Highly E-selective solvent-free Horner-Wadsworth-Emmons reaction catalyzed by DBU

Article abstract of DOI:10.1039/c1gc15134g

The solvent-free Horner-Wadsworth-Emmons reaction of triethyl phosphonoacetate with a variety of aldehydes was catalyzed by DBU in the presence of K₂CO₃ to give E-α,β-unsaturated esters highly selectively (99:1 for most of the reactions). The reaction with ketones gave trisubstituted olefins with good to high E-selectivity by DBU-Cs₂CO₃.

Full text of DOI:10.1039/c1gc15134g

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COMMUNICATION
Highly E-selective solvent-free Horner–Wadsworth–Emmons reaction
catalyzed by DBU†
Kaori Ando* and Kyohei Yamada
Received 3rd February 2011, Accepted 22nd March 2011
DOI: 10.1039/c1gc15134g
The solvent-free Horner–Wadsworth–Emmons reaction of
triethyl phosphonoacetate with a variety of aldehydes was
catalyzed by DBU in the presence of K2CO3 to give E-a,b-
unsaturated esters highly selectively (99 : 1 for most of the
reactions). The reaction with ketones gave trisubstituted
olefins with good to high E-selectivity by DBU-Cs2CO3.
Scheme 1 Solvent-free Horner–Wadsworth–Emmons reaction using
DBU.
Due to environmental concerns, safety considerations, reduction
of costs, and the simplicity of the process, solvent-free reactions
have drawn great attention in recent years.1 Furthermore,
an increased reactivity is expected due to the intimacy of
the reagents. The stereo-defined synthesis of carbon–carbon
double bonds with high selectivity is critically important for
not only the synthesis of the olefinic compounds but also
for stereoselective reactions. The Horner–Wadsworth–Emmons
modification of the Wittig reaction is a widely used method for
the preparation of a,b-unsaturated esters.2 The phosphonate
anions are strongly nucleophilic and react readily with carbonyl
compounds under mild conditions to form olefins in good
yields. As far as we know, only a few reports described
the solvent-free Horner–Wadsworth–Emmons (HWE) reaction
before we started this project. One is the solid phase reaction
by milling a highly p-conjugated solid aldehyde with p-Ar-
benzylphosphonates using t-BuOK3a–3b and the other is the
silica gel catalyzed reaction using 1,8-diazabicyclo[5.4.0]undec-
7-ene (DBU) as a base reported by Inanaga and co-workers.3c
During the course of our study on the Z-selective HWE reagents,
(ArO)2P(O)CH2CO2Et,4 we found their reaction with PhCHO
using DBU proceeded quickly in the absence of silica gel to
give mainly E-ethyl cinnamate. Using the conventional HWE
reagents, such as triethyl phosphonoacetate 1, E-a-unsaturated
esters and ketones were obtained in high yields with 96 to
>99% E-selectivity (Scheme 1).5 Although the used DBU was
recovered in a high yield, it is desirable to avoid the use of a
stoichiometric amount of amine. Here, we would like to report
the solvent-free HWE reaction catalyzed by DBU (as little as
0.03 eq. for the reaction with aldehydes) in the presence of K2CO3
as a base.
The solvent-free HWE reaction of 1 with benzaldehyde was
carried out in the presence of several inorganic bases. As
shown in Table 1, NaOH, KOH, K2CO3, Cs2CO3, and K3PO4
can promote the reaction to some extent in 98 : 2 to 99 : 1 E-
selectivity (51–80% yield).6 However, the combined yield of the
product 3a and the recovered 1 was rather low in the cases of
NaOH and KOH (entries 1–2). That is, both NaOH and KOH
induced some decomposition of 1 during the reaction. Although
the reaction using Cs2CO3 gave highest 80% yield after 2 h, we
chose K2CO3 as an inorganic base because of its low price.
