Two-carbon homologation of ketones via sily ketene acetals: Synthesis of α,β-unsaturated acids and α-trimethylsilyl δ-ketoacids

Article abstract of DOI:10.1016/j.jorganchem.2005.01.049

The reaction of C,O,O-tris(trimethylsilyl)ketene acetal 1 with saturated, cyclic and aromatic ketones 2 proceeds smoothly in the presence of titanium chloride to give (E)-α,β-unsaturated carboxylic acids 3 with fairly good stereoselectivity. With α,β-unsa

Full text of DOI:10.1016/j.jorganchem.2005.01.049

Journal of Organometallic Chemistry 690 (2005) 2172–2179
www.elsevier.com/locate/jorganchem
Two-carbon homologation of ketones via sily ketene acetals:
Synthesis of a,b-unsaturated acids and a-trimethylsilyl d-ketoacids
*
Moncef Bellassoued , Sinda Mouelhi, Pierre Fromentin, Aurelien Gonzalez
´
` ´ ´
Laboratoire de Synthese Organometallique, Universite de Cergy-Pontoise, 5 Mail Gay Lussac, Neuville sur Oise, 95031 Cergy-Pontoise Cedex, France
Received 15 November 2004; accepted 25 January 2005
Available online 14 April 2005
Abstract
The reaction of C,O,O-tris(trimethylsilyl)ketene acetal 1 with saturated, cyclic and aromatic ketones 2 proceeds smoothly in the
presence of titanium chloride to give (E)-a,b-unsaturated carboxylic acids 3 with fairly good stereoselectivity. With a,b-unsaturated
ketones 4, a-trimethylsilyl d-ketoacids 5 (syn + anti) are obtained according to Michael-type 1,4 addition. These diastereoisomers are
separated and the configurations of 5a are achieved by X-ray molecular analysis.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Trimethylsilyl acetate; Silyl ketene acetal; a,b-Unsaturated acids; a-Silyl ketoacids
1. Introduction
2. Results and discussion
We have shown in a previous work [1] that C,O,O-
tris(trimethylsilyl)ketene acetal 1 is a versatile organo-
silicon reagent for the conversion of aldehydes into
(E)-a,b-alkenoic acids with two-carbon unit introduc-
tion (Scheme 1). Recently, we have reported the study
of stereochemical control in alkenoic acids formation
[2].
In this paper, we show that this study can be also ap-
plied to ketones. This complementary study is justified
by the fact that ketones are generally less reactive than
aldehydes. Moreover, in contrast to unsaturated alde-
hydes, a,b-unsaturated ketones lead to Michael-type
1,4 addition products.
2.1. Reaction with saturated, cyclic and aromatic ketones
The reaction has been initially performed with ace-
tophenone and various catalysts in order to determinate
the best conditions for this condensation-elimination
reaction. The results are listed in Table 1.
The attempts carried with Lewis acids (entries 1 to
5) show that only AlCl3 and TiCl4 lead to the ex-
pected acids 3a. However, with TiCl4, acetophenone
conversion is complete whatever the reaction tempera-
ture is (entries 4 and 5). Unfortunately in this case, a
(Z + E) mixture of the acids 3a is obtained. ZnBr2 and
HgI2, which have given very interesting results with
aldehydes [1,2], are totally inactive (entries 1, 2). Elec-
trophilic assistance of the carbonyl by complexation
with these Lewis acids seems to be insufficient to allow
nucleophilic addition of the trisilylated reagent 1.
With KOH, and CsF (entries 6,7), the acetophenone
conversion is very slow and does not occur with
*
Corresponding author.
E-mail address: moncef.bellassoued@chim.u-cergy.fr (M. Bellas-
soued).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.01.049

M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
2173
2.2. Reaction with a,b-unsaturated ketones
OSiMe3
CO2SiMe3
OSiMe3
OSiMe3
+
R CHO
R
R
Me3Si
Several groups were interested in silylated enol ethers
condensation with a,b-unsaturated ketones using Lewis
acids. These reactions were extended to alkylsilylketene
acetals. Michael-type 1,4 addition products were then
obtained [9–12].
