Tetrakis(dimethylamino)ethylene (TDAE)-Pd promoted reductive homo-coupling of aryl halides

Article abstract of DOI:10.1055/s-2002-22719

A combination of tetrakis(dimethylamino)ethylene (TDAE) and palladium catalysts promoted reductive homo-coupling of aryl halides efficiently to afford the corresponding biaryls in good to quantitative yields. TDAE acted as a very mild reductant, and easily reducible functional groups, such as a nitro formyl, ester, or nitrile group, remained unchanged.

Full text of DOI:10.1055/s-2002-22719

6
37
LETTER
Tetrakis(dimethylamino)ethylene (TDAE)-Pd Promoted Reductive Homo-
coupling of Aryl Halides
R
M
eductive Homo-coup
a
ling of
A
ry
n
H
alides abu Kuroboshi, Yoko Waki, Hideo Tanaka*
Department of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima-naka 3-1-1, Okayama 700-8530, Japan
E-mail: tanaka95@cc.okayama-u.ac.jp
Received 1 February 2002
the reductive homo-coupling of aryl halides under mild
Abstract: A combination of tetrakis(dimethylamino)ethylene
conditions, affording the corresponding biaryls
(
TDAE) and palladium catalysts promoted reductive homo-cou-
(
Figure 1). By use of this system, neither protonation to
pling of aryl halides efficiently to afford the corresponding biaryls
in good to quantitative yields. TDAE acted as a very mild reductant, give Ar-H nor reduction of other reducible functional
and easily reducible functional groups, such as a nitro, formyl, ester, groups such as a nitro, carbonyl, ester, or cyano group oc-
or nitrile group, remained unchanged.
curs at all.
Key words: reductive homo-coupling, palladium, aryl halides, bi-
aryls, organic reductant
Pd cat (5 mol%)
TDAE (200 mol%)
Me N NMe2
2
2
X
Me N NMe2
2
DMF, 50 °C
R
R
R
TDAE
Biaryl is an important class of compounds, and is widely
used as a core framework of liquid crystals, functionalized Figure 1
polymers, chiral ligands, etc. Reductive homo-coupling of
aryl halides (Ar-X) is a straightforward synthesis of biar-
yls. Ullmann coupling has been widely used, but usually
is performed under severe reaction conditions. Homo-
A typical procedure is as follows: a mixture of bromoben-
zene 1a (1.0 mmol), TDAE (2.0 mmol), and PdCl (Ph-
2
1
CN) (0.05 mmol) in DMF (5.0 mL) was heated at 50 °C
2
coupling by using excess amount of activated transition
for 4 hours. Usual work-up followed by recrystallization
afforded biphenyl 2a in almost quantitative yield
2
3
metals and transition metal complexes was reported. To
reduce the amount of expensive metal reagents such as a
(
Table 1, entry 1).
Proper choice of the Pd catalyst is essential for this reac-
tion (Table 1). PdCl (PhCN) , Pd(hfacac) (hfacac =
hexafluoroacetylacetonato), PdCl (MeCN) gave the bi-
transition metal complex, combined use of a transition4
metal catalyst and a cheap metal reductant, e.g., Al,
5
–7
8
2
2
2
Zn, and Mn has been investigated. However, these
metal reductants are not soluble in organic solvent, and re-
action sometimes starts only after a long induction period.
Moreover, they are usually so powerful that easily reduc-
ible functional groups, such as a nitro, carbonyl, ester, or
cyano group, could not survive. Organic reductants, such
as hydroquinone, amines, alkoxides, and formates, have
been used for regeneration of low-valent active metal re-
2
2
Table 1 Homo-coupling of Bromobenzene 1a with TDAE/Pd Cat-
alyst
Pd or Ni cat (5 mol%), TDAE (200 mol%)
2
Ph-Br
Ph-Ph
DMF, 50 °C
a
9
Entry
Pd or Ni Catalyst
PdCl (PhCN)
Yield (%)
agents. Electro-reductive homo-coupling of aryl halides
1
0
is also reported. However, protonated products (Ar-H)
were obtained as a major product from aryl halides having
an electron-withdrawing group, especially in the latter
case.
1
2
3
4
5
6
7
8
9
98
95
71
79
71
16
0
2
2
Pd(hfacac)2
PdCl (MeCN)
2
2
In previous papers,11 we reported a catalytic cross-cou-
pling of carbonyl compounds and alkenyl or allyl halides
can be promoted with a combination of tetrakis(dimethyl-
amino)ethylene (TDAE) and Ni/Cr catalysts. In these re-
actions, TDAE acts as a soluble and very mild organic
reductant, and the reaction proceeded very smoothly,
short reaction time and no appreciable induction period.
