Ru(II)-Catalyzed Synthesis of Fused Imidazo[1,2-a]pyridine-chromenones and Methylene-Tethered Bis-imidazo[1,2-a]pyridines and Regioselective O-Acetoxylation of Imidazo[1,2-a]pyridines

Abstract

Herein, we disclose an unprecedented protocol via ruthenium-catalyzed annulation for the synthesis of 6H-chromeno[4′,3′:4,5]imidazo[1,2-a]pyridin-6-one, and functionalized 2-(3-formylimidazo[1,2-a]pyridin-2-yl)phenyl acetate has been revealed by intramolecular chelation-assisted C–H activation. Additionally, a one-pot approach for creating bis(2-phenylimidazo[1,2-a]pyridin-3-yl)methane (BIP) has been realized through ruthenium catalysis with the use of formic acid. This method was used in gram-scale synthesis of BIP and step-economical late-stage functionalization of a marketed drug, zolimidine, in good yield.

DLPNO-CCSD(T) and DFT study of the acetate-assisted C–H activation of benzaldimine at [RuCl2(p-cymene)]2: the relevance of ligand exchange processes at ruthenium(ii) complexes in polar protic media

“…Second, the similarity between the activation energies calculated for the RDS and for the reversion of the C–H activation process in our model system compare well with (c) the reversibility of the C–H activation event previously reported for the ruthenium-catalyzed hydroarylation 7 e or deuteration 7 h of aromatic carbonyl compounds using imines as TDGs in apolar solvents and (d) with the results of deuterium exchange experiments reported for many other C–H bond ruthenations of arenes equipped with N -containing DGs in polar protic solvents such as water, methanol, acetic acid or HFIP. 51 Third, by using the Eyring equation, the activation barriers for the solvated reaction channels in the range of 22–24 kcal mol −1 allow the estimation of half-live times of 1–12 hours, which compare well with the reaction times of 5–20 hours reported for the cyclometallation of arylimines with the [Ru( p -cymene) 2 Cl 2 ] 2 complex in the presence of 4 equiv. of KOAc per ruthenium dimer complex at room temperature in methanol.…”

“…As the energy barrier for the forward reaction (29.0 [28.4] kcal mol −1 via TS(C 1 -D + ) ) is almost the same as the barrier required for the reversion of cyclometallation (from E to D + through cis -TS(D + -E + )2 , 29.5 [28.3] kcal mol −1 ), calculations show that the cyclometallation of benzaldimines in methanol should be reversible, as previously reported for ruthenium-catalyzed hydroarylation 7 e or deuteration 7 h of aromatic carbonyl compounds using imines as TDGs in apolar solvents and also in accordance with deuterium exchange experiments reported for many C–H bond ruthenations of related arenes equipped with N -containing DGs in polar protic solvents such as water, methanol, acetic acid or HFIP. 51…”

Synthesis and site selective C–H functionalization of imidazo-[1,2-a]pyridines

“…Our team have made a significant contribution to both the synthesis and C–H activation of IP chemistry. 15 In the continuation of our work on IP , we want to report herein the first review on the functionalization of IP at each carbon atom. In this review, work on the C–H functionalization of IP at C2 , C3 , C5 , C6 , C7 and C8 has been compiled.…”