Activation by oxidative addition

Alkanes can also be activated by oxidative addition of coordinatively unsaturated organo-metallic reagents. In the presence of carbon monoxide, C—C bond formation can ensue, e.g., the conversion of pentane to hexanal7. Note that this method, highly selective for primary sites, is complementary to the radical-based chemistry outlined above. 

For an X—Y substrate, activation in this manner can ultimately lead to cleavage of the X—Y bond in a process called oxidative addition (5, 6, 16). The metal complex center has undergone an increase in both coordination number and oxidation state since in this formalism the electron pairs in metal-ligand bonds are associated with the ligands (14, 15). While substrate activation by oxidative addition occurs in this way for H2 (16), the term oxidative addition really represents a stoichiometric transformation, and does not necessarily imply a specific mechanism. In fact, studies over the past decade have shown that the interaction of X—Y with a metal center to give X—M—Y proceeds by any of a variety of mechanisms determined by the substrate and the metal complex (16-18). However, once the X—M—Y species is formed, the X—Y substrate can be viewed as activated. 

In the literature [25, 26a,c-g], inverse kinetic isotope effects for the reductive elimination of alkanes from metal centers, which is the miaoscopic reverse of alkane activation by oxidative addition, have been explained by the presence of an a alkane intermediate. Recently, thermolysis of the diastereomerically pure complexes (R5),(5R)-[2,2-dimethylcyclopropyl) (Cp )-(PMe3)lrH] and (/ / ),(5 5)-[2,2-dimethylcyclopropyl)(Cp )(PMe3)IrH] (see Scheme VI.5) in CaDs has been shown [26h] to result in its interconversion to the other diastereomer. The analogous reaction of the deuterium-labeled complexes resulted additionally in scrambling of the deuterium from the a-position of the dimethylcyclopropyl ring to the metal hydride position. Diastereomer interconversion and isotopic scrambling occurred at similar rates and have been discussed in terms of a common intermediate mechanism involving a metal alkane complex (Scheme VI.5). 

The (postulated) hydrometallation pathway of hydroalkoxylation (or hydration) of olefins (Scheme 2b) relies on O-H bond activation by oxidative addition of RO-H to metal centers, a process that is studied eagerly in the organometallic chemistry community [3, 24]. However, the insertion of olefins into the M-H bonds of metal... 

C-H activation by oxidative addition generally proceeds by generation of an unsaturated metal fragment in the presence of a hydrocarbon solvent. As intermediates in the C-H bond activation process, cr-alkane complexes have widely been proposed as described in the preceding section. Several new metal systems have been found to undergo oxidative addition to hydrocarbon C-H bonds. 

Because the oxidation state increases, activation by oxidative addition is more effective for metals in a low state of oxidation. Therefore, noble metals of Group VIII that satisfy this requirement are the most suited for this purpose. (See Chaloner et al., 1994, for a detailed treatment of homogeneous hydrogenation.)... 

At least in certain cases, such as acetophenone, the problem described above may be solved by using another procedure for formal nucleophilic substitution (Semmelhack et al, 1973). This procedure is based on the observation that aryl and vinyl halides are greatly activated by oxidative addition to transition metals in low oxidation states (Semmelhack et al, 1971, 1972b). A simple example is described in the following scheme ... 

Scheme 5 Activation modes for B2pin2- (A) Activation by oxidative addition, (B) activation by o-bond metathesis, and (C) activation by Lewis bases.

Commercially available and inexpensive y-Fe203 magnetic nanoparticles (particle size 58 nm) also efficiently activate B2pin2 and promote a direct borylation of alkenes. " The mechanism of this unusual nano-Fc203-catalyzed aromatic borylation reaction is not clear. The kinetic isotope effect was measured to be 1.3, indicating that a C—H bond activation by oxidative addition to the iron catalyst is not likely. An electrophUic metalation by Fe—B species, followed by reductive ehmination, seems conceivable. 

The best procedures for 3-vinylation or 3-arylation of the indole ring involve palladium intermediates. Vinylations can be done by Heck reactions starting with 3-halo or 3-sulfonyloxyindoles. Under the standard conditions the active catalyst is a Pd(0) species which reacts with the indole by oxidative addition. A major con.sideration is the stability of the 3-halo or 3-sulfonyloxyindoles and usually an EW substituent is required on nitrogen. The range of alkenes which have been used successfully is quite broad and includes examples with both ER and EW substituents. Examples are given in Table 11.3. An alkene which has received special attention is methyl a-acetamidoacrylate which is useful for introduction of the tryptophan side-chain. This reaction will be discussed further in Chapter 13. 

However, these reactions remain hypothetical, and the mechanism of alkylation of low-valent coordinatively insufficient ions during their interaction with hydrocarbons calls for a detailed study. When the activation by some additives is performed the formation of the active transition metal-carbon bond by oxidative addition is also possible, e.g. in the case of such additives as alkylhalogenides or diazocompounds according to the schemes ... 

In 1979, the first isolation of the hydrido(hydroxo) complex by oxidative addition of water to an electron-rich platinum(O) complex was accomplished by Yoshida and Otsuka [22]. Highly coordinatively unsaturated bis(triisopropylphosphine)platinum (24b) can activate water very easily at room temperature to give the hydrido(hydroxo)... 

Merola reported the preparation of hydrido(carboxylato)iridium(lll) complexes, mer-[lrCl(0C(0)R)(H)(PMe3)3] (90) (R = Ph, Me), by oxidative addition of acetic acid or benzoic acid to [Ir(cod)(PMe3)3]Cl (67) [46]. The structure of 90 (R = Ph) in which the carboxylato ligand coordinates as an T -ligand, was confirmed by X-ray analysis. The reaction of 67 with salicylic acid yielded the product 91, which resulted from activation of the O-H bond of the carboxylato but not of the hydroxo group (Scheme 6-13). 

Allyl carbonate esters are also useful hydroxy-protecting groups and are introduced using allyl chloroformate. A number of Pd-based catalysts for allylic deprotection have been developed.209 They are based on a catalytic cycle in which Pd° reacts by oxidative addition and activates the allylic bond to nucleophilic substitution. Various nucleophiles are effective, including dimedone,210 pentane-2,4-dione,211 and amines.212... 

Hydrogenolysis of halides and benzylic groups presumably involves intermediates formed by oxidative addition to the active metal catalyst to generate intermediates similar to those involved in hydrogenation. The hydrogenolysis is completed by reductive elimination.58 Many other examples of this pattern of reactivity are discussed in Chapter 8. 

In catalytic reaction conditions (H2 pressure), by interaction of a solvent such as THF or acetone, the 16-electron cationic [Rh(diphos)(NBD)]+ affords a 12-electron unsaturated diphosphine intermediate, which is the real active species. The catalytic cycle begins with alkene binding, followed by oxidative addition of H2. These cationic catalysts can reduce alkenes to... 

Restoration of the decayed species to its active valence is thus the key to reactivating the catalyst. It has been known that organic halides with activated C—Cl bonds can add to lower-valent transition metals and convert them to their higher oxidation states by oxidative addition (12-16) ... 

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