Functionalization of C-H bonds

Recently, Francis etal. reported the selective modification of tryptophan indole side chains in several proteins with a diazo reagent catalyzed by dirhodium tetraacetate [44], and Ball etal. achieved remarkable rate accelerations for tryptophan modification ( 10 ) using dirhodium metallopeptides (Section 9.3.2) [45]. 

The synthesis of oxonium ylides by catalytic reactions of diazocarbonyl compounds with ethers has numerous applications in the preparation of natural products [127]. Two diastereomers of oxabicyclo[4.2.1]-nonane were obtained from ylide intermediates, which were produced from the 

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Although the activation and functionalization of C-H bonds of alkanes are the important, promising routes for synthesis of functionalized materials, it is difficult to achieve the functionalization of alkanes because they are unreactive due to the low reactivity of alkane C-H bonds. Carboxylation of alkanes to carboxylic acids is one of the interesting and important functionalization processes. 

In this review, the recent developments in catalytic functionalization of C-H bonds by iridium complexes will be emphasized. For more information on previous work and their details, there are excellent reviews published recently on C-H bond functionalization by transition metal complexes generally [1-9], as well as with an emphasis on iridium [11, 16]. 

Functionalization of C-H bonds by metal carbenoid or nitrenoid insertions represents a promising alternative to the more traditional approach of direct activation by a metal center. Carbenoids and nitrenoids show unusual regio- and stereoselectivity in insertions into C-H bonds, and unlike insertions of metal centers, these are intrinsically functionalizations rather than activations, which must be followed by functionalization (although in either case, loss of the functionalized group, to regenerate the active metal complex, is still required for catalysis) [129]. The use of dimeric Rh(n) complexes in this area has been extensively developed [129]. 

Extensive research over the past two decades on the catalytic functionalization of C-H bonds by complexes of iridium, as with other transition metals, has begun to pay significant dividends. Nevertheless, only a small fraction of the great potential offered by such chemistry has been realized, and there seems little doubt that progress will continue at a steady pace at least. 

Goldberg, K.I. and Goldman, A.S. (eds) (2004) Activation and Functionalization of C—H Bonds, AGS Symposium Series 885, American Chemical Society, Washington, DC. 

Functionalization of C—H bonds via aromatic substitution is an important means of adding functional groups to all kinds of arenes and as such is of significant relevance to many areas of chemistry. Notably, the key step in several industrially important reactions is an electrophilic attack on aromatic Jt-systems by carbocations or other strong electrophiles. 

The development of ruthenium complexes for other applications in radical chemistry is still in its infancy, but seems well suited to future expansion, thanks to the versatility of ruthenium as a catalytically active center. Large avenues have not been explored yet and remain open to research. For instance, the development of methodologies for the asymmetric functionalization of C-H bonds remains a challenge. The Kharasch-Sosnovsky reaction [51,52],in which the allylic carbon of an alkene is acyloxylated, its asymmetric counterpart, and the asymmetric version of the Kharasch reaction itself are practically terra incognita to ruthenium chemistry, and await the discovery of improved catalysts. 

Frauke Thrun, born in Hoyerswerda, Germany, has been studying chemistry at Technische Universitat Berlin since 2002 she joined the group of Timm Graening in 2007. She is currently working on the rhodium-catalyzed functionalization of C-H bonds for her diploma thesis. 

The selective activation and functionalization of C H bonds has attracted much attention in recent years. In spite of the common proposal, which postulates that NHC ligands coordinated to TM are relatively inert, several examples of C-H activation processes involving NHCs have been reported. Because of the high electron-donating property of NHCs, some TM NHC complexes have been found to undergo facile intramolecular C-H bond activation. 

During the past decade, several fundamental transformations of C-H bonds to other synthetically valuable bonds have been developed, and some basic applications of the catalytic functionalization of C-H bond to synthesis of polymers and the catalytic functionalization of natural products have been studied. During the next decade however, it is likely that fascinating developments will continue to be made in the direct use of C-H bonds in organic synthesis. 

The activation and functionalization of C-H bonds by the Pt" ion is particularly attractive because of the unusual regioselectivity, high oxidation level specificity, and mildness of reaction conditions. Moreover, Sen has recently reported that, in the presence of copper chloride at 120-160 °C, Shilov chemistry can be made catalytic with dioxygen as the ultimate oxidant [39]. A number of aliphatic acids were tested, and turnover numbers of up to 15/hour with respect to platinum were observed. H/D exchange studies also confirm the marked preference for the activation of primary C-H bonds in the presence of weaker secondary C-H bonds. This study constituted the first example of the direct use of dioxygen in the catalytic oxidation of unactivated primary C-H bonds under mild conditions that does not involve the use of a co-reductant (e. g., sacrificial metals, 2H + 2e", dihydrogen, or carbon monoxide see below). 

In 1989, Jordan reported Zr-catalyzed addition of the C-H bond in a-picoline to olefin [4]. Moore and coworkers found that Ru-catalyzed three component coupling of pyridine, carbon monoxide, and olefin took place, although the use of an excess amount of one component is required [5]. Subsequently, Murai and coworkers published highly efficient and selective functionalization of C-H bonds in aromatic ketones with olefins in the presence of a ruthenium catalyst [6],... 

In this chapter, we will survey the transition metal-catalyzed functionalizations of C-H bonds that were published up to the end of February 1998. Those catalytic reactions involving a step of electrophilic substitution by a metal ion, such as that of benzene with Pd(OAc)2, will not be dealt with. 

While it is difficult to design a catalytic procedure for the selective functionalization of C-H bonds, it is harder still to achieve catalytic functionalization of C-C bonds even though the C-C bonds are significantly weaker than C-H bonds. Two reasons are usually cited for the general lack of C-C activation compared to corresponding C-H activation by metals [ 12]. First, C-C bonds are ster-... 

The activation and functionalization of C-H bonds by the Pt(II) ion is particularly attractive because of the unusual regioselectivity, high oxidation level specificity, and the mildness of reaction conditions. Nevertheless, thus far it suffers from one crippling drawback dioxygen cannot be used efficiently as the reoxidant for the Pt° formed from Pt(II) during substrate oxidation [38]. 

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