C-H oxidative addition

Intramolecular C-H oxidative additions have been common for many years. These reactions are known as cyclometallations (or orthometallations when the metal undergoes addition of an ortho C-H bond of the aromatic group of a ligand). Examples are provided in Equations 6.22-6.25. Cyclometallations of azobenzene are common and constitute some of the earliest examples of C-H activation. Two examples with Co2(CO)j and Cp Ni are shown in Equation 6.22 the product from the reac- 

Example of a catalyst for allylic substitution activated by cyclometallation. 

---

The oxidative addition of alkane C-H bonds to Pt(II) has also been observed in these TpRa -based platinum systems. As shown in Scheme 19, methide abstraction from the anionic Pt(II) complex (K2-TpMe2)PtMe2 by the Lewis acid B(C6F5)3 resulted in C-H oxidative addition of the hydrocarbon solvent (88). When this was done in pentane solution, the pentyl(hydrido)platinum(IV) complex E (R = pentyl) was observed as a... 

The authors point out that the dependence of the site of electrophilic attack on the ligand trans to the hydride in the model systems may be important with respect to alkane activation. If the information is transferable to Pt-alkyls, protonation at the metal rather than the alkyl should be favored with weak (and hard ) a-donor ligands like Cl- and H20. These are the ligands involved in Shilov chemistry and so by the principle of microscopic reversibility, C-H oxidative addition may be favored over electrophilic activation for these related complexes. 

The first reports on c-alkane metal complexes date back to the 1970s, the work of Perutz and Turner on photochemically generated unsaturated metal carbonyls of Group 6 [4], which is well before the C-H oxidative addition studies of alkanes. The enthalpy gain of formation of c-alkane metal complexes... 

Pyridine-functionalized N-heterocyclic carbene Rh and Ir complexes have also been described as active precatalysts for C=0 bond TH. For example, Peris and coworkers observed the formation of metal hydrides by C—H oxidative addition of a pyridine-N-substituted imidazolium salt such as N-"Bu-N -(2-pyridylmethyl-imidazolium) hexafluorophosphate in the reaction leading to M-pyNHC complexes, that is [lr(cod)H(pyNHC)Cl] (58) [54]. Transmetallation from silver carbene... 

A subsequent study using neopentane as the alkane substrate gave evidence in support of the same mechanism, and also allowed resolution of near-coincident y(CO) absorptions due to [Cp Rh(CO)Kr] (1946 cm ) and [Cp Rh(CO)(di2-neopen-tane)] (1947 cm ) [18]. Further studies were able to quantify the reactivity of [Cp Rh(CO)Kr] towards a range of alkanes [20]. It was found that binding of the alkane to Rh becomes more favorable, thermodynamically, as the alkane size is increased, but that the rate of the C-H oxidative addition step shows less variation with linear alkane chain length. No reaction with methane was observed, which was explained by the ineffective binding of methane (relative to excess Kr) to Rh. 

The need for a base additive in this reaction implies the intermediacy of acetylide complexes (Scheme 9.10). As in the Rh(III)-catalyzed reaction, vinylidene acetylide S4 undergoes a-insertion to give the vinyl-iridium intermediate 55. A [l,3]-propargyl/ allenyl metallatropic shift can give rise to the cumulene intermediate 56. The individual steps of Miyaura s proposed mechanism have been established in stoichiometric experiments. In the case of ( )-selective head-to-head dimerization, vinylidene intermediates are not invoked. The authors argue that electron-rich phosphine ligands affect stereoselectivity by favoring alkyne C—H oxidative addition, a step often involved in vinylidene formation. 

The mechanism involving simple nitrogen-coordinated complexes also accounts for reactivities of certain sterically constrained systems. For instance, 3-(diethyamino)cyclohexene undergoes facile isomerization by the action of the BINAP-Rh catalyst (Scheme 18). The atomic arrangement of the substrate is ideal for the mechanism to involve a three-centered transition state for the C—H oxidative addition to produce the cyclometalated intermediate. The high reactivity of this cyclic substrate does not permit any other mechanisms that start from Rh-allylamine chelate complexes in which both the nitrogen and olefinic bond interact with the metallic center. On the other hand, fro/tt-3-(diethylamino)-4-isopropyl-l-methylcyclohexene is inert to the catalysis, because substantial I strain develops during the transition state of the C—H oxidative addition to Rh. 

The use of photochemical dinitrogen loss has been selectively employed in similar reactions with some notably enlightening results [124,125]. An early study shows that Cp Re(CO)(L)(N2) (L is P(OEt)3, P(OMe)3, PMe2Ph) photochemically produces frans-Cp Re(CO)(L)(Ph)Cl under UV irradiation in chlorobenzene, similar to the reports above [124]. However, the analogous reaction of Cp Re(CO)2(N2) with 1,4-difluorobenzene, produces both the C-H oxidative addition product Cp/Re(CO)2(Ar)H (Ar is 2,5-C6F2H3) and the coordinated benzene product, Cp Re(CO)2( 2-l,4-C6F2H4) [125]. The two isomers interconvert around 213 K. 

