±2.3% E and 22.4±2.3% Z was produced the major (endo-phenyl) isomer with 79.4±1.1% exo-d and 20.6±1.1% endo-d and the minor (exo-phenyl) isomer with 78.9±0.5% endo-d and 21.1±0.5% exo-d. Thus both adducts are produced with complete retention of alkene stereochemistry.     

Oxythallation of norbornene derivatives with thallium(III) acetate in methanol

Treatment of norbornene, norbornadiene, benzonorbornadiene, and chloro- and methoxy-benzonorbornadiene with thallium(III) acetate in methanol affords only the corresponding cis-exo-acetoxythallation adducts in a sharp contrast to oxymercuration of such strained olefins where methoxymercuration prevails. In the cases of substituted benzonorbornadienes the products are obtained as the regioisomeric mixtures, the isomer ratio being determined by ¹³C NMR. In the cases of 5-norbornene-2,3-dicarboxylic anhydride, 5-norbornene-2-methyl-2,3-dicarboxylic anhydride, and 5-norbornen-2-endo-carboxylic acid, lactonization occurs to give a trans-oxythallation adduct having a lactone ring, no introduction of either methoxy or acetoxy groups being observed. ¹H and/or ¹³C NMR data for several new oxythallation adducts are provided. The alkaline sodium borohydride reduction of adducts in methanol affords mainly the parent olefin together with 10–16% yields of the corresponding exo-alcohol.     

Kinetic studies of inverse electron demand Diels–Alder reactions (iEDDA) of norbornenes and 3,6-dipyridin-2-yl-1,2,4,5-tetrazine

Inverse electron demand Diels–Alder additions (iEDDA) between 1,2,4,5-tetrazines and olefins have recently found widespread application as a novel ‘click chemistry’ scheme and as a mild technique for the modification of materials. Norbornenes are, due to their straightforward synthetic availability, especially interesting in the latter context. Therefore, the reactivity of different norbornene-based compounds was compared with unsubstituted norbornene and other alkenes using UV-vis measurements for the determination of reaction rates under pseudo first order conditions. Thereby, exo,exo-5-norbornene-2,3-dimethanol was found to be almost as reactive as unsubstituted norbornene whereas (±)-endo,exo-dimethyl-5-norbornene-2,3-dicarboxylate reacted only insignificanty faster than unstrained alkenes.     

New exo/endo selectivity observed in monohydrolysis of dialkyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylates

New monohydrolysis reactions of several exo or endo dimethyl or diethyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylates showed higher selectivity toward monohydrolyses of exo-carboalkoxy groups, although the reaction centers are located away from the norbornene rings.     

Conjugate addition-Peterson olefination reactions: expedient routes to cross conjugated dienones

The synthesis of 5-alkylidenecyclopent-2-enones is readily achieved in two steps via a one-pot conjugate addition-Peterson olefination sequence, using exo-2-trimethylsilyl-3a,4,7,7a-tetrahydro-4,7-methanoinden-1-one, followed by a retro-Diels-Alder reaction.     

Experimental and DFT study of the aza-Diels-Alder reaction between cyclopentadiene and protonated benzylimine derivated from glyoxylates

The Diels-Alder reaction of protonated N-benzyl imine of methyl glyoxylate with cyclopentadiene in different solvents gave mixtures of exo/endo adducts. The exo/endo selectivity of the reaction was elucidated by NMR experiments. Theoretical calculations by means of density functional theory (DFT) at the B3LYP/6-31G(d) level have also been performed to elucidate the molecular mechanism of this reaction. The DFT results suggest a highly asynchronous concerted mechanism, which in turn can explain the preferred exo stereoselectivity of the reaction. Inclusion of solvent effects enhances the exo selectivity, and this effect increases with the polarity of the solvent, in good agreement with the experimental findings.     

Effect of substituents on addition polymerization of norbornene derivatives with two Me3Si-groups using Ni(II)/MAO catalyst

Addition polymerization and copolymerization of bis(Me₃Si)-substituted norbornene-type monomers such as 5,5-bis(trimethylsilyl)norbornene-2, 2,3-bis(trimethylsilyl)norbornadiene-2,5 and 3,4-bis(trimethylsilyl)tricyclo[4.2.1.0^2,5]nonene-7, in the presence of Ni(II) naphtenate/MAO catalyst were studied. Disubstituted norbornene and norbornadiene were found to be practically inactive in homopolymerization. On the other hand, their copolymerization with norbornene proceeded with moderate yields of copolymers containing predominantly norbornene units. Under studied reaction conditions 2,3-bis(trimethylsilyl)norbornadiene-2,5 was transformed into the only exo-trans-exo-dimer as a result of the [2+2]-cyclodimerization reaction. Moving Me₃Si-substituents one carbon atom away from norbornene double bond made 3,4-bis(trimethylsilyl)tricyclo[4.2.1.0^2,5]nonene-7 active in homopolymerization and allowed to obtain addition homo-polymer with two Me₃Si-substituents in each elementary unit. The reaction mechanism and steric effect of Me₃Si-substituents are also discussed.     

