Tricyclic Diene Research Articles

Epoxidation of the products of codimerization of cyclopentadiene and cyclohexadiene hydrocarbons catalyzed by lanthanide-molybdenum polyoxometalates

[4+2]-Codimerization of cyclohexa-1,3-diene, cyclopentadiene, and their methyl-substituted derivatives in the presence of H-forms of synthetic mordenite and natural clinoptilolite was studied. Application of zeolites as catalyst decreases the rate of di- and trimerization of cyclopentadiene and its methyl-substituted derivatives, increases the reaction selectivity with respect to their codimers with cyclohexa-1,3-diene and its methylsubstituted derivatives as well as 4-vinylcyclohexene. Epoxidation of the synthesized codimers with the adduct of hydrogen peroxide with urea in the presence of gadolinium- and neodymium-containing phosphorus molybdenum complexes as catalysts has been investigated, and optimal conditions for preparation of diepoxides of tricyclic dienes have been found.

Polynorbornene-Based Double-Stranded Ladderphanes with Cubane, Cuneane, Tricyclooctadiene, and Cyclooctatetraene Linkers

Double-stranded ladderphanes 2, 3, and 5 having cubane, cuneane, and cyclooctatetraene linkers are synthesized by ring-opening metathesis polymerization (ROMP) of the corresponding bisnorbornene monomers 10, 11, and 13, respectively. Attempts to polymerize the corresponding tricyclooctadiene-linked bisnorbornene 12 are not successful, starting monomer being recovered. Polymer with this tricyclic diene linker 4 is obtained from the rhodium-catalyzed isomerization of 2. The scanning tunneling microscopic (STM) image of 2 shows an ordered pattern on the graphite surface by self-assembly.

Enantiocontrolled Total Syntheses of Breviones A, B, and C

Enantiocontrolled total syntheses of the breviones A, B, and C have been accomplished using a highly diastereoselective oxidative coupling of an α-pyrone with a tricyclic diene prepared from an optically pure Wieland-Miescher ketone derivative through the 7-endo-trig mode of acyl radical cyclization.

Generation of Anti-trypanosomal Agents through Concise Synthesis and Structural Diversification of Sesquiterpene Analogues

To access high-quality small-molecule libraries to screen lead candidates for neglected diseases exemplified by human African trypanosomiasis, we sought to develop a synthetic process that would produce collections of cyclic scaffolds relevant to an assortment of natural products exhibiting desirable biological activities. By extracting the common structural features among several sesquiterpenes, including artemisinin, anthecularin, and transtaganolides, we designed six types of scaffolds with systematic structural variations consisting of three types of stereochemical relationships on the sp(3) ring-junctions and two distinct arrays of tricyclic frameworks. A modular and stereodivergent assembly of dienynes exploiting a versatile manifold produced a series of cyclization precursors. Divergent cyclizations of the dienynes employing tandem ring-closing metathesis reactions overrode variant reactivities of the cyclization precursors, leading to the six canonical sets of the tricyclic scaffolds incorporating a diene group. Screenings of trypanosomal activities of the canonical sets, as well as regio- and stereoisomers of the tricyclic dienes, allowed generation of several anti-trypanosomal agents defining the three-dimensional shape of the pharmacophore. The candidate tricyclic dienes were selected by primary screenings and further subjected to installation of a peroxide bridge, which generated artemisinin analogues that exhibited potent in vitro anti-trypanosomal activities comparable or even superior to those of artemisinin and the approved drugs, suramin and eflornithine.

DFT studies on the cascade rearrangement reactions of the cubylcarbinyl radical

DFT (U)B3LYP calculations with the 6-311 + G** basis set were carried out to investigate the mechanisms of cascade rearrangement reactions (involving eight reaction channels) of the cubylcarbinyl radical (radical 1). The rate constant for each reaction step was calculated on the basis of the conventional transition state theory. The reaction channel from radical 1 to the 4-(4-methylenecyclobut-2-enyl) radical is preferred kinetically, while the reaction channel from radical 1 to the 1-homocubyl radical is unfavorable. The mechanism of the conversion from radical 1 to the tricyclic dienes radical, which is experimentally uncertain, is predicted to be a stepwise process with the methylenesecocubyl radical as an intermediate instead of a concerted reaction. The energy barrier and rate constant of the initial reaction step are evaluated to be 2.8 kcal/mol and 3.0 × 1010 s−1, respectively, in excellent agreement with the corresponding experimental values. Copyright © 2010 John Wiley & Sons, Ltd.

