Hydrogen-carbon bonds unactivated

Startg. a-peracetoxynitrile irradiated 1 hr. with a 450 w. high-pressure Hanovia lamp in terf-butanol -> product. Y 56%. F. e., also in benzene, and reiterative functionalization of unactivated hydrogen-carbon bonds by repetition of the 2-step conversion, s. D. S. Watt, Am. Soc. 95, 271 (1976). 

The 20/1 y/5 ratio, when both carbons are unactivated methylenes, is also displayed by alkoxy radicals 75>. The slower 1,6-hydrogen transfer presumably reflects some of the strain in a 7-membered ring. It must also involve a more negative entropy. Rotations about three C—C bonds are frozen in the transition state, whereas only two C—C rotations need be frozen for y-hydrogen abstraction. 

Coverage in this chapter is restricted to the use of alkenes or alkynes as enophiles (equation 1 X = Y = C) and to the use of ene components in which a hydrogen is transferred. Coverage in Sections 1.2 and 1.3 is restricted to ene components in which all three heavy atoms are carbon (equation 1 Z = C). Thermal intramolecular ene reactions of enols (equation 1 Z = O) with unactivated alkenes are presented in Section 1.4. Metallo-ene reactions are covered in the following chapter. Use of carbonyl compounds as enophiles, which can be considered as a subset of the Prins reaction, is covered in depth in Volume 2, Chtqiter 2.1. Addition of enophiles to vinylsilanes and allylsilanes is covered in Volume 2, Chapter 2.2, while addition of enophiles to enol ethers is covered in Volume 2, Chapters 2.3-2.S. Addition of imines and iminium compounds to alkenes is presented in Volume 2, Part 4. Use of alkenes, aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.9. Coverage of singlet oxygen, azo, nitroso, S=N, S=0, Se=N or Se=0 enophiles are excluded since these reactions do not result in the formation of a carbon-carbon bond. 

The most important synthetic asset of the xanthate transfer methodology lies in its ability to induce carbon-carbon bond formation by intermolecular addition to unactivated olefins. Again, this is possible because the initial radical has a comparatively long lifetime in the medium. Unhindered, terminal olefins are the best substrates, but other types of olefins (especially strained or lacking allylic hydrogens) may be made to react in some cases. Three examples of additions are collected in Scheme 18. The first involves formation and capture of a trifluoroacetonyl radical, a species hitherto only studied by mass spectrometry but never employed in synthesis [34a]. This reaction represents a convenient route to various, otherwise inaccessible, trifluoromethyl ketones. In the second example a tetrazolylmethyl radical, also a previously unused intermediate, is intercepted by a latent allyl glycine [34b]. The amino acid moiety may be part of the xanthate partner as highlighted by the last example [34c]. 

Other Reductions. The (porphinato)irons could realize the reduction of alkenes and alkynes with NaBILj. Various unsaturated carbon-carbon bonds were saturated by meso-tetraphenylporphinatoiron chloride (TPPFe Cl) derivatives (up to 81% yield). Ruthenium(III) complexes also pair with NaBH in the reduction of unsaturated carbon-carbon bonds (as does cobalt boride). In the presence of a catalytic amount of Ru(PPh3)4H2 (0.5-1 mol %) and NaBHj, unsaturated carbon-carbon bonds in a wide variety of alkenes and alkynes were saturated in toluene at 100 Addition of water was required to provide a proton source. Similar systems with RUCI3 in aqueous solution reduce unsaturated bonds under milder conditions. Various unactivated mono- or disubstituted olefins and activated trisubstituted olefins were reduced with RUCI3 (10 mol %) and NaBH4 in THF-H2O at 0 °C to room temperature (eq 36). When the RuCl3-catalyzed reductions of olefins were carried out in aqueous amide solution, unactivated trisubstituted olefins were also hydrogenated. ... 

Barton devised this interesting photoinitiated method for functionalizing unactivated carbon-hydrogen bonds in response to a... 

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. 

Oxidative Functionalization of Unactivated Carbon Hydrogen Bonds in HCTD (22)... 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

DMD is suitable for the oxidation of most substrates with substances that are resistant to oxidation, however, the more reactive but also more expensive methyl (trifluoromethyl)dioxirane (TFD) is necessary. The oxidation is stereoselective for both dioxiranes and proceeds with complete retention of configuration at the oxidized carbon atom (Scheme 1) [20-22]. The reactivity follows the usual order of electrophilic oxidation-primary < secondary < tertiary < benzylic < allylic C-H bonds. Except for tertiary C-H bonds, which produce the oxidatively inert tertiary alcohols, further oxidation of the primary product (an alcohol) to a ketone or aldehyde (the latter is readily further oxidized to the corresponding acid) is possible, because the a-hydrogen of the alcohol is usually more reactive than that of the unactivated alkane, especially for allylic C-H bonds. 

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,... 

Hydroxylation of tertiary carbon atoms (6, 440 7, 271-273). The hydrogen succinates of alcohols bind strongly to silica gel. Unactivated tertiary C—H bonds in these bound substrates are oxidized efficiently with a solution of O3 in Ereon 11. This method is preferable to the oxygenation of acetates adsorbed on silica gel. Examples ... 

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]. 

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