Decisive role of water in efficient noncatalyzed synthesis of polyfunctional 1H-1,2,3-triazoles proceeding from γ-hydroxypropynals

A highly efficient method was developed for the synthesis of new polyfunctional 1H-1,2,3-triazoles by the reaction of γ-hydroxypropynals with trimethylsilyl azide in water at room temperature without catalyst. The addition of trimethylsilyl azide to γ-hydroxypropynals occurs regioselectively: Previously unknown hydroxyalkyl-1H-1,2,3-triazolecarbaldehydes have been isolated in 69-96% yields with the prevalence of 1,5-isomers and the content of minor 1,4-isomers equal 9-21%. In the reaction of γ-hydroxypropynals with sodium azide in DMSO the formation of 4-hydroxyalkyl-1H-1,2,3-triazole-5-carbaldehydes is accompanied by the dimerization of initial aldehydes into the corresponding 1,3-dioxolanes.     

Novel generation and cycloaddition reactivity of N-phenylsulfonylbenzonitrilimine via thermal decomposition of N-(phenylsulfonyl)benzohydrazonoyl chloride

Thermal decomposition of N(phenylsulfonyl)-benzohydrazonoyl chloride (1) in refluxing toluene generated N-phenylsulfonylbenzonitrilimine (2) which gave 1,3-dipolar cycloadducts with ethyl (4a) and methyl acrylate (4b), acrylonitrile (4c), styrene (4d), norbornene (4e), and norbornadiene (4f). The reactions with 4a–d, 2 afforded regiospecifically 5-R substituted pyrazolines 5a–d in lower yields. The raction of 2 with 4e gave only exo adduct 5e, while the reaction with 4f gave both exo- (5f_x) and endo adducts (5f_n) as well as their retro-Diels-Alder product 6.     

N-Arylation of 4-fluoro-5-trimethylsilyl-1H-pyrazole

The 1,3-dipolar cycloaddition reaction of fluoro(trimethylsilyl)acetylene prepared in situ with an excess of diazomethane smoothly proceeded to give the corresponding 4-fluoro-5-trimethylsilyl-1H-pyrazole in 84% yield. The copper iodide-catalyzed N-arylation of the fluorinated pyrazole with a variety of aryl iodides afforded N-aryl-4-fluoropyrazoles as desilylation products in good to excellent yields.     

Stereochemistry of dihydroxylation of <Emphasis Type="Italic">N</Emphasis>-arylbicyclo[2.2.1]-hept-5-ene-<Emphasis Type="Italic">endo</Emphasis>- and -<Emphasis Type="Italic">exo</Emphasis>-2,3-dicarboximides

Stereochemistry of the oxidation of N-arylbicyclo[2.2.1]hept-5-ene-endo-and-exo-2,3-dicarboximides at the double bond with peroxyacetic acid generated in situ in the presence of sulfuric acid and with an anhydrous dioxane solution of peroxyacetic acid was studied. In both cases, the reaction was stereospecific, regardless of the substituent in the N-aryl group and configuration of the imide ring, but the reaction direction depended on the presence of water in the system. In the first case, the corresponding trans-5,6-dihydroxy derivatives were formed, while in the second, exo-5,6-epoxy derivatives. The oxidation of N-arylbicyclo[2.2.1]-hept-5-ene-endo-and-exo-2,3-dicarboximides with a solution of potassium permanganate in aqueous acetone gave the corresponding N-aryl-cis-5,6-dihydroxybicyclo[2.2.1]heptane-endo-and-exo-2,3-dicarboximides. The exo,cis,exo and exo,cis,endo configurations of the synthesized compounds were determined by ¹H NMR spectroscopy.     

Pd(II) -catalyzed addition polymerizations of strained polycyclic olefins

Cationic Pd(II) -complexes with weakly coordinating ligands were used for the olefin addition polymerization of strained polycyclic olefins. The cyclic structure of the monomers remained intact during the reaction which contrasts with products obtained from the olefin metathesis polymerization. The Pd(II) -catalyzed polymerizations showed the features of a “living” polymerization, when norbornene and selected exo-substituted norbornene derivatives were used as the monomers. Endo- and exo-dicyclopentadiene, exo-1,2-dihydrodicyclopentadiene, endo, exo-1,4,5,8-dimethano-1,2,3,4,4a,5,8,8a-octahydronaphthalene and endo, exo-1,4,5,8-dimethano-1,4,4,a,5,8,8a-hexahydronaphthalene were converted into the corresponding rigid polymers. The exo-substituted monomers were found to polymerize at a higher rate than the corresponding or similar endo-substituted monomers. The polymerization of norbornadiene and the subsequent thermal elimination of cyclopentadiene resulted in the formation of polyacetylene.     

