Stereoselective dabco-catalyzed synthesis of (E)-α-Ethynyl-α, β-unsaturated esters from allenyl acetates

Article abstract of DOI:10.1021/ol9001703

(E)-α-Ethynyl-α,β-unsaturated esters were exclusively prepared in good to excellent yields from treatment of allenyl acetates with 10 mol % DABCO in DMF at room temperature.

Full text of DOI:10.1021/ol9001703

ORGANIC
LETTERS
2009
Vol. 11, No. 6
1445-1448
Stereoselective DABCO-Catalyzed
Synthesis of
(E)-r-Ethynyl-r,ꢀ-Unsaturated Esters
from Allenyl Acetates
Yongsik Choe and Phil Ho Lee*
National Research Laboratory for Catalytic Organic Reaction, Department of
Chemistry, and Institute for Molecular Science and Fusion Technology, Kangwon
National UniVersity, Chuncheon 200-701, Republic of Korea
phlee@kangwon.ac.kr
Received January 27, 2009
ABSTRACT
(E)-r-Ethynyl-r,ꢀ-unsaturated esters were exclusively prepared in good to excellent yields from treatment of allenyl acetates with 10 mol %
DABCO in DMF at room temperature.
The construction of R-ethynyl-R,ꢀ-unsaturated esters is one
of the challenging problems in synthetic organic chemistry.1
In fact, many efficient synthetic methods for the preparation
of these compounds have been reported for decades.2
However, the need for a highly stereoselective synthesis of
(E)-R-ethynyl-R,ꢀ-unsaturated esters has remained.1 In gen-
eral, the stereoselective synthesis of these compounds was
accomplished by the transition metal-catalyzed cross-
coupling reactions of (Z)-R-halo-R,ꢀ-unsaturated esters with
terminal alkynes (Sonogashira reaction). Nevertheless, this
method is limited because the stereoselective preparation of
(Z)-R-halo-R,ꢀ-unsaturated esters is difficult and isomeriza-
tion of these compounds somewhat occurred during the cross-
coupling reactions.3 Although a highly stereoselective syn-
thesis of (Z)-R-halo-R,ꢀ-unsaturated esters via CrCl2-
mediated olefinations of aldehydes with trihaloacetates was
reported,4 the preparation of these compounds through
bromination-dehydrobromination,5 rearrangements,6 alkoxy-
carbonylation,7 deoxygenation of glycidic esters,8 thermal
eliminations,9 or Wittig/Horner-Emmons/ Peterson-type con-
densations10 often suffer from poor stereoselectivities,
unsatisfactory yields, costly reagents, and/or lengthy proce-
dures.11 Therefore, we tried to prepare exclusively (E)-R-
(3) (a) Zhang, X.; Qing, F.-L.; Yang, Y.; Yu, J.; Fu, X.-K. Tetrahedron
Lett. 2000, 41, 2953. (b) Olpp, T.; Bru¨ckner, R. Synthesis 2004, 2135.
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J. Am. Chem. Soc. 2003, 125, 3218.
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Utaka, M. J. Org. Chem. 1986, 58, 5952. (b) Rossi, R.; Bellina, F.; Bechini,
C.; Mannina, L.; Vergamini, P. Tetrahedron 1998, 54, 135. (c) Shi, W.;
Xiao, F.; Wang, J. J. Org. Chem. 2005, 70, 4318. (d) Wang, Y.; Burton,
D. J. Org. Lett. 2006, 8, 5295. (e) Lemay, A. B.; Vulic, K. S.; Ogilvie,
W. W. J. Org. Chem. 2006, 71, 3615. (f) Tsukada, N.; Niomiya, S.; Ayoama,
Y.; Inoue, Y. Org. Lett. 2007, 9, 2919.
(5) (a) Forti, L.; Ghelfi, F.; Pagnoni, U. M. Tetrahedron Lett. 1995, 36,
3023. (b) Kim, K. M.; Park, I. H. Synthesis 2004, 2641.
(6) Kruper, W. J., Jr.; Emmons, A. H. J. Org. Chem. 1991, 56, 3323.
(7) Alami, M.; Crousse, B.; Linstrumelle, G. Tetrahedron Lett. 1995,
36, 3687.
(2) (a) Rossi, R.; Bellina, F.; Bechini, C.; Mannina, L.; Vergamini, P.
Tetrahedron 1998, 54, 135. (b) Trost, B. M.; Gunzner, J. L.; Yasukata, T.
Tetrahedron Lett. 2001, 42, 3775. (c) Dai, W.-M.; Wu, A.; Hamaguchi,
W. Tetrahedron Lett. 2001, 42, 4211. (d) Lemay, A.; Vulic, K.; Ogilivie,
W. J. Org. Chem. 2006, 71, 3615.
(8) Buschmann, E.; Schafer, B. Tetrahedron 1994, 50, 2433.
(9) (a) Satoh, T.; Itoh, N.; Onda, K.; Kitoh, Y.; Yamakawa, K. Bull.
Chem. Soc. Jpn. 1992, 65, 2800. (b) Ishihara, T.; Shintani, A.; Yamanaka,
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10.1021/ol9001703 CCC: $40.75
Published on Web 02/16/2009
2009 American Chemical Society

