Metal-mediated direct C À C bond-forming reactions involving C À H bond cleavage are commonly of great interest in modern organic chemistry, because of their potential for providing an alternative to the conventional cross-coupling strategy with a stoichiometric amount of organometallic reagents and transformation of ubiquitous C À H bonds into diverse functions in a single synthetic operation.[1] In particular, various catalytic systems for the direct arylation, [2] alkenylation, [3] and alkynylation [4] of arenes and heteroarenes with the corresponding organic halides and pseudohalides have been widely explored. On the other hand, the direct alkylation reaction with alkyl halides has received less attention, probably due to its substantial difficulty in controlling undesired b-H elimination. Although recent efforts have enabled the use of activated alkylating reagents, such as benzylic electrophiles, [5] the reaction with unactivated alkyl halides, especially those possessing the b-hydrogen atoms, [6] thus, remains largely elusive.[7] Hoarau, [5c] Yu, [8] Wang, [9] and Daugulis [10] independently reported palladium-catalyzed alkylation processes, whereas Ackermann[11] also succeeded in a similar alkylation by using a ruthenium catalyst. However, most of them are restricted in substrate scope to arenes containing directing groups, and the alkyl donors are still limited to relatively reactive alkyl iodides and bromides. Here, we report effective palladium-and nickel-based catalysts for the direct alkylation of azole compounds. The present catalytic systems are composed of common catalyst precursors, and especially, the palladium-based system allows unactivated alkyl chlorides as well as bromides to serve as the promising alkyl sources. [12] Based on the literature for the successful cross-coupling reaction with alkyl electrophiles, [13] we began our study with a Pd/bulky phosphine catalyst system. Indeed, treatment of benzoxazole (1 a, 0.50 mmol) with 1-bromohexane (2 a, 0.60 mmol) in the presence of PdA C H T U N G T R E N N U N G (OAc) 2 (5 mol %), PCy 3 (Cy = cyclohexyl; 10 mol %), and LiO-tBu (1.5 mmol) in diglyme (3.0 mL) at 120 8C for 2 h provided the desired 2-hexylbenzoxazole (3 aa) albeit in 34 % yield (GC; Table 1, entry 1). With this interesting preliminary result in hand, we screened various monodentate bulky ligands involving [a] T.
