Arene ligand reactivity

Loss of Coordinated Arene. We previously stated that the arene ligand in ruthenium(II)-arene complexes is relatively inert towards displacement under physiological conditions. While this is generally true, there are a few exceptions to this rule and this type of reactivity can be used to advantage. Weakly bound arenes, for instance, can be thermally displaced, a property convenient for the synthesis of ruthenium-arene complexes that are not readily available through more common synthetic routes. This way, the reaction of a precursor dimer, [RuCl2(etb)]2 (etb, ethylbenzoate) (68), with either 3-phenyl-1-propylamine or... 

A new imidazole-functionalized calix[4]arene ligand, able to form a dinuclear Cu2+ complex, has been reported to hydrolyze HPNP and ethyl p-nitropheny lphosphate [70]. The dinuclear complex was found to be 22-and 330-fold more reactive than the corresponding monomer towards the above substrates, respectively. Dinuclear Cu2+ complexes of linked triazacyclononane ligands are reported to promote the hydrolysis of the monoribonucleotide GpppG, a model for the 5 -cap structure of mRNA [71]. The dinuclear complexes offer some 100-fold higher reactivity compared to the mononuclear Cu2+-triazacyclononane system. 

The isolation of the first halobenzene complex, (q6-chlorobenzene)tricarbonylchromium(0), allowed a test for a direct analog of classical SNAr reactivity.15 The activating effect of the Cr(CO>3 unit was found to be comparable to a single p-nitro substituent in reaction with methoxide in methanol and the substituted arene ligand was detached with mild oxidation (equation 2). 

The complexes are air stable indeed, a limitation is the need for powerful oxidizing agents, such as Jones reagent CrVI, to detach the arene ligand.38 They are highly reactive toward nucleophiles. This limits the number of compatible synthesis manipulations that can be carried on in the presence of the [(arene)Mn(CO)3] unit but broadens the scope of effective nucleophiles. 

Carbon nucleophiles of type (iii) add to the arene ligand and do not rearrange examples include the very reactive anions, such as 2-lithio-2-methyl-l,3-dithiane, and the less sterically encumbered anions, such as lithio acetonitrile and /-butyl lithioacetate. In these cases, the anion adds to an unsubstituted position (mainly ortho or meta to Cl, as in 22) and does not rearrange. Then iodine quenching, even after a long period at 25 °C, gives almost exclusively the products from formal substitution for hydrogen, as from (22) in Scheme 8. 

The complexation of an arene to the tricarbonylchromium unit promotes the addition of nucleophiles to the arene ring due to the strong electron-withdrawing ability of the Cr(CO)3 group. Other effects of the coordination of the metal on the reactivity of the arene ligand have been well-documented in the literature [1] and concern (Scheme 1) (i) the stabilization... 

Such a charge transfer from the ligated arene can lead to (a) nucleophilic addition or substitution, (b) electron transfer, and (c) proton elimination/transfer, thus revealing the dose relationship between all of these processes. The reactivity of the arene ligands towards nudeophiles in (arene)ML complexes depends on the electrophilidty of the metal fragments [MLn], this increasing in the order [Cr(CO)3] < [Mo(CO)3] [FeCp]+ < [Mn(CO)3]+ [2]. For example, in (arene)FeCp+, which is widely used for synthetic purposes, a chloro or nitro substituent on the arene is readily substituted by such nudeophiles as amides, eno-lates, thiolates, alkoxides, and carbanions [45]. 

T/6-Arene ruthenium and osmium offer specific properties for the reactivity of arene ligand. The activation toward nucleophiles or electrophiles is controlled mainly by the oxidation state of the metal (II or 0). Recently, from classic organometallic arene ruthenium and osmium chemistry has grown an area making significant contributions to the chemistry of cyclo-phanes. These compounds are potential precursors of organometallic polymers which show interesting electrical properties and conductivity. 

