C-H Activation and Functionalization

A range of studies have now appeared modeling complete catalytic cycles based on an initial C-H bond activation and the subsequent functionalization steps. The functionalization processes involve reactions with an insertion partner (an alkyne, an alkene, or a carbene/nitrene source) and lead to the formation of new heterocychc rings or direct replacement of the C—H bond with a new C-R group. In many cases, the focus of the computational studies is on these functionalization processes as well as the reoxidation steps (particularly with internal oxidants). The C-H activation in these catalytic processes is typically of the intramolecular AML A-6 type, although exceptions do exist, as will be detailed later. Input from parallel experimental studies, including the determination of kfj/ko KIEs, the observation of H/D exchange, competition experiments, and the isolation of key intermediates both complement and provide benchmark data 

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Cyclization process of arene-yne substrates has been reported with platinum(rv) catalyst (PtCL ), resulting in C-H activation and functionalization.142 This hydroarylation gives 6-< r/o-products in high yields with good tolerance to different functional groups like amine, ester, and ether. This method provides a rapid access to interesting molecules such as coumarins, chromenes, or dihydroquinolines. 

As previously mentioned, one of the earliest discoveries of homogeneous C-H activation and functionalization of alkanes was discovered by Shilov. In his initial studies, Shilov reported that solutions of K2[PtCl4] in D2O/CH3CO2D could incorporate deuterium into alkanes, even methane. Subsequent to this, he reported that addition of H2[PtCl6] to the K2[PtCl4] reaction mixture resulted in the oxidation of methane and other alkanes to alcohols and alkyl chlorides. Significantly, the observed selectivity of 1° > 2° > 3° C -H bonds reflects what is reported in other systems. 

Abstract The Shilov system, a mixture of di- and tetravalent chloroplatinate salts in aqueous solution, provided the first indication of the potential of organotransition metal complexes for activating and functionalizing alkanes under mild conditions the participation of higher-valent species plays a crucial role. In this chapter, we discuss the experimental and computational studies that have led to detailed mechanistic understanding of C-H activation and functionalization by both the original Shilov system and the many subsequent modifications that have been developed, and assess the prospects for practical, selective catalytic oxidation of alkanes using this chemistry. 

Once a CO has been lost, there are two possible mechanisms for the alkyl group transfer to boron (see below, where Beat = the boryl ligand). One is a direct insertion of the metal into R-H (step 2), and the other is a cr bond metathesis (step 3). The first possibility would require a reductive elimination (see Section 12.2.3) to form the alkylboronate ester (step 4). Both pathways would re-associate a CO to give the final organometallic product (step 5). The authors prefer the direct C-H activation, but this has yet to be proven. In summary, C-H activation and functionalization is an elusive process, one that hopefully will have further breakthroughs in the near future. 

Simultaneous C-H activation and functionalization of hydrocarbons allows abundant, inert hydrocarbons to serve as direct feedstocks for functionahzed compounds [50]. The versatility of organoboron compounds in organic synthesis makes the borylation of hydrocarbons an attractive goal [20, 25-27]. 

Astruc, D. C—H Activation and Functionalization of Alkanes andArenes. In Organo-metallic Chemistry and Catalysis, Springer Berlin, Heidelberg 2007 pp 409-429. 

Replacing a halide or the leaving group in the electrophilic component of a crosscoupling reaction with C—H bonds can be a significant step to develop a green synthetic transformation. It avoids the need to pre-modify the substrate and consequently makes the reaction atom-economical. C—H activation and functionalization in sp -sp cross-coupling reactions has been demonstrated with various transition... 

Summary OF chapter 17 C-H ACTIVATION AND FUNCTIONALIZATION OF ALKANES AND ARENES... 

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