The HWE reaction using K2CO3 as a base was further studied
(Table 2). As shown in entry 4 in Table 1, 51% yield of E-3a was
obtained by stirring with 2 eq. of K2CO3 (molar ratio of 1:
K2CO3 = 1 : 2) for 2 h. We hypothesized the moderate yield was
due to the inefficient mixing. When the reaction was performed
Table 1 Effect of an inorganic base on the solvent-free HWE reaction
of 1 with benzaldehydea
Entry
Base (mmol)
Time (h)
Yield%b
E : Z
1
2
3
4
5
6
NaOH (2.0)
KOH (2.0)
Na2CO3 (2.0)
K2CO3 (2.0)
Cs2CO3 (2.0)
K3PO4 (1.0)
2
2
2
2
2
2
53 (15)
74 (7)
—
51 (49)
80 (20)
63 (27)
99 : 1
99 : 1
—
98 : 2
98 : 2
99 : 1
Department of Chemistry, Faculty of Engineering, Gifu-University,
Yanagido 1-1, Gifu, 501-1193, Japan. E-mail: ando@gifu-u.ac.jp;
Fax: 81 58 293 2674; Tel: 81 58 293 2674
† Electronic supplementary information (ESI) available: Typical experi-
mental procedures (entry 11 in Table 3 and entry 10 in Table 4) and the
NMR charts of all the products. See DOI: 10.1039/c1gc15134g
a 1.0 mmol of 1 and 1.0 mmol of 2a were used except for entry 4, where
1.0 mmol of 1 and 1.1 mmol of 2a were used. b The yields are isolated
yields and the numbers in parentheses are the recovered yields of 1 (%)
calculated from the NMR spectra of the crude mixture.
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Table 2 HWE reaction of 1 with benzaldehyde using K2CO3
Table 3 The solvent-free HWE reaction of 1 with various aldehydes
using K2CO3-DBU
Entry K2CO3 DBU (eq) H2O (eq) Conditiona Yield%b E : Z
Entry
R
DBU (eq) Conditionsa Yield %b E : Z
1
2
3
4
5
6
7
8
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.5
—
—
—
—
—
8
8
RT, 2 h
RT, 2 h
RT, 6 h
RT, 2 h
RT, 2 h
RT, 2 h
RT, 2 h
RT, 2 h
RT, 2 h
RT, 2 h
RT, 2 h
51
73
96
52
31
93
Quant.
Quant.
96
98 : 2
99 : 1
99 : 1
98 : 2
96 : 4
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
1
Ph
Ph
0.03
0.03
0.03
0.1
RT, 2 h
RT, 5 h
RT, 2 h
RT, 5 h
RT, 2 h
RT, 20 h
3a 96
3a 95
3b 82
3b 97
3b 95
3c 81
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
>99 : 1
98 : 2
2c
3
11
111c
8
—
—
—
—
—
—
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-MeOC6H4
p-MeOC6H4
o-MeC6H4
Furfural
4d
5
0.1
0.1
0.05
0.03
0.01
0.03
0.2
6
7
8
9
10
11
12e
13
14
15
16
0.03
0.03
0.03
0.03
25 ◦C, 24 h 3c 99
9
10
11
87
61
RT, 2 h
RT, 2 h
RT, 4 h
RT, 4 h
25 ◦C, 7 h
RT, 4 h
RT, 24 h
RT, 24 h
RT, 3 h
3d 93
3e 92
3f 89
3g 96
3g 93
3h 97
3i 95
3j 92
3k 94
E-PhCH CH 0.03
a 1.0 mmol of 1 and 1.1 mmol of 2a were used. b Isolated yields. c The
n-C7H15
n-C7H15
c-C6H11
2-EtPentyl
t-Bu
0.03
0.03
0.03
0.03
0.03
0.03
reaction was performed in water (0.5 mol L-1).
in the presence of 8 eq. of water, E-3a was obtained in 73% yield
after 2 h and 96% yield after 6 h (entries 2–3). However, in the
presence of more than 11 eq. of water, the reaction was slower
than the solvent-free reaction and gave lower selectivity (96 : 4)
(entries 4–5). The catalytic activity of DBU was next examined.
