Two-carbon homologation of aldehydes via silyl ketene acetals: A new stereoselective approach to (E)-alkenoic acids

Article abstract of DOI:10.1021/jo980853y

Aldehydes are converted into (E)-α,β-unsaturated carboxylic acids using C,O,O-tris(trimethylsilyl)ketene acetal 1. This organosilicon reagent is easily generated from trimethylsilyl acetate, LDA, and chlorotrimethylsilane. The effectiveness of the reaction has been explored for a large variety of aldehydes with Lewis acids and fluorides as catalysts.

Full text of DOI:10.1021/jo980853y

J . Org. Chem. 1998, 63, 8785-8789
8785
Tw o-Ca r bon Hom ologa tion of Ald eh yd es via Silyl Keten e Aceta ls:
A New Ster eoselective Ap p r oa ch to (E)-Alk en oic Acid s
Moncef Bellassoued,* Nathalie Lensen, Mina Bakasse, and Sinda Mouelhi
Laboratoire de Synth e` se Organom e´ tallique associ e´ au CNRS, Universit e´ de Cergy-Pontoise, B aˆ timent des
Sciences de la Mati e` re, 5 Mail Gay Lussac, Neuville sur Oise, 95031 Cergy-Pontoise Cedex, France
Received May 6, 1998
Aldehydes are converted into (E)-R,â-unsaturated carboxylic acids using C,O,O-tris(trimethylsilyl)-
ketene acetal 1. This organosilicon reagent is easily generated from trimethylsilyl acetate, LDA,
and chlorotrimethylsilane. The effectiveness of the reaction has been explored for a large variety
of aldehydes with Lewis acids and fluorides as catalysts.
In tr od u ction
Sch em e 1
Direct conversion of aldehydes into their (E)-R,â-
ethylenic carboxylic acids is an interesting and very
useful reaction in organic synthesis. Beside the fact that
alkenoic acids are versatile synthons which allow numer-
ous transformations, this functionality is also widely
present in natural products such as the queen substance
1
2
of the honeybee and caffeic acid. Recently, products
bearing this functionality have been tested as new
enzymic browning inhibitors in replacement of sulfites.3
Alkenoic acids have also found many applications in the
total synthesis of biologically important subtances as, for
example, tetrahydromyricoidine.4
Sch em e 2
To our knowledge, four general methods are available
for the direct conversion of an aldehyde into an R,â-
ethylenic carboxylic acid (Scheme 1): (1) the Knoevenagel
5
aldehydes in the presence of a catalyst to give the
corresponding (E)-R,â-ethylenic acids (Scheme 2). In this
paper, we describe in detail our study on the preparation
and the condensation reactions of the C,O,O-tris(tri-
methylsilyl)ketene acetal 1 with a large panel of alde-
hydes. Furthermore, our recent work,11 concerning the
use of the couple “CsF, DMSO” in the synthesis of
polyenals by homologation of aldehydes and its efficacy,
prompted us to investigate deeply our preliminary work.
reaction with malonic acid, (2) the Peterson olefination
6
with (trimethylsilyl)acetic acid dianion, (3) the Wittig-
7
Horner type reactions, and lately (4) the cycloaddition
of (trimethylsilyl)ketene.8
Nevertheless, these techniques are more or less effec-
tive. The Knoevenagel reaction (1) gives low yields with
9
enolizable aldehydes, the Peterson olefination (2) and
the use of (trimethylsilyl)ketene (4) suffered from a lack
of stereoselectivity and the Wittig-Horner type reactions
(
3) required fairly stringent conditions to isolate the R,â-
7b
Resu lts a n d Discu ssion
unsaturated acids.
In a previous communication,10 we have reported that
P r ep a r a tion of C,O,O-Tr is(tr im eth ylsilyl)k eten e
Aceta l 1. To our knowledge, the preparation of trisilyl-
C,O,O-tris(trimethylsilyl)ketene acetal 1 reacted with
1
2
ated reagent 1 was described for the first time by Emde
*
Previous address: Universit e´ Pierre et Marie Curie(Paris VI), 4
starting from (trimethylsilyl)acetic ester and trimethyl-
silyl triflate. However, a mixture of three silylated
products was obtained from which compound 1 had to
be separated. We have now found that C,O,O-tris-
place J ussieu, Tour 45, 75252 Paris Cedex 05.