Herein, we describe a newly devised electron transfer sys-
tem, TDAE/Pd catalyst, which could efficiently promote
PdCl2
Pd(OAc)2
Pd (dba)
2
3
PdCl (PPh )
2
3 2
Pd(PPh3)4
0
PdCl (dppb)
0
2
1
0
1
NiBr2
0
Synlett 2002, No. 4, 29 03 2002. Article Identifier:
1
NiBr (PPh )
0
2
3 2
1
©
437-2096,E;2002,0,04,0637,0639,ftx,en;Y00902ST.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
a
Isolated yields after recrystallization.

6
38
M. Kuroboshi et al.
LETTER
phenyl 2a in good to excellent yields (entries 1–3). It is of
Table 2 Pd-TDAE Promoted Homo-coupling of Aryl Halides
interest to note that PdCl and Pd(OAc) also promoted
2
2
PdCl2(PhCN)2 (5 mol%)
TDAE, DMF, 50 °C
the homo-coupling reaction (entries 4, 5), suggesting that
TDAE might act as a ligand, and electron transfer from
TDAE to Pd may occur via this ligation. In contrast, phos-
phine ligands retarded this homo-coupling reaction; no
coupling reaction proceeded at all with PdCl (PPh ) ,
2
X
R
R
R
TDAE
TDAE
(60 mol%)
(200 mol%)
2
3 2
Substrate
Time Yield Time Yield
En-
try
Pd(PPh ) , and PdCl (dppb) (dppb = ((Ph P)CH CH ) ),
3
4
2
2
2
2 2
(%)a
(%)a
(
h)
(h)
and 1a was recovered quantitatively (entries 7–9). When
Pd is bonded with strongly electron-donating phosphine,
electron density of Pd might increase. Consequently, the
reduction potential of the palladium complex, Ar-
1
2
3
4
5
6
7
8
9
p-Me N-C H -Br
12
4
90
98
70
tr
12
4
81
92
2
6
4
p-MeO-C H -Br
6
4
Pd(II)(PR ) X, would shift to the more negative (Ar = Ph,
3
2
p-MeO-C H -I
5
6
4
1
0e
X = Br, R = Ph, E = –2.01 V vs. SCE) so that reduction
with a mild reductant TDAE might hardly occur.
p-MeO-C H -Cl
24
8
6
4
Combinations of Ni catalysts, such as NiBr2 and
p-Me-C H -Br
89
98
88
89
87
81
–b
4
83
6
4
NiBr (bpy), and TDAE did not promote the homo-cou-
2
C H -Br
4
6
5
pling at all, and most of 1a was recovered unchanged (en-
tries 10, 11).
p-HC(O)-C H -Br
2
3
3
3
3
4
2
90
94
90
79
98
83
6
4
The representative results of the TDAE/Pd catalyst-pro-
moted homo-coupling of several aryl halides are summa-
rized in Table 2. The biaryls were obtained successfully
from aryl bromides and iodide, but not from aryl chloride
p-NC-C H -Br
2
6
4
p-MeOC(O)-C H -Br
3
6
4
1
1
1
0
1
2
m,p-[MeOC(O)] C H -Br
3
2
6
3
(
entry 4). Aryl bromides bearing either an electron-donat-
p-O N-C H -Br
3
ing group (entries 1, 2, 5) or an electron-withdrawing
group (entries 7–11) gave the corresponding biaryls in
good yields. No detectable amounts of protonated by-
products (Ar-H) were obtained. It is worthy to note that
formyl (entry 7), cyano (entry 8), ester (entries 9, 10), and
nitro (entry 11) groups were not reduced under these reac-
tion conditions. Heteroaryl halide such as 2- and 4-bro-
mopyridine gave 2,2 - and 4,4 -bipyridine in 75% and
2
6
4
2-pyridine-Br
4-pyridine-Brc
3
75
52
13
6
a
Isolated yields.
b
A complex mixture of products including 4-amino-4 -nitrobiphenyl
was obtained.
c
HCl salt was used.
5
2% yield, respectively (entries 12 and 13), while 3-bro-
mopyridine did not give 3,3 -bipyridine at all. On the oth-
er hand, no reaction occurred with p-bromophenol (R = p-
-
1
II
Pd0
X
OH) and p-bromoaniline (R = p-NH ), presumably be-
X
Pd X
TDAE TDAE2+
2
R
R
R
cause of undesired interaction of these polar functional
groups with Pd. Further investigation revealed that 60
mol% of TDAE was enough to complete the homo-cou-
pling. Indeed, 60 mol% of TDAE gave 4,4 -dinitrobiphe-
nyl from 1-bromo-4-nitrobenzene in good yield, whereas
over-reduction occurred with 200 mol% of TDAE to give
a complex mixture of products including 4-amino-4 -ni-
trobiphenyl (entry 11).
