Radical clock tests

The pioneering work on the calibration of intramolecular cy-clization of the 5-hexenyl radical by Ingold and co-workers provided the basis for the development of a large number of radical clocks." These are now used both for the calibration of rate constants for intermolecular radical reactions and as mechanistic probes to test for the intermediacy of radical intermediates in a variety of processes. Furthermore, the ready availability of bimolecular rate constants from competitive product studies using free radical clocks without the use of time-resolved experiments has greatly enhanced the synthetic utility of free radical chemistry. The same concept has recently been extended to radical ion chemistry. For example, rate constants for carbon—carbon bond cleavage reactions of a variety of radical cations and anions derived from substituted diarylethanes have been measured by direct time-resolved techniques. " ... 

In their seminal paper on the rhodium(ll)-catalyzed C—H insertion with PhI=NNs, the group of Muller reached the conclusion that the reaction proceeds through the concerted asynchronous insertion of a rhodium-bound nitrene species.This hypothesis was supported by a Hammett analysis (/9= —0.90 vs. tr+), the absence of ring-opened products in reactions involving cyclopropyl radical clocks, and the stereospecific C(sp )—H ami-nation of (Ji)-2-phenylbutane that occurs with complete retention of configuration. However, the very low yields obtained for these test reactions as well as the kinetic isotope effect measured for the reaction from (1,3-D2)-adamantane (KIE = 3.5 0.2) put this conclusion into question as these did not rule out the possible involvement of radicals that could undergo fast recombination. Nevertheless, this initial study already highlighted the discrepancies that could be observed between the carbene and nitrene chemistries in terms of mechanism. The electronic structure of nitrenes, contrary... 

Miiller has used cyclopropyl clock experiments to test for the possible intermediacy of radical species prior to C-N bond formation (Scheme 17.7). The diphenylcyclopro-pane derivative 3, which fragments at a rate of 2x10 ° s , affords nosylated amine 4 no product from ring opening is observed. Such a result mitigates the viability of a productive stepwise oxidation process, though it is important to note that sulfonamide 4 is formed in only 5% yield. 

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