A one-pot synthesis of terminal alkynes from anti-3-aryl-2,3- dibromopropanoic acids under microwave irradiation

Article abstract of DOI:10.1246/cl.2005.28

A facile one-pot synthesis of terminal alkynes was achieved by microwave irradiation of a mixture of anti-3-aryl-2,3-dibromopropanoic acids, Et ₃N and DMF and subsequent irradiation in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). This method requires short reaction time (1-2 min) and gives terminal alkynes in high yields. Copyright

Full text of DOI:10.1246/cl.2005.28

28
Chemistry Letters Vol.34, No.1 (2005)
A One-pot Synthesis of Terminal Alkynes
from anti-3-Aryl-2,3-dibromopropanoic Acids under Microwave Irradiation
Chunxiang Kuang,ꢀy Hisanori Senboku,yy and Masao Tokudayy
yDepartment of Materials Chemistry, Graduate School of Engineering, Osaka University, Toyonaka 560-0043
yyDivision of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628
(Received October 4, 2004; CL-041168)
A facile one-pot synthesis of terminal alkynes was achieved
terminal alkynes. In the first step (MW1), treatment of anti-3-ar-
yl-2,3-dibromopropanoic acids with triethylamine in DMF under
microwave irradiation within 0.5–1.0 min resulted in (Z)-1-bro-
mo-1-alkenes with the high Z=E selectively and excellent yields.
As to the second step (MW2), it was found that bases such as
Et3N, pyridine, DABCO, NaOH, K2CO3, or t-BuOK were not
effective in this one-pot reaction. DBU was found to be the best
base in this one-pot system. DBU is not typically used to convert
vinyl halides into alkynes, in general, this conversion requires
alkoxides.6 Schuda et al. have reported that (Z)-vinyl bromide
was nearly quantitatively converted into terminal alkynes in 2
days with DBU in refluxing benzene and that the corresponding
(E)-isomer did not react with DBU.9 We found that under micro-
wave irradiation the reaction of anti-3-aryl-2,3-dibromopropa-
noic acids and triethylamine in DMF followed by addition of
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) proceeded smoothly
to afford the corresponding terminal alkynes in high yields.10
Yields of the terminal alkynes (3) are shown in Table 1.
These results indicate that terminal alkynes were obtained in
higher yields and in shorter reaction time by the microwave irra-
diation method. It would be very convenient for this one-pot re-
action to use same base in two successive steps. Unfortunately,
by microwave irradiation of a mixture of anti-3-aryl-2,3-dibro-
mopropanoic acids, Et3N and DMF and subsequent irradiation
in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
This method requires short reaction time (1–2 min) and gives
terminal alkynes in high yields.
Terminal alkynes are useful and versatile intermediates
in organic synthesis. Most frequently used methods for the
conversion of aldehydes to terminal alkynes include the reac-
tions of Corey–Fuchs,1 Wittig/Horner–Emmons,2 and Gilbert–
Seyferth,3 and its modification.4 However, the need for phospho-
rus reagents limits the usefulness of these applications due to
toxicity, exothermicity, and voluminous waste stream, particu-
larly for large-scale preparations. Recently, Wang et al. have re-
ported a procedure for the synthesis of terminal alkynes from al-
dehydes through a three-step reaction sequence: addition of di-
halomethyllithium to aldehyde, sulfonation of the adducts, and
then elimination of chloride and tosylate followed by elimina-
tion of HX to generate the desired alkynes.5 However, this
synthetic method also has several drawbacks, such as the use
of arylsulfonyl chloride and excess organolithium, and very
low temperature.
In 1997, Matveeva et al. reported that the (Z)-vinyl bro-
mides could be converted into the corresponding acetylenes in
the presence of alkoxides in a moderate yields.6 On the other
hand, our previous study showed that microwave irradiation of
anti-2,3-dibromopropanoic acids (1) in DMF in the presence
of triethylamine for 0.5–1.0 min stereoselectively afforded (Z)-
vinyl bromides (2) in nearly quantitative yields (Scheme 1).7
Table 1. One-pot synthesis of terminal alkynes by microwave
irradiation of anti-3-aryl-2,3-dibromopropanoic acids
Product (3)
Entry
Ar of 1
MW1 / MW2
min
Yield of 3
%
a
3a
3b
C6H5
1
2
0.5 / 1.0
0.5 / 1.0
88
95
2-Naphthyl
3c
3d
4-BrC6H4
4-ClC6H4
3
4
1.0 / 1.0