(
1) Callow, R. K.; J ohnston, N. C. Bee World 1960, 41, 152.
(2) Cho, H.; Ueda, M.; Tamaoka, M.; Hamaguchi, M.; Aisaka, K.;
Kiso, Y.; Inoue, T.; Ogino, R.; Tatsuoka, T.; Ishihara, T.; Noguchi, T.;
Morita, I.; Murota, S. J . Med. Chem. 1991, 34, 1503.
(trimethylsilyl)ketene acetal 1 can be easily obtained in
(
(
(
(
3) Walker, J . R. L.; Ferrar, P. H. Chem. Ind. 1995, 836.
4) Song, J .; Hesse, M. Tetrahedron 1993, 49, 6797.
5) J ones, G. Org. React. 1967, 15, 204.
excellent yield from trimethylsilyl acetate (Scheme 3):
deprotonation of the latter by 1 equiv of LDA at -70 °C
overnight followed by trimethlysilyl chloride trapping
6) Grieco, P. A.; Wang, C.-L. J .; Burke, S. D. J . Chem. Soc., Chem.
Commun. 1975, 537.
7) (a) Koppel, G. A.; Kinnick, M. D. Tetrahedron Lett. 1974, 711.
b) Coutrot, P.; Snoussi, M.; Savignac, P. Synthesis 1978, 133. (c)
Lombardo, L.; Taylor, R. J . K. Synthesis 1978, 131.
8) (a) Concepcion, A. B.; Maruoka, K.; Yamamoto, H. Tetrahedron
995, 51, 4011. (b) Black, T. H.; Zhang, Y.; Huang, J .; Smith, D. C.;
Yates, B. E. Synth. Commun. 1995, 25, 15.
9) House, H. O. Modern Synthetic Reactions; W. A. Benjamin:
Menlo Park, CA, 1972; p 649.
10) Bellassoued, M.; Gaudemar, M. Tetrahedron Lett. 1988, 29,
551.
1
3
affords the R-silylated (trimethylsilyl)acetic ester
4
(
(
which is then subjected to a similar treatment to give
the desired trisilylated reagent 1 in a 74% overall yield.
(
1
(11) Bellassoued, M.; Salemkour, M. Tetrahedron 1996, 52, 4607.
(12) Emde, H.; Domsch, D.; Feger, H.; Frick, U.; G o¨ tz, A.; Hergott,
H. H.; Hofmann, K.; Kober, W.; Kr a¨ geloh, K.; Oesterle, T.; Steppan,
W.; West, W.; Simchen, G. Synthesis 1982, 1.
(
(
4
(13) Bellassoued, M.; Gaudemar, M. Tetrahedron Lett. 1990, 31, 209.
1
0.1021/jo980853y CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/10/1998

8
786 J . Org. Chem., Vol. 63, No. 24, 1998
Bellassoued et al.
Sch em e 3
Ta ble 1. Rea ction of C,O,O-Tr is(tr im eth ylsilyl)k eten e
could be suppressed completely using mercuric iodide
Aceta l 1 w ith Ben za ld eh yd e in th e P r esen ce of
(entry 5) or titanium tetrachloride (entry 8). One par-
a
Va r iou s Ca ta lysts
ticular aspect of the reaction carried out with HgI in
2
toluene is the influence of the temperature on the nature
of the adduct obtained (entries 5-7). Indeed, at room
temperature for 1 h, siloxy acid 2a , the single reaction
product, was easily isolated. At higher temperature (50
°
C), a gradual conversion of 2a to the alkene 3a was
observed and found to be complete after 2 h. Ferric
chloride seemed to be a good catalyst for this reaction
but gave unfortunately a mixture of the two products 2a
2
and 3a (entries 9, 10). Surprisingly, when MgBr was
used to carry out the condensation, a loss of chemical
reactivity was observed with recovery of the starting
benzaldehyde (entries 11, 12). On the basis of these
cat.
(10%)
temp
(°C)
time
(h)
yield
(%) 2a
yield
(%) 3a
b
b,c
entry
solvent
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
ZnBr2
ZnBr2
ZnBr2
ZnBr2
HgI2
HgI2
HgI2
TiCl4
FeCl3
FeCl3
THF
THF
rt
rt
24
3
0.2
1
1
1
0
0
95
85
8
48
0
47
100
0
35
31
20
0
2 2
results, ZnBr and HgI were found to be mild Lewis acid
toluene rt
toluene 110
toluene rt
toluene 50
toluene 50
88
52
96
59
0
100
65
65
0
0
0
20
0
0
catalysts for the reaction of 1 with benzaldehyde.
