Oxidative radical rebound

Intermediates that take place in the catalytic cyclic of carbon-hydrogen bond oxidation are quite similar to those previously described for olefin oxidation (Fe -OOH (a) and H0-Fe =0 (b) (Schemes 13.28 and 13.30). The proposed mechanism involves the abstraction of a CH hydrogen atom from the substrate by the high-valent iron-oxo species (b), followed by an allq l radical rebound affording the product and regenerating the iron-catalyst... 

One important line of investigation which has supported the radical rebound hypothesis is the use of radical clock substrate probes. These probes rearrange in a diagnostic way on a very rapid and calibrated time scale when a hydrocarbon radical is formed. In the case of P450, rearranged products have been isolated after oxidation and have been used as evidence of an intermediate substrate radical. In this way, even though the lifetime of the radical is too short for it to be observed directly, its character can be explored by the judicious choice of substrate analogues. 

Another method for conducting cyclizations catalytic in Cp2TiCl is shown in Scheme 14. It relies on the thermodynamically favorable ring closure of THF from 5-titanoxy radicals [81,82]. This step is mechanistically related to the oxygen rebound steps of oxidation reactions. While the scope of this transformation remains to be established, the presence of substituted THF-derivatives in many natural products renders the method potentially attractive. 

The mechanism of cytochrome P450 catalysis is probably constant across the system. It is determined by the ability of a high valent formal (FeO) species to carry out one-electron oxidations through the abstraction of hydrogen atoms or electrons. The resultant substrate radical can then recombine with the newly created hydroxyl radical (oxygen rebound) to form the oxidized metabolite. Where a heteroatom is the (rich) source of the electron more than one product is possible. There can be direct recombination to yield the heteroatom oxide or radical relocalization within the... 

These results, as well as rate studies " and kinetic isotope effects ", support a concerted, 5ptra-structured oxenoid-type transition state for the CH oxidations". The original oxygen-rebound mechanism has been discounted (see the computational work in Section I.D). Recently, however, the stepwise radical mechanism was revived in terms of the so-called molecule-induced homolysis , but such radical-type reactivity was severely criticized on the basis of experimental" and theoretical grounds. 

The reaction follows the consensus mechanism for aliphatic —H activation by oxyl-ferryl compounds (35) in which the first step is H-atom abstraction via TS1 to give a hydroxo-Fe(III) complex with a C-centered alkyl radical, labeled IN. This is followed by a rebound step via TS2 to give the final product, ethanol and the ferrous active site. Overall, this is a two-electron oxidation process where the bonding orbital serves as the electron donor and the H-atom abstraction is rate limiting. 

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