A convenient method for the synthesis of (Z)-α-haloacrylates: Lewis base-catalyzed carbonyl olefination using α-halo-C,O-bis(trimethylsilyl)ketene acetals

Article abstract of DOI:10.1016/j.tetlet.2009.02.019

A highly useful method for the stereoselective synthesis of (Z)-α-haloacrylates from various aldehydes that uses α-halogenated ethyl-C,O-bis(trimethylsilyl)ketene acetals in the presence of a Lewis base catalyst such as acetate salts was established. This

Full text of DOI:10.1016/j.tetlet.2009.02.019

Tetrahedron Letters 50 (2009) 3261–3262
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A convenient method for the synthesis of (Z)-
a
-haloacrylates: Lewis
base-catalyzed carbonyl olefination using
bis(trimethylsilyl)ketene acetals
a-halo-C,O-
Makoto Michida a, Takako Toriumi b, Teruaki Mukaiyama b,
*
a Process Technology Research Laboratories, Daiichi Sankyo Co., Ltd, 1-16-3 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
b Tokyo Chemical Industry Co., Ltd, 6-15-5 Toshima, Kita-ku, Tokyo 114-0003, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly useful method for the stereoselective synthesis of (Z)-a-haloacrylates from various aldehydes
Received 13 January 2009
Revised 4 February 2009
Accepted 5 February 2009
Available online 10 February 2009
that uses
a-halogenated ethyl-C,O-bis(trimethylsilyl)ketene acetals in the presence of a Lewis base cata-
lyst such as acetate salts was established. This procedure gives the corresponding
a
-halo- ,b-unsaturated
a
esters in high yields with excellent stereoselectivity from E/Z mixtures of ketene silyl acetals under mild
conditions.
Ó 2009 Elsevier Ltd. All rights reserved.
a
-Halo-
useful building blocks that have haloolefin moiety for synthesizing
polymers,1 or biologically active compounds.2 Among them,
a
,b-unsaturated carboxylic esters (
a
-haloacrylates) are
formed aldol intermediates via the following Lewis base-catalyzed
aldol-type reaction (Scheme 1).
a
-
In order to investigate carbonyl haloolefination reaction, prepa-
ration of reagents 1a and 1b was studied. Interestingly, it was
found that 1a and 1b were directly obtained with the E/Z = ca 1:1
mixtures from the corresponding inexpensive ethyl haloacetates
on treatment with LDA and TMSCl (Scheme 2).12 It is noted that
these olefinating reagents are easily purified by distillation.
chloro and
a-bromoacrylates are used frequently for C–C bond
forming reactions such as cross coupling reaction3 or nucleophilic
addition4 in keeping their olefinic geometries. The stereoselective
synthesis of
satile for the preparation of various trisubstituted olefins.
Among the synthetic approaches for -haloacrylates, reactions
of aldehydes and
-halophosphonium ylide (Wittig reaction)5
and -halophosphonoacetate (Horner–Wadsworth–Emmons reac-
a-haloacrylates, therefore, is quite important and ver-
a
Reactions of benzaldehyde 2a with a-chloro ketene acetal 1a
a
(Z:E = 1:1) were tried in the presence of 5 mol % each of various Le-
wis bases (Table 1). When the reaction was carried out in the pres-
ence of AcOn-Bu4N in CH2Cl2 that was previously reported as the
optimized conditions of this type of reaction, the desired product
3a was provided in poor yield (entry 1). On the other hand, the
yield increased when the reaction was carried out by using various
catalysts in DMF (entries 2–6) while its stereoselectivity was poor
in the case of AcOLi (entry 2). This result is assumed that the first
aldol reaction proceeds via a cyclic (Li-chelated) transition state
a
tion)6 are well known. These reactions are one of the most straight-
forward methods despite the stereoselectivities that are yet to be
solved, and preparations of reagents are often needed to use haz-
ardous or expensive reagents.7 Recently, Cr(II)-mediated carbonyl
olefination by using CrCl2 and trihaloacetate was reported.8 This
reaction is a quite useful method for the stereoselective synthesis
of (Z)-a-haloacrylates although it requires an excess amount of
hazardous metal compounds.
It was shown in our previous report that various acetate salts
worked as effective Lewis base catalysts in activating trimethylsilyl
(TMS) derivatives in their reactions with electrophiles.9 More re-
cently, it was also shown that ethyl-C,O-bis(trimethylsilyl)ketene
OTMS
OEt
TMS
X
O
AcOM
or
TMSOM
R
OEt
X
AcOTMS
or
acetals10 and
of ,b-unsaturated esters or (Z)-
ceeded with high stereoselectivity. Then,
lefination reactions were examined by using the above
combination to expand their utilities. That is, -haloacrylates are
a
-fluorinated ones11 are quite useful in the synthesis
a
a-fluoroacrylates, which pro-
TMS O
2
O
a
-chloro and -bromoo-
a
TMS
X
OM
OEt
TMS
R
H
COOEt
a
X
M
formed directly from aldehydes by the syn-elimination of the
O
X = Cl, Br
M = Li, Na, K, Cs, Nn-Bu
R
H
4
* Corresponding author. Fax: +81 3 3260 4185.
E-mail address: mukaiyam@abeam.ocn.ne.jp (T. Mukaiyama).
Scheme 1. Lewis base-catalyzed carbonyl olefination.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.019

