Unexpected reaction of dimethyl acetylenedicarboxylate with in situ generated arylketenes catalyzed by 1-methylimidazole

Article abstract of DOI:10.1021/ol050492q

(Chemical Equation Presented) An unexpected 1-methylimidazole-catalyzed reaction of dimethyl acetylenedicarboxylate (DMAD) with in situ generated arylketenes leading to the synthesis of dimethyl 2-arylidenesuccinates under mild conditions is described. A plausible mechanism has been proposed.

Full text of DOI:10.1021/ol050492q

ORGANIC
LETTERS
2005
Vol. 7, No. 11
2125-2127
Unexpected Reaction of Dimethyl
Acetylenedicarboxylate with in Situ
Generated Arylketenes Catalyzed by
1-Methylimidazole
Hanfeng Ding, Cheng Ma,* Yewei Yang, and Yanguang Wang*
Department of Chemistry, Zhejiang UniVersity, Hangzhou 310027, China
mcorg@zju.edu.cn; orgwyg@zju.edu.cn
Received March 8, 2005
ABSTRACT
An unexpected 1-methylimidazole-catalyzed reaction of dimethyl acetylenedicarboxylate (DMAD) with in situ generated arylketenes leading to
the synthesis of dimethyl 2-arylidenesuccinates under mild conditions is described. A plausible mechanism has been proposed.
The reaction of nucleophiles with activated acetylenes for
C-C bond formation is of great significance in organic
synthesis.1 In these reaction processes, zwitterionic species
are known to arise from the addition of nucleophiles such
as triphenylphosphine,1c,2 pyridine,1d,3 and a wide range of
tertiary amines2d,4 to activated acetylenes such as dimethyl
acetylenedicarboxylate (DMAD).5 Then, these intermediates
can be trapped by suitable substrates (such as dioxide,6
isocyanate,7 and carbonyl compounds3c-e), and this intercep-
tion can either be a two-component reaction or a multicom-
ponent reaction. However, to the best of our knowledge, no
attempts have been made to trap the zwitterionic intermedi-
ates with ketene.8,9 Here, the preliminary results of the
1-methylimidazole-catalyzed reaction of DMAD with in situ
generated aryl ketenes are reported.
Our studies were initiated by the reaction of p-nitrophe-
nylacetyl chloride with DMAD in the presence of 1-meth-
(1) (a) Dickstein, J. I.; Miller, S. I. The Chemistry of Functional Groups.
The Chemistry of Carbon-Carbon Triple Bond Part 2; Patai, S., Ed.;
Wiley: Chichester, 1978; Chapter 19, pp 813-955. (b) Winterfeldt, E.
Chemistry of Acetylenes; Vieche, H. G., Ed.; Dekker: New York, 1969; p
267. (c) Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1967, 6, 423. (d)
Acheson, R. M. AdV. Heterocycl. Chem. 1963, 1, 125.
(2) (a) Johnson, A. W.; Tebby, J. C. J. Chem. Soc. 1961, 2162. (b)
Butterfield, P. J.; Tebby, J. C.; Griffiths, D. V. J. Chem. Soc., Perkin Trans.
1 1979, 1189. (c) Tebby, J. C.; Wilson, I. F.; Grifiths, D. V. J. Chem. Soc.,
Perkin Trans. 1 1979, 2133. (d) Winterfeldt, E.; Dillinger, H. J. Chem.
Ber. 1966, 99, 1558. (e) Nozaki, K.; Ikeda, K.; Takaya, H. J. Org. Chem,
1996, 61, 4516. (f) Nair, V.; Nair, J. S.; Vinod, A. U. J. Chem. Soc., Perkin
Trans. 1 1998, 3129.
