Electrophilic metallation

Aromatic compounds react with mercuric salts to give arylmercury compounds.69 Mercuric acetate or mercuric trifluoroacetate are the usual reagents.70 The reaction shows substituent effects that are characteristic of electrophilic aromatic substitution.71 Mercuration is one of the few electrophilic aromatic substitutions in which proton loss from the a complex is rate determining. Mercuration of benzene shows an isotope effect kB/kD = 6,72 which indicates that the j complex must be formed reversibly. 

The synthetic utility of the mercuration reaction derives from subsequent transformations of the arylmercury compounds. As indicated in Section 7.3.3, these compounds are only weakly nucleophilic, but the carbon-mercury bond is reactive to various electrophiles. They are particularly useful for synthesis of nitroso compounds. The nitroso group can be introduced by reaction with nitrosyl chloride73 or nitrosonium tetrafluoroborate74 as the electrophile. Arylmercury compounds are also useful in certain palladium-catalyzed reactions, as discussed in Section 8.2. 

Thallium(III), particularly as the trifluoroacetate salt, is also a reactive electrophilic metallating species, and a variety of synthetic schemes based on arylthallium intermediates have been devised.75 Arylthallium compounds are converted to chlorides or bromides by reaction with the appropriate cupric halide.76 Reaction with potassium iodide gives aryl iodides.77 Fluorides are prepared by successive treatment with potassium fluoride and boron trifluoride.78 Procedures for converting arylthallium compounds to nitriles and phenols have also been described.79 

The thallium intermediates can be useful in directing substitution to specific positions when the site of thallation can be controlled in an advantageous way. The two principal means of control are chelation and the ability to effect thermal equilibration of arylthallium intermediates. Oxygen-containing groups normally direct thallation to the ortho position by a chelation effect. The thermodynamically favored position is 

Greal cart must be taken when using tins methoTTology because mercury and thallium compounds are extremely toxic. 

Salts of mercury(II) and thallium(HI), such as mercury(II) acetate, Hg(OAc)2, and thallium trifluoroacetate, Tl(OCOCF3)3, are reactive electrophilic metallating species which attack benzene directly. Electron-donating groups in the aromatic ring accelerate the reaction in the conventional manner and direct attack to the ortho and para positions. In addition, metal-chelating substituents, such as amide, promote the reaction and direct attack to the 2-position in a manner similar to that seen in the directed orthometallation reaction. 

The organomercury compounds formed in such reactions are not of great synthetic importance, although they do undergo nitrosation reactions with nitrosyl chloride, NOCl. They can also be used as the organometallic component in certain palladium-mediated coupling processes. 

Transition metal complexes are widely used in aromatic chemistry and organic synthesis in general. They are of particular value because com-plexation of an organic molecule to a metal centre often modifies its reactivity. The metal can subsequently be removed. After discussing the ways by which these complexes react, we will discuss their use in the synthesis of aromatic compounds. 

The chemistry of organometallic transition metal a-complexes can largely be explained by the operation of fundamental processes such as oxidative addition, reductive elimination and p-elimination. 

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Because Pd(II) salts, like Hgtll) salts, can effect electrophilic metallation of the indole ring at C3, it is also possible to carry out vinylation on indoles without 3-substituents. These reactions usually require the use of an equiv. of the Pd(ll) salt and also a Cu(If) or Ag(I) salt to effect reoxidation of the Pd. As in the standard Heck conditions, an EW substitution on the indole nitrogen is usually necessary. Entry 8 of Table 11.3 is an interesting example. The oxidative vinylation was achieved in 87% yield by using one equiv. of PdfOAcfj and one equiv. of chloranil as a co-oxidant. This example is also noteworthy in that the 4-broino substituent was unreactive under these conditions. Part B of Table 11.3 lists some other representative procedures. 

Replacement of Labile Chlorines. When PVC is manufactured, competing reactions to the normal head-to-tail free-radical polymerization can sometimes take place. These side reactions are few ia number yet their presence ia the finished resin can be devastating. These abnormal stmctures have weakened carbon—chlorine bonds and are more susceptible to certain displacement reactions than are the normal PVC carbon—chlorine bonds. Carboxylate and mercaptide salts of certain metals, particularly organotin, zinc, cadmium, and antimony, attack these labile chlorine sites and replace them with a more thermally stable C—O or C—S bound ligand. These electrophilic metal centers can readily coordinate with the electronegative polarized chlorine atoms found at sites similar to stmctures (3—6). 

The author anticipates that the further development of transition metal catalysis in ionic liquids will, to a significant extent, be driven by the availability of new ionic liquids with different anion systems. In particular, cheap, halogen-free systems combining weak coordination to electrophilic metal centers and low viscosity with high stability to hydrolysis are highly desirable. 