F lu or id e Ion Ca ta lyst. Recently, our group at Paris
VI has shown that a CsF-DMSO combination was very
efficient for the conversion of aldehydes into (2E,4E)
2
1
1
1
dienals using γ-trimethylsilyl crotonaldimine. We have
now found that fluoride ion was also efficient as catalyst
for the reaction of 1 with benzaldehyde. Some of the
results are reported in Table 1. Several sources of
fluoride ion have been tested since a variety of alkali
metal fluorides is commercially available. The correct
choice of the solvent is very important because of the
variable solubility shown by these ionic fluorides, and one
must find which particular fluoride-solvent combination
is the best for our condensation-olefination reaction. It
is obvious from the results obtained in Table 1, that, as
expected, the nature of the solvent is important. The
reaction works faster and gives better yields when not
only polar but also dissociating solvents are used with
CH2Cl2
toluene rt
THF rt
-70
0.5
24
2
24
24
0.5
0.5
24
24
1
1
16
1
1.45
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
MgBr2 toluene 110
MgBr2 THF
CsF
CsF
80
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
CH2Cl2
THF
THF
CH2Cl2
THF
DMSO
DMF
DMSO
DMSO
THF
0
80
96
0
CsF
NaF
NaF
NaF
NaF
LiF
KF
TBAF
TBAF
0
6
0
94
82
68
93
86
90
18
32
7
13
10
THF
a
All reactions were conducted on a 1.7 mmol scale following
the typical procedure described in the Experimental Section.
Estimated by H NMR on the crude reaction mixture with respect
to nonreacted aldehyde (molar percentage). The cinnamic acid
was fully characterized by spectrum comparison with authentic
commercial sample.
basic metal salts. Dichloromethane, which is a polar
14
solvent (E
T
(30) ) 41.1) but with a low dielectric
b
1
constant (ꢀ ) 8.9) is totally ineffective (entries 13, 16).
Tetrahydrofuran, which is also a polar, coordinating, but
c
not really a dissociating, solvent (E (30) ) 37.4, ꢀ ) 7.6),
T
is more effective, but the overall result depends also on
the nature of the catalyst (entries 14, 17, 22). These
results prompted us to postulate that a dissociating
solvent is essential for this reaction. Indeed, attempts
at using dimethylformamide and dimethyl sulfoxide
which are polar, dissociating, and coordinating solvents
Rea ction w ith Ben za ld eh yd e. Our goal was to
study the condensation of C,O,O-tris(trimethylsilyl)-
ketene acetal 1 with a large panel of aromatic, vinylic,
and aliphatic aldehydes. To obtain the best yield and a
total E stereoselectivity, a methodological study has been
carried out. The choice of the catalyst and the solvent
are important in stereochemical outcomes and yields.
Thus, we first examined the reaction of 1 with benzal-
dehyde to determine the best reaction conditions for this
Peterson-type reaction.
(E
T
(30) ) 43.8, ꢀ ) 37; E
T
(30) ) 45.0, ꢀ ) 47,
respectively) were fruitful (entries 15, 18, 19, 20, 21, 23).
From the reported examples of alkali metal fluoride-
promoted reactions of 1 with benzaldehyde, CsF and NaF
can be considered as the most active catalysts, the latter
being, however, less hygroscopic and appreciably less
expensive.
Lew is Acid Ca ta lyst. As shown in Table 1, several
Lewis acids were investigated in different solvents. First
(
entry 1), benzaldehyde was treated with 1 in the
Ster eoselective Syn th esis of (E)-Alk en oic Acid s.
To determine the scope and limitations of this new
method, the reaction has been performed on a variety of
structurally different aldehydes. The alkenoic acids
obtained are listed in Table 2. As can be seen from the
presence of a catalytic amount of zinc bromide in THF
at room temperature for 24 h. The reaction proceeded
to afford only the corresponding alkene 3a in almost
quantitative yield. The intermediate 2a seems to elimi-
nate hexamethyldisiloxane more easily in THF (entry 2)
than in toluene (entry 4). However, this elimination
(14) Reichardt, C. Angew. Chem., Int. Ed. Engl. I979, 18, 98.