(3) (a) Diels, O.; Alder, K. Liebigs Ann. Chem. 1932, 498, 16. (b)
Acheson, R. M.; Plunkett, A. O. J. Chem. Soc. 1964, 2676. (c) Nair, V.;
Sreekanth, A. R.; Vinod, A. U. Org. Lett. 2001, 3, 3495. (d) Nair, V.;
Sreekanth, A. R.; Abhilash, N.; Biju, A. T.; Remadevi, B.; Menon, R. S.;
Rath, N. P.; Srinivas, R. Synthesis 2003, 1895. (e) Shi, M.; Li, C.-Q. Org.
Lett. 2003, 5, 4273.
(5) Winterfeldt, E.; Schumann, D.; Dillinger, H. J. Chem. Ber. 1969,
102, 1656. (b) Dillinger, H. J.; Fengler, G.; Schumann, D.; Winterfeldt, E.
Tetrahedron. 1974, 30, 2553. (c) Dillinger, H. J.; Fengler, G.; Schumann,
D.; Winterfeldt, E. Tetrahedron 1974, 30, 2561.
(6) Acheson, R. M.; Plunkett, A. O. J. Chem. Soc. 1964, 2676.
(7) (a) Huisgen, R.; Morikawa, M.; Herbig, K.; Brunn, E. Chem Ber.
1967, 100, 1094. (b) Adib, M.; Mollahosseini, M.; Yavari, H. Synlett 2004,
6, 1086-1088.
(8) For [2 + 2] cycloaddition of ketene equivalents with electrophilic
acetylenes promoted by Lewis acid, see selected references: (a) Semmelhack,
M. F.; Tomada, S. J. Am. Chem. Soc. 1981, 103, 2427. (b) Semmelhack,
M. F.; Tomada, S.; Nagaoka, H.; Boettger, S. D.; Hurst, K. M. J. Am. Chem.
Soc. 1982, 104, 747. (c) Quendo, A.; Rousseau, G. Tetrahedron Lett. 1988,
29, 6443. (d) Quendo, A.; Ali, S. M.; Rousseau, G. J. Org. Chem. 1992,
57, 689.
(9) For uncatalyzed [2 + 2] cycloaddition of ketenetrimethylsilyl-acetates
with electrophilic acetylenes, see: (a) Misesch, M.; Wendling, F.; Franck-
Neumann, M. Tetrahedron Lett. 1999, 40, 839. (b) Misesch, M.; Wendling,
F. Eur. J. Org. Chem. 2000, 3381.
(4) Winterfeldt, E. Chem. Ber. 1964, 97, 1952.
10.1021/ol050492q CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/30/2005

ylimidazole and i-Pr2NEt10 in CH2Cl2 at -10 °C to room
temperature for 2 days. To our surprise, (E)-dimethyl 2-(4-
nitrobenzylidene)succinate 1 was isolated from the reaction
mixture (eq 1). Intrigued by this result, we carried the
reaction under various conditions, and the results are shown
in Table 1. In the presence of stoichiometric amounts of
nesuccinates 3a-k as a pair of (Z)- and (E)-isomers in
moderate to good yields (Table 2, eq 2).12,13 It is interesting
Table 2. Reaction of in Situ Generated Ketenes with DMAD
Catalyzed by 1-Methylimidazole (100 mol %)
Table 1. Reaction of p-Nitrophenylacetyl Chloride (2 mmol)
with DMAD (2 mmol) Catalyzed by Nitrogen Lewis Bases
under Various Conditions
timea
(h)
yieldb
(%)
entry
R
product
Z/E ratioc
1
2
3
4
5
6
7
8
9
Ph
4-ClC6H4
2-ClC6H4
3-ClC6H4
1-naphthyl
4-FC6H4
2-FC6H4
2,4-dichlorophenyl
3,4-dichlorophenyl
4-MeC6H4
48
48
60
48
48
48
48
48
48
60
60
3a
3b
3c
3d
3e
3f
3g
3h
3i
58
52
38
46
55
53
41
63
64
37
35
79:21
87:13
69:31
81:19
60:40
79:21
72:28
72:28
72:28
76:24
57:43
timeb yieldc
entry
Lewis basea
solvent
T (°C)
(h)
(%)
1
2
3
4
5
6
7
8
1-methylimidazoled DCM
1-methylimidazole DCM
1-methylimidazole THF
1-methylimidazole toluene -10 to +20
1-methylimidazole THF
-10 to +20
-10 to +20
-10 to +20
48
48
48
48
12
48
50
60
26
65
62
34
-10 to +80
-10 to +20
-10 to +20
-10 to +20
61
10
11
3j
3k
pyridine
DBU
i-Pr2NEt
DCM
DCM
DCM
trace
trace
trace
2-MeC6H4
a Reaction time for consuming all of the starting materials. b Isolated
yields. c Determined by GC-MS analysis and verified by isolated yields.
