New Copper Ligand for Ullmann Reaction
TABLE 4. Coupling of Aryl Halides with Various
the conversion of all of the substrates to the correspond-
ing arylamines, and aryl bromides containing an electron-
withdrawing group on the benzene ring afforded better
results (entries 1, 8, and 10 in Table 4). However, the
coupling of 1-bromo-3-nitrobenzene with 2,6-dimethyla-
niline (entry 9 in Table 4) did not give satisfactory results
because of steric effects. Aryl iodides showed higher
reactivity than aryl bromides in the coupling reaction.
For example, the coupling of 1-bromo-4-iodobenzene with
a
Amines
4
′-aminoacetophenone or N-methylaniline (entries 12 and
3 in Table 4) yielded the target product 3k or 3l
1
containing bromine on the benzene ring.
Conclusions
A general and efficient protocol for amination of aryl
halides with aromatic amines or aliphatic amines has
been developed by using diphenyl pyrrolidine-2-phospho-
nate as the new ligand of CuI in the Ullmann reaction.
In comparison to other transition-metal catalyst systems,
such as palladium-catalyzed arylamination, this protocol
is simple and avoids the use of air-sensitive and expen-
sive catalysts or additives.
Experimental Section
General Procedure for the Preparation of Compounds
a-p. A flask was charged with CuI (40 mg, 0.2 mmol),
3
diphenyl pyrrolidine-2-phosphonate hydrochloride (136 mg, 0.4
mmol), and potassium phosphate (552 mg, 4 mmol), evacuated,
and backfilled with nitrogen at low temperature. Aryl halide
(
2 mmol for entries 1-11 and 14-17 in Table 4, 3 mmol for
entries 12 and 13) and amine (3 mmol), DMF (3 mL, containing
% H O (v/v)) were added to the flask under nitrogen. The flask
2
2
was immersed in an oil bath, and the reaction mixture was
stirred at the indicated temperature for the corresponding
reaction time shown in the tables. The reaction mixture was
cooled to room temperature, 10 mL of ethyl acetate was added,
the resulting suspension was filtered, the filtrate was concen-
trated, and the residue was purified by column chromatogra-
phy on silica gel (hexanes-EtOAc ) 20:1-8:1) to provide the
desired product. Characterization data of two representative
compounds are shown as follows:
a
Reaction conditions: CuI (0.2 mmol), ligand (0.4 mmol), K3PO4
2
8
(
4 mmol) in DMF (3 mL, with 2% water (v/v)) under N2; (1) aryl
Diphenylamine (3a): white solid; yield 57%; mp 52-53
28b 1
halide (2 mmol), amine (3 mmol) for entries 1-11 and 14-17; (2)
°C (lit. mp 54 °C); H NMR (CDCl
3
, 300 MHz) δ 7.24-7.29
b
aryl halide (3 mmol), amine (2 mmol) for entries 12-13. Isolated
(m, 4H), 7.08 (d, 4H, J ) 7.57 Hz), 6.93 (t, 2H, J ) 7.22 Hz);
1
3
yield.
C NMR (CDCl
3
, 75 MHz) δ 143.1, 129.4, 121.2, 118.0; HR-
EI-MS M m/z calcd for C12 11N 169.0891, found 169.0885.
N-Dodecylbenzenamine (3o): milk-white oil; yield 73%;
1
+
H
29
(
DPP), which showed that the addition of the ligand could
promote the Ullmann arylation of amines, and further
experiments showed that the catalyst system containing
0 mol % of CuI and 20 mol % of ligand, relative to
substrates, was the optimal choice.
Comparison of DPP with Other Ligands. The
cross-coupling of aniline and aryl bromide in DMF
containing 2% water (v/v) using 20 mol % of other
standard ligands, such as N,N′-tetramethylethyldiamine
and proline, were tested in the presence of 10 mol % of
CuI and 2 equiv of K PO , respectively, and we found that
the corresponding conversion ratios were lower than 60%,
which was equal to the result using DPP as the ligand.
3
H NMR (CDCl , 300 MHz) δ 7.18 (t, 2H, J ) 7.54 Hz), 6.70
(t, 1H, J ) 7.20 Hz), 6.62 (d, 2H, J ) 7.89 Hz), 3.11 (t, 2H, J
) 7.03 Hz), 1.67-1.65 (m, 2H), 1.29 (m, 18H), 0.91 (t, 3H, J )
1
3
1
3
6.00 Hz); C NMR (CDCl , 75 MHz) δ 148.7, 129.3, 117.2,
1
12.8, 44.1, 32.1, 29.71, 29.6, 29.5, 27.3, 22.8, 14.2; HR-EI-
+
MS M m/z calcd for C18H31N 261.2457, found 261.2452.
Acknowledgment. This work was supported by the
Excellent Dissertation Foundation of the Chinese Min-
istry of Education (No. 200222), the Excellent Young
Teacher Program of MOE, P. R. C., and the National
Natural Science Foundation of China (Grant No.
19
2
4
3
4
2
0472042).
Supporting Information Available: General experimen-
tal methods, preparation of the ligand, characterization data,
Scope of Substrates. The scope of the copper-
1
13
and H and C NMR spectra of the ligand and compounds
a-p. This material is available free of charge via the Internet
catalyzed aryl amination reaction was explored by using
3
1
0 mol % of CuI as the copper source, 20 mol % of DPP
at http://pubs.acs.org.
3 4
as the ligand, 2 equiv of K PO as the base, and DMF
JO051221W
containing 2% water (v/v) as the solvent. The coupling
reaction of aryl halides with various amines was carried
out using the catalyst system, and the desired amination
products were obtained in moderate to good yields. As
shown in Table 4, we found that the ligand could promote
(
28) (a) Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. J. Org.
Chem. 2004, 69, 6504. (b) Koichi, S.; Toshiharu, O.; Toshihiko, O. J.
Am. Chem. Soc. 1981, 103, 645.
(29) Bytschkov, I.; Doye, S. Eur. J. Org. Chem. 2001, 4411.
J. Org. Chem, Vol. 70, No. 20, 2005 8109