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.     

Cyclopropanation and epoxidation of tricyclo[5.2.1.0]deca-2(6),8-dien-3-one

Cyclopropanation of tricyclo[5.2.1.0^2,6]deca-2(6),8-dien-3-one using dimethylsulfoxonium ylide gave a highly strained annulated cyclopropane in 68% yield with complete exo-face selectivity. Nucleophilic epoxidation gave a strained epoxide in 68% yield, again completely exo-face selective. Surprisingly, using methanol as the co-solvent in this epoxidation yielded a disubstituted tricyclodecenone in 85% yield instead of the epoxide. This result can be explained by a Payne-type rearrangement of the initially formed epoxide.     

Facial Selectivity in the Nucleophilic Additions of endo-Tricyclo[5.2.1.0~(2,6)]deca-2(6),8-dien-3-one

The endo-tricyclo [5.2.1.02,6] decadienone system 1 has been used as a versatile synthon for the synthesis of a great variety of natural products1. The availability of both antipodes of 1 in enantiopure form2, and the ability to undergo [4+2] cycloreversion makes it useful for the enantioselective synthesis of naturally occurring cyclopentanoids with defined stereochemistry and chirality3. Starting from the 1,4 reduced Hertz ester 2, synthesis of the reactive and strained tricyclodecadienone 4…     

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.     

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.     

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.     

Nitrochlorination of methyl tricyclo[4.1.0.02,7]heptane-1-carboxylate and phenyl tricyclo[4.1.0.02,7]hept-1-yl sulfone

Treatment of methyl tricyclo[4.1.0.0^2,7]heptane-1-carboxylate and phenyl tricyclo[4.1.0.0^2,7]hept-1-yl sulfone with a ～1:8 mixture of N₂O₄ and NOCl in diethyl ether at ?5 to 0°C gave products of formal anti-addition of NO₂Cl at the central C¹-C⁷ bond. In the reaction with phenyl tricyclo[4.1.0.0^2,7]hept-1-yl sulfone nitryl chloride acts as an effective chlorinating agent; as a result, a mixture of diastereoisomeric syn- and anti-6,7-dichlorobicyclo[3.1.1]hept-6-yl phenyl sulfones at a ratio of 7.5:1 is formed.     

A Stereospecific Approach to cis-anti-cis Triquinanes

Abstract

A methodology for the synthesis of compounds containing the cis-anti-cis fused triquinane system has been developed starting from tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-(exo)ol 6 involving Ireland ester Claisen rearrangement and intramolecular diazo ketone cyclopropanation reactions as key steps.     

Stereoselective Construction of Copaborneol and Longiborneol Frameworks by Intramolecular Double Michael Reaction

Stereoselective syntheses of tricyclo[5.3.0.0(3,8)]decane 22 and tricyclo[6.3.0.0(3,9)]undecane 26, the basic skeletons of copaborneol and longiborneol, were achieved by the intramolecular double Michael reactions of 2-cyclopenten-1-ones 15-17. The substrates were prepared starting with tricyclo[5.2.1.0(2,6)]deca-4,8-dien-3-one (6). The intramolecular double Michael reactions were carried out under three different conditions: TMSCl-Et(3)N-ZnCl(2), TMSI-(TMS)(2)NH, and Bu(2)BOTf-(TMS)(2)NH. The framework 26 of longiborneol was constructed in good yields using the latter two reagent systems.     

Catalytic hydrogenation of methyl 3,4-diazatricyclo-[5.2.1.0<Superscript>2,6</Superscript>]dec-4-ene-5-carboxylate

The hydrogenation at Raney nickel of the pyrazoline ring in methyl exo-3,4-diazatricyclo-[5.2.1.0^2,6]dec-4-ene-5-carboxylate takes place quantitatively with the preferential formation of the trans isomer of 5-amino-exo-3-azatricyclo[5.2.1.0^2,6]decan-4-one. The 3-methoxycarbonylmethyl-, 3-acetyl-, and 3-nitroso-substituted esters are not hydrogenated under these conditions.     

The Novel Adamantane Isomer Tricyclo[4.4.0.03,9]decane (2-Homotwistbrendane)

Two synthetic approaches to the novel C₁₀H₁₆ hydrocarbon tricyclo[4.4.0.0^3,9]decane ( 1 ; 2-homotwistbrendane), one of the 19 members of the adamantaneland, and its Lewis-acid-catalyzed rearrangement are described. One route starts from tricyclo[4.3.0.0^3,8]nonan-2-one ( 2 ; 2-twistbrendanone). The missing tenth C-atom is introduced by ring enlargement (Tiffeneau-Demjanov method). Starting from methyl 8,9,10-trinorborn-5-ene-2-endo-carboxylate ( 8 ), ring enlargement by one C-atom, regio- and stereoselective introduction of a C₁ unit to a 2-endo,6-endo-disubstituted bicyclo[3.2.1]octane, and ring closure by acyloin condensation are the key steps in the second approach.     

