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Reactions between 6-substitued fulvenes and the hydride complex RuHCl(PPh3)3 are described. Treatment of RuHCl(PPh3)3 with fulvenes without sp3-CH protons at the carbon α to the exocyclic carbon of fulvene produces cleanly monosubstituted cyclopentadienyl ruthenium complexes (η5-C5H4R)RuCl(PPh3)2 via hydride transfer to the electrophilic exocyclic carbon of fulvenes. When fulvenes containing sp3-CH protons at the carbon α to the exocyclic carbon were used, the reactions produce the expected (η5-C5H4R)RuCl(PPh3)2 complexes along with minor amounts of vinylcyclopentadienyl ruthenium complexes due to dehydrogenation.

The synthesis of the methylfulvene- and phenylfulvene-annelated dihydropyrenes 10 and 22 from the cyclopentadiene-fused dihydropyrene 7 in 68% and 80% yields, respectively, are reported. However, the attempted formation of the parent fulvene-fused dihydropyrene 18 failed, both from the cyclopentadiene 7 with formaldehyde and from the cyclopentadienone 5 in Wittig-type reactions. Chemical shift data for the methylfulvene (35) and phenylfulvene (36)-fused dihydropyrenes 10 and 22 were used to estimate the reduction in the dihydropyrene nucleus aromaticity (DHPN) (relative to benzene fusion) in 10 and 22 (12-16% and 22-25% respectively). Calculations revealed that this reduction in diatropicity, contrary to the situation with benzene fusion, is not due to any aromaticity of the annelating fulvenes but instead is caused by Mills-Nixon-type effects. We conclude that methyl- and phenylfulvene are nonaromatic. An improved synthetic route to the cyclopentadienone 5 was found in an unprecedented cyclization of the trans-cinnamic acid analogue 29 in 80% yield. This enabled an X-ray structure of 5 to be obtained, for comparison to that of the saturated ketone 4. Even though crystals of 5 and 4 show diastereomeric disorder, when the average bond length data of cyclopentadienone 5 is compared with those of cyclopentenone 4 and the parent and benzo dihydropyrenes 6 and 33, it is clearly evident that 5 has the opposite bond-alternation pattern, consistent with a [4n] fused annulene. From the bond length data, cyclopentadienone has approximately 87% of the effect of a benzene ring on bond alternation, which is in reasonable agreement with the previously found NMR value (78%). Structure and nucleus-independent chemical shift calculations support these results.

The reaction of 1-ethynyl-2-vinyl-3,4-dihydronaphthalenes and 1-ethynyl-2-vinylnaphthalenes over RuCl2(p-cymene) PPh3 leads to 9,10-dihydrophenanthrenes and phenanthrenes in those cases where the ethynyl group in the substrates carries a terminal proton. When 1-phenylethynyl-2-vinyl-3,4-dihydronaphthalenes or 1-phenylethynyl-2-vinylnaphthalenes are reacted over Pt(PPh3)4, 1-methylene-1H-benz[e]-4,5-dihydroindenes and 1-methylene-1H-benz[e]indenes are formed.

Herein we report the reactivity of N-(2,4-dicyano-1,5-dimethyl-3-arylcyclopenta-2,4-dienyl)-2,2,2- trifluoroacetamides and N,N-dimethyl-4-nitrosoaniline which provide compounds derived from Ehrlich-Sachs condensation, dihydrofuran derivatives and fulvene derivatives by adjusting the reaction conditions.

The syntheses and crystal structures of a series of 6-(substituted-phenyl) fulvenes are reported. In three instances the molecular structures determined by X-Ray crystallography were compared to the results of DFT calculations. In these cases only minor differences were found between the optimised DFT calculation and the molecule found in the crystal structure. This is of particular interest in the case of 6-(p-[N-acetyl]aminophenyl)fulvene which shows intermolecular hydrogen bonding.

