Multiple roles of silver salts in palladium-catalyzed C–H activations

Is silver a mere terminal oxidant in palladium catalyzed C–H bond activation reactions?

“…30,31 Interestingly, the number of attempts on the use of pre-designed heterobimetallic homogeneous catalysts has been on a steady increase in recent years. [32][33][34][35] In such heterobimetallic systems, the intermetallic interaction is generally exploited for ne-tuning the catalytic attributes. However, the inuence of metal salt additives in the catalytic cycle through intermetallic interaction is seldom documented.…”

Pd(II)‐Catalyzed, Bidentate Directing Group‐aided Alkylation of sp3 γ‐C−H Bonds: Access to 3‐Alkylated Thiophene/Furan and Benzothiophene/Benzofuran Motifs

“…To commence with our investigations on the Pd(II)‐catalyzed, bidentate directing group‐aided alkylation of sp 3 γ ‐C−H bonds, initially we prepared 3‐methylthiophene‐2‐carboxamide 4 a from its corresponding carboxylic acid chloride and the bidentate directing group 8‐aminoquinoline. Table illustrates the optimization reactions comprising of the 8‐aminoquinoline‐aided alkylation of sp 3 γ ‐C−H bond of the substrate 4 a with alkyl iodides 5 a , b in the presence of various Pd catalysts, additives, silver/potassium salts (iodide ion scavengers) and solvents. At first, we heated a mixture of thiophene‐2‐carboxamide 4 a , alkyl iodide 5 a , Pd(OAc) 2 (20 mol%) and Ag 2 CO 3 in the absence of any other additive at 120 °C in t ‐AmylOH for 36 h. This reaction did not afford the expected sp 3 γ ‐C−H alkylated thiophene‐2‐carboxamide 6 a (entry 1, Table ).…”

“…Next, we heated a mixture of the substrate 4 a (1 equiv), 5 a (6 equiv), Pd(OAc) 2 (5 mol%), Ag 2 CO 3 and (BnO) 2 PO 2 H (20 mol%) at 120 °C in t ‐AmylOH for 36 h. This reaction yielded the expected sp 3 γ ‐C−H alkylated thiophene‐2‐carboxamide 6 a in 35% yield (entry 4, Table ). It is well‐documented that a silver or potassium salt function as an iodide ion scavenger in the Pd(II)‐catalyzed C−H arylation/alkylation reactions . Furthermore, it is to be noted that Chen's group has demonstrated the advantage of using catalytic amounts of (BnO) 2 PO 2 H as an additive when silver carbonate is used as an iodide ion scavenger in the Pd(II)‐catalyzed C−H arylation/alkylation reactions.…”

Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020

“…While a common role of silver(I) is generally proposed to be the abstraction of halide from the catalyst to ensure turnover of palladium, several other roles have also been proposed including, an activator for palladium, aiding transmetalation by the formation of silver aryl species and as a reoxidant in oxidative couplings. 90 In addition to these roles, Wang and Dang published a mechanistic investigation in 2019, detailing another crucial role of silver beyond simple halide abstraction (Scheme 32). 91 A combination of computational and experimental investigations of the γ-C(sp 3 )-H arylation of t-amylamine were performed.…”