A route to enantiomerically-enriched α-silyl aldehydes from 2,3-epoxy alcohols

Article abstract of DOI:10.1016/S0957-4166(99)00383-3

Asymmetric epoxidation of (E)-3-trialkylsilyl-2-propen-1-ols gives the expected epoxides with high enantioselectivity. Ring opening reactions of these epoxides with organocopper reagents furnishes 1,2-diols which are readily cleaved with Pb(OAc)₄ to afford α-silyl aldehydes with no detectable loss of stereochemistry.

Full text of DOI:10.1016/S0957-4166(99)00383-3

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3601–3614
A route to enantiomerically-enriched α-silyl aldehydes from
2,3-epoxy alcohols
Denise C. Chauret, J. Michael Chong ∗ and Qing Ye
Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Waterloo, Waterloo,
Ontario, Canada, N2L 3G1
Received 3 August 1999; accepted 23 August 1999
Abstract
Asymmetric epoxidation of (E)-3-trialkylsilyl-2-propen-1-ols gives the expected epoxides with high enantio-
selectivity. Ring opening reactions of these epoxides with organocopper reagents furnishes 1,2-diols which are
readily cleaved with Pb(OAc)4 to afford α-silyl aldehydes with no detectable loss of stereochemistry. © 1999
Elsevier Science Ltd. All rights reserved.
1. Introduction
α-Silylcarbonyl compounds have served as important intermediates in organic synthesis.1 In some
applications, such as in the synthesis of stereodefined alkenes, racemic compounds may be employed.2
However, enantiomerically-enriched compounds are desirable for the synthesis of materials such as
enantiomerically-enriched allylsilanes,3 aldol products4 and α-hydroxyketones.5 At present, there are
only two enantioselective routes to α-silylcarbonyl compounds: one involves silylation of SAMP/RAMP
hydrazones6 and one involves Pd-catalyzed rearrangement of silyl-substituted vinyloxiranes.7 The
SAMP/RAMP method is very effective for α-silyl ketones but less so for α-silyl aldehydes due to partial
N-silylation or oxidation of the aldehyde during deprotection of the hydrazone.6 The vinyloxirane method
is limited to β,γ-unsaturated-α-silyl aldehydes containing large (e.g. i-Pr3Si, t-BuR2Si) trialkylsilyl
groups.7 We now report a general efficient route to α-silyl aldehydes which provides these compounds
in high enantiomeric purity.
The route that we envisaged is shown in Scheme 1. It is well-established that Sharpless asymmetric
epoxidation (AE) of E-allylic alcohols proceeds with high enantioselectivity.8 Use of E-3-trialkylsilyl-2-
propen-1-ols (1) would thus provide epoxides 2 which would be expected to react with organometallic
∗
Corresponding author. E-mail: jmchong@uwaterloo.ca
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00383-3

3602
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
reagents to give diols 3.2f,9 Oxidative cleavage of diols 3 would then furnish the desired α-silyl aldehydes
(4).
Scheme 1.
2. Results and discussion
2.1. Synthesis of 3-silyl epoxy alcohols
The requisite 3-silylated allylic alcohols were prepared using the sequence shown below. Thus,
silylation of the THP ether of propargyl alcohol followed by acid-catalyzed transacetalation gave silylated
propargylic alcohols in high yields.7b Reduction of these alcohols with REDAL gave exclusively the
E-allylic alcohols (81–97% yields).10 This route was superior to the direct silylation of the dianion
of propargyl alcohol which usually gave lower yields (50–60%). In general, commercially available
trialkylsilyl chlorides were used but in the case of alcohol 1d, the requisite silyl chloride was prepared in
situ from Me2SiCl2 and 4-MeOC6H4Li.11
.
(1)
As expected, allylic alcohols 1 underwent Sharpless epoxidation using catalytic amounts of Ti(O-i-
Pr)4 and tartrate rapidly and highly stereoselectively. In fact, allylic alcohols 1 are almost ideal substrates
for AE since the E silyl substituent allows for high enantioselectivity and reactivity.12 Epoxy alcohols 2
are readily isolated in high yields (82–99%) and enantiomeric purities (>95% based on 1H and 19F NMR
spectra of MTPA esters).13–15
2.2. Ring-opening reactions of 3-silyl epoxy alcohols with organometallic reagents
It has previously been shown that epoxysilanes tend to be opened by nucleophiles at the carbon
proximate to the silicon atom.2f,16 For organocopper reagents, the regioselectivity in the opening of
epoxysilanes may be controlled to some extent by varying the nature of the trialkylsilyl group and
the organocopper reagent.2f For the regiochemistry desired here, ‘higher order’ cyanocuprates were

D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3603
preferred.17 Results are shown in Table 1. In all cases with Me2CuCNLi2 and Bu2CuCNLi2, reactions
proceeded smoothly with complete regio- and stereoselectivity to give a single diol in high yields.
Table 1
Reaction of epoxysilanes 2 with organometallic reagentsa
Unfortunately, the 2° and 3° cuprates s-Bu2CuCNLi2 and t-Bu2CuCNLi2 were either unreactive (at
temperatures below −10°C) or gave rise to reduction products (e.g. 5, equiv. 2) at higher temperatures.
The decreased reactivity at lower temperatures may be due to steric factors while the formation of
reduction products may be ascribed to thermal decomposition of the cuprates to copper hydrides.18
.
(2)
We also examined the opening of epoxysilanes 2 with Grignard reagents in the presence of copper salts
(Table 1). In general, reactions with 1° Grignard reagents worked well although yields were slightly lower
than with organocuprates and small amounts of by-products were formed. However, it may sometimes
be advantageous to use Grignard reagents since they are often more easily prepared than organolithiums
(which are used as precursors to the organocuprates.) Also, as with organocuprates, 2° and 3° reagents
did not provide the desired products.

3604
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
To introduce an alkynyl group, organocopper reagents are generally ineffective.19 Hence, an alkynyl-
aluminum reagent was used.20 As with the organocopper reagents, only a single regioisomer was
observed.
2.3. Oxidative cleavage of diols 3 to α-silyl aldehydes
With a series of β,γ-dihydroxysilanes in hand, we turned our attention to the oxidative cleavage
of these 1,2-diols to aldehydes. To avoid possible complications under aqueous or acidic conditions,
cleavage was carried out using Pb(OAc)4 in dry CH2Cl2 containing solid NaHCO3 (Table 2). In each case,
the expected α-silyl aldehyde was isolated as the sole product in essentially pure form. They exhibited
IR, 1H and 13C NMR spectral data completely consistent with their assigned structures. However, it was
not surprising6 that they defied purification (silica gel chromatography, distillation) for microanalysis.
Table 2
Preparation of α-silyl aldehydes from diols
The enantiomeric purities of the α-silyl aldehydes were determined by reduction (LiAlH4, Et2O, 0°C)
1
to the corresponding primary alcohols and preparing the MTPA esters followed by analysis using H
and/or 19F NMR spectroscopy. In most cases, the enantiomeric excesses determined were the same as
those determined for the corresponding epoxy alcohol precursors. Thus, the epoxide ring opening and the
oxidative cleavage reactions must have occurred with little or no loss of stereochemical integrity. Only
with aldehyde 4i (R=CH2_CH) was racemization observed; it is highly likely that the activating effect of

