2-Chlorobicyclo[2.2.1]hept-5-ene-2-carboxamide and 2-chlorobicyclo[2.2.1]heptane-2-carboxamide as precursors of bicyclo[2.2.1]hept-5-en-2-one and bicyclo[2.2.1]heptan-2-one: resolution,absolute configuration and hydrogen-bonding properties

The absolute configuration of bicyclo[2.2.1]heptan-2-one has not been correlated with a crystal structure of a chemical precursor. The only chemical correlation available had an ambiguity, which could have reversed the assignment. Herein, we report the resolution of 2-chlorobicyclo[2.2.1]hept-5-en-2-exo-carboxamide on a cellulose triacetate column and the crystal structures of the enantiomerically pure and racemic α-chloroamide. We found the absolute configuration (1R,2R,4R) for the (+)-enantiomer of the α-chloroamide. This compound was converted to (+)-bicyclo[2.2.1]hept-5-ene-2-one by base hydrolysis, and the 5,6-unsaturated compounds converted to the saturated congeners. This is the first unambiguous experimental determination of the absolute configuration of bicyclo[2.2.1]heptan-2-one and of bicyclo[2.2.1]hept-5-ene-2-one. The three crystal structures of 2-chlorobicyclo[2.2.1]hept-5-en-2-exo-carboxamide reported herein reveal H-bonded dimers, with two distinct orientations of the bicyclic portion relative to the carboxamide dimer. In the racemic crystal, each dimer is composed of two enantiomers, and the bicyclic portions have their bridge carbon atom (C-7) on opposite sides of the H-bonded carboxamide dimer moiety. In the enantiomerically pure crystals, the major dimer had both C-7 atoms on the same side of the carboxamide dimer moiety while the minor dimer had the C-7 atoms on opposite sides. The dimers are present in solution, and can be easily monitored.     

Synthesis and Epoxidation of 5-(2-Aminoethyl)bicyclo[2.2.1]hept-2-ene Derivatives

A number of derivatives of 5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene (85-90% of the endo isomer) were synthesized by reactions with p-nitrobenzenesulfonyl chloride, p-toluenesulfonyl chloride, benzoyl chloride, p-nitrobenzoyl chloride, benzyl isocyanate, m-tolyl isocyanate, phenyl isothiocyanate, and endic anhydride. By reactions of the resulting sulfon- and carboxamides with peroxyphthalic acid generated in situ from phthalic anhydride and 40-45% hydrogen peroxide the corresponding epoxy derivatives were obtained. These reactions were not accompanied by heterocyclization into azabrendane derivatives, which is typical of homologous N-(p-nitrophenylsulfonyl)-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene.     

Photoreaction of 5-dicyanomethylenebicyclo[2.2.1]hept-2-ene

Irradiation of 5-dicyanomethylenebicyclo[2.2.1lhept-2-ene induces new types of photoreactions, i.e., unprecedented skeletal rearrangement leading to 7,7-dicyano-6-methylenebicyclo[3.1.1]hept-2-ene, and novel 1,3-carbon shifts to bicyclo[3.2.0]- and bicyclo[4.1.0]heptene.     

Chemo- and Stereoselective Coordination of 5,6-Dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene by d8- and d6-Metal Carbonyls. Diels-Alder reactivity of Dienes Perturbed by Remote Olefin Complexation

The endocyclic double bond C(2), C(3) in 5,6-dimethylidene-7-oxabicyclo[2.2.1]-hept-2-ene ( 1 ) can he coordinated selectively on its exo-face before complexation of the exocyclic s-cis-butadiene moiety. Irradiation of Ru₃(CO)₁₂ or Os₃(CO)₁₂ in the presence of 1 gave tetracarbonyl [(1R,2R, 3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo[2.2.1]-hept-2-ene)]ruthenium ( 6 ) or -osmium ( 8 ). Similarly, irradiation of Cr(CO)₆ or W(CO)₆ in the presence of 1 gave pentacarbonyl[(1R, 2R, 3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene)]chromium (10) or -tungsten (11) . Irradiation of complexes 6 and 11 in the presence of 1 led to further CO substitution giving bed-tricarbonyl-ae-bis[(1R,2R,3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene)]ruthenium ( 7 ) and trans-tetracarbonyl[(1R,2R,3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo-[2.2.1]hept-2-ene)]tungsten (12) , respectively. The diosmacyclobutane derivative cis-m?-[(1R,3R,3S,4S)-(5,6-dimethylidene-7-oxabicyclo[2.2.1]hepta-2,3-diyl)]bis(tetracarbonyl-osmium) (Os-Os) (9) wa also obtained. The Diels-Alder reactivity of the exocyclic s-cis-butadiene moiety in complexs 7 and 8 was found to be significantly higher than that of the free triene 1 .     