Total Synthesis of (+)-19-Deoxyicetexone, (−)-Icetexone, and (+)-5-Epi-icetexone

The first asymmetric total syntheses of 19-deoxyicetexone, icetexone, and 5-epi-icetexone was achieved from epimeric tricyclic dienes.

Diversity‐Oriented Synthesis of Enantiomerically Pure Steroidal Tetracycles Employing Stille/Diels–Alder Reaction Sequences

Various steroid analogues were synthesized by Stille coupling of bicyclo[4.3.0]nonenylstannanes cis-/trans-8 and 14 with cyclohexenol triflates 17 and 18 and subsequent Diels-Alder reactions of the resulting dienes. The enantiomerically pure bicyclo[4.3.0]nonenylstannanes cis- and trans-8 were prepared in good yields via the enol triflates cis- and trans-7, obtained from the bicyclo[4.3.0]non-2-en-3-one 5. The alkenylstannane 14 was obtained from the [2+2] cycloadduct 10 a produced from addition of dichloroketene to the enantiomerically pure and protected bishydroxycyclohexadiene 9 a (65 %). Treatment of 10 a with diazomethane, reduction of the dichloromethylene group, and trapping with tributyltin chloride after lithium-for-bromine exchange, yielded the bicyclo[4.3.0]nonenylstannane 14 (23 % over four steps). Stille couplings provided the tricyclic dienes cis-/trans-19 in good yields (73-77 %), whereas the tricyclic diene 20 was obtained in only 34 % yield at best. Diels-Alder reactions of trans-19 with various reactive dienophiles yielded the novel steroidal compounds trans-21 to trans-26 with complete diastereoselectivity. Heating the dienes cis-19 or 20 with maleic acid derivatives provided the corresponding tetracycles cis-23alpha,beta and 27alpha,beta with a cis-C,D ring junction, each as mixtures of two diastereomers. Less reactive dienophiles required higher temperatures to promote the relevant cycloaddition with trans-19 to furnish several stereoisomeric forms of trans-28 and trans-29 in significantly lower yields (31-45 %). The selected steroid analogues trans-22 and trans-23 were deprotected in two steps by using acid catalysis to provide trans-31 and trans-33 (91 and 80 % over two steps). Cyclopropanation of trans-30 yielded the cyclopropasteroid analogue 34 (74 %), treatment of which with trifluoroacetic acid furnished the cyclopropasteroid 35 and the 2-methyl-substituted steroid analogue 36 in 40 and 12 % yield, respectively. Aromatic B-ring steroids 38 (69 %) and 39 (5 %) were accessed by dehydrogenation of trans-24 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

3,8-Bis(4-chlorophenyl)-4,7-dimethyltricyclo[4.2.2.02,5]deca-3,7-diene

The title tricyclic diene, C24H22Cl2, is the product of thermal ring-opening of a corresponding basketane (penta­cyclo­[4.4.0.02,5.03,8.04,7]deca­ne) derivative. The cyclo­butene ring is planar to within 0.0032 (12) Å and its geometry is normal. The two 4-chloro­phenyl groups are oriented in an approximately face-to-face conformation with a dihedral angle of 44.14 (6)° between them. The 4-chloro­phenyl group bonded to the cyclo­butene ring lies almost in the plane of the cyclo­butene ring, with a dihedral angle of 8.29 (17)° between the ring planes. The average intra­molecular C⋯C distance between the two C=C bonds is 2.92 Å. In the crystal structure, the mol­ecules are well separated with no close C—H⋯Cl or C—H⋯π inter­molecular inter­actions.

One-pot enyne metathesis/Diels–Alder reaction for the construction of highly functionalized novel polycyclic aza-compounds

Various tricyclic dienes were synthesized via enyne metathesis using the first generation Grubbs catalyst. The enyne metathesis proceeded smoothly in refluxing CH 2Cl 2 with a low catalyst loading (3.0 mol %), giving good yields (72–89%) of the tricyclic products 6 and 16. The resulting 1,3-dienes are suitable precursors of polycyclic structures via a Diels–Alder process. One-pot RCM/Diels–Alder reactions of the enyne products with dienophiles proceeded smoothly to afford polycyclic compounds as a single cycloadduct. The structures of the Diels–Alder adducts were determined by 1H NMR spectra and X-ray analysis. The cycloadducts were formed via the approach of the dienophiles towards the diene in endo mode.

Abnormal Beckmann fragmentation/ring closing metathesis route for preparation of 18-nor-Δ 13(17)-androgens and their 18-nor-13,17-epoxide derivatives

The synthesis of 18-nor-Δ 13(17)-androgens and the structurally related 13,17-epoxides is described. The synthetic route involves the cleavage of 17-ketosteroids by an abnormal Beckmann rearrangement, modification of the D-ring cleavage product to obtain an intermediate tricyclic diene and ring closing metathesis of the diene to the 18-nor-Δ 13(17)-androgen. (3α,5α)-18-Norandrost-13(17)-en-3-ol and the derivative 13α,17α- and 13β,17β-epoxides were prepared by this route.

