recently, by others that if the solubility of copper salts is
increased then the aryl coupling reactions tend to occur at
milder temperatures.7
with iodobenzene using 1 as a catalyst and KO-t-Bu as the
base in toluene at 110 °C was complete (by GC) in 3 h.
HoweVer, the same reaction was complete in 90 min when
2 was used as the catalyst. These reactions were slower when
the catalyst was replaced with 10 mol % Cu(PPh3)3Br/10
mol % 1,10-phenanthroline.12 We also found that the reaction
rates were much faster with KO-t-Bu, when compared with
NaO-t-Bu or Cs2CO3. Other bases such as K3PO4, K2CO3,
N-ethylmorpholine, CsF, NaOCH3, and NaH were not
effective. Using this protocol, we were able to couple
bromobenzene with diphenylamine to form triphenylamine
in 36 h. We were also able to couple chlorobenzene with
diphenylamine in moderate yields. The protocol was suc-
cessfully used to couple electron-rich aryl halides with
diphenylamine (Table 1). Furthermore, the reaction of
In 1987, Paine concluded through mechanistic investiga-
tions that the active catalytic species in Ullmann reactions
are the soluble cuprous ions.8 More recently, it has been
observed that certain additives can accelerate the rate of these
reactions.1b,6,9 Encouraged by these precedences, we initiated
a study of chemically well-defined, stable, and soluble
copper(I) complexes that can be systematically modified to
act as catalysts for the formation of aryl-carbon and aryl-
heteroatom bonds.10 On the basis of these studies, we now
report synthetic protocols for the formation of aryl-oxygen,
aryl-nitrogen, and aryl-acetylene bonds using copper-
phenanthroline complexes as catalysts. To our knowledge,
this is the first copper(I)-based catalytic system that can be
used for the formation of aryl-carbon and aryl-heteroatom
bonds from aryl halides under mild reactions and tolerant to
functional groups. These protocols can be considered as
alternatives to palladium and do not require the use of
expensive and/or air-sensitive phosphine ligands that are
often required in the palladium chemistry.
Table 1. Reactions of Aryl Halides with Diphenylamine with
10 mol% of 2
entry
R1
X
time (h)
yield (%)
1
2
3
4
5
6
H
H
H
o-CH3
p-CH3
o-CH3
I
6
36
36
6
6
36
78
73
49a
88
70
50a
Br
Cl
I
I
Br
Cu(phen)(PPh3)Br (1) and Cu(neocup)(PPh3)Br (2) were
prepared by the addition of 1,10-phenanthroline or neo-
cuproine to a solution of tris(triphenylphosphine) copper(I)
bromide in chloroform at room temperature.11 These com-
plexes are soluble in organic solvents such as dichloro-
methane, chloroform, toluene (warm), benzene, NMP, DMF,
and DMSO. However, they are insoluble in diethyl ether or
hexane. Unlike soluble copper(I) salts such as copper triflate,
1 and 2 are stable to air and ambient moisture.
a GC yields.
p-toluidine with 2 equiv of bromobenzene yielded the
corresponding triphenylamine in 70% yield (see the Sup-
porting Information). We are currently exploring the scope
of this reaction for the conversion of anilines to correspond-
ing di- and triphenylamines.
We then examined the efficacy of 2 to act as a catalyst
for the formation of diaryl ethers. We found that aryl
bromides can be coupled with phenols to form diaryl ethers
in good yields using 10 mol % of 2 as a catalyst and Cs2-
CO3 as a base in toluene at 110 °C (entries 7-10, Table 2).
This protocol tolerates base-sensitive functional groups such
as ketones (entry 8, Table 2). However, yields of diaryl ethers
are substantially lower for aryl bromides bearing ortho
substituents (entries 12 and 13, Table 2).
We first chose to examine the propensity of these
complexes to act as catalysts for the formation of aryl-
nitrogen bonds. We found that the reaction of diphenylamine
(7) (a) Weingarten, H. J. Am. Chem. Soc. 1964, 29, 3624-3626. (b)
Cohen, T.; Crostea, I. J. Am. Chem. Soc. 1976, 98, 748-753. (c)
Capdevielle, P.; Maumy, M. Tetrahedron Lett. 1993, 34, 1007-1010. (d)
Marcoux, J.-F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
10539-10540. (e) Zhang, S.; Zhang, D.; Liebeskind, L. S. J. Org. Chem.
1997, 62, 2312-2313. (f) Kalinin, A. V.; Bower, J. F.; Riebel, P.; Snieckus,
V. J. Org. Chem. 1999, 64, 2986-2987.
(8) Paine, A. J. J. Am. Chem. Soc. 1987, 109, 1496-1502.
(9) (a) Kiyomori, A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron Lett.
1999, 40, 2657-2660. (b) Klapars, A.; Antilla, J. C.; Huang, X.; Buchwald,
S. L. J. Am. Chem. Soc. 2001, 123, 7727-7729. (c) Ma, D.; Zhang, Y.;
Yao, J.; Wu, S.; Tao, F. J. Am. Chem. Soc. 1998, 120, 12459-12467. (d)
Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura, M. J. Org. Chem.
1993, 58, 4716-4721. (e) Lang, F. R.; Zewge, D.; Houpis, I. N.; Volante,
R. P. Tetrahedron Lett. 2001, 49, 3251-3254.
(10) For our previous work on the use of Cu(PPh3)3Br for the formation
of aryl-oxygen and aryl-nitrogen bonds, see: (a) Gujadhur, R.; Venka-
taraman, D.; Kintigh, J. T. Tetrahedron Lett. 2001, 42, 4791-4793. (b)
Gujadhur, R.; Venkataraman, D. Synth. Commun. 2001, 31, 139-153.
(11) See the Supporting Information for the synthesis of 1 and 2. For
the synthesis of Cu(PPh3)3Br, see ref 10a.
Both 1 and 2 can be used as catalysts for coupling of aryl
iodides with aryl acetylenes using K2CO3 as the base, in
toluene at 110 °C. However, in contrast to the formation of
aryl-nitrogen bonds, 1 was a much better catalyst than 2.
Using our protocol, we were able to couple electron-rich and
(12) In contrast to Goodbrand’s observation, we found that 2,2′-bipyridyl
can accelerate the rate of the reaction. The yields and rates of Cu(bipy)-
(PPh3)Br are similar to that of Cu(phen)(PPh3)Br. Detailed kinetic studies
are in progress and will be reported in due course.
4316
Org. Lett., Vol. 3, No. 26, 2001