C -H activation

Aldehyde CH bonds are reactive in oxidative addition, so it is not unexpected to find that aldehydes readily undergo catalytic reactions involving this oxidative addition. Several catalysts decarbonylate aldehydes as a result of the acyl hydride formed after the C-H addition undergoing deinsertion of CO, followed by reductive elimination of the alkane product (Eq. 2.49). The hard step in the process is the thermally induced dissociation of the resulting tightly bound CO. One such catalyst is [Rh(triphos)Cl] (triphos = PhP(CH2CH2PPh2)2) [134]. 

The acyl derived from the aldehyde can also be intercepted by an alkyne, with 

Activation of Substrates with Non-Polar Single Bonds 

Excellent catalysts in this case are Ni(cod)2/P(C8Hi7)3, [135a] and [Rh(cod)Cl]2/dppf [135 b] (dppf = l,l -(diphenylphosphino)ferrocene. In the latter case, propargyl susbstituents are tolerated even though these could, in principle, give CH bond cleavage rather easily. 

An important catalytic process that relies on cyclometalation is the Murai reaction [136]. This involves heteroatom directed cyclometalation of an arene followed by insertion of an alkene and reductive elimination to give a net alkylation of the arene. The most common catalyst is RuH2(CO)(PPh3)3. An example of transformation brought about by this catalyst is shown in Eq. 2.51. 

Organic Synthesis Using Transition Metals, Second Edition. Roderick Bates. 2012 John Wiley Sons, Ltd. Published 2012 by John Wiley Sons, Ltd. 

Using transition-metal catalysts for C-C bond forming at carbons bearing acidic protons, such as the position a- to a carbonyl group is discussed in Section 2.11, as the C-H bond is activated by its position, and not primarily by the metal. The coupling of terminal alkynes, the Sonogashira reaction, is also discussed in Section 2.8. The use of carbene and nitrene complexes for bond formation through C-H activation is a well-established process. This is discussed in Section 8.5.2. 

Another classification of C-H activation methods is as inner-sphere and outer-sphere mechanisms. Inner-sphere mechanisms can be defined as those that involve the formation of a carbon-metal bond from a C-H bond, while outer-sphere mechanisms involve the cleavage of a C-H bond by a metal-containing species to generate a reactive intermediate, but without a metal-carbon bond. A disadvantage of this classification is that it assumes that the mechanism is known The reactions discussed in this chapter would be considered inner-sphere. Reactions such as the Fenton reaction would be considered outer-sphere. A grey area is likely to exist between the two mechanisms. Another disadvantage of this classification is that the term inner-sphere mechanism tells us nothing about the mechanism beyond the formation of a metal-carbon bond  

An additional, and practical, classification is between reactions that convert a C-H bond into a new functional group, which is useful for further bond formation, and reactions that convert a C-H bond directly into a new C-C bond. The latter are obviously more efficient, but may not always be practical in every 

Methane (natural gas) will become a more common feedstock for the chemical and energy industries in future, in which case methane activation will be needed. Some natural gas is found at geographically remote sites, where transport to consumers is hampered by methane being a permanent gas that cannot be liquefied at ambient temperature. A goal is to convert methane on-site to more easily transported materials such as MeOH or Mc20. 

Organometallic complexes often activate the C-H either by oxidative addition (Fig. 6.3, path a) or a-bond metathesis, or a-CAM (path b). These reactions favor attack at a terminal C-H bond, leading to subsequent terminal functionalization (e.g., PrH n-PrX), or at an arene C-H bond (e.g., ArH ArX). This selectivity usefully contrasts with standard organic reactions via radicals or carbonium ions that are selective for the most highly substituted or benzylic CH bonds (e.g., PrH i-PrX ArMe ArCH2X). Species such as i-Pr- or i-Pr+ are more stable and more rapidly formed than n-Pr- or n-Pr+. Numerous organic synthetic applications of C-H activation continue to be found (Chapter 14). 

