Oxidative rearrangements carbon-hydrogen bond activation

Isotope effects can be used to choose the most likely path. When ethylene is oxidized in deuterated water, the acetaldehyde contains no deuterium hence, all four hydrogens in the acetaldehyde must come from the ethylene. Thus, if the slow step of the reaction involves the formation of acetaldehyde, the activated complex for this slow step would involve a hydride transfer, and a primary isotope effect would be expected when deuterated ethylene is used. Actually, the isotope effect kn/ko was found to be only 1.07. In Paths 1 and 3, the slow step is, respectively, the decomposition of a 7r-complex and a a-complex to product, and they would be expected to display a primary isotope effect. However, in Path 2, the rate-determining step is the rearrangement of a 7r-complex to a (T-complex. Since no carbon-hydrogen bonds are broken, no primary isotope effect would be expected. Thus, Path 2 is consistent with all the experimental facts. Paths involving oxypalladation adducts, first suggested by the Russian workers (32), are now generally accepted (19, 28, 32). 

Figure 2. Schematic diagram of the second reaction of the fatty acid P-oxidation pathway catalyzed by co/i enoyl-CoA hydratase. Compounds 1 and 2 are 2-mmr-enoyl-CoA and L-3-hydroxyacyl-CoA, respectively. The protonated Glu transfers a proton to the a carbon of the substrate on the re face, whereas the deprotonated Glu" attracts a proton from water whose oxygen makes a nudeopbilic attack on the P-carbon of the substrate. The amino group of Gly" in the peptide backbone acts as a l rogen donor to form a hydrogen bond with the carbonyl oxygen so that an electronic rearrangement occurs in the acryloyl portion of the sul trate. The transition state is shown in the square brackets The product, L-3-hydroxyacyl-CoA, can then leave the active site. Two general acid-base functional groups, the ycarboxyl groups of Glu and Glu , play a major part in the hydratase catalysis...

The tripeptide nature of glutathione introduces a complication not seen with some simpler thiols. The glutamyl moiety has an electron-donating amino substituent which, when deprotonated, renders the hydrogen on the substituted carbon liable to abstraction by oxidizing agents. The sulphur-centred thiyl radical is reactive towards activated C-H bonds, as noted above (reaction (Ir)), and can abstract intramolecularly from this activated carbon if the amino substituent is deprotonated. The intramolecular rearrangement is thus base catalysed and can be represented by ... 

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