Two-carbon homologation of aldehydes via silyl ketene acetals. 2. Study of the stereochemical control in the formation of (E)-alkenoic acids

Article abstract of DOI:10.1021/jo010092q

The condensation of C,O,O-tris(trimethylsilyl)ketene acetal 1 with aldehydes 2 in the presence of catalytic amounts of mercuric iodide at room temperature affords syn and anti β-trimethylsiloxy α-trimethylsilyl alkanoic acid silyl esters 3 in good yields. These new compounds gave, under acidic or basic conditions, E and (or) Z enoic acids 4. The paths for the formation of these alkenoic acids are discussed.

Full text of DOI:10.1021/jo010092q

5054
J . Org. Chem. 2001, 66, 5054-5057
Tw o-Ca r bon Hom ologa tion of Ald eh yd es via Silyl Keten e Aceta ls.
2.1 Stu d y of th e Ster eoch em ica l Con tr ol in th e F or m a tion of
(E)-Alk en oic Acid s
Moncef Bellassoued,* Sinda Mouelhi, and Nathalie Lensen
Laboratoire de Synthe`se Organome´tallique associe´ au CNRS, Universite´ de Cergy-Pontoise, Baˆtiment des
Sciences de la Matie`re, 5 Mail Gay Lussac, Neuville sur Oise, 95031 Cergy-Pontoise Cedex, France
moncef.bellassoued@chim.u-cergy.fr
Received J anuary 23, 2001
The condensation of C,O,O-tris(trimethylsilyl)ketene acetal 1 with aldehydes 2 in the presence of
catalytic amounts of mercuric iodide at room temperature affords syn and anti â-trimethylsiloxy
R-trimethylsilyl alkanoic acid silyl esters 3 in good yields. These new compounds gave, under acidic
or basic conditions, E and (or) Z enoic acids 4. The paths for the formation of these alkenoic acids
are discussed.
Sch em e 1
In tr od u ction
Recently, we have developed a new and convenient
method for the direct conversion of aldehydes into (E)-
alkenoic acids 4 using C,O,O-tris(trimethylsilyl)ketene
acetal 1 through a condensation-elimination reaction1
(Scheme 1). We have noted, at the end of our article, that
further detailed study on the correlation between the
elimination mechanism and the product’s stereochemis-
try was in progress. We report here an account of our
investigations concerning this olefination process. We
also provide full characterization data for a series of
â-siloxy-R-silyl trimethylsilyl esters 3, the reaction-
sensitive intermediates.
Sch em e 2
Resu lts a n d Discu ssion
Our first investigations were focused on the reaction
of 1 with benzaldehyde 2a in the presence of catalytic
amounts of mercuric iodide2 at room temperature. The
mildness of these aldol conditions permitted the isolation
of the sensitive intermediates 3a .1 Typically, the silyl
ketene acetal 1 and benzaldehyde 2a were added to a
stirring suspension of HgI2 in toluene. TLC monitoring
revealed the complete conversion of the aldehyde into 3a
after 6 h. Simple workup, which consists of removing the
toluene under high vacuum, diluting the crude product
with cyclohexane, filtering away the catalyst and strip-
ping off the solvent, affords adducts 3a (anti + syn) in
96% yield (Scheme 2).
The diastereoselectivity of the reaction, as shown by
1H NMR on the crude product, is in the range of 67:33.
The vicinal coupling constant J ab is less (10.35 Hz) for
the major than for the minor isomer (10.91 Hz).
The major problem concerned the stereochemistry of
the intermediates 3a : which is syn and which is anti?
Since suitable crystals were not obtained for rigorous
assignment by X-ray spectroscopy, we sought another
approach to determine the configuration of these dia-
stereomers.