In the presence of 0.1 eq of DBU, the reaction proceeded faster
than the reaction in entry 2 to give E-3a in 93% yield after 2 h
(entry 6). In the absence of water, the reaction catalyzed by DBU
proceeded more efficiently to give a quantitative yield with 99 : 1
selectivity (entry 7). Although even as little as 0.01 eq. of DBU
can catalyze the reaction to give 87% yield after 2 h, the use of
0.03 eq. of DBU was set for the standard reaction conditions
(entries 8–10). The reduction of the quantity of K2CO3 to 1.5
eq. resulted in lower 61% yield (entry 11).
The solvent-free HWE reaction of 1 with a variety of
aldehydes were performed using K2CO3 (2 eq.) and DBU (0.03
eq.) and the results are summarized in Table 3.‡ Although the
10 mmol scale reaction needed a longer time (5 h) to complete
the reaction with benzaldehyde, 95% yield with 99 : 1 selectivity
was obtained (entry 2). The reaction with p-chlorobenzaldehyde
gave E-3b in 82% yield with 99 : 1 selectivity (entry 3). Since p-
chlorobenzaldehyde is a solid aldehyde and the reaction mixture
completely solidified 2 h later, we were afraid that the reaction
did not go to completion. When the reaction was performed in
the presence of 8 eq. of water or by increasing the quantity
of DBU to 0.2 eq., 97 and 95% yields were obtained with
the same 99 : 1 selectivity (entries 4–5). The reaction mixture
of p-methoxybenzaldehyde also solidified completely and the
reaction did not go to completion after 20 h to give 81% yield
(entry 6). When the reaction mixture was stirred vigorously at
25 ◦C,8 solidification did not occur and the yield was improved to
99% (entry 7). For the reaction with other aromatic aldehydes,
o-tolualdehyde and furfural, E-olefins were obtained without
difficulty in 92–93% yield with 99 : 1 selectivity by using the
standard conditions. The reaction with a-unsaturated aldehyde,
E-cinnamaldehyde also proceeded easily to give the E,E-diene
in 89% yield. The reaction with aliphatic aldehydes, n-octanal,
cyclohexancarboxaldehyde, 2-ethylhexanal, and pivalaldehyde
also gave E-olefins in 92–97% yields with 99 : 1 selectivity (entries
11–15). The 30 mmol scale reaction was performed at 25 ◦C to
BnOCHMe
a 1.0 mmol of 1 and 1.1 mmol of 2 were used except for entries 2 and 12.
b Isolated yields. c 10 mmol scale reaction. d The reaction was performed
in the presence of 8 eq. of H2O. e 30 mmol scale reaction.
give E-3g in 93% yield with 99 : 1 selectivity after 7 h (entry
12). The reaction of 2-benzyloxypropanal gave E-3k in 94%
yield with 98 : 2 selectivity. The same reaction in DME using
BuLi gave E/Z = 90 : 10 selectivity.4b The E-selectivity of the
HWE reaction with aldehydes having an a-oxygen functional
group is generally not high and the HWE reaction with those
aldehydes occasionally gave Z-olefins selectively.9 Thus, we
succeeded in not only reducing the quantity of DBU but also
increasing the E-selectivity. Since E-a,b-unsaturated esters are
versatile intermediates in organic synthesis, the development of
experimentally simple and highly E-selective protocols are still
needed.10
Solvent-free purification of the products was next attempted.
When the reaction of 1 (10 mmol) with benzaldehyde (10 mmol)
in the presence of K2CO3 (20 mmol) and DBU (0.3 mmol) was
completed, the reaction mixture was directly distilled under re-
duced pressure using a bulb-to-bulb apparatus. Disappointingly,
only 33% yield of the product was obtained (E : Z = 98 : 2). When
the residue was extracted with AcOEt, 58% of the product was
further obtained (E : Z = 99 : 1). Thus direct distillation without
using organic solvent is not practical. After the reaction mixture
was dissolved in AcOEt (2 mL) and the mixture was filtered,
the olefin was isolated in 84% yield by distillation.§ The total
amount of the used AcOEt was 8 mL. Thus, we could reduce
the quantity of organic solvent for the purification.
