Astruc D. - Modern arene chemistry (2002)(en)

12.2 General Features of the CpFeþ Activation of Arenes 403

12.2.3

Single-Electron Reduction and Oxidation

Whatever the arene, single-electron reduction is usually reversible on the classic time scale of cyclic voltammetry [24a]. With benzene or a monoor polyalkyl benzene ligand, it is possible to generate the green 19-electron neutral complex by one-electron reduction of the yellow 18-electron BF4 or PF6 precursor salt [24b]. In such cases, it is also possible to isolate the FeI complexes under careful conditions at low temperature, typically 10 C to 0 C. The CpFeI complexes are thermally stable at room temperature with hexamethylbenzene [25a], hexaethylbenzene [25a], and tris(tert-butyl)benzene (Scheme 2). The prototype complex CpFeI(h6-C6Me6) is thermally stable up to 100 C, and has been characterized by a variety of physical techniques [25], including X-ray crystal structure analysis [25b]. EPR and Mo¨ssbauer spectra of the FeI family of complexes show the dynamic rhombic distortion of these Jahn–Teller-active d7 species [25c] and He(I) photoelectron spectroscopy showed that their ionization potentials are among the lowest known, as low as those of alkali metals [25d]. Thus, these complexes are the most electron-rich molecules known, and CpFeI(h6-C6Me6), an excellent electron reservoir, is extensively used as a strong reductant (E ¼ 2 V vs. Cp2Fe0=þ, i.e. almost one volt more negative than cobaltocene) [25e]. In their monocationic form, these CpFeþ(h6-arene) complexes are isolobal with ferrocene. The 17-electron dication Cp*Fe2þ(h6-C6Me6), isolobal with ferrocenium, is thermally stable, and is a much stronger oxidant than ferrocenium, the di erence being about one volt due to the additional positive charge (Cp* ¼ h5-C5Me5, E ¼ 1 V vs. Cp2Fe0=þ). Thus, this latter complex is thermally stable in three redox forms, the 19-e FeI and 17-e FeIII forms being strongly reducing and oxidizing, respectively [26].

12.2.4

Deprotonation

Deprotonation of benzylic groups on the arene ligand of the CpFeþ(h6-arene) complexes is rather easy and can be achieved using, for instance, tBuOK (Scheme 2) [27]. This is again due to the positively charged iron group, which enhances the acidity of the arene ligand by about 15 pKa units in DMSO (pKa: Cp*Feþ(h6-C6Me6): 28.2; C6Me6: 43) [27b]. The X-ray crystal structure of the deep-red deprotonated complex shows a dihedral angle of 32 , which indicates some overlap between the p orbitals of the cyclohexadienyl ligand and those of the exocyclic double bond [27c]. The complex is soluble in pentane, which confirms that it is not zwitterionic. It shows a smooth nucleophilic reactivity with a large variety of electrophiles, however, which is useful for creating many C–heteroatom bonds (Scheme 3) [27d].

Although other deprotonated complexes are sometimes not as stable as [CpFe(h5- C6Me5CH2)], they can be generated and used at low temperature to form the desired bonds [27e]. Using the base and electrophile in excess, the reactions can be carried out at room temperature because the deprotonated species immediately reacts with the electrophile in situ. This kind of deprotonation/alkylation sequence underpins the star and dendrimer construction described herein (vide infra). In this way, the complexes [FeCp(h6-arene)][PF6] also act as proton reservoirs [33].

404 12 Activation of Simple Arenes by the CpFeþ Group

Scheme 3. Benzylation activation of arenes by the 12-electron CpFeþ and the 13-electron CpFe groups (see also Scheme 4).

12.2.5

Reaction of the 19-Electron FeI Complex with O2: Extraordinary Reactivity of Naked Superoxide and its Inhibition

The 19-electron FeI complex reacts rapidly with O2 at low temperature (1/2 O2 giving 1/2 H2O2) or at ambient temperature (1/4 O2 giving 1/2 H2O) to yield what is seemingly the product of CaH abstraction, [CpFe(h5-C6Me5CH2)], nearly quantitatively. The reaction actually proceeds via the ion pair [CpFeþ(h6-C6Me6), O2 ], however [27a, 27d]. The superoxide

12.2 General Features of the CpFeþ Activation of Arenes 405

radical anion intermediate is generated by an electron-transfer step that is exergonic by almost one volt (Scheme 4).

Scheme 4. Fast CaH activation reaction in the 19-electron complex [CpFeI(h6-C6Me6)] with O2 and ‘‘quantitative’’ salt e ect of NaþPF6 in THF.

