Halogen Bond-Activated Visible-Light-Mediated Regioselective C–H Arylation of 2-Phenylimidazo-[1,2-a]pyridines

Abstract

An efficient method for transition metal-free halogen bond-assisted regioselective C–H arylation of 2-phenylimidazo-[1,2-a]­pyridines under visible-light condition has been developed. The halogen bond between an aryl halide and base KO t Bu initiates an electron transfer process and generates an aryl radical, which catalyzes its coupling with 2-phenylimidazo-[1,2-a]­pyridines to give arylated products in good yield. Several control experiments, density functional theory calculations, and ultraviolet–visible analysis indicate the presence of a halogen bond between an aryl halide and KO t Bu. This methodology has been successfully utilized to synthesize antileishmanial agents.

Control of Selectivity in Homogeneous Catalysis through Noncovalent Interactions

“…According to the σ‐hole theory, [83] the strength of halogen bonding Ha⋅⋅⋅Nu in organic and coordination compounds typically increases in the order F≪Cl<Br<I, thus the iodine atom can act as the best halogen bond donor in noncovalent catalysis [84] . In fact, due to the low halogen bond donor ability of chlorine and bromine atoms at chlorobenzene and bromobenzene, respectively, they failed to provide the corresponding product of the reaction with 2‐(4‐substituted phenyl)imidazo[1,2‐ a ]pyridine, whereas 2‐(4‐substituted phenyl)‐3‐phenylimidazo [1,2‐ a ]pyridines in high yield (58 % −Cl, 70 % −H and 73 % −CH 3 ) were obtained by applying iodobenzene as a starting material in the regioselective C−H functionalization under visible light at room temperature (Scheme 7a) [85] . Several control and UV‐visible experiments as well as DFT calculations suggest the presence of a negative charge assisted halogen bond between iodo‐benzene and the t BuO − anion, which initiates the regioselective C−H activation reaction by generating the intermediate A (Scheme 7b) [85] .…”

“…[84] In fact, due to the low halogen bond donor ability of chlorine and bromine atoms at chlorobenzene and bromobenzene, respectively, they failed to provide the corresponding product of the reaction with 2-(4substituted phenyl)imidazo[1,2-a]pyridine, whereas 2-(4-substituted phenyl)-3-phenylimidazo [1,2-a]pyridines in high yield (58 % À Cl, 70 % À H and 73 % À CH 3 ) were obtained by applying iodobenzene as a starting material in the regioselective CÀ H functionalization under visible light at room temperature (Scheme 7a). [85] Several control and UV-visible experiments as Scheme 6. The bifunctional hydrogen bond donor-catalyzed reaction of (E)-N-benzylidenecyanamide with 3-(mesitylthio)-3-oxopropanoic acid (a); optimized transition states (b).…”

“…[85] Chemistry-A European Journal well as DFT calculations suggest the presence of a negative charge assisted halogen bond between iodo-benzene and the t BuO À anion, which initiates the regioselective CÀ H activation reaction by generating the intermediate A (Scheme 7b). [85] In contrast to organocatalysis, the use of halogen bonding in metal complex catalysis is very limited, whereas a cooperation of coordination bond with this type of weak interactions can also direct the stereoselective catalytic transformations. For example, the enantiopure (> 99 % ee) (R)-6-(iodomethyl)-6phenyltetrahydro-2H-pyran-2-one was isolated in quantitative yield ).…”

“… Halogen bond‐assisted regioselective C−H functionalization at 2‐(4‐substituted phenyl)imidazo[1,2‐ a ]pyridine [85] …”

Electrochemical C–H Arylation of Quinazolinone with Aryl Tetrafluoroborate Diazonium Salts in Aqueous Solution of Ionic Liquids

“…These strategies provide representative methods for the synthesis of 2-arylquinazolinone, but these methods require conditions such as a high temperature and long reaction time. With the development of synthesis methods, the direct C–H activated arylation has gradually become one of the favorable tools for effectively constructing various aryl substituted heterocyclic and fused ring compounds. − In 2015, Besson and his colleagues developed a region-specific C2–H arylation reaction of N-substituted quinazolin-4 (3 H )-one with various aryl or (hetero) aryl halides under microwave irradiation (Scheme c) . This method could synthesize 2-arylquinazolinone more efficiently in a shorter time, but expensive transition metals were used during the reaction process.…”