The solvent-free HWE reaction of 1 with ketones was studied
and the results are shown in Table 4. We have already reported
the solvent-fee HWE reaction of 1 with cyclohexanone using
DBU (3 eq.).5 Unfortunately, the reaction proceeded very
slowly to give 5a in only 20% yield after 45 h. However,
in the presence of K2CO3 (2 eq.) and DBU (0.05 eq.), the
reaction gave 5a in 79% yield after 2 d and in 88% yield by
increasing the quantity of DBU (0.2 eq.) (entries 1 and 2).
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Table 4 The solvent-free HWE reaction of 1 with various ketone
reduced the E-selectivity. The reaction with 2-octanone 4i gave
catalyzed by DBUa
80% yield with 79 : 21 E-selectivity at room temperature (entry
18). The reaction with the aliphatic ketones 4g and 4i at 25 ◦C did
not improve the selectivity and 79 : 21 E-selectivity was obtained
in 70% and 74% yields, respectively. Although the solvent-
free HWE reaction of 1 with the aliphatic ketones gave the
trisubstituted olefins in moderate E-selectivity, the reaction with
the substituted acetophenones using Cs2CO3 and DBU showed
outstanding E-selectivity and very useful for the synthesis of
those trisubstituted olefins.
Entry Ketone Base, eq.
DBU (eq) Conditions Yield %b E : Z
1
2
4a
4a
4a
4a
4b
4b
4b
4b
4c
4d
4e
4e
4f
K2CO3 2.0 0.05
K2CO3 2.0 0.2
K2CO3 2.0 0.05c
Cs2CO3 1.2 0.2
K2CO3 2.0 0.6
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
K3PO4 1.0 0.3
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
Cs2CO3 1.2 0.2
K2CO3 1.5 0.2
Cs2CO3 1.2 0.2
RT, 2 d
RT, 2 d
RT, 2 d
RT, 18 h
5a 79
5a 88
5a 83
5a 84
—
—
—
—
3
4d
5
60 ◦C, 16 h 5b 48
98 : 2
97 : 3
97 : 3
97 : 3
95 : 5
99 : 1
91 : 9
97 : 3
87 : 13
94 : 6
97 : 3
81 : 19
66 : 34
79 : 21
6
RT, 3 d
5b 64
7e
8d
9
40 ◦C, 3 d 5b 81
RT, 5 d
RT, 3 d
RT, 3 d
RT, 3 d
5b 65
5c 80
5d 78
5e 37
10
11
12
13
14
15
25 ◦C, 7 d 5e 50
RT, 3 d
5f 52
4f
25 ◦C, 3 d 5f 63
4f
40 ◦C, 3 d 5f 81
16d 4g
RT, 3 d
RT, 1 d
RT, 3 d
5g 72
5h 78
5i 80
In the presence of M2CO3 (M = K, Cs), DBU can easily
deprotonate the phosphonate reagent 1 to give the enolate
(Fig. 1). A similar explanation was suggested for the HWE
reaction of 1 in the presence of LiCl-DBU by Masamune and
Roush.14 The HWE reaction occurs with the addition of the
enolate to aldehydes, followed by oxaphosphetane formation,
P–C bond cleavage, and then O–C bond cleavage to give
the olefins.15 The oxaphosphetane formation TS2 is the rate-
determining step and E-TS2 is more stable than Z-TS2 because
of the steric repulsion between the ester moiety and the alkyl
substituent of aldehydes in Z-TS2.14 Therefore, E-olefins were
obtained selectively. Also, it should be noted that DBU can be
reproduced by the reaction of the protonated DBU with M2CO3.
