Palladium-Catalyzed 2-fold C–H Activation/C–C Coupling for C4-Arylation of Indoles Using Weak Chelation

Abstract

Palladium-catalyzed weak chelation-assisted regioselective C4-arylation of indoles has been accomplished using a readily available arene at moderate temperature. The C4-arylation, weak chelating benzoyl (Bz) directing group, cross-dehydrogenative coupling (CDC), broad substrate scope, and late-stage diversifications are the important practical features.

Synergic Palladium Catalysis for Aerobic Oxidative Coupling

“…[2][3][4][5][6] Molecular oxygen, quinones, stoichiometric amounts of metal salts and hyper-valent iodine have all been deployed for the re-oxidation of Pd catalysts in oxidative reactions. [7][8][9][10][11][12] The application of molecular oxygen as a terminal oxidant for the catalyst (that is, to re-oxidize transition metals that have re-oxidized Pd) represents an especially powerful tool for organic transformation. [13] A practical example is the Wacker oxidation, which provides an aldehyde from ethylene and water.…”

“…Oxidative reactions catalyzed by Pd generally utilize the Pd(ll)/Pd(0) cycle and incorporate a re‐oxidation step to reactivate the catalyst [2–6] . Molecular oxygen, quinones, stoichiometric amounts of metal salts and hyper‐valent iodine have all been deployed for the re‐oxidation of Pd catalysts in oxidative reactions [7–12] . The application of molecular oxygen as a terminal oxidant for the catalyst (that is, to re‐oxidize transition metals that have re‐oxidized Pd) represents an especially powerful tool for organic transformation [13] …”

Mechanistic Insights into Cobalt-Catalyzed Regioselective C4-Alkenylation of 3-Acetylindole: A Detailed Theoretical Study

“…26−29 The success of this strategy relies on the selective formation of a six-membered metallacycle including the C4 site. 30,31 However, this strategy is challenged by the possible formation of a thermodynamically more favorable fivemembered metallacycle at the C2 site. 25,29,32 Thus, to deliver exclusive C4 selectivity, readily tailored DGs and efficient TM catalysts are required to overcome the competing C2 metalation.…”

“…Encouragingly, installing a directing group (DG) at the C3 position of indoles could increase the activity of the proximal C4 site and hence lead to the desired C4–H functionalization. − The success of this strategy relies on the selective formation of a six-membered metallacycle including the C4 site. , However, this strategy is challenged by the possible formation of a thermodynamically more favorable five-membered metallacycle at the C2 site. ,, Thus, to deliver exclusive C4 selectivity, readily tailored DGs and efficient TM catalysts are required to overcome the competing C2 metalation. ,− Most of the DGs on the C3 site arise from the carbonyl-based groups, e.g., aldehyde, ketone, carboxyl, and acylamide. In general, C4 functionalization of indole could be achieved by the weak coordinating DGs, e.g., −CHO, −COCF 3 , and −CO t Bu, , while strong coordinating DGs, e.g., −CONHMe, −COMe, and −COPh, prefer C2-site reactions .…”

Expedient Ni-catalyzed C–H/C–H cross-dehydrogenative coupling of aryl amides with azoles

“…3 To surmount these shortcomings, the oxidative C–H/C–H cross-dehydrogenative coupling of (hetero)arenes has been realized by means of transition-metals, photoredox or electrochemical approaches. 4 However, the positional-selective functionalization remains an appealing yet a significant challenge owing to the omnipresence of C–H bonds in organic molecules. The implementation of the directing group (DG) strategy, 5,6 which consists of a coordinating site that directs the metal centre into the close proximity of a specific C–H bond and thereby facilitates the selective cleavage, has thus witnessed remarkable advancements in recent years and led to sought-after strategies for C–C bond formations using (hetero)arenes.…”