Two-Carbon Homologation of Aldehydes
J . Org. Chem., Vol. 63, No. 24, 1998 8787
Ta ble 2. Syn th esis of Alk en oic Acid s 3 Usin g Rea gen t 1
data, the reaction was exceptionally effective for a large
class of aldehydes. Nonenolizable aromatic aldehydes
with electroattracting or electrodonor groups were tested
and gave the corresponding R,â-ethylenic carboxylic acids
in good yield and with a total E stereoselectivity (entries
a-d). Heteroaromatic aldehydes were also tested and
gave the desired products (entries e-g). With saturated
aldehydes, the reaction was also very efficient (entries
h-k). This methodology was thus successfully applied
to the synthesis of (E)-2-decenoic acid (entry k), an
intermediate in the total synthesis of tetrahydromyri-
coidine.4 The reaction has also been performed on a
number of R,â-ethylenic aldehydes (entries l-o). Con-
jugated alkenoic acids, resulting from 1,2 addition were
exclusively formed in high yields and with a total E
stereoselectivity.
Rea ction Mech a n ism . A tentative reaction mecha-
nism with fluoride ion is shown in Scheme 4. It is very
reasonable to assume that the reaction is initiated by
fluoride ion to generate the enolate 1′ which then reacts
with the aldehyde to give the alkoxide 2′. The reaction
of the latter with 1 affords the corresponding â-siloxy
ester and the enolate 1′ generated in the reaction media.
Further elimination of (trimethylsilyl)alkoxide gives the
corresponding alkene. Alternatively, the reaction could
also be catalyzed by the in situ formed (trimethylsilyl)-
alkoxide. In fact, when this reaction was tested using
potassium tert-butoxide as catalyst, the cinnamoester was

8
788 J . Org. Chem., Vol. 63, No. 24, 1998
Bellassoued et al.
Sch em e 4
Sch em e 5
obtained with almost quantitative yield. This result
clearly supports the postulated mechanism.
amine is distilled from CaH
2
and stored over molecular sieves.
LDA is prepared in situ according to the method of Gaud-
emar.15
The mechanism by which Lewis acids catalyze this
reaction is not very clear at present, but we presume that
the mechanism is formally analogous to the Lewis acid-
catalyzed addition of silyl enol ethers to carbonyl com-
pounds. Indeed, the reaction may proceed via the prior
Chemical shifts are given in ppm (J in MHz) relative to
tetramethylsilane. Flash column chromatography is done on
Merck grade 60 silica gel (230-400 mesh) with a mixture of
cyclohexane/ethyl acetate as eluent.
P r ep a r a tion of Tr im eth ylsilyl r-Tr im eth ylsilyla ted
2
complexation of the CdO with the Lewis acid (ZnBr in
1
5
Aceta te (4). LDA is prepared as described in reference from
phenanthrene (2.3 g, 12.5 mmol), diisopropylamine (10.6 g, 110
mmol), and hammered lithium (0.7 g, 100 mmol) in ether (20
mL)-THF (20 mL). To this solution, trimethylsilyl acetate
Scheme 5). Subsequent reaction of 1 with the aldehyde
according to the well-established Zimmerman-Traxler
chairlike transition-state model affords the corresponding
silyl zinc chelate I. Further Peterson-type elimination
of II gives the unsaturated trimethylsilyl ester with
regeneration of the catalyst.
Concerning the stereoselectivity of the reaction, in all
cases only E isomers of 3 are formed. This result is very
likely due to a thermodynamical control of the reaction.
However, a mixture of the diastereoisomers 2 is formed.
The study of the correlation between the elimination
mechanism and the product’s stereochemistry is under
investigation.
(10.56 g, 80 mmol) in 10 mL of THF is added at -70 °C over
30 min, and the solution is stirred at the same temperature
overnight. Chlorotrimethylsilane (13 mL, 100 mmol) is added
over 5 min at -70 °C, and the reaction mixture is then allowed
to reach room temperature. The precipitate is filtered off on
Celite, the solvent evaporated, and the product distilled in
1
vacuo; bp: 61 °C (10 mmHg); yield: 82%; H NMR (400 MHz,
CDCl
3
3 3 3 3
) δ 0.11 (s, 9 H, Si(CH ) ), 0.26 (s, 9 H, OSi(CH ) ), 1.89
(
(
15) Gaudemar-Bardone, F.; Gaudemar, M. Synthesis 1979, 463.