SiMe3
1
CO2H
Regarding trisilylated reagent 1 condensation with
a,b-ethylenic ketones, we have found that TiCl4 was
the best catalyst for this reaction. a-Trimethylsilyl d-
ketoacids 5, unknown in the literature, are obtained
in good yields (entries 1–3, Table 3). With cyclohexe-
none 4d, the expected d-ketoacid 5d was obtained
along with the by-product 6d issued from a double
1,4 Michael-type condensation (Scheme 2). Proportion
of 6d depends on the way of introduction of the trisi-
lylated reagent 1 versus cyclohexenone. The intermedi-
ate A that arises from condensation of 1 on 4d, reacts
on cyclohexenone to give 6d. The proportion of the
latter is lowered when cyclohexenone is added very
slowly to the mixture of trisilylated reagent 1 and TiCl4
(entry 5).
This kind of double Michael-type 1,4 addition (Mi-
chael–Michael tandem reaction) has already been re-
ported in the literature [13] for alkylsilylketene acetals.
d-Ketoacids 5a, 5b and 5d are obtained as mixture of
diastereoisomers which were separated by cold precipi-
tation (5a) or column chromatography (5b and 5d). Sep-
aration of diastereoisomers 5a leads to two solids. One
of them is crystalline, which allowed us to find out its
configuration using X-ray crystallography and therefore
to conclude on the configuration of the other diastereo-
isomer (Scheme 3).
Scheme 1.
NaF (entry 8). In fluoride catalyzed reaction (entries 7
and 8), we have observed in the reaction mixture, be-
fore hydrolysis, the silylated enolate derived from ace-
tophenone. This enol arises from an exchange between
this highly enolizable ketone and the trisilylated re-
agent 1. Therefore, TiCl4 seems to be the best catalyst
for this reaction.
To determine the scope and limitations of this new di-
rect synthesis of a,b-unsaturated b-disubstitued acids 3,
several saturated, cyclic and aromatic ketones were
used. Results are reported in Table 2.
Firstly, it is to be noticed that with ketones, we have
never isolated the intermediates that lead to the corre-
sponding alkenoic acids 3 by Peterson-type elimination.
Condensation and elimination reactions must both be
fast, even at very low temperature (ꢀ70 ꢁC). Entry 3
shows that benzophenone is completely inactive at low
temperature, even after six days. Nevertheless, at room
temperature, a good yield of the corresponding ethylenic
acid is obtained (entry 4). Meanwhile, with unsymmetri-
cal ketones, the reaction gave a (Z + E) mixture of the
acids 3.
Structure assigned by X-ray (Fig. 1) shows that ste-
reoisomer 5a1, which coupling constant Ja,b = 11.25
Table 1
Reaction of C,O,O-tris(trimethylsilyl)ketene acetal 1 with acetophenone in the presence of various catalysts
O
CO2H
Ph
OSiMe3
OSiMe3
1- Catalyst
+
CH3
Ph
Me3Si
CH3
2- NH4Cl-H2O
1
2a
3a
Entry
Catalyst
Solvent
Temp. (ꢁC)
Time (h)
2a/3aa
1
2
3
4
5
6
7
8
a
10% ZnBr2
10% HgI2
1 eq AlCl3
1 eq TiCl4
1 eq TiCl4
1% KOH
10% CsF
THF
rt
5.5
5.0
5.0
9.0
6.5
5.5
5.0
24.0
100/0
100/0
48/52
0/100b
0/100b
92/8
Toluene
CH2Cl2
CH2Cl2
CH2 Cl2
DMF
rt
rt
ꢀ70
ꢀ70 (1 h) ! rt
rt
rt
rt
DMF
DMSO
95/5
100/0
10% NaF
Estimated by 13H NMR on the crude reaction mixture.
Mixture of (E + Z) isomers.
b

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M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
Table 2
Synthesis of b-disubstitued ethylenic acids 3 using trisilylated reagent 1
Entry
1
Ketones 2
Temp. (ꢁC)
ꢀ70
Time (h)
9.0
Acids 3
Yielda (%)
95
E/Zb
Ref.
