Direct C–H bond activation: palladium-on-carbon as a reusable heterogeneous catalyst for C-2 arylation of indoles with arylboronic acids

Abstract

We report a methodology for exclusive C-2 arylated indoles without the aid of any ligand or directing group in air.

Sustainable protocols for direct C–H bond arylation of (hetero)arenes

“…A more consistent investigation was reported only in 2020, when Bora and co-workers described the use of palladium-oncarbon in the C2 regioselective direct C-H arylation of functionalized N-methylindoles 31 with various aryl boronic acids: reactions were performed in MeOH at 50 °C for 7 h, using 5 mol% of Pd/C catalyst and 40 mol% of silver trifluoroacetate as the oxidant, affording the corresponding 2-aryl N-methylindoles 32 in yields ranging between 65 and 88% (Scheme 13). 47 Hot filtration test revealed residual Pd level (<0.01 ppm) in the filtrate, suggesting the heterogeneous nature of active catalyst species; moreover, Pd/C catalyst was recycled four times with only a little loss in reactivity, probably due to the physical loss of the catalyst rather than to metal leaching. Despite these invaluable advantages, it is worth emphasizing that the use of boronic acids as arylating agents involved here the production of boron salts as by-products, which could still contaminate the coupling products, although their removal is generally easier with respect to palladium.…”

“…Scheme 13 Pd/C catalysed, C2 regioselective oxidative direct C-H arylation of functionalized N-methylindoles 31 with various aryl boronic acids, developed in 2020 by Bora and co-workers. 47 Scheme 14 Regioselective direct C-H arylation of indole 33 catalysed by Pd/Met-SWCNT, developed in 2015 by Veisi and co-workers: 49 with aryl bromides/chlorides as arylating agents, 3-arylindoles 34 were obtained; with aryl iodides, N-arylated indoles 35 were isolated.…”

Heterogeneous Pd/C‐Catalyzed Ligand‐Free Direct C‐2 Functionalization of Indoles with Aryl Iodides

“…The use of the stoichiometric amount of silver salts essential for catalyst regeneration, suffers from high costs and raises environmental concerns [20] . Moreover, the use of transition metal catalysts in homogeneous form creates difficulties in the separation as well as recovery of the metal catalysts [3,10a,21] . On the contrary, heterogeneous catalysis provides an easy separation along with the possibility of catalyst reusability.…”

Transition-Metal-Free Borylation of Aryl Bromide Using a Simple Diboron Source

“…Arylboronic acids play an important role in organic reactions, including the Chan–Lam coupling, − the Petasis borono–Mannich reaction, and the Suzuki–Miyaura cross-coupling (SMC) reaction, , ipso -hydroxylation, ipso -nitration, o -arylation of oximes, and arylation of indoles . In addition, boronic acid is a valuable chemical in various research fields, such as molecular self-assembly, sensors, and medical chemistry .…”

“…A rylboronic acids play an important role in organic reactions, including the Chan−Lam coupling, 1−3 the Petasis borono−Mannich reaction, 4 and the Suzuki−Miyaura cross-coupling (SMC) reaction, 5,6 ipso-hydroxylation, 7 ipsonitration, 8 o-arylation of oximes, 9 and arylation of indoles. 10 In addition, boronic acid is a valuable chemical in various research fields, such as molecular self-assembly, 11 sensors, 12 and medical chemistry. 13 The classical method for the preparation of boronic acid involves the use of organomagnesium (RMgX) 14 or organolithium (RLi) 15 reagents with trialkyl borates at low temperatures (−78 °C for Li and −10 °C for Mg), followed by hydrolysis.…”