Alkylations of tricyclo[5.2.1.0]deca-4,8-dien-3-one by a cuprate reaction

Alkylation at C₆ of tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one (R=H) was achieved by treatment of 6-bromotricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one with lithium dimethylcuprate and subsequently with an appropriate electrophile. The best results were obtained in THF as the solvent. A wide range of alkyl halides, bromo ketones and esters, and acetyl chloride resulted in C₆-tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-ones in moderate to good yields. This alkylation reaction proceeds via a C₆-carbanionic Cu intermediate, which is likely stabilized by the enone olefinic bond. 6-Bromo-endo-tricyclo[5.2.1.0^2,6]dec-8-en-3-one, which lacks this double bond, behaves differently. Treatment with lithium dimethylcuprate leads to dehydrobromination to give tricyclo[5.2.1.0^2,6]deca-2(6),8-dien-3-one in high yield.     

Lipase-mediated kinetic resolution of a synthetic equivalent of 2-hydroxymethylcyclopentadien-5-ol

Racemic 3-hydroxy-2-hydroxymethyl-endo-tricyclo[5.2.1.0^2,6]-dec-4,8-diene serving as a synthetic equivalent of 2-hydroxymethylcyclopentadien-5-ol has been resolved by employing lipase-mediated kinetic transesterification with vinyl acetate in an organic solvent.     

Transformations of cycloalkanes under the action of organoaluminum compounds and transition metal complexes in the presence of polychloromethanes

A catalytic system comprising an organoaluminum compound, polychloromethane, and a transition metal complex transforms cyclohexane into dimethyldecalins, cyclooctane into dimethyl- and ethylcyclohexanes, and endo-tricyclo[5.2.1.0^2,6]decane into its exo-isomer under mild conditions.     

Catalytic synthesis and transformations of magnesacycloalkanes

Catalytic cyclometallation of bicyclo[2.2.1]hept-2-ene, spirocyclo[2.2.1]hept-2-ene-7.1'-cyclopropane andendo-tricyclo[5.2.1.0^2,6]deca-3,8-diene (dicyclopentadiene) with R₂Mg (R =n-Pr,n-Bu) leading to the formation of polycyclic magnesacyclopentanes (MC) has been studied. The yield of MC and the selectivity of the reaction have been shown to depend on the ratio of starting reagents, the solvent, and temperature. The most probable scheme of the transformation studied is proposed.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 165–169, January, 1993.     

Structure and Thermal Behaviour of Methylcyclopentadiene Dimers

The mixture of isomeric dimethyl-endo-tricyclo[5.2.1.0^2,6]deca-3,8-dienes ( A ) resulting from Diels-Alder reactions of 1-, 2-, and 5-methylcyclopenta-1,3-dienes ( i – iii , respectively) at 20° was shown by GLC analysis to consist of at least 10 components (Table 1). The structures of the six major isomers 1 – 6 , representing 96% of the total mixture, were established by ¹H- and ¹³C-NMR spectroscopy. Whereas on heating up to 110° the proportions of 1 , 2 , 4 , and 6 remain nearly unaffected (±2 %), the dimers 3 and 5 , formed in 22 % and 24 % yield, respectively, at 20°, isomerise above 70° reversibly via [3,3]-sigmatropic rearrangement and equilibrate at 110° to a ca. 10:1 ratio.     

Unusual pathway of the tantalum-catalyzed carboalumination reaction of alkenes with triethylaluminum

Carboalumination of 1-alkenes (1-hexene, 1-octene, 1-decene) with Et₃Al in the presence of catalytic amounts of TaCl₅ results in a mixture of 2-(R-substituted)- and 3-(R-substituted)-n-butylaluminums (1:1 ratio) in total yields of 75–85%. The TaCl₅-catalyzed reaction of bicyclo[2.2.1]hept-2-ene, endo-tricyclo[5.2.1.0^2,6]deca-3,8-diene, and (exo/endo)-5-methylbicyclo[2.1.1]hept-2-ene with Et₃Al leads to the formation of diethyl[2-exo-(2′-norbornylethyl)]aluminums in high yields. DFT calculations confirm the thermodynamic preference of the final exo product. The multistep reaction mechanisms for the formation of the resultant organoaluminums through tantalacyclopentanes as key intermediates are also discussed.     