3262
M. Michida et al. / Tetrahedron Letters 50 (2009) 3261–3262
Table 3
2.5 eq. LDA
2.75 eq. TMSCl
TMS
X
OTMS
OEt
O
AcONa-catalyzed carbonyl haloolefination of various aldehydes
X
OEt
O
THF, 78°C
O
TMS
X
OTMS
OEt
Cat. AcONab
DMF, r t, 2 h
1a b
+
OEt
R
H
1a X = Cl : 50%
1b X = Br : 58%
X
g
2b g
1a, 1b
(1.2 equiv)a
3b g, 4b
Scheme 2. Preparation of ketene acetals 1a and 1b.
Entry
Aldehyde
2
X
Product
Yieldc (%)
Z:Eb
Table 1
1
2
3
4
5
6
7
8
9
2-ClC6H4
2-ClC6H4
4-ClC6H4
4-ClC6H4
4-Me2NC6H4
4-Me2NC6H4
4-MeO2CC6H4
4-MeO2CC6H4
2-Furyl
2-Furyl
2-Thiophen
2-Thiophen
b
b
c
c
d
d
e
e
f
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
3b
4b
3c
4c
3d
4d
3e
4e
3f
85
77
76
72
92
67
81
58
93
79
94
74
99:1
99:1
99:1
97:3
94:6
92:8
98:2
98:2
98:2
95:5
97:3
97:3
Optimization of chloroolefination
O
O
Catalyst
(5 mol %)
TMS
Cl
OTMS
OEt
+
H
OEt
Solvent, rt, 2 h
Cl
2a
1a (1.2 equiv)a
3a
Entry
Catalyst
Solvent
Yieldb (%)
Z:Eb
10
11
12
f
g
g
4f
3g
4g
1
2
3
4
5
6
AcOn-Bu4N
AcOLi
AcONa
AcOK
AcOCs
CH2Cl2
DMF
DMF
DMF
DMF
DMF
37
83
88
70
64
71
99:1
78:22
98:2
99:1
97:3
98:2
a
Ketene acetals 1a and1b in a ratio of ca 1:1 were used
1a: 5 mol % of AcONa, 1b: 20 mol % of AcONa were used.
Isolated yield.
b
c
AcOn-Bu4N
d
Diastereomeric ratios were determined by GC analysis.
a
Ketene acetal 1a in a ratio of ca 1:1 was used.
Yields and ratios were determined by GC analysis using internal standard.
b
ence of a catalytic amount of AcONa, this reaction was observed to
proceed smoothly in good to high yield with high Z-selectivity
even when E/Z mixture of the ketene acetals was used. In this reac-
tion, TMS2O that was formed together was removed easily by evap-
oration. Moreover, these reagents can be prepared in one step from
inexpensive ethyl haloacetate. Further studies on this type of reac-
tion are now in progress.
which affords syn/anti mixture of the aldol intermediate. Conse-
quently, AcONa was the catalyst (entry 3) that gave the best result
both in yield and stereoselectivity.13
Next, reactions of
a-bromo-substituted ketene acetal 1b
(Z:E = 1:1) were studied (Table 2). When the reactions using
5 mol % of various catalysts were carried out, reactions did not
complete and a large amount of 2a and 1a remained (entries 1–
5). In order to complete the reaction, the catalyst loading increased
to 10 and 20 mol % (entries 6 and 7). As a result, the reaction pro-
ceeded to complete when 20 mol % of AcONa was used and affor-
References and notes
1. (a) Egen, M.; Voss, R.; Griesebock, B.; Zentel, R.; Romanov, S.; Torres, C. S. Chem.
Mater. 2003, 15, 3786; (b) Marvel, C. S.; Weil, E. D.; Wakefield, L. B.; Fairbanks,
C. W. J. Am. Chem. Soc. 1953, 75, 2326.
ded the corresponding (Z)-a-bromoacrylate 4a in good yield with
2. (a) Hanessian, S.; Yun, H. Y.; Hou, Y. H.; Tintelnot-Blomney, M. J. Org. Chem.
2005, 70, 6746; (b) Lavilla, R.; Coll, O.; Bosch, J.; Orozco, M.; Luque, F. J. Eur. J.
Org. Chem. 2001, 3719; (c) Toyoda, M.; Asano, T.; Ihara, M. Org. Lett. 2005, 7,
3929.
3. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b) Stille, J. K.; Tanaka, K.;
Katsumura, S. Org. Lett. 2000, 2, 373.
high stereoselectivity.
Further, reactions of various aldehydes with ketene acetals 1a