a Unless otherwise specified, all of the reactions were carried out in the
presence of 100 mol % Lewis base. b Reaction time for consuming all of
the starting materials. c Isolated yield. d 20 mol %.
that the products 3a-k were obtained with dominant (Z)-
selectivity.14
1-methylimidazole, 1 could be obtained in 26-65% yields
with (E)-selectivity in various solvents (entries 2-4). While
using other Lewis base such as pyridine, DBU, or i-Pr2NEt
as catalyst, only a trace of 1 is formed (entries 6-8).
Moreover, the catalyst loading below 100 mol % afforded a
significantly reduced yield of 1 (entry 1).
To explore the mechanism of the 1-methylimidazole-
catalyzed reaction, one further experiment was performed
under the same conditions but using D2O in place of H2O
with phenylacetyl chloride as substrate (Scheme 1). The
isolated product (Z)-4 was determined by 1H NMR (see the
Supporting Information). It is shown that only the two
protons connected to the R-C of product (Z)-4 were deuter-
ated.
The structure of 1 was characterized by spectroscopic
1
analysis. In the H NMR spectrum, the olefinic proton
resonated at δ 7.92.11 The 13C NMR signals for the two ester
carbonyls of 1 were seen at δ 167.2 and 171.2. Finally, the
structure and stereochemistry of 1 were established unam-
biguously by X-ray analysis (Figure 1).
On the basis of our results, we propose the following
mechanism for the 1-methylimidazole-catalyzed reaction of
(10) i-Pr2NEt was used as additional base to form the corresponding
ketene in situ.
(11) The chemical shift of the vinyl proton in E-isomer of substituted
3-alkoxycarbonyl-â,γ-unsaturated esters has been reported in the range of
δ ) 7.83-8.00; see: McCombie, S. W.; Luchaco, C. A. Tetrahedron Lett.
1997, 38, 5775.
(12) Representative Experimental Procedure. A mixture of DMAD
(2 mmol) and phenylacetyl chloride (2 mmol) in DCM (3 mL) was added
dropwise to the solution of 1-methylimidazole (2 mmol) and i-Pr2NEt (3
mmol) in dry DCM (5 mL) under a nitrogen atmosphere at -10 °C, and
the resulting solution was stirred for 6 h. Then, the reaction solution was
allowed to warm to rt, and water (2 mmol) was added. After an additional
2 days at this temperature, the solvent was then removed under vacuum,
and the residue was chromatographed on a silica gel column with a
hexanes-ethyl acetate mixture (7:1) to afford (Z)-3a and (E)-3a. GC-MS
analysis: (Z)-3a (tR ) 6.19 min); (E)-3a (tR ) 6.42 min).
(13) The stereochemistry of 3 is determined by the chemical shift of
vinyl proton in 1H NMR spectra. We assigned the chemical shift in the
range of δ 7.79-8.41 as the (E)-isomer, while that in the range of δ 6.77-
7.01 was assigned as the (Z)-isomer. See Shen, Y.-C.; Zhang, Y.-M.
Heteroatom Chem. 2003, 14, 276.
