Optimal Balance in the Catalyst Dynamics Enables C(2)−H Arylation of (Benz)imidazoles and (Benz)oxazoles by an In Situ‐Generated Ni/NHC System

Abstract

An efficient method for the C(2)−H arylation of (benz)imidazoles and (benz)oxazoles with aryl chlorides and aryl bromides under Ni/NHC catalysis has been developed. The main benefit of the method is the in situ generation of active Ni/NHC complexes from the air‐tolerant bench‐stable precursors NiCl2Py2, IMes⋅HCl, and potassium tert‐butoxide, which plays a dual role as base and Ni(II) to Ni(0) reductant. The approach represents a user‐friendly alternative for procedures relying on the use of toxic phosphine ligands or unstable air‐sensitive Ni(cod)2. The concept highlighted in the present study shows that mapping a competitive picture of catalyst dynamics and revealing the competitive processes towards the destruction and stabilization of catalytically active species enables a highly efficient catalytic system to be built under simple conditions.

A Simple Protocol for the C−N Cross‐Coupling of Aryl Chlorides with Amines Applying Ni/NHC Catalysis

“…In complex 4 e , the cyclopentadienyl anion promotes decomposition of the catalytic system in the presence of t BuONa accompanied by fast darkening of the reaction mixture. A similar effect of Cp ligands on Ni/NHC systems in the presence of strong bases such as sodium or potassium tert ‐butoxide was reported recently [16b,c] …”

“…The inapplicability of these nickel precursors correlates well with the low activity of complexes 4 d (entry 6) and 4 e (entry 7) containing the same acac and Cp ligands, which obviously provide inhibitory effects in the studied conditions. The deleterious effect of acac and Cp ligands was also reported recently for Ni/NHC catalytic systems in CH arylation reactions [16b,c] …”

“…Among the well‐defined complexes 4 a–e , only complex 4 c demonstrated good catalytic activity in the model reaction conducted in conditions very close to the conditions reported for CH‐arylation of heterocycles with aryl chlorides, [16c] except that t BuONa was used instead of t BuOK (Table 1, Entries 1–7, Table S1). Under catalysis with complex 4 c , the yield of 3 a increased from 42 % to 98 % with increasing reaction time from 1 h to 8 h (Table 1, Entries 3–5).…”

“…A cross‐coupling between chlorobenzene 1 a and aniline 2 a was selected as a model reaction for precatalyst evaluation (Scheme 1). We compared the activity of well‐defined Ni/NHC complexes 4 a–e , most of which were appreciably active in catalysis of some CH‐arylation and C−C cross‐coupling reactions of aryl chlorides, [16b,c,17] with the activity of catalytic systems generated in situ from various nickel(II) precursors and imidazolium NHC‐proligands 5 a–d (Scheme 1).…”

“…Remarkably, the yield of compound 3 a in the in situ‐ generated Ni/NHC system was higher than that in the system formed from the well‐defined precatalyst 4 c (Table 1, compare entries 3 and 10, entries 4 and 11). It should be mentioned that higher efficiency of in situ‐ generated Ni/NHC systems compared to systems formed from well‐defined (NHC) 2 NiCl 2 complexes containing the same NHC ligands was recently observed in the CH‐arylation of nitrogen heterocycles [16c] . This may be explained, proposedly, by higher rates of Ni(II) to Ni(0) reduction in in situ‐ generated systems than in similar systems containing more stable bis‐NHC nickel(II) complexes.…”