Oxidation of carbon-hydrogen bonds

Drugs that are susceptible to oxidation of carbon-hydrogen bonds include ethers (which oxidise to form highly explosive peroxides), aliphatic amines (which oxidise at the a hydrogen atom) and aldehydes (which are easily oxidised to carboxylic acids and peroxy acids). Examples of these reactions are shown in Figure 8.6. 

Cytochrome P-450 describes a group of enzymes that use a heme group to perform oxidations, including in particular oxidations of carbon-hydrogen bonds. Many model systems had been examined for such processes, but they had not included any defined binding of a substrate in such a way as to achieve pre-selected functionalization of particular carbon atoms. Thus we initiated a series of studies of such systems in which we used cyclodextrins as binding groups for the substrates to hold them, in water, in such a position as to achieve selective functionalizations. 

Oxidation of carbon corresponds to an increase in the number of bonds between carbon and oxygen or to a decrease in the number of carbon-hydrogen bonds Conversely reduction corresponds to an increase in the number of carbon-hydrogen bonds or to a decrease in the number of carbon-oxygen bonds From Table 2 4 it can be seen that each successive increase m oxidation state increases the number of bonds between carbon and oxygen and decreases the number of carbon-hydrogen bonds Methane has four C—H bonds and no C—O bonds car bon dioxide has four C—O bonds and no C—H bonds... 

Kalyani D, Sanford MS (2007) Chelate-Directed Oxidative Functionalization of Carbon-Hydrogen Bonds Synthetic Applications and Mechanistic Insights. 24 85-116 Kanno K, see Takahashi T (2005) 8 217-236... 

The indirect anodic cleavage of carbon-hydrogen bonds in the benzyl position using triarylamine mediators was also used for mild and selective deblocking of hydroxy, carboxyl, and amino groups. The primarily formed cation radical of the protective group is readily deprotonated in the benzyl position by an added base (Eq. (107)). This benzylic radical is easily further oxidized to the benzyl cation which subsequently is cleaved by attack of a nucleophile, such as water (Eq. (108)). 

In the absence of such n- and n-electrons, oxidation can involve the cr-electrons of carbon-hydrogen bonds (Ullrich, 1972 White and Coon, 1980, Guengerich and MacDonald, 1984) ... 

Fig. 9 may be viewed, also, as a localized molecular orbital representation of, e.g., a hydrocarbon (cf. Fig. 13, ref. 7). Thus, replacement of (i) the domains of the Si4+ cations (the atomic cores of silicon atoms) by the domains of C4+ cations (the atomic cores of carbon atoms r = 0.15 A 2>), (ii) the domains of the bridging (i.e., bonding) oxide ions by the domains of the electron-pairs of aliphatic carbon-carbon single bonds (r 0.6e A 40)), and (iii) the domains of the non-bridging oxide ions by the domains of the protonated electron-pairs of carbon-hydrogen bonds... 

Now there are many examples of the formation of metal-carbon bonds by the splitting of carbon-hydrogen bonds in complexes of transition metals in low oxidation states with aromatic or unsaturated hydrocarbon moieties, but only one other example has been discovered of the splitting of a saturated aliphatic carbon-hydrogen bond. The fact that an aliphatic carbon-hydrogen bond can be split at all holds out hope that at some time a system may be discovered capable of reacting under mild conditions with saturated hydrocarbons, with all its implications for the petrochemical industry. 

A subsequent study ° from the Arnold group showed an intriguing stereoelectronic effect in oxidative benzylic carbon-hydrogen bond cleavage reactions of substrates 8 and 9 (Scheme 3.7). In this study, electron transfer reactions were conducted in the presence of a nonnucleophilic base. Radical cation formation also weakens benzylic carbon-hydrogen bonds, thereby enhancing their acidity. Deprotonation of benzylic hydrogens yields benzylic radicals that can be reduced by the radical anion of dicyanobenzene to form benzylic anions that will be protonated by solvent. This sequence of oxidation, deprotonation, reduction, and protonation provides a sequence by which epimerization can be effected at the benzylic center. In this study, tram isomer 10 showed no propensity to isomerize to cis isomer 11 (equation 1 in Scheme 3.7), but 11 readily converted to 10 (equation 2 in Scheme 3.7). The reactions were repeated in deuterated solvents to assure that these observations resulted from kinetic rather than thermodynamic factors. Trans isomer 9 showed no incorporation of deuterium (equation 3 in Scheme 3.7) whereas cis isomer 11 showed complete deuterium incorporation. The authors attributed this difference in reactivity to... 

Oxidation of Carbon-Hydrogen and Carbon-Carbon Single Bonds 793... 

The oxidation of carbon-boron bond converts boranes into alkyl or aryl borates, which may be hydrolyzed subsequently to alcohols and boric acid [991], The oxidation is carried out with hydrogen peroxide [183,1201, 1202] or trimethyiamine oxide [991, 992]. Phenylboronic acids are oxidized to phenols biochemically [1034]. 

Oxidative-addition and reductive elimination reactions of transition metal complexes are crucial to many homogeneously catalyzed reactions and are important for bond formation. Reactant molecules such as H2 and Oj undergo oxidative addition to many transition metal centers. Oxidative addition of carbon-hydrogen bonds has been an active area of research. Reductive elimination is the process whereby products are eliminated from transition metal centers. 

NAD oxidizes a compound by accepting a hydride ion from it. In this way, the number of carbon-hydrogen bonds in the compound decreases (the compound is oxidized) and the number of carbon-hydrogen bonds in NAD increases (NAD is reduced). NAD can accept a hydride ion at the 4-position of the pyridine ring because the electrons can be delocalized onto the positively charged nitrogen atom. Although NAD could also accept a hydride ion at the 2-position, the hydride ion is always delivered to the 4-position in enzyme-catalyzed reactions. 

Dick AR, Sanford MS (2006) Transition metal catalyzed oxidative functionalization of carbon-hydrogen bonds. Tetrahedron 62 2439-2463... 

This chapter presents developments in the activation and functionalization of carbon-hydrogen bonds that have been discovered since 1993. Major breakthroughs in hydrocarbon activation appeared in the early 1980s, and in the following decade, an explosion of discoveries was seen in new examples of metal complexes that could activate C-H bonds. Mechanisms for cleavage included oxidative addition, electrophilic cleavage, radical H-abstraction, and metal atom reactions, and several texts are available that summarize the first decade of this work. " ... 

Oxidation of carbon corresponds to an increase in the number of bonds between carbon and oxygen or to a decrease in the number of carbon-hydrogen bonds. Conversely, reduction corresponds to an increase in the number of carbon-hydrogen bonds or to a decrease in the number of carbon-oxygen bonds. 

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