Studies on Cage Compounds. Synthesis of 8,11-Diazenediyl-4,4-Dimethoxy-2,3,5,6-Tetrachloropentacyclo[5.4.0.02,5.03,10.05,9]Undecane

The title compound ( 7 ) was synthesized in six steps from 1,8,9,10-tetrachloro-11,11-dimethoxy-endo-tricyclo[6.2.1.0^2,7]undeca-4,9-diene-3,6-dione ( 4 ) in an overall yield of 36%. The key intermediate, 1,8,9,10-tetrachloro-11,11-dimethoxy-endo-tricyclo-[6.2.1.0^2,7]undeca-3,5,9-triene ( 12 ), obtained from 4 by reduction, mesylation and then 1,4-elimination, was allowed to react with diethyl azodicarboxylate to afford the Diels-Alder adduct 16 . Photochemical closure of 16 , followed by hydrolysis and decarboxylation, gave the title compound. The title compound failed to give either the homopentaprismanone derivative 3 or the diene 9 by the photochemical or thermal elimination of molecular nitrogen.     

NMR studies on bridged polycyclic compounds: Spin system transitions due to induced solvent shifts

An NMR study of some bridged bicyclo and tricyclo compounds yielded unusual spectra with respect to solvent effects and virtual coupling. As is the general case for most large polycyclic systems a complete analysis of the spectrum is not possible and the structural details derived from NMR are based on a partial analysis of the spectrum. If the accessible resonances correspond to protons adjacent to methylene groups, the resonance patterns and the chemical shifts may be strongly dependent upon solvent. For 6-endo-hydroxy, bicyclo[2.2.1]heptane-2,endo-carboxylic acid lactone (1), 6-endo-hydroxy, 2-exo-methyl-bicyclo[2.2.2]octane-2-endo-carboxylic acid lactone (2), and exo-3,4,exo-8,9-diepoxy, endo-tricyclo[5,2,1,0^2,6]decane (3), resonances for each fall in this class and the change induced by solvent are attributed to virtual coupling as well as a change in the overall splitting pattern.     

Reactive species from aromatics and oxa-di-π-methane rearrangement: a stereoselective synthesis of (±)-hirsutene from salicyl alcohol

A total synthesis of hirsutene, a triquinane sesquiterpene, from salicyl alcohol is reported. Oxidation of salicyl alcohol in the presence of cyclopentadiene gave 9-spiroepoxy-endo-tricyclo[5.2.2.0^2,6]undeca-4,10-dien-8-one which was elaborated to the 3-hydroxy-2-methyl-endo-tricyclo[5.2.2.0^2,6]undeca-10-en-8-one containing major structural and functional features of hirsutene. Photochemical sigmatropic 1,2-acyl shift in 3-hydroxy-2-methyl-endo-tricyclo[5.2.2.0^2,6]undeca-10-en-8-one followed by radical induced cleavage of peripheral cyclopropane bond, olefination and Simmon-Smith reaction furnished 11-hydroxy-1-methyl-4-spirocyclopropanetricyclo[6.3.0.0^2,6]undecane that upon treatment with hydrogen on PtO₂ and PCC oxidation gave 1,4,4-trimethyltricyclo[6.3.0.0^2,6]undecan-11-one, a known precursor. Wittig methylenation on this precursor gave hirsutene.     

C,C-Double Bond Participation in the Acid-Catalyzed Cyclization of 9exo-Methyl-anti10,11-tricyclo[4.2.1.12,5]deca-3,7-diene-9endo, 10endo-diol. Influence of Steric Compression on the Product Distribution

Acid treatment of 9exo-methyl-anti^10,11-tricyclo[4.2.1.1^2,5]deca-3,7-diene-9endo, 10endo-diol ( 8 ) leads to the two isomeric pentacyclic ethers 7 and 9 by intramolecular nucleophilic substitution of a protonated OH-group with participation of a C,C-double bond. The higher steric compression in diol 8 on the side of the tertiary OH-group at C(9) and the C(3), C(4)-double bond, accounts for the preferred formation of 7 over 9 .     

