Until now, various ligands have been disclosed such as
diamine derivatives,5 amino acids,6 N-hydroxyimides,7 phos-
phine oxides,8 imidazole derivatives,9 diketones or diphenols,10
and fluorapatite.11 Indeed, significant progress was achieved
through the use of the ligands mentioned above in the past years.
However, most catalyst systems enjoyed only narrow hetero-
cyclic substrates. Moreover, the high cost and availability (some
ligands were often prepared by multistep synthesis) limited their
applications to laboratory-scale reactions. Thus, it is necessary
to design a simple, efficient, and versatile ligand for these
coupling reactions.
1,2,3,4-Tetrahydro-8-hydroxyquinoline-Promoted
Copper-Catalyzed Coupling of Nitrogen
Nucleophiles and Aryl Bromides
Huifeng Wang, Yaming Li,* Fangfang Sun, Yang Feng,
Kun Jin, and Xiuna Wang
State Key Laboratory of Fine Chemicals, Dalian UniVersity
of Technology, Dalian 116012, China
In 1998, Ma reported an accelerating effect in the amination
of aryl halides induced by the structure of R-amino acid and
recently demonstrated that amino acids as ligands could promote
Ullmann aryl amination.12 Similarly, Buchwald reported that
ꢀ-amino ethanol itself could also assist in the arylation reaction
with aryl iodides.13 Soon after that, Twieg described that some
amino alcohols could serve as accelerating ligands for copper-
catalyzed amination.14 Recently, we found that 2-aminophenol
was a new type of self-accelerating chelate substrate, coupling
with iodobenzene to provide triarylamine under mild conditions
with 85% yield. However, the N-arylation of aniline with
iodobenzene hardly occurred under the same conditions (Scheme
1). Obviously, the 2-aminophenol accelerated the N-arylation
of iodobenzene and showed more reactive than aniline. This is
a unique example for the copper catalyzed single-step synthesis
of tribenzenamine derivative from amine without ligand addi-
tion.15 The applicability and selectivity between di- and triary-
lamine for this reaction are being studied in our laboratory. On
the other hand, inspired by the accerating effect of 2-aminophe-
nol, we anticipated that it might be a potential ligand for the
Ullmann copper-catalyzed reactions.
ReceiVed July 18, 2008
Based on the dramatic accelerating effect of 2-aminophenol,
three ligands derived from 2-aminophenol were developed.
Copper-catalyzed coupling reaction of nitrogen-containing
nucleophiles with aryl bromides was efficiently carried out
under mild conditions using 1,2,3,4-tetrahydro-8-hydrox-
yquinoline as a novel, simple, and versatile ligand.
(4) (a) Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M. Eur. J. Org.
Chem. 2004, 695. (b) Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M.
Chem.sEur. J. 2004, 10, 5607. (c) Taillefer, M.; Cristau, H. J.; Cellier, P. P.;
Spindler, J. F. WO 03/53225, 2003. (d) Taillefer, M.; Cristau, H. J.; Cellier,
P. P.; Spindler, J. F.; Ouali, A. WO 03/101966, 2003.
N-Arylazoles and N-arylamines are important compounds
widely employed in the biochemical, pharmaceutical, and
material fields.1 One traditional method for their synthesis is
the Ullmann-type coupling reaction of nitrogen nucleophiles
with relatively available aryl halides. However, the well-known
reaction generally suffers from several shortcomings such as
high reaction temperature, the use of stoichiometric amounts
of copper reagents, moderate yield, and poor substrate generality,
which restrict its industrial applications.2 Interestingly, copper-
catalyzed Ullmann amination reactions can be considerably
accelerated by some organic ligands. The original reports based
on diamine- and imine-type ligands for arylation of imidazoles
by Buchwald and Taillefer generated great interest in exploiting
a more effective procedure for copper-catalyzed coupling
reactions.3,4
(5) (a) Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J. Org.
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Chem. 2007, 72, 6190.
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Kumar, K. B. S.; Srinivas, P.; Balasubrahmanyam, V.; Venkanna, G. T. J. Mol.
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2006, 12, 3636.
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Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863. (c) Nandurkar, N. S.; Bhanushali,
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M. L.; Venkanna, G. T.; Sreedhar, B. J. Am. Chem. Soc. 2005, 127, 9948.
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10.1021/jo8015488 CCC: $40.75
Published on Web 10/09/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8639–8642 8639