C-H activation processes

Sames and coworkers have very recently introduced BF3 OEt2 catalysis to promote room temperature hydroalkylation of electron deflcient olefins as a formal sp C-H functionalization process. Coordination of the Lewis acid to the alkene moiety of the tetrahydropyran (121) facilitates a 1,5-hydride shift to afford a zwitterionic species, (122), which is followed by nucleophilic attack at the oxocarbonium center to furnish the requisite spirocyclic pyran (123) (Equation 74) [77]. 

The same authors have extended this process to aldehyde- and ketone-containing tetrahydropyran substrates (124) and have obtained excellent yields of the corresponding spirocyclic products (125) (Equation 75) [78]. 

0Et2 has also been used in promoting rhodium-catalyzed C-H bond activation processes. Tu and coworkers have recently reported that a combination 

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The special salt effect is a constant feature of the activation of substrates in cages subsequent to ET from electron-reservoir complexes. In the present case, the salt effect inhibits the C-H activation process [59], but in other cases, the result of the special effect can be favorable. For instance, when the reduction of a substrate is expected, one wishes to avoid the cage reaction with the sandwich. An example is the reduction of alkynes and of aldehydes or ketones [60], These reductions follow a pathway which is comparable to the one observed in the reaction with 02. In the absence of Na + PFg, coupling of the substrate with the sandwich is observed. Thus one equiv. Na+PFg is used to avoid this cage coupling and, in the presence of ethanol as a proton donor, hydrogenation is obtained (Scheme VII). 

There has been little insight into potential decomposition pathways for the Ni(II) system due to sparse experimental evidence. Polymerization results with catalysts bearing different alkyl and fluorinated substituents have suggested that a C-H activation process analogous to that occuring with the Pd(II) catalysts is unlikely with Ni(TT) [28], Instead, side reactions between Ni and the aluminum coactivator, present as it is in such large excess, have been implicated. The formation of nickel dialkyl species and their subsequent reductive elimination to Ni(0) is one possible deactivation mechanism [68]. 

An important section of the C-H activation chemical literature, up until the early 2000s, has already been reviewed and excellent reviews are appearing at an exponential rate (vide infra).6>6a 6g This review will effectively serve as an update to our earlier work as well as cover a wider scope of metals and processes. An attempt, wherever possible, is made to avoid repetition. Undoubtedly, many important contributions are omitted in the area of C-H activation chemistry, for which the authors apologize, although this is inevitable in a review of this size due to space considerations. However, the reader is invited to consult the reviews and references cited hereafter, which should provide ample exposure to the area of C-H activation processes. 

Acetic acid analogs can also be formed from a one-step C-H activation process using a palladium sulfate catalyst.15 A free radical process was ruled out for this formal eight-electron oxidation due to the high selectivities observed (90% based on methane converted) (Equation (7)). 

A stoichiometric reaction, leading to a similar product distribution, lends support to a C-H activation process, giving rise to an iridium hydride intermediate (Equation (41)). 

In closely related experiments it was shown that sp C—H activation takes place reversibly within the coordinahon sphere of the electron-rich Ir(I)-diphosphine complex 58 (Scheme 6.9) to form an alkyl-amino-hydrido derivative 57 reminiscent of the CCM intermediate 24 the solid-state structure of 57 is shown in Figure 6.13 [40]. It appears that C—H activation only takes place after coordination of the amine function to the Ir(I) center (complex 58, NMR characterized). Amine coordination allows to break the chloro bridge of 59 and to augment the electron density of the metal center, thus favoring oxidative addihon of the C—H bond. Most importantly, the microscopic reverse of this C—H activation process (i.e. C—H reductive elimination) models the final step of the CCM cycle (see Scheme 6.1) indeed, the reaction of Scheme 6.10 is cleanly reversible at 373 K. 

Among the historic developments of studies on C—H activation, several methods and conditions have been used, from thermal studies to photochemical activation, with all of which have been mediated by derivatives of metals ranging from transition metals to lanthanides and actinides. Hence, given the importance that the chemistry surrounding the C—H activation process entails, several excellent reviews and monographs have already been published [6]. Unfortunately, in most of these cases the chemistry described has been devoted entirely to descriptions of the activation of a particular C—H bond in a given process, and consequently some division has arisen as to how the C—H activation process does in fact proceed... 

From the outset, iridium compounds have played an important role in the better understanding of the C—H activation process, and consequently in the development of efficient alkane dehydrogenation reactions [8]. Hence, in this chapter we will review the participation of iridium complexes in the optimization of chemical processes for C—H activation which, today, have led to some highly promising... 