A New Access to Multifunctional Linear Triquinanes and Their Homologues via α,β‐Unsaturated Fischer Carbene Complexes

AbstractTwelve differently substituted tricyclic hydroxy ketones 7, 8 with [5‐5‐x] (x = 5, 6, 7) combinations of ring sizes were prepared in a single step in 43–91 % yields (10 examples with 74–91 %) from the corresponding protected (2'‐oxocycloalkyl)methyl‐substituted cyclopentadienes 6, which were obtained by cocyclization of the alkynes 5 with the β‐dimethylamino‐substituted α,β‐unsaturated Fischer carbene complexes 4 in 38–81 % yield (6 examples with 66–81 %). In most cases, the cis,anti,cis‐isomers anti‐7 were the major products. While the twofold cis‐fusion is favored by minimal ring strain, hydrogen bonding between the hydroxy and the carbonyl group probably favors the anti‐configuration of the tricyclic skeletons. Acid‐catalyzed dehydration of the hydroxy ketones anti‐7aa, anti‐7ba, anti‐7ca afforded the corresponding tricyclic dienes 15aa/16aa, 15ba, and 15ca/16ca, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

1,2,4,5,6,7,8,9-Octachlorotricyclo[5.2.1.02,6]deca-4,8-diene-3,10-diol

The title compound, C10H4Cl8O2, is a poly­chloro-substituted tricyclic diene, comprised of a norbornene section with a cis–endo cyclo­pentene fused to it. This strained ring system has been described before, but not with the two hydroxyl substituents found here. It was synthesized as a possible precursor to homocubane or cubane cage systems, but conditions for a cage closure reaction have not yet been found.

En Route to 7,7,8,8-Tetraethynyl-p-quinodimethane (TEQ)

The cross-conjugated 1,1-diethynylethylene derivatives 8b−10b were prepared from the corresponding bromides 16, 19, and 17 by Sonogashira coupling with trimethylsilylethyne and hydrolysis of the TMS-protected intermediates thus formed. Coupling of the tetrabromide 18 with (trimethylsilylethynyl)magnesium bromide in the presence of 1,3-[bis(diphenylphosphanyl)propane]nickel(II) chloride yielded the protected tetraalkyne 32, from which the 7,7,8,8-tetraethynyl-tetrahydro-p-quinodimethane 33 was liberated by fluoride treatment. Although 33 is a highly unstable cross-conjugated hydrocarbon, it could be converted into its tetraphenyl derivative by Sonogashira coupling with phenyl iodide. Both 32 and the corresponding tetraphenyl derivative were oxidized to the 7,7,8,8-tetraethynyl-dihydro-p-quinodimethane derivatives 35 and 36, respectively, on treatment with DDQ in dioxane. Further dehydrogenation of 35 to 34 failed, however. Alkylation of 9b with trimethylaluminium in the presence of zirconocene dichloride as catalyst yielded the semicyclic dendralene 37, which on irradiation isomerized to the tricyclic diene 42, presumably via the bicyclobutane 39 and a vinylcyclopropane rearrangement. Hydration of 9b furnished 43 and 44, the primary hydration product 38 either undergoing ketene elimination (formation of 43) or a 1,5-hydrogen shift reaction (to 44) from its tautomer 41. Analogously, the still more highly unsaturated derivative 31 was alkylated to give the [5]dendralene derivative 45 and hydrated to give a mixture of the β-diketones 46 and 49, the latter being produced from 46 by 1,2-methyl migration. The thermal cyclization of 10b to the homoacepentalene derivative 51 failed. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Stereoselectivities of Diels-Alder cycloadditions of tricyclic dienes to MTAD, PTAD, and N-methylmaleimide

Diels-Alder cycloadditions of 1,2,3,4,9,9-hexachloro-1α,4α,4aα,8aβ-tetrahydro-1,4-methanonaphthalene ( 5) and 1,2,3,4,9,9-hexachloro-1α,4α,6,7-tetrahydro-1,4-methanonaphthalene ( 6) to 4-methyl- and 4-phenyl-1,2,4-triazoline-3,5-dione [MTAD and PTAD, respectively] and to N-methylmaleimide (NMM) have been studied. The structures of several of the resulting cycloadducts were determined unequivocally by X-ray crystallographic methods.