16) (a) Balakrishnan, P.; Baumstark A. L.; Boykin, D. W. Org.
Magn. Reson. 1984, 22, 753. (b) J ovanovic, B.; Misic-Vukovic, M.;
Drmanic, S.; Csanadi, J . Heterocycles 1994, 37, 1495.
Con clu sion
(17) (a) Royer, R.; Bodo, B.; Demerseman, P.; Clavel, J .-M. Bull. Soc.
Chim. Fr. 1971, 2929. (b) Copinga, S.; Tepper, P. G.; Grol, C. J .; Horn,
A. S.; Dubocovich, M. L. J . Med. Chem. 1993, 36, 2891.
(18) Koepp, E.; V o¨ gtle, F. Synthesis 1987, 177.
In conclusion and from the results reported here, it is
clear that this new method is a straightforward process
for direct homologation of aldehydes into R,â-ethylenic
carboxylic acids. C,O,O-Tris(trimethylsilyl)ketene acetal
(
(
19) Mori, A.; Takeshita, H. Bull. Chem. Soc. J pn. 1987, 60, 3037.
20) (a) Taniguchi, Y.; Kat oˆ , H. Chem. Pharm. Bull. 1973, 21, 2070.
(
b) Freeman, F.; Chang, L. Y.; Kappos, J . C.; Sumarta, L. J . Org. Chem.
1987, 52, 1460.
21) Wenkert, E.; Halls, T. D. J .; Kunesch, G.; Orito, K.; Stephens,
R. L.; Temple, W. A.; Yadav, J . S. J . Am. Chem. Soc. 1979, 101, 5370.
22) Mori, K.; Brevet, J .-L. Synthesis 1991, 1125.
1
reacts with aldehydes in the presence of a catalytic
(
amount of catalyst at room temperature to give the
desired R,â-ethylenic carboxylic acids with a good yield
and a total E stereoselectivity. The mildness of the
reaction conditions (room temperature), the good yields
of the products obtained, and the simple workup proce-
dure show the usefulness of the trisilylated reagent 1.
(
(23) (a) Royer, J .; Beugelmans-Verrier, M. Tetrahedron 1979, 35,
369. (b) Pirrung, M. C.; Han, H.; Ludwig, R. T. J . Org. Chem. 1994,
9, 2430.
2
5
(
24) (a) Beckwith, A. L. J .; Cross, R. T.; Gream, G. E. Aust. J . Chem.
1974, 27, 1693. (b) Freeman, F.; Kappos, J . C. J . Org. Chem. 1986, 51,
654.
1
(
25) Saljoughian, M.; Williams, P. G. J . Org. Chem. 1987, 52, 3481.
Exp er im en ta l Section
(26) (a) Ressler, C.; Goodman, F. J .; Tsutsui, R.; Tsutsumi, M. J .
Org. Chem. 1979, 44, 2027. (b) Crombie, L.; Crombie, W. M. L. J . Chem.
Soc., Perkin Trans. 1 1994, 1267.
Gen er a l. All experiments are carried out under a nitrogen
atmosphere. Unless otherwise noted, starting materials are
obtained from commercial suppliers and are used without
further purification. Tetrahydrofuran and diethyl ether are
distilled over sodium and benzophenone prior to use. Tri-
methylchlorosilane is distilled over magnesium. Diisopropyl-
(
27) (a) Murali, D.; Rao, G. S. K. Synthesis 1987, 254. (b) Veith, M.;
Lorenz, M.; Boland, W.; Simon, H.; Dettner, K. Tetrahedron 1994, 50,
859. (c) Abarbri, M.; Parrain, J .-L.; Cintrat, J .-C.; Duch eˆ ne, A.
6
Synthesis 1996, 82.
(28) Kamal, A.; Haider, Y.; Akhtar, R.; Qureshi, A. A. Pak. J . Sci.
Ind. Res. 1971, 14, 63.

