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The ring expansion of 7-halogenobicyclo[4.1.0] heptenones and related compounds provides a useful new method for the preparation of the seven-membered conjugated carbocyclic compounds known as tropones and tropolones. This methodology has been exploited in the synthesis of various biologically active troponoid natural products including nezukone, the thujaplicins, thujaplicinol, MY3-469 and colchicine.

C 10 H 16 O 4 cristallise dans P2 1 /n avec a=8.264, b=6.988, c=18.288A, β=96.27°, Z=4; affinement jusqu'a R=0.043. C 16 H 18 O 5 cristallise dans P2 1 /n avec a=12.792, b=8.937, c=13.089A, β=91.37°, Z=4; affinement jusqu'a R=0.048. C 16 H 18 O 5 cristallise dans Pbca avec a=10.773, b=25.953, c=10.818A, Z=8; affinement jusqu'a R=0.048. L'heterocycle dioxolane adopte une conformation entre la demi-chaise et l'enveloppe pour les deux premiers composes, une conformation enveloppe pour le dernier.

One-pot syntheses of the trichlorinated troponoid compounds (8), (10), (12) and (18) have been achieved by reacting tetrachlorocyclopropene (5) with various trimethylsiloxybuta-1,3-dienes.

The title compounds, (3aα,5α,6α)-4,4,6-trichloro-7-methoxy-3,4,5,6-tetrahydro-2H-3a,5-methanoazulene and (3aα,6α)-(E)-8,8-dichloro-5-chloromethylene-6-methoxy-1,2,3,4,5,6-hexahydrο-3a,6-methanο-3aH-indene, both C12H13C130, were formed by mild thermolyses of two related [4.3.1]propellanes and are of interest in the development of new methods for preparing novel analogues of the anti-cancer drug Taxol.

X-ray analyses have established the structures of (3aα,7aα)-6-chloromethyl-8,8-dichloro-2,3-dihydro-5-methoxy-3a,7a-methano-1H-indene, C 12 H 13 Cl 3 O, and (3aα,8aα)6,9,9-trichloro-2,3 5,8-tetrahydro-1H,4H-3a,8a-methanoazulen-5-one, C 11 H 11 Cl 3 O, which have resulted from different modes of cyclopropane ring cleavage within the framework of two closely related gem-di-chloro[4.3.1]propellanes.

C 10 H 16 O 4 cristallise dans P2 1 /n avec a=8.264, b=6.988, c=18.288A, β=96.27°, Z=4; affinement jusqu'a R=0.043. C 16 H 18 O 5 cristallise dans P2 1 /n avec a=12.792, b=8.937, c=13.089A, β=91.37°, Z=4; affinement jusqu'a R=0.048. C 16 H 18 O 5 cristallise dans Pbca avec a=10.773, b=25.953, c=10.818A, Z=8; affinement jusqu'a R=0.048. L'heterocycle dioxolane adopte une conformation entre la demi-chaise et l'enveloppe pour les deux premiers composes, une conformation enveloppe pour le dernier.

C 16 H 16 O 4 cristallise dans P2 1 2 1 2 1 avec a=7,330, b=8,992 et c=21,416 A, Z=4; affinement jusqu'a R=0,032. C 16 H 16 O 4 cristallise dans C2/c avec a=26,131, b=7,634 et c=14,158 A, β=104,78 o , Z=8; affinement jusqu'a R=0,047. Les deux molecules assurent une conformation a l'etat solide qui ressemble a celle de l'isocolchicine plutot qu'a celle de la cochicine. L'angle diedre entre les cycles est 52,6 et 43,4 o respectivement (53 o dans la colchicine)

X-ray analyses have established the structures of (3aα,7aα)-6-chloromethyl-8,8-dichloro-2,3-dihydro-5-methoxy-3a,7a-methano-1H-indene, C 12 H 13 Cl 3 O, and (3aα,8aα)6,9,9-trichloro-2,3 5,8-tetrahydro-1H,4H-3a,8a-methanoazulen-5-one, C 11 H 11 Cl 3 O, which have resulted from different modes of cyclopropane ring cleavage within the framework of two closely related gem-di-chloro[4.3.1]propellanes.

The title compounds, (3aα,5α,6α)-4,4,6-trichloro-7-methoxy-3,4,5,6-tetrahydro-2H-3a,5-methanoazulene and (3aα,6α)-(E)-8,8-dichloro-5-chloromethylene-6-methoxy-1,2,3,4,5,6-hexahydrο-3a,6-methanο-3aH-indene, both C12H13C130, were formed by mild thermolyses of two related [4.3.1]propellanes and are of interest in the development of new methods for preparing novel analogues of the anti-cancer drug Taxol.