Reactivity of 5-<Emphasis Type="Italic">endo</Emphasis>-hydroxy-4-azatricyclo[5.2.1.0<Superscript>2,6</Superscript>]dec-8-en-3-ones and their isomerization initiated by acids and bases

Study of isomerization of 5-endo-hydroxy-4-azatricyclo[5.2.1.0^2,6]dec-8-en-3-ones under the action of Lewis acids (MgBr₂, AlCl₃), CF₃COOH, and NaH showed that the optimum catalyst of the process was trifluoroacetic acid. In reaction of 4-benzyl-5-endo-hydroxy-4-azatricyclo-[5.2.1.0^2,6]dec-8-en-3-one with anhydrous AlCl₃ in benzene was unexpectedly isolated N-benzyl-3-(diphenylmethyl)bicyclo[2.2.1]hept-5-ene-2-carboxamide. A convenient method was developed for the preparation of 5-exo-alkoxy-4-alkyl(aryl)-4-azatricyclo[5.2.1.0^2,6]dec- 8-en-3-ones.     

Orbital control of stereochemistry in acid-catalysed addition reactions of endo -tricyclo[3.2.1.02,4]0ct-6-ene

The reaction of endo-tricyclo[3.2.1.0^2,4]oct-6-ene 1 with methanol in the presence of catalytic amounts of toluene-p-sulphonic acid has been shown to give 2-exo- and endo-methoxybicyclo[3.2.1]oct-3-ene (2c) and (2d) and 2-endo-methoxybicyclo[3.2.1]oct-6-ene (13). The formation of 2-exo- methoxybicyclo[3.2.1]oct-3-ene (2c), the major product of reaction, has been probed by deuterium labelling experiments and a series of 6-exo-7-exo- dideuterobicyclo[3.2.1]oct-3-enes synthesised for ²H, ¹H and ¹³C NMR spectral analysis in order unambiguously to determine the stereochemistry of proton attack on endo-tricyclo[3.2.1 0^2,4]oct-6-ene (1). The formation of 2-exo-methoxybicyclo[3.2.1]oct-3-ene (2c) has been determined to involve corner protonation of the cyclopropyl moiety and skeletal rearrangement to an allylic cation with a small but measurable memory effect     

Die Cyclopropylcarbinyl-Cyclobutyl-Homoallyl-Umlagerung. I. Teil. Synthese von Tricyclo[3.2.1.02,7]octan-3-ol,endo- und exo-Tricyclo[3.2.1.03,6]octan-4-ol und exo-Bicyclo[3.2.1]-oct-2-en-7-ol

Tricyclo[3.2.1.0^2,7]octan-3-ol ( 1 ) and its 4-isomer 7 were obtained by hydroboration of tricyclo[3.2.1.0^2,7]oct-3-ene ( 5 ). The former alcohol 1 is quantitatively converted to the isomeric alcohol exo-bicyclo[3.2.1]oct-2-en-7-ol ( 3 ) by treatment with aqueous acid. Photolysis of 1-diazo-3-(cyclopent-3-enyl)-propan-2-one ( 12c ) gave a high yield of tricyclo[3.2.1.0^3,6]octan-4-one ( 10a ). Reduction of the latter ketone produced a mixture of endo- and exo-tricyclo[3.2.1.0^3,6]octan-4-ol 2 and 9 , respectively. Oxidation of these secondary alcohols with silver carbonate in benzene furnished a mixture of the ketone 10a and the lactone 14 of 6-hydroxy-bicyclo[2.1.1]heptane-2-carboxylic acid. The latter is thought to be formed by oxydation of the hydrate of the strained ketone 10a .     

