P a lla d iu m -Ca ta lyzed Ar yla tion of r,r-Disu bstitu ted Ar ylm eth a n ols
via Clea va ge of a C-C or a C-H Bon d To Give Bia r yls
Yoshito Terao, Hiroyuki Wakui, Michiyo Nomoto, Tetsuya Satoh, Masahiro Miura,* and
Masakatsu Nomura
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, J apan
miura@chem.eng.osaka-u.ac.jp
Received March 28, 2003
The palladium-catalyzed arylation of R,R-disubstituted arylmethanols with aryl halides proceeds
not only via C-H bond cleavage at the ortho-position, but also via cleavage of the sp2-sp3 C-C
bond with the liberation of ketones (â-carbon elimination) to give the corresponding biaryls. Both
reactions appear to occur through common arylpalladium(II) alcoholate intermediates. The results
of systematic studies with respect to which C-C or C-H bond is preferentially cleaved in the
arylation are reported. Among the important findings is the selective elimination of ortho-substituted
aryl groups even from aryl(diphenyl)methanols due to steric reasons. Thus, various biaryls having
ortho-substituents can be produced efficiently by treatment of the corresponding aryl(diphenyl or
dimethyl)methanols with aryl bromides and chlorides.
In tr od u ction
As an example of aryl-aryl coupling via C-H bond
cleavage, we reported that appropriately functionalized
aromatic substrates such as phenols5a,b and aromatic
ketones5c and amides5d,e efficiently undergo direct inter-
molecular ortho-arylation on treatment with aryl halides
in the presence of palladium catalysts, in which coordina-
tion of the functional groups to intermediary arylpalla-
dium(II) species is the key. In the course of our study on
the reaction, we also found another unique aryl-aryl
coupling via C-C bond cleavage. Thus, aromatic alcohols
such as R,R-disubstituted arylmethanols react with aryl
halides not only via the C-H bond cleavage, but also via
cleavage of the sp2-sp3 C-C bond with the liberation of
ketones to give biaryls (Scheme 1).6-8 The reaction of the
alcohols appears to be of importance in both mechanistic
and synthetic aspects. It proceeds via â-carbon elimina-
tion in competition with ortho-metalation. The catalytic
examples of â-carbon elimination in transition metal
alcoholates are very limited, although some efficient
Transition metal-catalyzed cross-coupling is now rec-
ognized to be one of the most useful C-C bond formation
reactions.1 For the synthesis of biaryls, whose skeletons
are found in a wide range of important compounds
including natural products and organic functional ma-
terials,2 palladium- or nickel-catalyzed coupling of aryl-
metals (metal ) Mg, Zn, B, Sn, Si, etc.) with aryl halides
via transmetalation is very often employed.
Meanwhile, transition metal-catalyzed organic reac-
tions via cleavage of C-H3,4d and C-C4 bonds have
attracted much attention from atom-economic and
chemoselective points of view, and various catalytic
processes involving different modes to activate the rela-
tively inert bonds have been developed, especially for the
past decade. Among the most promising activation strat-
egies is to utilize the proximate effect by coordination of
a functional group in a given substrate to the metal
center of a catalyst.
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10.1021/jo0344034 CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/22/2003
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J . Org. Chem. 2003, 68, 5236-5243