Radical clock experiments

A concerted [2 + 2] cycloaddition pathway in which an oxametallocycle intermediate is generated upon reaction of the substrate olefin with the Mn(V)oxo salen complex 8 has also been proposed (Scheme 1.4.5). Indeed, early computational calculations coupled with initial results from radical clock experiments supported the notion.More recently, however, experimental and computational evidence dismissing the oxametallocycle as a viable intermediate have emerged. In addition, epoxidation of highly substituted olefins in the presence of an axial ligand would require a seven-coordinate Mn(salen) intermediate, which, in turn, would incur severe steric interactions. " The presence of an oxametallocycle intermediate would also require an extra bond breaking and bond making step to rationalize the observation of trans-epoxides from dy-olefms (Scheme 1.4.5). 

Based on DFT calculations, Shaik and coworkers proposed a two-state reactivity process. The doublet and quartet states of P450 Compound I (see Figure 17) have virtually identical reactivity but follow very different pathways. The low-spin doublet state leads to a substrate radical transition state with no barrier to the rebound step, whereas the high-spin quartet state generates a radical with a significant barrier to rebound. In this model, predominance of the low-spin pathway explains the apparently short ( 100 fs) radical lifetimes in some radical clock experiments, while the high-spin pathway accounts for the finite radical lifetimes in others. The calculations further suggested that the doublet... 

Scheme 49 Radical clock experiments to detect radical intermediates...

N-F reagents acting as electrophiles, because radical clock experiments with these systems do not support a radical process [69, 70]. 

A second important lesson from the radical clock experiments relates to the extremely large rate constants determined for the radical recombination step with substrate 22. The rate constant of 1.5 x 10 s is on the time-scale of a bond... 

The radical clock experiments with MMO from M. capsulatus (Bath) and M. trichosporium OB3b carried out in our laboratory indicate that there may not be a single mechanism operative for these enzyme systems. Instead, the mechanism may depend on factors such as the steric and energetic requirements of the substrate, as well as the temperature employed in the MMO hydroxylation reaction. Differences in the MMO systems from the two different organisms include their optimal hydroxylation temperatures as well as sequence variations in the coupling protein B from the two organisms. ... 

The radical clock experiments as well as the stereochemical outcome of the reaction along with the reactivity profiles observed pointed to an ET process as the operating mechanism. Linear-free energy relationships were also consistent with this mechanistic pathway (see succeeding text). ET may proceed in two ways, usually referred to as inner-sphere and outer-sphere ET, which can be contemplated as the two extremes of a continuous mechanism [204]. Both processes are dissociative in nature for alkyl halides and presumably do not involve a discrete radical anion, RX" [205]. The situation may, however, be different for aryl halides. Radical anions do exist, and aryl halides probably undergo a stepwise reaction with an electron donor to give rise to RX [206]. 

Radical domino strategies have been scarcely described in the construction of polycyclic cyclopropanic structures. Indeed, radicals formed by 3-exo-trig cyclization are being rapidly reopened, and this property is notably used in radical clocks experiments. In order to suppress this unwanted event, Malacria and Fensterbank have devised a (dichloromethyl)dimethylsilyl ether able to play both roles of the initiation and termination sites of the radical process [108]. By designing an appropriate acyclic structure 98, the expected cyclopropanic compounds 99 have been obtained in good yields and diastereoselectivities after addition of MeLi to the silyloxycyclopentene intermediate (Scheme 5.35). 

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