Cross-over insertion

Since the two-spin state forms can lead to different products, the products obtained will be a mixture that reflects the initial fractionation of the reaction between the two-spin states. The fractionation in turn is a reflection of the interplay and the probability of cross-over between the two-spin states (8). Thus, the two-state reactivity paradigm resolves the dilemma of whether a radical recombination or a direct insertion mechanism governs cytochrome P450-catalyzed hydroxylation actually they are both involved and the degree to which either is expressed depends upon the specific substrate hydroxylated and the specific enzyme. 

A simple and straightforward way to distinguish between a direct insertion process and one going through free radicals is by a cross-over experiment. Cyclohexane and cyclohexane-di2 are often used as the probe for crossover, and hence the reactive multiplicity of the carbenes in question (Scheme 9.8). 

Several alternatives are open to the reactive nitrene species residing adjacent to the nucleus. The singlet nitrene can attack a suitable proximate, electron-rich centre or it may insert in the thiophene double bond to form an azirine which can subsequently undergo further transformations. A third alternative is for the singlet to cross over to the triplet state and then undergo the reactions characteristic of this biradical species. 

It was also demonstrated that reaction of 6 with ethanol leads cleanly to methyl M-phenylcarbamate and tribntyltin ethoxide (Fignre 6.2.6). There is no report of any cross-over products. Others have argued that mixed carboxylate/alkoxides such as 7 are the active species, but it was admitted that the carboxylate had a higher affinity for tin than alkoxide and thus formation of the critical first catalytic intermediate in the process is not favorable. Indeed, NMR was used to measure an equilibrium constant of 8.3 x 10 for exchange of 2-propanol into di-n-butyltin dilaurate (DBTDL) (Ki of Figure 6.2.7). But at the extremely high hydroxyl/catalyst ratios observed in real systems, this can result in a significant conversion of the catalyst to the first intermediate proposed in the insertion mechanism. 

It was obvious that what was needed was detailed knowledge, at the nucleotide level, of the sequences involved in the excision of petite genomes. The simplest interpretation of the sequence data was that excision was clue to a crossing-over process, and that the primary event in the spontaneous petite mutation was very similar to the excision of the lambda prophage from the E.coli chromosome, or to (he dissociation of a bacterial transposon from its host plasmid in this case, the GC clusters and sequences in the AT spacers play the same role as the insertion sequences delimiting a bacterial transposon. 

Other reports were more fortuitous, as in the unexpected formation of 565 (Scheme 55) upon alkylation of Bp Rh(CO)(py) (566,) with methyl iodide. The mechanism for this was established to be intramolecular (from cross-over experiments with and H-labelled 566), and proposed to proceed by oxidative addition of Mel, with subsequent migratory insertion of CO. The nature of the hydride migration process from boron remains to be determined. On prolonged heating (45 °C), 565 evolves into 567 a rare example of reverse a-hydride migration from metal to carbene. 

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