Regioselective allylgallation of terminal alkynes

Article abstract of DOI:10.1039/b417975g

The reactions of terminal alkynes with allylgallium reagents generated in situ from gallium and allyl bromides gave the corresponding 1,4-dienes in good yield via Markovnikov addition in THF at 70°C. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b417975g

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Regioselective allylgallation of terminal alkynes
Phil Ho Lee,* Yunkiu Heo, Dong Seomoon, Sundae Kim and Kooyeon Lee
Received (in Cambridge, UK) 30th November 2004, Accepted 27th January 2005
First published as an Advance Article on the web 9th February 2005
DOI: 10.1039/b417975g
Table 1 Reaction optimization of allylgallation of phenylacetylenea
The reactions of terminal alkynes with allylgallium reagents
generated in situ from gallium and allyl bromides gave the
corresponding 1,4-dienes in good yield via Markovnikov
addition in THF at 70 uC.
Ga
Entry (equiv.) Solvent Additive (uC)
Temp Time Yield
(%)b
The carbometalation of C–C multiple bonds is a very important
organic transformation.1 In particular, the development of
allylmetalation of simple unactivated alkynes toward the synthesis
of 1,4-dienes is valuable in organic synthesis because of the utility
of 1,4-dienes and the limited number of allylmetals available for
this purpose.2 To date various allylmetalations have been reported
on the basis of nucleophilic character of allylmetals obtained from
allyl halides and metals (Ta, Zr, Zn, Al, Ti, Si, and Sn).2 Although
organoindium reagents generated from the reaction of indium with
allyl halides have been used extensively in carbonyl addition
reactions,3 additions to C–C multiple bonds and nitriles,4 and
cross-coupling reactions,5 organogallium reagents have not been
explored to a great extent in organic syntheses.6 As part of the
continuing effort to expand the synthetic utility of Group IIIa (In
and Ga),4g,7 we now report the efficient synthesis of 1,4-dienes via
allylation of alkynes by organogallium reagents (Scheme 1).
We first investigated various experimental conditions in a model
reaction using phenylacetylene and allyl bromide (Table 1).
Although treatment of phenylacetylene with allyl bromide and
gallium did not produce the desired compounds in THF at 25 uC
(entry 1), refluxing the reaction mixture at 70 uC gave 2-phenyl-1,4-
pentadiene, which is the Markovnikov addition product, in 82%
yield (entry 2). No trace of the corresponding anti-Markovnikov
addition product was detected by NMR spectroscopy in this
reaction. The use of additives such as LiI, LiBr, and I2 furnished
1,4-diene in 87%, 90%, and 85% yields, respectively, in THF at
70 uC (entries 6–8). Of the reaction conditions examined, the best
results were obtained with 2.0 equiv. of gallium and 8.0 equiv. of
allyl bromide in THF at 70 uC for 4 h, which provided 1,4-diene in
95% yield (entry 5).8 THF was the best solvent among several
reaction media (DMF, THF, PhCH3, CH3CN, THF–H2O, and
DMF–H2O) that were evaluated.
(h)
1
2
1.0
1.0
1.0
2.0
2.0
1.0
1.0
2.0
THF
THF
DMF
THF
THF
THF
THF
THF
25
70
70
70
70
70
70
70
12
5
0
82
3
12
12
4
12
6
0
67
4c
5
95(92)d
87
90
6e
7f
8g
a
LiI
LiBr
I2
5
85
Reactions of Grignard type performed with 1.0 equiv. of
phenylacetylene and 8.0 equiv. of allyl bromide in the presence of
2.0 equiv. of gallium (cut ingot-gallium into small pieces), unless
b
otherwise noted. GC yields were obtained on the basis of an
internal standard (dodecane). 3 equiv. of allyl bromide were used.
c
d
e
Isolated yield. 3 equiv. of LiI were used. 3 equiv. of LiBr were
f
g
used. 5 mol% of I2 was used.
and 3-phenyl-1-propyne reacted with allylgallium reagent to give
4-methylene-1-decene and 2-benzyl-1,4-pentadiene in 70% and
72% yields, respectively (entries 1 and 3). Treatment of 1-octyne
with 3-bromo-2-methylpropene and gallium afforded the desired
product in 62% yield (entry 2). In the course of the present study,
we observed a very interesting and dramatic effect of a hydroxyl
group, if it is suitably positioned relative to the triple bond, on the