D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3605
the vinyl group is responsible for the stereochemical lability of this aldehyde. However, it is interesting
to note that an alkynyl group (aldehyde 4l) does not have this same effect.
We also examined the stereochemical purity of aldehydes after prolonged storage. After one month at
4°C, there was no detectable racemization. However, extensive chemical decomposition occurred after
six months at 4°C or after one week at room temperature.
In conclusion, we have developed a general route to enantiomerically-enriched α-silyl aldehydes.
Since chirality is introduced using Sharpless asymmetric epoxidation, either enantiomer may be easily
accessed (by the appropriate choice of tartrates) with high enantiomeric excess. Many different silyl gro-
ups are tolerated; and the α-epoxysilanes may be opened with high regioselectivity and stereoselectivity
using organocuprates, Grignard reagents and alkynyl-aluminum reagents.
3. Experimental
3.1. General
All reactions involving air or moisture sensitive reagents were performed under argon using oven-dried
glassware. THF and ether were distilled from Na/benzophenone; CH2Cl2 and Et3N were distilled from
CaH2. Anhydrous t-butylhydroperoxide in isooctane was prepared and titrated according to the procedure
of Sharpless.8d Sodium bicarbonate was oven dried prior to use. 4-Bromo-1-butene was passed through a
short column of basic aluminum before being used. CuBr·SMe2 was recrystallized from Me2S/hexane.21
Allylic alcohols 1a, 1b and 1c were prepared essentially as described by Malacria et al. except that
PPTS/EtOH was used instead of p-TsOH/MeOH to cleave the THP ether.7b Infrared spectra were
obtained using a MB-100 FT spectrophotometer as neat liquids (NaCl plates) or as KBr pellets. NMR
spectra were recorded using Bruker AM-250 or AC-200 spectrometers as CDCl3 solutions with Me4Si
(1H δ 0.0) or CDCl3 (13C δ 77.0) as internal standards unless otherwise noted. For 19F NMR spectra,
CF3COOH was used as an external standard (76.53 ppm upfield from CFCl3) and peak positions are
reported in ppm upfield from CFCl3. Mass spectra were recorded on a VG Quattro II mass spectrometer
(electrospray ionization) or on a Hewlett–Packard 5890 series II/5971A MSD instrument (electron impact
ionization). Optical rotations were determined on a Perkin–Elmer 241 digital polarimeter. Elemental
analyses were performed by M-H-W Laboratories, Phoenix, Arizona.
1
All enantiomeric excesses (ee) reported were determined by H NMR or 19F NMR analysis of the
derived (+)-MTPA esters obtained by treatment of alcohols with triethylamine, (+)-MTPA-Cl and DMAP
in CH2Cl2.22 In each case, an authentic mixture of diastereomers was prepared using (ꢀ)-MTPA-Cl23 as
the derivatizing agent.
3.1.1. E-3-(p-Methoxyphenyl)dimethylsilyl-2-propen-1-ol (1d)
p-Bromoanisole (100 mmol) was dissolved in ether (100 mL), then t-BuLi (129 mL of a 1.7 M solution
in pentane, 220 mmol) was added dropwise into the solution at −78°C. After the reaction mixture was
stirred for 15 min at −78°C, it was warmed up to 0°C for 15 min. In order to remove the excess t-BuLi, the
reaction mixture was stirred for 30 min at rt. Subsequently, dichlorodimethylsilane (13 mL, 100 mmol)
was added dropwise to the re-cooled reaction mixture (−78°C). The total reaction mixture was stirred for
2 h at −78°C. The resulting (p-methoxyphenyl)dimethylsilyl chloride was used in situ.
To a solution of THP-protected propargyl alcohol in THF (0.5 mL per mmol protected alcohol) at
−40°C was added dropwise n-BuLi (1.0 equiv., 1.6 M solution in hexane). The reaction mixture was
stirred at −40°C for 30 min, then the THF solution of (p-methoxyphenyl)dimethylsilyl chloride (1.0

3606
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
equiv.) was added dropwise. The reaction was warmed to rt and stirred overnight; then the mixture was
concentrated to dryness. Ether (50 mL) was added. The organic phase was washed with saturated NH4Cl
solution (50 mL), separated, then dried over MgSO4 and concentrated. Ethanol (1 mL per mmol protected
alcohol) and PPTS (0.1 equiv.) were added to the residue, and the resulting mixture was stirred for 7
h at 55°C. At the end of the reaction, solid NaHCO3 was added, ethanol was removed in vacuo and
the mixture was diluted with ether (100 mL). The organic phase was washed with saturated NaHCO3
solution, dried over MgSO4 and concentrated. The resulting oil was purified by column chromatography
[(20 g silica gel per g residue, hexane:ether (3:1)] to afford the expected 3-trialkylsilylpropargyl alcohol
in 64% yield: IR (neat, NaCl) 3358 (br), 3014, 2956, 2837, 1594, 1249, 1182, 779 cm−1; 1H NMR (250
MHz, CDCl3) δ 7.54–7.50 (m, 2H), 6.92–6.89 (m, 2H), 4.28 (s, 2H), 3.80 (s, 3H), 1.56 (br, 1H), 0.38 (s,
6H); 13C NMR (63 MHz, CDCl3) δ 160.7, 135.1, 127.3, 113.7, 105.3, 88.9, 55.0, 51.5, −0.9; MS (EI)
m/z 220 (M, 37), 205 (100), 167 (17), 145 (40), 121 (25), 75 (25). Anal. calcd for C12H16O2Si: C, 65.41;
H, 7.32. Found: C, 65.55; H, 7.26.
A solution of REDAL (2.0 equiv., 75% solution in toluene) was added dropwise into an ether solution
of the silylated propargyl alcohol (1 mL per mmol alcohol) at 0°C. At first, the reaction was stirred for
2 h at 0°C, then allowed to warm to rt for 1 h. HCl (1 M) solution was added dropwise to quench the
reaction at 0°C until the reaction mixture became clear. The phases were separated and the aqueous phase
was extracted with ether (3×30 mL). The total organic layer was washed with water (50 mL) and brine
(50 mL), dried over MgSO4 and concentrated. The resulting oil (94% yield) was used without further
purification. IR (neat, NaCl) 3348 (br), 3040, 1593, 1246, 1182, 818 cm−1; 1H NMR (250 MHz, CDCl3)
δ 7.47–7.41 (m, 2H), 6.93–6.87 (m, 2H), 6.23, 6.02 (AB of ABX2, JAB=18.7 Hz, JAX=4.1 Hz, JBX=1.5
Hz, 1H), 4.20 (dd, J=4.1, 1.5 Hz, 2H), 3.81 (s, 3H), 1.40 (s, 1H), 0.33 (s, 6H); 13C NMR (63 MHz,
CDCl3) δ 160.4, 146.4, 135.2, 129.2, 127.6, 113.6, 65.4, 55.0, −2.5; MS (EI) m/z 222 (M+, 4), 207 (15),
189 (83), 165 (39), 151 (37), 135 (28), 115 (16), 99 (41), 75 (100), 59 (20), 45 (16), 43 (16). Anal. calcd
for C12H18O2Si: C, 64.82; H, 8.16. Found: C, 64.63; H, 7.91.
3.2. General procedure A: preparation of (2S,3S)-trialkylsilyl-2,3-epoxy-1-propanols (2)
To a slurry of powdered 3 Å molecular sieves (0.05 g per mmol silylallylic alcohol) in CH2Cl2, L-
(+)-diethyl tartrate (0.14 equiv.) was added. After cooling to −20°C, titanium tetraisopropoxide (0.12
equiv.) was added dropwise. Pre-dried (4 Å molecular sieves) t-butylhydroperoxide (2.0 equiv., 5.1 M
solution in isooctane) was subsequently added dropwise. The mixture was stirred at −20°C for 30 min.
Then a pre-dried (4 Å molecular sieves) solution of allylic alcohol 1 (X mmol) in CH2Cl2 (0.5 mL per
mmol silylallylic alcohol) was added dropwise. The reaction was stirred at −20°C for 5 h, whereupon
it was added to a 0°C solution of FeSO4·7H2O (0.33 g per mmol of allylic alcohol) and tartaric acid
(0.1 g per mmol of allylic alcohol) in water (1 mL per mmol of allylic alcohol), and stirred for 10
min without a cooling bath. The phases were separated and the aqueous layer was extracted with ether
(3×30 mL). The combined organic phase was stirred over 30% NaOH in brine (1 mL per mmol of
allylic alcohol) at 0°C for 1 h. After the phases were separated again and the aqueous layer was extracted
with ether:hexane 1:1 (3×20 mL), the combined organic phase was dried over MgSO4, concentrated and
purified by column chromatography (20 g silica gel per g epoxy alcohol, hexane:ethyl acetate 2:1) to
afford (2S, 3S)-trialkylsilyl-2,3-epoxy-1-propanols (2).
3.2.1. (2S,3S)-t-Butyldimethylsilyl-2,3-epoxy-1-propanol (2a)
Following general procedure A, the title compound was prepared as a colorless oil in 99% yield: [α]25
D
−18.5 (c 1.00, MeOH), lit.7b [α]20 −26.9 (c 11.85, CHCl3); IR (neat, NaCl) 3374 (br), 2939, 2884, 2836,
D

