Copper(II) NHC Catalyst for the Formation of Phenol from Arylboronic Acid

Abstract

Arylboronic acids are commonly used in modern organic chemistry to form new C–C and C–heteroatom bonds. These activated organic synthons show reactivity with heteroatoms in a range of substrates under ambient oxidative conditions. This broad reactivity has limited their use in protic, renewable solvents like water, ethanol, and methanol. Here, we report our efforts to study and optimize the activation of arylboronic acids by a copper(II) N-heterocyclic carbene (NHC) complex in aqueous solution and in a range of alcohols to generate phenol and aryl ethers, respectively. The optimized reactivity showcases the ability to make targeted C–O bonds, but also identifies conditions where water and alcohol activation could be limiting for C–C and C–heteroatom bond-forming reactions. This copper(II) complex shows strong reactivity toward arylboronic acid activation in aqueous medium at ambient temperature. The relationship between product formation and temperature and catalyst loading are described. Additionally, the effects of buffer, pH, base, and co-solvent are explored with respect to phenol and ether generation reactions. Characterization of the new copper(II) NCN-pincer complex by X-ray crystallography, HR-MS, cyclic voltammetry, FT-IR and UV-Vis spectral studies is reported.

Cu−NHC Complex for Chan‐Evans‐Lam Cross‐Coupling Reactions of N‐Heterocyclic Compounds and Arylboronic Acids

“…Throughout this manuscript this NCN‐coordinating NHC complex is generally described as Cu 2+ bPymBI, where it is applied to CEL reactions optimized in renewable solvents and under aerobic, mild conditions (Scheme 1C). This detailed catalytic study shows good reactivity toward imidazoles and a range of other amines [12,13] …”

“…Imidazole was initially reported as a sluggish substrate for arylation by Cu−NHC complexes [12,13] . Both tri‐ and tetradentate Cu−NHC complexes showed low yields for imidazole arylation using typical CEL reaction conditions [12] .…”

“…When these Cu 2+ salts (including Cu(OAc) 2 , CuCl 2 , and Cu(OTf) 2 ) were surveyed with the addition of 1 equivalent of Na 2 CO 3 , only Cu(OAc) 2 supported some conversion, showing that the counter anion plays an important role in the catalysis (entries 5–7). When 8.0 mol% Cu 2+ bPymBI was used to couple 2 a (0.5 mmol) with 1 a (0.25 mmol) in methanol at 70 °C for 24 h generated the N ‐arylated product 3 a in <7 % yields (Table1, entry 4) [12] . However, when 8.0 mol% Cu 2+ bPymBI was used to couple 2 a (0.5 mmol) with 1 a (0.25 mmol) in methanol with 1.0 eq of Na 2 CO 3 at 70 °C for 24 h generated the N ‐arylated product 3 a in 89 % yield.…”

“…Imidazole was initially reported as a sluggish substrate for arylation by CuÀ NHC complexes. [12,13] Both tri-and tetradentate CuÀ NHC complexes showed low yields for imidazole arylation using typical CEL reaction conditions. [12] Here report our efforts to optimize imidazole arylation by coupling 1 a and phenylboronic acid 2 a using a the Cu 2 + bPymBI complex.…”

“…This detailed catalytic study shows good reactivity toward imidazoles and a range of other amines. [12,13]…”