Synthesis and characterization of tetramethylene-syn-sesterbicyclo[2.2.2]octene

The synthesis of syn-sesterbicyclo[2.2.2]octene (7) bilaterally grafted by an exocyclic s-cis-butadiene moiety is achieved from 1,8,9,10-tetrachloro-11,11-dimethoxy-endo-tricyclo[6.2.1.0^2,7]undeca-3,5,9-triene (8) employing repetitive Diels-Alder cycloadditions between 1,3-cyclohexadiene, generated from p-benzoquinone, and diethyl fumarate or maleic anhydride as the exocyclic butadienyl equivalent, followed by subsequent transformation to the conjugated diene moieties. In comparison with the corresponding sesquibicyclo[2.2.2]octene 6, the ¹H NMR demonstrates the anisotropic shielding effect operating within the three parallel laticyclic double bonds. However, the UV absorption of 7 shows less effect by the increase of laticyclic conjugated ethylene units.     

Synthesis of Tetracyclo[6.2.2.23,6.02,7]tetradeca-4,9,11,13-Tetraene

The title hydrocarbon 3, a C₁₄H₁₄ tetracyclic tetraene of C_2v-symmetry, was synthesized by new routes starting from 1,8,9,10-tetrachloro-11,11-dimethoxytricyclo[6.2.1.0^2,7]undeca-3,5,9-triene (1). The Diels-Alder cycloaddition of 1 with 2-chloroacrylyl chloride, a ketene equivalent, followed by subsequent reduction, dechlorination and deacctalization afforded the ketol 12 as a key intermediate. Elaboration of target compound 3 was carried out by either the method of ring enlargement of 12 or (better) the route of Diels-Alder reaction of decarbonylated 12 with trans-1,2-bis(phenylsulfonyl)ethcnc, an acetylene equivalent, to give trienol 17, followed by dehydration. Upon irradiation, 3 underwent intercyclic [2 + 2]-addition to caged hexacyclic diene 4. At 120°C, 3 decomposed into barrelene and benzene quantitatively.     

Unusual photorearrangement of 1,7-disubstituted 7-azabenzonorbornadiene

1-(11-Benzoyl-11-azatricyclo[6.2.1.0^2,7]undeca-2,4,6,9-tetraen-1-yl)ethanone was synthesized by cycloaddition of 2-acetyl-N-benzoylpyrrole to benzyne. Direct photolysis of 1-(11-benzoyl-11-azatricyclo-[6.2.1.0^2,7]undeca-2,4,6,9-tetraen-1-yl)ethanone in benzene gave N-(4-acetylnaphthalen-1-yl)benzamide. The formation of this product is discussed in terms of radical-stabilizing and destabilizing effect of electron-withdrawing group in the formation of cyclopropane ring. Published in Russian in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4, pp. 626–629. The text was submitted by the authors in English.     

Synthesis of Anellated Pyranose Derivatives on the Basis of Levoglucosenone

ABSTRACT

1,6-Anhydro-2-(dicyanomethylene)-2,3-dideoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranose (1) reacted with tosyl azide or sulfur and triethylamine to furnish the 5-aza-10, 11-dioxatricyclo[6.2.1.0^2,6]undeca-2(6),3-diene-3-carbonitrile 2 and the 10,11-dioxa-5-thiatricyclo[6.2.1.0^2,6]undeca-2(6),3-diene-3-carbonitrile 3, respectively. The reactions of 1 with arylisothiocyanates furnished the 11,12-dioxa-5-thiatricyclo[7.2.1.0^2,7]dodeca-2(7),3-diene-3-carbonitriles 4 and 5. 3 underwent cyclization with triethyl orthoformate and ammonia or hydrazine hydrate to afford the 5,7-diaza-14,15-dioxa-9-thiatetracyclo[10.2.1.0^2,10.0^3.8]pentadecatetra(tri)enes 7 and 8, respectively.     

Stereoselective cycloaddition of diphenylisobenzofuran to N-arylitaconimides

A reaction of 1,3-diphenylisobenzofuran with N-arylitaconimides gives the [4+2] cycloaddition products with the 11′-oxaspiro[pyrrolidine-3,9′-tricyclo[6.2.1.0 ^2,7 ]undeca-2′,4′,6′-triene-2,5-dione] skeleton as a single diastereomer.     

