Regio- and Stereoselective Dimerization of Terminal Alkynes to Enynes in InCl3-NaBH4-MeCN System

Article abstract of DOI:10.1055/s-2004-815428

A novel method to prepare (E)-enynes is described in this paper. The InCl₃-NaBH₄-MeCN system showed high regio- and stereoselectivity for the dimerization of terminal alkynes to enynes.

Full text of DOI:10.1055/s-2004-815428

LETTER
561
Regio- and Stereoselective Dimerization of Terminal Alkynes to Enynes in
InCl –NaBH –MeCN System
3
4
R
C
egio- and Stereo
h
selective
D
i
u
m
erization
o
n
f
Termina
l
A
-
lkyne
s
t
Y
Enynes an Wang, Hua Su, De-Yu Yang*
Department of Chemistry, Xixi Campus, Zhejiang University, Hangzhou 310028, P. R. China
Fax +86(571)88212853; E-mail: deyu18@hotmail.com
Received 5 September 2003
ever, it was found that Cl InH could be obtained smoothly
2
Abstract: A novel method to prepare (E)-enynes is described in this
at –15 °C. The yield of the reaction was good and pro-
ceeded with high regio- and stereoselectivity (Scheme 1).
When the system was tested in the dimerization of phenyl-
acetylene, it was found that this reaction occurred smooth-
ly using NaBH and KBH while no product was observed
paper. The InCl –NaBH –MeCN system showed high regio- and
3
4
stereoselectivity for the dimerization of terminal alkynes to enynes.
Key words: terminal alkynes, dimerizations, head-to-head, InCl3–
NaBH –MeCN system, enynes
4
4
4
with LiBH under the same conditions (Table 1).
4
Enynes are valuable intermediates in the synthesis of
many compounds including biological activity natural
products. Various synthetic methods to enynes have been
InCl -MBH -MeCN
3
4
PhC CH
1
–15 °C to r.t.
explored. Among them, the dimerization of terminal
alkynes in the presence of a transition metal catalyst is pri-
Ph
H
Ph
H
H
H
H
+
+
2
mary and very effective. In addition, the coupling reac-
H
3
Ph
Ph
tion of aryl halides with copper(I) acetylides, palladium-
catalyzed coupling of aryl and vinyl halides with terminal
Ph
Ph
4
5
alkynes and with alkynylmetals have also been devel-
oped. Palladium-catalyzed vinylation of phenylpropioloyl
(
E)-Ia
(Z)-IIa
IIIa
6
Scheme 1
chloride can also give enynes. Recently the organoindi-
um compounds were explored gradually and have been
applied in organic synthesis more and more widely.7 In The product ratio of (E)- and (Z)-1,4-disubstituted enyne
–10
this paper we wish to present a novel synthesis to (E)- (I and I ) and 1,3-disubstitued enyne (III ) showed high
a
a
a
enynes by the head-to-head dimerization of terminal regio- and stereoselectivity. The stereostructure was
alkynes in a mild and nontoxic system in a one-pot reac- consistent with the previous papers.2b
tion.
Under the same conditions [InCl (3mmol), NaBH (10
3
4
Dichloroindium hydride (Cl InH) was generated first us- mmol), MeCN (10 mL), –15 °C to r.t., 15 h], for a wide
2
ing the transmetalation between indium trichloride and array of terminal alkynes it was found that the reaction
8
tributylstannane at –78 °C. Very recently the indium(III) could also take place smoothly (Scheme 2). Excellent
chloride–sodium borohydride system has been proven to yields for the regio- and stereoselective dimerization of
9
replace the toxic tributyltin hydride system. Aromatic terminal alkynes could be obtained (Table 2).
and alkyl aldehydes, an a,b-unsaturated aldehyde could
be reduced by Cl InH. Furthermore, the hydroindation
8
,9
Table 1 Dimerization of Phenylacetylenea
2
of C≡C with dichloroindium hydride (Cl InH) and the
2
Producte
Entry
1b
MBH4
LiBH4
NaBH4
KBH4
NaBH4
KBH4
coupling reaction of vinylindium with aryl halides has
1
0
been well explored. But to our surprise while studying
hydroindation we found that the different products were
obtained when we changed the ratio of the starting mate-
–
2b
I :II :III = 92:2:6
a
a
a
rials. For instance, when the InCl /PhC≡CH ratio was 3:2, 3b
3
I :II :III = 90:4:6
a a a
the major product after hydrolysis was PhCH=CH , which
2
4c
PhCH=CH2
PhCH=CH2
–
1
was determined by H NMR and MS; when the InCl /
3
PhC≡CH ratio was 3:7, the major product came from
5c
1
dimerization of PhC≡CH on the basis of H NMR and MS.
6d
8
–10
NaBH4
In the previous papers,
Cl InH could only be obtained
2
under liquid nitrogen (–78 °C). In our experiments, how-
a
Reaction conditions: MBH (10 mmol), MeCN (10 mL), deionized
4
H O (5 mL).
2
b
InCl (3 mmol), PhC≡CH (7 mmol).
3
SYNLETT 2004, No. 3, pp 0561–0563
Advanced online publication: 26.01.2004
DOI: 10.1055/s-2004-815428; Art ID: U17703ST
1
8.
0
2.
2
0
0
4
c
InCl (3 mmol), PhC≡CH (2 mmol).
3
d
Pd(PPh ) (3% mol).
3
4
e
1
By H NMR. (400 MHz).
©
Georg Thieme Verlag Stuttgart · New York