It was characterized by its EPR spectra. The reaction of KO2 with [FeCp(h6-C6Me6)][PF6] in DMSO also gives the deprotonated complex [CpFe(h5-C6Me5CH2)] [27d]. Thus, the basic and nucleophilic properties of the anion are enhanced in the ion pair due to the absence of other interactive counteranions and to the subsequent disproportionation to peroxide and dioxygen. These properties are dramatically inhibited by the presence of one equivalent of NaPF6, which quantitatively changes the course of the reactions of the FeI complexes with O2 in THF, giving sodium peroxide and [FeCp(h6-C6Me6)][PF6] instead of deprotonation or nucleophilic reaction (nucleophilic addition of O2 to the arene ligand is observed in the absence of a benzylic proton) [28a]. Thus, a simple sodium salt e ciently plays the same role as the superoxide dismutase enzymes in the aerobic biological systems [28b].

12.2.6

Nucleophilic Reactions

Nucleophilic substitution of halides in the CpFeþ complexes of halogenoarenes proceeds very easily under mild conditions [16–20, 23]. In the absence of other functional groups, chloroarenes, which are the least expensive of the halogeno derivatives, are readily complexed to the CpFeþ group upon reaction with ferrocene in the presence of aluminum chloride. In contrast to the Cr(CO)3-chloroarene complexes (see the comparison of nucleophilic reactivities in Scheme 4), they undergo facile nucleophilic substitution [19, 29] upon treatment with alcohols and thiols in the presence of Na2CO3 or K2CO3, and with amines even under mild aqueous conditions [22]. Likewise, o-dichlorobenzene complexes lead to various (O, N, S) heterocycles through double substitution [30]. Reactions with hard carbanions yield

40612 Activation of Simple Arenes by the CpFeþ Group

cyclohexadienyl complexes, even in the case of the chlorobenzene complex, whereby the carbanion attack occurs at the ortho arene carbon. With stabilized carbanions, however, the reaction starts similarly, and then the incoming group migrates from the ortho to the ipso position, which is followed by elimination of chloride to provide the substituted arene complex. The reaction can continue by a second attack at the ortho position in the case of CN , which finally yields a metal-free ortho-dicyanoarene after decomplexation of the cyanocyclohexadienyl complex using an appropriate single-electron oxidant [31]. Nucleophilic substitution of chloride in these cationic chloroarene iron complexes by a variety of anions (azide, amides, alkoxides, thiolates, stabilized carbanions, etc.) is thus also possible under mild conditions.

12.2.7

Heterolytic Cleavage of Aryl Ethers

A particularly useful type of nucleophilic reaction is that of the aryl ether complexes

[FeCp(h6-PhOR)][PF6], which are readily cleaved in a heterolytic manner to give the phenolate complex [FeþCp(h6-PhO )] [32]. The latter is best described as a cyclohexadienyloxo complex [FeCp(h5-C6H5 bO)] isolobal with the cyclohexadienylmethylene complex [FeCp(h5- C6H5 bCH2)] obtained by deprotonation of the cationic toluene complex. With the stabilizing Cp* ligand, the same cleavage reaction of [FeCp*(h6-PhOEt)][PF6] gives the cleavage product [FeCp*(h5-C6H5 bO)], the X-ray crystal structure of which reveals the H-bonding ability of this cyclohexadienyloxo ligand. The reverse reaction, alkylation of the phenolate or cyclo-

hexadienyloxo complex using an alkyl iodide, is possible under ambient conditions in the

presence of a salt, ideally NaPF6, the ‘‘magic salt’’ for e cient salt e ects. Thus, the complexes [FeCp(h6-PhOR)][PF6] and [FeþCp(h6-PhO )] represent the two stable forms of an alkyl reservoir system. This cleavage reaction is used for the synthesis of our phenol dendron

(vide infra).

12.3

CpFeB-Induced Hexafunctionalization of Hexamethylbenzene for the Synthesis of Metallo-Stars

Reaction of [FeCp(C6Me6)][PF6] [33–35] with excess KOH (or tBuOK) in THF or DME and excess alkyl iodide, allyl bromide, or benzyl bromide leads to one-pot hexasubstitution (Scheme 5a) [36–38]. With allyl bromide (or iodide) in DME, the hexaallylated complex has been isolated and its X-ray crystal structure determined, but the extremely bulky dodecaallylation [52] product can also be reached when the reaction time is extended to two weeks at 40 C. The chains are fixed in a directionality such that conversion to the enantiomer is not possible, thus making the metal complex chiral (Scheme 5b).