Low and high temperature bromination of exocyclic dienes: high temperature bromination. Part 16

The electrophilic addition of bromine to an exocyclic diene, 5,6-dimethylenebicyclo[2.2.1]hept-2-ene, in CCl₄ at 0°C led to the formation of non-rearranged (73%) and rearranged products (27%). However, high temperature bromination of the exocyclic diene at 77°C suppressed the formation of the rearranged products. Similarly, bromination of 9,10-dimethylenetricyclo[6.2.1.0^2,7]undeca-2,4,6-triene at −10°C gave only the exo-1,2-addition product. Bromination at +5°C resulted in the formation of a mixture consisting of exo-1,2- and 1,4-addition products in a ratio of (1:4). High temperature bromination at 77°C resulted in the formation of the endo-1,2-addition product. Furthermore, it has been shown that the 1,4-addition product converts smoothly to the 1,2-addition product. The formation mechanism of the products is discussed and supported by calculations.     

Stereoselective Synthesis of Tricyclo[6.2.2.02,7]dodecane-3,6,9,10-tetrol via Selective Reduction of α,β-Unsaturated 1,4-DIKetone

Stereoselective synthesis of tricyclo[6.2.2.0^2,7]dodecane-3,6,9,10-tetrol was developed starting from p-benzoquinone. The endo selective Diels–Alder cycloaddition of p-benzoquinone and 1,3-cyclohexadiene afforded the corresponding bicyclic diketone. The synthesis of the title compound was based on the cycloadduct by selective reduction with NaBH₄, acetylation with AcCl, and hydroxylation with OsO₄-NMO.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]     

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°.     

A Regiospecific Photochemical Rearrangement of 2-Azabenzotricyclo[5.2.2.01,5]- to 2-Azabenzotricyclo[6.2.1.01,5]undecatrienone

The 2-azatricyclo[5.2.2.0^1,5]undeca-4,8,10-trien-3-ones 1a and 1b gave on irradiation the 2-azatricyclo-[6.2.1.0^1,5]undeca-4,6,9-trien-3-ones 2a and 2b , respectively. The rearrangement was found to be solvent-, oxygen-, and wavelength-independant.     

The predictable behaviour of cations deriving from endo-4-chlorotetracyclo[3.3.0.0.2,8O.3,6]octane.

Silver cation-initiated ionization of the title compound in aqueous dioxane gives the exo and endo-tetracyclo[3.3.0.0.^2,8O.^4,6]octane-3-ols (35 and 65%). Thermal isomerization in chloroform gives the exo and endo isomers of 4-chlorobicyclo[3.2.1]octa-2,6-dienes (3.5 and 1.5%) and 6-chlorotricyclo[3.2.1.0.^2,7]oct-3-ene (90 and 5%). The behaviour of the cations involved is compatible with MINDO/3 calculations.     

Regioselectivity of the Diels-Alder Additions of 2-Substituted 5,6 Dimethylidenenorbornanes and-bicyclo[2.2.2]octanes

The cycloadditions of methyl propynoate and methyl vinyl ketone to 5,6-dimethylidene-2-norbornanone ( 6 ) are para′-regioselective

1 “Para” (p) designs in this paper the 4, 9-disubstituted tricclo[6.2.1.0^{2, 7}] undecane- and 4, 9-disubsstituted tricycle[6.2.20^2,7] dodecane derivatives, “meta” (m) design the corresponding 4, 10-disubstituted compounds.

. A smaller para -regioselectivity is observed for the addition of methyl propynoate to 5,6-dimethylidene-2bicyclo[2.2.2]octanone ( 10 ). No regioselectivity is observed with 5,6-dimethylidene-2exo-norbornyl alcohol ( 3 ), acetate ( 5 ) and 5,6-dimethylidene-2exo-bicyclo[2.2.2]octanol ( 9 ). PMO arguments based on the shape of the HOMO's and subHOMO's of the dienes allow to rationalize these observations. Unpredictable para′- or ‘meta’regioselectivities are found for the Diels,-Alder additions of 5,6-dimethylidene-2endo-norbornyl alcohol ( 2 ), acetate ( 4 ) and 5,6-dimethylidene-2endo-bicyclo[2.2.2]octanol ( 8 ). The carbonyl group of β,γ unsaturated ketones such as 6 and 10 can act as an electron donating homoconjugated substituent. The n(CO) ? σ[C(1), C(2)] ? π[C(5), C(6)] hyperconjugative interaction can override the usual electron-withdrawing effect of this function.     