When 3g (E : Z = 95 : 5) prepared from 1 using BuLi in DME
at 0 ◦C was treated with K2CO3 (2 eq.) and DBU (0.03 eq.)
for 4 h, neither the isomerization nor the decomposition was
observed. Thus, the E : Z ratio of the product prepared from 1
with aliphatic aldehyde was not changed under the reaction
conditions. However, when 5f (E : Z = 87 : 23) (entry 13 in
Table 4) was treated with Cs2CO3 (1.2 eq.) and DBU (0.2 eq.)
at 25 ◦C for 3 d, the E : Z ratio was improved to 90 : 10 without
decomposition. We believe the high E-selectivity obtained in
the solvent-free conditions described here was mainly kinetically
controlled. However, some isomerization to the more thermody-
namically stable E-olefins may occur especially for the reaction
with aromatic ketones.
17
18
4h
4i
a 1.0 mmol of 1 and 1.0 mmol of 4 were used unless otherwise noted.
b Isolated yields. c TMG was used instead of DBU. d 1.2 mmol of 1 and
1.0 mmol of 4 were used. e 1.0 mmol of 1 and 1.2 mmol of 4 were used.
1,1,3,3-Tetramethylguanidine (TMG) was also effective to give
5a in 83% yield (entry 3).5 It is interesting to note that Simoni
et al. reported that no olefinic products were detected from the
reaction of 1 with cyclohexanone and aliphatic ketones using
TMG, 1,5,7-triazabicylco[4.4.0]dec-5-ene (MTB) and its methyl
derivative (MTBD) in refluxing THF after 24 h.11,12 In contrast
to aldehydes, both the HWE reaction and the Wittig reaction
with ketones generally gave olefins with low to moderate E-
selectivity in low to moderate yields.2,7g,7h,11,13 When the reaction
of 1 with acetophenone 4b was performed in a similar manner,
the reaction hardly proceeded at all. Increasing the amount
of DBU to 0.6 eq. and increasing the temperature to 60 ◦C,
48% yield of 5b was obtained after 16 h with very high 98 : 2
selectivity (entry 5). Using 1.2 eq. of Cs2CO3 or 1.0 eq. of
K3PO4 instead of K2CO3, 81% and 65% yields were obtained
with 97 : 3 E-selectivity (entries 7 and 8). The reaction of 1 with
the p-Cl and p-NO2 substituted acetophenones 4c–4d also gave
very high 95 : 5 and 99 : 1 selectivity in high yields using Cs2CO3
and DBU (0.2 eq.) (entries 9 and 10). When the reaction of 1
with p-methoxyacetophenone 4e was performed using the same
conditions, only 37% yield was obtained with 91 : 9 selectivity at
room temperature8 (entry 11). Happily, when the reaction was
performed at 25 ◦C, 97 : 3 selectivity was obtained in 50% yield
(entry 12). At 40 ◦C, the same selectivity and the same yield
were obtained. The improvement of the selectivity at higher
temperature was also observed for p-methylacetophenone 4f.
Although 87 : 13 selectivity was obtained at room temperature,8
the selectivity was increased to 94 : 6 at 25 ◦C and to 96 : 4 at 40 ◦C
(entries 13–15). The reaction with 2-methylcyclohexanone 4g in
the similar conditions gave 72% yield with 81 : 19 E-selectivity
(entry 16). The reaction of a-tetrahydropyranyloxy acetone 4h
was less E-selective. It seems that the a-oxygen functionality
Fig. 1 The reaction mechanism of the solvent-free HWE reaction.