[3]
78/22
HO2C
2a
2a
3a
O
H3C
H3C
Ph
CH3
Ph
3a
HO2C
O
2
3
4
5
6
7
8
ꢀ70 ! rt
ꢀ70
3.0
144.0
120.0
4.0
89
0
80/20
[3]
Ph
2b
Ph
2b
Ph
CH3
Ph
3b
Ph
3b
Ph
3c
HO2C
O
–
[4,5]
[4,5]
[5]
Ph
Ph
HO2C
O
ꢀ70 ! rt
ꢀ70 ! rt
ꢀ70
80
95
88
90
85
95
–
Ph
O
Ph
HO2C
2c
–
HO2C
HO2C
HO2C
HO2C
2d
2d
3d
O
1.5
70/30
70/30
88/12
70/30
[6,7]
[6,7]
[8]
3d
O
O
ꢀ70 ! rt
ꢀ70
3.0
36.0
3.0
2e
2e
3e
O
9
ꢀ70 ! rt
[8]
3e
a
Isolated yields.
The stereochemistry of each compound was determined by the 13H RMN spectrum of the crude product.
b
Hz, corresponds to the anti isomer. Indeed, Fig. 1 shows
that phenyl and trimethylsilyl groups are positioned in
anti one by the other. By means of this assignment, it
can be settled that the configuration of the second dia-
stereoisomer 5a2 (Ja,b = 11.52 Hz) is syn.
Unfortunately, determination of the other d-ketoac-
ids (5b and 5d) configuration using X-ray spectroscopy
was not possible since diastereoisomers 5b are in a pow-
der form and diastereoisomers 5d are oils.
tones are also very useful intermediates in total synthesis
of biologically active products. Since a-silyl-d-ketoacids
5 are not described in the literature, it strikes us as interest-
ing to study their potentiality in a-silyl lactones synthesis.
We firstly reduced the a-silyl-d-ketoacid 5a mixture
(syn/anti = 53/47) using sodium borohydride in ethanol
(Scheme 4). We obtained, after acid hydrolysis, the desily-
lated lactones 8a as two diastereoisomers along with the
d-hydroxy-a-trimethylsilyl acid 7a (one diastereoisomer).
In order to determine which of the two stereoisomers
5a (syn or anti) gave the d-hydroxy-a-trimethylsilyl acid
7a and which gave the two lactones 8a, we have reduced
each diastereoisomer 5a separately.
2.3. Reduction of a-silyl-d-ketoacids 5
It is known that d-ketoacids leads, after carbonyl
reduction, to the corresponding lactones. The latters
belong to an important class of natural compounds. Lac-
Reduction of d-ketoacid 5a anti afforded the two lac-
tones 8a syn and anti in a 20/80 ratio (Scheme 5). Their

M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
2175
Table 3
Reaction of trisilylated reagent 1 with various a,b-unsaturated ketones
O
O
R'
1- TiCl4 -70˚C
2- NH4Cl-H2O
OSiMe3
CO2H
SiMe3
+
R
R'
R
Me3Si
OSiMe3
-70˚C
20˚C
Entry
1
Ketones 4
Time (h)
Acids 5
Yield (%)a
81
Diastereoisomeric ratiob
53/47
O
3.0
O
Ph
CO H
2
Ph
4a
5a
SiMe
3
O
O
Ph
2
3
7.0
3.5
80
80
50/50
Ph
Ph
CO H
2
4b
Ph
5b
SiMe
3
O
O
–
CO H
2
4c
5c
SiMe
3
O
O
4
1.5
1.5
54 (26)c
67/33
67/33
H
CO2H
4d
5d
O
SiMe3
O
5
41 (8)c,d
H
CO2H
4d
5d
SiMe3
a
Isolated yield.
Estimated by 13H NMR on the crude reaction mixture.
b
c
Formation of a by-product 6d.
Reverse order addition: ketone diluted in dichloromethane is added to a solution of trisilylated reagent 1 and TiCl4 in dichloromethane.
d
configuration assignments were done using the literature
OSiMe3
O
data [14].