With alkyl iodides, the reaction using tBuOK leads only to dehalogenation of the alkyl iodide giving the terminal alkene. Thus, one must use KOH, and the reactions with various alkyl iodides (even long-chain ones) have been shown to work very well with this reagent to give the hexaalkylated FeII-centered complexes. The yellow 18-electron complexes can be reduced to the dark-green 19-electron complexes (Scheme 6), but the stabilities of these organoiron radicals decrease as the chain length of the alkyl group is increased. Nevertheless, it

12.3 CpFeþ-Induced Hexafunctionalization of Hexamethylbenzene for the Synthesis of Metallo-Stars 407

Scheme 5. The peralkylation or perfunctionalization reaction: this reaction is made possible by the proton-reservoir property of the starting organometallic cation (see Schemes 2 and 3) and is spontaneously reproduced by iteration many times until a steric limit is reached: a) hexasubstitution compounds are formed with methyl

and alkyl iodides and benzyl halides. With allyl bromide, the room temperature reaction can be stopped at the stage of the hexabutenyl derivative or b) can be continued under prolonged heating conditions (40 C) to give the (chiral) dodecaallyl compound that has a sterically blocked directionality.

Scheme 6. High-yielding, large-scale synthesis of metal-centered stars with tentacles: application of the peralkylation reaction to long-chain alkyl iodides under mild conditions and redox activity.

40812 Activation of Simple Arenes by the CpFeþ Group

was possible to isolate the 19-electron complexes up to the hexahexylbenzene complex at low temperature and to record their temperature-dependent Mo¨ssbauer spectra between 4.2 and 200 K. The rhombic distortion, observed initially for [FeCp(C6Me6)] and due to the Jahn– Teller e ect, is weaker and milder in these complexes [39].

The hexaalkylation was also performed with alkyl iodides containing functional groups at the alkyl chain termini. For instance, alkyl iodides bearing methoxy [36] or olefinic endgroups [40] were prepared. Finally, 1-ferrocenylbutyl iodide reacts nicely to give the hexaferrocene star containing the CpFeþ center (Scheme 7).

Scheme 7. Branching out: synthesis of hexaferrocenylalkyl metal-centered redox stars.

This heptanuclear complex is of interest because of its various redox states. The six ferrocenyl units are independent, as evidenced by a single cyclic voltammetry wave. They could be oxidized to give the mixed-valence heptacation, in which the central iron group withstands oxidation and retains its FeII state, because it is protected by the positive charge [41a] (this protection can be estimated to be approximately 1.5 V) [41b]. The central iron serves as an internal reference to count the number of peripheral ferrocenes by comparing intensity ratios in either the cyclic voltammogram or the Mo¨ssbauer spectrum of the oxidized FeII/FeIII complex (Scheme 8) [41a].

Scheme 8. Oxidation or reduction of metallo-stars to localized mixedvalence complexes. Fe centers for which the oxidation state is not indicated in the scheme are FeII.

12.3 CpFeþ-Induced Hexafunctionalization of Hexamethylbenzene for the Synthesis of Metallo-Stars 409

Both the hexaand dodecaallylation reactions are readily controllable. On the other hand, the reactions with excess benzyl bromide [42] or p-alkoxybenzyl bromide [43, 44] give only the hexabenzylated or hexaalkoxybenzylated complexes as the ultimate reaction products. Cleavage of the methyl group from the p-methoxybenzyl derivatives synthesized in this way yielded hexaphenolate stars, which could be combined with halogen-containing Fe-sandwich electrophilic compounds such as chlorocarbonylferrocene or [FeCp(h6-C6H5Cl)][PF6] (Scheme 9) [43, 44].

Scheme 9. Synthesis of metallo-stars starting with the CpFeþ-induced hexaalkoxybenzylation of hexamethylbenzene. Examples of redox-active hexametallic stars synthesized by reactions of metal-free hexaphenate with organometallic

electrophiles such as ferrocenoyl chloride or [FeCp(h6- p-CH3C6H4F)][PF6]. The hepta-iron complex consisting of the [CpFe(h6-C6R6)]þ- centered hexaferrocene star was obtained in a same way by omitting the decomplexation step 2).

Alkynyl halides cannot be used in the CpFeþ-induced hexafunctionalization reaction, but alkynyl substituents can be introduced via the hexaalkene derivative by bromination followed by dehydrohalogenation of the dodecabromo compound [45]. The hexaalkene is also an excellent starting point for further syntheses, especially using hydroelementation reactions. Hydrosilylation reactions catalyzed by Speir’s reagent led to long-chain hexasilanes [46], and hydrozirconation has also been achieved using [Cp2Zr(H)(Cl)] [47]. The hexazirconium compound thus obtained is an intermediate for the synthesis of the hexaiodo derivative (Scheme 10) [47].

410 12 Activation of Simple Arenes by the CpFeþ Group

Scheme 10. Hydroelementation reactions in the functionalization of hexa-olefin stars: hydrosilylation, hydrozirconation, and hydroboration.

