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.     

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.     

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.     

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.     

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.     

Intramolecular Diels—Alder reaction of 4-(N-furfuryl)aminobut-1-enes. New approach to the synthesis of 6,8a-epoxyoctahydroisoquinoline (3-aza-11-oxatricyclo[6.2.1.01,6]undec-9-ene) derivatives

The intramolecular Diels—Alder reaction of readily accessible 4-substituted 4-(N-furfuryl)aminobut-1-enes was studied and a new one-step method was developed for the synthesis of 6,8a-epoxy-1,2,3,4,4a,5,6,8a-octahydroisoquinoline (3-aza-11-oxatricyclo[6.2.1.0^1,6]undec-9-ene) derivatives. The [4+2]-cycloaddition proceeds stereoselectively to form exo-adducts. The influence of substituents at the nitrogen atom in 4-(N-furfuryl)aminobut-1-enes on the cycloaddition pathway was examined.     

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 Sonogashira coupling of 2- and 4-ethynyl derivatives of proton sponge with 1,8-diiodonaphthalene: Novel cascade transformations into naphtho[1,2-k]fluoranthenes and acenaphtho[1,2-b]benzo[g]indoles

The Sonogashira coupling of 2-ethynyl, 4-ethynyl and 2,7-diethynyl derivatives of 1,8-bis(dimethylamino)naphthalene (proton sponge) with 1-iodo- and 1,8-diiodonaphthalenes has been studied. The reaction of the above alkynes with 1-iodonaphthalene gave the expected naphthylethynyl derivatives of proton sponge. At the same time, the coupling of 2-ethynyl- and 2,7-diethynyl-1,8-bis(dimethylamino)naphthalenes with 1,8-diiodonaphthalene resulted in the formation of N,N,7-trimethyl-7H-acenaphtho[1,2-b]benzo[g]indol-8-amines. The reaction of 1,8-diiodonaphthalene with 4-ethynyl-1,8-bis(dimethylamino)naphthalene produced 14-(4,5-bis(dimethylamino)naphthalen-1-yl)-N¹¹,N¹¹,N¹²,N¹²-tetramethylnaphtho[1,2-k]fluoranthene-11,12-diamine together with 4-((8-iodonaphthalen-1-yl)ethynyl)-N¹,N¹,N⁸,N⁸-tetramethylnaphthalene-1,8-diamine. It was suggested that the mechanisms of the two novel cascade transformations stem from the specific nature of the proton sponge substrates.     

Photochemische reaktionen von übergansmetall-olefinkomplexen: III. [4 + 6]-cycloaddition konjugierter diene an hexacarbonyl-μ-η6:6(-1,1′-bi(2,4,6-cycloheptatrien-1-yl)dichrom(O)

UV irradiation of hexacarbonyl-μ-η^6:6-1,1′-bi(2,4,6-cycloheptatrien-1-yl)dichromium(O) (I) in THF in the presence of 1,3-butadiene (A), E-1,3-pentadiene (B) and EE-2,4-hexadiene (C) causes preferentially a twofold [4 + 6]-cycloaddition and formation of the hexacarbonyl-μ-2–5 : 8.9-η-2′–5′ : 8′,9′-η-11,11′-bi(bicyclo-[4.4.1]undeca-2,4,8-trien-11-yl)dichromium(O) complexes (IVA–IVC). Partial decomplexation after the first [4 + 6]-cycloaddition yields isomeric tricarbonyl-2–5:8,9-η- (IIA–IIC) and tricarbonyl-2′–7′-η-{11-(2′,4′,6′-cycloheptatrien-1′-yl)bicyclo[4.4.1]undeca-2,4,8-triene}chromium(O) complexes (IIIA–IIIC). With 2,3-dimethyl-1,3-butadiene (D) mainly dicarbonyl-2–6 : 2′–4′-η-{1-(2′,3′-dimethyl-3′-buten-1′,2′-diyl)-7-(8″,9″-dimethylbicyclo[4.4.1]undeca-2″, 4″,8″-trien-11″-yl)cyclohepta-3,5-dien-2-yl}chromium(O) (VD) besides small amounts of pentacarbonyl-μ-2–6 : 2′–4′-η-2″–7″-η-{1-(2′,3′-dimethyl-3′-buten-1′,2′-diyl)-7-(2″, 4″,6″-cycloheptatrien-1″-yl)cyclohepta-3,5-dien-2-yl}dichromium(O) (VID) and tricarbonyl-2′-7′-η-{11-(2′,4′,6′-cycloheptatrien-1′-yl)-8,9-dimethyl-bicyclo[4.4.1]undeca-2,4,8-triene}-chromium(O) (IIID) is obtained. VD adds readily CO to yield tricarbonyl-2–5 : 8,9-η-11,11′-bi(8,9-dimethyl-bicyclo[4.4.1]undeca-2,4,8-trien-11-yl)chromium(O) (VIID). Finally D adds to VID under formation of pentacarbonyl-μ-2–6 : 2′–4′-η-2″–5″ : 8″,9″-η-{1-(2′,3′-dimethyl-3′-buten-1′,2′-diyl)-7-(8″,9″-dimethyl-bicyclo[4.4.1]- undeca-2″,4″,8″-trien-11″-yl)cyclohepta-3,5-dien-2-yl}dichromium(O) (VIIID). From IVA–IVC the hydrocarbon ligands (IXA–IXC) can be liberated by P(OCH₃)₃ in good yields. The structures of the compounds IIA–IXC were determined by IR     