The isolation, structure, and stereochemistry of traversiadiene. The precursor hydrocarbon of traversianal biosynthesis

A tricyclic diene, traversiadiene, isolated from cultures of Cercosporatraversiana has been shown to have the structure and stereochemistry of the previously postulated hydrocarbon intermediate on the biosynthetic pathway to traversianal (1). Detailed:1H and 13C magnetic resonance studies, including homo- and heteronuclear correlation spectra, led to the gross structure, and the stereochemistry was established through a series of nuclear Overhauser effect difference spectra. Keywords: diterpene, traversiadiene, 1H and 13C magnetic resonance spectra.

Cobalt-mediated synthesis of tricyclic dienes incorporating fused four-membered rings. Unprecedented rearrangements and structural characterization of a cobalt-diene complex by two-dimensional NMR spectroscopy

On etudie la cyclisation intramoleculaire (2+2+2) catalysee par CpC(CO) 2 des enediynes suivants: undecene-1diyne-5,10 et dodecene-1diyne-5,11

Cobalt‐Mediated [2 + 2 + 2]‐Cycloadditions: A Maturing Synthetic Strategy [New Synthetic Methods (43)

AbstractDicarbonyl (η5‐cyclopentadienyl)cobalt functions as a matrix on which a variety of unsaturated organic substrates undergo mutual bond formation. In this way α,ω‐diynes cocyclize with monoalkynes to give annelated benzenes, while o‐diethynylbenzenes furnish biphenylenes, and α,ω‐enynes lead to the formation of complexed bi‐and tricyclic dienes. Nitriles cocyclize with two alkynyl groups to give pyridines and other heterocycles, isocyanates allow access to annelated 2‐pyridones, and incorporation of carbon monoxide provides complexed cyclopentadienones. In many cases remarkable chemo‐, regio‐, and stereoselectivity are observed, partially facilitated by use of the trimethylsilyl substituent as a controlling group. The scope and level of maturity of the method are demonstrated by the synthesis of a series of hitherto inaccessible, novel, and theoretically interesting molecules, and by its utilization in several unique approaches to a variety of natural products, e.g. protoberberines, steroids, vitamin B6, and camptothecin.

Intramolecular cobalt-mediated [2 + 2 + 2] cycloaddition of linear enediynes. A useful synthetic entry into cobalt-protected tricyclic dienes and their synthetic elaboration

Intramolecular cobalt-mediated [2 + 2 + 2] cycloaddition of linear enediynes. A useful synthetic entry into cobalt-protected tricyclic dienes and their synthetic elaboration

Abkömmlinge der 3‐Chinolincarbonsäure mit Sauerstoffsubstitution in Stellung 4, 5 and 8: Synthese, Reaktionen, NMR.‐Studien

Derivatives of 3‐Quinolinecarboxylic Acid with Oxygen Substitution in Positions 4, 5 and 8: Synthesis, Reactions, NMR. StudiesStarting from either 1, 4‐dibenzyloxybenzene (7) or 2, 5‐dimethoxyaniline (16), synthetic routes have been developed to benzenoid and quinoid derivatives of 4‐oxo‐1, 4‐dihydro‐3‐quinolinecarboxylic acid with O‐bearing substituents in the positions 5 and 8 (compounds 12‐15, 19, 20, 23, and 24). With the 1‐ethyl‐4, 5, 8 trioxo acid 14 as a dienophile, a series of linear tricyclic diene adducts (29‐32) has been prepared, the structures of which were further modified by aromatization, reduction or dehydrogenation (compounds 33‐40). A series of benzenoid and quinoid compounds with an additional substituent in position 6 or 7 (Table 1) has been derived mainly from the quinone 14, primarily by addition of nucleophiles and eventually subsequent steps, and by aromatic electrophilic substitution of the 1‐ethyl‐5, 8‐dimethoxy acid 23. The substitution pattern of some of these compounds has been elucidated by detailed 13C‐NMR. studies (Table 2) and/or nuclear Overhauser‐effect studies (Table 3). Correlations, based essentially on chemical arguments, allowed to define the structures of most of the residual new compounds (Table 4).

Notizen: Konkurrenzreaktionen einiger tricyclischer Diene zur [2+2]PhotocycIoaddition / Competitive Reaction of Some Tricyclic Dienes to [2+2]Photocycloaddition

Abstract The UV-behaviour of some chlorinated tri-cyclic dienes (1 a-e) was studied in acetone. Cycloaddition (2 a-b and 2 d-e), hydrogen-transfer (3 c′ and 3 d) and photo ene-(3 c)-reaction products could be isolated and identified with the help of spectroscopic methods.