Figure 1. X-ray crystal structure of 1.
(14) The consecutive reaction of bis[2,2,2-trifluoroethyl] with sodium
hydride, dimethyl maleate, and aldehydes gives 3-alkoxycarbonyl-â,γ-
unsaturated esters with Z-selectivity was reported; see ref 13.
The reaction was found to be applicable to a number of
other arylacetyl chlorides and gave the dimethyl 2-arylide-
2126
Org. Lett., Vol. 7, No. 11, 2005

nucleophilic addition of D2O to afford â-ester acid derivative
9. Finally, spontaneous decarboxylation of 9 generates the
product 4.17
Scheme 1
It is noteworthy that 3-alkoxycarbonyl-â,γ-unsaturated
esters are useful intermediates for the synthesis of substituted
tetrahydrofurans and therefore have attracted much interest
in recent years.18 Although several methods have been
reported for the synthesis of these compounds, most of them
suffer from drawbacks such as the use of harsh conditions
and employment of strong base and/or tedious procedures.19
In conclusion, we have described a novel 1-methylimida-
zole-catalyzed reaction of DMAD with in situ generated
arylketenes leading to the synthesis of dimethyl 2-arylidene-
succinates under mild conditions. Further investigations are
underway to elucidate the mechanistic details and to disclose
the scope and limitations of this reaction.
DMAD with in situ generated arylketenes (Scheme 2). Thus,
the formal [2 + 2] cycloaddition of the zwitterion 5 to the
Scheme 2. Plausible Reaction Mechanism in the Reaction of
Arylketenes with DMAD Catalyzed by 1-Methylimidazole
Acknowledgment. We thank Dr. J.-M. Gu for X-ray
diffraction analysis.
Supporting Information Available: Crystallographicin-
formation files (CIF) for 1 and experimental procedures and
characterization data of 1, 3ak, and (Z)-4. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL050492Q
(15) Mayr, H. Angew. Chem., Int. Ed. Engl. 1975, 14, 500.
(16) A substituent may rotate either inward or outward in the electrocyclic
ring opening of cyclobutenones, for the theoretical predictions of substituent
effects on the electrocyclic ring openings of cyclobutenones; see: Ni-
wayama, S.; Kallel, E. A.; Spellmeyer, D. C.; Sheu, C.; Houk, K. N. J.
Org. Chem. 1996, 61, 2517.
(17) The reaction of acyclic ketenetrimethylsilylacetals with DMAD
afforded ring opening products of [2 + 2] cycloadduct in the presence of
catalytic amounts of ZrCl4. See: Mitani, M.; Sudoh, T.; Koyama, K. Bull.
Chem. Soc. Jpn. 1995, 68, 1683.
(18) Gordaliza, M.; Miguel del Corral, J. M.; Castro, M. A.; Salinero,
M. A.; San Feliciano, A.; Dorado, J. M.; Valle, F. Synlett 1996, 1201 and
references therein. (b) Perron, E.; Abizafi, K. F. Chem. ReV., 1989, 89,
1617.
(19) (a) Yvon, B. L.; Datta, P. K.; Le, T. N.; Charlton, J. L. Synthesis
2001, 1556. (b) Ayres, D. C.; Carpenter, B. G.; Denney, J. J. Chem. Soc.
1965, 3578. (c) Johnson, W. S.; Daub, G. H. In Organic Reactions; John
Wiley: New York, 1951; Vol. VI, pp 1-73. (d) Ballini, R.; Rinaldi, A.
Tetrahedron Lett. 1994, 35, 9247. (e) Ballini, R.; Marcantoni E.; Perella,
S. J. Org. Chem. 1999, 64, 2954.
ketene 6 affords cyclobutenone 7, followed by electrocyclic
ring opening under basic condition to give unstable vi-
nylketene 8.15,16 The latter intermediate is trapped by
Org. Lett., Vol. 7, No. 11, 2005
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