D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3607
1466, 1442, 1381, 1362, 1252, 1103, 1056, 1007, 837, 901 cm−1; 1H NMR (250 MHz, CDCl3) δ 3.97,
3.57 (AB of ABX, JAB=12.3 Hz, J=4.5, 2.4 Hz, 2H), 2.99 (ddd, X of ABX, J=4.5, 3.7, 2.4 Hz, 1H), 2.31
(d, J=3.7 Hz, 1H), 0.94 (s, 9H), 0.00 (s, 3H), −0.02 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 63.5, 55.7,
46.3, 26.3, 16.4, −8.5, −8.6; MS (EI) m/z 171 (M+−OH, 1), 75 (100), 57 (10). Anal. calcd for C9H20O2Si:
C, 57.39; H, 10.70. Found: C, 57.60; H, 10.55.
3.2.2. (2S,3S)-Dimethylphenylsilyl-2,3-epoxy-1-propanol (2b)
Following general procedure A, the title compound was prepared as a colorless oil in 82% yield: [α]25
D
−11.7 (c 1.00, MeOH), lit.7b [α]20 −11.6 (c 12.85, CHCl3); H NMR (250 MHz, CDCl3) δ 7.56–7.51
1
D
(m, 2H), 7.39–7.33 (m, 3H), 3.93, 3.54 (AB of ABX, JAB=12.5 Hz, J=4.7, 2.3 Hz, 2H), 3.00 (ddd, X of
ABX, J=4.7, 3.6, 2.3 Hz, 1H), 2.43 (d, J=3.6 Hz, 1H), 0.35 (s, 3H), 0.32 (s, 3H); 13C NMR (63 MHz,
CDCl3) δ 135.5, 133.7, 129.4, 127.7, 63.2, 56.3, 47.5, −5.3, −5.5; MS (EI) m/z 209 (M+1, 17), 191 (21),
149 (18), 135 (69), 117 (100), 105 (12), 91 (21), 75 (58), 55 (11), 45 (6). Anal. calcd for C11H16O2Si: C,
63.42; H, 7.74. Found: C, 63.43; H, 7.52.
3.2.3. (2S,3S)-Triethylsilyl-2,3-epoxy-1-propanol (2c)
Following general procedure A, the title compound was prepared as a colorless oil in 97% yield:
[α]25 −8.9 (c 1.00, MeOH); IR (neat, NaCl) 3388 (br), 2954, 1460, 1102, 1055 cm−1; H NMR (250
1
D
MHz, CDCl3) δ 3.96, 3.53 (AB of ABX, JAB=12.4 Hz, J=4.8, 2.2 Hz, 2H), 3.03 (ddd, X of ABX, J=4.8,
3.7, 2.2 Hz, 1H), 2.28 (d, J=3.7 Hz, 1H), 0.95 (t, J=7.7 Hz, 9H), 0.60 (q, J=7.7 Hz, 6H); 13C NMR (63
MHz, CDCl3) δ 63.6, 55.7, 46.6, 7.0, 1.6; MS (EI) m/z 207 (M+H+H2O, 18), 159 (3), 131 (2), 103 (55),
87 (15), 75 (100), 47 (13), 45 (9), 29 (4). Anal. calcd for C9H20O2Si: C, 57.39; H, 10.70. Found: C,
57.16; H, 10.59.
3.2.4. (2S,3S)-(p-Methoxyphenyl)dimethylsilyl-2,3-epoxy-1-propanol (2d)
Following general procedure A, the title compound was prepared as a colorless oil in 89% yield: [α]25
D
1
−10.8 (c 1.20, MeOH); IR (neat, NaCl) 3407 (br), 2950, 2837, 1593, 1248, 1183, 1045, 829 cm−1; H
NMR (250 MHz, CDCl3) δ 7.47–7.42 (m, 2H), 6.93–6.88 (m, 2H), 3.92, 3.56 (AB of ABX, JAB=9.1 Hz,
J=4.4, 2.4 Hz, 2H), 3.80 (s, 3H), 2.98 (ddd, X of ABX, J=4.4, 3.7, 2.4 Hz, 1H), 2.40 (d, J=3.7 Hz, 1H),
1.60 (br s, 1H), 0.32 (s, 3H), 0.29 (each s, 3H); 13C NMR (63 MHz, CDCl3) δ 160.9, 135.4, 126.3, 113.8,
63.2, 56.0, 55.0, 47.8, −4.9, −5.1; MS (EI) m/z 223 (M−Me, 87), 208 (14), 165 (92), 147 (65), 131 (40),
115 (100), 91 (13). Anal. calcd for C12H18O3Si: C, 60.47; H, 7.61. Found: C, 60.38; H, 7.52.
3.3. General procedure B: methyl and butyl cuprate openings of (2S,3S)-trialkylsilyl-2,3-epoxy-1-
propanols
To a suspension of CuCN (3.0 equiv., unless otherwise specified) in ether (5 mL per mmol α-
epoxysilane) at 0°C or −20 to −40°C was added dropwise MeLi or n-BuLi (6.0 equiv., unless otherwise
specified). α-Epoxysilane 2 (X mmol) was added dropwise as a solution in ether (1 mL per mmol α-
epoxysilane). Then, the reaction was stirred at 0°C or −20 to −40°C for 2 h. Saturated NH4Cl (pH
8) solution (5 mL per mmol α-epoxysilane) was added dropwise to quench the reaction. The phases
were separated and the aqueous layer was extracted with ether (3×3 mL per mmol α-epoxysilane). The
combined organic phase was dried over MgSO4, concentrated and purified by column chromatography
(20 g silica gel per g residue, CH2Cl2:ether 5:1) to afford β,γ-dihydroxysilanes 3.