Two-Carbon Homologation of Aldehydes
); MS: M•+ ) 204. Anal. Calcd for C
J . Org. Chem., Vol. 63, No. 24, 1998 8789
(
s, 2 H, CH
2
8
H
20
O
2
Si
2
:
7.53 Hz, H-6 Ar), 7.92 (d, J ) 16 Hz, 1 H, H-3), 12.4 (s, 1 H,
COOH); 13C NMR δ 54.4, 110.5, 116.7, 119.7, 122.0, 128.2,
130.9, 141.4, 157.5, 171.7; IR (KBr): 3500-2500 (OH), 1685
C, 47.00; H, 9.86. Found: C, 47.02; H, 9.81.
P r ep a r a tion of C,O,O-Tr is(tr im eth ylsilyl)k eten e Ac-
eta l (1). To a cooled (-80 °C) solution of LDA prepared as
above is added a solution of trimethylsilyl R-trimethylsilylated
acetate 4 (14.28 g, 70 mmol) in THF (10 mL) during 30 min.
The resulting mixture is stirred at the same temperature for
•
+
(CdO). MS: M ) 178. Anal. Calcd for C H O : C, 67.40;
1
0
10
3
H, 5.65. Found: C, 67.39; H, 5.63.
(
E,E)-3,3′-(1,4-P h en ylen e)bis-2-p r op en oic a cid (3d ): re-
1
2 3
crystallized in H O; H NMR (250 MHz, CDCl ) δ 6.60 (d, 2
1
h and then quenched with chlorotrimethylsilane (13 mL, 100
H, J ) 16.0 Hz, H-2), 7.59 (d, 2 H, J ) 16.0 Hz, H-3), 7.70 (s,
mmol) at -80 °C. After being stirred at the same temperature
for 30 min, the solution is gradually warmed to room temper-
ature and filtered through a pad of Celite. The solvent is
4
1
M
H, Ar), 12.45 (s, 1 H, COOH); 13C NMR δ 121.0, 128.6, 136.7,
40.8, 160.3; IR (KBr): 3500-2500 (OH), 1682 (CdO). MS:
•
+
10 4
) 218. Anal. Calcd for C12H O : C, 66.05; H, 4.61.
Found: C, 66.02; H, 4.63.
removed under reduced pressure and the residue distilled;
1
bp: 86 °C (10 mmHg); yield: 91%; H NMR (400 MHz, CDCl
3
)
δ 0.00 (s, 9 H, Si(CH
OSi(CH ), 2.95 (s, 1 H, CHd); MS: M ) 276. Anal. Calcd
for C11 Si : C, 47.76; H, 10.20. Found: C, 47.70; H, 10.15.
3 3 3 3
) ), 0.17 (s, 9 H, OSi(CH ) ), 0.23 (s, 9 H,
(E)-3-(2-Th ien yl)-2-p r op en oic a cid (3f): recrystallized in
•
+
1
)
3
ethanol; mp ) 146-148 °C; H NMR (250 MHz, CDCl ) δ 6.22
3
3
H
28
O
2
3
(d, 1 H, J ) 15.7 Hz, H-2), 7.20 (dd, 1 H, J ) 3.3 Hz, H-4 Ar),
7.50 (d, 1 H, J ) 3.3 Hz, H-3 Ar), 7.70 (m, 1 H, H-5 Ar), 7.75
(d, 1 H, J ) 15.7 Hz, H-3); 13C NMR δ 117.9, 129.0, 129.9,
132.1, 137.2, 139.4, 167.7; IR (KBr): 3500-2500 (OH), 1672
P r ep a r a t ion of 3-H yd r oxy-3-p h en yl-2-(t r im et h ylsil-
oxy)p r op ion ic Acid (2a ). P r oced u r e A. To a cooled (-70
°
C) dichloromethane (10 mL) solution of benzaldehyde (0.40
•
+
g, 1.7 mmol) is added via syringe TiCl
4
(10%). Reagent 1 (0.55
(CdO). MS: M ) 154. Anal. Calcd for C H O S: C, 54.53;
7
6
2
g, 2 mmol) in dichloromethane (3 mL) is added dropwise and
H, 3.92. Found: C, 54.54; H, 3.93.