The full potential of this C-H activation process, as a surrogate Mannich reaction, was realized in the direct asymmetric synthesis of threo-methylphenidate (Ritalin) 217 (Eq. 28) [140]. C-H insertion of N-Boc-piperidine 216 using second-generation Rh2-(S-biDOSP)2 and methyl phenyldiazoacetate resulted in a 71 29 diastereomeric mixture, where the desired threo-diastereomer was obtained in 52% yield with 86% enantiomeric excess. Winkler and co-workers screened several dirhodium tetracarboxami-dates and found Rh2(R-MEPY)4 to be the catalyst that gives the highest diastereoselec-tivity for this reaction [142]. 

In summary, the chemistry of the donor/acceptor-substituted carbenoids represents a new avenue of research for metal-catalyzed decomposition of diazo compounds. The resulting carbenoids are more chemoselective than the conventional carbenoids, which allows reactions to be achieved that were previously inaccessible. The discovery of pan-tolactone as an effective chiral auxiliary, and rhodium prolinates as exceptional chiral catalysts for this class of rhodium-carbenoid intermediate, broadens the synthetic utility of this chemistry. The successful development of the asymmetric intermolecular C-H activation process underscores the potential of this class of carbenoids for organic synthesis. 

It is an axiom of modern organometallic chemistry that the pursuit of late transition metal complexes is ultimately driven by the need to formulate ever more efficient catalysts and reagents for chemical synthesis. In this respect, the field of poly(pyrazolyl)borate chemistry is no different from any other, albeit that in the case of the group 10 triad the breadth of study is perhaps more limited than for other metals and/or ligands. This section provides an overview of prominent results in respect of both catalysis and the C—H activation processes that underpin them. 

ReCp(CO)2(H)(MR3) and ReCp(CO)2H2 are the products of photoinduced oxidative addition of (89) to H MR3 bonds (M = Si, Ge, Sn) (see Section 8.1.5). Photochemical activation of (89) or (90) in the presence of B2pin2 gave cis and /ran5 -ReCp (CO)2(Bpin)2, that is, oxidative addition to the B-B bond. Most remarkable, however, is the fact that further irradiation of this compound or of a mixture of (90) and B2pin2 in pentane led to regiospecific terminal C-H activation of the pentane with formation of CsHnBpin and HBpin. The mechanism of this elegant C H activation process does not seem to take place via C H activation on intermediate ReCp (CO)2.i ... 

Scheme 12 Cross metathesis as a reaction equivalent to vinyl C-H activation processes of substitution and insertion...

The selective activation and functionalization of C H bonds has attracted much attention in recent years. In spite of the common proposal, which postulates that NHC ligands coordinated to TM are relatively inert, several examples of C-H activation processes involving NHCs have been reported. Because of the high electron-donating property of NHCs, some TM NHC complexes have been found to undergo facile intramolecular C-H bond activation. 

Following their work on orthometallation with iridium-based complexes. Peris etal. investigated the difference between aromatic and aliphatic C-H activation processes. They reported the preparation and reactivity of alkyl-functionalized imidazolylidene complexes of iridium (III) undergoing intramolecular cyclometallation. As shown in... 

In this system, the cyclometallation may be favored by the presence of the methyl substituents on the NHC backbone, increasing the a-donor character of the NHC ligand and enhancing the C H activation process. These reactions have been successfully apphed to introduce other ligands onto the metal center, such as alkoxy or amino groups that can be used as proton sponge. 

In the absence of donor ligands, the binuclear zirconium fulvalene complex reacts with Ph3C[B(C6F5)4] to give the relatively inert (g-CH2)(g-CH3) doubly-bridged binuclear cationic complex 71 7550 (Equation (45)). This C-H activation process via ct-H elimination and loss of CH4 is facile even at — 60 °C. 

A unique preference was found using the nonsynunetric P,N system for C-C activation without detecting the normally competing C-H activation process [Eq. (6.122)]. As shown earlier [see Eqs. (6.73) and (6.74)],fine-tuning the structure of complexes allowed selective intramolecular C-H or C-C activations." Exclusive C-C activation could also be achieved with a bisphosphinite ligand. "... 

Metal-mediated C-H activation processes are useful for the annulation of the indole ring. Palladium-mediated intramolecular annulation reactions were utilized in the preparation of... 

Other palladium-catalyzed 1,5-C-H activation processes reported are extensions of known work. In these examples, palladium activates the C-H bond, but whether the migration occurs or not is still debatable. An aryl to imidoyl C-H activation takes place in substrate 28 (7) under the same reaction conditions that promote the 1,4-palladium migration. However, this reaction affords a much lower yield (compare with Scheme 10), which implies a relatively low efficiency for this 1,5-C-H activation. Mechanistically, the reaction can either go through a direct C-H activation to form a six-membered palladacycle, followed by reductive elimination, or a proton channeling-based palladium migration, followed by an arylation with the original aromatic ring. The exact path has not been established experimentally or computationally. 

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