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barrier of the oxidative addition became much lower by the
coordination of Mg2+ to the phenolic species, as
demonstrated by our previous single crystal of 2-
NapOMgBr complex. The formed magnesium salts, such as
MgBr2 and MgO, could also increase the leaving ability of
Ar-OMgBr. The transmetalation step became energetically
favored by the interaction of magnesium ions with the
oxygen anion via six-membered (or fused 4,4-bicyclic)
transition state (TS) and the formation of magnesium salts
[10a]. The desired methylated product was obtained through
reductive elimination with the regeneration of Ni(0) species
to fulfill the catalytic cycle. During this process, the electron-
rich, bulky and stable ligand was required to improve the
abilities of the nickel catalyst at the oxidative addition and
reductive elimination steps.
In summary, we for the first time developed the nickel-catalyzed
methylation of arenols with methyl Grignard reagent under mild
conditions. This protocol was featured as good functional group
tolerance. The NHC ligand was also a good choice to the
extended π system, while the stable, electron-rich and bulky
phosphine ligand CMPhos was more robust in our protocol.
Benzyl alcohol and biphenols were also methylated with
CMPhos as a ligand. Further extension of substrate scope to the
alkylation of arenols and other alcohols is underway.Main Text
Paragraph.
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Experimental Section
General procedure for the methylation of arenols: To an oven-dried
schlenk tube with a stirring bar was added 1a (28.8 mg, 0.2 mmol) in the
air. The tube was removed to the glove box and then CMPhos (16.2 mg,
0.04 mmol, 20 mol%) and Ni(cod)2 (2.8 mg, 0.01 mmol, 5 mol%) were
added, followed by the sequential injections of toluene (1 mL) and
MeMgBr (0.2 mL, 3 equiv, 0.6 mmol). The tube was sealed by plastic
septa and moved out of the glove box. The mixture was stirred at 80 oC
for 12 h. Then the mixture was cooled to room temperature and directly
purified by column chromatography with hexane as the eluent to afford
1b as a white solid (24.2 mg, 85%).
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Acknowledgements
Support of this work by the “973” Project from the MOST
(2015CB856600 and 2013CB228102) and NSFC (Nos. 21332001
and 21431008) is gratefully acknowledged.
Keywords: arenol • methylation • nickel • catalysis • cross
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