Reaction products of methyl tricyclo[4.1.0.02,7]heptane-1-carboxylate and tricyclo[4.1.0.02,7]hept-1-yl phenyl sulfone with dinitrogen tetraoxide

The reaction of methyl tricyclo[4.1.0.0^2,7]hepatne-1-carboxylate with dinitrogen tetraoxide in diethyl ether at ?10 to 0°C, followed by treatment of the reaction mixture with methanol, gave approximately equal amounts of methyl exo,syn-6,7-dinitro-and exo-6-hydroxy-syn-7-nitrobicyclo[3.1.1]heptane-endo-6-carboxylates. Tricyclo[4.1.0.0^2,7]hept-1-yl phenyl sulfone reacted with dinitrogen tetraoxide under analogous conditions to produce a mixture of diastereoisomeric exo,syn-and endo,syn-6,7-dinitro-6-phenylsulfonylbicyclo-[3.1.1]heptanes and 6,6-dimethoxy-endo-7-nitrobicyclo[3.1.1]heptane at a ratio of 4.5:2:1. Probable factors responsible for the different stereoselectivities in the addition of N₂O₄ at the central C¹-C⁷ bond of the initial tricycloheptane compounds were discussed. The structural parameters of the dinitro ester and related dinitro sulfone were compared on the basis of the X-ray diffraction data.     

The mannich reaction in the synthesis of N,S-containing heterocycles 4. Aminomethylation of 6-amino-3,5-dicyano-1,4-dihydropyridine-2-thiolates: A convenient regioselective route to 3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec-2-ene derivatives

Treatment of N-methylmorpholinium 4-R-6-amino-3,5-dicyano-1,4-dihydropyridine-2-thiolates (R = 2-ClC₆H₄ and 2-MeOC₆H₄) with primary amines in the presence of an excess of formaldehyde gave 13-R-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile derivatives in high yields (66–95%). In a similar way, aminomethylation of 3-R-10-amino-7,11-dicyano-9-aza-3-azoniaspiro[5.5]undeca-7,10-diene-8-thiolates (R = Me and Et) afforded 1′-alkyl-8-thioxospiro[3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-13,4′-piperidine]-1,9-dicarbonitriles in 43–91% yields. Alternatively, these compounds were obtained by multicomponent cyclocondensation of N-alkylpiperidin-4-ones, cyanothioacetamide, primary amines, and aqueous formaldehyde. The starting 3-R-10-amino-7,11-dicyano-9-aza-3-azoniaspiro[5.5]undeca-7,10-diene-8-thiolates were prepared by a new method from N-alkylpiperidin-4-ones and cyanothioacetamide. The structure of 5,11-bis(4-ethoxyphenyl)-13-(2-methoxyphenyl)-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile was examined by X-ray diffraction analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1014–1022, May, 2007.     

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.     

Products of ozone oxidation of some saturated cyclic hydrocarbons

Low-temperature ozone oxidation of a series of saturated carbocyclic hydrocarbons afforded the corresponding alcohols and/or ketones in high yield through intermediate trioxidanes. exo,endo-Tetracyclo-[6.2.1.0^3,5]undecane-2,7-dione and exo,endo,endo-hexacyclo[9.3.1.0^3,8.0^4,6.0^5,9.0^12,14]pentadecane-2,10-dione were isolated, and exo,endo,exo-pentacyclo[6.3.1.0^2,7.0^3,5.0^9,11]dodecyl-, exo,exo,exo-heptacyclo-[9.3.1.0^2,10.0^3,8.0^4,6.0^5,9.0^12,14]pentadecyl, and 1-methylcyclohexyltrioxidanes were identified and characterized for the first time.     

Synthesis and biological evaluation of rigid polycyclic derivatives of the Diels-Alder adduct tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione

Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformations of the Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca-4,9-dien-3,6-dione in order to obtain cage-like compounds and derivatives, followed by an evaluation of their biological activity.     

