Chelation-assistant strategy

A chelation-assisted strategy is another useful method for C—C bond cleavage. In this method, the substrates containing a coordinating functional group will first coordinate to a metal and form a stable metallacycle. A representative example of this strategy is the activation of the a-C—C bond to the carbonyl group in 8-quinolinyl alkyl... 

Keywords C-C bond activatiOTi Chelation-assistant strategy Cooperative catalysis Ketone Organic catalyst Retro-Mannich fragmentation Transition metal... 

Very recently, a new strategy for the hydroesterification and hydroamidation of olefins was reported by Chang and coworkers [83]. They used a chelation-assisted protocol for the hydroesterification of olefins. The reaction of 2-pyridylmethyl formate with 1-hexene in the presence of a Ru3(CO)12 catalyst gave the hydroesterification product in 98% yield as a mixture of linear and branched isomers (Eq. 54). The chain length of the methylene tether is important for a successful reaction. Thus, the reaction of 2-pyridyl formate (n=0) afforded 2-hydroxypyridine, a decarbonylation product, and the reaction of 2-pyridiylethyl formate (n=2) resulted in a low conversion (7% conversion) of the starting formate. From these results, the formation of a six-membered ruthenacycle intermediate is crucial for this chelation-assisted hydroesterification. 

Interestingly, none of the stereoselective reactions described previously assembles a new chiral center instead, the applied strategies rely on previously existing, special chiral characteristics of the substrates (prochiral moieties or fluxional axial chirahty). In contrast to these approaches, a recently published report relies solely on catalyst design to generate a new stereocenter in the product through chelate-assisted hydroarylation (Scheme 23.54) [166]. The most selective Rh catalyst 31 uses a biaryl-substituted Cp ring as the structural element to induce enantioselectivity. After the reaction, the hydroarylation product with a new quaternary stereocenter can be isolated in 87% yield and 91% ee. 

An example of a C-H bond activation process that employs this strategy is found in the pioneering work by Suggs et al. Specifically, Rh(I)-promoted activation of an a-C-C bond to ketone in 8-quinolinyl ketone 12 takes place via formation of a stable five-membered ring acylrhodium(III) complex (Scheme 3a) [18,19]. Examples of chelation-assisted C-C bond activation processes are foimd in reactions of the bidentate pincer-type compound 13 [20] (Scheme 3b) and ortho-a.cyl 2-phenyloxazole derivative 14 [21] (Scheme 3c). 

Jun et al. demonstrated a Rh(I)-catalyzed cyclization of an N-benzyl aromatic ketimine with diphenylacetylene to provide isoquinoline 44 [27]. The chelation-assisted C-H activation strategy was employed for the first time for isoquinoline synthesis. However, the reaction required a high temperature (150 C) and led to two different isoquinoline derivatives 44 and 44. Based on the experimental results, the authors proposed a plausible reaction mechanism that involved ortho-alkenylation, 6. r-electrocyclization, intermolecular nucleophilic substitution, and dehydrogenative aromatization (Eq. (5.43)). 

Despite the intrinsic difficulties mentioned above, a number of strategies have been devised to realize oxidative addition of C-C a-bonds. For example, release of ring strain of a substrate molecule affords both kinetic and thermodynamic drive for oxidative addition. A chelating effect also assists both kinetically and... 

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