The mixture of the diastereomers (syn + anti) obtained
previously was treated with 1 equiv of TiCl4 in dichlo-
romethane at room temperature. Quenching the reaction
with water gave a mixture of (E) and (Z) 4a alkenoic
acids. Their E/Z ratio corresponded to the ratio (67/33)
of the starting â-siloxytrimethylsilyl esters 3a . Since
elimination of hexamethyldisiloxane is highly regulated
to the anti manner in acidic medium,3,4 the major
diastereomer is assigned to anti 3a and the minor isomer
to syn 3a . For rigorous proof, the diastereomers 6a were
(1) Part 1: Bellassoued, M.; Lensen, N.; Bakasse, M.; Mouelhi, S. J .
Org. Chem. 1998, 63, 8785.
(2) Dicker, I. B. J . Org. Chem. 1993, 58, 2324.
(3) Hudrlik, P. F.; Peterson, D. J . Am. Chem. Soc. 1975, 97, 1464.
(4) Ager, D. J . Synthesis 1984, 384.
10.1021/jo010092q CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/23/2001

Homologation of Aldehydes via Silyl Ketene Acetals
J . Org. Chem., Vol. 66, No. 15, 2001 5055
Sch em e 3
obtained from a mixture of 3a (syn + anti) by being
passed through a silica gel column and separated at the
same time. Each isomer was treated with TiCl4 at room
temperature for 1 h. After quenching of the reaction with
H2O, anti 6a afforded (E) 4a and syn 6a gave (Z) 4a
(Scheme 2).
Pure syn 6a could also be obtained when benzaldehyde
and reagent 1 were treated at -78 °C with TiCl4 in CH2-
Cl2 with quenching of the reaction at -78 °C. However,
when the reaction was performed at -78 °C and then
warmed to 25 °C for 1 h before quenching of the reaction
at -78 °C, cinnamic acids 4a were found with a diaster-
eomeric ratio E/ Z ) 67/33. This result may be explained
as follows: an equilibrium between syn and anti 3a (or
their corresponding titanium complex derivatives) could
take place during the temperature rise. Subsequent
elimination yields the mixture of (E) and (Z) cinnamic
acids 4a .
Interestingly, when the reaction of 1 with 2a was
carried out in the presence of catalytic amounts of ZnBr2
(10%) in tetrahydrofuran at room temperature for 4 h,
only (E) cinnamic acid 4a was obtained (95% yield).1
Several attemps to isolate the presumable intermediate
anti 3a (or its derivatives) failed. However, addition of
zinc bromide (10%) at room temperature to a mixture of
the preformed intermediates 3a (anti/ syn ) 67/33) leads
to the formation of (E) and (Z) 4a in the ratio E/ Z ) 67/
33. These results allowed us to speculate reasonably that
anti 3a is the only intermediate when the reaction of 1
with 2a was catalyzed by ZnBr2.
Next, we investigated the fluoride-promoted reaction
of 1 with benzaldehyde 2a (Scheme 3).1 When the
reaction was performed at -30 °C in the presence of
cesium fluoride (10%) for 30 min and then quenched at
the same temperature with water, â-siloxy-R-silyl acid
anti 5a was isolated (30%) with (E) cinnamic acid 4a
(70%). As the same reaction, carried out at room tem-
perature, gave the (E) 4a isomer exclusively, we assumed
that formation of the (E) cinnamic acid 4a occurred via
the two diastereoisomers anti and syn 3a . The latter
undergoes, in the basic medium, spontaneous elimination
even at low temperature (-30 °C). Elimination of hex-
amethyldisiloxane from the syn isomer 3a might be
expected to be preferred because of the configuration
required for syn-elimination, affording the thermody-
namically more stable E alkenoic acid. However, the
difficulty of the syn-elimination in anti 3a at -30 °C,
leads, with the elevation of temperature, to the formation
of syn 3a isomer through a retro-aldol reaction or by 1,3-
migration of the silyl group5 (Scheme 3). In fact, when
this reaction was tested at room temperature starting
from a mixture of the â-siloxy-R-silyl esters 3a (anti/ syn
) 67/33), synthesized using mercuric iodide, we obtained
only the E isomer 4a in almost quantitative yield. This
result clearly supports the postulated elimination path-
way since we have already verified that (Z) trimethylsilyl
cinnamate did not isomerize to the more stable E isomer
in the presence of CsF. Similar results were obtained
using potassium tert-butoxide or KOH as catalyst.6
Last, a systematic study of the reaction reveals that
the preparation of â-siloxy-R-silyltrimethylsilyl esters 3
can be performed cleanly by reaction of 1 with a variety
of structurally different aldehydes 2. As shown in Table
1, aromatic, vinylic, and aliphatic aldehydes afford the
corresponding intermediates 3 in good yield. All these
compounds are, to our knowledge, unknown and could
be used as prodrugs for cinnamic acids analogues. The
usefulness of these condensations lies also in the subse-
quent chemistry of the silyl moiety to obtain polyfunc-
tionalized products.