We have next reduced the d-ketoacid 5a syn
(Scheme 6).
TiCl4
1
5d
+
Me3SiO2C
NH4Cl, H2O
SiMe3
4d
This reduction gave exclusively one diastereoisomer
of d-hydroxy-a-trimethylsilyl acid 7a (white powder)
which is unknown in the literature. The determination
of its configuration and the reduction of the other
d-ketoacids 5 are currently being investigated in our
laboratory. The results will be reported in due course.
A
4d, TiCl4, -70˚C
O
OSiMe3
O
O
NH4Cl
3. Conclusion
HO2C
Me3SiO2C
SiMe3
SiMe3
In conclusion, reaction of the organosilicon reagent 1
with saturated, cyclic and aromatic ketones leads to a,b-
ethylenic acids 3 in good yields. E isomer is the major
6d
B
Scheme 2.

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M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
O
Ph
Hb
CO2H
Ha
5a1
+
5a2
Crystals
Powder
Me3Si
Jab=11.25 Hz
Jab=11.52 Hz
47% Jab=11.25 Hz
53% Jab=11.52 Hz
X-ray
O
Ph
CO2H
SiMe3
5a anti
Scheme 3.
reaction product. Attempts to study the relationship be-
tween (Z,E) isomers of the alkenoic acids 3 obtained and
the configuration (syn, anti) of the intermediates failed.
The latter compounds could not be isolated, even at
low temperature. The reaction of 1 with a,b-ethylenic
ketones affords exclusively the expected d-ketoacids
5 according to Michael-type 1,4 addition. These
compounds are obtained as a mixture of two diastereo-
isomers (syn + anti) which were separated and the con-
figurations of 5a were achieved by X-ray analysis.
4. Experimental
4.1. General information
All reactions involving water-sensitive compounds
were carried out in oven-dried glassware and under
Fig. 1. Cameron view of 5a. (Ellipsoid at 30% probability level.)
O
1) NaBH4, EtOH
O
Ph
OH Ph
O
0˚C to 25˚C
CO2H
CO2H
+
Me
Ph
2) HCl 1M
SiMe3
5a
anti / syn =47 / 53
SiMe3
8a
7a
53%
47%
Scheme 4.
O
O
O
1) NaBH4, EtOH
0˚C to 25˚C
O
Ph
O
CO2H
+
Me
Ph
Me
Ph
2) HCl 1M
SiMe3
5a anti
8a anti
8a syn
80%
20%
Jab=11.25 Hz
Scheme 5.

M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
2177
1) NaBH4, EtOH
0˚C to 25˚C
IR (KBr): 3500–2500 (OH), 1680 (C@O); MS:
O
Ph
OH Ph
M
Å+ = 162. Anal. Calc. for C10H10O2: C, 74.06; H,
6.21. Found: C, 74.21; H, 6.08.
CO2H
CO2H
2) HCl 1M
SiMe3
5a syn
SiMe3
4.2.3. (Z)-3-Phenyl but-2-enoic acid (3a)
Data from (Z + E) mixture:
13H NMR (CDCl3) d 2.17 (d, 3H, J = 1.21 Hz, CH3),
5.93 (d, 1H, J = 1.21 Hz, H-2), 7.16–7.37 (m, 5H, ArH);
13C NMR (CDCl3) d 27.55, 117.02, 126.81, 127.89,
127.93, 140.22, 158.28, 171.37.
7a
Jab=11.52 Hz
Scheme 6.
IR (KBr): 3500–2500 (OH), 1680 (C@O); MS (Z + E
mixture): MÅ+ = 162.
nitrogen atmosphere. Unless otherwise noted, starting
materials were purchased from commercial sources
and used as received. C,O,O-Tris(tri-methylsilyl)ketene
acetal 1 was prepared according to our previously re-
ported procedure [1]. Zinc bromide was prepared by
heating ground zinc and 1,2-dibromoethane in THF at
reflux [15]. All the solvents were dried and distilled prior
to use.