Desymmetrization of meso 7-aza-2,3-bis(phenylsulfonyl) bicyclo[2.2.1]hept-2-ene: a re-examination. Kinetic resolution of racemic 3-arylsulfonyl-7-aza-2-bromobicyclo[2.2.1]hepta-2,5-dienes

The inexpensive large scale preparation of N-methoxycarbonyl-7-aza-2,3-bis(phenylsulfonyl)bicyclo[2.2.1]hept-2-ene and the re-examination of its stereoselective desymmetrization are reported. Moreover, the kinetic resolution of N-protected 3-arylsulfonyl-7-aza-2-bromobicyclo[2.2.1]hepta-2,5-dienes promoted by (R,R)-hydrobenzoin is described, representing a new tool to fix the absolute stereochemistry of the 7-azabicyclo[2.2.1] skeleton.     

1H-NMR Spectra of Cyclohexa-1,4-dienes and Cyclohexenes Annellated to Bicyclo[2.2.1]hept-2-enes. The Inter-Ring Homoallylic H,H Coupling Constants as Stereochemical Probes

The 360-MHz-¹H-NMR spectra of cyclohexa-1,4-dienes and cyclohexenes annellated to bicyclo[2.2.1]hept-2-enes and 7-oxabicyclo[2.2.1]hept-2-enes show inter-ring homoallylic coupling constants between the bridgehead protons of the bicyclo[2.2.1]heptenes and the exo-protons of the allylic methylene groups (0.8 ± 0.15 Hz for bicyclo[2.2.1]hept-2-enes; 0.8–1.4 Hz for 7-oxabicyclo[2.2.1]hept-2-enes). Contrastingly, the corresponding coupling between the bridgehead protons and the endo-protons is absent. The observed values are compared with those calculated by the INDO and CNDO/2 methods and discussed in the light of the bicyclo[2.2.1]hept-2-ene bond π-anisotropy. Vicinal as well as intra-ring homoallylic coupling constants are consistent with a small puckering of the cyclohexa-1,4-diene rings toward the endo-face. The allylic exo-methylene protons are more deshielded than the endo-protons independent of the nature of the substituents, the nature of the bridges, and the degree of unsaturation of the annellated systems. These results constitute a probe for the configuration of cyclohexa-1,4-dienes and cyclohexenes annellated to these bicyclic skeletons.     

外式双环[2.2.1]庚烷(庚-5-烯)-2,3-二甲酸酐膦二肽衍生物的合成

选择有机磷基团对斑蝥素的结构骨架进行修饰改造,以外式双环[2.2.1]庚-5-烯-2,3-二甲酸酐为原料,设计合成了一系列斑蝥素类似物。化合物的结构经1HNMR,MS及元素分析确证。     

Synthesis of 2-(Bicyclo[2.2.1]hept-2-yloxy)ethyl Carboxylates

Esterification of aliphatic carboxylic acids with 2-(bicyclo[2.2.1]hept-2-yloxy)ethanol and 2-(5-methylbicyclo[2.2.1]hept-2-yloxy)ethanol in the presence of KU-2-8 cation exchanger (H⁺ form) afforded a series of new compounds containing both ester and ether moieties.     

Optical resolution of 7-oxabicyclo[2.2.1]hept-21-ene derivatives. Diastereoselectivity in the formation of cyanohydrine-brucine complexes

A new, practical method for the optical resolution of bicyclic ketones if illusttrated by the preparation of (+)-(1R,4R)-7-oxabicyclo[2.2.1]bept-5-en-2-one ((+)- 1 ) and (+)-(1R, 2S,4R)-2-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-yul acetate ((+)- 4 ). It involves the diastereoselective formation of a brucine complex with the corresponding cyanhydrine mixture.     