1
Selected H NMR spectral data for anti 3a -h and syn
3a -h are listed in the same table. We noticed that the
chemical shifts of the R-hydrogens (Ha) are less for the
major than for the minor isomer and conversely those of
the â-hydrogens (Hb) are larger for the major than for
the minor isomer. The vicinal coupling constant J ab is
less for the major than for the minor isomer. Moreover,
mixtures of diastereoisomers 3b-h were also treated
with TiCl4 to give mixtures of (E) and (Z) 4. Their E/Z
ratios corresponded with the ratios of major and minor
3. Therefore the stereochemistry of the major isomer was
assigned as anti and the minor isomer as syn. These data
are in agreement with those of the â-hydroxy-R-silyl alkyl
esters.7,8
Con clu sion
The stereochemical outcome of this olefination reaction
is intriguing. However, from the results reported here,
(5) Larcheveˆque, M.; Debal, A. J . Chem. Soc., Chem. Commun. 1981,
877.
(6) Lensen, N.; Mouelhi, S.; Bellassoued, M. Synth. Commun. In
press.
(7) Matsuda, I.; Izumi, Y. Tetrahedron Lett. 1981, 22, 1805.
(8) Akai, S.; Tsuzuki, Y.; Matsuda, S.; Kitagaki, S.; Kita, Y. Synlett
1991, 911.

5056 J . Org. Chem., Vol. 66, No. 15, 2001
Bellassoued et. al.
Ta ble 1. P r ep a r a tion of â-Siloxy-r-tr im eth ylsilyla lk a n oic Acid Tr im eth ylsilyl Ester s 3 a n d Selected 1H NMR Sp ectr a l
Da ta
a
b
1
Isolated yield. The ratio of anti and syn of each compound was determined by the H NMR spectrum of the crude product.
-0.12 (s, 9 H, CSi(CH3)3), 0.00 (s, 9 H, OSi(CH3)3), 0.14 (s, 9
H, COOSi(CH3)3), 2.55 (d, 1 H, J ) 10.35 Hz, H-2), 5.08 (d, 1
H, J ) 10.35 Hz, H-3), 7.22-7.48 (m, 5 H, ArH); 13C NMR
(CDCl3) δ -1.45, -0.42, 0.25, 51.12, 75.51, 126.84, 127.39,
127.93, 145.17, 173.52.
we can assume that the geometrical ratio of cinnamic
acids 4a reflects the diastereochemical ratio of the
intermediates 3a when the reactions are carried out in
the presence of TiCl4 or ZnBr2. In the case of cesium
fluoride-catalyzed reaction, formation of the (E) 4a occurs
via the two diastereomers syn and anti 3a . Equilibration
of the latter to the preferred syn isomer followed by
synchronous elimination to the E-olefin seems very likely.
Syn : 1H NMR (acetone-d6) δ -0.28 (s, 9 H, CSi(CH3)3),
-0.15 (s, 9 H, OSi(CH3)3), 0.26 (s, 9 H, COOSi(CH3)3), 2.62 (d,
1 H, J ) 10.91 Hz, H-2), 5.07 (d, 1 H, J ) 10.91 Hz, H-3),
7.22-7.48 (m, 5 H, ArH); 13C NMR (CDCl3) δ -2.44, -0.05,
0.01, 51.58, 75.41, 127.44, 128.01, 128.27, 143.38, 174.35.