A related topic that was already discussed in these first DFT/MM works is that of branching. The scheme shown in Fig. 1 would always produce always a linear polymer if ethylene was used as olefin. But a simple process of / C-H oxidative addition/reductive elimination, coupled with olefin rotation, can produce a branched polymer, as shown in Fig. 4. Calculations on the branching process for cationic diimine Ni(II) complexes [36, 37] indicated a small increase between 0.9 and 2.5 kcal/mol in the barrier for this process, associated with the introduction of the bulky substituents in the catalysts. 

It was proposed that reaction 2 proceeded via C-H oxidative addition, although driven largely by the electrophilidty of the cation [6]. 

Oxidative addition of C2 - H bonds of imidazolium salts to low valent metals was first observed by Nolan and coworkers in 2001, who proposed a NHC - Pd - H intermediate in the catalytic cycle of the dehalogenation of aryl halides with Pd(dba)2 in the presence of imidazolium salts [154]. More direct evidence of this process was described by Crabtree and coworkers two years later [155]. The reaction between a pyridine-imidazolium salt and Pd2(dba)3 afforded the preparation of bis-NHC - Pd(II) complexes by C2 - H oxidative addition (Scheme 40). The presumed Pd - H intermediates were not detected. The authors proposed a mechanism via two successive C - H oxidative additions followed by reductive elimination of H2 [ 155]. 

The isolation of the first NHC - M - H complexes obtained by oxidative addition of an imidazolium salt to a low valent group 10 metal was achieved by Cavell and coworkers in 2003 [156]. A NHC-Pt(O) complex with two monoalkene ligands reacted with an imidazolium salt to provide an isolable NHC-PtH complex (Scheme 41). Carbene metal hydrides of Ni and Pd were obtained one year later by C - H oxidative addition of the corresponding imidazolium salts to bis-NHC Ni(0) and Pd(0) complexes (Scheme 41) [157]. 

Blocking the C2 position with alkyl groups may afford C - H oxidative additions of the imidazolium salts yielding abnormal carbenes. This strategy was followed in the reaction a Pt(0) complex with C2-methylated imidazolium salts, which provided the oxidative addition of the C4,5 - H bond, as shown in Scheme 42 [158]. This behavior provides evidence that the substitution of imidazolium-based ionic liquids at the C2 may not be enough to prevent their involvement in reactions for which they are solvents. 

Coordinatively unsaturated 14- or 16-electron fragments L M, where M has a d6, ds, or dw configuration, are capable of oxidatively adding C—H bonds of arenes and alkanes and have been studied in considerable detail. Calculations suggest that the reaction proceeds via an i -alkane complex.125 More electron-rich as well as heavier transition metal centers, i.e., 3rd-row metals, facilitate C—H oxidative addition. In the case of C—H addition to Pd and Pt phosphine complexes MI, high activation barriers ( 30 kcal mol-1) have been calculated for monodentate phosphines, whereas chelating phosphines lead to values as low as 4 kcal mol-1 (M = Pt).126... 

The oxidative addition of alkanes to Rh1 and Ir1 species CpML is very facile. In the case of the tris(pyrazolyl)borate complex Tp Rh(CO)2 [Tp = HB(2,4-Me2pyr)3], the lifetimes of the intermediates were determined by ultrafast time-resolved infrared spectroscopy. In this case de-chelation of one of the pyrazolyl arms was found to precede the C—H oxidative addition step. The proposed intermediates for R—H addition and their lifetimes are shown in Fig. 21-1.127... 

More recently, the reductive elimination of alkanes from Pt(IV) complexes has become an intense area of investigation as it represents the reverse of the C-H oxidative addition reaction that has been shown to be catalytic in the presence of the Pt(II)/Pt(fV) couple. ... 

One of the significant challenges in synthetic chemistry is to follow a C H activation step with further bond making or breaking transformations. In the processes described above, the C H oxidative addition product is the thermodynamic sink of the reaction. Three processes that have transcended this difficulty are carbonylation, dehydration, and borylation. 

Alkylidenes have been prepared by reduction of alkyli-dynes, by C H oxidative addition from alkyls, and by treatment of unsaturated metal clusters with diazoalkanes. In most instances, the alkylidene adopts a /r2-h coordination mode. However, alkylidenes with heteroatom substituents may also be found in terminal coordination modes. The latter are typically prepared by the Fischer-type carbene route (see Fischer-type Carbene Complexes) (sequential addition of nucleophilic and electrophilic alkylating agents to carbonyl or isocyanide ligands), by condensation of metal fragments with mono- or dimetallic carbene complexes, or by C-H activation of alkylamines. These heteroatom substituted carbenes may also bind in a p3-ri mode, as in (12). 

With the development of powerful methods for molecular orbital calculations (e.g. DFT) (see Molecular Orbital Theory), several computational studies of the C-H oxidative addition (see Alkane Carbon-Hydrogen Bond Activation) process have been undertaken. One has used CpRh(PH3) to model the reactive intermediate Cp Rh(PMe3) proposed for the reaction shown in equation (13). The results... 

---