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The influence of the intramolecular H-bonding formation on the aromaticity of some substituted penta-fulvenes is investigated using magnetic (NICS(0), NICS(1) and NICS(1) zz ), geometrical (HOMA) and electronic (FLU and SA) criteria to consider the multidimensional character of aromaticity. It is found that the formation of intramolecular hydrogen bond changes aromatic character of a substituted penta-fulvene. The variations of SA and HOMA indices due to the formation of intramolecular H-bondig significantly correlate with the properties of the considered hydrogen bond, while the other indices do not give any meaningful results. It seems that the hydrogen bond influences the geometrical and electronic dimensions of aromaticity.

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.

Fulvenes undergo an easy [6+3] cycloaddition with 3-oxidopyrylium betaines leading to 5–8 fused oxabridged cyclooctanoids.

The preparation and characterization of a series of deuterium-labelled (fulvene)M(CO) 3 (M = Cr, Mo) complexes is reported. (η 5 -6-Dimethylaminofulvene-d 2 )Cr(CO) 3 and (η 5 -6-dimethylaminofulvene-d 2 )Mo(CO) 3 were obtained in high yields by reacting the deuterated fulvene ligands with (MeCN) 3 M(CO) 3 (M = Cr, Mo). In addition, syntheses of 6,6-diphenylfulvene-d 10 and 6,6-diphenyl-1,2-benzofulvene-d 10 as well as the corresponding tricarbonylchromium complexes are described.

Pentafulvenes with alkyl and/or aryl substituents at the exocyclic position are formed rapidly in high yields through reaction of crystalline sodium cyclopentadienide directly with the appropriate ketones.

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

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.

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.

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

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.

Cycloaddition reactions of 2-oxo-2H-cyclohepta[b]furan derivatives participating as 8π and 4π components respectively towards different dienes and dienophiles are described. The observed reactivity and periselectivity have been rationalized by AM1 calculations.

A convenient and general synthesis of 6-aryl and 6,6-diaryl ring-functionalized fulvenes from ferrocenyl amide carbinols via a combined Directed ortho Metalation — acid catalyzed fragmentation ( Scheme 2 ) is reported.

The exocyclic substituent control of stereoselectivity, periselectivity, and regioselectivity in the unsymmetrical cycloaddition reactions of electron-deficient heptafulvenes with electron-rich fulvenes are discussed.

A new and concise synthesis of the useful synthetic intermediate 1 is described which also allows access to a novel C 2 -symmetric keton 2 . The route relies on the Sharpless asymmetric dihydroxylation of fulvenes.

The compound (ethene) 2 (toluene)iron ( 1 ) is prepared by cocondensation of iron and toluene and subsequent treatment with ethene. Reaction of ( 1 ) with 6,6-dimethylfulvene leads to the known products ansa-ferrocens and 1,1′-bis(isopropyl)ferrocene. Reaction of ( 1 ) with 6,6-diphenylfulvene ( 2 ) gives 1,1′-bis(benzhydryl)ferrocene ( 3 ). The intermediate in the formation of ( 3 ), bis(diphenylfulvene)iron ( 4 ) was isolated. ( 4 ) was characterized by MS and a X-ray structure determination and its structure compared with the structure of the free ligand ( 2 ). The structure of ( 4 ) was also determined by DFT-ab-initio calculations.

