Sp3 C—H bonds

Murahashi S-I, Nakae T, Terai H, Komiya N (2008) Ruthenium-catalyzed oxidative cyana-tion of tertiary amines with molecular oxygen or hydrogen peroxide and sodium cyanide sp3 C-H bond activation and carbon-carbon bond formation. J Am Chem Soc 130 11005-11012... 

Reaction of rhenium atoms with alkyl-substituted arenes forms dirhenium- l-arylidene compounds (2 2) (Figure 3). The products require insertion, presumably sequential, into two carbon-hydrogen bonds of the alkyl substituent. These reactions seem highly specific and require only the presence of an alkyl-substituted benzene that possesses a CH2 or CH3 substituent. Thus, co-condensation of rhenium atoms with ethylbenzene gives two isomers (see Figure 3) in which the products arise from insertion into the carbon-hydrogen bonds of the methylene or the methyl group. The product distribution in this reaction is in accord with statistical attack at all available sp3 C-H bonds. 

When aryl (sp2) and benzylic (sp3) C-H bonds are available, as in 2-(2-tolyl)pyridine, an Si-aryl bond is formed preferentially despite the higher dissociation energy for a C-H aryl bond compared with a benzylic C-H (110 vs. 90kcal mol 1). 

Alkylation of sp3 C-H bonds adjacent to a heteroatom such as nitrogen and oxygen is possible. The early works using tungsten or iridium complexes involved the reaction of dimethylamine with 1-pentene (Equation (29)) and the alkylation of a C-H bond adjacent to oxygen with / r/-butylethylene.34,34a,34b... 

The alkylation of the sp3 C-H bonds adjacent to a heteroatom becomes more practical when the chelation assistance exists in the reaction system. The ruthenium-catalyzed alkylation of the sp3, C-H bond occurs in the reaction of benzyl(3-methylpyridin-2-yl)amine with 1-hexene (Equation (30)).35 The coordination of the pyridine nitrogen to the ruthenium complex assists the C-H bond cleavage. The ruthenium-catalyzed alkylation is much improved by use of 2-propanol as a solvent 36 The reaction of 2-(2-pyrrolidyl)pyridine with ethene affords the double alkylation product (Equation (31)). 

Interestingly, the alkenylation of sp3 C-H bond is observed in the iridium-catalyzed coupling reaction of aldehydes, amines, and alkynes (Equation (56)).62... 

The intramolecular arylation of sp3 C-H bonds is observed in the reaction of l-/ r/-butyl-2-iodobenzene under palladium catalysis (Equation (71)) 94 94a 94b The oxidative addition of Arl to Pd(0) gives an ArPdl species, which undergoes the electrophilic substitution at the tert-butyl group to afford the palladacycle. To this palladacycle, another molecule of Arl oxidatively adds, giving the Pd(iv) complex. 

The carbonylation of the sp3 C-H bond adjacent to a nitrogen atom is also possible by means of chelation-assisted C-H bond activation.121 The carbonylation reaction of A-(2-pyridyl)pyrrolidine occurs at the a-position of the pyrrolidine ring by using [RhCl(cod)]2 as a catalyst and 2-propanol as a solvent. Cyclic amines exhibit a high reactivity (up to 84%) (Equation (93)), while acyclic amines show relatively low reactivity (18%). The use of Ru3(CO)i2 as a catalyst does not result in a carbonylation reaction, but instead the addition of the sp3 C-H bond across the olefin bond to give an alkylation product, as mentioned before (Section 10.05.4). 

The palladium-catalyzed reaction of benzol]quinoline in the presence of PhI(OAc)2 as an oxidant in MeCN gives an 11 1 mixture of 10-acetoxy- and 10-hydroxybenzo[ ]quinolines in 86% yield (Equation (98)).135 This chelation-directed oxidation can be extended to the benzylic C-H bond of 8-methylquinoline. The inactivated sp3 C-H bonds of oximes and pyridines undergo the same palladium-catalyzed oxidation with PhI(OAc)2 (Equation (99)).1... 

Moreover, sp3 C-H bond activation is one of the most significant subjects because aliphatic hydrocarbons including methane exist abundantly in nature. 

Molecular Activation. The strong reducing power of trivalent uranium enables interaction with both inert and less inert functions such as sp3 C—H bond, N2, and H20 displaying a variety of transformations and unusual bonding features. 

Given the very high reactivity of the trivalent state of U toward an exceedingly inert molecule, such as N2 or an even less reactive sp3 C—H bond, enhanced reactivity with water may be anticipated. This behavior has been elucidated by... 

Examples of oxidative coupling to vinyl derivatives remain limited in number, however, because the reaction takes a different course whenever allylic hydrogen atoms are present in a substrate (Scheme3, f andg). Under these conditions allylic sp3 C-H bonds are activated and such reactions are therefore allylic oxidations (SectionIV.1.2.4). In recent years, however, several examples of reactions of type g (Scheme 3) have been performed enantioselectively and called asymmetric... 

