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.     

Photochemical Experiments with 2,3-Bis(Tert-Butylsulfonyl)Bicyclo[2.2.2]Octa-2,5-Diene and Related Systems

The irradiation of 2,3-bis(tert-butylsulfonyl)norbornadiene (5) and 2-(tert-butylsulfonyl)norbornadiene (6) yielded the expected quadricyclane derivatives as stable molecules. The irradiation of 2,3-bis(tert-butylsulfonyl)bicyclo[2.2.2]octa-2,5-diene(7) 2,3-bis(tert-butylsulfonyl)-exo-7,8-epoxybicyclo[2.2.2]-octa-2,5-diene (8) and 8,9-bis(tert-butylsulfonyl)-4-anti-phenyl-3,5-dioxa-exo-tricyclo[5.2.2.0^2,6] undeca-8,10-diene 9a and its syn-isomer 9b yielded the corresponding tetracyclic and pentacyclic systems, respectively. The photoproducts of 8 and 9 reverted to the starting products slowly at room temperature. The half-life of the photoproduct of 7 was determined to be 34 min at 50 °C. Compound 9a reacted with n-BuLi to yield the unexpected desulfonylation product 27a.     

The stepwise heats of hydrogenation of barrelene,an ab initio study

Ab initio Hartree-Fock calculations at the 6–31G*//3–21G level of theory are reported for bicyclo[2.2.2]-2,5,7-octatriene (barrelene), 1 , bicyclo[2.2.2]-2,5-octadiene, 2 , bicyclo[2.2.2]-2-octene, 3 , and bicyclo-[2.2.2]octane, 4 . The stepwise heats of hydrogenation of 1 were found to be 38.1, 31.8, and 28.4 kcal/mol, respectively. The unusually large heat of hydrogenation for the first double bond is attributed to the destabilizing electronic effects involving the interaction of the three double bonds of 1 .     

4-Aminobicyclo[2.2.2]octanone Derivatives with Antiplasmodial and Antitrypanosomal Activities

4-Aminobicyclo[2.2.2]octanones were converted to their N-oxides and to 4-aminobicyclo[2.2.2]octanes. Furthermore, the 6,7-bis-(4-methoxyphenyl) analogues were synthesized. All products were screened for their activities against Trypanosoma b. rhodesiense and Plasmodium falciparum. The pharmacological results were compared with those of formerly tested bicyclo[2.2.2]octanones and bicyclo[2.2.2]octanols. Structure-activity relationships are discussed.     

Synthesis and mesomorphic properties of chiral liquid crystal dimers derived from azobenzene and substituted naphthol

Symmetrical liquid crystal dimers bis{2-alkyl-(S)-(+)-2-(6-[4-4′-decyloxyphenylazo)-benzoyloxy]-2-naphthyl)propinate} have conveniently been designed, synthesised and their mesomorphic properties were investigated. These dimers possess two identical mesogenic units with each of them attached to the terminal end of a flexible spacer (–C _n H_2n ; where n = 6–10). The respective mesogenic unit was made up from a naphthyl ring attached to the alkyloxylated azobenzene via the ester (COO–) bond. The chiral moiety attached to the 6-position of the naphthyl ring possesses a terminal carboxylic group COO– which linked up the mesogenic unit and the spacer. The thermal and optical properties for the ultimate compounds at different temperature were studied explicitly with the aids of differential scanning calorimetry and polarising optical microscopy. All dimers exhibit unambiguously the monotropic nematic and smectic A phases. The homeotropic alignment of the molecules within the anisotropic region was further confirmed through the application of homogeneously treated cell.     

The Synthesis and Liquid-Crystal Transition Temperatures of Some Fluoro-Substituted Benzonitriles

Various laterally fluoro-substituted benzonitriles have been prepared containing a trans-4-(n-alkyl)cyclohexane ring linked to the 4-position of the benzonitriles either through a methyleneoxy (? CH₂O–) or an ethylene (? CH₂CH₂-) bridge. The bridging group links the benzonitrile and cyclohexane rings either directly or through an additional 1,4-bonded cyclohexane or benzene ring. The synthesis and liquid-crystal transition temperatures of these new compounds are described. In several cases the nematic-isotropic transition temperatures of F-substituted benzonitriles are found to be higher than those of the non-laterally substituted analogues.     