The allenylcarbene complex [OsCl2{=CPh(η2-CH=C=CHPh)}(PPh3)2] undergoes coupling reactions with HC≡CSiMe3 and PhC≡CC≡CPh to produce the fulvene complexes [OsCl2{η6-C5H2(Ph)(SiMe3)(=CHPh)}(PPh3)] and [OsCl2{η6-C5H(Ph)2(C≡CPh)(=CHPh)}(PPh3)], respectively. A similar coupling reaction also occurs between [OsCl2{=CPh(η2-CH=C=CHPh)}(PPh3)2] and styrene.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

A detailed investigation on the reaction of pentafulvenes with N-substituted-1,2,4-triazoline-3,5-diones leading to the formation of five- and seven-membered azapolycycles is described. The observed reactivity is explained based on the electronic and frontier molecular orbital features of pentafulvene and triazoline dione, which suggested that the latter molecule can add to the former one via a [4 + 2] cycloaddition or it can undergo a nucleophilic reaction at the exo carbon atom of pentafulvene. These reactions would ultimately give the same product and the energetics of them suggested that both mechanisms are operative in the reaction conditions.

The first Ag(I)-catalyzed [6 + 3] cycloaddition/isomerization of fulvenes and isocyanoacetates for the facile access to fused dihydropyridines with high functionality is reported.

This method is suitable for the synthesis of a variety of fulvene derivatives, though not all 1,3-dicarbonyl substrates yield the desired product, e.

Desymmetrization of fulvene-derived bicyclic hydrazines by a palladium/Lewis acid catalyzed reaction with allyl and vinyl stannanes leading to the efficient synthesis of synthetically important alkylidene cyclopentenes is described.

Azlactone anions-the key intermediates in the classical Erlenmeyer synthesis of amino acids-apparently possess aromatic stabilization, as indicated by the relative rate of base catalyzed deuterium exchange in the following analogs: 1-methyl-2-phenyl-5(4H)-imidazolone > 2-phenyl-5(4H)-oxazolone (azlactone) > 3,3-dimethyl-2-phenyl-4(3H)-pyrrolone. This is paralleled by the relative rate of condensation of these compounds with hexadeuteroacetone. Reported pK(a) data also suggest that the azlactone products of the Erlenmeyer synthesis are analogs of the fulvenes. (c) 2006 Elsevier Ltd. All rights reserved.

Synthesis of rigid ansa-zirconocene precatalyst systems with a C2-bridge embedded in a spirane scaffold is described. Fulvenes were key intermediates in regio- and stereoselective preparation of the appropriate spirane ligands. Substitution in the cyclopentadienyl group in the ligand was effected by fulvene methodology. The zirconocenes were active precatalysts for the polymerisation of propene when activated with MAO. The structure of the parent zirconocene dichloride has been verified by X-ray crystal analysis.

A series of new linear and cyclic polyenes including siloles, butadienes, cyclcobutenes, fulvenes, and 4H-pyrans are designed and synthesized. When molecularly dissolved in common organic solvents, all the polyenes are practically nonemissive. Addition of poor solvents induces the polyenes to cluster into nanoaggregates, which turns the emission of the polyenes “on” and boosts their luminescence efficiencies dramatically (hence “aggregation-induced emission” or AIE). The emission color ranges from blue to red, depending on the chromophoric structures. Polyene nanoparticles on TLC plates show bright blue fluorescence which switches off reversibly in an atmosphere of volatile organic compounds. Addition of poor solvents to solution of cyclic polyenes bearing cholsteryl moieties leads to polarized green and anisotropic red emissions dependant on the solvent ratios. The different emissions may be caused by different packing patterns of the polyene crystals under different conditions.

The Chemistry of several condensed selenophenes, and tellurophenes (1–4) will be presented. The synthesis of mixed selenium-tellurium fulvenes (5) and generation of 2,4-bis-methyleneditelluretane (6) will be discussed.

