Journal of the American Chemical Society
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ferent ratios of RMgX/R2Mg since the cross‐coupling reac‐
tions were conducted with an excess amount of a Grignard
reagent and the Schlenk equilibrium should be much faster
than the cross‐coupling reaction. For the same reason, the
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In summary, we have developed the first general method for
the alkylation of anisole derivatives via C‐O bond activa‐
tion.41 Although significant progress has been made in the
cross‐coupling using alkylmetal reagents,42 this method al‐
lows for the introduction of a variety of ‐hydrogen‐
containing alkyl groups directly to the ipso position of meth‐
oxyarenes. Given the prevalence of methoxyarene substruc‐
ture in biologically active compounds or ‐conjugated mate‐
rials, this method should serve as a useful protocol for their
derivatization. The markedly higher reactivity of RMgI than
RMgCl or RMgBr in this alkylative cross‐coupling calls for
special attention to the effect of the specific halide used
when developing catalytic reactions using Grignard reagents.
A theoretical study on the mechanism of this cross‐coupling
and further expansion of the scope of the nucleophiles in
methoxy cross‐coupling reactions are currently underway in
our laboratories.
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ASSOCIATED CONTENT
Supporting Information
Detailed experimental procedures and characterization of
new compounds are available free of charge via the Internet
AUTHOR INFORMATION
Corresponding Author
*E‐mail: tobisu@chem.eng.osaka‐u.ac.jp;
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was supported by a Grant‐in‐Aid for Scientific
Research from MEXT, Japan and ACT‐C from JST, Japan. We
also thank the Instrumental Analysis Center, Faculty of En‐
gineering, Osaka University, for their assistance with HRMS.
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