氮杂环卡宾

N‑Heterocyclic Carbene-Palladium(II)-1-Methylimidazole Complex-Catalyzed Direct C−H Bond Arylation of(Benz)imidazoles with Aryl Chlorides

Zheng-Song Gu,†Wen-Xin Chen,†and Li-Xiong Shao*,†,‡

†College of Chemistry and Materials Engineering,Wenzhou University,Chashan University Town,Wenzhou,Zhejiang Province 325035,People’s Republic of China

‡College of Chemistry and Life Sciences,Zhejiang Normal University,Jinhua,Zhejiang Province321004,People’s Republic of China *Supporting Information

INTRODUCTION

C2-arylated(benz)imidazoles are frequently found in various pharmaceuticals,biologically active compounds and materials.1 Recently,the transition metal-catalyzed direct C−H bond arylation of(benz)imidazoles has been noticed as a potentially more efficient and convenient alternative for the straightfor-ward synthesis of such compounds.2However,during the past years,the scope of the arylating reagents is limited to the more active aryl iodides and bromides.3To the best of our knowledge,only very few examples on the palladium-catalyzed direct C2-arylation of(benz)imidazoles using aryl chlorides in the presence of phosphine ligands were reported to date, despite their lower cost and more easy availability.4Therefore, despite that some progress has been made in the direct C2-arylation of(benz)imidazoles,the research for efficient methods using the more applicable,while less active,aryl chlorides as the arylating reagents is still in great demand.5 Previously,we have reported that a well-defined N-heterocyclic carbene-Pd(II)-1-methylimidazole[NHC-Pd(II)-Im]complex 1can easily activate aryl chlorides in traditional C−C couplings such asα-arylation of carbonyl compounds,6Suzuki−Miyaura coupling,7Mizoroki−Heck reaction,8Hiyama reaction9and C−N coupling.10Furthermore,in a very recent communication,we found that NHC-Pd(II)-Im complex1can also efficiently catalyze the direct C−H bond arylation of(benzo)oxazoles using aryl chlorides as the arylating reagents.11These results thus prompted us to further investigate its application in activating aryl chlorides toward the direct C2-arylation of (benz)imidazoles.Herein,we report these results in detail.■RESULTS AND DISCUSSION

Initially,1-methylbenzimidazole2a(0.49mmol)was chosen as the model substrate for the reaction with chlorobenzene3a(2.0equiv)in the presence of NHC-Pd(II)-Im complex1(2.0mol

%)under various conditions.For example,in thefirst round, toluene/H2O(2.0mL/0.5equiv)was chosen as the solvents to evaluate the effect of bases.The best result was achieved using

KO t Bu as the base to give the desired product4a in89%yield (Table1,entry6),while in the presence of other bases such as

K2CO3,KOH,K3PO4·3H2O,LiO t Bu and NaO t Bu,almost no product could be detected(Table1,entries1−5).The replacement of solvents from toluene/H2O to THF/H2O and

dioxane/H2O resulted in product4a only being isolated in48 and40%yields,respectively(Table1,entries7and8).In addition,in the presence of other solvents such as DMSO/ H2O,DMF/H2O,CH3CN/H2O and DME/H2O,no desired product could be detected(Table1,entries9−12). Furthermore,after careful investigations,it was found that the amount of H2O dramatically affected the reaction.That is,the introduction of0.5equiv of H2O was found to be necessary for such transformation.For instance,only18%yield of product4a was obtained when dry toluene was used as the solvent(Table 1,entry13).When1.0equiv of H2O was added,a significantly higher yield(84%)was achieved(Table1,entry14).However, when the amount of H2O was increased to3.0equiv,the yield of4a drastically decreased to5%(Table1,entry15).These results thus encouraged us to further investigate the effect of H2O.

It is known that KO t Bu will be partially hydrolyzed to KOH

and HO t Bu under the above reaction conditions.Therefore, three more control experiments were carried out:(1)the combination of KO t Bu(1.5equiv),KOH(0.5equiv)and HO t Bu(0.5equiv)was introduced instead of KO t Bu(2.0

Received:May9,2014

Published:May28,2014

©2014American Chemical /10.1021/jo5010058|.Chem.2014,79,5806−5811