3608
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3.3.1. (2S,3S)-3-t-Butyldimethylsilyl-1,2-butanediol (3a)
Following general procedure B, using CuCN (3.0 equiv.) and MeLi (6.0 equiv., 1.4 M solution in
ether) at 0°C, the title compound was prepared without purification, as a viscous colorless oil in 97%
yield: [α]25 +9.2 (c 1.00, MeOH); IR (neat, NaCl) 3359 (br), 2954, 1048, 995 cm−1; H NMR (250
1
D
MHz, CDCl3) δ 3.83 (ddd, X of ABX, J=8.7, 5.5, 2.7 Hz, 1H), 3.63, 3.49 (AB of ABX, JAB=10.9 Hz,
J=8.7, 2.7 Hz, 2H), 2.01 (br, 2H), 1.19 (quint, J=7.4 Hz, 1H), 0.94 (d, J=7.4 Hz, 3H), 0.84 (s, 9H), 0.00 (s,
3H), −0.03 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 74.6, 65.1, 27.2, 22.3, 17.3, 10.7, −5.8, −6.2; MS (EI)
m/z 173 (M−CH2OH, 4), 129 (15), 75 (100), 55 (72). Anal. calcd for C10H24O2Si: C, 58.77; H, 11.84.
Found: C, 58.75; H, 11.69.
3.3.2. (2S,3S)-3-t-Butyldimethylsilyl-1,2-heptanediol (3b)
Following general procedure B, using CuCN (5.0 equiv.) and n-BuLi (10.0 equiv., 1.6 M solution in
hexane) at −20 to −40°C, the title compound was prepared without purification, as a viscous colorless
oil in 85% yield: [α]25 +10.0 (c 1.00, MeOH); IR (neat, NaCl) 3371 (br), 2942, 1043 cm−1; H NMR
1
(250 MHz, CDCl3) δD3.95 (ddd, X of ABX, J=7.8, 4.1, 3.6 Hz, 1H), 3.65, 3.57 (AB of ABX, JAB=10.8
Hz, J=7.8, 3.6 Hz, 2H), 1.70–1.17 (m, 6H), 1.08–0.75 (m, 13H), 0.10 (s, 3H), 0.06 (s, 3H); 13C NMR
(63 MHz, CDCl3) δ 74.6, 66.0, 33.1, 29.6, 28.0, 27.2, 23.0, 18.8, 14.0, −4.5, −6.2; MS (EI) m/z 246 (M,
2), 245 (13), 189 (18), 177 (100), 149 (17), 115 (22), 87 (21), 55 (36). Anal. calcd for C13H30O2Si: C,
63.35; H, 12.26. Found: C, 63.18; H, 12.26.
3.3.3. (2S,3S)-3-Dimethylphenylsilyl-1,2-butanediol (3c)
Following general procedure B, using CuCN (3.0 equiv.) and MeLi (6.0 equiv., 1.4 M solution in
ether) at 0°C, the title compound was prepared without purification, as a viscous colorless oil in 94%
yield: [α]25 +4.1 (c 1.00, MeOH); IR (neat, NaCl) 3370 (br), 2954, 1056, 774, 702 cm−1; 1H NMR (250
D
MHz, CDCl3) δ 7.55–7.51 (m, 2H), 7.38–7.33 (m, 3H), 3.64–3.60 (m, 2H), 3.39 (dd, J=11.4, 8.1 Hz,
1H), 1.22 (quint, J=7.5 Hz, 1H), 0.92 (d, J=7.5 Hz, 3H), 0.35 (s, 3H), 0.34 (s, 3H); 13C NMR (63 MHz,
CDCl3) δ 138.6, 133.9, 129.0, 127.8, 75.1, 65.6, 24.4, 11.4, −3.4, −3.5; MS (EI) m/z 209 (M−Me, 36),
191 (19), 149 (31), 137 (72), 135 (85), 91 (18), 75 (100), 55 (100), 43 (10). Anal. calcd for C12H20O2Si:
C, 64.24; H, 8.98. Found: C, 64.12; H, 9.03.
3.3.4. (2S,3S)-3-Dimethylphenylsilyl-1,2-heptanediol (3d)
Following general procedure B, using CuCN (5.0 eq) and n-BuLi (10.0 equiv., 1.6 M solution in
hexane) at −20 to −40°C, the title compound was prepared without purification, as a viscous colorless oil
in 84% yield: [α]25 +22.2 (c 1.00, MeOH); 1H NMR (250 MHz, CDCl3) δ 7.56–7.51 (m, 2H), 7.38–7.33
D
(m, 3H), 3.80 (ddd, X of ABX, J=8.7, 5.6, 3.0 Hz, 1H), 3.49, 3.34 (AB of ABX, JAB=10.9 Hz, JAX=8.7,
J
BX=3.0 Hz, 2H), 1.37–1.13 (m, 6H), 1.02 (q, J=5.6 Hz, 1H), 0.81 (t, J=6.8 Hz, 3H), 0.36 (s, 3H), 0.35
(s, 3H); 13C NMR (63 MHz, CDCl3) δ 139.4, 128.8, 127.7, 74.5, 66.3, 32.1, 30.5, 27.1, 22.8, 13.8, −2.3,
−2.6; MS (EI) m/z 233 (11), 211 (18), 171 (22), 153 (37), 137 (70), 135 (67), 97 (100), 75 (76), 55 (85).
Anal. calcd for C15H26O2Si: C, 67.62; H, 9.83. Found: C, 67.40; H, 9.62.
3.3.5. (2S,3S)-3-Triethylsilyl-1,2-butanediol (3e)
Following general procedure B, using CuCN (3.0 equiv.) and MeLi (6.0 equiv., 1.4 M solution in
ether) at 0°C, the title compound was prepared without purification, as a viscous colorless oil in 93%
yield: [α]25 −1.6 (c 1.00, MeOH); IR (neat, NaCl) 3360 (br), 2952, 1238, 1051, 726 cm−1; H NMR
1
D
(250 MHz, CDCl3) δ 3.74–3.70 (m, 2H), 3.46 (dd, J=11.3, 8.5 Hz, 1H), 2.01–1.90 (m, 2H), 1.09 (quint,
J=7.3 Hz, 1H), 0.97–0.91 (m, 12H), 0.58 (q, J=7.7 Hz, 6H); 13C NMR (63 MHz, CDCl3) δ 74.9, 65.8,

