Microwave-assisted cross-coupling reaction of alkynylstibanes with aryl iodides in the presence of ammonium salt

Article abstract of DOI:10.1248/cpb.53.1369

The scope of microwave-assisted coupling reaction of alkynylstibane and aryl iodides to form diarylalkynes is presented. Highly efficient reaction took place smoothly in dimethyl sulfoxide in the presence of cetyltrimethylammonium bromide with much shorter time (1 min) and lower catalyst loading (0.5 mol%) than the conventional method (heating for 24 h with 10 mol% catalyst).

Full text of DOI:10.1248/cpb.53.1369

October 2005
Communications to the Editor
Chem. Pharm. Bull. 53(10) 1369—1371 (2005)
1369
tion in solvents with higher dielectric constant.1) Other ap-
proach is the coexistence of an appropriate MW coupler such
as ammonium salt17—21) or ionic liquid4,22—28) as an additive.
We therefore attempted the reaction using several solvents in
the absence or presence of ammonium salt. As can be seen in
Table 1, a survey of suitable solvents for this reaction showed
that dimethyl sulfoxide (DMSO) was superior to other sol-
vents. Thus, coupling products 3a and 4 were obtained in
47% and 33% yields, respectively, when the reaction of 1
with 2a (1.5 eq) was carried out in DMSO under MW irradi-
ation at 80 °C for 3 min. Also apparent was that the coexis-
tence of tetra-alkylammonium salts facilitates the formation
of the coupling products. Detailed study on ammonium salts
as additives revealed that cetyltrimethylammonium bromide
(CTMAB) is the best choice among three kinds of ammo-
nium salts examined here for the present reaction, and no no-
ticeable difference in the yields of the coupling products was
observed even when only 0.5 mol% of the Pd catalyst was
used with CTMAB (Table 2). The reaction of 1 and 2a in the
absence of Pd catalyst under the same conditions gave the
Microwave-Assisted Cross-Coupling
Reaction of Alkynylstibanes with Aryl
Iodides in the Presence of Ammonium
Salt
Naoki KAKUSAWA and Jyoji KURITA*
Faculty of Pharmaceutical Sciences, Hokuriku University;
Kanagawa-machi, Kanazawa 920–1181, Japan.
Received June 23, 2005; accepted August 1, 2005; published online
August 4, 2005
The scope of microwave-assisted coupling reaction of alkynyl-
stibane and aryl iodides to form diarylalkynes is presented.
Highly efficient reaction took place smoothly in dimethyl sulfox-
ide in the presence of cetyltrimethylammonium bromide with
much shorter time (1 min) and lower catalyst loading
(0.5 mol%) than the conventional method (heating for 24 h with
10 mol% catalyst).
Key words microwave; cross-coupling; alkynylstibane; aryl iodide; pal-
ladium catalyst; phase transfer catalyst
The use of microwave (MW) oven as a new tool for syn-
thetic chemistry is a fast-growing area, and the technique has
been accepted as a method for reducing reaction times and
for increasing yields of product, as well as for improving se-
lectivity compared to conventional methods.1,2) As a result,
this has opened up the possibility of optimizing various reac-
tions in a short time.3—6) We have recently reported that
ethynylstibanes (Ph2Sb R) resulted in cross-coupling reac-
tion to afford ethynylketones (R COR1) on heating with
acyl chlorides (R1COCl) in the presence of a Pd catalyst
[PdCl2(PPh3)2].7) However, the ethynylation of aryl halides
(Ar-X) proceeded sluggishly under the same reaction condi-
tions; the reaction needs greater loading of the Pd catalyst
(10 mol%) and longer reaction time (24 h at 80 °C), and the
yield of the coupling product (R Ar) is low (16% yield).
Thereafter, we also demonstrated that the same reaction of
Ph2Sb R with Ar-X or vinyl halides proceeded more effi-
ciently in amine solvents, in that Sb···N intermolecular co-
ordination would facilitate the coupling reaction.8,9) Taking
Chart 1
Table 1. Palladium-Catalyzed Coupling Reaction of 1 with 2a in Various
Solvents under MW Irradiationa)
Yield/%b)
Entry: Solvent
Max. Temp./°C
3a
4
1: DCE
2: benzene
3: THF
4: triethylamine
5: DMSO
83
80
66
88
80
9
6
4
20
47
20
10
9
10
33
a) A mixture of 1 (1 mmol), 2a (1.5 mmol), and Pd cat. (5 mol%) in solvent (3 ml)
these results and knowing that MW irradiation is highly ef- was irradiated using CEM Discover MW system for 3 min. b) GC yields.
fective for a variety of transition metal-catalyzed reaction
into consideration,10—16) the reaction of diphenyl(phenyl-
ethynyl)stibane 1 with aryl halides 2 was performed under
MW irradiation to improve the reaction. In this note we re-
Table 2. Palladium-Catalyzed Coupling Reaction of 1 with 2a in the Pres-
ence of Ammonium Salta)
port the results of our investigations on the Pd-catalyzed cou-
pling reaction in the presence of ammonium salts as an aid
for effective MW absorption in a polar solvent. Under opti-
mal reaction conditions, the reaction took place quite effec-
tively in extremely short time (1 min) to afford the coupling
products diarylacetylene 3 along with 1,4-diphenyl-1,3-bu-
tadiyne 4 in good yields even when only 0.5 mol% of the
palladium catalyst was employed.
Initial attempts for the reaction of 1 with iodobenzene 2a
in the presence of 5 mol% of PdCl2(PPh3)2 under MW irradi-
ation in 1,2-dichloroethane (DCE) gave cross-coupling prod-
uct 3a (9%) and homo-coupling product 4 (20%) in low
yields. The MW effect is known to be operative in a highly
Yield/%b)
3a
Entry:
R4NBr/(mol eq)
Pd cat.
/mol%
Solvent
4
1: None
Neat
Neat
Neat
Neat
DMSO
DMSO
DMSO
DMSO
5
5
5
5
5
5
1
0.5
27
48
50
53
55
62
63
63
14
18
22
28
27
21
23
23
2: TBABc) (0.5)
3: BTEABd) (0.5)
4: CTMABe) (0.5)
5: CTMAB (0.5)
6: CTMAB (1)
7: CTMAB (1)
8: CTMAB (1)
a) A mixture of 1 (1 mmol), 2a (1.5 mmol), and Pd cat. (5 mol%) in DMSO (3 ml)
was irradiated using the MW system (300 W, Max. Temp. 130 °C) for 3 min. b) GC
yields. c) Tetrabutylammonium bromide. d) Benzyltriethyl-ammonium bromide.
polarized medium, so it is preferable to carried out the reac- e) Cetyltrimethylammonium bromide.
∗ To whom correspondence should be addressed. e-mail: j-kurita@hokuriku-u.ac.jp
© 2005 Pharmaceutical Society of Japan