1H and 13C NMR spectra were recorded at 250 MHz
using CDCl3 or acetone-d6 as solvent. Chemical shifts
are given in ppm (J in Hz) relative to chloroform or ace-
tone. Melting points are uncorrected. Flash chromatog-
raphy was done on Merck grade 60 silica gel (230–400
mesh) using mixtures of cyclohexane and ethyl acetate
as eluent.
4.2.4. 3,3-Diphenyl prop-2-enoic acid (3b)
Recrystallized in ethanol; mp = 158 ꢁC (Lit. [5],
mp = 158–160 ꢁC). 13H NMR (CDCl3) d 6.28 (s, 1H,
H-2), 7.11–7.32 (m, 10H, ArH); 13C NMR (CDCl3) d
116.43, 127.88, 128.37, 128.41, 128.50, 129.23, 129.70,
138.36, 140.80, 158.98, 171.18.
IR (KBr): 3600–2500 (OH), 1680 (C@O). MS:
M
Å+ = 224. Anal. Calc. for C15H12O2: C, 80.34; H,
5.39. Found: C, 80.09; H, 5.25.
4.2.5. Cyclohexylidene ethanoic acid (3c)
Recrystallized in petroleum ether; mp = 88–89 ꢁC
(Lit. [5], mp = 90–91.5 ꢁC).
13H NMR (CDCl3) d 1.54 (m, 6H, H-b, H-b0, H-c),
2.22 (m, 2H, H-a), 2.73 (m, 2H, H-a0), 5.55 (s, 1H, H-
2); 13C NMR (CDCl3) d 26.16, 27.85, 28.63, 30.06,
38.23, 112.45, 166.77, 172.20.
4.2. Preparation of unsaturated acids 3 and d-keto-a-
trimethylsilyl acids 5
4.2.1. General procedure
IR (KBr): 3600–2400 (OH), 1700 (C@O). MS:
To a dichloromethane (20 mL) solution of ketone
(1.7 mmol) is added TiCl4 (1.7 mmol) at ꢀ70 ꢁC. Tri-
silylated reagent 1 (2 mmol) is added dropwise at the
same temperature. Reaction is checked using TLC un-
til disappearance of the starting ketone. The resulting
red solution is then quenched with a saturated NH4Cl
solution (20 mL) at ꢀ70 ꢁC and the mixture is raised
to room temperature. The aqueous layer is extracted
by dichloromethane (3 · 20 mL). The organic layers
are washed with H2O (20 mL) and dried over MgSO4.
The solvent is removed under reduced pressure. Acid–
base workup, to remove any remaining nonacidic
organic material, gives acids 3 (or 5) which are puri-
fied by recrystallization or flash chromatography.
Physical, spectral and analytical data for all com-
pounds follow.
M
Å+ = 140. Anal. Calc. for C8H12O2: C, 68.54; H, 8.63.
Found: C, 68.40; H, 8.50.
4.2.6. (E)-3-Methylpent-2-enoic acid (3d)
Column flash chromatography was done using cyclo-
hexane/ethyl acetate (90/10) as eluent. Oil.
Data from (Z + E) mixture:
13H NMR (CDCl3) d 1.05 (t, 3H, J = 7.46 Hz, H-5),
2.14 (d, 3H, J = 1.16 Hz, H-40), 2.17 (q, 2H, J = 7.46
Hz, H-4), 5.66 (q, 1H, J = 1.16 Hz, H-2).
IR (KBr): 3500–2500 (OH), 1686 (C@O); MS (E + Z
mixture): MÅ+ = 114.
4.2.7. (Z)-3-Methylpent-2-enoic acid (3d)
Data from (Z + E) mixture:
13H NMR (CDCl3) d 1.04 (t, 3H, J = 7.56 Hz, H-5),
1.89 (d, 3H, J = 1.33 Hz, H-40), 2.61 (q, 2H, J = 15.11
Hz, J = 7.56 Hz, H-4), 5.62 (q, 1H, J = 1.33 Hz, H-2).
IR (KBr): 3500–2500 (OH), 1686 (C@O); MS (Z + E
mixture): MÅ+ = 114.
4.2.2. (E)-3-Phenyl but-2-enoic acid (3a)
Recrystallized in petroleum ether; mp = 97 ꢁC (Lit.