D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3609
21.7, 10.9, 7.6, 3.1; MS (EI) m/z 204 (M, 1), 151 (17), 133 (30), 115 (49), 103 (100), 87 (53), 75 (99), 55
(99). Anal. calcd for C10H24O2Si: C, 58.77; H, 11.84. Found: C, 58.65; H, 11.90.
3.3.6. (2S,3S)-3-Triethylsilyl-1,2-heptanediol (3f)
Following general procedure B, using CuCN (5.0 equiv.) and n-BuLi (10.0 equiv., 1.6 M solution in
hexane) at −20 to −40°C, the title compound was prepared without purification, as a viscous colorless oil
in 93% yield: [α]25 +12.0 (c 1.00, MeOH); IR (neat, NaCl) 3369 (br), 1055, 1011, 723 cm−1; 1H NMR
D
(250 MHz, CDCl3) δ 3.85 (ddd, X of ABX, J=8.7, 5.5, 2.8 Hz, 1H), 3.60, 3.48 (AB of ABX, JAB=10.6
Hz, JAX=8.7, JBX=2.8 Hz, 2H), 1.36–1.15 (m, 7H), 0.94 (t, J=7.7 Hz, 9H), 0.86 (t, J=7.0 Hz, 3H), 0.59 (q,
J=7.7 Hz, 6H); 13C NMR (63 MHz, CDCl3) δ 74.5, 66.4, 32.7, 27.8, 23.1, 13.9, 7.7, 3.7; MS (EI) m/z 246
(M, 2), 189 (18), 177 (100), 167 (7), 149 (17), 115 (22), 87 (21), 55 (36). Anal. calcd for C13H30O2Si:
C, 63.35; H, 12.26. Found: C, 63.13; H, 12.32.
3.3.7. (2S,3S)-3-(p-Methoxyphenyl)dimethylsilyl-1,2-butanediol (3g)
Following general procedure B, using CuCN (3.0 equiv.) and MeLi (6.0 equiv., 1.4 M solution in
ether) at 0°C, the title compound was prepared without purification, as a viscous colorless oil in 95%
yield: [α]25 +8.7 (c 1.10, MeOH); IR (neat, NaCl) 3376 (br), 1593, 1247, 1182, 1038, 824, 772 cm−1;
D
1H NMR (250 MHz, CDCl3) δ 7.47–7.42 (m, 2H), 6.93–6.88 (m, 2H), 3.80 (s, 3H), 3.66–3.62 (m, 2H),
3.52 (dd, J=11.0, 8.2 Hz, 1H), 3.00–2.50 (br, 2H), 1.18 (quint, J=7.5 Hz, 1H), 0.90 (d, J=7.5 Hz, 3H),
0.31 (s, 6H); 13C NMR (63 MHz, CDCl3) δ 160.3, 135.3, 129.2, 113.5, 75.1, 65.5, 54.9, 24.5, 11.2, −3.4;
MS (EI) m/z 253 (M−1, 1), 223 (2), 207 (40), 165 (100), 133 (35), 105 (6), 91 (8), 75 (7), 55 (24), 45 (3),
43 (5). Anal. calcd for C13H22O3Si: C, 61.38; H, 8.72. Found: C, 61.54; H, 8.57.
3.3.8. (2S,3S)-3-(p-Methoxyphenyl)dimethylsilyl-1,2-heptanediol (3h)
Following general procedure B, using CuCN (5.0 equiv.) and n-BuLi (10.0 equiv., 1.6 M solution in
hexane) at −20 to −40°C, the title compound was prepared without purification, as a viscous colorless oil
in 90% yield: [α]25 +20.3 (c 1.00, MeOH); IR (neat, NaCl) 3387 (br), 3045, 1593, 1247, 1182, 1038,
D
1
822, 770 cm−1; H NMR (250 MHz, CDCl3) δ 7.53–7.49 (m, 2H), 6.96–6.92 (m, 2H), 3.85–3.83 (m,
4H), 3.53, 3.41 (AB of ABX, JAB=13.6 Hz, JAX=8.8, JBX=2.5 Hz, 2H), 2.43 (br, 2H), 1.44–0.84 (m,
10H), 0.38 (s, 3H), 0.37 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 160.2, 135.4, 130.1, 113.5, 74.6, 66.3,
55.0, 32.2, 30.7, 27.2, 22.9, 13.9, −2.2, −2.4; MS (EI) m/z 263 (M−CH2OH, 4), 207 (13), 165 (100), 147
(24), 133 (23), 96 (14), 91 (13), 75 (17), 55 (14). Anal. calcd for C16H28O3Si: C, 64.48; H, 9.52. Found:
C, 64.83; H, 9.34.
3.3.9. (2S)-3-t-Butyldimethylsilyl-1,2-propanediol (5)
Following general procedure D, using CuCN (5.0 equiv.) and t-BuLi (10.0 equiv., 1.7 M solution
in pentane), the title compound was prepared as a white solid by-product from 2a in 32% yield: mp
63.0–64.0°C; [α]25 +10.8 (c 0.60, CH3OH); IR (KBr) 3302 (br), 2950, 2931, 2858, 1469, 1387, 1369,
D
1253, 1197, 1078, 1054, 1020, 871, 834, 788 cm−1; 1H NMR (250 MHz, CDCl3) δ 3.88–3.78 (m, 1H),
3.61–3.55 (m, 1H), 3.34–3.27 (m, 1H), 2.73 (br, 2H), 0.83 (s, 9H), 0.78–0.62 (m, 2H), 0.00 (s, 3H), 0.01
(s, 3H); 13C NMR (63 MHz, CDCl3) δ 70.435, 69.2, 26.4, 16.4, 17.1, −5.2, −5.7; MS (ES) m/z 208
(M+18, 100). Anal. calcd for C9H22O2Si: C, 56.78; H, 11.65. Found: C, 56.81; H, 11.48.

3610
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3.4. General procedure C: epoxysilane ring opening by Grignard reagents
To a slurry of CuI (0.5 equiv.) in ether (5 mL per mmol α-epoxysilane) at −20 to −40°C was added
RMgX solution (5.0 equiv.). The mixture was stirred for 5 min at −20 to −40°C, then a solution of α-
epoxysilane 2 (X mmol) in ether (1 mL per mmol α-epoxysilane) was added dropwise. The reaction
was stirred at −20 to −40°C for 2 h. Then saturated NH4Cl (pH 8) solution (5 mL per mmol α-
epoxysilane) was added to quench the reaction. The phases were separated and the aqueous layer was
extracted with ether (3×15 mL). The combined organic phase was dried over MgSO4, concentrated and
purified by column chromatography (20 g silica gel per g residue, hexane:ether 3:2), producing the β,γ-
dihydroxysilanes 3.
3.4.1. (2S,3S)-3-t-Butyldimethylsilyl-1,2-heptanediol (3b)
Following general procedure C, using BuMgCl (5.0 equiv., 2.0 M solution in THF), compound 3b was
also prepared in 83% yield. The spectral data observed were identical to those described in Section 3.3.2.
3.4.2. (2S,3S)-3-Triethylsilyl-1,2-heptanediol (3f)
Following general procedure C, using BuMgCl (5.0 equiv., 2.0 M solution in THF), compound 3f was
also prepared in 81% yield. The spectral data observed were identical to those described in Section 3.3.6.
3.4.3. (2S,3S)-3-t-Butyldimethylsilyl-4-pentene-1,2-diol (3i)
Following general procedure C, using CH2_CHMgBr (5.0 equiv., 1.0 M solution in THF), the title
compound was prepared as a white solid in 57% yield: mp 49.5–50.5°C; [α]25 +9.6 (c 1.00, CHCl3);
D
1
IR (KBr) 3276 (br), 3070, 2944, 2858, 1627, 1466, 1330, 1254, 1037, 903, 832, 785, 676 cm−1; H
NMR (250 MHz, CDCl3) δ 5.72–5.52 (m, 1H), 5.05–4.95 (m, 2H), 3.85 (ddd, J=7.9, 4.6, 2.8 Hz, 1H),
3.65–3.57 (m, 2H), 2.04 (m, 1H), 0.90 (s, 9H), 0.03 (s, 3H), 0.00 (s, 3H); 13C NMR (63 MHz, CDCl3)
δ 136.1, 116.39, 72.6, 66.1, 38.4, 27.2, 17.7, −5.6, −5.7; MS (ES) m/z 234 (M+18, 100). Anal. calcd for
C11H24O2Si: C, 61.06; H, 11.18. Found: C, 60.87; H, 10.79.
3.4.4. (2S,3S)-3-t-Butyldimethylsilyl-5-hexene-1,2-diol (3j)
Following general procedure C, CH2_CHCH2MgCl was prepared by the reaction of CH2_CHCH2Cl
(5.0 equiv.) with Mg (5.05 equiv.) in ether at 0°C in the presence of a small amount of iodine, the title
compound was prepared as a viscous colorless oil in 33% yield: [α]25 +8.4 (c 1.10, CHCl3); IR (neat,
D
NaCl) 3372 (br), 3065, 2941, 2858, 1637, 1467, 1412, 1362, 1252, 1045, 910, 825, 767 cm−1; 1H NMR
(250 MHz, CDCl3) δ 5.90–5.77 (m, 1H), 5.07–4.96 (m, 2H), 3.87–3.83 (m, 1H), 3.61–3.54 (m, 2H),
2.23–2.09 (m, 4H), 1.24–1.13 (m, 1H), 0.88 (s, 9H), 0.04 (s, 3H), 0.00 (s, 3H); 13C NMR (63 MHz,
CDCl3) δ 140.1, 115.4, 74.7, 65.9, 32.3, 27.8, 27.2, 17.4, −4.7, −5.6; MS (ES) m/z 246 (M+18, 100).
Anal. calcd for C12H26O2Si: C, 62.55; H, 11.37. Found: C, 62.60; H, 11.57.
3.4.5. (2S,3S)-3-t-Butyldimethylsilyl-6-heptene-1,2-diol (3k)
Following general procedure C, CH2_CH(CH2)2MgBr was prepared by the reaction of
CH2_CH(CH2)2Br (5.0 equiv.) with Mg (5.05 equiv.) in ether at rt in the presence of a small
amount of iodine, the title compound was prepared as a viscous colorless oil in 82% yield: [α]25 +8.4 (c
D
1.00, CHCl3); IR (neat, NaCl) 3376 (br), 3077, 2939, 2857, 1698, 1640, 1466, 1442, 1382, 1251, 1040,
1
910, 826, 767 cm−1; H NMR (250 MHz, CDCl3) δ 5.84–5.68 (m, 1H), 5.03–4.92 (m, 2H), 3.94–3.90
(m, 1H), 3.58–3.53 (m, 2H), 2.23–2.17 (m, 2H), 1.55–1.46 (m, 2H), 1.04–0.97 (m, 1H), 0.88 (s, 9H),
−0.01 (s, 3H), −0.02 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 138.7, 114.8, 74.5, 65.9, 34.8, 27.2, 26.5,

