Hydrogen atom abstraction reactions intramolecular

The success of such reactions depends on the intramolecular hydrogen transfer being faster than hydrogen atom abstraction from the stannane reagent. In the example shown, hydrogen transfer is favored by the thermodynamic driving force of radical stabilization, by the intramolecular nature of the hydrogen transfer, and by the steric effects of the central quaternary carbon. This substitution pattern often favors intramolecular reactions as a result of conformational effects. 

In this section we focus on intramolecular functionalization. Such reactions normally achieve selectivity on the basis of proximity of the reacting centers. In acyclic molecules, intramolecular functionalization normally involves hydrogen atom abstraction via a six-membered cyclic TS. The net result is introduction of functionality at the S-atom in relation to the radical site. 

The peroxyl radical of a hydrocarbon can attack the C—H bond of another hydrocarbon. In addition to this bimolecular abstraction, the reaction of intramolecular hydrogen atom abstraction is known when peroxyl radical attacks its own C—H bond to form as final product dihydroperoxide. This effect of intramolecular chain propagation was first observed by Rust in the 2,4-dimethylpentane oxidation experiments [130] ... 

The rate of this intramolecular isomerization depends on the chain length, with the maximum in the case of a six-atomic transition state, i.e., when the tertiary C—H bond is in the (3-position with respect to the peroxyl group [13]. For the values of rate constants of intramolecular attack on the tertiary and secondary C—H bond, see Table 2.9. The parameters of peroxyl radical reactivity in reactions of intra- and intermolecular hydrogen atom abstraction are compared and discussed in Chapter 6. 

Miwa GT, Walsh JS, Kedderis GL, et al. The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions. J Biol Chem 1983 258(23) 14445-14449. 

In contrast to the photo physical processes just described, photochemical processes produce new chemical species. Such processes can be characterized by the type of chemistry induced by light absorption photodissociation, intramolecular rearrangements, photoisomerization, photodimerization, hydrogen atom abstraction, and photosensitized reactions. 

Many of the limitations of C—C bond formation by C —H insertion outlined for intermolecular reactions (Section 1.2.1.) can be overcome by making the reaction intramolecular. Thus, hydrogen atom abstraction followed by intramolecular radical-radical coupling or radical addition to an alkene are increasingly popular processes. Two-electron carbene insertions, either thermal or transition metal catalyzed, have also been used extensively. In either case, ring construction involves net C—C bond formation at a previously unactivated C-H site. 

Photochemical C —H insertion of ketone 1 proceeds by initial photoexcitation to give an excited state that can be usefully considered as a 1,2-diradical. Intramolecular hydrogen atom abstraction then proceeds to give a 1,4- or 1,5-diradical, which can collapse to form the new bond. This approach has been used to construct both four- and ftve-membered rings12 11. Photochemical-ly mediated cyclobutanol formation is known as the Norrish Type II reaction. 

The restricted motion of molecules and of fragments such as free radicals formed by photodissociation results in interesting differences in the photochemistry of some molecules in solution or as guests in inclusion compounds. To take one example, the aliphatic ketone 5-nonanone can yield fragmentation or cyclization products via the biradical formed through intramolecular hydrogen atom abstraction (Figure 8.18). In the photolysis of the inclusion compound the cyclization is the preferred reaction, and there is a marked selectivity in favour of the ay-isomer of the cyclobutanol. 

Absolute rate constants for intramolecular reactions of amidyl radicals have been determined by ESR spectroscopy at low temperature and extrapolated to 27°C (82JA6071). The rate constants for intramolecular 1,5-hydrogen atom abstraction, kMs, from alkyl and acyl side chains are 1 x 105 and 4 x 104 s 1, respectively. If the C-5 hydrogen on the acyl... 

The major intermolecular reaction of triplet aryl nitrenes in solution is hydrogen atom abstaction to form primary amines. For a photoaffinity reagent bound to a receptor, this would result in a failure to couple. However, it is possible that the intramolecular photochemistry of aryl azides is more relevant, and here numerous examples of insertion by triplets have been noted. Presumably, these are two step processes hydrogen atom abstraction, followed by radical coupling (cf. Figs. 2.1 and 2.3). 

For these systems, direct hydrogen abstraction by benzophenone triplets was observed in benzene whereas in a polar solvent electron transfer and hydrogen-atom abstraction were observed. Electron transfer followed by an intramolecular proton transfer was observed in these systems although such proton-transfer reactions are not observed in unlinked systems of primary and secondary amines. The observed differences between the linked and unlinked systems have been attributed to the dependence of electron transfer, proton transfer, and hydrogen transfer on mutual distance and orientation. In the unlinked systems, rotational and translational motion of two reacting molecules are usually much faster than those in linked systems. 

To distinguish between paths A and B in Scheme 2, Dinnocenzo and coworkers [78-80] determined intramolecular isotope effects for deprotonation from the radical cations (path A) and for hydrogen-atom abstraction from a series of substituted 7V,A-dimethylanilines (path B) these were compared with isotope effects for N-demethylation of the same series of 7V,7V-dimethylanilines. The deprotonation iso-tope-effect profile for the radical cations of A, iV-dimethylanilines were determined by monitoring electron-transfer reactions from A, A -dimethylanilines to [Fe(phen)3] ... 

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