One of the most useful hydroelementation reactions is hydroboration, leading to the hexaborane, which can then be oxidized to the hexaol using H2O2 under basic conditions [37]. This chemistry can be carried out on the iron complex or, alternatively, on the free hexaalkene, which may be liberated from the metal by photolysis in CH2Cl2 or MeCN using visible light [36]. The polyol stars and dendrimers can be transformed into mesylates and iodo derivatives, which are useful for further functionalization. The hexaol is indeed the best source of the hexaiodo derivative, using either HI in acetic acid or, even better, by trimethylsilylation using Me3SiCl followed by iodination using NaI [50]. Williamson coupling reactions of the hexaol with 4-bromomethylpyridine or -polypyridine led to the hexapyridine and hexapolypyridine, and thence to their ruthenium complexes [48, 49]. This hexaiodo star was also condensed with p-hydroxybenzaldehyde to give a hexabenzaldehyde star, which could be further reacted with substrates bearing a primary amino group. Indeed, this reaction yielded a water-soluble hexametallic redox catalyst, which proved to be active in the electroreduction of nitrate and nitrite to ammonia on a Hg cathode in basic aqueous solution, vide infra (Scheme 11) [51].

12.4 CpFeþ-Induced Octafunctionalization of Durene in the Synthesis of Metallodendrimer Precursors 411

Scheme 11. Hexafunctionalization of aromatic stars with the heterodifunctional, water-soluble organometallic redox catalyst (bottom) for the cathodic reduction of nitrates and nitrites to ammonia in water.

12.4

CpFeB-Induced Octafunctionalization of Durene in the Synthesis of Metallodendrimer Precursors

In the same way as the hexafunctionalization of hexamethylbenzene leads to stars, the octafunctionalization of durene leads to dendritic cores (Scheme 12).

The first of these octaalkylation reactions was reported as early as 1982, and led to a primitive dendritic core containing a metal-sandwich unit [36]. Thus, like the hexafunctionalization, this reaction is very specific. Two hydrogen atoms of each methyl group are re-

412 12 Activation of Simple Arenes by the CpFeþ Group

Scheme 12. Octa-alkylation, -allylation, or -benzylation of durene in high yields by a series of eight deprotonation/alkylation (or allylation or benzylation) sequences induced by the 12-electron activating group CpFeþ in a one-pot reaction under mild conditions.

placed by two methyl, allyl, or benzyl groups [52]. This is due to the fact that each methyl group has only one methyl neighbor in durene instead of two such neighbors in hexamethylbenzene. It is remarkable that the consequence of this di erence is so clear-cut. We believe that this is due to the respective rates of the organometallic reaction and the reaction between the base and the halide. The octabenzylation reaction has since been used for further dendritic construction. Indeed, the p-chlorocarbonylation of the octabenzyl core is remarkably regioselective and has been used to facilitate reactions with amines of interest such as Newkome’s tripodal amine terminated by nitrile groups [53]. This reaction provides a rapid route to the 24-nitrile dendrimer [54]. Another reaction of interest in the present context is that of the octachlorocarbonylbenzyl core with 1-ferrocenylpentylamine, which provides the expected octaferrocenyl compound (Scheme 13) [55].

The reaction of the octaiodomethylbenzyl core with [Fe(h5-C5H5)(h5-C6Me5CH2)], i.e. the deprotonated form of [Fe(h5-C5H5)(h6-C6Me6)][PF6], led to the yellow octa-sandwich C6H2- 1,2,4,5-[CH(CH2CH2-p-C6H4CH2CH2-h6-C6Me5FeCpþI )2]4, which proved to be almost insoluble (Scheme 14). Its structure was indicated by the yellow color and the Mo¨ssbauer spectrum, both being characteristic of the FeCp(arene)þ frame [55].

A very interesting series of dendrimers containing 24 transition metal sandwich units has been synthesized from the 24-nitrile dendrimer by reduction of the nitrile groups to primary amines followed by reaction of the 24-amine dendrimer with chlorocarbonylferrocene or with [Fe(h5-C5Me5)(h6-C6H5F)][PF6] (Scheme 15) [54]. Both 24-branch metallodendrimers proved very useful and complementary for molecular recognition, as will be discussed later in this chapter.

Double branching, i.e. the replacement by two groups of two of the three hydrogen atoms on each methyl substituent of an aromatic ligand coordinated to an activating cationic group CpMþ in an 18-electron complex is not restricted to the case of durene. It is also encountered in the o-xylene ligand [36, 52], in the pentamethylcyclopentadienyl ligand (in pentamethyl cobaltocenium [56] and in penta- [57] and decamethylrhodocenium [58]), and even in the hexamethylbenzene ligand. As mentioned above, with this latter ligand, only allyl groups could be introduced in a double branching arrangement, this reaction requiring two weeks at 40 C [52] whereas single branching was complete after only one day at this temperature. The extremely bulky dodecaallyl complex formed is chiral, but its directionality is completely blocked (no interconversion between the clockwise and counterclockwise directionalities) [37], in contrast to the directionality of decafunctionalized ligands coordinated to CpCoþ or CpRhþ, the interconversion of which could be observed by 1H NMR (at least for the