Reaction of 2,5-dimethyl-3,4-diphenylcyclopent-2-enone ( 1 ) with Ph 3 PCH 2 in THF gave 2,5-dimethyl-3,4-diphenylcyclopent-2-enel-ylidene ( 2 ) in 75% yield. Treatment of 2 with one equivalent Br 2 , followed by twp equivalents of triethylamine gave 1,4-dimethyl-2,3-diphenylfulvene ( 3 ) in 60% overall yield. Treatment of 3 with LiCH 3 and LiC 6 H 5 followed by FeCL 2 gave [ η 5 -1-CH 3 CH 2 -2,5-(CH 3 ) 2 -3,4-(C 2 H 5 ) 2 -3,4-(C 6 H 5 )C 2 ] 2 Fe and [ η 5 -1-C 6 H 5 CH 2 -2,5-(CH 3 ) 2 -3,4-(C 6 H 5 ) 2 C 5 ] 2 Fe, respectively, in good yield. Treatment of 3 with LiNHC(CH 3 ) 3 and LiP(C 6 H 5 ) 2 followed by FeCl 2 gave [ η 5 -1-(CH 3 ) 3 CNHCH 2 -2,5-(CH 3 ) 2 -3,4-(C 6 H 5 ) 2 -3,4-(C 6 H 5 ) 2 C 5 ] 2 Fe and [ η 5 -1-(C 6 H 5 ) 2 PCH 2 -2,5-(CH 3 ) 2 -3,4-(C 6 H 5 ) 2 C] 2 Fe, respectively, in good yield. Treatment of 3 with (R)-LiNHCH(CH 3 )C 6 H 5 followed by FeCl 2 gave the corresponding enantiomerically pure ferrocene complex (R,R)-[ η 5 -1-C 6 H 5 CH(CH 3 )NHCH 2 -2,5-(CH 3 ) 2 -3,4-(C 6 H 5 ) 2 C 5 ] 2 Fe in 44% yield.

A kinetically stabilized 1,3,6-triphosphafulvene displayed regioselective reactivity toward nucleophiles at the external phosphorus atom (position 6) to afford the corresponding phosphinodiphospholide anions, which gave phosphinodiphospholes after quenching with electrophiles, as well as being readily reduced by sodium naphthalenide suggesting properties similar to fulvenes.

A heterocycloaddition route to complex, naturally-occurring aminocyclopentitols and other 1,2,3,4,5-pentasubstituted cyclopentanes is described based on the photooxygenation of a substituted fulvene.

3,5-Di- tert -butyl-, 4- tert -butyl- and 3-methoxy- o -benzoquinones have been shown to undergo facile thermal cycloaddition to symmetrical and unsymmetrical fulvenes to give bicyclo[2.2.2]octene diones in high yields.

3,5-Di-tert-butyl-, 4-tert-butyl-, and 3-methoxy-o-benzoquinones have been shown to undergo thermal cycloaddition to symmetrical and unsymmetrical fulvenes to give bicyclo[2.2.2]octen-7,8-diones in high yields.

An efficient synthesis of polysubstituted pentafulvenes from 4-alkylidenecyclopentenones is reported via a two-step procedure consisting of addition of an organometallic reagent (or reduction) followed by dehydration.

o -Thioquinones undergo facile hetero Diels–Alder reactions with pentafulvenes leading to 1,4-benzoxathiins.

Intramolecular [4+2] cycloaddition of fulvenes 2a,b gives 6-oxatricyclo[6.4.0.0 2,10 ]dodeca-2,11-diene-[4,5-a]naphtho- endo 9-carboxylic acid alkyl esters 3a,b . Compounds 3a,b are the first representatives of this bridged tricyclic ring system.

Unlike ferrocene, cobalticinium cation is chemically inactive towards electrophilic substitutions and for this reason the number of derivatives in this series is limited. Substituted cobalticinium salts are usually prepared indirectly from substituted cyclopentadienyl derivatives. These intermediates can be obtained by treating substituted cyclopentadienes with strong bases or by reducing fulvenes. Various homo- and hereto-substituted cobalticinium salts have been prepared using this type of reaction. Due to the remarkable stability of the metallocenic skeleton of cobalticinium ion, we have succeeded in obtaining new derivatives transforming ring-substituted cobalticinium salts by known reactions.