IR (CDCl3): 1695 (CdO). MS: M•+ ) 382. Anal. Calcd for
18H34O3Si3: C, 56.49; H, 8.95. Found: C, 56.38; H, 8.91.
Exp er im en ta l Section
C
Gen er a l In for m a tion . All experiments were carried out
under a nitrogen atmosphere using freshly distilled solvents
under anhydrous conditions. Starting aldehydes and catalysts
were purchased from commercial sources and used as received.
C,O,O-Tris(trimethylsilyl)ketene acetal 1 was prepared using
our previously reported procedure.1 1H and 13C NMR spectra
were recorded at 250 MHz using CDCl3 or acetone-d6 as
solvent. Chemical shifts were given in ppm (J in hertz) relative
to chloroform or acetone. Melting points are uncorrected. Flash
column chromatography was carried out 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 3-(Tr im eth ylsiloxy)-2-
(tr im eth ylsilyl)p r op a n oa tes (3). Gen er a l P r oced u r e. A
toluene (10 mL) solution of aldehyde 2 (1.7 mmol) and 1 (0.552
g, 2 mmol) was added to HgI2 (0.077 g, 0.17 mmol) at room
temperature. The reaction was stirred for 5 h; then 10 mL of
distilled cyclohexane was added. After decantation, the solu-
tion was removed by a syringe and the solvent was stripped
off under high vacuum. The residual oil showed anti and syn
compounds 3. The ratio of these diastereoisomers was deter-
mined from integrated values of protons of 1H NMR (yields
and ratios are listed in Table 1). Since syn and anti isomers 3
are unseparable, some data (infrared, mass, and microanaly-
ses) were collected from the mixture of diastereoisomers.
Tr im eth ylsilyl 3-P h en yl-3-(tr im eth ylsiloxy)-2-(tr im e-
th ylsilyl)p r op a n oa te (3a ). An ti: 1H NMR (acetone-d6) δ
Tr im eth ylsilyl 3-(3-P h en oxyph en yl)-3-(tr im eth ylsiloxy)-
2-(tr im eth ylsilyl)p r op a n oa te (3b). An ti: 1H NMR (acetone-
d6) δ 0.00 (s, 9 H, CSi(CH3)3), 0.16 (s, 9 H, OSi(CH3)3), 0.21 (s,
9 H, COOSi(CH3)3), 2.60 (d, 1 H, J ) 10.35 Hz, H-2), 5.08 (d,
1 H, J ) 10.35 Hz, H-3), 6.95-7.42 (m, 9 H, ArH); 13C NMR
(CDCl3) δ -1.52, -0.43, 0.22, 50.93, 75.07, 118.31, 118.49,
121.92, 122.82, 128.09, 129.20, 129.53, 146.99, 156.67, 157.43,
172.86.
Syn : 1H NMR (acetone-d6) δ -0.15 (s, 9 H, CSi(CH3)3),
-0.02 (s, 9 H, OSi(CH3)3), 0.36 (s, 9 H, COOSi(CH3)3), 2.63 (d,
1 H, J ) 10.90 Hz, H-2), 5.05 (d, 1 H, J ) 10.90 Hz, H-3),
6.95-7.42 (m, 9 H, ArH); 13C NMR (CDCl3) δ -2.41, -0.16,
0.01, 51.37, 74.96, 118.26, 118.91, 122.24, 123.07, 125.18,
128.88, 129.60, 145.16, 157.20, 157.30, 173.58.
IR (CDCl3): 1695 (CdO). MS: M•+ ) 474. Anal. Calcd for
24H38O4Si3: C, 60.71; H, 8.07. Found: C, 60.67; H, 8.01.