A Photoelectron-spectroscopic investigation of the Homoconjugative Interaction between π- and Walsh-Orbitals in endo- and exo-Cyclopropano-norbornene

Photoelectron spectra of endo- and exo-cyclopropano-norbornene ( = endo- and exo-tricyclo[3.2.1.0^2.4]octa-6-ene) show that a significant homoconjugation exists between the π-orbital of the double bond and the symmetric Walsh-es-orbital of the cyclopropane ring in the exo-isomer, whereas the interaction is negligeable in the endo-derivative.     

Saturation kinetics and relative reactivity of the double bonds of alicyclic dienes in their hydrogenation

The kinetics of the liquid-phase hydrogenation of cyclodienes with various structures (endo-tricyclo[ 5.2.1.0^2,6]decadiene-3,8 and cis,cis-1,5-cyclooctadiene) by hydrogen over a finely dispersed 1%Pd/C catalyst at atmospheric pressure has been studied. The catalyst provides the possibility for successive saturation of the double bonds of the dienes. The reactivities of the cyclodienes determined by their electron-donating properties have been compared. The solvent nature is the determining factor in the ratio of hydrogen absorption rates in the case of successive saturation of the double bonds of the hydrocarbons. The hydrogenation kinetics of cyclic dienes, including dicyclopentadiene, can be modeled using the Langmuir–Hinshelwood equation when the process is carried out in a perfectly mixed flow reactor.     

Synthesen von Tricyclo [5.2.1.04,8]decan (2-Homobrendan)

Syntheses of Tricyclo [5.2.1.0^4,8]decane (2-Homobrendane) Three different approaches to tricyclo [5.2.1.0^4,8] decane (5) (and derivatives thereof), one of the 19 isomeric hydrocarbons of the ‘adamantaneland’, are described: (1) Cyclization of properly functionalized bicyclo [3.2.1]octanes as 32 (cyclialkylation), 40+42 (thermocyclization) and 44+45 (photocyclization); (2) Silver-(I)-ion catalyzed rearrangement of 5,7- and 5,10-Dehydroprotoadamantane ( 63 and 64 , respectively) yielding tricyclo[5.2.1.0^4,8]dec-2- (39) and -5-ene (59) , respectively; (3) Thermal eliminative rearrangement of the 10endo-p-toluenesulfonate and -methanesulfonate of protoadamantane ( 71 and 72 ) and protoadamant-4-ene ( 76 and 77 ), respectively, yielding tricyclo [5.2.1.0^4,8]dec-2-ene (39) and -2, 5-diene (15) , respectively.     

New Tricyclic Amides. Synthesis,Structure, and Oxidation with Peroxyphthalic Acid

4-Azatricyclo[5.2.1.0^2,6]dec-8-ene was synthesized and brought into reactions with benzoyl, o-chlorobenzoyl, p-bromobenzoyl, p-, m-, and o-nitrobenzoyl, and bicyclo[2.2.1]hept-2-ene-endo-5,endo-6-dicarboximidoacetyl chlorides in chloroform in the presence of pyridine. The tricyclic amides thus obtained were epoxidated with peroxyphthalic acid prepared in situ by reaction of phthalic anhydride with a 35% aqueous solution of hydrogen peroxide. The structure of newly synthesized compounds was confirmed by IR and ¹H and ¹³C NMR spectroscopy and mass spectrometry. Their NMR spectra were compared with those of previously synthesized N-arylsulfonyl-4-azatricyclo[5.2.1.0^2,6]dec-8-enes on the basis of conformational composition of the corresponding p-nitrophenyl-substituted derivatives, which was determined by PM3 semi-empirical quantum-chemical calculations.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 837–845.Original Russian Text Copyright © 2005 by L. Kas’yan, Okovityi, Tarabara, A. Kas’yan, Bondarenko.     