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In summary, we showed the solvent-free HWE reaction of 1
with aldehydes can be catalyzed by DBU (as little as 0.03 eq.) in
the presence of K2CO3 as a base. The reaction with a variety of
aldehydes gave high yields of the E-olefins with extremely high E-
selectivity (in most of the cases, 99 : 1 selectivity). After filtration,
almost pure products can be easily obtained by distillation
under reduced pressure. The HWE reaction of 1 with the
substituted acetophenones using Cs2CO3 and DBU also showed
outstanding E-selectivity and is very useful for the synthesis
of trisubstituted olefins. Since it is very difficult to separate
the E and Z isomers, it is important to prepare the olefins
highly selectively. We believe the method reported here is simple,
environmentally friendly, and safe, and it does not require
any expensive catalysts or bases. The additional advantages
of work-up simplicity, reproducibility, and extremely high E-
selectivity make this methodology a serious candidate for not
only laboratory use but also widespread industrial applications.
3 (a) J. Yang, X. Tao, C. X. Yuan, Y. X. Yan, L. Wang, Z. Liu, Y. Ren
and M. H. Jiang, J. Am. Chem. Soc., 2005, 127, 3278; (b) Z.-J. Hu,
P.-P. Sun, L. Li, Y.-P. Tian, J.-X. Yang, J.-Y. Wu, H.-P. Zhou, L.-M.
Tao, C.-K. Wang, M. Li, G.-H. Cheng, H.-H. Tang, X.-T. Tao and
M.-H. Jiang, Chem. Phys., 2009, 355, 91; (c) Y. Z. Jin, N. Yasuda and
J. Inanaga, Green Chem., 2002, 4, 498.
4 (a) K. Ando, Tetrahedron Lett., 1995, 36, 4105; (b) K. Ando, J. Org.
Chem., 1997, 62, 1934; (c) K. Ando, J. Org. Chem., 1998, 63, 8411;
(d) K. Ando, J. Org. Chem., 1999, 64, 8406; (e) K. Ando, T. Oishi, M.
Hirama, H. Ohno and T. Ibuka, J. Org. Chem., 2000, 65, 4745; (f) K.
Ando, S. Nagaya and Y. Tarumi, Tetrahedron Lett., 2009, 50, 5689;
(g) K. Ando, K. Narumiya, H. Takada and T. Teruya, Org. Lett.,
2010, 12, 1460; (h) K. Ando and Y. Suzuki, Tetrahedron Lett., 2010,
51, 2323; (i) K. Ando, K. Narumiya, H. Takada and T. Teruya, Org.
Lett., 2010, 12, 1460.
5 K. Ando and K. Yamada, Tetrahedron Lett., 2010, 51, 3297.
6 The E : Z ratios were determined by integration of the vinyl proton
signals in 400 MHz 1H NMR spectra of the crude reaction mixture.
1
All the HWE products were known compounds. H NMR spectra
are identical to the reported values: 3a–3c, 3e, 3f–3k,5 3d,7a 5a,7b both
E- and Z-5b–5d,7c both E- and Z-5e–5f,7d both E- and Z-5g,7e E-5h,7f
both E- and Z-5i.7g,7h
.
7 (a) B. Mu, T. Li, W. Xu, G. Zeng, P. Liu and Y. Wu, Tetrahedron, 2007,
63, 11475; (b) K. Miura, M. Ebine, K. Ootsuka, J. Ichikawa and A.
Hosomi, Chem. Lett., 2009, 38, 832; (c) Y. Chen, L. Huang and X. P.
Zhang, Org. Lett., 2003, 5, 2493; (d) J. Simard-Mercier, J. L. Jiang,
M. L. Ho, A. B. Flynn and W. W. Ogilvie, J. Org. Chem., 2008, 73,
5899; (e) L. Strekowski, M. Visnick and M. A. Battiste, Tetrahedron
Lett., 1984, 25, 5603; (f) S. Amslinger, K. Kis, S. Hecht, P. Adam, F.
Rohdich, D. Arigoni, A. Bacher and W. Eisenreich, J. Org. Chem.,
2002, 67, 4590; (g) D. H. Appella, Y. Moritani, R. Shintani, E. M.
Ferreira and S. L. Buchwald, J. Am. Chem. Soc., 1999, 121, 9473;
(h) S. Ge´nard and H. Patin, Bull. Soc. Chim. Fr., 1991, 128, 397.