Tr im eth ylsilyl 3-(4-Ch lor op h en yl)-3-(tr im eth ylsiloxy)-
C
2-(tr im eth ylsilyl)p r op a n oa te (3c). An ti: 1H NMR (CDCl3)
δ -0.12 (s, 9 H, CSi(CH3)3), 0.04 (s, 9 H, OSi(CH3)3), 0.14 (s, 9
H, COOSi(CH3)3), 2.49 (d, 1 H, J ) 10.34 Hz, H-2), 5.00 (d, 1
H, J ) 10.34 Hz, H-3), 7.22 (m, 4 H, ArH); 13C NMR (CDCl3)
δ -1.46, -0.39, 0.29, 51.23, 74.80, 128.11, 128.12, 133.05,
143.55, 172.95.
Syn : 1H NMR (CDCl3) δ -0.26 (s, 9 H, CSi(CH3)3), -0.13
(s, 9 H, OSi(CH3)3), 0.28 (s, 9 H, COOSi(CH3)3), 2.57 (d, 1 H,
J ) 10.86 Hz, H-2), 4.99 (d, 1 H, J ) 10.86 Hz, H-3), 7.22 (m,

Homologation of Aldehydes via Silyl Ketene Acetals
J . Org. Chem., Vol. 66, No. 15, 2001 5057
4 H, ArH); 13C NMR (CDCl3) δ -2.33, -0.08, 0.03, 51.55, 74.63,
128.67, 128.50, 133.66, 141.74, 173.58.
9.57 Hz, H-2), 4.24 (m, 1 H, J ) 9.57 Hz, H-3); 13C NMR
(CDCl3) δ -1.05, 0.16, 0.64, 14.10, 22.11, 23.75, 29.36, 29.78,
31.66, 38.00, 46.75, 72.68, 173.59.
IR (KBr): 1693 (CdO). MS: M•+ ) 416; 418. Anal. Calcd
for C18H33ClO3Si3: C, 51.82; H, 7.97. Found: C, 51.78; H, 7.92.
Tr im eth ylsilyl 3-(3-Th ien yl)-3-(tr im eth ylsiloxy)-2-(tr i-
m eth ylsilyl)p r op a n oa te (3d ). An ti: 1H NMR (CDCl3) δ 0.07
(s, 9 H, CSi(CH3)3), 0.23 (s, 9 H, OSi(CH3)3), 0.30 (s, 9 H,
COOSi(CH3)3), 2.72 (d, 1 H, J ) 10.36 Hz, H-2), 5.31 (d, 1 H,
J ) 10.36 Hz, H-3), 7.27 (m, 3 H, ArH); 13C NMR (CDCl3) δ
-1.48, -0.38, 0.11, 50.37, 70.99, 121.33, 125.41, 126.11, 146.11,
173.15.
IR (KBr): 1693 (CdO). MS: M•+ ) 404. Anal. Calcd for
19H44O3Si3: C, 56.37; H, 10.96. Found: C, 56.29; H, 10.90.
C
P r ep a r a tion of 3-(Tr im eth ylsiloxy)-3-p h en yl-2-(tr im -
eth ylsilyl)p r op a n oic Acid (5a ). A toluene (10 mL) solution
of benzaldehyde 2a (0.172 mL, 1.7 mmol) and 1 (0.552 g, 2
mmol) was added to HgI2 (0.077 g, 0.17 mmol) at room
temperature. The reaction was stirred for 5 h, and 10 mL of
distilled cyclohexane was added by a syringe to the mixture.
After 1 h, the solution was filtered and placed under high
vacuum to remove toluene and cyclohexane. The limpid
residual oil was quenched by NH4Cl (10 mL) for 1.5 h and
extracted with ether (3 × 20 mL). The organic layers were
washed with H2O (30 mL) and dried over MgSO4, and the
solvent was evaporated under reduced pressure, affording a
white powder (yield: 85%). The solid crude product, analyzed
by 1H NMR, showed a mixture of anti and syn isomers (5a )
(anti/syn ) 67/33). The ratio of the diastereoisomers was
determined from integrated values of hydrogens at the C-3
carbon.