An approach to the synthesis of isolongifolene

An efficient synthesis of 7, 7-dimethyltricyclo [6.2.1.0^1,6] undeca-2, 5-dien-4-one 2, an advanced intermediate for the synthesis of the tricyclic sesquiterpene isolongifolene 1, has been carried out utilising Ar₁-5 participation reaction as the key step.     

Wacker oxidation methodology for the synthesis of the benzo-fused acetal core of marticin

Methodology for the synthesis of the benzo-fused acetal core of marticin is described in this paper. Condensation of readily available 1-(2-allyl-3,6-dimethoxyphenyl)ethanone with diethyl oxalate under Claisen condensation conditions furnished (Z)-ethyl 4-(2-allyl-3,6-dimethoxyphenyl)-2-hydroxy-4-oxobut-2-enoate. Treatment of this with LiAlH₄ resulted in the formation of the diol, 1-(2-allyl-3,6-dimethoxyphenyl)-3,4-dihydroxybutan-1-one. Conversion of primary alcohol of the diol into the TBDMS ether followed by further reaction with LiAlH₄ and exposure to Wacker oxidation conditions resulted in the formation of (3,6-dimethoxy-9-methyl-10,13-dioxatricyclo[7.3.1.0^2,7]trideca-2,4,6-trien-11-yl)methanol, the core of marticin.     

SYNTHESIS OF ANELLATED ANHYDROPYRANOSES ON THE BASIS OF 1,6-ANHYDRO-3-DEOXY-4-METHYLSULFANYL-3-[(METHYLSULFANYL)METHYLENE]-β-D-ERYTHRO-HEXOPYRANOS-2-ULOSE

(Z)-1,6-Anhydro-3-deoxy-4-methylsulfanyl-3-[(methylsulfanyl)methylene]-β-D-erythro-hexopyranos-2-ulose (1) reacted with diethyl malonate, 1,3-diketones, N-aryl-3-oxobutyramides and dialkyl 3-oxoglutarate, respectively, in the presence of potassium carbonate and crown ether to yield diethyl 2-(1,6-anhydro-4-methylsulfanyl—D-arabino-hex-2-ulopyranos-3-ylmethylene) malonate (2), 1-{(1R,2S,8S,9R)-2-hydroxy-4-methyl-8-methylthio-3,11,12- trioxatricyclo7.2.1.0^2,7dodeca-4,6-dien-5-yl} ethanone (3), (1R,2S,12S,13R)-2-hydroxy-12-methylthio-3,15,16-trioxatetracyclo[11.2.1. 0^2,11. 0^4,9] hexadeca- 4(9),10-dien-8-one (4), (1R,8S,9R)-5-acetyl-3-aryl-8-methylthio-11,12-dioxa- 3-azatricyclo-[7.2.1.0^2,7]dodeca-2(7),5-dien-4-ones (5,6) and dialkyl (1R,8S,-9R)-4-hydroxy-8-methylthio-11,12-dioxatricyclo[7.2.1.0^2,7]dodeca-2(7),3,5-triene-3,5-dicarboxylates (7,8), respectively.     

