Cheng-Yuan Liu1 | Taveechai Wititsuwannakul2 | Chu-Han Hsieh1,3 | Chung-Yu Tsai1,3 | Ting-Hsuan Wang1 | Ram Ambre1 | Wen-Ching Chen1 | Panida Surawatanawong2,4 | Tiow-Gan Ong1,5

1Institute of Chemistry, Academia Sinica, Nangang, Taipei, Taiwan, Republic of China
2Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol
University, Bangkok, Thailand
3Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan,
Republic of China
4Center of Sustainable Energy and Green Materials, Mahidol University, Salaya, Nakhon Pathom, Thailand
5The Department of Applied Chemistry, National Chiao-Tung University, Hsinchu, Taiwan, Republic of China

We report the alkylation and arylation cross-coupling of aryl ethers based on C–O bond
activation using a nickel catalyst and organoaluminum reagents. Ni(cod)2 in combination with
1,2-bis(dicyclohexylphosphino)ethane ligand in toluene solution at 130°C are the best conditions.
The naphthyl ether or methoxy pyridine derivatives are suitable substrates for alkylation and
arylation reaction with a wider scope of aluminum reagents in good yields. Computational
analysis on the pyridine substrate is provided to help delineate the mechanistic pathway and
demonstrate the important aspects of the cooperative interaction bimetallic catalysis. First, the
coordination of AlMe3 to the O atom of pyridine is essential for C–O activation. Second, the β-H
transfer from methoxy to pyridine could be discouraged through the use of bidentate phosphine
as a ligand. Finally, excess AlMe3 reagent is critical for facilitating a reductive elimination process.

Reference: Liu, C.-Y.; Wititsuwannakul, T.; Hsieh, C.-H.; Tsai, C.-Y.; Wang, T.-H.; Ambre, R.; Chen, W.-C.;
Surawatanawong, P.; Ong, T.-G. J. Chin. Chem. Soc. 2020, 67, 376-382.