It has been demonstrated that group 6 Fischer-type metal carbene complexes can in principle undergo carbene transfer reactions in the presence of suitable transition metals [122]. It was therefore interesting to test the compatibility of ruthenium-based metathesis catalysts and electrophilic metal carbene functionalities. A series of examples of the formation of oxacyclic carbene complexes by metathesis (e.g., 128, 129, Scheme 26) was published by Dotz et al. [123]. These include substrates where double bonds conjugated to the pentacarbonyl metal moiety participate in the metathesis reaction. Evidence is... 

The general term metallation describes that process in which reaction of an unsaturated system with a metal or an electrophilic metal salt results in formation of an unsaturated organometallic compound by formal replacement of a C—H bond by a C—metal bond, as for example in the mercuration of benzene (Scheme 3). The term oxymetallation is used to describe the... 

With the ArH ArTlX2 Arl reaction sequence available as a rapid and reliable probe for aromatic thallation, a detailed study was undertaken of the various factors affecting orientation in this electrophilic metallation process (153). The results, which are summarized below, demonstrate that aromatic thallation is subject to an almost unprecedented degree of orientation control coupled with the ease with which thallium can then be displaced by other substitutent groups (this aspect of the synthetic exploitation of aromatic thallation is discussed in detail below), the sequential processes of thallation followed by displacement represent a new and versatile method for aromatic substitution which both rivals and complements the classic Sandmeyer reaction. 

The first step of both mechanisms is the same, namely the addition of pyridine at the electrophilic metal atom of the triorganotin halide to give a pentacoordinate adduct. 

It was found in the case of O-benzyl systems that palladium oxide is much more effective than palladium metal. No such effect was observed with the N-benzyl system.8 It is possible that the N-compounds can poison the electrophile metal ions, and the hydrogenolysis of the N-benzyl bond can take place only by the hydrogenolytic cleavage instead of the insertion mechanism. This is supported by the experimental finding that the product amine can inhibit the catalyst, and this can be minimized by buffering at a pH less than 4. 

Successful syntheses by classical electrophilic aromatic decarboxylation (Section III,E) offer promise that a range of aryl organometallics containing strongly electron-donating groups could be prepared for electrophilic metals (e.g., Tlm, PbIV, Aum). 

The reason for the different behavior of dienes like 41 and monoenes 37 or 42 is not yet established. It is hard to believe that simple steric factors should make up for the different orientation of the olefin that approaches a metal carbene intermediate. More likely is stereochemical control by an ylide-type interaction between the halogen atom of the (sterically more flexible) monoenes 37 or 42 and the electrophilic metal carbene. 

A mechanistic picture which reconciles the experimental results is given in Scheme 24. It is assumed that both the heteroatom and the double bond of the allyl halide compete for an electrophilic metal carbene. Heteroatom attack yields a metalated ylide 129, which may go on to ylide 131 by demetalation and/or to allylmetal complex 130. Symmetry-allowed [2,3] rearrangement of 131 accounts for product 132, and metal elimination from 130 gives rise to products 132 and 133, corresponding to [2,3] and [1,2] rearrangement, respectively, as well as haloacetate (if R3 = CHc ). 

Exclusive O/H insertion takes place in the Rh2(OAc)4-catalyzed reaction of diethyl diazomalonate with a,(J-unsaturated y-hydroxyesters 167 a-c163). This is not surprising in view of the reluctance of electrophilic metal carbenes to add to electron-poor double bonds (see Sect. 2.3.2). However, the more electron-rich double bond of p-methoxybenzyl clavulanate 168 also cannot compete with the O—H function for the same carbenoid 164). The steric situation at the trisubstituted double bonds of 167 and 168 may be reason enough to render an attack there highly unfavorable as compared to the easily accessible O—H function, no matter how nucleophilic the double bond is. 

The dominant role of the traditional copper catalysts, generally used under heterogeneous conditions, has not been challenged as yet. Only a few reports shed light on the efficiency of alternative catalysts. Copper(II) triflate allows high-yield intramolecular cyclopropanation of y,8-unsaturated diazoketone 182160) it is superior to CuS04 (53 % yield 192 ) or Rh2(OAc)4160). The solvent is crucial for an efficient conversion If the reaction is carried out in ether, the solvent competes with the double bond for the electrophilic metal carbene to give 184, presumably via an oxonium ylide intermediate. 

Interaction of a carbonyl group with an electrophilic metal carbene would be expected to lead to a carbonyl ylide. In fact, such compounds have been isolated in recent years 14) the strategy comprises intramolecular generation of a carbonyl ylide whose substituent pattern guarantees efficient stabilization of the dipolar electronic structure. The highly reactive 1,3-dipolar species are usually characterized by [3 + 2] cycloaddition to alkynes and activated alkenes. Furthermore, cycloaddition to ketones and aldehydes has been reported for l-methoxy-2-benzopyrylium-4-olate 286, which was generated by Cu(acac)2-catalyzed decomposition of o-methoxycarbonyl-m-diazoacetophenone 285 2681... 