D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3611
26.0, 17.4, −4.5, −5.6; MS (ES) m/z 262 (M+18, 100). Anal. calcd for C13H28O2Si: C, 63.88; H, 11.55.
Found: C, 63.79; H, 11.39.
3.4.6. (2S,3S)-3-t-Butyldimethylsilyl-1,2-pentanediol (3l)
Following general procedure C, using EtMgBr (5.0 equiv., 2.0 M solution in THF), the title compound
was prepared as a viscous colorless oil in 84% yield: [α]25 +5.9 (c 0.84, CHCl3); IR (neat, NaCl) 3369
D
(br), 2944, 2858, 1465, 1361, 1251, 1047, 1008, 827, 766 cm−1; 1H NMR (250 MHz, CDCl3) δ 3.95–3.61
(m, 1H), 3.56–3.44 (m, 2H), 1.56–1.42 (m, 2H), 1.21–1.15 (m, 1H), 0.96 (t, J=6.9 Hz, 3H), 0.88 (s, 9H),
0.03 (s, 3H), 0.00 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 74.5, 66.01, 30.0, 27.2, 20.7, 17.4, 15.5, −4.4,
−5.6; MS (ES) m/z 236 (M+18, 100). Anal. calcd for C11H26O2Si: C, 60.49; H, 11.99. Found: C, 60.49;
H, 11.81.
3.4.7. (2S,3S)-3-Triethylsilyl-5-hexene-1,2-diol (3m)
Following general procedure C, CH2_CHCH2MgCl was prepared by the reaction of CH2_CHCH2Cl
(5.0 equiv.) with Mg (5.05 equiv.) in ether at 0°C in the presence of a small amount of iodine, the title
compound was prepared as a viscous colorless oil in 57% yield: [α]25 +9.0 (c 1.00 CHCl3); IR (neat,
D
NaCl) 3370 (br), 3076, 2952, 2876, 1637, 1459, 1417, 1320, 1237, 1170, 1037, 909, 851, 725 cm−1; 1H
NMR (250 MHz, CDCl3) δ 5.89–5.72 (m, 1H), 5.07–4.96 (m, 2H), 3.86–3.82 (m, 1H), 3.63–3.46 (m,
2H), 2.58 (br, 2H), 2.19 (t, J=6.7 Hz, 2H), 1.23–1.13 (m, 1H), 0.96 (t, J=7.8 Hz, 9H), 0.62 (q, J=7.8
Hz, 6H); 13C NMR (63 MHz, CDCl3) δ 139.7, 115.3, 74.3, 66.2, 31.6, 27.8, 7.7. 3.7; MS (ES) m/z 246
(M+18, 100). Anal. calcd for C12H26O2Si: C, 62.55; H, 11.37. Found: C, 62.39; H, 11.16.
3.4.8. (2S,3S)-3-t-Butyldimethylsilyl-4-nonyne-1,2-diol (3n)
To a solution of 1-hexyne (0.739 g, 8.7 mmol) in THF (10 mL), n-BuLi (5.8 mL, 8.7 mmol, 1.5
M solution in hexane) was added dropwise at −40°C, followed by stirring for 30 min at −40°C. Then,
Et2AlCl (8.7 mL, 8.7 mmol, 1.0 M solution in hexane) was added dropwise. The reaction mixture was
stirred at −40°C for 15 min, then permitted to warm to 0°C for 15 min. The mixture was re-cooled
to −40°C and a solution of 2a (0.551 g, 2.9 mmol) in toluene (20 mL) was added dropwise. The final
reaction mixture was slowly warmed up to rt and stirred for 5 h at rt. Saturated NaHCO3 solution was
added to quench the reaction at 0°C. The phases were separated and the aqueous layer was extracted
with ether (3×10 mL). The combined organic phase was dried over MgSO4, concentrated and purified
by column chromatography (30 g silica gel, hexane:ether 1:1), affording the title compound (0.572 g)
as a viscous colorless oil in 73% yield: [α]25 −23.4 (c 1.05, CHCl3); IR (neat, NaCl) 3358 (br), 2942,
D
2858, 1488, 1252, 1059, 1027, 834, 775 cm−1; 1H NMR (250 MHz, CDCl3) δ 3.77–3.55 (m, 3H), 2.42
(br, 2H), 2.21–2.09 (m, 2H), 1.48–1.17 (m, 5H), 0.92 (s, 9H), 0.86 (t, J=6.9 Hz, 3H), 0.13 (s, 3H), 0.09
(s, 6H); 13C NMR (63 MHz, CDCl3) δ 73.3, 71.8, 66.0, 63.7, 31.1, 26.9, 23.0, 22.0, 18.6, 17.4, 13.5,
−6.2, −6.4; MS (ES) m/z 288 (M+18, 100). Anal. calcd for C15H30O2Si: C, 66.61; H, 11.18. Found: C,
66.30; H, 11.02.
3.5. General procedure D: preparation of (2S)-trialkylsilylaldehydes
To a solution of lead tetraacetate (1.1 equiv.) in CH2Cl2 (5 mL per mmol β,γ-dihydroxysilane)
was added NaHCO3 (2.2 equiv.). After the mixture was stirred for 5 min at 0°C, a solution of β,γ-
dihydroxysilane 3 (X mmol) in CH2Cl2 (2 mL per mmol β,γ-dihydroxysilane) was added dropwise.
The reaction was stirred at 0°C for 2 h and quenched by adding saturated NaHCO3 solution (5 mL
per mmol β,γ-dihydroxysilane). The phases were separated and the aqueous layer was extracted with

