Ruthenium(II)‐catalysed Functionalisation of CH Bonds via a Six‐membered Cyclometallate: Monoarylation of Aryl 2‐pyridyl Ketones

Abstract

Selective monoarylation of aryl 2-pyridyl ketones with a variety of arylbromides via arene sp 2 CÀH bond activation/functionalisation is achieved with a [RuCl 2 (p-cymene)] 2 / p-CF 3 C 6 H 4 CO 2 H catalytic system. The reaction via a 6-membered ruthenacycle is more difficult to perform than via a 5membered cyclometallate but the activation of only one ortho CÀH bond is unprecedentedly highly selective. A variety of functional 2-pyridine derivatives are easily obtained. It is shown via H/D exchange that the carboxylic acid favours the reversible CÀH bond activation.Catalytic CÀH bond activation has become an important method leading to various CÀC bond cross-coupling reactions. [1] Recently, non-expensive ruthenium(II) catalysts that are easy to prepare, often stable to air and water, have shown high efficiency for cross-coupling reactions from sp 2 CÀH bonds through arylation with (hetero)arylhalides or through oxidative dehydrogenative alkenylation. [2][3][4] The diarylation of ortho CÀH bonds of functional arenes has now become easy to perform with ruthenium(II) catalysts when the formation of a 5-membered ruthenacycle intermediate is possible (I in Scheme 1), [2,3,5] especially with carboxylate-ruthenium catalysts, [6, 7] even in water. [4, 8] The selective monoarylation versus diarylation of functional arenes containing two non-protected ortho sp 2 CÀH bonds, has been shown difficult to achieve via a 5-membered cyclometallate intermediate, [9] unless the [RuCl 2 (PPh 3 )(arene)] catalyst operating in water was used [10] (I in Scheme 1).Compounds containing the aryl 2-pyridyl ketone moiety have shown bioactivity, such as in grossularines [11] and nonplanar b-carboline-based analogues. [12] These unique properties of 2-pyridyl (hetero)aryl ketones and the potential of their derivatives as functional ligands motivate the search for selective aryl CÀH bond activation for further functionalisation, but via a 6-membered metallacycle (II, in Scheme 1). In comparison to 5-membered metallacycles, the activation of sp 2 CÀH bond by deprotonation via a 6-membered metallacycle intermediate is relatively scarce .[13] Such a metallacycle was easily obtained from phenyl 2-pyridyl ketone on reaction with [Cp*IrCl 2 ] 2[14] (II, M = IrClCp*, in Scheme 1). By contrast, the same aryl ketone on reaction with [RuCl 2 (p-cymene)] 2 /NaBPh 4 leads to the chelation of both N and O heteroatoms, thus favouring a 5-membered metallacycle but without CÀH bond activation/cleavage and formation of the 6-membered ruthenacycle. [15,16] Here we report the first selective catalytic ortho monoarylation of aryl 2-pyridyl ketones in the presence of ruthenium(II) catalyst, via a 6-membered ruthenacycle, with the association to a catalytic amount of a carboxylate derivative of p-CF 3 C 6 H 4 CO 2 H as a proton shuttle [Eq. (1)]The first attempt to perform the catalytic arylation of phenyl 2-pyridyl ketone 1 a with 2 equiv of PhBr with [RuCl 2 (pcymene)] 2 /4 KOAc catalyst system revealed that at 150 8C, NMP was the most efficient solvent with ...

Ligand‐Tuned C–H Bond Activation/Arylation of 2‐Arylpyridines over Pyridine‐Based N,O/N,N Ligated Ruthenium–Arene Complexes

“…In recent years, reactions that proceed through directed C–H bond activation have been illustrated by the formation of cyclometalated intermediates, an important intermediate of C–H bond‐activation reactions , . Along with a variety of transition metals, including palladium, iridium, and rhodium, which form cyclometalated species, ruthenium‐based complexes have also shown appreciable reactivity towards the formation of cyclometalated species . Moreover, ruthenium complexes offer excellent water solubility, which provides the opportunity for catalytic C–H bond activation/functionalization under environmentally benign conditions, using water as a solvent , , , …”

“…In particular, catalytic systems based on ruthenium–arene complexes for the C–H bond activation/functionalization of various heteroarenes have also been vastly explored, where the role of ligands has been found to be a crucial factor . For instance, Inoue et al have used bulky phosphines to tune the selectivity of monoarylated products during ortho arylation of heteroarenes.…”

Ruthenium‐Catalyzed C‐H Bond Activation/Arylation Accelerated by Biomass‐Derived Ligands

“…Notably, presence of the prominent mass peak at m/z 390 corresponding to the cyclometalated species [Ru‐B] under base free condition upon the treatment of [(η 6 ‐ p ‐cymene)RuCl 2 ] 2 with 2‐phenylpyridine (Ru: 1a = 1:5) in the presence of levulinic acid ( L1 ) at 80 °C, substantiate the crucial role of levulinic acid ( L1 ) in achieving high catalytic activity. Earlier reports also inferred the presence of analogous cyclometalated species [Ru‐B] as one of the key intermediate in several Ru(II) catalyzed C‐H bond activation reactions . Further to investigate the role of acetyl and carboxylate groups, we performed the catalytic reaction by replacing levulinic acid ( L1 ) with dicarbonyl compounds (2,5‐hexanedione ( L8 ) and 2,3‐butanedione ( L9 )) and aliphatic carboxylic acids (1‐butanoic acid ( L10 ), 1‐hexanoic acid ( L11 ), 1,6‐hexanedioic acid ( L12 )) (Scheme S1).…”

Real Sociedad Española de Química Prizes 2014

“…He has reported in ChemCatChem on ruthenium(II)-catalyzed formation of C À H bonds. [8] Dixneuf was also recently announced as the winner of the inaugural Prix Chine-France, which is awarded jointly by the Chinese and French Chemical Societies.…”

“…He has reported in Chem-CatChem on ruthenium(II)-catalyzed formation of C À H bonds. [8] Dixneuf was also recently announced as the winner of the inaugural Prix Chine-France, which is awarded jointly by the Chinese and French Chemical Societies. The Premios Jóvenes Investigadores are awarded to young researchers who are under the age of 40 and obtained their doctorate no more than 10 years ago.…”