Intermolecular Nucleophilic Substitution with Heteroatom Nucleophiles. A patent issued in 1965 claims substitution for fluoride on fluorobenzene-Cr(CO)3 in dimethyl sulfoxide (DMSO) by a long list of nucleophiles including alkoxides (from simple alcohols, cholesterol, ethylene glycol, pinacol, and dihydroxyacetone), carboxylates, amines, and carbanions (from triphenyhnethane, indene, cyclohexanone, acetone, cyclopentadiene, phenylacetylene, acetic acid, and propiolic acid). In the reaction of methoxide with halobenzene-Cr(CO)3, the fluorobenzene complex is ca. 2000 times more reactive than the chlorobenzene complex. The difference is taken as evidence for a rate-limiting attack on the arene ligand followed by fast loss of halide the concentration of the cyclohexadienyl anion complex does not build up. In the reaction of fluorobenzene-Cr(CO)3 with amine nucleophiles, the coordinated aniline product appears rapidly at 25 °C, and a carefiil mechanistic study suggests that the loss of halide is now rate limiting. 

While carbon nucleophiles were suggested to be efficient in substitution for fluoride in the 1966 patent, the first examples in the primary literature appeared in 1974 i62,i69 is now clear that there are three reactivity classes of carbon nucleophiles (Scheme 39) (a) stabilized carbanions (from carbon acids with pA a < ca. 18) (b) more reactive carbanions (P a > 20), which give complete conversion to cyclohexadi-enyl addition products prior to slow equilibration via reversible anion addition and (c) more reactive carbanions (pATa > 20), which give irreversible addition to the arene ligand. ... 

A widely observed reaction of cationic arene complexes is the addition of hydride, alkyl, or aryl anions to the arene ligand giving cyclohexa-dienyl derivatives 51, 154, 185, 243, 251). Other nucleophiles such as CN , OMe , and Ng" have been employed, but the products are generally less stable 185, 432). The following order of reactivity of TT-complexes toward nucleophiles has been noted cycloheptatriene > arene > C Ph > C5H5 103). However, the order will depend to some extent on the system 17). 

Thermolysis of [PhHC(Me2pz)2Mo(CO)4] in DME gives [PhHC(Me2pz)2Mo(CO)3], Comparison of the structural details of these two compounds and the reactivity of the latter compound show that it is the first example containing an intramolecularly coordinated //2-arene ligand (Scheme 10b).199... 

Bis(trichlorosilyl)nickel(II) complex 4, having an r/ -arene hgand,is prepared by reaction of hexachloro disilane with highly reactive, vaporized nickel in the presence of toluene (Eq. 2) [12]. Worthy of note is that the arene ligand is displaced by three molecules of carbon monoxide to give 5 [13]. 

Catalytic HPNP-tranesterification reactivity (Fig. 40, bottom has been reported for zinc complexes assembled using calix[4]arene ligands (Fig. 65).172,248 251 Complex 9 induces a 23,000-fold rate enhancement over the uncatalyzed intramolecular cyclization reaction of HPNP.248 Kinetic and mechanistic studies indicate strong binding of the HPNP substrate to the complex (K— 5.5 x 10-4M-1) and a kc ll value of 7.7 x 10 4s 1 at pH = 7.0 in acetonitrile/20 mM HEPES (1 1) at 25 °C. As 9 is 50 times more active for HPNP transesterification than 8, which contains only one zinc center, cooperativity between metal centers occurs in the former complex. Notably, the monozinc calix[4]arene complex 8 is 6 times more reactive than 7. This result provides evidence that the hydrophobic calix[4]arene moiety plays an important role in the reaction. 

Coordination of an aromatic ring tp a transition metal can reverse the usual reactivity of the ring, from nucleophilic to electrophilic. Nucleophilic reagents can add to f/ -arene ligands to produce t -cyclohexadienyl complexes ... 

When a carbon monoxide ligand is replaced by Iriphenylphosphine (in LV), the electrophilic reactivity of the arene ligand is lower, but transient / -cyclohexadienyl ligands are again implicated in reactions with nucleophiles . ... 

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