Diels-alder reactions of polyfluorocyclohexa-1,3-dienes. Part VIII [1]. Reaction of trifluoroacetonitrile with perfluorotricyclo[6,2,2,O2,7]dodeca-2,6,9-triene. A synthesis of perfluoro-3-methylisoquinoline

The Diels-Alder reaction between perfluorotricyclo[6,2,2,0^2,7]dodeca-2,6,9-triene (1) and trifluoroacetonitrile provides a route to perfluoro-3-methylisoquinoline (5) and perfluoro-9-aza-10-methyltricyclo[6,2,2,0^2,7]dodeca-2,4,6,9-tetraene (3) which yields (5) on pyrolysis. Perfluorobenzobicyclo[2,2,2]oct-2-ene (4) is formed as a biproduct resulting from the initial Diels-Alder addition between (1) and tetrafluoroethylene.     

Chemo-, regio-, and stereoselectivity in acid-catalyzed hydromethoxylation of tricyclo[4.1.0.0<Superscript>2,7</Superscript>]hept-1-yl and 7-methyltricyclo[4.1.0.0<Superscript>2,7</Superscript>]hept-1-yl phenyl sulfones

Hydromethoxylation of tricyclo[4.1.0.0^2,7]hept-1-yl and 7-methyltricyclo[4.1.0.0^2,7]hept-1-yl phenyl sulfones with methanol at 20°C in the presence of a catalytic amount of perchloric acid is initiated by the endo attack of proton at the C¹ atom, and the subsequent cleavage of the side C¹–C² bond leads to formation of mixtures of diastereoisomeric exo-7-phenylsulfonyl-2-methoxybicyclo[4.1.0]heptanes, the endo-2 isomer prevailing. Probable factors responsible for the observed chemo-, regio-, and stereoselectivity of the addition are discussed.     

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.     

Transformations of 3-nitropyridin-4(1<Emphasis Type="Italic">H</Emphasis>)-one and 1-Methyl-3-nitropyridin-4(1<Emphasis Type="Italic">H</Emphasis>)-one in reaction with hydrazine

Hydrazinolysis of 3-nitropyridin-4(1H)-one and its N-methyl derivative leads to the formation of 1-(1H-pyrazol-3-yl)ethanone hydrazone whose structure was confirmed by independent synthesis from authentic 3-acetyl-1H-pyrazole and comparison of the IR and ¹H NMR spectra. Oxidation of 1-(1H-pyrazol-3- yl)ethanone hydrazone with potassium permanganate gave 1H-pyrazole-3-carboxylic acid.     

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°.     

Application of directed metalation in synthesis. Part 7: Synthesis of suitably functionalised benzo[b]thiophenes as key intermediates in the synthesis of benzothienopyranones

One-pot syntheses of (3-hydroxybenzo[b]thiophen-2-yl) aryl methanones from ortho-methylsulfanylaryl N,N-diethyl amides and of 1-(3-hydroxybenzo[b]thiophen-2-yl)ethanone and 1-(3-hydroxybenzo[b]thiophen-2-yl)propan-1-one via an anionic ortho-Fries rearrangement are described. The hydroxy ketones were used as key intermediates in the synthesis of benzothienopyranones.     

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.     

Synthesis of 1-{4a,6-dimethyl-4a,9a-dihydropyrano-[3,4-<Emphasis Type="Italic">b</Emphasis>]indol-9(1<Emphasis Type="Italic">H</Emphasis>)-yl}ethanone

Heating of the bromination product of 4-methyl-3,6-dihydro-2H-pyran with 4-toluidine or 2-bromo-4-methylamiline in triethylamine gave 4-methyl-N-(4-methylphenyl)- and N-(2-bromo-4-methylphenyl)-4-methyl-3,6-dihydro-2H-pyran-3-amines which were converted into the corresponding amides by reaction with bromo- or chloroacetyl chloride. 1-{4a,6-Dimethyl-4a,9a-dihydropyrano[3,4-b]indol-9(1H)-yl} ethanone was synthesized in good yield by heating N-(2-bromo-4-methylphenyl)-N-(4-methyl-3,6-dihydro-2Hpyran-3-yl)acetamide in boiling toluene in the presence of palladium(II) acetate, triphenylphosphine, copper(II) acetate, triethylamine, and potassium carbonate.