and 1b were tried in the presence of a catalytic amount of AcONa
(Table 3). Then, aromatic aldehydes having electron-donating or -
withdrawing groups reacted smoothly to afford the corresponding
esters 3b–e and 4b–e in good to high yields with high Z-selectivi-
ties (entries 1–8). Reactions of heteroarylaldehydes 1f and 1g pro-
ceeded as well to give 3f–g and 4f–g (entries 9–12).
Thus, a convenient method for the stereoselective synthesis of
(Z)-a-haloacrylates by using a-chloro and a-bromo-C,O-bis(tri-
methylsilyl)ketene acetals 1a and 1b was established. In the pres-
4. José, M. C.; Mónica, H. J. Org. Chem. 2005, 70, 4714.
5. (a) Ohno, H.; Mizutani, T.; Kadoh, Y.; Aso, A.; Miyamura, K.; Fujii, N.; Tanaka, T.
J. Org. Chem. 2007, 72, 4378; (b) Humphrey, J. M.; Liao, Y. S.; Ali, A.; Rein, T.;
Wong, Y. L.; Chen, H. J.; Courtney, A. K.; Martin, S. F. J. Am. Chem. Soc. 2002, 124,
8584.
6. (a) Tago, K.; Kogen, H. Org. Lett. 2000, 2, 1975; (b) Sano, S.; Ando, T.; Yokoyama,
K.; Nagao, Y. Synlett 1998, 777.
7. (a) Huang, Z.; Yu, X. C.; Huang, X. Tetrahedron Lett. 2002, 43, 6823; (b) Denny, D.
B.; Ross, K. W. J. Org. Chem. 1962, 27, 998.
8. (a) Barma, D. K.; Kundu, A.; Zhang, H. M.; Mioskowski, C.; Falck, J. R. J. Am.
Chem. Soc. 2003, 125, 3218; (b) Falck, J. R.; Bejot, R.; Barma, D. K.;
Bandyopadhyay, A.; Joseph, S.; Mioskowski, C. J. Org. Chem. 2006, 71, 8178.
9. (a) Nakagawa, T.; Fujisawa, H.; Mukaiyama, T. Chem. Lett. 2003, 32, 462; (b)
Takahashi, E.; Fujisawa, H.; Mukaiyama, T. Chem. Lett. 2005, 34, 84; (c) Kawano,
Y.; Kaneko, N.; Mukaiyama, T. Chem. Lett. 2005, 34, 11.
Table 2
Optimization of bromoolefination
O
O
TMS
Br
OTMS
Catalyst
+
H
OEt
10. Michida, M.; Mukaiyama, T. Chem. Lett. 2008, 37, 704.
11. Michida, M.; Mukaiyama, T. Chem. Lett. 2008, 37, 890.
OEt
a
Br
4a
DMF, rt, 2 h
12. Preparation of 1a: To a mixture of ethyl chloroacetate (103.7 mmol) and TMSCl
(285.2 mmol) in THF (40 mL) at À78 °C was added dropwise a THF solution
(60 mL) of lithium diisopropylamide prepared by reaction of diisopropylamine
(259.3 mmol) with n-BuLi (2.6 M in hexane, 259.3 mmol). The resulting
mixture was stirred for 2 h and gradually raised to room temperature. To the
reaction mixture was added dry hexane (200 mL) and filtered. The filtrate was
evaporated, which was distilled to afford the desired product as clear liquid
(50% isolated yield, E/Z = 1:1).
13. To a stirred solution of aldehyde (0.5 mmol) and AcONa (0.025 mmol) in DMF
(2.5 mL) was added dropwise ketene acetal 1a (0.6 mmol) at room temperature
and stirred for 2 h. The reaction mixture was quenched by aqueous 1 M HCl
(0.5 mL) and extracted with brine (5 mL) and AcOEt (15 mL). The organic layer
was dried over anhydrous Na2SO4 and the solvent was evaporated under
reduced pressure. The crude product was purified by preparative TLC to give
the desired product.
2a
1b (1.2 equiv)
Entry
Catalyst (mol %)
Yieldb (%)
Z:Eb
1
2
3
4
5
6
7
AcOLi
AcONa
AcOK
(5)
(5)
(5)
(5)
(5)
(10)
(20)
30
24
21
15
7
69:31
96:4
97:3
94:6
92:8
96:4
97:3
AcOCs
AcOn-Bu4N
AcONa
AcONa
38
75
a
Ketene acetal 1b in a ratio of ca 1:1 was used.
Yields and ratios were determined by GC analysis using internal standard.
b