Fulvenes synthesis

Siegel, H., Some preparatively useful [4 + 2]cycloaddi tions of 6,6-di phenyl fulvene, Synthesis, 798, 1985. 

A new fulvene synthesis is the reaction of the iodostyrene 458 with two molecules of ethynyltrimethylsilane in the presence of Pd(CH3CN)2Cl2 (equation 52)291. palladium(II) acetate-triphenylphosphine-catalysed reaction of (E)- or (Z)-vinyl bromides 459 (R = Ph or EtO) with diphenylacetylene or 3-hexyne results in the fulvenes 460 (R = Ph or EtO, R2 = Ph or Bu)292. 

Kurata, Kawase, and Oda s group developed a new one-pot fulvene synthesis the method uses the reaction of AiAf-dimethylformamide (DMF) or NJ -dimethyl chlorocarbamate (ClCONMe2) with aryl lithium reagents to provide fulvene derivatives without the isolation of rather unstable precursor ketones (Scheme 6.28a). As shown in Scheme 6.28a, CP anion and the corresponding ketone are generated in situ [61]. The procedure provides a fulvene oligomer 115 without isolation of the precursor ketone 116 (Scheme 6.28b) [62]. 

Goering, B.K., Li, J., and Ganem, B. (1995) Aminocyclopentitols from fulvenes synthesis of (+)-trehazolin and the pentasubstituted cydopentane ofkerufFaride. Tetrahedron Lett., 36, 8905-8908. 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

This procedure illustrates formylation by N,N-dimethylamino-methoxymethylium methyl sulfate, a compound which can be produced readily by reaction of easily available materials. 6-(Dimethylamino)fulvene is a useful intermediate for the synthesis of various f used-ring nonbenzenoid aromatic compounds. 

Of the fundamental nonalternant hydrocarbons, only two prototypes were known about fifteen years ago azulene (XI, Fig. 5), the molecular structure of which was determined by Pfau and Plattner and fulvene (XIX) synthesized by Thiec and Wiemann. Early in the 1960 s many other interesting prototypes have come to be synthesized. Doering succeeded in synthesizing heptafulvene (XX) fulvalene (XXI) and heptafulvalene (XXIII). Prinzbach and Rosswog reported the synthesis of sesquifulvalene (XXII). Preparation of a condensed bicyclic nonalternant hydrocarbon, heptalene (VII), was reported by Dauben and Bertelli . On the other hand, its 5-membered analogue, pentalene (I), has remained, up to the present, unvanquished to many attempts made by synthetic chemists. Very recently, de Mayo and his associates have succeeded in synthesizing its closest derivative, 1-methylpentalene. It is added in this connection that dimethyl derivatives of condensed tricyclic nonaltemant hydrocarbons composed of 5- and 7-membered rings (XIV and XV), known as Hafner s hydrocarbons, were synthesized by Hafner and Schneider already in 1958. 

More recently, a very efficient asymmetric carbolithiation of N,N-dimethyl-aminofulvene 30, leading to a chiral cyclopentadienide anion, was reported by Hayashi et al. [6] for the synthesis of chiral metallocenes (Scheme 6). By adding an aryl lithium such as 31 complexed with a chiral ligand on fulvene 30, a cyclopentadienide ion 32 bearing a stereogenic center at the a position was generated. This anion was reacted with [RhCl(nbd)]2 to yield... 

The key step in the following synthesis of indenes by the azolide method is an intramolecular C-acylation of a fulvene intermediate. The added dimethylaminopyridine (DMAP) was thought to act as an acyltransfer agent, and diazabicycloundecene (DBU) as cyclization initiator via fulvene deprotonation [116]... 

Two additional synthetic routes to ( )-j8-vetivone (350) have been developed. In one of these a suitably substituted spirocyclic system [cf. (349)] is constructed by addition of Me2CuLi to the fulvene derivative (348)/ Subsequent functional group modification (cf. Scheme 32) provides ( )-j8 -vetivone (350). In the other total synthesis d the well-known intramolecular alkylation of para-substituted phenols has been used to produce a spirocyclic intermediate (353) which can be converted into ( )-/3-vetivone (350) (cf. Scheme 33). 

Cyclopentyl isoxazolidine cycloadduct 324 was prepared by intramolecular nitrone cycloaddition by Baldwin et al. (280,281,352,353) as part of studies toward a total synthesis of pretazettine (Scheme 1.69). Related adducts have been prepared elsewhere (354—356) including fluorine-substituted carbocycles (357) and the adducts prepared by lOAC by Shipman and co-workers (333,334) who demonstrated their potential as a route to aminocyclopentitols (Scheme 1.66, Section 1.11.2). Such bicyclic structures have been prepared in rather unique intermolecular fashion by Chandrasekhar and co-workers (357a) from the cycloaddition of C,N-diphenyl nitrone to fulvene (325). 

An azulene synthesis involves the addition of 6-(iV,iV-dimethylamino)fulvene (208) to a thiophene sulfone (77TL639, 77JA4199). 

The preparation of system 57 from cyclopentadienyl anion and s-tetrazines151154 and the synthesis of the same system from fulvenes and s-tetrazines143 are based on a similar principle. By its nature, the preparation of 4//-cyclopenta[c]cinnolines (68) from nickelocene and o-dihalo-benzenes163 is analogous. 

Many attempts were made to synthesize the diazaazulene derivative 4,7-diphenyl-5,6-diazaazulene 34. A directed synthesis of diazaazulene 34 by [6+4] cycloaddition of fulvenes with 1,2,4,5-tetrazenes when attempted with 2-cyclopenta-dienyliden-l,3-dioxolane led to the formation of cyclopcnta[z/ pyridazines via a [4+2] cycloaddition pathway <2001TH1>. 

The cobalt(I)-catalysed 6 + 2-cycloadditions of cyclooctatetraene with monosubsti-tuted alkynes produced monosubstituted bicyclo[4.2.2]deca-2,4,7,8-tetraenes in good yields.185 The 6 + 3-cycloaddition of fulvenes (145) with 3-oxidopyrylium betaines (144) formed 5-8 fused oxa-bridged cyclooctanoids (146,147), which can be manipulated by cycloaddition reactions to produce key intermediates (148,149) for the synthesis of fused cyclooctanoid natural products e.g. lancifodilactones (Scheme 38).186,187... 

Fulvalene zirconium(III) compounds, reactions, 4, 751 Fulvene chromium carbonyls, synthesis and characteristics,... 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6-(di-methylamino)fulvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), diphenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopentane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-S-oxazolone (an important intermediate in amino acid chemistry). 

Scheme 2 Synthesis of benzyl-substituted titanocenes through the hydridolithiation reaction of aryl-substituted fulvenes using superhydride...

Carbolithiation proved to be a very effective approach to highly cytotoxic titanocenes. The reaction of aryl or heteroaryl lithium species with 6-/V,/V-d i me thy I am i n o fulvene and subsequent transmetallation reaction led to dimethylamino-functiona-lised titanocenes with IC50 values of 6.8, 5.5 and 5.4 pM. Furthermore, this reaction proved to be tolerant to many substituents and to be a versatile tool for the synthesis of a wide variety of substituted titanocene dichlorides as seen in Scheme 3. 

Scheme 3 Synthesis of dimethylamino-functionalised titanocenes from the carbolithiation reaction of 6-/V,/V-dimcthylamino fulvene and aryl lithium species...

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