1370
Vol. 53, No. 10
Table 3. Palladium-Catalyzed Coupling Reaction of 1 and 2 under Various Reaction Conditions
Yields of the products/%a)
Method B (MW-Irrn.)c)
2
Ar
Method A (conventional)b)
Method C (MW-Irrn.)d)
3
4
3
4
3
4
a
b
c
d
e
f
g
h
C6H5
49
77
73
89
46
30
32
35
21
11
20
5
47
—
64
79
59
30
32
59
33
—
21
21
29
25
34
25
63
76
75
83
75
57
48
48
23
21
14
14
19
16
26
41
o-NO2C6H4
m-NO2C6H4
p-NO2C6H4
p-CH3COC6H4
o-CH3C6H4
p-CH3C6H4
p-CH3OC6H4
7
20
20
25
a) GC yields. b) Method A: A mixture of 1 (1 mmol), 2 (1.5 mmol), and Pd cat. (10 mol%) in Et2NH (5 ml) was refluxed (55 °C) for 24 h under argon atmosphere. c)
Method B: A mixture of 1 (1 mmol), 2 (1.5 mmol), and Pd cat. (5 mol%) in DMSO (3 ml) was irradiated using the MW system (300 W, Max. Temp. 130 °C for 2a, e—g, and 80 °C
for 2b—d) for 3 min. d) Method C: A mixture of 1 (1 mmol), 2 (5 mmol), CTMAB (1 mmol), and Pd cat. (0.5 mol%) in DMSO (3 ml) was irradiated using the MW system
(300 W, Max. Temp. 130 °C for 2a, e—g, and 80 °C for 2b—d) for 1 min.
products 3a (21%) and 4 (4%) in poor yields, indicating the versity, which are gratefully acknowledged.
presence of the catalyst is not essential in the present reac-
tion. However, prolonged MW irradiation (10 min) of the re-
References and Notes
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time (1 min) (Method C), and the results are summarized in
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ready comparison with those of Method C. In most cases, su-
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October 2005
1371
29) The microwave apparatus used here should have a protective cage
around it in case of explosion, especially when aryl iodides having
nitro group 2b—d is used at over 120 °C. Typical Procedure: A vial
(10 ml: designed for CEM Discover MW system) containing a solution
of 1 (188 mg, 0.5 mmol), 2a (510 mg, 2.5 mmol), CTMAB (182 mg,
yields of the products were determined by GLC analysis (5% SE-30,
1.6 m, column temp. 210 °C) using biphenyl (tRꢀ1.25 min) as an inter-
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