Development of Stoichiometric C—H Bond Activation

FIGURE 25.5 C—H activation upon photolysis of firCTi-Cp XPMCjXHlj]. 

Oxidative addition is still one of the key processes observed in the literature. In fact, a better understanding of the steric and electronic properties of complexes that can promote C—H bond activation throughout this mechanism has been widely studied. The recent work of Conejero and coworkers [13] highlights this interest by the alteration of the environment of the V-heterocyclic carbene (NHC) ligands on a series of stable T-shaped [Pt(NHC )(NHC)][BAFj, where NHC represents the cyclometallated ligand, species (Fig. 25.6). 

FIGURE 25.6 Structural representation of [Pt(NHC )(NCH)][BAFj complexes. NHC refers to the cyclometallated ligand. The NHC for t-butyl (NHC ItBu, left), t-propyl (NHC IPr, center), and mesytilen (NHC IMes, right) are depicted. 

FIGURE 25.7 Methyl exchange reaction of Cp LuCH, with CH via a a-bond metathesis mechanism [14]. 

The use of computational methods has also been extended to understand the factors that make a-bond metathesis favorable. Ziegler et al. [15] investigated the ability of [Cp Sc—H] and [CpjSc—CHj] to undergo a-bond metathesis with the C—H bonds of methane, ethene, and ethyne. A barrier of 10.8 kcal/mol was computed for the exchange of the methyl substituent in [Cp ScGHj] complex, which correlates with the experimental process of Lu described earlier (11.7 kcal/mol). Lower barriers were computed for ethene and ethyne. The authors concluded that the o-bond metathesis in this system was favored due to greater s character and lower p character at the carbon atom included in the Sc- R- H R moiety, which favors the directionality of the new a-bond formed. 

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The syntheses of benzyl derivatives from benzylic C—H are well developed. Traditionally, multi-step syntheses had to be used. Furthermore, a stoichiometric amount of base was used and toxic halides were produced. To avoid such problems, various catalytic methods have been developed recently via direct functionalization of benzylic C—H bonds. More recently, our group has reported the FeCl2-catalyzed oxidative activation of benzylic C—H bonds followed by a cross-coupling reaction to form C—C bonds (Equation 11.1) [7]. The reactions selectively cleave benzylic C—H bonds and avoid further oxidation. The present methodology opens a window for iron-catalyzed C—H bond oxidation and C—C bond formation. 

Vinod and coworkers were the first to develop a selective procedure for the oxidation of benzylic C-H bonds to the corresponding carbonyl functionalities using a catalytic amount of 2-iodobenzoic acid and Oxone as a stoichiometric oxidant in aqueous acetonitrile under reflux conditions (Scheme 4.52) [83]. The authors hypothesized that the active hypervalent iodine oxidant generated in situ might not be IBX (90) (Scheme 4.47) but, instead, a soluble derivative of IBX (108) that incorporates a peroxysulfate ligand. This intermediate is believed to oxidize a benzylic C-H bond via a single-electron transfer (SET) mechanism [83]. 

Very recently, Jun et al. [179] have described the synthesis of isoquinoUnes 181 and pyridines 182 by the [Cp RhCy2-catalyzed Al-annulation reaction between aryl or a,p-unsaturated ketones 179-180, alkynes 178, and NH OAc, employing stoichiometric amounts of Cu(OAc)j as the oxidant and microwave irradiation. The reaction is successful with a wide family of arylketones 179 and enones 180 to afford the desired isoquinolines 181 and pyridines 182 in good to excellent yields (Scheme 3.69). A four-component reaction could be developed by in situ generation of enones by aldol reaction between an enolizable ketone and formaldehyde, affording the desired products in moderate yields. The proposed mechanism involves the Rh" -promoted consecutive N—H and p-C—H bond activation of imine XXXVII, generated from ketone/enone and NH, ... 

Currently, one of the most sought after procedures in organometallic chemistry is a homogeneous catalytic cycle that involves the activation of a C-H bond in an alkane. We have just examined the oxidative addition of C-X bonds, and in Section 12.3 we will show how this activation of the C-X bond leads to further chemistry. Regardless of how useful this may be, one still needs a C-X bond to start. It would be very useful to directly activate a C-H bond in an alkane, without needing to first create a C-X bond. However, the oxidative addition of a standard C-H bond is a rare reaction. A handful of systems have been developed, and we discuss two. No homogeneous catalytic cycles have yet to be developed, so the examples are simply stoichiometric reactions. 

Although C-H bond activation is an extremely promising strategy for the development of sustainable chemical processes, by minimising waste and extra reaction steps needed to introduce functional handles, the above examples do require further work before they can truly be described as green . For example, some of the harsh stoichiometric oxidants required should be replaced by oxygen or air to improve the environmental impact of these reactions. 

Allylic C-H Bond Activation and Allylic Oxidations. A new system has been developed for the allylic acetoxylation of alkenes. This uses Pd(OAc)2 as catalyst, 1,4-benzoquinone (BQ) as a co-catalyst/electron-transfer mediator, hydrogen peroxide as the stoichiometric oxidant and acetic acid as the solvent (eq 73). ... 

After these pioneering studies, a number of other research groups reported on the cleavage of C-H bonds via the use of a stoichiometric amount of transition-metal complexes [7]. To date, several types of catalytic reactions involving C-H bond cleavage, for example, alkyl, alkenyl, aryl, formyl, and active methylene C-H bonds have been developed [8]. In many cases,for these types of catalytic reactions, ruthenium, rhodium, iridium, platinum, and palladium complexes all show catalytic activity. 

Recently our group has developed concerted PCET-based methods for the activation of amide N-H bonds to form neutral amidyl radicals. Long recognized as valuable synthons for C-N bond formation [203, 208-213], these intermediates have not enjoyed widespread application in synthesis because of the inability to access these intermediates directly from native amide N-H bond precursors. The most common methods of amidyl generation typically require N-functionalized amides or the use of strong stoichiometric oxidants to effectively furnish the radical species. Few methods for catalytic amidyl generation have been reported [214]. We suspected that PCET could provide an amenable solution to producing neutral amidyls under mild catalytic conditions directly by activation of the amide N-H bond. 

Stoichiometric Aryl C-H Bond Amination Toward the goal of developing catalysts that can activate strong C-H bonds. Berry and coworkers have investigated diruthenium terminal nitrides supported by formamidinate ligands in a paddlewheel arrangement. Unlike mononuclear Ru nitrides, the RUj " "... 

The selectivity of C-H activation is a key issue in developing practical C-H functionalization strategies, as most relevant substrates will have multiple C-H bonds that are available for activation. As part of our ongoing collaboration with the Davies group, a series of competition experiments were devised to probe the relative reactivity of C(sp )-H bonds in iV-alkylimines, H-Li s, and phenylpyridine, H-Lg [64]. These substrates all undergo directed C-H activation in the presence of [Cp MCl2]2 and NaOAc to give well-defined cyclometallated species as their chloride adducts (Fig. 7). Stoichiometric reactions with H-L3 in... 

More efficient for the posterior construction of C-C bonds within aminometalla-tion processes have been copper-catalyzed C- H functionaHzation reactions. A series ofimpressive protocols to this end were developed by Chemler [68]. Based on a series of stoichiometric developments, Chemler could devise carboamination reactions, in which a nitrogen substituent undergoes radical C-H activation/C-C couphng. 

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