regioselectivity. Although allylation of 5-hexyn-1-ol provided
5-methylene-7-octen-1-ol in 51% yield (entry 4), 1-phenyl-2-
propyn-1-ol gave 1-phenyl-1,2,5-hexatriene in 60% yield via anti-
Markovnikov addition to the triple bond followed by elimination
(entry 5). This implies that the change in selectivity for the
formation of 1-phenyl-1,2,5-hexatriene via the anti-Markovnikov
addition in the reaction of 1-phenyl-2-propyn-1-ol was caused by
the coordination of the carbinol oxygen to an organogallium
intermediate. Exposure of silylacetylene to 3-bromo-2-methylpro-
pene and gallium produced 4-methyl-2-trimethylsilyl-1,4-
pentadiene in 91% yield under the present conditions (entry 7).
Both electron-rich (entries 10–13) and electron-deficient (entries 14
and 15) aromatic acetylenes are suitable substrates for allylgalla-
tion reactions and provide the corresponding 1,4-dienes in good to
excellent yields. Treatment of 1,7-octadiyne with excess of
allylgallium reagent gave rise to 4,9-di(methylene)-1,11-dodeca-
diene in 67% yield in THF for 18 h (entry 17). Under the optimum
conditions, 1,7-octadiyne produced the desired product in 45%
yield together with the double allylation product (entry 16).
Internal alkynes failed to react with allylgallium reagents in
contrast with terminal alkynes.
To demonstrate the efficiency and scope of the present method,
organogallium reagents generated in situ from gallium and allyl
bromides were added to a variety of alkynes. The results are
summarized in Table 2. Under the optimized conditions, 1-octyne
Scheme 1
*phlee@kangwon.ac.kr
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Table 2 Allylgallation of terminal alkynes with allyl bromide and galliuma
Entry
1
Alkyne
Allyl bromide
Time (h)
8
Product
Yield (%)b
70
2
10
62
3
4
6
8
72
51
5
6
5
8
60
53
7
8
6
4
4
4
91c
92
80
96
9
10
11
12
13
14
15
16
6
6
95
94
6
64
4
60
5
53
12
45(15)d,(35)e
17
18
67f
a
Reactions of Grignard type performed with terminal acetylene (1 mmol), allylic bromide (8.0 mmol), and Ga (2.0 mmol) in THF at 70 uC,
unless otherwise noted. Isolated yield. GC yield was obtained on the basis of an internal standard (dodecane). GC yield of starting
b
c
d
e
material. GC yield of 4,9-di(methylene)-1,11-dodecadiene. Alkyne (1 mmol), allyl bromide (16 mmol), and Ga (4 mmol) were used.
f
Although subjecting allylgallium reagent to the mixture of 1 equiv.
of benzaldehyde and 1 equiv. of phenylacetylene chemoselectively
afforded 1-phenyl-3-butenol in 71% yield, competition reaction of
acetophenone and phenylacetylene under the present conditions
produced 2-phenyl-1,4-pentadiene in 81% yield (Scheme 2).
In summary, we have demonstrated that allylation of alkynes by
Scheme 2
organogallium reagents produces 1,4-dienes in good yields. A
variety of aliphatic and aromatic terminal acetylenes participate in
this reaction. The present method complements existing synthetic
methods as a result of advantageous features such as the ready
availability of allyl bromide and operational simplicity. Further
studies to explain the utility and mechanism of this reaction are
under investigation.
were obtained from the central instrumental facility in Kangwon
National University. We thank Professor T. Livinghouse of
Montana State University for the proof of this manuscript.
Phil Ho Lee,* Yunkiu Heo, Dong Seomoon, Sundae Kim and
Kooyeon Lee
Department of Chemistry, Kangwon National University, Chunchon
200-701, Republic of Korea. E-mail: phlee@kangwon.ac.kr;
Fax: +82 33 253 7582; Tel: +82 33 250 8493
This study is supported by the Grant No. R02-2003-000-10023-0
of the Basic Research Program of the KOSEF, Kangwon National
University, and the CMDS at KAIST. The NMR and mass data
This journal is ß The Royal Society of Chemistry 2005
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Korean Chem. Soc., 2005, 26, 157; (j) P. H. Lee, D. Seomoon and K. Lee,
Org. Lett., 2005, 7, 343.
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1876 | Chem. Commun., 2005, 1874–1876
This journal is ß The Royal Society of Chemistry 2005