ethynyl-R,ꢀ-unsaturated esters from another precursor with-
out the use of (Z)-R-halo-R,ꢀ-unsaturated esters. As part of
our continuing studies into the utility of allene functional
groups in synthesis,12 we report herein the preparation of
the exclusive synthesis of (E)-R-ethynyl-R,ꢀ-unsaturated
esters from allenyl acetates catalyzed by DABCO.
First, a variety of allenyl acetates were prepared from the
reaction of aldehydes with organoindium reagent in situ
generated from ethyl 4-bromobutynoate and indium in the
presence of lithium iodide in DMF and subsequent acety-
lation (Scheme 1).12k
enylphosphine and DABCO were subsequently examined.
The use of triphenylphosphine (0.2 equiv) provided 2d in
69% yield in DMF for 0.5 h (entry 4). In the case of DABCO
(0.2 equiv), the desired product 2d was exclusively produced
in 75% yield in DMF (entry 5). DMF was the best solvent
among several reaction media examined (DMF, THF, and
CH3CN) (entries 5-7). Of the reactions screened, the best
results were obtained with DABCO (0.1 equiv) in DMF at
25 °C for 2.5 h, producing ethyl (E)-R-ethynyl cinnamate
(2d) in 81% with complete stereoselectivity (entry 8).
However, exposure of 1d to DABCO (2.0 equiv) gave 2d
in 54% yield (entry 9). There is no ethyl (Z)-R-ethynyl
cinnamate formed in any reactions. In addition, the corre-
sponding allenyl alcohol did not react with DABCO.
To demonstrate the efficiency and scope of the present
method, we applied the catalytic system to a variety of allenyl
acetates (Table 2). Allenyl acetate 1a was treated with
Scheme 1. Preparation of Allenyl Acetates
Table 2. DABCO-Catalyzed Synthesis of
(E)-R-Ethynyl-R,ꢀ-Unsaturated Esters from Allenyl Esters
reactant time product yield
Initially, allenyl acetates were treated with a variety of
acid or base. These results are summarized in Table 1.
entry
R
(1)
(h)
(2)
(%)a
1
2
3
4
5
6
7
8
n-Pr
C6H11
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
3.5
4
1
2.5
0.5
0.5
1
3
2
1
1
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
72
82
70
81
86
88
73
84
72
80
80
81
81
84
PhCHdCBr
Ph
4-Cl-C6H4
3-Br-C6H4
2-I-C6H4
2,4,6-Me3-C6H2
3-MeO-C6H4
3,5-(MeO)2-C6H3
3,4-(OCH2O)-C6H3
4-Ac-C6H4
4-MeO2C-C6H4
2-Furyl
Table 1. Reaction Optimization
9
10
11
12
13
14
entry
reagent (equiv)
solvent
time (h)
yield (%)a
0.5
0.5
0.5
1
2
3
4
5
6
7
8
9
PPTS (0.2)
AcOH (0.2)
Pyridine (0.2)
PPh3 (0.2)
DABCO (0.2)
DABCO (0.2)
DABCO (0.20
DABCO (0.1)
DABCO (2.0)
CH2Cl2
DMF
DMF
DMF
DMF
THF
CH3CN
DMF
THF
6
12
0
0
0.67
0.5
0.5
4.5
4.5
2.5
0.5
75
69
75
50
70
81
54
a Isolated yield.
DABCO (0.1 equiv) in DMF for 3.5 h to selectively produce
ethyl 2(E)-ethynyl-2-hexenoate (2a) in 72% yield (entry 1).
In the case of allenyl acetate obtained from cyclohexanecar-
baldehyde, ethyl 2(E)-ethynyl-3-cyclohexylacrylate 2b was
exclusively produced in 82% yield (entry 2). Under the
optimum reaction conditions, allenyl acetate 1c prepared from
trans-2-bromocinnamaldehyde gave rise to the corresponding
(E)-R-ethynyl-R,ꢀ-unsaturated ester 2c in 70% yield (entry
3). Altering the electron demand of the substituents on
aromatic rings did not diminish the efficiency and selectivity
(entries 5-12). Allenyl acetates (1e, 1f and 1g) possessing
4-chlorophenyl, 3-bromophenyl, and 2-iodophenyl group
were cleanly converted to the desired products (2e, 2f, and
2g) in good to excellent yields (entries 5-7). Treatment of
a Isolated yield.
Allenyl acetate (1d) did not react with PPTS or AcOH
(entries 1 and 2). Surprisingly, treatment of 1d with pyridine
(0.2 equiv) in DMF selectively produced ethyl (E)-R-ethynyl
cinnamate (2d) in 75% yield (entry 3). The E selectivity was
1
determined by the chemical shift of the vinyl proton in H
NMR spectrum of the product 2d. The vinyl proton in the E
isomer of 2d appeared at upfield due to the shielding effect
from the ester group.3b Encouraged by this result, triph-
1446
Org. Lett., Vol. 11, No. 6, 2009

