K. Ando, Y. Suzuki / Tetrahedron Letters 51 (2010) 2323–2325
2325
OH
OH
ronellal gave only 46% yield of 12 (Z:E = 63:37) together with
unidentified by-product using 3.2 equiv of 3 and NaH, we obtained
12 in 98% yield with 97:3 selectivity using 2.0 equiv of 4 (entry 8).
This shows the mildness of our reaction condition using NaI and
DBU. The reaction with 2-ethylhexanal was also performed using
NaH (entry 10). Although the selectivity is higher than the result
1) t-BuOH, H2SO4, 50 °C, 2 h
y. 60%
t-Bu
2) PhCH2OH, DCC, DMAP
CH2Cl2, RT, 2 h, y. 86%
O
O
OH
OCH2Ph
19
20
t-Bu
O
from NaI–DBU, the yield is lower. For
a,b-unsaturated aldehydes,
O
PCl3, o-t-BuC6H4OH, Pr3N, toluene,
-40 to -20 °C, then EtOH, RT, 2 h
2E-hexenal, and 2E-cinnamaldehyde, the reaction underwent in
high yields (92–99%) with moderate Z-selectivity (85:15–87:13)
using t-BuOK. The use of Triton B (benzyltrimethylammonium
hydroxide 40% in MeOH) reduced both the yield and the selectivity
(entry 12).
P
OEt
t-Bu
PhCH2O
O
y. 80%
21
t-Bu
In summary, we have demonstrated the synthesis and the use of
1) BrCH2CO2Et, 160 °C, 6 h,
y. 94%
O
P
O
O
CH2CO2Et
t-Bu
a novel polymer-supported HWE reagent 4, which gave Z-
unsaturated esters with high selectivity. t-BuOK for aromatic and
,b-unsaturated aldehydes and NaI–DBU for aliphatic aldehydes
a,b-
2) Pd/C, AcOEt, RT, 16 h,
quant
HO
O
a
are the choice of base. The development of a method to recycle
the resin is under investigation.
22
4
t-Bu
O
O(CH2)4OH
O
O
O
DCC, DMAP
P
CH2CO2Et
t-Bu
Acknowledgment
4
CH2Cl2, RT, 21 h
O
O
This work was supported by Grants-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan.
Scheme 4.
References and notes
Table 3
The HWE reaction of 4 with aldehydes
1. For reviews: (a) Solinas, A.; Taddei, M. Synthesis 2007, 2409–2453; (b) Gonthier,
E.; Breinbauer, R. Mol. Divers. 2005, 9, 51–62; (c) Booth, R. J.; Hodges, J. C. Acc.
Chem. Res. 1999, 32, 18–26.
2. (a) Bernard, M.; Ford, W. T. J. Org. Chem. 1983, 48, 326–332; (b) Hughes, I.
Tetrahedron Lett. 1996, 37, 7595–7598; (c) Bolli, M. H.; Ley, S. V. J. Chem. Soc.,
Perkin Trans. 1 1998, 2243–2246.
t
-Bu
O
1) base, THF, 0 °C
2) RCHO
O
P
O
O
CH2CO2Et
4
O
O
3. (a) Nicolaou, K. C.; Pastor, J.; Winssinger, N.; Murphy, F. J. Am. Chem. Soc. 1998,
120, 5132–5133; (b) Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.; Zecri, F. J. Org.
Lett. 1999, 1, 579–582; (c) Salvino, J. M.; Kiesow, T. J.; Darnbrough, S.;
Labaudiniere, R. J. Comb. Chem. 1999, 1, 134–139; (d) Wipf, P.; Henninger, T. C. J.
Org. Chem. 1997, 62, 1586–1587; (e) Johnson, C. R.; Zhang, B. Tetrahedron Lett.
1995, 36, 9253–9256.
4. Martina, S. L. X.; Taylor, R. J. K. Tetrahedron Lett. 2004, 45, 3279–3282.
5. Still, W. C.; Gennari, C. Tetrahderon Lett. 1983, 24, 4405–4408.
6. (a) Ando, K. Tetrahedron Lett. 1995, 36, 4105–4108; (b) Ando, K. J. Org. Chem.