The hetero [6+3] cycloaddition of fulvenes to benzoquinones and iodoanilines provides an efficient route to the synthesis of cyclopenta[c]-4H-chromen-8-ol, benzo[d]cyclopenta[e]-3H-3-azin-8-ol and other 11hetero steroids. The structure of the cyclopenta[c]chromene skeleton was confirmed by the X-ray structure analysis of the p-bromobenzoate of 39. A small library consisting of 110 examples was prepared by reacting benzoquinones or iodoanilines with resin 17.

Starting from 2-furylfulvene (1a), 2-thiophenylfulvene (1b), and 1-methyl-2-pyrrolylfulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di-(2-furyl)ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-di-(2-thiophenyl)ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis-(1-methyl-2-pyrrolyl)ethanediyl] titanium dichloride (2c) were synthesized. When titanocenes (2a–c) were tested against pig kidney carcinoma cells (LLC-PK), inhibitory concentrations (50%) of 4.5 × 10−4M, 2.9 × 10−4M and 2.0 × 10−4M respectively were observed. Copyright © 2005 John Wiley & Sons, Ltd.

Condensation reactions between various dienes and dienophiles have been screened for reversibility. Functionalized fulvenes, bearing in particular biological groups, and cyanolefins have been found to react rapidly and reversibly, in the temperature range from -10 to +50 degrees C. These results pave the way for the development of dynamic combinatorial libraries based on reversible Diels-Alder chemistry.

[reaction: see text] The coupling reaction of 1,4-diiodo-1,3-alkadienes with a Grignard reagent in the presence of a catalytic amount of Pd(PPh3)4 proceeded with excellent site-selectivity. Synthetic application of the reaction was demonstrated by a regio- and stereoselective synthesis of 1,3,6-trisubstituted fulvenes.

Starting from 6-(p N;N-dimethylanilinyl)fulvene (1a) or 6-(pentamethylphenyl)fulvene (1b) [1,2-di(cyclopentadienyl)-1,2-di(p N;N-dimethylaminophenyl)ethanediyl] titanium dichloride (2a) and [1,2-di(cyclopentadienyl)-1,2-bis(pentamethylphe-nyl)ethanediyl] titanium dichloride (2b) and their corresponding dithiocyanato complexes (3a, 3b) were synthesized. Titanocene 2bdid not show a cytotoxic effect, but when 2a was tested against pig kidney carcinoma cells (LLC-PK) or human ovarian carcinomacells (A2780/cp70) inhibitory concentrations (IC 50 ) of 2.7 10 4 and 1.9 10 4 M, respectively, were observed. 2004 Elsevier B.V. All rights reserved. Keywords: Anti-cancer drug; cis-Platinum; Titanocene; Fulvene; LLC-PK; A2780/cp70 1. IntroductionDespite the resounding success of cis-platinum andclosely related platinum anti-tumor agents, the move-ment of other transition-metal anti-cancer drugs to-wards the clinic has been exceptionally slow [1–3].Metallocene dichlorides (Cp 2 MCl 2 )withM¼Ti, V, Nband Mo show remarkable anti-tumor activity [4,5].However, only titanocene dichloride has reached Phase Iclinical trials so far, with a maximum tolerable dose of315 mg/m

[reaction: see text] Bu(3)Sn-mediated 5-exo-dig radical cyclization of diaryl enediynes provides a mild and efficient approach to tin-substituted fulvenes. Further synthetic opportunities opened by this process and general factors responsible for the observed regio- and stereoselectivity are outlined.

2H-Azirine reacts with fulvenes to give either alkylated fulvene azirines (ultrasound) or the formal [6+3] cycloaddition adducts (Lewis acid). The later constitutes an efficient and novel route to [2]pyrindines.

The stereoselectivity, periselectivity, and regioselectivity in the cycloaddition reactions of 8-( p -chlorophenyl)-8-azaheptafulvene with cyclopentadiene and symmetrical/unsymmetrical fulvenes is described.