4-Aminobicyclo[2.2.2]octanone Derivatives with Antiplasmodial and Antitrypanosomal Activities

Summary. 4-Aminobicyclo[2.2.2]octanones were converted to their N-oxides and to 4-aminobicyclo[2.2.2]octanes. Furthermore, the 6,7-bis-(4-methoxyphenyl) analogues were synthesized. All products were screened for their activities against Trypanosoma b. rhodesiense and Plasmodium falciparum. The pharmacological results were compared with those of formerly tested bicyclo[2.2.2]octanones and bicyclo[2.2.2]octanols. Structure-activity relationships are discussed.Received April 8, 2003; accepted April 14, 2003 Published online September 25, 2003     

Effect of the variation of swallow-tailed groups on the mesomorphic and electro-optical properties of chiral compounds derived from (S)-2-(6-hydroxy-2-naphthyl)propionic acid

Three homologous series of chiral swallow-tailed compounds, alkyl (S)-2-{6-[4-(4′-alkoxyphenyl)benzoyloxy]-2-naphthyl}propionates, (S)HNP(p,n,q) derived from (S)-2-(6-hydroxy-2-naphthyl)propionic acid in conjugation with a variety of swallow-tailed groups, attached to the external side of the chiral centre, have been synthesized and their mesomorphic and electro-optical properties studied. Both (S)HNP(p,1,2) and (S)HNP(p,1,3) exhibited an enantiotropic antiferroelectric SmC*_A phase. This implys that the swallow-tailed groups in the molecules favour zigzag pairing of the molecules in the smectic phase. The maximum P _S values of compounds (S)HNP(p,1,2) in the antiferroelectric phase were measured in the range 21–30 nC cm^-2; those of compounds (S)HNP(p,1,3) were in the range 15–23 nC cm^-2, indicating that these chiral compounds possess low polarity. The electro-optical response of the compounds in the antiferroelectric SmC*_A phase displayed thresholdless V-shaped switching.     

The synthesis and transition temperatures of ester derivatives of 2-fluoro-4-hydroxy- and 3-fluoro-4-hydroxybenzonitriles also incorporating aliphatic ring systems

The synthesis and liquid-crystal transition temperatures of forty ester derivatives of 2-fluoro-4-hydroxybenzonitrile and 3-fluoro-4-hydroxybenzonitrile are reported. The esters contain the trans-1,4-disubstituted cyclohexane or the 1,4-disubstituted bicyclo[2.2.2]octane rings (some contain an additional phenyl ring). Many of the novel F-substituted esters exhibit substantially higher nematic-isotropic transition temperatures than the corresponding unsubstituted esters. The order of clearing points of these laterally substiuted esters differing only in the presence of a benzene ring and the above-mentioned rings id established.     

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.     

Asymmetric Conjugate Alkynylation of Cyclic α,β‐Unsaturated Carbonyl Compounds with a Chiral Diene Rhodium Catalyst

Asymmetric conjugate alkynylation of cyclic α,β‐unsaturated carbonyl compounds (ketones, esters, and amides) was realized by use of diphenyl[(triisopropylsilyl)ethynyl]methanol as an alkynylating reagent in the presence of a rhodium catalyst coordinated with a new chiral diene ligand (Fc‐bod; bod=bicyclo[2.2.2]octa‐2,5‐diene, Fc=ferrocenyl) to give high yields of the corresponding β‐alkynyl‐substituted carbonyl compounds with 95–98 % ee.     

Structural Requirements for the Antiprotozoal Activity of 4-Aminobicyclo[2.2.2]octan-2-ols

Several 4-aminobicyclo[2.2.2]octan-2-ones and -ols were synthesized using different pathways. The new compounds were investigated for their activity against Trypanosoma b. rhodesiense, the causative organism of East African sleeping sickness and Plasmodium falciparum the protozoan parasite which causes Malaria tropica. The results are compared to the activities of known compounds and the influence of the substitution of the bicyclo[2.2.2]octane skeleton on the biological activities is discussed.     