The diels-alder dimerisation of 2,3-dichlorocyclopentadienone and of 2,3,8,9-tetrachlorobicyclo[4.3.0]nona-2,4,8-trien-7-one

The Diels-Alder dimer of 2,3-dichlorocyclopentadienone, shown to be endo-4,5,7,8-tetrachlorotricyclo[5.2.1.0^2,6]deca-4,8-dien-3,10-dione 1, forms 2,3,8,9-tetrachlorobicyclo[4.3.0]nona-2,4,8-trien-7-one 3 on thermal extrusion of carbon monoxide. The trienone 3 itself dimerises at ca. 160°, with loss of hydrogen chloride, affording two stereoisomeric aromatic derivatives 8 and 9.     

Stereospecific Hydroformylation of endo-Dicyclopentadiene in the Presence of Rhodium Complex Catalysts. A Route to endo-Tricyclo[5.2.1.02,6]Dec-8-exo-Ylcarbinol,Precursor of 4-Homoisotwistane

Since the discovery of a potent antiviral activity of 3-amino-4-homoisotwistane (tricyclo [5.3.1.0]undecane, VIII) our efforts have been directed to find out better methods of synthesizing the parent hydrocarbons. In this communication is reported synthesis of a new precursor to 4-homoisotwistane (VIII), endo-tricyclo [5.2.1.0]dec-8-exo-ylcarbinol (IIIx), via hydroformylation of endo-dicyclo-pentadiene (endo-tricyclo [5.2.1.0]deca-3,8-diene) (I) in the presence of rhodium complex catalysts.     

Stereospecific total synthesis of (±) pentenomycins by flash vacuum thermolysis of substituted tricyclo[5.2.1.02,6]decenones

The synthesis of 4-functionalized tricyclo[5.2.1.0^2,6]decenones $\text{9}$, starting from furans, is described. These structures are shown to be suitable precursors for the synthesis of cyclopentenoids such as pentenomycin and analogs.     

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.     

Tetracyclo[5.3.0.02,803,6]deca-4,9-diene. A new (CH)10 hydrocarbon

Irradiation of tricyclo[5.3.0.0^2,8]deca-3,5-dien-9-one ethylene acetal yields tetracyclo[5.3.0.0^2,80^3,6]dec-4-en-9-one ethylene acetal as main product which can be converted to the title compound, a new (CH)¹⁰ hydrocarbon.     

A simple synthesis of bis-annulated bicyclo[2.2.2]octenones containing a β,γ-enone chromophore and photochemical reactions: a new entry into angular tetraquinane and other polycyclic systems

Synthesis of endotetracyclo[5.5.2.0.^2,60^8,12]tetradeca-3(4),8(12)-dien-13-one from 5-indanol and photoreactions in singlet and triplet excited state leading to complex polycyclic systems is reported. Crystal structure of 14-spiroepoxyendotetracyclo[5.5.2.0.^2,60^8,12] tetradeca-3(4),8(12)-dien-13-one is also reported.     

Synthesis of bi- and tricyclic acrylates in the presence of boron trifluoride etherate

The addition of acrylic acid to bicyclo[2.2.1]heptene hydrocarbons and tricyclo[5.2.1.0^2,6]deca-3,8-diene catalyzed with BF₃·O(C₂H₅)₂ was studied and bi- and tricyclic esters of acrylic acid were synthesized that were reactive monomers for preparation of macromolecular compounds.     

Photochemistry of tricyclo [4.2.2.02,5] deca-3,7-dien-9-one: a source of many interesting polycycles

New syntheses of tricyclo [4.2.2.0^2,5] deca-3,7-dien-9-one are described. Direct and sensitised photolysis of this ring system provides facile entry to several novel polycyclics.     

Synthesis of 7-sulfonyl-substituted norpinan-6-ones and -thiones from 1-bromotricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptane

1-Bromotricyclo[4.1.0.0^2,7]heptane reacted with benzene- and methanesulfonyl thiocyanates in benzene at 20°C via anti addition to the central C¹–C⁷ bicyclobutane bond with formation of 6-endo-bromo-6-exo-thiocyanato-7-syn-(R-sulfonyl)bicyclo[3.1.1]heptanes. Treatment of the benzenesulfonyl thiocyanate adduct with potassium tert-butoxide in THF at 20°C gave 7-endo-(benzenesulfonyl)norpinan-6-one, whereas the reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene in methylene chloride afforded 7-exo-(benzenesulfonyl)-norpinane-6-thione which was converted into 7-exo-(benzenesulfonyl)norpinan-6-one by alkaline hydrolysis.