the resulting mixture stirred at -70 °C for 1 h. After
(
E)-3-(3-P yr id in yl)-2-p r op en oic a cid (3g): recrystallized
quenching with H
2
O (20 mL) at the same temperature, the
1
in H
2
O; mp ) 232-234 °C; H NMR (250 MHz, DMSO) δ 6.58
solution is raised to room temperature. The aqueous layer is
(
d, 1 H, J ) 16 Hz, H-2), 7.30 (dd, 1 H, J ) 8.2, 5.2 Hz, H-5
extracted with ether (3 × 20 mL), and the combined organic
Ar), 7.50 (d, 1 H, J ) 16 Hz, H-3), 8.00 (dt, 1 H, J ) 8.5, 2 Hz,
H-4 Ar), 8.48 (dd, 1 H, H-6 Ar), 8.75 (d, 1 H, J ) 2 Hz, H-2
Ar); 13C NMR δ 121.7, 123.9, 130.2, 134.6, 140.4, 149.7, 150.7,
4
phases are dried over MgSO . The solvent is evaporated in
vacuo. Purification by recrystallization in pentane gives pure
product 2a (yield: 95%).
P r oced u r e B. To a toluene (10 mL) solution of benzalde-
1
M
9
67.3; IR (Nujol mull): 3500-2500 (OH), 1700 (CdO). MS:
•
+
8 7 2
) 149. Anal. Calcd for C H O N: C, 64.42; H, 4.73; N,
2
hyde (1.7 mmol) and 1 (2 mmol) is added HgI (10%) at room
.39. Found: C, 64.45; H, 4.69; N, 9.35.
temperature. After being heated at 50 °C for 2 h, the mixture
is placed under high vacuum to remove toluene, and then 20
mL of hexane is added and the solid is eliminated by filtration
(E)-4,4-Dim eth yl-2-p en ten oic a cid (3j): recrystallized in
1
hexane; mp ) 79 °C; H NMR (250 MHz, CDCl
3
) δ 1.01 (s, 9
through Celite. The product is quenched with H
and extracted with ether (3 × 20 mL). The organic layers are
washed with H O (20 mL) and dried over MgSO , and the
2
O (20 mL)
H, Me), 5.60 (d, 1 H, J ) 15.9 Hz, H-2), 6.90 (d, 1 H, J ) 15.9
Hz, H-3), 11.3 (s, 1 H, COOH); 13C NMR δ 29.11, 34.53, 116.65,
162.00, 173.22; IR (KBr): 3500-2500 (OH), 1689 (CdO).
2
4
•
+
solvent is evaporated under reduced pressure affording 2a
which is purified by recrystallization in pentane (yield: 96%);
MS: M ) 128. Anal. Calcd for C H O : C, 65.59; H, 9.43.
7
12
2
Found: C, 65.60; H, 9.39.
E)-2-Decen oic a cid (3k ): oil; H NMR (250 MHz, CDCl
δ 0.88 (t, 3 H, J ) 7.2 Hz, Me), 1.20-1.40 (m, 8 H, H-6-9),
.47 (m, 2 H, J ) 7.3 Hz, H-5), 2.23 (dt, 2 H, J ) 1.5, 7.0 Hz,
1
mp: 120-122 °C; H NMR (250 MHz, CDCl
3
) δ 0.11 (s, 9 H,
1
(
3
)
Si(CH
3
)
3
), 2.62 (d, 1 H, J ) 7.78 Hz, H-2), 5.20 (d, 1 H, J )
.78 Hz, H-3), 7.19-7.42 (m, 5 H, ArH), 11.0 (s, 1 H, COOH);
3
7
1
1
C NMR (CDCl
3
) δ 0.00, 48.15, 74.35, 128.58, 128.84, 129.50,
H-4), 5.70 (td, 1 H, J ) 15.6, 1.5 Hz, H-2), 6.95 (td, 1 H, J )
1
M
44.07, 181.41; IR (KBr): 3500-2500 (OH), 1681 (CdO); MS:
15.6, 7.0 Hz, H-3), 10.6 (s, 1 H, COOH); 13C NMR δ 14.36,
•
+
18 3
) 238. Anal. Calcd for C12H O Si: C, 60.46; H, 7.61.
2
(
2.98, 29.41, 29.48, 32.14, 32.66, 121.10, 152.70, 172.73; IR
Found: C, 60.44; H, 7.59.
•+
CHCl
Calcd for C10
0.61.
(E,E)-5-P h en yl-2,4-p en ta d ien oic a cid (3l): recrystallized
3
): 3500-2500 (OH), 1697 (CdO). MS: M ) 170. Anal.