Synthesis of 6,9-Dipropyl-1,4-Dioxaspiro[4.5] Deca-6,8-Diene-2,10-Dione and its Diels-Alder Reactions with Substituted Acetylenes

The title compound, a masked 3,6-di-n-propyl-o-benzoquinone, was synthesized from 3,6-di-n-propylcatechol in 82% yield. Its Diels-Alder reactions with methyl propiolate, phenylacetylene, 1-octyne, dimethyl acetylenedicarboxylate, diphenylacetylene and 3-hexyne were studied. The yields of the adducts were excellent except for the last two cases in which the unimolecular decomposition of the title compound to generate 3,6-di-n-propylcatechol methylene ether predominates. The regiochemistry of the adducts derived from monosubstituted acetylenes were determined by the correlation of ¹³C chemical shifts of the adducts and the corresponding bicyclo[2.2.2]octa-5,7-diene-2,3-diones obtained from the hydrolysis of the spirolactone ring of the Diels-Alder adducts. Photolysis of these α-diketones gave the corresponding aromatic compounds in high yields. These synthetic sequences provide an effective entry to bicyclo[2.2.2]octa-5,7-diene-2,3-diones and polysubstituted benzene derivatives.     

Polyesters containing bicyclo[2.2.2]octane and bicyclo[3.2.2]nonane rings

Polyesters containing bicyclo[2.2.2]octane and bicyclo[3.2.2]nonane rings are prepared from 1,4-bis(carboethoxy)bicyclo[2.2.2]octane, 1,4-bis(hydroxymethyl)bicyclo[2.2.2]-octane and the 1,5-disubstituted bicyclo[3.2.2]nonane analogs. These polyesters are compared to the related polymers containing 1,4-phenylene and trans-1,4-cyclohexylene rings in terms of their melting point, thermal stabilities and oxidative stabilities. The lower symmetry of the bicyclo[3.2.2]nonane ring produces lower-melting polymers than the other ring systems. The remaining three rings are approximately equivalent in their effect on the melting point of a polymer provided that no more than one bicyclo[2.2.2]octane ring is present per polymer repeat unit. Two such rings produce a highermelting polymer than any other combination. Both the thermal and oxidative stabilities of the polyesters is improved by the presence of the bicyclo rings. This is attributed to the rings providing an approximation of a ladder polymer.     

The Non-planarity of the Bicyclo[2.2.1]hept-2-ene Double bond. Crystal Structures of Bicyclo[2.2.2]oct-2-ene,Bicyclo[2.2.1]hept-2-ene,and Bicyclo[2.1.1]hex-2-ene Systems

The crystal structures of (1R,4R,5S,8S)-9,10-dimethylidentricyclo[6.2.1.0^2,7]undec2(7)-ene-4,5-dicarboxylic anhydride ( 3 ), (1R,4R,5S,8S)11-isopropylidene-9,10-dimethylidenetricyclo[6.2.1.m^2,7]undec-2(7)-ene-4,5-dicarboxylic anhydride ( 6 ), (1R,4R,5S8S)-9,10-dimethylidenetricyclo[6.2.2.0^2,7]dodec-2(7)-ene-4,5-dicarboxylic anhydride ( 9 ), (1R4R5S8S)-TRICYCLO[6.2.2.0^2,7]dodeca-2(7), 9-diene-4,5-dicarboxylic anhydride ( 12 ) and (4R,5S)-tricyclo[6.1.1.0^2.7]dec-2(7)-ene-4,5-dicarboxylic acid ( 16 ) were established by X-ray diffraction. The alkyl substituents onto the endocyclic bicyclo[2.2.1]hept-2-ene double bond deviate from the C(1), C(2), C(3), C(4), plane by 13.5°4 in 3 and by 13.9° in 6 , leaning toward the endo-face. No such out-of-plane deformations were observed with the bicyclo[2.2.2]oct-2-ene derivatives 9 and 12 . The exocyclic s-cis-butadiene moieties in 3, 6 and 9 do not deviate significantly from planarity. The deviation from planarity of the double bond n bicyclo[2.2.1]hept-2-ene derivatives and planarity in bicyclo[2.2.2]oct-2-ene analogues is shown to be general by analysis of all known structures in the Cambridge Crystallographic Data File. The non-planarity of the bicyclo[2.2.1]hept-2-ene double bond cannot be attributed only to bond-angle deformations which would favour rehybridizatoin of the olefinic C-atoms since the double bond in the more strained bicyclo[2.1.1]hex-2-ene drivative 16 deviates from planarity by less than 4°.     

