KOH-promoted reaction of C,O,O-tris(trimethylsilyl) ketene acetal with aldehydes: Practical and easy access to (E)-α,β-ethylenic carboxylic acids

Article abstract of DOI:10.1081/SCC-100103529

The use of a catalytic amount of KOH has been found to be very efficient in promoting reaction of silylketene acetal 1 with aldehydes 2 to afford the corresponding (E)-α,β-ethylenic carboxylic acids 3 under very mild conditions.

Full text of DOI:10.1081/SCC-100103529

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KOH-PROMOTED REACTION OF
C,O,O-TRIS(TRIMETHYLSILYL)
KETENE ACETAL WITH
ALDEHYDES: PRACTICAL AND
EASY ACCESS TO (E)-α,β-
ETHYLENIC CARBOXYLIC
ACIDS
Nathalie Lensen a , Sinda Mouelhi a & Moncef
Bellassoued b
a Université de Cergy-Pontoise , Laboratoire de
Synthèse Organométallique Associé au C.N.R.S.,
5 Mail Gay-Lussac, Neuville-sur-Oise, Cergy-
Pontoise, Cedex, 95031, France
b Université de Cergy-Pontoise , Laboratoire de
Synthèse Organométallique Associé au C.N.R.S.,
5 Mail Gay-Lussac, Neuville-sur-Oise, Cergy-
Pontoise, Cedex, 95031, France
Published online: 09 Nov 2006.
To cite this article: Nathalie Lensen , Sinda Mouelhi & Moncef Bellassoued
(2001) KOH-PROMOTED REACTION OF C,O,O-TRIS(TRIMETHYLSILYL) KETENE
ACETAL WITH ALDEHYDES: PRACTICAL AND EASY ACCESS TO (E)-α,β-ETHYLENIC
CARBOXYLIC ACIDS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:7, 1007-1011, DOI: 10.1081/
SCC-100103529

To link to this article: http://dx.doi.org/10.1081/SCC-100103529
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SYNTHETIC COMMUNICATIONS, 31(7), 1007–1011 (2001)
KOH-PROMOTED REACTION OF
C,O,O-TRIS(TRIMETHYLSILYL) KETENE
ACETAL WITH ALDEHYDES: PRACTICAL
AND EASY ACCESS TO (E)-a,b-ETHYLENIC
CARBOXYLIC ACIDS
Nathalie Lensen, Sinda Mouelhi, and Moncef Bellassoued*
Laboratoire de Synthese Organometallique Associe au
C.N.R.S., Universite de Cergy-Pontoise, 5 Mail
Gay-Lussac, Neuville-sur-Oise, 95031 Cergy-Pontoise
Cedex, France
ABSTRACT
The use of a catalytic amount of KOH has been found to
be very efficient in promoting reaction of silylketene acetal 1
with aldehydes 2 to afford the corresponding (E)-ꢀ,ꢁ-ethylenic
carboxylic acids 3 under very mild conditions.
Conjugated (E)-ethylenic carboxylic acids have great importance in
synthetic chemistry, and new methods are constantly sought with the aim
of obtaining more simple and efficient routes to prepare them with high E
stereoselectivity. We have recently reported the use of Lewis acids and
fluorides as catalysts in the reaction of C,O,O-tris(trimethylsilyl)ketene
acetal 1 with aldehydes 2, leading to the corresponding alkenoic acids 3.1
* Corresponding author.
1007
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1008
LENSEN, MOUELHI, AND BELLASSOUED
Scheme.
We have found that solid KOH can induce cleavage of the O-Si bond
of trimethylsilylenols at room temperature. The enolate generated in situ
can efficiently be used in aldolization reactions.2 The simplicity with which
solid KOH can be handled, therefore, encouraged us to explore its potential
as a catalyst for the direct synthesis of unsaturated carboxylic acids 3 by
means of the silyl ketene acetal 1 (Scheme). We report herein our findings of
this investigation.
We first examined the reaction of 1 with benzaldehyde to determine
the best conditions for this aldolization-olefination process. Potassium
hydroxide (1%) is indeed an excellent promoter for this reaction. Too
much catalyst is harmful, probably because of the retrograde aldol reaction.
The use of N,N-dimethylformamide (DMF) or dimethyl sulfoxide (DMSO)
as solvent seems to be essential, since most of the benzaldehyde was recov-
ered when the reaction was performed in tetrahydrofuran (THF). It is note-
worthy that the reaction is very clean and, in all cases, no side-products were
observed.
Finally, in order to check the generality of this new procedure, a
large array of aldehydes was used. The results are summarized in the
Table.
The reaction was exceptionally effective with aromatic as well
as aliphatic aldehydes. Non-enolizable aromatic aldehydes with electron-
withdrawing or electron-donating groups give in all cases the desired ꢀ,ꢁ-
ethylenic carboxylic acids 3 in good yields and with a total E stereoselectivity.
Unsaturated aldehydes undergo 1,2-addition exclusively, leading to the cor-
responding conjugated alkenoic acids. It is of interest to notice that, from a
synthetic viewpoint, the reaction was also quite efficient with enolizable
aldehydes. Moreover, the use of KOH is also quite effective in the reaction
of 1 with phenylacetaldehyde, leading to (E)-4-phenyl-2-butenoic acid17 3j,
which is difficult to obtain by other methods.
In conclusion, the results reported here show that solid KOH (1%) is
an extremely useful alternative promoter to Lewis acids and fluorides, which
are usually used in the aldol-type reactions of silyl enol ethers. The use of
KOH constitutes a significant improvement because of its low cost, reduced
health hazard, and ease in handling.