1.0 / 1.0
95
93
Br
Cl
Br
Et3N /DMF
MW1
DBU
Ar
CO2H
Ar
Ar
Br
MW2
Br
3e
3f
5
6
1.0 / 1.0
1.0 / 1.0
90
88
2-ClC6H4
4-FC6H4
Cl
1
2
3
F
Scheme 1. One-pot synthesis of terminal alkynes.
3g
3-FC6H4
7
1.0 / 1.0
90
In this paper, we report a very simple and general method
F
for the synthesis of terminal alkynes (3) from anti-3-aryl-2,3-
dibromopropanoic acids by microwave irradiation method
(Scheme 1). The starting anti-3-aryl-2,3-dibromopropanoic
acids were easily prepared by Knoevenagel condensation of
the corresponding aldehydes and subsequent bromination of
the substituted trans-cinnamic acids.8 To the best of our knowl-
edge, the one-pot synthesis of terminal alkynes from anti-3-aryl-
2,3-dibromopropanoic acids has not been reported.
3h
3i
3-CF3C6H4
8
9
1.0 / 1.0
1.0 / 1.0
91
99
F3C
4-CH3O2CC6H4
H3CO2C
3j
3-NO2C6H4
10
1.0 / 1.0
87
O2N
Various conditions were examined to optimize the yields of
aIsolated yields.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.1 (2005)
29
when DBU instead of Et3N was used in the first step, a mixture
of (Z)- and (E)-vinyl bromide (approximate to 92/8) was
formed, and this stereoselectivity was much lower than those us-
ing Et3N. Since DBU did only cause an elimination of (Z)-vinyl
bromides under these conditions, a mixture of terminal alkynes
and unreacted (E)-vinyl bromides were obtained.
In summary, we have developed a new procedure for one-
pot conversion of anti-3-aryl-2,3-dibromopropanoic acids into
terminal alkynes in excellent yields within a few minutes by mi-
crowave irradiation method which is a economical and environ-
ment friendly process.
7
8
C. Kuang, H. Senboku, and M. Tokuda, Tetrahedron Lett.,
42, 3893 (2001).
a) J. McNulty, J. A. Steere, and S. Wolf, Tetrahedron
Lett., 39, 8013 (1998). b) Q. L. Wang, Y. Ma, and B. Zuo,
Synth. Commun., 27, 4107 (1997). c) S. H. Kim, H.-X.
Wei, S. Willis, and G. Li, Synth. Commun., 29, 4179 (1999).
P. F. Schuda and M. R. Heimann, J. Org. Chem., 47, 2484
(1982).
9
10 Typical experimental procedure is as follows (Table 1, Entry
9): A mixture of anti-2,3-dibromo-3-(4-methoxycarbonyl-
phenyl)propanoic acid (2i, 1 mmol) and triethylamine
(1.05 mmol) was added to 2 mL of DMF. The mixture
was kept in a microwave oven operated at 2450 MHz
(TOSHIBA, ER-V11, 200 watts) and was irradiated for
1.0 min without any stirring. The reaction mixture was then
removed from the oven and cooled to room temperature. 1,8-
Diazabicyclo[5.4.0]undec-7-ene (DBU) (2 mmol) was added
to the reaction mixture and the mixture was also irradiated
for 1.0 min without any stirring. Water and ether were added
to the reaction mixture and the organic layer was separated.
Aqueous layer was extracted with ether. The combined
organic layers were washed with water and brine, and
dried over anhydrous magnesium sulfate. After evaporation
of the solvent, the crude product was purified by column
chromatography on silica gel with EtOAc–hexane to give
methyl 4-ethynylbenzoate (3i) in 99% yield. Mp 94–95 ꢁC;
This work was supported by a Grant-in-Aid for Exploratory
Research (No. 13875171) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
References and Notes
1
2
3
4
E. J. Corey and P. L. Fuchs, Tetrahedron Lett., 13, 3769
(1972).
E. J. Corey, K. Achiwa, and J. A. Katzenellenbogen, J. Am.
Chem. Soc., 91, 4318 (1969).
J. C. Gilbert and U. Weerasooriya, J. Org. Chem., 47, 1837
(1982).
a) S. Muller, B. Liepold, G. J. Roth, and H. J. Bestman,
¨
Synlett, 1996, 521. b) G. J. Roth, B. Liepold, S. G. Muller,
¨
and H. J. Bestmann, Synthesis, 2004, 59.
5
6
a) Z. Wang, J. Yin, S. Campagna, J. A. Pesti, and J. M.
Fortunak, J. Org. Chem., 64, 6918 (1999). b) Z. Wang, S.
Campagna, K. Yang, G. Xu, M. E. Pierce, J. M. Fortunak,
and P. N. Confalone, J. Org. Chem., 65, 1889 (2000).
a) E. D. Matveeva, A. S. Erin, and A. L. Kurz, Russ. J.
Org. Chem., 33, 1065 (1997). b) M. Makosza and A. A.
Chesnokov, Tetrahedron, 58, 7295 (2002).
IR (nujol) 2106, 1733, 1275 cmꢂ1 1H NMR (270 MHz,
;
CDCl3) ꢀ 3.23 (1H, s), 3.92 (3H, s), 7.55 (2H, d, J ¼ 8:5
Hz), 7.98 (2H, d, J ¼ 8:5 Hz); 13C NMR (67.5 MHz, CDCl3)
ꢀ 52.25, 80.00, 82.77, 126.73, 129.43, 130.11, 132.05,
166.39. EIMS m=z 160 (Mþ, 53), 129 (100), 101 (52);
HRMS Calcd for C10H8O2. m=z 160.0524. Found m=z
160.0508.
Published on the web (Advance View) November 27, 2004; DOI 10.1246/cl.2005.28