The sp3 C-H bond adjacent to oxygen in 2-alkoxypyridines undergoes selective oxidation in moderate yield in the presence of catalytic Pd(OAc)2 and stoichiometric amounts of PhI(OAc)2 in dichloromethane <2004JA9542>. Selectivity in this process arises from chelation of Pd(ll) to the pyridine nitrogen. 2-Methoxypyridine undergoes regioselective oxidation to acetal 109 in 66% yield on treatment with 5 mol% Pd(OAc)2 and 1.1 equiv of PhI(OAc)2 in dichloromethane at 100 °C (Equation 74) while -butoxypyridine is oxidized in 44% yield and isopropyloxypyridine is oxidized in 42% yield. 

More importantly, this silver system catalyzes the intermolecular amination of hydrocarbons, as shown in Table 6.3. In addition to animating weaker benzylic C-H bonds, stronger aliphatic C-H bonds such as those in cyclohexane were also reactive. Although yields with more inert hydrocarbons were modest with the bathophenan-throline system, the discovery of the first silver-catalyzed intermolecular amination opens opportunities for further developments. This reaction favored tertiary cyclic sp3 C-H bonds over secondary cyclic sp3 C-H bonds, and showed limited success with simple linear alkanes. No conversion was observed with any aromatic C-H bonds. The compound NsNH2 was tested as the nitrene precursor with different oxidants. The use of PhI(OAc)2 as oxidant gave the expected amination product with a lower yield, while persulfate and peroxides showed no reactivity. 

Catalytic C-C bond formation via sp- C-H bond cleavage represents the ultimate reaction in organic synthesis. A relatively ideal catalytic reaction system involves the use of sp3 C-H bonds adjacent to a heteroatom such as nitrogen and oxygen atoms. Recently, Jim et al. [69] succeeded in the Ru3(CO)12-catalyzed alkylation of an sp3 C-H bond a to the nitrogen atom in benzyl-(3-methyl-2-pyridinyl)amine by means of chelation assistance (Eq. 43). In this case, the coordination of the pyridine nitrogen to the ruthenium complex followed by C-H... 

Isomerization of Homoallyl Alcohols Through Activation of the sp3 C-H Bond... 

Chatani, N. et al. 2001. Ru3(CO)i2-catalyzed coupling reaction of sp3 C-H bonds adjacent to a nitrogen atom in aUcylamines with alkenes. Journal of the American Chemical Society, 123 10935 1. 

Of special interest is the behavior of 1-aza-zirconacyclopentene complexes which allows electrophilic sp, sp2, and sp3 C-H bond activations as well as M-H bond activations (M=N, O, P, S) and the preparation of the first C-metallated diazoalkanes LnMC(N2)R with an early transition metal. 

In place of carbon monoxide, isocyanides are often used as the isoelectronic compound. In 1986, Jones et al. reported that the low-valent ruthenium phosphine complex catalyzed intramolecular insertion of isocyanide into the sp3 C-H bond under thermal conditions (Eq. 33) [60,61 ]. Their finding provided a new route for synthesis of indole. An interesting feature of their reaction is that C-H bond cleavage occurs even in the presence of an excess of the trapping ligand, i.e., isocyanide. 

Ishikawa found the Ni(PEt3)4-catalyzed silylation of aromatic compounds with 3,4-benzo-1,1,2,2-tetraethyl-1,2-disilacyclobutene, providing the l-(di-ethylarylsilyl)-2-(diethylsilyl)benzene in high yields (Eq. 44) [89]. In the case of the reaction of mesitylene, interestingly, the sp3 C-H bond adds to the disilacy-clobutene, albeit in low yield (28% yield) [89]. Platinum(O) complexes are also applicable to this silylation reaction as the catalyst [90]. 

O/t/20-arylation of benzoic acids is often preferable to ortho-arylation of benzamides if conversion of the amide moiety to other functional groups is desired. However, only a few reports have dealt with the orf/io-functionalization of free benzoic acids due to challenges that involve such transformations. The reactions can be complicated by decarboxylation of the product and the starting material. Despite those difficulties, several methods for direct o/t/io-arylation of benzoic acids have been developed. Yu has shown that arylboronates are effective in arylation of benzoic acids under palladium catalysis [59], The reactions require the presence of palladium acetate catalyst, silver carbonate oxidant, and benzoquinone. Even more interestingly, the procedure is applicable to the arylation of unactivated sp3 C-H bonds in tertiary carboxylic acids such as pivalic acid (Scheme 13) if aryl iodide coupling partner is used. Aryl trifluoroborates can also be used [60],... 

Scheme 21 Auxiliary-assisted arylation of unactivated sp3 C-H bonds...

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