[3], mp = 95–97 ꢁC).
13H NMR (CDCl3) d 2.57 (d, 3H, J = 1.22 Hz, CH3),
6.14 (d, 1H, J = 1.22 Hz, H-2), 7.33–7.37 (m, 3H, ArH),
7.44–7.48 (m, 2H, ArH), 11.55 (s, 1H, COOH); 13C
NMR (CDCl3) d 18.29, 116.50, 126.38, 128.53, 129.32,
141.98, 158.49, 172.50.
4.2.8. (E)-3,5-Dimethylhex-2-enoic acid (3e)
Column flash chromatography was done using cyclo-
hexane/ethyl acetate (90/10) as eluent. Oil.

2178
M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
Data from (Z + E) mixture:
4.2.11.1. Isomer I. White powder; mp = 132–134 ꢁC.
13H NMR (CDCl3) d ꢀ0.20 (s, 9H, SiMe3), 2.67 (d,
1H, J = 11.5 Hz, H-2), 3.36 (ddd, 2H, J = 15.8 Hz,
J = 10.3 Hz, J = 3.6 Hz, H-4), 3.83 (td, 1H, J = 11.5
Hz, J = 10.3 Hz, J = 3.6 Hz, H-3), 7.05–7.46 (m, 8H,
ArH), 7.75–7.78 (m, 2H, ArH); 13C NMR (CDCl3) d
ꢀ2.17, 40.52, 44.41, 46.38, 127.04, 127.88, 128.06,
128.49, 132.81, 136.96, 141.84, 180.48, 198.24.
13H NMR (CDCl3) d 0.87 (d, 6H, J = 6.34 Hz, H-6,
H-60), 1.85 (m, 1H, H-5), 2.01 (d, 2H, J = 7.21 Hz, H-
4), 2.12 (s, 3H, CH3), 5.64 (s, 1H, H-2).
IR (KBr): 3500–2500 (OH), 1690(C@O); MS (E + Z
mixture): MÅ+ = 142.
4.2.9. (Z)-3,5-Dimethylhex-2-enoic acid (3e)
Data from (Z + E) mixture:
IR (KBr): 1700 (C@O acid), 1695 (C@O ketone). MS:
MH+ = 341. Anal. Calc. for C20H24O3Si: C, 70.55; H,
7.10. Found: C, 70.70; H, 7.22.
13H NMR (CDCl3) d 0.89 (d, 6H, J = 6.24 Hz, H-6,
H-60), 1.85 (m, 1H, H-5), 1.88 (s, 3H, CH3), 2.55 (d,
2H, J = 7.45 Hz, H-4), 5.70 (s, 1H, H-2).
IR (KBr): 3500–2500 (OH), 1690(C@O); MS (E + Z
mixture): MÅ+ = 142.
4.2.11.2. Isomer II. White powder; mp = 150–151 ꢁC.
13H NMR (CDCl3) d 0.22 (s, 9H, SiMe3), 2.67 (d, 1H,
J = 10.8 Hz, H-2), 3.38 (ddd, 2H, J = 16.35 Hz, J = 10.1
Hz, J = 3.9 Hz, H-4), 3.91 (ddd, 1H, J = 10.8 Hz,
J = 10.1 Hz, J = 3.9 Hz, H-3), 7.09–7.57 (m, 8H,
ArH), 7.78–7.81 (m, 2H, ArH); 13C NMR (CDCl3) d
ꢀ1.31, 40.17, 44.07, 44.40, 126.51, 127.90, 128.13,
128.45, 132.92, 137.08, 143.57, 178.91, 198.03.
4.2.10. 5-Oxo-3-phenyl-2-trimethylsilyl hexanoic acid
(5a)
4.2.10.1. Anti. Recrystallized in pentane/carbon tetra-
chloride (60/40); mp = 139–140 ꢁC.
