Search

Longer cumulenes have come to draw considerable attention due to their unique properties and reactivities, leading to various hydrocarbons. In this manuscript, we describe the reaction of tetrakis(p-methoxyphenyl)[5]cumulene with iodine to afford poly-functionalized fulvenes via unexpected migration of a terminal aryl ring under ambient conditions. The obtained iodinated fulvenes were utilized in Suzuki-Miyaura cross-coupling reactions affording penta- and fully-arylated fulvenes successfully.

International audience; Azulene, acenaphthylene and fulvene derivatives exhibit important physical properties useful in materials chemistry as well as valuable biological properties. Since about two decades ago, the metal-catalyzed functionalization of such compounds, via C-H bond activation of their 5-membered carbocyclic ring, proved to be a very convenient method for the synthesis of a wide variety of azulene, acenaphthylene and fulvene derivatives. For such reactions, there is no need to prefunctionalize the 5-membered carbocyclic rings. In this review, the progress in the synthesis of azulene, acenaphthylene and fulvene derivatives via metal-catalyzed C-H bond activation of their 5-membered carbocyclic ring are summarized.

An unexpected transformation of 1,6-diarylhexa-1,5-diene-3,4-diones (cinnamils) to 2,3,8-triaryl vinyl fulvenes via N-Heterocyclic Carbene (NHC) catalysis is reported. Mechanistic as well as synthetic novelty is the hallmark of this reaction.

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.

Introduction of a triisopropylsilyl group into allyl and allenyl carbinols greatly enhances the efficiency of gold(I)-catalyzed cyclodehydration, which can provide rapid access to a library of various compounds including 1H-indenes (Table 2 and Scheme 5), benzofulvenes (Table 3), indan-2-ones (Scheme 2), fulvenes (Table 4), cyclopentadienes (Table 4), 5H-dibenzo[a,c][7]annulenes (Scheme 6) and dibenzosuberones (Scheme 6). The developed method enables unprecedented product generality for several classes of cyclodehydration reactions, which is particularly notable for the preparation of 1H-indenes. The first synthesis of non-benzo-fused fulvenes via cyclodehydration of allenyl vinyl carbinols could be accomplished. The protocol is remarkable for mild conditions, operational convenience, and easy access to starting materials.

In situ generated acetone pyrrolidine enamine undergoes [6 + 2] cycloadditions with fulvenes to give 1,2-dihydropentalenes. This ring annulation method works particularly well with 6-monosubstituted fulvenes and is subject to steric hindrance at C-6 of the fulvene. On the basis of mechanistic studies, optimal conditions have been developed for a one-pot synthesis of 1,2-dihydropentalenes using catalytic amounts of pyrrolidine.

t-Butylcyclopentadienyllithium was allowed to react with (2,4,6-tri-t-butylphenyl)phosphonous dichloride to afford the corresponding chloro-5-cyclopentadienylchlorophosphine as a mixture of diastereomers, the structure of one of which was determined by X-ray crystallography. The mixture of 5-cyclopentadienylchlorophosphine diastereomers was treated with a base to furnish novel 2-t-butyl-6-(2,4,6-tri-t-butylphenyl)-6-phosphafulvenes, and each geometrical isomer of them was fully characterized by X-ray crystallography. The E/Z ratio of the 6-phosphafulvene obtained was considerably dependent on the diastereomeric ratio of the chlorophosphine precursor.

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.

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 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.

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.

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

[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 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.

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.

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.

The synthetic methods of trifluoromethylated cyclopentadienes/fulvenes/norbornenes have been developed using 3-CF3-1,4-dien-3-ols as the synthons, which can be easily prepared by the regiospecific 1,2-addition of the Ruppert–Prakash reagent (TMSCF3) to divinyl ketones. All the reactions are carried out under mild, metal-free conditions to afford the corresponding products in high to excellent yields.

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.

The effects of the nature and amount of base, substrate structure, amount of added water and solvent on the condensation of carbonyl compounds with cyclopentadiene in the presence of secondary amines were investigated. Based on these studies, a new efficient and green synthesis of fulvenes was developed. United States Department of Health & Human Services National Institutes of Health NIH National Institute of General Medical Sciences (NIGMS) (1SC1GM082340) National Science Foundation (DBI-0521342) (DUE-9451624)

International audience; Herein, a Pd-catalyzed reaction of simple and diverse bromothiophenes with alkynes via regioselective C-S bond activation is reported. This provides a new approach to prepare sulfur-based heterocycles and fulvenes.

The synthesis of indenols and fulvenes was achieved through Rh-catalyzed C−H bond activation of simple and diverse aryl ketone derivatives and subsequent coupling with internal alkynes. The process was found to involve either an α or γ dehydration step, depending on the substrate disposition and representing diverse pathways toward functionalized fulvenes.

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

An unusual peroxide base-promoted isomerization is uncovered. Saturated endoperoxides derived from fulvenes give rise to 2-vinyl-2-cyclopentenones upon treatment with DBU in CH 2 Cl 2 in a one-pot reaction. This methodology is applied to a convenient synthesis of dihydrojasmone. Moreover, functional groups placed on the side chain at C-6 participate in the base-catalyzed isomerizations via conjugate attack at the enone moiety to give 2-cyclopentenones carrying oxygen heterocycles at C-2.

[reaction: see text] Regioselective and stereoselective inverse-electron-demand Diels-Alder reaction of N-sulfonyl-1-aza-1,3-butadiene with fulvenes are described. The methodology provides an efficient and novel route to tetrahydro-[1]pyrindine systems.