1997, 62, 1934–1939; (c) Ando, K. J. Org. Chem. 1998, 63, 8411–8416; (d) Ando,
K. J. Org. Chem. 1999, 64, 8406–8408; (e) Ando, K.; Oishi, T.; Hirama, M.; Ohno,
H.; Ibuka, T. J. Org. Chem. 2000, 65, 4745–4749; (f) Ando, K. J. Synth. Org. Chem.
Jpn. 2000, 58, 869–876; (g) Ando, K. Synlett 2001, 1272–1274.
R
CO2Et
-12
Z
t
-Bu
2.0eq
4
Entry
RCHO
Base
Conditions
Yield (%)
Z:E
97:3
96:4
97:3
89:11
91:9
96:4
97:3
97:3
96:4
97:3
1
2
3
4
5
6
7
8
9
10
11
12
13
PhCHO
t-BuOK
t-BuOK
t-BuOK
t-BuOK
NaI, DBU
NaI, DBU
NaI, DBU
NaI, DBU
NaI, DBU
NaH
À78 °C to RT
À78 °C to RT
À78 to 0 °C
À78 to 0 °C
0 °C, 1 h
À78 to 0 °C
À78 °C to RT
À78 to 0 °C
À78 °C to RT
À78 °C to RT
À78 °C to RT
À78 to 0 °C
À78 to 0 °C
94
93
97
97
92
98
86
98
92
78
92
41
99
Furfural
p-ClPhCHO
p-MeOPhCHO
n-Octanal
n-Octanal
c-HexylCHO
Citronellal
2-Et-Hexanal
2-Et-Hexanal
2E-Hexenal
2E-Hexenal
7. For the reaction mechanism of the HWE reaction, see: Ando, K. J. Org. Chem.
1999, 64, 6815–6821.
8. t-BuOK is a practical base for the reaction of our reagents 2 with aromatic
aldehydes.6b Although it is also a good base for that at low temperature, Triton
B causes decomposition of 2 at 0 °C. For the reaction of 2 with aliphatic
aldehydes, sodium bases are the choice.6b,e
9. Touchard, F. P.; Capelle, N.; Mercier, M. Adv. Synth. Catal. 2005, 347, 707–711.
10. Ando, K.; Nagaya, S.; Tarumi, Y. Tetrahedron Lett. 2009, 50, 5689–5691.
11. The Z:E ratios were determined by integration of the vinyl proton signals of the
crude reaction mixture in the 400 MHz 1H NMR spectra. The non-polymer
supported compounds described in this paper were characterized by 400 MHz
1H NMR spectra and mass spectroscopy.
12. A typical procedure of the HWE reaction of 4 (entry 6 in Table 3): The resin 4
(0.307 g, 0.20 mmol) in THF (5 mL) was treated with NaI (0.033 g, 0.22 mmol)
and DBU (0.033 mL, 0.22 mmol) at 0 °C for 30 min under Ar atmosphere. After
n-octanal (0.016 mL, 0.10 mmol) was added at À78 °C, the resulting mixture
was gradually warmed to 0 °C over 3 h. The reaction was quenched with
saturated NH4Cl, and the resin was filtered and washed with hexane (10 mL).
The organic filtrate was concentrated to give 12 (R = n-C7H15) (Z:E = 96:4) in
90% purity. The product was isolated by flash chromatography (hexane/
AcOEt = 30:1) as a colorless oil (0.0196 g, yield 98%).
t-BuOK
Triton B
t-BuOK
85:15
73:27
87:13
E-PhCH@CHCHO
higher 96:4 selectivity was obtained in 98% yield (entry 6). Since
the former study shows that the Z-selectivity is higher at lower
temperature,6 this HWE reaction must occur at lower than 0 °C.
After we found this, the reaction was performed by the addition
of aldehyde at À78 °C and the mixture was allowed to warm up
to 0 °C over 2–4 h. For other aliphatic aldehydes, cyclohexanecarb-
oxaldehyde, citronellal, and 2-ethylhexanal, the reaction of 4 also
gave high Z-selectivity (96:4–97:3) in high yields (86–98%) using
NaI–DBU (entries 7–9). Although Taylor-reported reaction with cit-