Syn : 1H NMR (CDCl3) δ -0.06 (s, 9 H, CSi(CH3)3), 0.05 (s,
9 H, OSi(CH3)3), 0.45 (s, 9 H, COOSi(CH3)3), 2.77 (d, 1 H, J )
11.01 Hz, H-2), 5.31 (d, 1 H, J ) 11.01 Hz, H-3), 7.27 (m, 3 H,
ArH); 13C NMR (CDCl3) δ -2.59, -0.12, -0.06, 50.93, 70.55,
121.63, 126.11, 126.73, 144.34, 173.71.
IR (KBr): 1693 (CdO). MS: M•+ ) 388. Anal. Calcd for
16H32O3SSi3: C, 49.43; H, 8.30. Found: C, 49.39; H, 8.25.
C
Tr im eth ylsilyl 5-P h en yl-3-(tr im eth ylsiloxy)-2-(tr im e-
th ylsilyl)-4-p en ten oa te (3e). An ti: 1H NMR (CDCl3) δ -0.13
(s, 9 H, CSi(CH3)3), -0.10 (s, 9 H, OSi(CH3)3), 0.09 (s, 9 H,
COOSi(CH3)3), 2.17 (d, 1 H, J ) 9.80 Hz, H-2), 4.52 (dd, 1 H,
J ) 9.80 Hz, 8.39 Hz, H-3), 5.89 (dd, 1 H, J ) 15.90 Hz, 8.39
Hz, H-4), 6.32 (d, 1 H, J ) 15.90 Hz, H-5), 7.23 (m, 5 H, ArH);
13C NMR (CDCl3) δ -0.15, 0.41, 0.59, 49.68, 74.06, 126.29,
127.69, 128.57, 129.90, 130.77, 136.32, 173.47.
An ti: 1H NMR (acetone-d6) δ -0.07 (s, 9 H, CSi(CH3)3), 0.21
(s, 9 H, OSi(CH3)3), 2.63 (d, 1 H, J ) 10.40 Hz, H-2), 5.15 (d,
1 H, J ) 10.40 Hz, H-3), 7.28-7.47 (m, 5 H, ArH); 13C NMR
(acetone-d6) δ -1.16, 0.40, 49.91, 76.30, 127.60, 128.31, 128.79,
145.76, 174.50.
1
Syn : H NMR (CDCl3) δ -0.10 (s, 9 H, CSi(CH3)3), -0.05
(s, 9 H, OSi(CH3)3), 0.00 (s, 9 H, COOSi(CH3)3), 2.21 (d, 1 H,
J ) 10.00 Hz, H-2), 4.49 (dd, 1 H, J ) 10.00 Hz, 8.22 Hz, H-3),
5.90 (dd, 1 H, J ) 15.80 Hz, 8.22 Hz, H-4), 6.23 (d, 1 H, J )
15.80 Hz, H-5), 7.23 (m, 5 H, ArH); 13C NMR (CDCl3) δ -1.78,
-1.44, -0.29, 48.71, 74.59, 126.29, 127.44, 128.41, 131.25,
132.72, 136.56, 173.08.
Syn : 1H NMR (acetone-d6) δ -0.23 (s, 9 H, CSi(CH3)3),
-0.09 (s, 9 H, OSi(CH3)3), 2.64 (d, 1 H, J ) 10.75 Hz, H-2),
5.13 (d, 1 H, J ) 10.75 Hz, H-3), 7.28-7.47 (m, 5 H, ArH); 13
C
NMR (acetone-d6) δ -2.24, -0.18, 50.37, 75.95, 127.60, 128.79,
129.07, 144.12, 175.85.
IR (KBr): 1693 (CdO). MS: M•+ ) 408. Anal. Calcd for
20H36O3Si3: C, 58.77; H, 8.88. Found: C, 58.71; H, 8.81.