Adducts of Tricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptane hydrocarbons with methane- and Halomethanesulfonyl Thiocyanates and their transformations in the presence of bases (nucleophiles)

1-R-Tricyclo[4.1.0.0^2,7]heptanes (R = H, Me, Ph) take up methane- and halomethanesulfonyl thiocyanates XCH₂SO₂SCN (X = H, Cl, Br) at the central C¹–C⁷ bond in benzene at 20°C with high anti-selectivity to give bicyclo[3.1.1]heptane derivatives with the 7-endo-oriented sulfonyl group and the thiocyanato group in the geminal position with respect to the R substituent. The syn-adducts lose HSCN molecule by the action of potassium tert-butoxide in THF at 0°C or on heating in boiling aqueous dioxane containing NaOH with formation of 1-(X-methylsulfonyl)tricyclo[4.1.0.0^2,7]heptanes. Under analogous conditions the anti-adducts (X = Me) are converted into 1,2-bis(7-syn-methylsulfonyl-6-endo-R-bicyclo[3.1.1]hept-6-exo-yl)disulfanes. The anti-adduct derived from unsubstituted tricyclo[4.1.0.0^2,7]heptane and MeSO₂SCN reacted with methyllithium or phenylmagnesium bromide to produce 7-anti-methyl(phenyl)sulfanyl-6-endo-methylsulfonylbicyclo-[3.1.1]heptanes which were also obtained by photochemical addition of MeSO₂SMe(or Ph) to tricyclo-[4.1.0.0^2,7]heptane. Geometric parameters of radical intermediates in the sulfonylation of 1-R-tricyclo-[4.1.0.0^2,7]heptanes were optimized ab initio using 6-31G basis set.     

Tricyclo [3.3.2.03,7]decan (9-Homo-nor-adamantan) Synthese und Umwandlungen

Tricyclo[3.3.2.0^3,7]decane (9-Homo-nor-adamantane). Synthesis and Transformations A synthesis of tricyclo [3.3.2.0^3,7]decane (=9-homo-nor-adamantane; 1 ), which belongs to the adamantaneland, a family of nineteen isomeric C₁₀H₁₆ hydrocarbons, is described, as well as derivatives thereof. Treatment of protoadamantan-5endo-ol (11) with either thionyl chloride or phosphorus pentachloride yielded under rearrangement the chloride 18 , and solvolysis of the 5endo-chloro-protoadamantane (16) led to the acetate 26, 18 and 26 having both the tricyclo [3.3.2.0^3,7]decane skeleton. Subsequent transformations gave the title compound 1 as well as the corresponding olefin 8 .     

The π-Anisotropy of the Double Bond of a syn-11-Oxasesquinorbornene Derivative.. Stereoselectivity of the Diels–Alder additions of (2-norborneno)[c]furan. Crystal structure of 11-oxa-endo-tetracyclo[6.2.1.13,6.02,7]-dodec-2(7)-ene-9,10-exo-dicarboxylic anhydride

The reaction of (2-norborneno)[c]furan ( 4 ) with maleic anhydride gave 11-oxa-endo-tetracyclo[6.2.1.1^3,6.0^2,7]dodec-2(7)-ene-9,10-exo-dicarboxylic anhydride ( 5 ) and, with methyl acetylenedicarboxylate, methyl 11-oxa-endo-tetracyclo [6.2.1.1^3,6.0^2,7]dodeca-2(7),9-diene-9,10-dicarboxylate ( 7 ). The syn-11-oxa-sesquinorbornenes 5 and 7 could be equilibrated with their cycloaddents. They are at least 2 kcal/mol more stable than the corresponding anti-sesquinorbornenes 6 and 8 . The structure of 7 was deduced from its spectral data, by epoxidation with air or a peracid to give the exo-epoxide 13 and by catalytic hydrogenation to give 14 . The structure of 5 was established by single-crystal X-ray diffraction. A dihedral angle of 163° was measured between the C(1,2,7,8) and C(2,3,6,7) planes in 5 . This important deviation from planarity for the C(2,7) double bond is attributed to (π, ω)-repulsive interactions that make the π-electron density of 2-norbornene and 7-oxa-2-norbornene derivatives preferentially polarized toward the exo-face. This finding is discussed in relation with the relative stability of the syn- and anti- 11-oxasesquinorbornenes and with the endo-stereoselectivity of the cycloadditions of the norbornenofuran 4 .