P r ep a r a tion of r,â-Un sa tu r a ted Acid s (3a -o). Gen -
er a l P r oced u r e. A detailed procedure for the reaction of 1
with carbonyl compounds is given below. All reactions are
carried out in similar manner under nitrogen at room tem-
perature. Solvents, catalysts, reaction times, and yields are
reported in Table 2. Physical, spectral, and analytical data
for typical compounds (3c, 3d , 3f, 3g, 3j, 3k , 3l, 3o) follow.
Full spectral data for closely related compounds (3b, 3e, 3h ,
18 2
H O
: C, 70.54; H, 10.65. Found: C, 70.50; H,
1
1
in ether; mp ) 163-164 °C; H NMR (250 MHz, CDCl ) δ 5.90
3
(d, 1 H, J ) 15.0 Hz, H-2), 6.70-6.80 (m, 2 H, H-4-5), 7.10-
7.30 (m, 3 H, Ar), 7.40 (d, 2 H, J ) 7.9 Hz, Ar), 7.49 (dd, 1 H,
J ) 15.0, H-3); 13C NMR δ 123.30, 124.63, 128.39, 128.80,
3
i, 3m , 3n ) are given in Supporting Information.
131.00, 136.15, 141.88, 146.34, 169.88; IR (KBr): 3500-2600
P r oced u r e Usin g Zin c Br om id e. To a stirred solution
•+
(
O
OH), 1682 (CdO). MS: M ) 174. Anal. Calcd for C11
H
10
-
of the corresponding aldehyde (1.7 mmol) and zinc bromide
0.17 mmol) in THF (5 mL), is added 1 (2 mmol) dropwise at
2
: C, 75.84; H, 5.78. Found: C, 75.88; H, 5.76.
(
(
E,E,E)-2,4,6-Octa tr ien oic a cid (3o): recrystallized in
room temperature. After being stirred at the same tempera-
ture, the mixture is hydrolyzed with a saturated solution of
1
hexane; mp ) 185-187 °C; H NMR (400 MHz, DMSO) δ 1.71
(
(
1
d, 3 H, J ) 6.6 Hz, Me), 5.75 (d, 1 H, J ) 15.2 Hz, H-2), 5.86
m, 1 H, H-7), 6.06 (dd, 1 H, J ) 14.8, 10.8 Hz, H-6), 6.20 (dd,
NH Cl (20 mL). Acid-base workup, to remove any remaining
4
nonacidic organic material, gives acids 3 which are purified
by recrystallization or flash chromatography (silica gel, cyclo-
hexane/ethyl acetate, 30:70).
H, J ) 14.8, 11.3 Hz, H-4), 6.45 (dd, 1 H, J ) 14.8, 11.3 Hz,
13
H-5), 7.10 (dd, 1 H, J ) 15.2, 11.2 Hz, H-3); C NMR δ 19.17,
21.77, 128.66, 132.15, 135.71, 141.63, 145.28, 169.48; IR
1
(
P r oced u r e Usin g F lu or id e Ion . To a stirred solution of
aldehyde (1.7 mmol) and reagent 1 (2 mmol) in solvent (5 mL)
is added the metal fluoride (0.2 mmol). The reaction mixture
is then hydrolyzed with water (20 mL). Acid-base workup,
to remove any remaining nonacidic organic material, gives
acids 3 which are purified by recrystallization or flash chro-
matography (silica gel, cyclohexane/ethyl acetate, 30:70).
•
+
KBr): 3400-2500 (OH), 1682 (CdO); MS: M ) 138. Anal.
Calcd for C : C, 69.54; H, 7.29. Found: C, 69.50; H, 7.25.
8
10 2
H O
Su p p or tin g In for m a tion Ava ila ble: Spectral and ana-
lytical data for 3b, 3e, 3h , 3i, 3m , and 3n (2 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
(
E)-3-(2-Meth oxyp h en yl)-2-p r op en oic a cid (3c): recrys-
1
tallized in ethanol; mp ) 183-186 °C; H NMR (250 MHz,
CDCl ), δ 3.95 (s, 3 H, Me), 6.58 (d, 1 H, J ) 16 Hz, H-2), 7.02
td, 1 H, J ) 7.53, 7.4 Hz, H-5 Ar), 7.15 (d, 1 H, J ) 8 Hz, H-3
Ar), 7.47 (td, 1 H, J ) 8, 7.4 Hz, H-4 Ar), 7.75 (d, 1 H, J )
3
(
J O980853Y