Hydrogen from unactivated substrates

In the hydroxylation of unactivated C-H bonds in hydrocarbons by cytochromes P-450, a hydrogen atom is thought to be abstracted from the substrate C-H bond by a high-valent iron-oxo intermediate, forming a carbon radical which captures an hydroxyl radical from iron (Scheme 8) [27, 118, 119]. 

As shown in the manganese- and ruthenium-catalyzed intermolecular nitrene insertions, most of these results supposed the transfer of a nitrene group from iminoiodanes of formula PhI=NR to substrates that contain a somewhat activated carbon-hydrogen bond (Scheme 14). Allylic or benzylic C-H bonds, C-H bonds a to oxygen, and very recently, Q spz)-Y bonds of heterocycles have been the preferred reaction sites for the above catalytic systems, whereas very few examples of the tosylamidation of unactivated C-H bonds have been reported to date. 

Free radicals provide the only feasible means of aetivating eertain key C6C, C60 or C6N bonds in otherwise inert substrate moleeules this is aehieved by abstraction of a hydrogen atom from an unactivated carbon (Frey, 1990). The resulting unpaired electron leaves the earbon atom highly reaetive and amenable to various further reaetions. In the ease of AdoCbl,... 

Support for the bound free-radical hypothesis (i.e., Scheme 3) comes from a variety of sources and has been summarized in several comprehensive reviews [5, 6, 26-30]. Early evidence was obtained from electron spin resonance (ESR) [31] and ultraviolet (UV) [32] spectroscopic results. Additionally, labeling experiments provided evidence of hydrogen transfer between the substrate of a variety of Bi2-dependent enzymes and the coenzyme [33, 34]. Although objections have been raised to the hydrogen-transfer step [29] on the basis that the abstractions are proposed to take place at relatively unactivated positions, calculations of the thermodynamics of the hydrogen-transfer steps support this mechanistic proposal [21, 35]. 

On the other hand, the direct arylation of carbanionic species generated from substrates having relatively acidic hydrogens such as active methylene compounds and ketones can occur (mechanism B) [5,6]. Aryl halides are also capable of coupling directly with appropriately functionalized aromatic substrates and five-membered heteroaromatic compounds as formal carbon nucleophiles via cleavage of their unactivated C-H bonds [5,7-9]. The Fujiwra-Moritani reaction, which is the arylation of alkenes with arenes, is also useful for preparing arylalkenes without employing any halides (mechanism D) [10,11]. 

The most extensive studies we have done in geometrically directed functionalizations have involved the template directed chlorination of unactivated C-H bonds. These have been reviewed in detail [6], so only a few examples will be mentioned. The first system examined [7] involved attachment of an iodoaryl group to a steroid substrate, conversion of the iodine atom to an ICI2 group, and free radical chain chlorination. After initiation of the chain a radical was produced carrying a single chlorine on the iodine atom this chlorine then removed a hydrogen atom from the attached substrate. 

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