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

Abstract

Water-soluble ruthenium(II)-arene complexes [(η 6arene)Ru(κ 2 -L)] n+ (n = 0, 1) ([Ru]-1-[Ru]-10) containing pyridine-based bischelating N,O/N,N donor ligands (L1-L5) are synthesized and employed for the catalytic C-H bond activation/ arylation of a wide range of 2-phenylpyridines and aryl halides in water, affording the corresponding mono-and biarylated products. Exploring the reactivity of the synthesized complexes, our investigations, including time-dependent 1 H NMR spectroscopic studies with ruthenium-arene catalysts, demonstrate a remarkable structure-activity relationship for the ligand-tuned C-H activation/arylation of 2-phenylpyridine, where the complexes with bischelating N,O donor-based ligands (acteylpyridine and picolinate) outperform those with N,N donor ligands [a] ditives, driven by steric bulkiness, in tuning the selectivity of C-H arylation products. [13] Later, we also explored aniline-based ruthenium-arene complexes for C-H bond arylation in water, where the strength of the aniline-ruthenium bond and substitution on the aniline ligand were found to be crucial factors for tuning the selectivity of mono-versus biarylated products during the reaction. [14] Further, in our deliberate efforts to develop an efficient catalytic system for C-H activation/functionalization reactions, [13,14] herein we have synthesized a series of ruthenium(II)-arene complexes containing pyridine-based N,O and N,N donor ligands, and we have systematically investigated their catalytic performance for ortho C-H bond activation/arylation of 2-phenylpyridine with several aryl halides in water. The synthesized ruthenium-arene complexes have been well-characterized using NMR spectroscopy and mass spectrometric analysis, and the molecular structure of a few of the representative complexes have been authenticated by single-crystal X-ray diffraction studies. Attempts have also been made to establish the relationship between the pattern of bonding of the ligands to the ruthenium metal center and the observed catalytic activity of these complexes for ortho C-H bond-activation/arylation reactions using time-scaled 1 H NMR spectroscopy. Results and Discussion Synthesis of Water-Soluble Ruthenium(II)-Arene Complexes [Ru]-1 to [Ru]-10Water-soluble ruthenium-arene complexes ([Ru]-1-[Ru]-10) containing pyridine-based N,O and N,N donor ligands were synthesized in good yield by reacting the respective ruthenium(II)arene dimer with the readily available ortho-substituted pyridine-based N,O/N,N donor bidentate ligands, with substituents ranging from carboxylic [pyridine-2-carboxylic acid (L1)], acetyl [2-acetylpyridine (L2)], ester [2-methylpicolinate (L3)], and imino groups [N-benzyl-pyridylimine (L4) and N-butyl-pyridylimine (L5)], as shown in Scheme 1. Scheme 1. Synthesis of ruthenium-arene complexes [Ru]-1-[Ru]-10 containing pyridine-based N,O and N,N donor ligands.

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

“…Further, it was also evident from the DFT calculations that the species 2A‐I having acetyl group in the close proximity of ortho proton of 2‐phenylpyridine was stable by 2.7 kcal/mol than the species 2A‐II having carboxylate group in that place. These results are in concurrence with earlier reports,, , suggesting that presumably the acetyl group was involved in the C‐H bond activation of 2‐phenylpyridine (Figure S5). Further, upon replacing the ligand L1 with 2,5‐hexanedione ( L8 ), free energy calculations revealed that the C‐H activation reaction was highly unfavorable in the presence of L8 (Δ G = 30.7 kcal/mol) (Table S2).…”

“…The above findings inferred that the facile coordination of the ligand L1 in a bidentate manner with the ruthenium center via acetyl and carboxylate‐O – groups, as also evidenced by the presence of levulinate coordinated arene‐Ru species ( [Ru]‐A ) (m/z = 351, [M] – Cl) during mass studies, is presumably responsible for the observed accelerated catalytic activity. In this context, previous studies also revealed that analogous bis‐chelating ligands may display coordination/de‐coordination behavior during the catalytic reaction and hence significantly tune the catalytic reactivity (Scheme S2) , , . It is also evident from the literature that the enhanced catalytic activity in Ru‐picolinate systems was due to the involvement of acetyl group in C‐H deprotonation, while remain coordinated with metal center with strongly coordinating pyridine …”

“…In this context, previous studies also revealed that analogous bis‐chelating ligands may display coordination/de‐coordination behavior during the catalytic reaction and hence significantly tune the catalytic reactivity (Scheme S2) , , . It is also evident from the literature that the enhanced catalytic activity in Ru‐picolinate systems was due to the involvement of acetyl group in C‐H deprotonation, while remain coordinated with metal center with strongly coordinating pyridine …”

“…These findings can be attributed to the strong coordination behavior of L7 with the Ru(II) metal center. Previous studies also demonstrated enhanced catalytic activity for C‐H bond arylation reaction over 2‐acetylpyridine ligated Ru(II) complex as compared to 2‐picolinate ligated Ru(II) complex . Notably, carboxylate additives, such as acetates and pivalates are well explored for the Ru(II) catalyzed C‐H bond activation reactions,, where these carboxylates facilitated the deprotonation of C‐H bond by coordinating with the Ru center.…”

“…Furthermore, accelerated Ru(II) catalyzed C‐H bond arylation has also been achieved in the presence of acetamide ligand where the pendent acyl group of Ru‐coordinated acetamide facilitated the deprotonation of C‐H bond . In a recent report, we have also explored several pyridine based bidentate ligands and observed that 2‐acetylpyridine ligand greatly enhanced the catalytic activity for C‐H bond arylation reaction . The observed ligand‐induced enhancement in the catalytic activity was attributed to the involvement of acetyl group in the deprotonation step due to its close proximity to the ortho C‐H bond of 2‐phenylpyridine (Scheme ).…”