3612
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
ether (3×5 mL). The combined organic phase was dried (MgSO4) and concentrated to give crude (2S)-
trialkylsilylaldehydes 4.
3.5.1. (S)-2-t-Butyldimethylsilylpropanal (4a)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 96% yield: [α]25 −15.9 (c 1.00, MeOH), lit.6 [α]22 −114.6 (c 1.27, PhH); IR (neat, NaCl) 2945,
D
D
2859, 2800, 2712, 1696, 1467, 1256, 1121, 966, 823, 769 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.74 (d,
J=2.1 Hz, 1H), 2.50 (td, J=6.7, 2.1 Hz, 1H), 1.18 (d, J=6.7 Hz, 3H), 0.93 (s, 9H), 0.05 (s, 3H), 0.03 (s,
3H); 13C NMR (63 MHz, CDCl3) δ 203.5, 41.2, 26.9, 17.7, 9.1, −6.7, −6.8.
3.5.2. (S)-2-t-Butyldimethylsilylhexanal (4b)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 97% yield: [α]25 −6.1 (c 1.00, MeOH); IR (neat, NaCl) 2943, 2858, 2708, 1698, 1466, 1255,
D
1
1124, 949, 829, 768 cm−1; H NMR (250 MHz, CDCl3) δ 9.65 (d, J=3.6 Hz, 1H), 2.01–1.98 (m, 1H),
1.45–1.09 (m, 6H), 0.90 (s, 9H), 0.87 (t, J=6.8 Hz, 3H), 0.04 (s, 3H), 0.00 (s, 3H); 13C NMR (63 MHz,
CDCl3) δ 203.6, 48.3, 33.3, 26.9, 26.7, 24.8, 22.5, 13.9, −6.4, −6.5.
3.5.3. (S)-2-Dimethylphenylsilylpropanal (4c)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 90% yield: [α]25 −9.6 (c 0.50, MeOH); IR (neat, NaCl) 3070, 2960, 2805, 2704, 1695, 1427, 1254,
D
1187, 1118, 822, 701 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.62 (d, J=2.2 Hz, 1H), 7.50–7.47 (m, 2H),
7.32–7.28 (m, 3H), 2.60 (td, J=6.7, 2.2 Hz, 1H), 1.13 (d, J=6.7 Hz, 3H), 0.39 (s, 3H), 0.38 (s, 3H); 13
C
NMR (63 MHz, CDCl3) δ 203.0, 136.7, 133.7, 129.8, 128.1, 43.0, 8.2, −4.6, −4.7.
3.5.4. (S)-2-Dimethylphenylsilylhexanal (4d)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 93% yield: [α]25 −3.8 (c 1.00, MeOH); IR (neat, NaCl) 3070, 3040, 2957, 2930, 2864, 2715, 1695,
D
1428, 1254, 1117, 826, 700 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.62 (d, J=3.3 Hz, 1H), 7.59–7.33 (m,
5H), 1.94–1.92 (m, 1H), 1.33–1.05 (m, 6H), 0.80 (t, J=6.8 Hz, 3H), 0.37 (s, 3H), 0.36 (s, 3H); 13C NMR
(63 MHz, CDCl3) δ 203.8, 135.6, 133.7, 129.7, 128.0, 50.0, 32.7, 24.0, 22.4, 13.8, −4.1, −4.4.
3.5.5. (S)-2-Triethylsilylpropanal (4e)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 93% yield: [α]25 −12.3 (c 0.50, MeOH); IR (neat, NaCl) 2956, 2878, 2800, 2708, 1694, 1461,
D
1414, 1229, 1137, 1011, 868, 725 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.70 (d, J=2.2 Hz, 1H), 2.51 (td,
J=6.6, 2.2 Hz, 1H), 2.27 (d, J=6.6 Hz, 3H), 0.95 (t, J=7.7 Hz, 9H), 0.64 (q, J=7.7 Hz, 6H); 13C NMR (63
MHz, CDCl3) δ 203.49, 40.81, 8.10, 7.22, 2.55.
3.5.6. (S)-2-Triethylsilylhexanal (4f)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 90% yield: [α]25 −23.6 (c 0.50, MeOH), IR (neat, NaCl) 2949, 2876, 2800, 2705, 1695, 1462,
D
1
1415, 1239, 1125, 1010, 725 cm−1; H NMR (250 MHz, CDCl3) δ 9.66 (d, J=3.5 Hz, 1H), 2.02–2.01
(m, 1H), 1.38–1.16 (m, 6H), 0.98 (t, J=7.7 Hz, 9H), 0.87 (t, J=6.8 Hz, 3H), 0.64 (q, J=7.7 Hz, 6H); 13
C
NMR (63 MHz, CDCl3) δ 203.6, 48.0, 33.3, 24.0, 22.5, 13.8, 7.3, 2.7.

D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
3613
3.5.7. (S)-2-(p-Methoxyphenyl)dimethylsilylpropanal (4g)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 90% yield: [α]25 −2.7 (c 1.00, MeOH); IR (neat, NaCl) 2920, 2850, 2714, 1696, 1594, 1503,
D
1
1459, 1278, 1290, 1250, 1113, 822, 774 cm−1; H NMR (250 MHz, CDCl3) δ 9.61 (d, J=2.1 Hz, 1H,
CH3CHCHO), 7.49–7.40 (m, 2H, Ar-H), 6.93–6.83 (m, 2H, Ar-H), 3.80 (s, 3H CH3O-Ar), 2.55 (td,
J=6.5, 2.2 Hz, 1H, CH3CHCHO), 2.07 (d, J=6.5 Hz, 3H, CH3CHCHO), 0.35 [s, 6H, (CH3)2Si]; 13C
NMR (63 MHz, CDCl3) δ 203.82, 160.81, 135.37, 127.03, 113.63, 65.81, 31.85, 15.33, −4.38, −4.97.
3.5.8. (S)-2-(p-Methoxyphenyl)dimethylsilylhexanal (4h)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 86% yield: [α]25 −4.0 (c 1.00, MeOH); IR (neat, NaCl) 2956, 3931, 2863, 2713, 1695, 1594, 1503,
D
1462, 1279, 1250, 1183, 1113, 822, 773 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.56 (d, J=3.4 Hz, 1H),
7.47–7.40 (m, 2H), 6.98–6.91 (m, 2H), 3.81 (s, 3H), 2.08–2.05 (m, 1H), 1.35–1.12 (m, 6H), 0.82 (t, J=6.8
Hz, 3H), 0.37 (s, 3H), 0.36 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 204.0, 160.9, 135.2, 126.3, 113.8,
55.0, 50.3, 32.9, 24.0, 22.4, 13.8, −4.0, −4.2.
3.5.9. (S)-2-t-Butyldimethylsilyl-3-butenal (4i)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 85% yield: [α]25 −8.9 (c 1.10, CHCl3); IR (neat, NaCl) 3057, 2932, 2860, 2810, 2705, 1709, 1466,
D
1255, 1007, 836, 780 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.66 (d, J=3.3 Hz, 1H), 6.13–6.06 (m, 1H),
5.01–4.85 (m, 2H), 3.31 (dd, J=6.3, 3.3 Hz, 1H), 0.89 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H); 13C NMR (63
MHz, CDCl3) δ 199.6, 131.2, 114.7, 55.1, 26.8, 18.0, −6.3, −6.8. (Note: the rotation value is not a real
result due to the racemization during the reaction.)
3.5.10. (S)-2-t-Butyldimethylsilyl-4-pentenal (4j)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 93% yield: [α]25 −61.5 (c 5.00, CHCl3); IR (neat, NaCl) 3078, 2955, 2951, 2859, 2810, 2715,
D
1698, 1640, 1468, 1255, 1053, 828, 807 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.59 (d, J=3.1 Hz, 1H),
5.75–5.59 (m, 1H), 5.14–4.80 (m, 2H), 2.72–2.69 (m, 2H), 2.15–2.10 (m, 1H), 0.85 (s, 9H), 0.00 (s, 3H),
−0.03 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 202.6, 137.8, 114.9, 47.1, 29.0, 26.8, 17.7, −6.4, −6.6.
3.5.11. (S)-2-t-Butyldimethylsilyl-5-hexenal (4k)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 94% yield: [α]25 −43.2 (c 5.00, CHCl3); IR (neat, NaCl) 3078, 2941, 2859, 2811, 2711, 1697,
D
1
1640, 1468, 1255, 1108, 913, 825, 769 cm−1; H NMR (250 MHz, CDCl3) δ 9.60 (d, J=3.2 Hz, 1H),
5.75–5.59 (m, 1H) 4.93–4.73 (m, 2H), 2.17–1.77 (m, 4H), 1.46–1.37 (m, 1H), 0.85 (s, 9H), 0.00 (s, 3H),
−0.04 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 202.9, 137.6, 115.5, 47.3, 34.5, 26.7, 24.3, 17.7, −6.5, −6.6.
3.5.12. (S)-2-t-Butyldimethylsilyl-3-octynal (4l)
Following general procedure D, the title compound was prepared without purification, as a colorless
oil in 89% yield: [α]25 −10.6 (c 1.00, CHCl3); IR (neat, NaCl) 2956, 2931, 2859, 2800, 2715, 1702,
D
1630, 1467, 1365, 1252, 1009, 828, 774 cm−1; 1H NMR (250 MHz, CDCl3) δ 9.47 (d, J=3.8 Hz, 1H),
2.32–2.10 (m, 3H) 1.49–1.25 (m, 4H), 0.90 (s, 9H), 0.86 (t, J=6.9 Hz, 3H), 0.10 (s, 3H), 0.05 (s, 3H);
13C NMR (63 MHz, CDCl3) δ 198.2, 79.2, 72.9, 55.3, 26.3, 23.0, 21.8, 18.6, 17.8, 13.3, −6.7, −7.6.

