Mechanistic view of Ru-catalyzed C–H bond activation and functionalization: computational advances

Abstract

Ru-Catalyzed aromatic C-H bond activation and functionalization have emerged as important topics because they have resulted in remarkable progress in organic synthesis. Both experimental and theoretical studies of their mechanisms are important for the design of new synthetic methodologies. In this review, a mechanistic view of the Ru-mediated C-H bond cleavage step is first given to reveal the C-H bond activation modes, including oxidative addition, metathesis and base-assisted deprotonation. In this process, directing groups play an important role in determining the reactivity of the C-H bond. The C-H bond activation generally leads to the formation of a Ru-C bond, which is further functionalized in the subsequent steps. The mechanisms of Ru-catalyzed arylation, alkylation, and alkenylation of arenes are summarized, and these transformations can be categorized into cross-coupling with electrophiles or oxidative coupling with nucleophiles. In addition, the mechanism of ortho-ruthenation-enabled remote C-H bond functionalization is also discussed.

Ortho C–H arylation of arenes at room temperature using visible light ruthenium C–H activation

“…7 The two Rucatalyzed processes, meta-alkylation and ortho-arylation, operate through very different frameworks in the thermal regime, with the former thought to involve discrete 2 and 3 carbon-centered radicals adding to Ru(III) metallacycles (Scheme 1A), 8 and the latter involving more typical oxidative additions of aryl halides to a Ru(II) center. 9 The role of photoexcitation on a putative arylation process was thus interesting to examine in light of this dichotomy; as the photoreductive formation of highly reactive aryl radicals in analogy to Ru-meta alkylation chemistry was unlikely to be a signicant factor.…”

Recent Advances in C–H Bond Functionalization with Ruthenium-Based Catalysts

“…These reactions on ruthenium-catalysed C-H bond functionalization have been presented in numerous research papers and review articles by several groups [15,16,25,26,[38][39][40]. Furthermore, the mechanistic study of ruthenium-catalysed C-H bond functionalization was recently described by the research group of Lan [41] in the context of arylation, alkylation and alkenylation,and by Nelson and co-workers on selective ortho-arylation directed by Lewis basic groups [42]. However, new reactions and methodologies ofC-H bond functionalization with ruthenium-based catalysts are being discovered.…”

Conformationally Driven Ru(II)-Catalyzed Multiple ortho-C–H Bond Activation in Diphenylpyrazine Derivatives in Water: Where Is the Limit?

“…Heteroarylation via C-H bond activation has been largely applied to material science, for example, the synthesis of conjugated dyes [8] and polymers [9]. Although Pd [10][11][12][13][14] and Rh [15][16][17][18] catalysts are very efficient in enabling the selective functionalization of C-H bonds, the use of easy-to-prepare, air-stable, often stable in water and functional groups tolerant Ru(II) complexes have attracted much interest in the development of efficient catalytic systems for these processes [19][20][21][22][23][24][25][26]. Despite the ubiquity of C-H bonds in organic molecules, the regioselectivity of C-H bond functionalization can elegantly be controlled by chelation assistance of directing groups [27][28][29][30][31][32].…”