Although the reaction mechanism is not clear at present,12
a plausible mechanism is shown in Figure 1. The Pd(II)
species is reduced with TDAE to generate a Pd(0) species.
Oxidative addition of aryl halide 1 to thus-generated Pd(0)
would afford arylpalladium(II) 3, which would be subse-
quently reduced with TDAE to give arylpalladium(0) spe-
cies 4. The second oxidative addition of 1 to 4 may
produce biarylpalladium(II) 5, which would give biaryl 2
through reductive elimination (Figure 2).
4
1
3
PdCl2(PhCN)2 Pd0
TDAE TDAE2+
R
1
PdII
5
R
R
Pd0
R
R
2
Figure 2
In this reaction, TDAE acts as a mild reductant, and can
promote homo-coupling of aryl halide smoothly without
producing protonated products (Ar-H) and reducing other
easily reducible functional groups. Proper choice of the
Pd catalyst is essential for the homo-coupling reaction: the
In conclusion, TDAE can promote reductive homo-cou- yield of the homo-coupling products decreased as
pling of aryl bromides and iodide in the presence of a Pd PdCl(PhCN) >Pd(hfacac) >PdCl >PdCl (MeCN) >Pd-
2
2
2
2
2
catalyst to afford the corresponding biaryls in good yields. (OAc) >Pd (dba) . Phosphine ligands retard the reaction.
2
2
3
Synlett 2002, No. 4, 637–639 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Reductive Homo-coupling of Aryl Halides
639
References
(9) (a) Pd-hydroquione: Hennings, D. D.; Iwama, T.; Rawal, V.
H. Org. Lett. 1999, 1, 1205. (b) Pd-amine: Luo, F.-T.;
Jeevanandam, A.; Basu, M. K. Tetrahedron Lett. 1998, 39,
(
(
1) Fanta, P. E. Synthesis 1974, 9.
2) (a) Activated Ni: Inaba, S.-I.; Matsumoto, H.; Rieke, R. D.
Tetrahedron Lett. 1982, 23, 4215. (b) Li-Naph:
Matsumoto, H.; Inaba, S.-I.; Rieke, R. D. J. Org. Chem.
7
939. (c) See also: Clark, F. R. S.; Norman, R. O. C.;
Thomas, C. B. J. Chem. Soc., Perkin Trans. 1 1975, 121.
d) Pd-HCO Na: Bamfield, P.; Quan, P. M. Synthesis 1978,
(
2
1983, 48, 840. (c) See also: Chao, C. S.; Cheng, C. H.;
537. (e) See also: Newkome, G. R.; Puckett, W. E.; Kiefer,
Chang, C. T. J. Org. Chem. 1983, 48, 4904;
electrochemical. (d) In: Ranu, B. C.; Dutta, P.; Sarkar, A.
Tetrahedron Lett. 1998, 39, 9557.
G. E.; Gupta, V. K.; Xia, Y.; Coreil, M.; Hackney, M. A. J.
Org. Chem. 1982, 47, 4116. (f) Ni-t-BuONa: Vanderesse,
R.; Lourak, M.; Fort, Y.; Caubere, P. Tetrahedron Lett.
1986, 27, 5483. (g) See also: Massicot, F.; Schneider, R.;
Fort, Y. J. Chem. Res., Synop. 1999, 664. (h) Pd-IPA:
Penalva, V.; Hassan, J.; Lavenot, L.; Gozzi, C.; Lemaire, M.
Tetrahedron Lett. 1998, 39, 2559. (i) See also: Hassan, J.;
Penalva, V.; Lavenot, L.; Gozzi, C.; Lemaire, M.
(
3) (a) Ni(PPh ) : Hart, D. J.; Hong, W.-P.; Hsu, L.-Y. J. Org.
3
4
Chem. 1987, 52, 4665. (b) Ni(PPh ) -NiCl (PPh ) /Zn/
3
3
2
3 2
PPh : Kende, A. S.; Liebeskind, L. S.; Braitsch, D. M.
3
Tetrahedron Lett. 1975, 3375. (c) Ni(COD) : Semelhack,
M. F.; Helquist, P. M.; Jones, L. D. J. Am. Chem. Soc. 1971,
2
93, 5908. (d) See also: Semmelhack, M. F.; Ryono, L. S. J.