Diels-Alder reaction of α-tropolone and electron-deficient dienophiles prompted by Et3N or silica gel: a new synthetic method of highly functionalized homobarrelenone derivatives

A Diels-Alder reaction of α-tropolone and electron-deficient dienophiles prompted by Et₃N or silica gel was performed. Reaction with the highly reactive dienophile, N-methylmaleimide, proceeded smoothly in the presence of Et₃N or silica gel to yield adducts as a mixture of endo and exo isomers. Both catalysts accelerated endo/exo isomerization of the product, and detailed examination of the reaction using hinokitiol and N-methylmaleimide revealed that isomerization proceeds via an intramolecular path without retro Diels-Alder reaction. Successful cycloaddition reactions were established with six other dienophiles: acrylonitrile, methyl acrylate, ethyl vinyl ketone, dimethyl fumalate, dimethyl malate, and dimethyl acetylenedicarboxylate, and the corresponding adducts were obtained in good to moderate yields.     

Rhodium catalyzed hydroformylation of 2-phenylsulfonylbicyclo[2.2.1] alkenes: effect of the phenylsulfonyl group

The preliminary results of the hydroformylation of 2-phenylsulfonyl substituted norbornene and norbornadiene derivatives catalyzed by the unmodified Rh(CO)₂acac system are presented. The reaction, occurring under standard oxo conditions, gives polyfunctionalized exo norbornene- and exo norbornanecarboxaldehydes. The effect of the phenylsulfonyl group has been evaluated: it has been found that the steric properties of the sulfonyl substituent, more than the electronic ones, influence the regioselectivity of the process.     

Water‐soluble polymers from acid‐functionalized norbornenes

Unprotected exo,exo‐5‐norbornene‐2,3‐dicarboxylic acid and exo,exo‐7‐oxa‐5‐norbornene‐2,3‐dicarboxylic acid were polymerized via ring‐opening metathesis polymerization. This reaction yielded polymers with molecular weights (M_n from GPC) ranging from 31 to 242 kg/mol and polydispersity indices between 1.05 and 1.12, using Grubbs' third generation catalyst. The water solubility as a function of pH value of the polymers was investigated by dynamic light scattering (DLS). DLS and acid‐base titration revealed that the oxanorbornene polymer was water soluble over a wider pH range than its norbornene analog. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1266–1273, 2009     

Highly Norbornylated Cellulose and Its “Click” Modification by an Inverse-Electron Demand Diels–Alder (iEDDA) Reaction

A facile, catalyst-free synthesis of a norbornylated cellulosic material (NC) with a high degree of substitution (2.9) is presented by direct reaction of trimethylsilyl cellulose with norbornene acid chloride. The resulting NC is highly soluble in organic solvents and its reactive double bonds were exploited for the copper-free inverse-electron demand Diels–Alder (iEDDA) “click” reaction with 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine. Reaction kinetics are comparable to the well-known Huisgen type 1,3-dipolar cycloaddition of azide with alkynes, while avoiding toxic catalysts.     

Enantioselective Heck-type hydroarylation of norbornene with phenyl iodide catalyzed by palladium/quinolinyl-oxazolines

Enantioselective Heck-type hydroarylation of norbornene with phenyl iodide catalyzed by the palladium complex of quinolinyl-oxazolines is described. Using DMSO as the solvent and HCOOH/Et₃N as the hydride source, exo-2-phenybicyclo[2.2.1]heptane is produced in reasonable yields and up to 74% ee.     

exo-Selective inverse-electron-demand hetero Diels–Alder reactions of norbornene with 5-benzylidine-2-arylimino-3-aryl-thiazolidine-4-thiones at room temperature

2-Arylimino-3-aryl-thiazolidine-4-thiones were synthesized from the corresponding thiazolidine-4-ones using Lawesson's reagent (LR) and converted into 5-benzylidine-2-arylimino-3-aryl-thiazolidine-4-thiones by reaction with benzaldehyde, which were then used as heterodienes in the inverse-electron-demand hetero Diels–Alder cycloadditions with norbornene as a dienophile at 25 ^°C. The reactions with norbornene were found to proceed with 100% exo-selectivity as determined by NMR experiments. The hetero Diels–Alder reactions with axially chiral heterodienes with ΔG^#>116 kJ/mol showed kinetic atroposelectivities up to 11:1. However, the products were found to equilibrate, as revealed by the 97.1 kJ/mol barrier to hindered rotation of the most sterically hindered product, to produce 2:1 diastereoselectivities after the 24 h reaction time.