The title compound, (3aα, 10aα)-11,11-dibromo-6-methoxy-2,3,3a, 10a-tetrahydro-1H,4H-3a, 10a-methano-benz[f]azulen-9(10H)-one, C 16 H 16 Br 2 O 2 , is shown to contain a C6-methoxylated aromatic ring and bears some resemblance to the ABC ring system of paclitaxel (Taxol TM ).

The X-ray crystal structure of the title compound, C 10 H 11 Br 2 N, reveals that the three- and five-membered rings are fused to one another in a spiro fashion and that there is an E arrangement of substituents about the carbon-carbon double bond.

The X-ray crystal structure of C 19 H 20 BrNO 6 .0.5C 3 H 8 O, an ABC-ring analogue of the diterpene paclitaxel, establishes that the stereochemistry at C(10) is opposite to that seen in the natural product.

The X-ray crystal structure of the title compound, C 12 H 11 Br 4 NO 2 , reveals that the two three-membered rings are in an anti relationship to one another.

The X-ray structure analysis of the title compound, C12H11Br5O2, established the presence of the 2,3,3a,4,5,6-hexahydro-3a,6-methanoazulene ring system, which was produced by a reaction sequence involving unexpected skeletal rearrangement processes.

The X-ray crystal structure determination of the title compound (C20H22BrNO5, systematic name methyl 14-bromo-6-methoxy-1,3-dioxo-2,3,3a,9,10,11,12,13,13a,13b-decahydro-1H-8,12-methanocyclodeca[e]isoindol-12-yl acetate), an ABC-ring analogue of the diterpene paclitaxel reveals that the stereochemical relationships between C(3), C(4) and C(5) (C13a, C13b and C3a, respectively, by systematic numbering) are the same as observed in the natural product.

The ketone (+/-)-5, which embodies the bicyclic core associated with the title tRNA synthetase inhibitors 1 and 2, has been prepared via a three-component coupling reaction involving 2-(hydroxymethyl)cyclopent-2-enone (15), methylamine (6) and propiolamide (10); straightforward elaboration of the readily derived acetates (-)-21 and (+)-21 has provided the biologically active analogues 23 and 24, respectively, of the title compounds.

C 9 H 16 N 2 O 2 , M r =184.2, rhombohe dral, R3, a=12.594 (2) A, α=118.03 (1) o , V=720 (2) A 3 , Z=3, D x =1.274 Mg m -3 , A(Cu Kα)= 1.5418 A, μ=0.70 mm -1 , F(000)=300, T=290 (1) K, final R=0.047 for 1191 reflections with I ≥2σ(I). Although the title molecule (I) is a meso compound, it does not have exact mirror symmetry in the solid state. The observed distortions, which no doubt arise from the fusion of the two rings, results in two enantiomeric forms with any given crystal containing only the one enantiomer (e.g. with 3aS, 4R,7S,7aR configurations)

The title compound, C 12 H 12 O 2 , represents the first example of a molecule containing the perhydro-1,4-dioxacyclopropa[cd]pentalene ring system which has been subjected to single-crystal X-ray analysis.

The X-ray analysis of the title compound, C 14 H 12 BrNO, established the Z geometry about the propenyl double bond and also confirmed that the propenyl side chain is attached to the heterocyclic ring at the N atom rather than through the O atom.

Convergent routes to the title nuclei, (1) and (6), have been developed. Thus, Suzuki coupling of boronic acid (8) with aryl bromide (9) gave the biarylylcarbamate (7) which, on treatment with phosphorus oxychloride (POCl3), underwent Bischler-Napieralski cyclization to give, after acid hydrolysis, the Amaryllidaceae alkaloid crinasiadine (1). The cyclization reaction proceeds via an intermediate chlorophenanthridine (11) which can be isolated and N- methylated. Hydrolysis of the resulting iminium species (17) then afforded N- methylcrinasiadine (2). On the other hand, hydrogenolytic dechlorination of compound (II) affords trisphaeridine (14). Related chemistry has been employed in the preparation of 2,3,4,4a-tetrahydro[1,3] dioxolo [4,5-j]phenanthridin-6(5H)-one (6), the tetracyclic skeleton associated with the narcissus alkaloids lycoricidine (3) and narciclasine (4). Thus, treatment of the gem- dibromocyclopropane (20) with silver cyanate resulted in ring opening thereby affording the allylic isocyanate (25) which could be intercepted with added methanol to give carbamate (24). Suzuki coupling of this last compound with boronic acid (8) gave product (18) which was subjected to treatment with and resulted in the formation of (�)-(6). This latter sequence could be adapted to the preparation of both (R)-(6) and (S)-(6).

One-pot syntheses of the trichlorinated troponoid compounds (8), (10), (12) and (18) have been achieved by reacting tetrachlorocyclopropene (5) with various trimethylsiloxybuta-1,3-dienes.

