-
industrial-scale formation of these bonds. Recently, a grow-
ing number of papers have focused on the deliberate use of
additional ligands to facilitate copper-catalyzed N-arylation
of amines/amides, O-arylation of phenols, and S-arylation
1,1,1-tris(diphenylphosphanyl)ethane; X ) halide, thiophe-
nolate, phenylacetylide] are phosphorescent in solution and
1
1
in the solid state. It is suggested that the emission is
facilitated by the rigid tetrahedral structure, which is imposed
by the tripod ligand. Nevertheless, no further reports dealing
with these tripodal ligands in metal-catalyzed cross-coupling
reactions have been presented to date. Finally, Buchwald and
co-workers have highlighted that ethylene glycol can act as
an effective bidentate O-donor ligand in the copper-catalyzed
N- and S-arylation of aryl iodides with amines and thiols,
respectively. Notably, they also pointed out that amides
and anilines were poor substrates in their Cu-catalyzed
protocol. On the basis of these studies, we were prompted
to examine whether this tripodal ligand can be presented as
a new class of tridentate O-donor ligands suitable to be used
in copper-catalyzed cross-coupling reactions. Herein, we
report that this inexpensive and commercially available triol,
1,1,1-tris(hydroxymethyl)ethane, can be used as an efficient,
versatile, and novel tripod ligand in the copper-catalyzed
formation of C-N, C-O, and C-S bonds between aryl
iodides and amides, phenols, and thiols, respectively.
As a model study, we first chose to study the effect of
1,1,1-tris(hydroxymethyl)ethane as a tripod ligand on the
efficiency of the Cu(I)-catalyzed aryl amidation reaction of
iodobenzene with 2-pyrrolidone, and the results are sum-
marized in Table 1. When the reaction was performed with
6
of thiols. Among a variety of multidentate chelating ligands
used, neutral bidentate chelators appear to be in the majority
of the copper-catalyzed coupling reaction protocols. The
variety of donor combinations mostly includes N,N-, O,O-,
and N,O-chelators. Notably, only few examples have been
reported to demonstrate that the versatility of the same
ligands without any additional modification can be used in
three or more kinds of copper-catalyzed cross-coupling
reactions for the formation of aryl-heteroatom and/or aryl-
carbon bonds, such as neocuproine (2,9-dimethyl-1,10-
phenanthroline; a bidentate ligand with N,N-chelators for
1
2
7
Ar-N, Ar-O, and Ar-S bond formations), pyrrolidine-2-
phosphonic acid phenyl monoester (a bidentate ligand with
N,O-chelators for Ar-N, Ar-O, and Ar-P bond forma-
8
tions), and Chxn-Py-Al (a tetradentate ligand with N,N,N,N-
9
chelators for Ar-N, Ar-O, and Ar-C bond formations).
However, the high cost and/or the tedious preparation
procedure of the ligands used in these important protocols
are drawbacks. Hence, it is still essential to search other new,
less costly, and versatile ligands for this copper-catalyzed
protocol.
1,1,1-Tris(hydroxymethyl)ethane, an inexpensive and com-
mercially available tripod ligand, has been used in the
10
synthesis of some metal clusters for their magnetic studies.
Results show that this tripodal ligand can change the spin
ground states of the species due to the nature of its special
skeleton. On the other hand, an interesting study has been
Table 1. Cu(I)-Catalyzed Amidation of Iodobenzene with
I
reported that complexes of the type Cu (tripod)X [tripod )
(5) (a) Shakespeare, W. C. Tetrahedron Lett. 1999, 40, 2035. (b) Yin,
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2
428. For N-arylation, see: (d) Okano, K.; Tokuyama, H.; Fukuyama, H.
Org. Lett. 2003, 5, 4987. (e) Buck, E.; Song, Z. J.; Tschaen, D.; Dormer,
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(
7
i) Xie, Y. X.; Pi, S. F.; Wang, J.; Yin, D. L.; Li, J. H. J. Org. Chem. 2006,
1, 8324. (j) Yeh, V. S. C.; Wiedeman, P. E. Tetrahedron Lett. 2006, 47,
6
011. (k) Zhang, Z.; Mao, J.; Zhu, D.; Wu, F.; Chen, H.; Wan, B.
Tetrahedron 2006, 62, 4435. (l) Kantam, M. L.; Venkanna, G. T.; Sridhar,
C. H.; Kumar, K. B. S. Tetrahedron Lett. 2006, 47, 3897. For O-arylation,
see: (m) Marcoux, J. F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc.
a
Reaction conditions: PhI (1 mmol), Cu(I) (5 or 10 mol %), tripod ligand
1
997, 119, 10539. (n) Ma, D.; Cai, Q. Org. Lett. 2003, 5, 3799. (o) Fagan,
P. J.; Hauptman, E.; Shapiro, R.; Casalnuovo, A. J. Am. Chem. Soc. 2000,
22, 5043. (p) Cristau, H. J.; Cellier, P. P.; Hamada, S.; Spindler, J. F.;
(
(
1
5 or 10 mol %), 2-pyrrolidone (1.2 mmol), and base (2.03 mmol) in solvent
0.5 M) at 110 °C for 24 h. Isolated yield. c At 80 °C. d DMF/dioxane )
b
1
:9. e Using neopentyl alcohol as a monodentate ligand. Using neopentyl
f
Tailefer, M. Org. Lett. 2004, 6, 913. For S-arylation, see: (q) Deng, W.;
Zou, Y.; Wang, Y. F.; Liu, L.; Guo, Q. X. Synlett 2004, 1254. (r) Palomo,
C.; Oiarbide, M.; Lopez, R.; Gomez-Bengoa, E. Tetrahedron Lett. 2000,
glycol (2,2-dimethyl-1,3-propanediol) as a bidentate ligand.
4
1, 1283.
(7) (a) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001,
5
mol % of Cu(I) and 5 mol % of tripod ligand in the
3
2
, 4315. (b) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett.
002, 4, 2803.
(
presence of K PO as a base in toluene at 80 °C for 24 h,
the expected coupling product of 1-phenylpyrrolidin-2-one
3
4
8) Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Chem.-Eur. J. 2006,
2, 3636.
9) Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M. Chem.-
Eur. J. 2004, 10, 5607.
10) Rajaraman, G.; Murugesu, M.; Sanudo, E. C.; Soler, M.; Werns-
1
(
(11) Pawlowski, V.; Knor, G.; Lennartz, C.; Vogler, A. Eur. J. Inorg.
Chem. 2005, 3167.
(
dorfer, W.; Helliwell, M.; Muryn, C.; Raftery, J.; Teat, S. J.; Christou, G.;
Brechin, E. K. J. Am. Chem. Soc. 2004, 126, 15445.
(12) (a) Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4,
581. (b) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517.
5610
Org. Lett., Vol. 8, No. 24, 2006