Synthesis and properties of novel extended BODIPYs with rigid skeletons

Novel extended BODIPYs fused with bicyclo rings were synthesized from bicyclopyrroles by combining Knoevenagel condensation, Suzuki coupling, and O-chelation. The absorption maxima of the BODIPYs ranged from the visible to near-infrared region and the compounds showed good solubility in organic solvents. The solubility of the bicycloBODIPY with 2-naphthyl groups at the α-position of the pyrrole units was particularly high. Heating converted distyrylBODIPY with bicyclo[2.2.2]octene to benzoBODIPY with absorption (748.5?nm) and fluorescence (775.0?nm) in the near-infrared region.     

Structural Requirements for the Antiprotozoal Activity of 4-Aminobicyclo[2.2.2]octan-2-ols

Summary. Several 4-aminobicyclo[2.2.2]octan-2-ones and -ols were synthesized using different pathways. The new compounds were investigated for their activity against Trypanosoma b. rhodesiense, the causative organism of East African sleeping sickness and Plasmodium falciparum the protozoan parasite which causes Malaria tropica. The results are compared to the activities of known compounds and the influence of the substitution of the bicyclo[2.2.2]octane skeleton on the biological activities is discussed.     

Michael reaction on example of unsaturated ketones of bicyclo[3.3.1]nonane series

Conclusions The reaction of bicyclo[3.3.1]-3,7-nonadiene-2,6-dione with nitromethane under the conditions of the Michael reaction in ether solution proceeds with the formation of 2,6-bis(nitromethyl)bicyclo[3.3.1]-nonane-4,8-dione, while in methanol this reaction leads to the formation of a derivative with the bicyclo[2.2.2]octane structure, specifically 3-carbomethoxymethyl-2-nitrobicyclo[2.2.2]-5-octanone.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2624–2626, November, 1981.The authors thank Yu. T. Struchkova, A. I. Akhmedova, and A. I. Yanovskii for running the x-ray structure analysis.     

Face Selectivity of the Diels-Alder Additions of 2-Substituted 5,6-bis((E)-chloromethylidene)bicyclo[2.2.2]octanes

The preparation of 5,6-bis((E)-chlorommethylidene)bicyclo[2.2.2]oct-2-ene ( 13 ), 2,3-bis((E)-chloromethyl idene)-5exo,6exo- and -5endo,6endo-epoxybicyclo[2.2.2] octane ( 14 and 15 ), 5,6-bis((E)-chloromethylidene)-2exo- and -2endo-bicyclo[2.2.2] octanol ( 16 and 17 ) and 5,6-bis((E)-chloromethylidene)-2-bicyclo[2.2.2]octanone ( 18 ) are described. The face selectivity (endo-face vs. exo-face attack onto the exo-cyclic diene) of their cycloadditions to tetracyanoethylene has been determined in benzene at 20°. It is 78/22, 80/20, 60/40, 68/32, 3/97 and 30/70 for 13 , 14 , 15 , 16 , 17 and 18 , respectively.     

Heterogenous Oxidation of [2.2.1] Bridged Bicyclic Alkenes with KMnO4-CuSO4.5H2O: An Alternative Ozonolysis

Seven [2.2.1] bridged alkenes were cleaved to the corresponding dialdehyde products by neutral heterogenous oxidation with KMnO₄-CuSO₄.5H₂O. While endo, endo-dimethyl bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylate, [2.2.2] bridged alkene, gave the corresponding α-hydroxy ketone, endo, endo-dimethyl bicyclo[3.2.2]non-8-ene-6,7-dicarboxylate afforded a diketone product.