Stereoselective synthesis of 1,2,3-triol derivatives from α,β-unsaturated acylsilanes

Article abstract of DOI:10.1002/hc.21176

The stereoselective synthesis of 1,2,3- triol derivatives having contiguous stereogenic centers from α,β-unsaturated acylsilanes 1 was described. The oxidation of an olefin moiety of 1 with osmium tetroxide proceeded smoothly to give the corresponding 2,3- syn-dihydroxyacylsilanes 2. The protection of two hydroxy groups of 2 followed by a nucleophilic reaction to the silyl carbonyl group gave the corresponding silylated triol derivatives (7 and 8) with high stereoselectivity, depending on the kind of nucleophilic reagents. The deprotection for 7 and 8 and the following protodesilylation gave two isomers of possible four 1,2,3- triol derivatives. The stereoselective triol synthesis by asymmetric diolization of α-silylated allyl alcohols 11 derived by nucleophilic addition to 1 was also investigated.

Full text of DOI:10.1002/hc.21176

Heteroatom Chemistry
Volume 25, Number 6, 2014
Stereoselective Synthesis of 1,2,3-Triol
Derivatives from α,β-Unsaturated Acylsilanes
Mitsunori Honda, Takayoshi Nakamura, Takumi Sumigawa,
Ko-Ki Kunimoto, and Masahito Segi
Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa
University, Kanazawa, Ishikawa 920-1192, Japan
Received 26 February 2014; revised 19 April 2014
group, and silyl group, are presented in these com-
ABSTRACT: The stereoselective synthesis of 1,2,3-
pounds. Indeed, a number of synthetic processes
triol derivatives having contiguous stereogenic centers
using these functional groups of α,β-unsaturated
from α,β-unsaturated acylsilanes 1 was described. The
acylsilanes have been reported [2]. For instance,
oxidation of an olefin moiety of 1 with osmium tetrox-
α,β-unsaturated acylsilanes were used as starting
ide proceeded smoothly to give the corresponding 2,3-
materials to synthesize the various compounds,
syn-dihydroxyacylsilanes 2. The protection of two hy-
vinylcyclopropane-1,2-diols [2e], 3-cyclopentenols
droxy groups of 2 followed by a nucleophilic reaction
[2f], and (Z)-disubstituted silyl enol ethers [2b],
to the silyl carbonyl group gave the corresponding sily-
stereoselectively. However, it has not been known
lated triol derivatives (7 and 8) with high stereoselec-
the stereoselective synthesis of 1,2,3-triols from α,β-
tivity, depending on the kind of nucleophilic reagents.
unsaturated acylsilanes. In this paper, the stereose-
The deprotection for 7 and 8 and the following pro-
lective synthesis of 1,2,3-triol derivatives having con-
todesilylation gave two isomers of possible four 1,2,3-
tiguous stereogenic centers from α,β-unsaturated
triol derivatives. The stereoselective triol synthesis by
acylsilanes as starting materials, using the feature
asymmetric diolization of α-silylated allyl alcohols 11
of a silyl group as a directing group for a stere-
derived by nucleophilic addition to 1 was also inves-
oselective reaction and a good leaving group, was
ꢀC
tigated.
2014 Wiley Periodicals, Inc. Heteroatom
described. Previously, we have reported the nu-
cleophilic addition to β-methoxyacylsilane possess-
ing stereogenic centers at the α and β positions
(Scheme 1) [3a,b,d]. In this reaction, the silyl group
acted as a directing group to obtain the high stere-
oselectivity, and the two diastereomers 1,2-syn iso-
mer and 1,2-anti isomer were yielded at will with
high stereoselectivity depending on the kind of nu-
cleophiles and the reaction conditions [3a,d]. The
reaction of β-methoxyacylsilane with methyllithium
proceeded via 1,5-chelation intermediates A or B.
The intermediate B is favored because of the steric
repulsion between the silyl group and the sub-
stituent R2 on the α position. Then, the methyl an-
ion attacks the carbonyl group of B from a less-
hindered site to afford the 1,2-syn isomer. On the
other hand, in the reaction with trimethylaluminum,
six-membered ring transition state D constructed
Chem. 25:565–577, 2014; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.21176
INTRODUCTION
Acylsilanes are a useful class of compounds in
organic synthesis, and a number of methods for
the preparation and the utilization of acylsilanes
have been developed [1]. Especially, α,β-unsaturated
acylsilanes are expected to be useful synthetic in-
termediates since three easily convertible func-
tional groups, carbon–carbon double bond, carbonyl
Correspondence to: Mitsunori Honda; e-mail: honda
@se.kanazawa-u.ac.jp. Masahito Segi; e-mail: segi@se.kanazawa-
u.ac.jp.
Dedicated to 77th birthday of Professor Renji Okazaki.
2014 Wiley Periodicals, Inc.
ꢀC
565

