Nickel-catalyzed and Li-mediated regiospecific C–H arylation of benzothiophenes

Abstract

A sustainable nickel-catalyzed direct C–H arylation of benzothiophenes, benzofuran and selenophene is reported for the first time.

Heterogenization of a Molecular Ni Catalyst within a Porous Macroligand for the Direct C–H Arylation of Heteroarenes

“…We then explored the catalytic potential of Ni@BpyMP-1 for the direct C-H arylation of benzothiophene in the presence of lithium bis(trimethylsilyl)amide (LiHMDS) 27 in toluene (Scheme 3 and Table 2 entry 1 The 2-phenylbenzothiophene was obtained with 50% yield and 100% regioselectivity for the arylation of benzothiophene at the C2 position using 2.02wt%Ni@BpyMP-1 catalyst (2 mol% of Ni with respect to benzothiophene). As compared to the homogeneous system (Table 2, entry 2), 27 the heterogeneous catalyst 2.02wt%Ni@BpyMP-1 retains the high regioselectivity of the reaction, albeit with a slightly lower yield.…”

“…We then explored the catalytic potential of Ni@BpyMP-1 for the direct C-H arylation of benzothiophene in the presence of lithium bis(trimethylsilyl)amide (LiHMDS) 27 in toluene (Scheme 3 and Table 2 entry 1 The 2-phenylbenzothiophene was obtained with 50% yield and 100% regioselectivity for the arylation of benzothiophene at the C2 position using 2.02wt%Ni@BpyMP-1 catalyst (2 mol% of Ni with respect to benzothiophene). As compared to the homogeneous system (Table 2, entry 2), 27 the heterogeneous catalyst 2.02wt%Ni@BpyMP-1 retains the high regioselectivity of the reaction, albeit with a slightly lower yield. The heterogenization of the catalytic system within a porous polymer also allows a threefold decrease of the formation of the N-phenyl-bis(trimethylsilyl)amine (Ph-HMDS), side product from the reaction between iodobenzene and LiHMDS, compared to the homogeneous reaction (6% conversion of iodobenzene instead of 18%; see Supporting Information, Table S3 and section S5.3 for details).…”

“…Under homogeneous conditions, the reaction yield could be further enhanced by replacing toluene with ethereal solvents such as dioxane. 27 Unfortunately, almost no catalytic activity could be observed under heterogeneous conditions using ethereal solvents (Table 2, entries 4-7). The detrimental effect of dioxane as solvent is also evidenced in reaction performed in a mixture where the reaction yield drastically dropped from 50% in pure toluene to 25% and 5% when toluene contained 1 vol% and 10 vol% of dioxane, respectively (see Table S3).…”

Recent Developments in C−H Functionalisation of Benzofurans and Benzothiophenes

“…C−H arylation of benzofurans and benzothiophenes using earth‐abundant (transition) metal systems are less commonly reported, although there are a few recent examples. Canivet and co‐workers have developed the Ni‐catalysed and Li‐mediated arylation of benzothiophenes in the C2 position [12] . The reaction proceeds by coupling benzothiophenes with aryl iodides 135 using NiCl 2 (bpy) with LiHMDS in dioxane at 120 °C for 16 h (Scheme 38).…”

“…Benzofurans and benzothiophenes share some chemical properties, most notably their most acidic proton at C2‐position has a similar p K a (33 and 32 in THF respectively) [12] . The C3‐position of benzofuran is more nucleophilic than benzothiophene [13] .…”