Directed hydroarylation mechanisms

The first example of direct enantioselective addition of a C—H bond to a ketone was reported by Shibata and co-workers in 2009 using the cationic Ir/ (S)-Hg-BINAP as the catalyst in the synthesis of a chiral 4-acetyl-3-hydroxy-3-methyl-2-oxindole with 72% ee. Recently, Yamamoto and co-workers developed a cationic Ir/(R,R)-Me-BIPAM catalyzed asymmetric intramolecular direct hydroarylation of a-keto amides 178 affording the chiral 3-substi-tuted 3-hydroxy-2-oxindoles 179 in high yields with complete regioselectivity and high enantioselectivity (84-98% ee). In their proposed reaction mechanism, the aryl iridium complex formed via C—H bond activation is coordinated with the two carbonyl groups of the amide (Scheme 5.65). 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

The hydroarylation of olefins is relatively uncommon in photochemistry, despite a high interest in this process which allows the formation of an aryl-carbon bond via the direct activation of an aromatic, with no need for leaving groups in both components of the reaction. The process follows a photo-EOCAS (Electrophile-Olefin Combination Aromatic Substitution) mechanism [32], and is initiated by a PET reaction between an electron-rich aromatic and an electron-poor olefin, as illustrated in Scheme 3.14. 

The competitive experiments and KIE reactions show that C-H bmid cleavage is a rate-determining step and leads to a SeAr-like metallation. A five-membered ruthenacycle intermediate was proposed via an ortho C-H deprotonation directed by the carbonyl group with ruthenium catalyst by analogy to the alkenylation mechanism (Scheme 16). Then alkyne insertion into the resulting Ru-C bond gave a seven-membered intermediate, and the hydroarylated product was produced by protonolysis of the Ru-C bond (Scheme 17) [163, 164]. 

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