Tetrahedron 1998, 54, 13793. (j) Pd-N H : Nakajima, R.;
2
4
Am. Chem. Soc. 1975, 97, 3873. (e) See also: Semmelhack,
M. F.; Helquist, P.; Jones, L. D.; Keller, L.; Mendelson, L.;
Ryono, L. S.; Smith, J. G.; Stauffer, R. D. J. Am. Chem. Soc.
Shintani, Y.; Hara, T. Bull. Chem. Soc. Jpn. 1980, 53, 1767.
10) (a) Gosmini, C.; Nedelec, J.-Y.; Périchon, J. Tetrahedron
Lett. 2000, 41, 201. (b) Courtois, V.; Barhdadi, R.; Condon,
S.; Troupel, M. Tetrahedron Lett. 1999, 40, 5993.
(
1981, 103, 6460. (f) Ni(OAc) /NaH/t-AmONa: Loubinoux,
2
B.; Vandersse, R.; Caubere, P. Tetrahedron Lett. 1977,
951.
(
c) Gosmini, C.; Lasry, S.; Nedelec, J.-Y.; Périchon, J.
3
Tetrahedron 1998, 54, 1289. (d) Courtois, V.; Barhdadi, R.;
Troupel, M.; Périshon, J. Tetrahedron 1997, 53, 11569.
(
(
4) Tanaka, H.; Sumida, S.-I.; Kobayashi, N.; Komatsu, N.;
Torii, S. Inorg. Chim. Acta 1994, 222, 323.
5) Zn-cat. Ni (NiX ): (a) Takagi, K.; Hayama, N.; Inokawa, S.
(e) Jutand, A.; Mosleh, A. J. Org. Chem. 1997, 62, 261.
2
(f) Amatore, C.; Jutand, A. Acta Chem. Scand. 1990, 44,
Tetrahedron Lett. 1979, 917. (b) Takagi, K.; Hayama, N.;
Sasaki, K. Bull. Chem. Soc. Jpn. 1980, 53, 3691.
7
2
55. (g) Amatore, C.; Jutand, A. Organometallics 1988, 7,
203. (h) Torii, S.; Tanaka, H.; Morisaki, K. Tetrahedron
(
c) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.;
Lett. 1985, 26, 1655. (i) Schiavon, G.; Bontempelli, G.;
Corain, B. J. Chem. Soc., Dalton Trans. 1981, 1074.
Montanucci, M. Synthesis 1984, 737. (d) Colon, I.; Kelsey,
D. R. J. Org. Chem. 1986, 51, 2627.
(
j) Mori, M.; Hashimoto, Y.; Ban, Y. Tetrahedron Lett.
(
(
(
6) NiCl (PPh ) : (a) Zenbayashi, M.; Tamao, K.; Yoshida, J.;
2
3
2
1980, 21, 631. (k) Troupel, M.; Rollin, Y.; Sibille, S.;
Fauvarque, J.-F.; Perichon, J. J. Chem. Res., Synop. 1980,
Kumada, M. Tetrahedron Lett. 1977, 4089. (b) Takagi, K.;
Hayama, N.; Sasaki, K. Bull. Chem. Soc. Jpn. 1984, 57,
26. (l) Jennings, P. W.; Pillsbury, D. G.; Hall, J. L.; Brice, V.
1887. (c) Percec, V.; Bae, J.-Y.; Zhao, M.; Hill, D. H. J. Org.
T. J. Org. Chem. 1976, 41, 719.
Chem. 1995, 60, 176.
(
(
11) (a) Kuroboshi, M.; Tanaka, M.; Kishimoto, S.; Goto, K.;
Mochizuki, M.; Tanaka, H. Tetrahedron Lett. 2000, 41, 81.
7) NiCl (PPh ) /TEAI: (a) Iyoda, M.; Sato, K.; Oda, M.
2
3 2
Tetrahedron Lett. 1985, 26, 3829. (b) Iyoda, M.; Otsuka,
H.; Sato, K.; Nisato, N.; Oda, M. Bull. Chem. Soc. Jpn. 1990,
(
b) Kuroboshi, M.; Goto, K.; Mochizuki, M.; Tanaka, H.
Synlett 1999, 1930.
63, 80. (c) Krische, B.; Hellberg, J.; Lilja, C. J. Chem. Soc.,
12) A tentative mechanism is proposed based on our previous
paper: Amatore, C.; Carre, E.; Jutand, A.; Tanaka, H.; Ren,
Q.; Torii, S. Chem.–Eur. J. 1996, 2, 957.
Chem. Commun. 1987, 1476.
8) Mn-cat. Ni/Cr: Chen, C. Synlett 2000, 1491.
Synlett 2002, No. 4, 637–639 ISSN 0936-5214 © Thieme Stuttgart · New York