DL-139-CH7-UC1-4
(E )-a,b-ETHYLENIC CARBOXYLIC ACIDS
1009
Table. Conversion of Aldehydes 2 into Acids 3 by Means of Silylketene Acetal 1
Time
(h)
Yield
(%)
Lit.
Yield (%)
M.p.
(ꢁC)
Lit.
m.p. (ꢁC)
Acids 3
R
3a
3b
3c
3d
3e
Ph–
0.5
4.0
3.5
5.0
5.0
96
70
80
75
94
923
504
953
695
806
132–133
256
1323
255–25612
2863
233–23513
111–1136
p-NCPh–
p-O2NPh–
p-(Me)2NPh–
m-PhOPh–
286
230–232
111–112
3f
4.0
4.0
93
88
457
788
233
232–23514
146–14715
3g
146–148
3h
3i
5.0
4.0
86
81
793
569
164–166
186–187
1633
1879
3j
PhCH2–
nC7H15–
1 min
5.0
55
76
310
6511
62–63
oil
64–6516
oil11
3k
EXPERIMENTAL
All experiments were carried out under a nitrogen atmosphere. Unless
otherwise noted, starting materials were obtained from commercial
suppliers and were used without further purification. Tetrahydrofuran and
diethyl ether were distilled from sodium and benzophenone prior to use.
Chlorotrimethylsilane was distilled from magnesium. Diisopropylamine was
distilled from CaH2 and stored over molecular sieves. Lithium diisopropyl-
amide (LDA) was prepared in situ according to the method of Gaudemar.18
Chemical shifts are given in ppm (J in Hz) relative to TMS. TLC monitoring
was performed using a mixture of cyclohexane–ethyl acetate as eluent
(70/30).
Preparationof C,O,O-Tris(trimethylsilyl)ketene Acetal 1
To a cooled (ꢀ80ꢁC) solution of LDA prepared from phenanthrene
(2.3 g, 12.5 mmol), diisopropylamine (11.1 g, 0.11 mol), hammered lithium
(0.7 g, 0.1 mol) in ether (20 mL)-THF (20 mL) was added a solution of

1010
LENSEN, MOUELHI, AND BELLASSOUED
trimethylsilyl ꢀ-trimethylsilylated acetate19 (14.28 g, 0.07 mol) in THF
(10 mL) during 30 min. The resulting mixture was stirred at the same tem-
perature for 1 h, then quenched with chlorotrimethylsilane (13 mL, 0.1 mol)
at ꢀ80ꢁC. After being stirred at the same temperature for 30 min, the
solution was gradually warmed to room temperature and filtered through
a pad of Celite. The solvent was removed under reduced pressure and the
residue distilled; b.p. 86ꢁC (10 mmHg); yield 91%; H NMR (400 MHz,
1
CDCl3) ꢂ 0.00 (s, 9H, Si(CH3)3), 0.17 (s, 9H, OSi(CH3)3), 0.23 (s, 9H,
OSi(CH3)3), 2.95 (s, 1H, CH ¼ ); MS: Mþ ¼ 276. Anal. calcd for
C11H28O2Si3: C, 47.76; H, 10.20. Found: C, 47.70; H, 10.15.
Synthesis of Unsaturated Carboxylic Acids 3: Typical Procedure
To a stirred solution of the corresponding aldehyde 2 (1.7 mmol) and
reagent 1 (0.552 g, 2 mmol) in 5 mL of DMF, was added solid KOH
(1.1 10ꢀ3 g, 0.02 mmol) at room temperature. After being stirred at room
temperature until the total disappearance of the starting material, the reac-
tion mixture was then hydrolyzed with a saturated solution of NH4Cl
(20 mL). Acid-basic work-up, to remove any remaining non-acidic material,
gave acids 3, which were purified by recrystallization. The acids were fully
characterized by melting points and spectra comparison with authentic
samples.
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(E )-a,b-ETHYLENIC CARBOXYLIC ACIDS
1011
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from petroleum ether), m.p. 62ꢀ–63ꢀC; H NMR (250 MHz, CDCl3):
1
ꢀ 3.50 (dd, 2H, J ¼ 6.81 Hz, J ¼ 1.50 Hz), 5.77 (dt, 1 H, J ¼ 15.53 Hz,
J ¼ 1.50 Hz), 7.39 (m, 6H), 11.61 (s, 1H); 13C NMR ꢀ 38.5, 121.6, 126.7,
128.7, 128.8, 137.2, 150.1, 171.8.
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Accepted June 5, 2000