allenyl acetates having 2,4,6-trimethylphenyl and 3,5-
dimethoxyphenyl group with DABCO (0.1 equiv) exclusively
provided (E)-R-ethynyl-R,ꢀ-unsaturated esters (2h and 2j)
in 84% and 80% yields, respectively (entries 8 and 10). The
present method worked equally well even though the
derivatives of allenyl acetate (1l and 1m) bearing electron-
withdrawing groups such as ketone and ester were employed
(entries 12 and 13). Allenyl acetate (1n) possessing furyl
group turned out to be compatible with the reaction condi-
tions (entry 14). Surprisingly, no (Z)-R-ethynyl-R,ꢀ-unsatur-
ated esters are formed in any reactions. Unfortunately,
tetrasubstituted alkenes bearing ethynyl group could not be
prepared because acetylation of the corresponding 3°-alcohol
did not proceed.
signals at δ 6.67 (d, J ) 3.98 Hz, 1H) and δ 6.16 (d, J )
3.94 Hz, 1H), indicating that R-ethynyl-R,ꢀ-unsaturated ester
2d are produced through the vinylammonium salt as inter-
mediate (Figure 1).
Scheme 2. Plausible Reaction Pathway
Figure 1.
1H NMR (300 MHz, DMF-d7, 25 °C) spectrum of the
reaction mixture of 1d and DABCO.
A piece of mechanistic evidence involves the exclusive
formation of (E)-R-ethynyl-R,ꢀ-unsaturated esters. The ap-
propriate overlap to expel the acetate group requires overlap
of the π-system with the antibonding orbital of the C-OAc
bond as it reacts with DABCO. Then, the two appropriate
conformations (A and B) are possible. The conformation A
should be preferred due to a simple steric argument (Scheme
3).
Scheme 3. Reason of Exclusive Formation of
(E)-R-Ethynyl-R,ꢀ-Unsaturated Esters
One possible reaction mechanism is shown in path A of
Scheme 2. SN 2′-type displacement of allenyl acetate with
DABCO affords the vinylammonium salt 4 as an intermedi-
ate. Subsequent elimination reaction of 4 produces (E)-R-
ethynyl-R,ꢀ-unsaturated esters 2d and regenerates the DAB-
CO catalyst to continue catalytic cycle. Displacement of
allenyl acetate through abstract of allenyl proton by DABCO
can be postulated as another possible mechanism of the
reaction in path B.13However, the latter mechanism is ruled
out because the vinylammonium salt 4 is detected in NMR
In summary, we have developed an exclusive synthetic
method of (E)-R-ethynyl-R,ꢀ-unsaturated esters from the
treatment of allenyl acetates with DABCO (0.1 equiv) in
DMF at room temperature.
Acknowledgment. Dedicated to Professor Bong Rae Cho
on the occasion of his 60th birthday. This work was
1
study. H NMR (400 MHz, DMF-d7, 25 °C) study of the
reaction mixture of 1d and DABCO showed new vinylic
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1447

supported by the Korea Science and Engineering Foundation
(KOSEF) through the National Research Laboratory Program
funded by the Ministry of Science and Technology (No.
M10600000203-06J0000-20310) and Korea Sanhak Founda-
tion. Dr. Sung Hong Kim at the KBSI (Daegu) is thanked
for obtaining the MS data. The NMR data were obtained
from the central instrumental facility in Kangwon National
University.
Supporting Information Available: Experimental pro-
cedure and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
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