5
62
C.-Y. Wang et al.
LETTER
R
H
H
R
H
H
R
InCl3-NaBH4-MeCN
RC
H
CH
RC CH
.
.
. InCl2
+
–15 °C to r.t.
InCl2
H
H
(E)-I
R
A
C
+
B
R
H
H
H
+
.
InCl2
+
RC
. C
CH
CR + HInCl2
H
R
H
R
C
D
(
Z)-II
R
III
R
H
R
H
Scheme 2
.
.
+
C
CR
H
Table 2 Dimerization of Terminal Alkynes to Enynes in InCl –
3
a
NaBH –MeCN System
4
R
(
E)-I
A
D
Entry
Terminal alkyne
PhC≡CH
p-CH PhC≡CH
I:II:IIIb
92:2:6
90:3:7
91:6:3
90:4:6
93:2:5
89:3:8
90:4:6
88:5:7
Yield (%)c,d
H
H
R
a
b
c
d
e
f
86
86
85
82
78
80
81
80
.
.
C
+
CR
R
3
H
H
R
(CH ) CHC≡CH
3
2
D
(Z)-II
B
(CH ) SiC≡CH
3
3
Scheme 3
t-BuC≡CH
n-C H C≡CH
5
11
g
n-BuC≡CH
Acknowledgment
The generous financial support of Zhejiang Natural Science Found-
ation of China is gratefully acknowledged.
h
n-C H C≡CH
8
17
a
Reation conditions: InCl (3 mmol), NaBH (10 mmol), MeCN (10
3
4
mL), terminal alkynes (7 mmol), –15 °C to r.t., 15 h;. deionized H O
2
(
5 mL).
References
b
1
Determined by H NMR (400 MHz).
Isolated yield by terminal alkynes.
The dimeric compounds were known.
c
(1) For example, see: (a) Joh, T.; Doyama, K.; Fujiwara, K.;
d
2a,b
Maeshima, K.; Takashi, S. Organometallics 1991, 10, 508.
(
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According to the above results of (E)-I and (Z)-II, we pro-
pose a mechanism, which proceeds via a radical addition
and coupling (Scheme 3). There is an equilibration be-
tween two configurations of the alkenyl radical (A and B).
A precedent for such an equilibration has been reported in
(d) Nicolaou, K. C.; Dai, W. M.; Tsay, S. C.; Estevez, V. A.;
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(
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1
2
996, 15, 3968. (b) Yang, C. L.; Nolan, S. P. J. Org. Chem.
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1
1
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(
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3
4
Organometallics 1997, 16, 3910. (e) Bruneau, C.; Dixneuf,
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cessfully applied to the dimerization of terminal alkynes.
This system has been proved to be highly regio- and
stereoselective. Thus, our results show that dimerization
of terminal alkyne in InCl –NaBH –MeCN system repre-
3
4
sents a very convenient synthesis of (E)-enynes.
Organometallics 1999, 18, 2407. (i) Nishiura, M.; Hou, Z.
M.; Wakatauki, Y.; Yamaki, T.; Miyamoto, T. J. Am. Chem.
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General Procedure
A mixture of InCl (3 mmol) in dry MeCN (10 mL) and NaBH
3
4
(
(
10 mmol) was stirred at –15 °C under nitrogen. Terminal alkyne
7 mmol) was added by syringe. The reaction mixture was warmed
(
(
3) (a) Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963, 28,
2163. (b) Stephens, R. D.; Castro, C. E. J. Org. Chem. 1963,
to room temperature and stirred for 15 hours. The completion of the
reactions was monitored by TLC. In order to destroy the excessive
28, 3313. (c) Castro, C. E.; Gaughan, E. J.; Owsley, D. C. J.
Org. Chem. 1966, 31, 4071.
NaBH deionized water (5 mL) was added to the reaction mixture.
4
4) (a) Cassar, L. J. Organomet. Chem. 1975, 93, 253.
The reaction mixture was stirred for ten minutes and then filtered.
The filtrate was extracted with diethyl ether. The combined organic
layer was dried over MgSO and concentrated in vacuum. Purifica-
(b) Dieck, H. A.; Heck, R. F. J. Organomet. Chem. 1975, 93,
259.
4
tion by silica gel column [100–200 mesh, 3 ft × 1 inch, petroleum
ether (bp 30–60 °C) as eluent] afforded the corresponding products.
Synlett 2004, No. 3, 561–563 © Thieme Stuttgart · New York

LETTER
Regio- and Stereoselective Dimerization of Terminal Alkynes to Enynes
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Synlett 2004, No. 3, 561–563 © Thieme Stuttgart · New York