13H NMR (CDCl3) d 0.10 (s, 9H, SiMe3), 1.80 (s, 3H,
H-6), 2.41 (d, 1H, J = 11.25 Hz, H-2), 2.69 (dd, 2H,
J = 8.75 Hz, J = 6.25 Hz, H-4), 3.54 (ddd, 1H,
J = 11.25 Hz, J = 8.75 Hz, J = 6.25 Hz, H-3), 7.04–
7.16 (m, 5H, ArH); 13C NMR (CDCl3) d ꢀ1.44, 30.84,
40.53, 44.17, 49.42, 126.72, 127.71, 128.30, 143.14,
179.07, 206.92.
IR (KBr): 1689 (C@O acid), 1674 (C@O ketone). MS:
MH+ = 341. Anal. Calc. for C20H24O3Si: C, 70.55; H,
7.10. Found: C,70.41; H, 7.19.
4.2.12. 3,3-Dimethyl-5-oxo-2-trimethylsilylhexanoic
acid (5c)
IR (KBr): 1713 (C@O acid), 1680 (C@O ketone). MS:
MH+ = 279. Anal. Calc. for C15H22O3Si: C, 64.71; H,
7.96. Found: C, 64.90; H, 7.83.
Column flash chromatography was done using cyclo-
hexane/ethyl acetate (70/30) as eluent. Oil.
13H NMR (CDCl3) d 0.12 (s, 9H, SiMe3), 1.16 (s, 6H,
CH3), 2.07 (s, 3H, H-6), 2.36 (d, 1H, J = 15.8 Hz, H-4),
2.37 (s, 1H, H-2), 2.78 (d, 1H, J = 15.8 Hz, H-40); 13C
NMR (CDCl3) d 0.22, 27.42, 28.02, 32.19, 35.86,
48.68, 53.85, 180.84, 208.45.
IR (KBr): 1718 (C@O acid), 1683 (C@O ketone). MS:
MH+ = 231. Anal. Calc. for C11H22O3Si: C, 57.35; H,
9.63. Found: C, 57.57; H, 9.40.
X-ray crystal data of 5a: C15H22O3Si; M = 278.4;
˚
space group = P21/c; a = 10.553(3) A; b = 14.121(4) A;
˚
3
˚
˚
c = 11.758(8) A; V = 1672(1) A ; Z = 4; T = 295 K;
l = 0.136 mmꢀ1; reflections total 3268; reflections
observed (I > 3r(I)) 1529; parameters refined 174;
final values, Robs = 0.0500; wRall = 0.0753; GOF =
1.088.
4.2.10.2. Syn. Recrystallized in pentane/carbon tetra-
chloride (60/40); mp = 115–117 ꢁC.
4.2.13. 2-(3-Oxocyclohexyl)-2-trimethylsilylethanoic
acid (5d)
The two diastereoisomers were separated by column
flash chromatography using cyclohexane/ethyl acetate
(90/10) as eluent.
13H NMR (CDCl3) d ꢀ0.21 (s, 9H, SiMe3), 1.86 (s,
3H, H-6), 2.40 (d, 1H, J = 11.5 Hz, H-2), 2.82 (ddd,
2H, J = 15.5 Hz, J = 10.4 Hz, J = 3.7 Hz, H-4), 3.61
(ddd, 1H, J = 11.5 Hz, J = 10.4 Hz, J = 3.7 Hz, H-3),
7.11–7.27 (m, 5H, ArH); 13C NMR (CDCl3) d ꢀ2.24,
30.57, 40.25, 44.58, 51.13, 127.13, 128.34, 128.51,
141.77, 181.11, 207.13.
4.2.13.1. Isomer I. Oil: 13H NMR (CDCl3) d 0.08 (s,
9H, SiMe3), 1.43–2.50 (m, 10H); 13C NMR (CDCl3) d
ꢀ1.62, 24.87, 30.91, 38.06, 40.74, 44.04, 47.27, 180.14,
210.87.
IR (KBr): 1716 (C@O acid), 1685 (C@O ketone). MS:
MH+ = 229. Anal. Calc. for C11H20O3Si: C, 57.85; H,
8.83. Found: C, 57.50; H, 8.72.
IR (KBr): 1720 (C@O acid), 1685 (C@O ketone). MS:
MH+ = 279. Anal. Calc. for C15H22O3Si: C, 64.71; H,
7.96. Found: C, 64.48; H, 7.82.
4.2.11. 5-Oxo-3,5-diphenyl-2-trimethylsilylhexanoic
acid (5b)
The two diastereoisomers were separated by column
flash chromatography using cyclohexane/ethyl acetate
(80/20) as eluent.