IR (KBr): 1700 (CdO). MS: M•+ ) 310. Anal. Calcd for
15H26O3Si2: C, 58.02; H, 8.44. Found: C, 58.05; H, 8.37.
C
C
Tr im eth ylsilyl 5-Meth yl-3-(tr im eth ylsiloxy)-2-(tr im e-
th ylsilyl)-4-h exen oa te (3f). An ti: 1H NMR (CDCl3) δ 0.05
(s, 9 H, CSi(CH3)3), 0.10 (s, 9 H, OSi(CH3)3), 0.20 (s, 9 H,
COOSi(CH3)3), 1.65 (s, 3H, CH3), 1.66 (s, 3H, CH3), 2.20 (d, 1
H, J ) 9.90 Hz, H-2), 4.80 (dd, 1 H, J ) 9.90 Hz, 9.50 Hz,
H-3), 5.07 (d, 1 H, J ) 9.50 Hz, H-4); 13C NMR (CDCl3) δ -1.48,
-0.25, 0.55, 18.44, 25.61, 49.15, 69.44, 129.43, 131.94, 173.41.
P r ep a r a tion of 3-Hyd r oxy-3-p h en yl-2-(tr im eth ylsilyl)-
p r op a n oic Acid (6a ). P r oced u r e A. A mixture of propanoate
3a was chromatographed (silica gel, cyclohexane/ethyl acetate
70/30); two fractions were isolated containing pure isomers syn
6a (30%) and anti 6a (60%).
P r oced u r e B. To a cooled (-70 °C) dichloromethane (10
mL) solution of benzaldehyde 2a (0.172 mL, 1.7 mmol) was
added TiCl4 (1.7 mmol) via a syringe. Reagent 1 (0.552 g, 2
mmol) was added dropwise, and the resulting mixture was
stirred at -70 °C for 1 h. After quenching with a saturated
NH4Cl solution (10 mL) at the same temperature, the tem-
perature of the solution was raised to room temperature. The
aqueous layer was extracted with dichloromethane (2 × 20
mL) and ether (1 × 20 mL), and the combined organic phases
were washed with water and dried over MgSO4. The solvents
were evaporated in vacuo. Purification by recrystallization in
pentane gave pure syn 3-hydroxy-3-phenyl-2-(trimethylsilyl)-
propanoic acid 6a (yield: 95%).
An ti: recrystallized in cyclohexane; mp ) 87-94 °C; 1H
NMR (acetone-d6) δ -0.01 (s, 9 H, CSi(CH3)3), 2.68 (d, 1 H, J
) 7.28 Hz, H-2), 2.95 (s, 1 H, OH), 5.01 (d, 1 H, J ) 7.28 Hz,
H-3), 7.24-7.44 (m, 5 H, ArH); 13C NMR (CDCl3) -2.08, 46.23,
72.47, 126.04, 127.71, 128.43, 143.10, 180.53; IR (KBr) 3345
(OH), 1690 (CdO); MS M•+ ) 238. Anal. Calcd for C12H18O3-
Si: C, 60.46; H, 7.61. Found: C, 60.44; H, 7.59.
1
Syn : H NMR (CDCl3) δ 0.01 (s, 9 H, CSi(CH3)3), 0.04 (s, 9
H, OSi(CH3)3), 0.27 (s, 9 H, COOSi(CH3)3), 1.67 (s, 3H, CH3),
1.71 (s, 3H, CH3), 2.29 (d, 1 H, J ) 10.28 Hz, H-2), 4.79 (dd, 1
H, J ) 10.28 Hz, 9.50 Hz, H-3), 5.07 (d, 1 H, J ) 9.50 Hz,
H-4); 13C NMR (CDCl3) δ -1.87, -0.07, 0.38, 18.90, 25.68,
50.22, 69.22, 127.84, 132.54, 174.03.
IR (KBr): 1693 (CdO). MS: M•+ ) 360. Anal. Calcd for
16H36O3Si3: C, 53.28; H, 10.06. Found: C, 53.20; H, 10.01.