When the cis/trans stereoselectivity of cyclopropanation with ethyl diazoacetate in the presence of CuCl P(0-z-Pr)3, Rh6(CO)16 or PdCl2 2 PhCN was plotted against that obtained with Rh2(OAc)4, a linear correlation was observed in every case, with slopes of 1.74,1.04 and 0.59, respectively (based on 22 olefins, T = 298 K) S9). These relationships as well as the results of regioselectivity studies carried out with 1,3-dienes point to the similar nature of the intermediates involved in Cu-, Rh-and Pd-catalyzed cyclopropanation. Furthermore, obvious parallels in reactivity in the transformations of Scheme 45 for a variety of catalysts based on Cu, Rh, Fe, Ru, Re and Mo suggest the conclusion that electrophilic metal carbenes are not only involved in cyclopropanation but also in ylide-forming reactions66. ... 

Aromatic electrophilic substitution has also been used in the synthesis of arylcadmium species. In a recent example, aniline was shown to undergo electrophilic metallation upon treatment with Cd(OCOCF3)2, yielding the /wra-substituted cadmium derivative 183 (Equation (61)).246... 

Addition of either nucleophilic or electrophilic metallic species can result in the capping of triangular- or square-metal faces in carbonyl clusters. These redox reactions provide high yield syntheses of higher nuclearity clusters and somewhat resemble surface reconstruction on metals. With a few examples,... 

Heterolytic Splitting of H-H, Si-H, and Other sigma Bonds on Electrophilic Metal Centers Gregory J. Kubas... 

Other soft, electrophilic metals, including mercury(ll) analogs, are also known to activate methane.16... 

While the alkoxymetallation process has typically been affected by highly electrophilic metal salts, high-valent metal species generated by an oxidative addition have also been used to activate alkynes through the formation of 7r-complexes. In such cases, the metal-carbon emerging from the attack of an oxygen nucleophile may enter a reaction manifold that leads to an additional C-G bond formation rather than a simple protic quench. This approach, pioneered by Arcadi and Cacci, has proved to be a powerful strategy for the synthesis of structurally diverse substituted... 

Electrophilic metal complexes that have shown Markovnikov-type selectivity include catalysts based on Ru(n),383-386 Fe(m),387 Au(i) and Au(m),380,388 and Ir(m).389 Notable among these examples are Zeise s salt390 (entries 1 and 2) and the PtCl4/CO system (entry 3), the latter of which has proved to be effective for the hydration of a wide... 

Treatment of alkylidene-bridged zirconium—aluminum species with HMPA activates the C—A1 bond of the alkylidene unit, making it susceptible to electrophilic attack [146]. Ligand-based activation of the C—A1 bond can also be used to convert alkylidene-bridged zirconium-aluminum reagents to other bimetallic species. Thus, treatment of 3 with HMPA followed by addition of a weakly electrophilic metal salt can give rise to a new heterome-tallic species. Slow addition of a solution of R3SnCl in toluene to a solution of 3 and 1... 

Electrophilic metals or metal complexes, when incorporated into either the acyl or alcohol functions of the ester, might be expected to increase the rate of addition of amine. This might occur through direct carbonyl-0 or alcohol-0 coordination (21 or 22, Scheme 21) or by being positioned at a discrete distance from these (cf. 23 and 24). When the metal is attached to the alcohol function loss of this group might also be accelerated (in a stepwise addition-elimination reaction), but with acyl activation loss of alcohol might be expected to be retarded. 

Boratabenzene-bridged multidecker sandwiches are few in number, all prepared in the Herberich group. Stacking reactions of Cp Ru(HsCsBMe) with electrophilic metal reagents gave complexes 106 and 107. 2 interestingly,... 

Activation of one the double bonds of the allene by coordination to an electrophilic metal center such as Hg(II), Ag(I), Pd(II), Rh(I), Cu(I) or Au(III). Then an intramolecular nucleophile can attack and the product is formed by protodemetallation of the intermediate (Scheme 15.1). Depending on electronic and steric factors, either the proximal or the distal Jt-bond of the allene 1 is activated in that way (2 and/or 3). For each of these two possibilities now an exo or endo attack of the nucleophile is conceivable, leading to intermediates 4—7. An equilibrium between both 5 and 6 and 9 is possible. Finally, from 4 the vinyl-substituted 8 is formed. From 5, 6 or 9 the exocyclic alkene 10 and/or the endocyclic alkene 11 can be observed. Compound 7 would deliver the endocyclic alkene 12. 

We have already reviewed the activation of alkenes, alkynes, and carbon monoxide towards nucleophilic attack. The heterolytic splitting of dihydrogen is also an example of this activation it will be discussed in Section 2.10. The reaction of nucleophiles with silanes co-ordinated to an electrophilic metal can be regarded as an example of activation towards nucleophilic attack (Figure 2.28). Complexes of Ir(III) and Pd(II) give t.o.f. for this reaction as high as 300,000 mol.mol. fh"1. 

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