8 Most of the reactions in Table 3 and Table 4 were performed in winter
time. The room temperature in the night was between 5 and 15 ◦C.
9 (a) B. M. Trost, S. M. Mignani and T. N. Nanninga, J. Am.
Chem. Soc., 1988, 110, 1602; (b) M. C. Bowden and G. Pattenden,
Tetrahedron Lett., 1988, 29, 711.
10 (a) V. R. Chintareddy, A. Ellern and J. G. Verkade, J. Org. Chem.,
2010, 75, 7166; (b) T. D. W. Claridge, S. G. Davies, J. A. Lee, R. L.
Nicholson, P. M. Roberts, A. J. Russell, A. D. Smith and S. M. Toms,
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11 D. Simoni, M. Rossi, R. Rondanin, A. Mazzali, R. Baruchello, C.
Malagutti, M. Roberti and F. P. Invidiata, Org. Lett., 2000, 2, 3765.
12 The HWE reaction of (MeO)2P(O)CH(NHCbz)CO2Me with 4-
substituted cyclohexanones (4 eq.) using DBU (1.05 eq.) in CH2Cl2
for 3–5 days was reported: C. Cativiela, M. D´ıaz-de-Villegas, J. A.
Ga´lvez and G. Su, ARKIVOC, 2004, 59.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Notes and references
‡ A typical experimental procedure (entry 12 in Table 3): To a mixture
of 1 (6.73 g, 30 mmol), DBU (0.13 mL, 0.9 mmol), and finely ground
K2CO3 (8.29 g, 60 mmol) was added n-octanal (5.15 mL, 33 mmol) and
the resulting mixture was stirred using a magnetic stirrer for 7 h at 25 ◦C
under Ar atmosphere. The reaction was quenched with water (20 mL)
and extracted with AcOEt (2 ¥ 10 mL). The combined extracts were
washed with brine, dried (MgSO4), and concentrated to give 4g (E : Z =
99 : 1). The product was isolated by flash chromatography (hexane–
AcOEt = 15 : 1) as a colorless oil (5.52 g, 93% yield).
§ To a mixture of 1 (2.24 g, 10 mmol), DBU (0.045 mL, 0.3 mmol), and
finely ground K2CO3 (2.77 g, 20 mmol) was added PhCHO (1.01 mL,
10 mmol) and the resulting mixture was stirred using a magnetic stirrer
for 4 h at room temperature under Ar atmosphere. AcOEt (2 mL) was
added to the crude mixture and the solid was filtered off. The solid was
rinsed with AcOEt (6 mL) and the combined filtrate was concentrated.
The resulting oil was distilled under reduced pressure using a bulb-to-
bulb apparatus (10 mm Hg/240 ◦C) to give 3a (1.51 g, yield 84%) (E : Z =
99 : 1).
13 (a) B. M. Choudary, M. L. Kantam, C. R. V. Reddy, B. Bharathi and
F. Figueras, J. Catal., 2003, 218, 191; (b) A. Spinella, T. Fortunati
and A. Soriente, Synlett, 1997, 93; (c) T. Eguchi, T. Aoyama and
K. Kakinuma, Tetrahedron Lett., 1992, 33, 5545; (d) F. Bonadies, A.
Cardilli, A. Lattanzi, L. R. Orelli and A. Scettri, Tetrahedron Lett.,
1994, 35, 3383.
14 M. A. Blanchette, W. Choy, J. T. Davis, A. P. Essenfeld, S. Masamune,
W. R. Roush and T. Sakai, Tetrahedron Lett., 1984, 25, 2183.
15 For a computational study on the reaction mechanism of the HWE
reaction, see: K. Ando, J. Org. Chem., 1999, 64, 6815.
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Afonso and A. F. Trindade, Chem. Rev., 2009, 109, 2703; (b) M. A. P.
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1146 | Green Chem., 2011, 13, 1143–1146
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