Reactions of Bi-, Tri-, and tetracyclic amines with succinic anhydride

Succinic anhydride reacted with cage-like amines {bicyclo[2.2.1]hept-5-en-exo-and-endo-2-yl-methanamines, 2-(bicyclo[2.2.1]hept-5-en-endo-2-yl)ethanamine, exo-5,6-epoxybicyclo[2.2.1]heptan-exo-2-yl-methanamine, tetracyclo[6.2.1.1^3,6.0^2,7]dodec-9-en-endo-4-ylmethanamine, 1-(bicyclo[2.2.1]heptan-2-yl)ethanamine, and 4-azatricyclo[5.2.1.0^2,6]dec-8-ene} to give the corresponding amido acids having a cage-like fragment. The latter were converted into carboximides by the action of hexamethyldisilazane in boiling benzene in the presence of zinc(II) chloride and then into epoxy derivatives. The structure of the newly synthesized compounds was confirmed by IR and NMR spectroscopy.     

Nucleophilic addition to C,C?double bonds. Part IX. Kinetics and mechanism of the base-catalyzed intramolecular cyclization of olefinic alcohols

The base-catalyzed intramolecular cyclization of polycyclic olefinic alcohols of type a (10-endo-hydroxy-anti^9,10-tricyclo [4.2.1.1^2,5]dec-7-en-9-ones (type h ), anti^9,10-tricyclo[4.2.1.1^2,5] dec-3-en-9-endo-ols (type j ), and anti^10,11-tricyclo[4.3.1.1^2,5]undec-3-en-10-endo-ols (type 1 )) to the ethers d and f , resp., has been studied. A mechanism for the nucleophilic addition of the corresponding alkoxide anion b to the isolated C,C? double bond is discussed. It is proposed that b is formed (fast acid/base equilibrium) in the first step. For the subsequent reaction sequence, there are two well distinguishable pathways: (a) Compounds with an additional carbonyl group ( h ) cyclize via a homoenolate-like intermediate c , which is protonated stereoselectively on the exo-side by the hydroxylic solvent. (b) Compounds without a carbonyl group ( j and l ) cyclize 10²-10⁴ times slower, and the reaction proceeds via a carbanion-like transition state e . The proton transfer from the hydroxylic solvent is clearly coupled with the C,O? bond formation. Steric compression in the olefinic alcohols a influences the cyclization rate: (a) Alcohols with a smaller ring ( h , X = CH₂CH₂) cyclize 70–200 times faster than the ones with a larger ring ( 1 , X = CH₂CH₂CH₂). (b) Replacement of the H-atom at the carbinol C-atom by a CH₃ group enhances the rate of ether formation by a factor of 50–100. Due to through-bond interactions between the C,C-double bonds, olefinic alcohols with an additional endocyclic C,C-double bond ( h and j , X = CH?CH) cyclize 20–300 times faster than the corresponding monoolefinic ones ( h and j , X = CH₂CH₂).     

Synthesis of novel thienonorbornylpurine derivatives

The synthesis and antiviral evaluation of 6-amino- and 6-chloro-9-(exo-bicyclo[2.2.1]hept-2yl)-9H-purine derivatives with thiophene and tetrahydrothiophenes annelated to a norbornane moiety are described. The key step in the synthesis of derivatives with the symmetrically annelated thiophene was the Mitsunobu reaction of endo-4-thiatricyclo[5.2.1.0^2,6]deca-2,5-dien-8-ol with 6-chloropurine. The key alcohol was obtained by DDQ mediated aromatization of the corresponding tetrahydro derivatives, which were used for the preparation of the target tetrahydrothieno analogs. The key intermediate for the synthesis of derivatives with the asymmetrically annelated thiophene was 8-exo-azido-3-thiatricyclo[5.2.1.0^2,6]deca-2(6),4-diene, which was prepared from 5-exo-azido[2.2.1]heptan-2-one by aldol condensation with O-ethyl S-(2-oxoethyl) carbonodithioate, deprotection and cyclization. The target compounds were obtained by the construction of the purine base on an amine, which was obtained by LAH reduction of the key azide. The synthesized compounds were evaluated for antiviral and cytostatic activity.