A series of proaromatic electron acceptors derived from fulvenes were synthesized from tetrachlorocyclopentadiene and previously unknown 1,4-dicyano- and 1,4-dialkoxycarbonyl-2,3-dimethoxy cyclopentadienes. Two reversible one-electron reductions steps observed for fulvalenes coalesce into one two-electron reduction step upon increasing the length of the conjugating bridge.

1st International Symposium on Bioorganometallic Chemistry (ISBOMC 02), PARIS, FRANCE, JUN 18-20, 2002; International audience; CpRe(CO)(3) substituted derivatives were obtained in good yields (44-96%) from fulvenes and Re-2(CO)(10) in boiling mesitylene. This new methodology was applied to the synthesis of CpRe(CO)(3) substituted steroids with success. (C) 2002 Elsevier Science B.V. All rights reserved.

Fulvenes acting as 4π components in an intramolecular [4+2] cycloaddition reaction leading to the formation of novel 6-oxatricyclo [6.4.0.02,10] dodeca-2,11-diene ring systems have been described. Importance of steric buttressing effect in promoting the reaction has been discussed.

The convenient syntheses of new organophosphorus-substituted benzofulvenes with indenyl moieties from bis(trimethylsilyl) inden-2-ylphosphonate and substituted azomethines in the presence of the effective initiator-sodium hydride are developed. The following treatment of phosphonates with methanolic sodium methylate gives stable water-soluble disodium salts of corresponding phosphonic acids.

o-Carboryne (1,2-dehydro-o-carborane) generated in situ from the precursor 1-iodo-2-lithio-o-carborane reacts with 6,6′-diarylfulvenes to give a series of carboranonorbornadienes in moderate yields with excellent regioselectivity. The resultant [4+2] cycloadducts can be further derivatized, thus leading to the formation of a variety of highly functionalized carboranes. This study shows that such Diels–Alder reaction serves as a convenient method for the preparation of a new class of multifunctionalized o-carborane derivatives that might find applications in medicine and materials science.

The frustrated Lewis pair (FLP) mediated hydrosilylation of pentafulvenes is described yielding allyl silanes with high regioselectivity in excellent yields. While phenyl substituted allyl silanes undergo B(C6F5)3-mediated rearrangement to vinyl silanes, dimethyl derivatives experience FLP-catalyzed hydrogenation followed by an unprecedented protodesilylation. This observation allowed the metal-free hydrogenation of 6,6-dimethylfulvene to iso-propyl cyclopentene according to a FLP-catalyzed triple domino reaction consisting of hydrosilylation, hydrogenation and protodesilylation. The mechanisms were investigated by deuteration experiments.

A base-promoted [3 + 2] annulation reaction of ethyl α-chlorocyclopropaneformates with 1,3-dicarbonyl compounds is described. This method provides an efficient and straightforward route to acidic multi-substituted fulvenes with distinctive properties.

Enantioenriched heterocyclic piperidines are important structural motifs present in numerous natural products and biologically active molecules. This article outlines our recent efforts to develop a straightforward access to highly functionalized piperidine derivatives with multiple stereogenic centers, in good yields and excellent stereoselectivities, via copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar [6+3] cycloadditions of azomethine ylides with fulvenes.

Under optimized conditions the uncommon cascade reaction gives vinyl fulvenes and ortho-terphenyl derivatives as by-products.

Fulvenes generated from steroids have been efficiently engaged in a process implying nucleophilic or basic attack followed by a transmetallation reaction in the presence of BrRe(CO)5 to afford the corresponding CpRe(CO)3 substituted compounds. This new strategy is of relevant interest for the synthesis of new potential radiopharmaceuticals.

A one-pot Ag2CO3 mediated oxidative dimerization of 1,3-diketone followed by cycloaddition to fulvenes is described. This methodology has been applied to the synthesis of 7-oxatricyclo[6.4.0.02,6]dodecanes and/or 8-oxatricyclo[7.4.0.03,7]tridecanes.