3614
D. C. Chauret et al. / Tetrahedron: Asymmetry 10 (1999) 3601–3614
Acknowledgements
Financial support from the Natural Sciences and Engineering Research Council of Canada in the form
of a postgraduate scholarship (to DCC) and a research grant (to JMC) is gratefully acknowledged.
References
1. For reviews, see: (a) Colvin, E. W. Silicon Reagents in Organic Synthesis; Academic Press: New York, 1988. (b) Colvin,
E. W. In Comprehensive Organometallic Chemistry II; Abel, E. W.; Stone, F. G. A.; Wilkinson, G., Eds.; Pergamon Press:
Oxford, 1995; Vol. 11, pp. 317–354.
2. (a) Hudrlik, P. F.; Kulkarni, A. K. J. Am. Chem. Soc. 1981, 103, 6251–6253. (b) Hudrlik, P. F.; Hudrlik, A. M.; Misra,
R. N.; Peterson, D.; Withers, G. P.; Kulkarni, A. K. J. Org. Chem. 1980, 45, 4444–4448. (c) Hudrlik, P. F.; Misra, R.
N.; Withers, G. P.; Hudrlik, A. M.; Rona, R. J.; Arcoleo, J. P. Tetrahedron Lett. 1976, 1453–1456. (d) Barrett, A. G. M.;
Flygare, J. A. J. Org. Chem. 1991, 56, 638–642. (e) Barrett, A. G. M.; Hill, J. M.; Wallace, E. M. J. Org. Chem. 1992, 57,
386–389. (f) Chauret, D. C.; Chong, J. M. Tetrahedron Lett. 1993, 34, 3695–3698.
3. Bhushan, V.; Lohray, B. B.; Enders, D. Tetrahedron Lett. 1993, 34, 5067–5070.
4. (a) Enders, D.; Lohray, B. B. Angew. Chem., Int. Ed. Engl. 1988, 27, 581–583. (b) Lohray, B. B.; Zimbiniski, R.
Tetrahedron Lett. 1990, 31, 7273–7276.
5. Enders, D.; Lohray, B. B. Helv. Chim. Acta 1989, 72, 980–984.
6. (a) Enders, D.; Lohray, B. B. Angew. Chem., Int. Ed. Engl. 1987, 26, 351–352. (b) Enders, D.; Lohray, B. B.; Burkamp,
F.; Bhushan, V.; Hett, R. Liebigs Ann. Chem. 1996, 189–200.
7. (a) Le Bideau, F.; Aubert, C.; Malacria, M. Tetrahedron: Asymmetry 1995, 6, 697–700. (b) Le Bideau, F.; Gilloir, F.;
Nilsson, Y.; Aubert, C.; Malacria, M. Tetrahedron 1996, 52, 7487–7510. (c) Courillon, C.; Le Fol, R.; Vandendris, E.;
Malacria, M. Tetrahedron Lett. 1997, 38, 5493–5496.
8. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974–5976. (b) Finn, M. G.; Sharpless, K. B. Asymmetric
Synthesis; Morrison, J. D., Ed.; Academic Press: Florida, 1985; Vol. 5, pp. 247–308. (c) Sharpless, K. B.; Woodard, S. S.;
Finn, M. G. Pure Appl. Chem. 1983, 55, 1823–1836. (d) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune,
H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765–5780.
9. (a) Tamao, K.; Nakajo, E.; Ito, Y. J. Org. Chem. 1987, 52, 4412–4414. (b) Hudrlik, P. F.; Peterson, D.; Rona, R. J. J. Org.
Chem. 1975, 40, 2263–2264.
10. (a) Jones, T. K.; Denmark, S. E. J. Org. Chem. 1982, 47, 4595–4597. (b) Jones, T. K.; Denmark, S. E. Org. Synth. 1986,
64, 182–188.
11. The (p-methoxyphenyl)dimethylsilyl group were introduced as a possible hydroxyl group equivalent. For a leading
reference, see: Fleming, I. Chemtracts Org. Chem. 1996, 9, 1–64.
12. (a) Kitano, Y.; Matsumoto, T.; Sato, F. Tetrahedron 1988, 44, 4073–4086. (b) Yoshida, J.; Maekawa, T.; Morita, Y.; Isoe,
S. J. Org. Chem. 1992, 57, 1321–1322.
13. Dale, J. A.; Dull, D. A.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543–2549.
14. Hall, W. E.; Seeholzer, K.; Baumeister, M.; Ugi, I. Tetrahedron 1986, 42, 547–552.
15. Where 19F NMR signals for the two diastereomers were resolved, the signal for the minor isomer could be compared to the
13C satellites (0.55% intensity) of the major signal for a precise assay; with 1H NMR spectra, overlapping ABX patterns
were usually observed, and a value of >95% indicates that signals for the minor isomer were not detected.
16. Davis, A. P.; Hughes, G. J.; Lowndes, P. R.; Robbins, C. M.; Thomas, E. J.; Whitman, G. H. J. Chem. Soc., Perkin. Trans.
1 1981, 1934–1941.
17. For recent discussions regarding the nature of ‘higher order’ cuprates, see: (a) Bertz, S. H.; Nilsson, K.; Davidsson, Ö.;
Snyder, J. P. Angew. Chem., Int. Ed. Engl. 1998, 37, 314–317. (b) Lipshutz, B. H.; James, B. J. Org. Chem. 1994, 59,
7585–7587.
18. Whitesides, G. M.; Stedronsky, E. R.; Casey, C. P.; San Fillipo Jr., J. J. Am. Chem. Soc. 1970, 92, 1426–1427.
19. (a) Corey, E. J.; Beames, D. J. J. Am. Chem. Soc. 1972, 94, 7210–7211. (b) Mandeville, W. H.; Whitesides, G. M. J. Org.
Chem. 1974, 39, 400–405. (c) Kim, S.; Park, J. H.; Jon, S. Y. Bull. Korean Chem. Soc. 1995, 16, 783–786.
20. (a) Fried, J.; Lin, C. H.; Sih, J. C.; Dalven, P.; Cooper, G. F. J. Am. Chem. Soc. 1972, 94, 4342–4343. (b) Suzuki, T.;
Saimoto, H.; Tomioka, H.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1982, 23, 3597–3600.
21. House, H. O.; Chu, C.-Y.; Wilkins, J. M.; Umen, M. J. J. Org. Chem. 1975, 40, 1460–1469.
22. See footnote 45 in Ref. 8d.
23. Chong, J. M.; Loewith, R. Synth. Commun. 1993, 23, 2145–2150.