Derivatives of exo-5-Aminomethyl-endo-5-methylbicyclo[2.2.1]hept-2-ene and exo-5-Aminomethyl-endo-5-methyl-exo-2,3-epoxybicyclo[2.2.1]heptane

exo-5-Aminomethyl-endo-5-methylbicyclo[2.2.1]hept-2-ene and its 2,3-epoxy derivative were synthesized, and their geometric parameters and conformational properties, in particular the barriers to rotation of the aminomethyl fragment about the exocyclic C⁵ÄC bond, were studied by the molecular-mechanics method (MMX) and compared with those found for structurally related exo-5-aminomethylbicyclo[2.2.1]hept-2-ene. The title compounds were brought into reactions with electrophilic reagents: arenesulfonyl chlorides, isocyanates, and isothiocyanates.     

v-Triazolines. part XXI. Spiro[bicyclo[2.2.1]hept-2-ene[54']1',2'.s'-triazole]derivatives from cyclopentadiene and 5-amino-4-methylene-v-triazolines

1R^*, 4R^*, 5S^*, 5'S^*-5'-Amino-1'-(4-nitrophenyl)-4',5'-dihydrospiro[bicyclo [2.2. 1]hept-2-ene[5.4]-1',2',3'-triazoles]$\text{2}$ have been obtained both by ?4 +2]-cycloaddition of cyclopentadiene to amino-methylene-1-(4-nitrophenyl)-4,5-dihydro-v-triazoles $\text{1}$ and by [3+2]-cycloaddition of 4-nitrophenylazide to 5-aminomethylene-2-norborenes $\text{4}$. The configuration has been fully established by X-ray crystallographic analysis. The course of the cycloaddition and the thermal behaviour of $\text{2}$ are discussed.     

Epoxidation of Bicyclo[2.2.1]hept-5-ene-2,3-endo- and Exodicarboxylic Acid N-Arylimides

Epoxidation of endo- and exo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid N-arylimides with a solution of peracetic acid in anhydrous dioxane affords 5,6-exo-epoxybicycloheptanedicarboxylic acid N-arylimides. The epoxidation reaction is not sensitive to the configuration of the imide fragment, to the character and position of the substituent in the aromatic ring. The reaction is determined only by oxidation conditions.     

Synthesis of monoethers by addition of aliphatic diols to bicyclo[2.2.1]hept-2-enes

Addition of aliphatic diols to bicyclo[2.2.1]hept-2-ene and its 5-alkyl-substituted derivatives in the presence of naphthalene-1,5-disulfonic acid leads to the formation of the corresponding bicyclo[2.2.1]hept-2-yl monoethers in high yields.     

Double bond isomerization of 5-vinylbicyclo[2.2.1]hept-2-ene to 5-ethylidenebicyclo[2.2.1]hept-2-ene over alkaline earth oxides

All the alkaline earth oxides exhibit activities for double, bond isomerization of 5-vinylbicyclo[2.2.1]hept-2-ene (VBH) to 5-ethylidenebicyclo[2.2.1]hept-2-ene (EBH) at a reaction temperature of 273 K. The order of the activity on the basis of unit weight of catalyst was CaO>MgO>SrO>BaO when compared under optimum pretreatment conditions. The E/Z ratio in the products is determined by the reaction temperature regardless of the type of catalyst; the ratios were 82/18 and 88/12 for the reaction temperatures of 323 and 273 K, respectively.     

Addition of bromine to 2-methyl-2-azabicyclo[2.2.1]hept-5-ene

Addition of bromine to 2-methyl-2-azabicyclo[2.2.1]hept-5-ene was studied. Unexpectedly, 3-bromo-1-methyl-1-azoniatricyclo[2.2.1.0^2,6]heptane tribromide was isolated rather than the product of bromine addition to the double bond. The former reacted with the starting alkene in a polar solvent to form the corresponding monobromide.     