Catalysis by coordination compounds also plays an important role in the field because high valent Fe and Mn 0x0 complexes can abstract a hydrogen atom from a C-H bond, leading to fast rebound of the newly formed OH group to the C radical to give the alcohol (Eq. 12.24), 

In suitable cases, desaturation can occur by double H atom abstraction CH-CH -F M=0 — C=C -f- M(0H2). Both in enzymes and even in some synthetic catalysts, the resulting radical type selectivity can be modified by molecular recognition between the catalyst and substrate, so that the substrate is held in an orientation that dictates the selectivity.  

In line with the proposed intermediacy of alkane CH a complexes, several such complexes are now known, one of which, 12.15, is even stable in the solid state.  

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Dimethylthiophene reacts photochemically with rran.s-Rh(PMe3)2(CO)Cl to yield the isomeric products 218 (R = Me) and 219 because of C—H activation of thiophene (960M872) as well as species 220 (R = Me). Unsubstituted thiophene in similar conditions gives five products, the 3-thienyl activated isomers 218 (R = H) and 219 (R = H), the 2-thienyl isomers, 221 and 222, and 2-thienyl analogs of 220 (R = H). 

The pentamethylcyclopentadienyl derivatives of rhodium Cp RhL (L = PMe3, C2H4) oxidatively add thiophene preferentially via the C—S activation route compared to that based on the C—H activation [880M1171,94JOM(472)311]. The Tp derivatives by contrast yield mainly the latter. Tp Rh(PEt3) acts almost selectively and forms exclusively 225 (R = Et), whereas Tp Rh(PMc3) forms a major amount of 225 (R = Me) and minor amount of 226 (960M2678). 

Complex 105 in an atmosphere of carbon monoxide experiences rearrangement to 106, which through C-H activation gives the final product 107 with i -coordiantion of the 3,4-diphosphacyclopentadienone hgand (97JCS(CC)1539). 

Similar pyrimidine-to-pyridine conversions were also reported for purine and 8-azapurine with C-H active acetonitriles, ethyl acetoacetate, acetylacetone with dimedone 8-azapurine is converted into triazolotetra-hydroquinoline (Scheme 15) (73JCS(P1)1620, S(Pl)1625, S(P1)1794). 

Similarly, when both the Cp and arene ligands are permethylated, the reaction of 02 with the Fe1 complex leads to C-H activation of the more acidic benzyl bond [57]. When no benzylic hydrogen is present, superoxide reacts as a nucleophile and adds onto the benzene ligand of the FeCp(arene)+ cation to give a peroxocyclohexadienyl radical which couples with a Fe Cp(arene) radical. A symmetrical bridging peroxo complex [(Fe"Cp)2(r 5-C6H60)2] is obtained. The C-H activation reactions of the 19e Fe1 radicals BH can be summarized as follows... 

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). 

Scheme 23 Formation of tetrahydroazepinones 113 and methylenepyrrolidines 111 by a formal [5+2] cycloaddition with C-H activation [85]...

In this case the use of the Sm(II) "ate" complex Na[Sm N(SiMe3)2 3] as starting material afforded yet another novel C-substituted amidinate complex resulting from y C-H activation of a N(SiMe3)2 ligand (Scheme 194). All new... 

Rh(TMP)- under these conditions, and in fact the selective activation of methane in benzene solution is a distinctive and unusual feature of this system, given that aryl C—H activation ought to be thermodynamically favored over alkyl C—H activation. The proposed linear transition state proposed in Fig. 8 is the key to this different reactivity. The corresponding trimolecular transition state for an arene would be expected to be bent, and this would be precluded by the bulky TMP... 

The partial oxidation of propylene occurs via a similar mechanism, although the surface structure of the bismuth-molybdenum oxide is much more complicated than in Fig. 9.17. As Fig. 9.18 shows, crystallographically different oxygen atoms play different roles. Bridging O atoms between Bi and Mo are believed to be responsible for C-H activation and H abstraction from the methyl group, after which the propylene adsorbs in the form of an allyl group (H2C=CH-CH2). This is most likely the rate-determining step of the mechanism. Terminal O atoms bound to Mo are considered to be those that insert in the hydrocarbon. Sites located on bismuth activate and dissociate the O2 which fills the vacancies left in the coordination of molybdenum after acrolein desorption. 

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