Direct carbon-hydrogen bond functionalizations

This chapter mainly treats transition metal-catalyzed direct functionalization of carbon-hydrogen bonds in organic compounds. This methodology is emphasized by focusing on important functionalizations for synthetic use. The contents reviewed here are as follows (i) alkylation of C-H bonds, (ii) alkenylation of C-H bonds, (iii) arylation of C-H bonds, (iv) carbonylation of C-H bonds, (v) hydroxylation and the related reactions, and (vi) other reactions and applications. 

Kalyani D, Sanford MS (2007) Chelate-Directed Oxidative Functionalization of Carbon-Hydrogen Bonds Synthetic Applications and Mechanistic Insights. 24 85-116 Kanno K, see Takahashi T (2005) 8 217-236... 

Direct use of the carbon-hydrogen bond in organic synthesis with the aid of the homogeneous transition metal complexes has been the subject of recent interest. This review surveys some of the recent advances in the field of the transition metal-catalyzed functionalization of carbon-hydrogen bonds. 

The direct functionalization of carbon-hydrogen bonds is becoming a powerful tool in modem organic synthesis. The installation of new functionality where none existed previously allows rapid introduction of complexity into simple molecules. Such methodology has the potential to revolutionize the field of chemical synthesis if certain key requirements are met. First of all, the transformations must be regi-oselective, since C-H bonds are ubiquitous in organic molecules. Second, they must be stereoselective to be useful in the context of complex molecule synthesis... 

Hydrogen is present on a carbon surface as chemisorbed water, as surface functionalities (e.g., carboxylic acids, phenolic groups, amines), or is bonded directly to carbon atoms as a part of aromatic or aliphatic structures. The carbon-hydrogen bond is very stable but breaks on heating at about 1273 K. Nevertheless, the complete desorption of hydrogen does not happen at temperatures below 1473 K. 

Hydrogen is present in almost all forms of carbons. It is present as chemisorbed water, as a part of the surface functionalities (ca carboxylic acids, phenolic groups, amines) and it is also directly bonded to carbon atoms. The carbon-hydrogen bond is even more stable than the carbon-oxygen it only breaks when carbons are outgassed near 1273 K. The complete desorption of hydrogen requires heat treatment of the carbon material above 1473 K. 

The activation of unreactive C-H bonds remains a challenge for synthetic organic chemists. Activation of such bonds provides the opportunity to functionalize relatively cheap and abundant hydrocarbons. The clear advantages of directly forming carbon-carbon bonds from carbon-hydrogen bonds have driven the development of a variety of reactions in this area. Chatani et al. have reported carbonylation of sp C-H bonds of secondary amines. In this reaction, various secondary amines were employed as substrates, and it was found that the presence of a pyridine ring adjacent to the amine group was essential for the carbonylation to proceed. 

The behavior of 3 toward ether or amines on the one hand and toward phosphines, carbon monoxide, and COD on the other (Scheme 2), can be qualitatively explained on the basis of the HSAB concept4 (58). The decomposition of 3 by ethers or amines is then seen as the displacement of the halide anion as a weak hard base from its acid-base complex (3). On the other hand, CO, PR3, and olefins are soft bases and do not decompose (3) instead, complexation to the nickel atom occurs. The behavior of complexes 3 and 4 toward different kinds of electron donors explains in part why they are highly active as catalysts for the oligomerization of olefins in contrast to the dimeric ir-allylnickel halides (1) which show low catalytic activity. One of the functions of the Lewis acid is to remove charge from the nickel, thereby increasing the affinity of the nickel atom for soft donors such as CO, PR3, etc., and for substrate olefin molecules. A second possibility, an increase in reactivity of the nickel-carbon and nickel-hydrogen bonds toward complexed olefins, has as yet found no direct experimental support. 

Accordingly, many reactions can be performed on the sidewalls of the CNTs, such as halogenation, hydrogenation, radical, electrophilic and nucleophilic additions, and so on [25, 37, 39, 42-44]. Exhaustively explored examples are the nitrene cycloaddition, the 1,3-dipolar cycloaddition reaction (with azomethinylides), radical additions using diazonium salts or radical addition of aromatic/phenyl primary amines. The aryl diazonium reduction can be performed by electrochemical means by forming a phenyl radical (by the extrusion of N2) that couples to a double bond [44]. Similarly, electrochemical oxidation of aromatic or aliphatic primary amines yields an amine radical that can be added to the double bond on the carbon surface. The direct covalent attachment of functional moieties to the sidewalls strongly enhances the solubility of the nanotubes in solvents and can also be tailored for different... 

Carboxypeptidase A"" (CPA, EC 3.4.17.1) is a proteolytic enzyme that cleaves C-terminal amino acid residues with hydrophobic side chains selectively. Several X-ray structures are available" The active site of CPA consists of a hydrophobic pocket (primary substrate recognition site) that is primarily responsible for the substrate specificity, a guanidinium moiety of Argl45 that forms hydrogen bonds to the carboxylate of the substrate, and Glu270, whose carboxylate plays a critical role, functioning either as a nucleophile to attack the scissUe carboxamide carbonyl carbon of the substrate or as a base to activate the zinc-bound water molecule, which in turn attacks the scissile peptide bond ". However, semiempirical calculations had shown that the direct attack of... 

The final molecule of this series is methane, the tetrahedral structure of which follows if a fourth unit positive charge is removed from the nucleus in the ammonia lone-pair direction. There are now four equivalent bonding orbitals, which may be represented approximately as linear combinations of carbon s-p hybrid and hydrogen Is functions. The transformation from molecular orbitals into equivalent orbitals or vice versa is exactly the same as for the neon atom. 

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