We report accurate Ab Initio Hartree Fock (HF) and Density Functional Theory (DFT) studies of the static dipole polarizabilities and first hyperpolarizabilities of the [n] fulvene and the [n,m] fulvalene series of molecules (with n, m = 3,5,7). Calculations are also reported for the parent cycloalkenes: cyclopropene, cyclopentadiene and cycloheptatriene (1-3 respectively). Geometries were optimized at the HF/6-311G(3d,2p) level of theory. All the fulvenes (4-6) and the smaller fulvalenes (7, 9 and 10) are found to be planar. Pentaheptafulvalene (11) is slightly non-planar whilst heptafulvalene (12) has a folded C2h structure. Calculated C-C bond lengths are consistently smaller than the experimental values. Dipole polarizabilities and non-zero hyperpolarizabilities were calculated at the HF/6-311++G(3d,2p) and BLYP/6-311++G(3d,2p) levels of theory, using HF/6-311G(3d,2p) geometries. Dipole polarizabilities correlate well with those given on the basis of atom additivity. Molecules (8), (9) and (11) show very large dipole hyperpolarizabilities.

Dipolar cycloaddition reactions of aryl nitrile oxides to 6-(2-phenylethenyl)fulvene leading to isoxazolines are described.

Thiele condensation of the [2.2]paracyclophane derivatives 8, 12, 22, and 23 with cyclopentadiene (9) led to the monofulvenes 10, 11, and 13 and the bis(fulvenes) 24 and 25. Likewise, condensations of 8 with 1,2,3,4-tetrachlorocyclopentadiene (14) and 1,2,3,4-tetraphenylcyclopentadiene (16) provided the 4-fulvenyl[2.2]paracyclophanes 15 and 17. For comparison purposes, 8 was also condensed with lithium fluorenide (18) and lithium indenide (20) to give the benzo-annelated derivatives 19 and 21, respectively. Reactions of the dialdehydes 22 and 23 led to the bis(indenes) 26 and 27. 4-(6-Fulvenyl)[2.2]paracyclophane exists as two conformational isomers, 10 (major product) and 11 (minor product). By temperature-dependent NMR spectroscopy, the rotational barrier associated with 11 ⇄ 10 interconversion has been determined as ca. 26 kcal mol−1 at 70 °C. The structures of 19 and 27 have been established by single-crystal X-ray crystallography.

This is the first report on the selective synthesis of fulvenes via a [2+2+1] cyclotrimerization of alkynes under catalytic conditions. The reactions of aliphatic terminal alkynes 1a – e in the presence of a palladium catalyst in toluene gave the cyclotrimerization products 2a – e , not easily available through the previously known methods, in good to fair yields.

A simple and convenient route for one-pot synthesis of cyclopenta[d]pyridazine through 1,3-dipolar cycloaddition of fulvenes and hydrazonyl chlorides is described. The reaction of fulvenes with hydrazonyl chlorides in the presence of silver carbonate smoothly afforded a series of cyclopenta[d]pyridazines.

Attempted protection of the phosphines in the C 2 symmetric ferrocene, 1,1′-bis[( S )-4-isopropyloxazolin-2-yl]-2, 2′-diphenylphosphinoferrocene, as their sulfides failed to give the desired product. Fragmentation of the, typically stable, ferrocene system occurred with the phosphine substituted fulvene, 5-[(4 S )-4-isopropyl-1,3-oxazolan-2-yliden]-1,3-cyclopentadienyl (diphenyl)phosphine sulfide, being isolated.

The side-chain and substituent control of stereoselectivity, periselectivity and regioselectivity in the intramolecular [8 + 6] and [4 + 2] cycloadditions of electron-deficient 8-cyanoheptafulvenes connected at C-8 by trimethylene or tetramethylene chains to C-6 of electron-rich 6-methyl- or 6-phenylfulvenes are discussed.