The series of pentafulvenoid dyes has recently been enriched by the deeply coloured 1,2,3,4-tetrachloro-pentafulvene-6,6-dicarbonitrile, the first representative of the 6,6-di-acceptor-substituted fulvenes. This synthesis has initiated a study of the relationships between colour and constitution of 6,6-diamino- and 6,6-dicyano-pentafulvene, cyclopenta-dienone and the cyclopentadienon-immonium ion. The main tool of this study was the molecular orbital and configuration analysis method according to Baba, Takemura and Suzuki within the framework of the variable β Pariser-Parr-Pople method. A clear interpretation has been achieved in terms of both iso-π-electronic delocalized and localized reference structures.

Zusammenfassung Cyclopentadiene, trimethylsilylcyclopentadiene and fulvenes react with dialkyl, cycloalkyl or diaryl sulfoxides in the presence of trifluoro-acetic anhydride to form mono-, bis- or trissulfonio substituted derivatives.

Starting from technical methylcyclopentadiene two trimethylfulvenes are obtained (2,6,6 and 3,6,6 derivatives). When the corresponding cyclopentadienyl anions [Cp1★ and Cp2★ (Cp = C5H3MeCHMe2 1,2 or 1,3] are treated with η5-C5H5TiCl3 a complex mixture of substituted titanocene dichlorides is obtained. Some of them are redistribution compounds in which the two pentahapto ligands bear a planar chirality. The symmetric (Cp1★2TiCl2 and Cp2★2TiCl2) and mixed (Cp1★Cp2★TiCl2) dichlorides are obtained separately from TiCl4 and the respective fulvene or a mixture of fulvenes, but these chlorides are still, in each case, a mixture of several stereochemical forms. For the symmetric chlorides the separation and identification of these forms can be brought about by a preliminary transformation into diaryloxy [Cp2★Ti(OAr)2] or chloroaryloxy [Cp2★TiClOAr] complexes. For the separation of the mixed chlorides it is necessary to use the dithiolato complex of 1,2-dimercapto-4-methylbenzene which has two prochiral enantiopic faces.

Title fulvenes were synthesized through the reaction of the large-membered annulenones with diphenylketene, and examination of 1H-NMR spectra suggests that the fulvenes are atropic.

1,2,4,5-Tetrabromobenzenes and analogous napbthalanes react with one or two equivalents of n -butyllithum and various dienes (furans, pyrroles, cyclopentadienes, fulvenes) to form mono- or bis-cycloadducts. Highly substituted arenes can be obtained by removing the oxygen or nitrogens bridges from the furan or pyrrole adducts. By choice of conditions, two identical or two different rings can be fused to the di-aryne epuivalent. Improved short syntheses of permethylnaphthalene, -anthracene and -naphthacene are described. A new triphenylene synthesis is presented.

Dicyclopentadienylytrrium chloride reacts with aldehydes and ketones at 80°C in DME, generating fulvenes in excellent yields, while at lower temperature affording, after hydrolysis, cyclopentadienyl substituted alcohols.

A one-step synthesis of a new series of spiro-pyrazolines has been accomplished by the 1,3-dipolar cycloaddition of 1,3-diphenylnitrilimine with various fulvenes (2,3,4,5-tetraphenyl fulvene (1) and its analogues (2, 3), 9-benzalfluorene (7) and its analogues (8, 9) and 6,6-diphenylfluvene (13)). With the exception of 13 all other fulvenes undergo 1,3-dipolar cycloaddition across the exocyclic double bond to give the hitherto unreported spiro-pyrazoline derivatives (1-6, 10-12). In the case of 13, however, the addition of 1,3-dipole takes place at the site of endo-cyclic double bond, leading to the formation of a pyrazoline derivative (14).

Condensation of cyclopentadienyl anions obtained from fulvenes and tetra- chloride metal to prepare (η5-RC5H4)2MCl2, R = alkyl; M = Zr or Hf is described. The prochiral complexes (η5-RC5H4) (η5-C5H5)MCl2 are prepared in a similar way from MCl4 (M = Zr), but the best method uses (η5-C5H5)ZrCl3 or (η5-C5H5)HfCl3, 2THF. Preparation of this adduct is described.