4.2.13.2. Isomer II. Oil: 13H NMR (CDCl3) d 0.09 (s,
9H, SiMe3), 1.43–2.50 (m, 10H); 13C NMR (CDCl3) d
ꢀ1.67, 24.63, 31.02, 37.99, 40.89, 44.29, 47.56, 180.40,
211.03.

M. Bellassoued et al. / Journal of Organometallic Chemistry 690 (2005) 2172–2179
2179
IR (KBr): 1716 (C@O acid), 1685 (C@O ketone). MS:
MH+ = 229. Anal. Calc. for C11H20O3Si: C, 57.85; H,
8.83. Found: C, 57.39; H, 8.61.
(m, 5H, ArH); 13C NMR (CDCl3) d 21.2, 34.6, 35.8,
36.7, 73.8, 126.6, 127.0, 128.9, 143.0, 171.7.
IR (KBr): 1733 (C@O). MS: MH+ = 191. Anal. Calc.
for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.32; H,
7.66.
4.2.14. 2-[30-Oxocyclohexyl-2-(3-oxocyclohexyl)]-2-
trimethylsilyl acid (6d)
Column flash chromatography was done using cyclo-
hexane/ethyl acetate (70/30) as eluent. White powder.
13H NMR (CDCl3) d 0.12 (s, 9H, SiMe3), 0.79–2.40
(m, 18H); 13C NMR (CDCl3) d ꢀ1.5, 22.4, 23.2, 25.1,
29.2, 37.8, 38.9, 39.1, 39.8, 41.1, 45.7, 179.9, 210.7,
213.4.
4.3.2.2. Syn. Oil: 13H NMR (CDCl3) d 1.42 (d, 3H,
J = 6.28 Hz, CH3), 1.70 (m, 1H, H-5), 2.13 (m, 1H, H-
5), 2.50 (dd, 1H, J = 17.8 Hz, J = 11.5 Hz, H-3), 2.87
(ddd, 1H, J = 17.8 Hz, J = 5.9 Hz, J = 2.0 Hz, H-3),
3.16 (m, 1H, H-4), 4.54 (m, 1H, H-6), 7.12–7.38 (m,
5H, ArH); 13C NMR (CDCl3) d 21.9, 37.4, 37.6, 38.0,
73.9, 126.5, 127.2, 129.0, 143.0, 170.9.
IR (KBr): 1734 (C@O). MS: MH+ = 190. Anal. Calc.
for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.32; H,
7.65.
MS: MH+ = 325.
4.3. Reduction of d-keto-a-trimethylsilyl acids 5a
1.2 mmol of syn 5a (0.335 g) is dissolved in ethanol (6
mL) and the solution cooled at 0 ꢁC. Sodium borohy-
dride (0.054 g, 1.44 mmol) is added portionwise. The
mixture is then stirred for 1.5 h at this temperature
and hydrolyzed by 5 mL of hydrochloric acid 1 M.
The alcohol is removed under reduced pressure and
the resulting aqueous layer is extracted by ethyl acetate
(3 · 20 mL). The organic layer is dried over magnesium
sulphate and the solvent is removed under reduced
pressure.
Appendix A. Supplementary data
Supplementary data associated with this article can
be found, in the online version at doi:10.1016/
j.jorganchem.2005.01.049.
References
When 5a anti is reduced, the resulting lactones 8a are
separated by flash chromatography using a mixture of
ethyl acetate/ cyclohexane (10/90) as eluent.
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ˆ
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13H NMR (acetone-d6) d ꢀ0.21 (s, 9H, SiMe3), 1.16
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J = 6.3 Hz, CH3), 2.02 (m, 2H, H-5), 2.74 (m, 2H, H-
3), 3.33 (m, 1H, H-4), 4.53 (m, 1H, H-6), 7.13–7.35
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