Esters Synthesis by Addition of Monocarboxylic Acids to exo-5-Substituted Bicyclo[2.2.1]hept-2-ene Hydrocarbons

New alicyclic esters were synthesized by addition at heating of aliphatic monocarboxylic saturated acids C₁-C₄ to exo-5-phenyl-, exo-5-cyclohexyl-, and exo-5-(cyclohex-3-enyl)bicyclo[2.2.1]hept-2-enes. Among the esters obtained the acetates has more pleasant odor with fruit tint, and they may be used as a component of synthetic perfumes.     

Synthesis and Some Reactions of New N-[Aryl(Benzyl,Cyclohexyl, Propyl)sulfonyl]-4-azatricyclo[5.2.1.02,6]dec-8-enes

A synthesis was accomplished of 4-azatricyclo[5.2.1.02,6]dec-8-ene by aminolysis of bicyclo[2.2.1]hept-2-ene-endo,endo-5,6-dicarboxylic acid anhydride followed by transformation of amidoacid into imide that was subsequently reduced by lithium aluminum hydride. The reaction of the key tricyclic amine with sulfonyl chlorides afforded N-[aryl(benzyl, cyclohexyl, propyl)sulfonyl]-4-azatricyclo[5.2.1.02,6]dec-8-enes.The sulfonamides were subjected to epoxidation with perphthalic acid. By reaction of sulfonamides with p-nitrophenyl azide triazolines were obtained. The structure of compounds synthesized was confirmed by IR, ^1Hand ¹³ NMR spectra.     

Regioselective Electrophilic Additions of Bicyclo[2.2.n]alk-2-enes Controlled by Remote Epoxide Functions

The electrophilic additions of 2-nitrobenzenesulfenyl chloride to (1RS,2SR,4RS)-spiro[bicyclo[2.2.1]hept-5-ene-2,2′-oxirane] ( 12 ) and (1RS,2SR,4RS)-spiro[bicyclo[2.2.2]oct-5-ene-2,2′-oxirane] ( 14 ) were not regioselective under condition of kinetic control. However, good regioselectivity was observed for the addition of 2-nitro-benzenesulfenyl chloride to (1RS,2RS,4RS)-spiro[bicyclo[2.2.1]hept-5-ene-2,2′-oxirane] ( 13 ), giving (1RS,2SR,4SR,5RS,6RS)-6-exo-(2-nitrophenylthio)spiro[bicyclo[2.2.1]heptane-2.2′-oxirane]-5-endo-yl chloride ( 24 ) and for the exo addition to (1RS,2RS.4RS)-spiro[bicyclo[2.2.2]oct05-ene-2,2′-oxirane] ( 15 ), giving preferntially (1RS,2SR,4SR,5RS,6 RS)-6-exo-(2-nitrophenylthio) spiro[bicyxlo[2.2.2]octane-2,2′-oxirane]-5-endo-yl chloride ( 30 ). The facial selectivity (electrophilic exo vs. endo attack on the bucyclic alkene) depended on the relative configuration of the spiroepoxide ring in the bicyclo[2.2.2]octenes 14 and 15 . The exo-epoxide 14 was attacked preferentially (6:1) on the endo face by sulfenyl whereas exo attack was preferred (7:2) in the case of the endo-epoxide 15 . No products resulting from transannular ring expansion of the spiro-epoxide moieties could be detected.     

W(II)-catalyzed hydroarylation of bicyclo[2.2.1]hept-2-ene by simple arenes

The tungsten(II) carbonyl compound (CO)₄W(μ-Cl)₃W(SnCl₃)(CO)₃ has been found to be a very effective catalyst for the hydroarylation of bicyclo[2.2.1]hept-2-ene (norbornene) conducted in arene solution at room temperature. Norbornene adducts with benzene, toluene, para-xylene, and mesitylene have been isolated and their structures have been unambiguously established by means of ¹H and ¹³C NMR spectroscopy. On the basis of ¹H NMR monitoring of several catalytic reactions, a possible mechanism involving coordination of norbornene to the W(II) atom and its activation has been proposed.     

Bicyclo[3.1.0]hex-(1,5)-ene and bicyclo[4.1.0]hept-(1,6)-ene

The formation and trapping of bicyclo[3.1.0]hex-(1,5)-ene and bicyclo[4.1.0]hept-(1,6)-ene from the corresponding vicinal dibromides is described.