CH bond oxidations

Surprisingly, the study of this system indicated that the kinetic selectivity for aliphatic CH bond oxidative addition favours intermolecular reaction over intramolecular when neat hydrocarbon is the solvent there is, however, a moderate thermodynamic preference for the intramolecular reaction. Therefore, thermodynamic but not kinetic terms would favour the unimolecular cyclometallation reactions and it is possible that some systems may activate alkane CH bonds intermolecularly but that the products may not have been observed because of its thermal instability. 

In solvents that strongly resist anodic oxidation as MeCN, CH2CI2/CF3CO2H, or T SOjH CH-bonds in the alkyl chain can be oxidized. In acetonitrile a preferential acetamidation in the (co-2)- and ((B-l)-position occurs (Eq. 43) [352]. 

Palladium-catalyzed directed intramolecular activations of aryl C-H bonds have been reported, as in the phenyla-tion of heterocycle analogs. Palladacycles are proposed intermediates, acting as effective catalysts, and the mechanism is likely to proceed via oxidation of Pd(ll) to Pd(iv) by the iodonium salt, as for the Equation (57), which described the activation of benzylic i/-CH bonds (Equations (121)—(123).109... 

These radicals decompose according to the /3-scission rule, which implies that the bond that will break is one position removed from the radical site, so that an olefin can form without a hydrogen shift. Thus the isopropyl radical gives propene and a H atom, while the //-propyl radical gives ethene and a methyl radical. The /3-scission rule states that when there is a choice between a CC single bond and a CH bond, the CC bond is normally the one that breaks because it is weaker than the CH bond. Even though there are six primary CH bonds in propane and these are somewhat more tightly bound than the two secondary ones, one finds substantially more ethene than propene as an intermediate in the oxidation process. The experimental results [12] shown in Fig. 3.12 verify this conclusion. The same experimental effort found the olefin trends shown in Table 3.2. Note that it is possible to estimate the order reported from the principles just described. 

If the initial intermediate or the original fuel is a large monoolefin, the radicals will abstract H from those carbon atoms that are singly bonded because the CH bond strengths of doubly bonded carbons are large (see Appendix D). Thus, the evidence [12, 32] is building that, during oxidation, all nonaromatic hydrocarbons primarily form ethene and propene (and some butene and isobutene) and that the oxidative attack that eventually leads to CO is almost solely from these small intermediates. Thus the study of ethene oxidation is crucially important for all alkyl hydrocarbons. 

Essentially, the oxidation chemistry of the aliphatics higher than C2 has already been discussed since the initiation step is mainly CC bond cleavage with some CH bond cleavage. But the initiation steps for pure ethene or acetylene oxidation are somewhat different. For ethene the major initiation steps are [4, 39a]... 

For the anodic substitution of unactivated CH-bonds, some fairly selective reactions for tertiary CH-bonds in hydrocarbons and y—CH-bonds in esters or ketones are available [85-87]. However, in some cases, a better control of follow-up oxidations remains to be developed. Chemically, a number of selective reactions are available, such as the ozone on silica gel for tertiary CH-bonds [88], the Barton or Hoffmann-LoefHer-Freytag reaction for y-CH-bonds [89], and for remote CH-bonds, Cprop)2NCl/H [90, 91], photochlorination of fatty acids adsorbed on alumina [92] or template-directed oxidations [93]. 

Oxidation of Remote CH Bonds in Ketones, Carboxylic Acids, and... 

The nonactivated CH bond in aliphatic hydrocarbons is oxidized at a potential that lies mostly more anodic than 2.5 V [vs. SCE (saturated calomel electrode)] [5, 6]. This necessitates electrolytes with high anodic decomposition potentials. 

In trifluoroacetic acid [0.4 M TBABF4 (tetrabutyl ammonium tetrafluoroborate)] unbranched alkanes are oxidized in fair to good yields to the corresponding triflu-oroacetates (Table 2) [16]. As mechanism, a 2e-oxidation and deprotonation to an intermediate carbenium ion, that undergoes solvolysis is proposed. The isomer distribution points to a fairly unselective CH oxidation at the methylene groups. Branched hydrocarbons are preferentially oxidized at the tertiary CH bond [17]. 

The CH bonds of steroids surprisingly can be oxidized even in methanol as a solvent. The electrolysis of androstane in 0.1 M NaCl04 methanol/dichloromethane at a glassy carbon anode produces after 53% conversion 14% 6-methoxyandrostane and 27% 6-(methoxymethoxy) androstane [18, 19]. This remarkable regioselectivity is possibly... 

The reaction occurs by oxidation of the CH bond to a radical cation that is de-protonated to a radical. This is further oxidized to a carbocation that reacts with the nucleophiles in the electrolyte. The regiochemistry is controlled by inductive deactivation (—I-substituents) as well as by activation (+I-substituents), which leads to a reactivity tert.H > sec.H > prim.H. In steroids, a preferential adsorption appears to play a role. 

With ketones, a remote regioselective acetamidation is found. This result is mechanistically in accordance with the oxidation of the oxygen atom of the carbonyl group to a radical cation that abstracts a hydrogen from a remote CH bond. The generated radical is then oxidized to a cation, that reacts with acetonitrile to get the acetamide (Fig. 3) [15],... 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

Allylic CH bonds Aliphatic alkenes frequently undergo allylic substitution by oxidation of the double bond to a radical cation that undergoes deprotonation at the allylic position and subsequent oxidation of the resulting allyl radical to a cation, which finally combines with the nucleophiles from the electrolyte [21, 22]. The selectivity is mostly low. Regioselec-tive allylic substitution or dehydrogenation is, however, found in some cases with activated alkenes, for example, -ionone that reacts to (1) (Fig. 5) as a major product [23], menthone enolacetate that yields 90% (2) [24], and 3,7-dimethyl-6-octen-l-ol... 

CH bonds a to an amino group Anodic methoxylation of unsymmetrical tertiary amines takes place preferentially at the methyl group (Fig. 6) [28-30]. Substitution at a CH bond a to an amino group proceeds by oxidation of the amino group to a radical cation, followed by deprotonation at the adjacent CH bond to a radical. This is oxidized to a cation, which undergoes solvolysis, in this case, methanolysis. The regioselectivity has been explained by assuming that an adsorbed amine from which the intermediate cation is formed is as distant as possible from the anode... 

The catalytic homogeneous oxidation at low temperatures is therefore economically interesting, but also very difficult to achieve due to the high stability of CH-bonds. Partial oxidation is particularly hard in alkanes as classical oxidation procedures tend to over oxidize them. In the case of methane this would result in the formation of CH2O, CO and CO2. Low valent transition metals, however, are capable of activating the CH bond and rendering that problem less important as the difference in reactivity between the CH bond in methane and methanol is not that big. 

---