examples, Larock and co-workers recently reported that
involving the Suzuki-Miyaura coupling with organoboron
reagents in the termination step.4a We also demonstrated that
two molecules of alkynes can be inserted between aryl
halides and arylboronic acids to produce the corresponding
1:2:1 coupling products, 1,4-diaryl-1,3-butadienes, when
using a suitable base such as silver carbonate.6
During the course of our further study of the catalytic
arylation of alkynes,6,7 we observed that the 1:1:1 coupling
of aryl halides, diarylacetylenes, and monosubstituted alkenes
can take place selectively under palladium catalysis by
employing appropriate conditions. This is a novel example
for the above intermolecular three-component coupling
involving the Mizoroki-Heck reaction with alkenes in the
termination.8
In an initial attempt, 4-iodotoluene (1a) was treated with
diphenylacetylene (2a) (1 equiv) and butyl acrylate (3a) (1
equiv) under conditions similar to those employed for the
reaction of 1a with 2a and arylboronic acids.6 In the presence
of Pd(OAc)2 (5 mol %) and Ag2CO3 (1 equiv) in 1-propanol/
H2O (9:1) at 120 °C for 20 h, butyl 5-(4-methylphenyl)-4,5-
diphenyl-2,4-pentadienoate (4a) was formed in 16% yield
along with a normal Mizoroki-Heck-type product, butyl
3-(4-methylphenyl)-2-propenoate (5a), in 25% yield (Table
1, entry 1). In this case, a trace amount of 1:2 coupling
product, methyl(tetraphenyl)naphthalene, was also detected
by GC-MS.7d The reaction was found to be enhanced
significantly by using DMF/H2O as solvent (entry 2). Various
bases could be used in place of Ag2CO3 (entries 3-7), and
among those examined, relatively weak and less expensive
NaHCO3 gave the best result (entry 7). As expected, the use
of excess 2a (4 equiv) improved the selectivity for the desired
three-component coupling product 4a (entry 4 vs 3). When
the reaction was conducted with the addition of LiCl (0.7
equiv) as promoter at 130 °C, 4a was obtained in a further
improved yield of 72% with a suppressed amount of 5a
(entry 9). The NMR spectra of 4a isolated in entry 9 indicated
that it consists of two geometrical isomers ((2E,4E)/(2E,4Z)
) 1.2:1).9 Either decreasing and increasing the amount of
LiCl resulted in a reduction in the yield of 4a (entries 10
and 11). 4-Bromotoluene could be used in place of 1a with
the addition of P(p-tolyl)3 (0.2 mmol) as ligand (entry 13).
As expected, the reaction using the substrate combination
of an aryl iodide and a diarylacetylene, in which same aryl
groups are contained, with 3a gave the corresponding butyl
Scheme 2a
Table 1. Reaction of 4-Iodotoluene (1a) with
Diphenylacetylene (2a) and Butyl Acrylate (3a)a
% yieldb
entry base (mmol) LiCl (mmol) T (°C) time (h) 4a
5a
1c,d Ag2CO3(1)
120
120
120
120
120
120
120
120
130
130
130
130
130
20
2
0.5
0.5
2
0.5
2.5
1.5
1
1
2
0.5
4
16
20
29
53
53
51
60
64
25
36
58
40
28
35
31
28
a Determined by GC (the value in parentheses indicates yield
after purification).
2c
3c
4
5
6
7
8
9
10
Ag2CO3(1)
Cs2CO3(2)
Cs2CO3(2)
Na2CO3(2)
NaOAc (2)
NaHCO3(2)
NaHCO3(2)
NaHCO3(2)
NaHCO3(2)
NaHCO3(2)
NaHCO3(2)
4,5,5-triaryl-2,4-pentadienoate as the predominant product.
Thus, dienes 6a-d were obtained from 1a-d and 2a-d
(Scheme 2).
The reaction of 1b and 2a with alkenes other than 3a was
next examined (Scheme 3). The alkenes with an electron-
0.7
0.7
0.5
1.0
0.7
0.7
72 (50)e 12
53
63
70
58
15
12
14
24
11
12f
(4) Intermolecular reaction with organoboron reagents: (a) Zhou, C.;
Emrich, D. E.; Larock, R. C. Org. Lett. 2003, 5, 1579. (b) Zhang, X.; Larock,
R. C. Org. Lett. 2003, 5, 2993. See also: (c) Thadani, A. N.; Rawal, V. H.
Org. Lett. 2002, 4, 4317.
(5) Intermolecular reaction with terminal alkynes: (a) Pal, M.; Para-
suraman, K.; Subramanian, V.; Dakarapu, R.; Yeleswarapu, K. R. Tetra-
hedron Lett. 2004, 45, 2305. (b) Pottier, L. R.; Peyrat, J.-F.; Alami, M.;
Brion, J.-D. Synlett 2004, 1503.
13f,g NaHCO3(2)
a Reaction conditions: 1a (1 mmol), 2a (4 mmol), 3a (1 mmol), Pd(OAc)2
(0.05 mmol), and NaHCO3 in DMF/H2O (9:1, 5 mL) under N2. b GC yield
based on the amount of 1a used. Value in parentheses indicates yield after
purification. c 2a (1 mmol) was used. d In 1-propanol/H2O (9:1, 5 mL).
e (2E,4E)/(2E, 4Z) ) 1.2:1. f With P(p-tolyl)3 (0.2 mmol). g 4-Bromotoluene
(1 mmol) was used in place of 1a.
(6) Satoh, T.; Ogino, S.; Miura, M.; Nomura, M. Angew. Chem., Int.
Ed. 2004, 43, 5063.
1782
Org. Lett., Vol. 7, No. 9, 2005