Summary Tricarbonyl-η-1,3,5-cycloheptatrienechromium (0) (I) reacts with 6-mono-and 6-disubstituted fulvenes under UV-irradiation in two different ways. One possibility is the formation of a C−C bond between C(1) of the cycloheptatriene ligand and C(6) of the fulvene yielding dicarbonylchromium complexes of substituted η3-cyclohepta-2′, 4′-dien-1′, 6′-ylen-η5-cyclopentadienylidenemethanes. Alternatively, hydride transfer from the cycloheptatriene to C(6) of the fulvene occurs and dicarbonyl-η3-cycloheptatrienylchromium complexes with substituted η5-cyclopentadienyl ligands are obtained. There is evidence for steric influence of the 6-substituents of the fulvenes on the way of reaction.

Zusammenfassung New fulvenes, a fulvalene and a 4H-imidazole have been obtained from 2.4.5-tris-diethylamino-dehydroimidazolium chloride. According to MNDO calculations the CH tautomers of aminoimidazoles can be more stable than the NH forms.

The 13C NMR spectra of tricarbonylchromium complexes of dimethylaminofulvene diphenylfulvene have been studied. Comparison of the 13C NMR spectra of these complexes with those of the corresponding non-coordinated fulvenes shows that the contribution from the ylidic structure of the π-ligand in the first complex increases when the Cr atom becomes coordinated, while in the second complex this coordination does not favour a formation of the ylidic structure of the π-ligand.

The complexes R3SnV(CO)5PPh3 and R3SnV(CO)6 (R = Ph, Et, n-Bu, CH2Ph), for which an improved synthesis is described, react with pentafulvenes C5H4CZ2 to give ring-substituted cyclopentadienyl (Cp) or fulvene (Fv) complexes. Less polar fulvenes form alkyl-Cp complexes (Z2 = Ph2 and (p-substituted Ph)2) or alkenyl-Cp complexes (Z2 = Me2, (CH2)4, (CH2)5) with the elimination of the stannyl ligand, while the reaction with polar fulvenes (Z2 = H, NMe2; (NMe2)2 and S(CH2)2S) gives the Fv complexes C5H4CZ2V(CO)3SnR3 with the stannyl ligand still coordinated to vanadium. A Fv complex, V(NO)(CO)2C5H4CHNMe2, is also obtained from the reaction of V(NO)(CO)5 with dimethylaminofulvene. The IR, 1H, 13C and 51V NMR data show that the dipolar (i.e. the h5-cyclopentadienyloidal) resonance structure predominates in all but the dimercaptofulvene complex.

C 6 H 5 Mn(CO) 5 (I) reacts photochemically with 6,6-dimethyl- or 6,6-diphenylfulvene (II, III) to labile C 6 H 5 (CO) 4 Mn(η 2 -fulvene) complexes. These rearrange thermally by insertion of the two ring double bonds of the fulvenes into the MnC 6 H 5 bond to 1,2- and 1,3-substituted (CO) 4 Mn(η-3-cyclopenten-5-yl) complexes (IV–VII) which were separated by HPLC. The formation of the 1,3-substituted isomers V and VII is accompanied by a 1,5-H shift. V and VII readily loose one CO at room temperature and further rearrange to 1,3-disubstituted (CO) 3 Mn(η-cyclopentadienyl) (VIII, IX). The latter are also formed by thermal reactions of I with II, or III, respectively. The structures of the isolated complexes IV–IX were elucidated by IR, 1 H NMR and mass spectroscopy.

A universal method for synthesizing tricarbonyl(fulvene)metal complexes of Group VIa is described. The compounds are formed by reaction of the fulvenes with the tris(acetonitril) complexes, (CH3CN)3M(CO)3 (M = Cr, Mo, W), and they have been characterized spectroscopically. The tricarbonyl(fulvene)chromium compounds react with alkyllithium to form anions of substituted cyclopentadienyl complexes.