The ring expansion of 7-halogenobicyclo[4.1.0] heptenones and related compounds provides a useful new method for the preparation of the seven-membered conjugated carbocyclic compounds known as tropones and tropolones. This methodology has been exploited in the synthesis of various biologically active troponoid natural products including nezukone, the thujaplicins, thujaplicinol, MY3-469 and colchicine.

The dehydrohalogenation of 8,8-dichloro- and 8,8-dibromo- bicyclo[5,1,0]octa-2,4-diene (4c,d)gives rise to the (E)- and (Z)-isomers of β-t-butoxystyrene (2c). Plausible pathways for the conversion are discussed and evidence in support of bicyclo[4,2,0]octa- 2,4-dienes as intermediates in the conversion is presented. The results support the intervention of halobicyclo[5,1,0]octa-2,4-dienes in the conversion of tetra- and tri-halo-cis-transoid-cis- tricyclo[5,1,0,03,5]octanes (1a-d) to styrenes(2a-c).

Treatment of 4,4,8,8-tetrabromo-cis-transoid-cis-tracyclo[5,1,0,03,5]octane (If) with potassium t-butoxide leads to mixtures of the (E)- and (Z)-isomers of 4- and 3-bronlo-β-t-butoxystyrene (5e,f) and (9e,f) respectively, whereas the 4,4,endo-8-tribromo analogue (1g) affords the parent styrenes (5c,d). On the other hand the tetra- and tri-bromo-cis-transoid-cis-tricyclo[5,1,0,02,4] octanes (8f-h)give complex and unresolved product mixtures. Evidence is presented which eliminates the involvement of halogenocyclooctatetraenes and p-halogenophenylacetylenes in these reactions.

A simple and efficient synthesis of 3,3-dibromo- and 3,3-dichloro-cis- transoid-cis-tricyclo[5,1,0,02,4]-oct-5-ene (3a,b) (gem-dihalo-anti- bishomobenzenes) has been developed from bicyclo[4,1,0]hept-3-ene (9).

A simple and efficient synthesis of 3,3-dibromo- and 3,3-dichloro-cis- transoid-cis-tricyclo[5,1,0,02,4]-oct-5-ene (3a,b) (gem-dihalo-anti- bishomobenzenes) has been developed from bicyclo[4,1,0]hept-3-ene (9).

The bis-dichloro and bis-dibromo carbene adducts (1c-h) of 1-methoxy-, 1,4-dimethoxy- and 1,5-dimethoxy-cyclohexa-1,4-diene undergo regiospecific dehydrohalogenation by strong base to the 4,8,8- trihalomethoxybicyclo[5,1,0]octa-2,4-dienes (7c-h), in contrast to the 1,7-dimethoxytricyclooctane(1i) and its methyl derivatives (1j-m), which are unchanged. The dienes (7c-h) are resistant to further dehydrohalogenation.

Treatment of 4,4,8,8-tetrabromo-cis-transoid-cis-tracyclo[5,1,0,03,5]octane (If) with potassium t-butoxide leads to mixtures of the (E)- and (Z)-isomers of 4- and 3-bronlo-β-t-butoxystyrene (5e,f) and (9e,f) respectively, whereas the 4,4,endo-8-tribromo analogue (1g) affords the parent styrenes (5c,d). On the other hand the tetra- and tri-bromo-cis-transoid-cis-tricyclo[5,1,0,02,4] octanes (8f-h)give complex and unresolved product mixtures. Evidence is presented which eliminates the involvement of halogenocyclooctatetraenes and p-halogenophenylacetylenes in these reactions.

The dehydrohalogenation of 8,8-dichloro- and 8,8-dibromo- bicyclo[5,1,0]octa-2,4-diene (4c,d)gives rise to the (E)- and (Z)-isomers of β-t-butoxystyrene (2c). Plausible pathways for the conversion are discussed and evidence in support of bicyclo[4,2,0]octa- 2,4-dienes as intermediates in the conversion is presented. The results support the intervention of halobicyclo[5,1,0]octa-2,4-dienes in the conversion of tetra- and tri-halo-cis-transoid-cis- tricyclo[5,1,0,03,5]octanes (1a-d) to styrenes(2a-c).

The [5.3.1] propelladiene (1) has been synthesized in six steps from the readily available [4.3.1] propellene (10a). Epoxidation of (10a) gives oxide (11a) which undergoes base-promoted rearrangement to allylic alcohol (12a). Simmons-Smith cyclopropanation of (12a) then gives the tetracyclic alcohol (13a). Mild thermolysis of the derived mesylate (14a) affords the ring-expanded isomer (20) which reacts with 1,8-diazabicyclo [5.4.0]undec-7-ene to give diene (1). A similar sequence of reactions has been used in the preparation of dienol (2) from acetal (10b). Compounds (1) and (2) react with 4-phenyl-4H-1,2,4-triazoline- 3,5-dione to give the Diels-Alder adducts (29a) and (29b) respectively.