C
Tr im eth ylsilyl 4-Meth yl-3-(tr im eth ylsiloxy)-2-(tr im e-
th ylsilyl)p en ta n oa te (3g). An ti: 1H NMR (CDCl3) δ 0.06 (s,
9 H, CSi(CH3)3), 0.08 (s, 9 H, OSi(CH3)3), 0.22 (s, 9 H, COOSi-
(CH3)3), 0.76 (d, 3H, CH3, J ) 7.0 Hz), 0.83 (d, 3H, CH3, J )
6.80 Hz), 1.83 (m, 1H, H-4), 2.33 (d, 1 H, J ) 8.48 Hz, H-2),
4.26 (dd, 1 H, J ) 8.48 Hz, 4.25 Hz, H-3); 13C NMR (CDCl3) δ
-1.16, -0.43, 0.55, 15.42, 18.09, 29.49, 35.16, 42.61, 174.71.
1
Syn : H NMR (CDCl3) δ 0.08 (s, 9 H, CSi(CH3)3), 0.21 (s, 9
H, OSi(CH3)3), 0.24 (s, 9 H, COOSi(CH3)3), 0.92 (d, 3H, CH3,
J
) 6.80 Hz), 1.0 (d, 3H, CH3, J ) 7.30 Hz), 1.83 (m, 1H, H-4),
2.41 (d, 1 H, J ) 10.86 Hz, H-2), 4.04 (d, 1 H, J ) 10.86 Hz,
H-3); 13C NMR (CDCl3) δ -2.17, -0.94, 0.51, 15.16, 18.25,
29.49, 35.06, 41.26, 174.71.
Syn : recrystallized in pentane; mp ) 135-137 °C; 1H NMR
(acetone-d6) δ 0.20 (s, 9 H, CSi(CH3)3), 2.57 (d, 1 H, J ) 10.32
Hz, H-2), 4.45 (s, 1 H, OH), 5.11 (d, 1 H, J ) 10.32 Hz, H-3),
7.15-7.45 (m, 5 H, ArH); 13C NMR (CDCl3) δ -1.18, 46.94,
72.97, 125.80, 127.66, 128.41, 143.68, 180.11; IR (KBr) 3394
(OH), 1672 (CdO); MS M•+ ) 238. Anal. Calcd for C12H18O3-
Si: C, 60.46; H, 7.61. Found: C, 60.48; H, 7.58.
IR (KBr): 1693 (CdO). MS: M•+ ) 348. Anal. Calcd for
15H36O3Si3: C, 51.67; H, 10.41. Found: C, 51.60; H, 10.30.
C
Tr im eth ylsilyl 3-(Tr im eth ylsiloxy)-2-(tr im eth ylsilyl)-
1
d eca n oa te (3h ). An ti: H NMR (CDCl3) δ 0.07 (s, 9 H, CSi-
(CH3)3), 0.09 (s, 9 H, OSi(CH3)3), 0.24 (s, 9 H, COOSi(CH3)3),
0.88 (t, 3H, CH3), 1.27 (m, 10 H, H-5-9), 1.42 (m, 2 H, H-4),
2.27 (d, 1 H, J ) 8.28 Hz, H-2), 4.24 (m, 1 H, H-3); 13C NMR
(CDCl3) δ -1.35, -0.11, 0.73, 14.10, 22.68, 24.29, 28.99, 29.90,
31.84, 36.39, 47.64, 72.41, 174.30.
Su p p or t in g In for m a t ion Ava ila b le: NMR spectra of
compounds prepared. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
Syn : H NMR (CDCl3) δ 0.07 (s, 9 H, CSi(CH3)3), 0.22 (s, 9
H, OSi(CH3)3), 0.23 (s, 9 H, COOSi(CH3)3), 0.88 (t, 3H, CH3),
1.27 (m, 10 H, H-5-9), 1.61 (m, 2 H, H-4), 2.32 (d, 1 H, J )
J O010092Q