566 Honda et al.
SCHEME 1 Stereocontrolled synthesis of 1,3-diol derivatives from β-methoxyacylsilanes.
with two trimethylaluminum molecules and acylsi-
lane seems to be favored compared to C by the less
strain between the nucleophilic group and the sub-
stituent R1 on the β position. As a result, 1,2-anti
isomer is exclusively yielded. Furthermore, the pro-
todesilylation of the resulting α-silylalcohols with
tetrabutylammonium fluoride proceeded smoothly
with complete retention of the configuration [3,
4]. Consequently, this method is thought to be
a useful method for the stereoselective construc-
tion of 1,3-diol derivatives. Thus, we considered
that a similar nucleophilic addition reaction to 2,3-
dihydroxyacylsilane derived from the dihydroxyla-
tion of the alkene moiety of α,β-unsaturated acyl-
silane and the following protodesilylation give the
corresponding 1,2,3-triol with high stereoselectivity
(Scheme 2). Such 1,2,3-triol units having contiguous
stereogenic centers are a very common pattern in the
structure of many naturally occurring compounds;
however, the facile stereoselective synthesis of de-
sired isomers among four generable diastereomeric
1,2,3-triols was less well known [5]. So, our method
will be useful for the stereoselective construction of
1,2,3-triol derivatives. In addition, another route to
1,2,3-triol, the nucleophilic addition reaction to α,β-
unsaturated acylsilanes and the following dihydrox-
ylation of the resulting α-silylated allyl alcohols, is
also described.
RESULTS AND DISCUSSION
The preparation of α,β-unsaturated acylsilanes
was accomplished by as follows (Scheme 3): The
Mukaiyama aldol reaction of silyl enol ether derived
from acetylsilanes with acetals [6] followed by the
SCHEME 3 Synthesis of α,β-unsaturated acylsilanes via the
Mukaiyama aldol reaction.
SCHEME 2 Our synthetic strategy for constructing 1,2,3-
triol.
Heteroatom Chemistry DOI 10.1002/hc

Stereoselective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated Acylsilanes 567
TABLE 1 Nucleophilic Addition to 2,3-Dihydroxyacylsilane
Entry
Nucleophile
Solvent
Yield (%)a
4/5b
1
2
3
4
MeLi
Et2O
Et2O
Toluene
CH2CI2
24
13
60
16
82:18
64:36
42:58
28:72
n-BuLi
Me3AI
MeLic
SCHEME 4 Synthesis of 2,3-syn-2,3-dihydroxyacylsilanes.
treatment of the resulting β-methoxyacylsilanes with
hydrochloric acid in THF gave the desired (E)-α,β-
unsaturated acylsilanes 1 with high stereoselectivity
in good yields.
Molar ratio; 2a/RLi = 1:3, 2a/Me3AI = 1:4.
aIsolated yield.
bDetermined by 1H NMR analysis.
cAn equimolar amount of TiCI4 was used as an additive.
Then the dihydroxylation of an olefin moiety of 1
was carried out. The oxidation with osmium tetrox-
ide [7] proceeded smoothly to give the correspond-
ing 2,3-syn-dihydroxyacylsilanes 2 in high yields in-
dependent of the kind of the substituent on C-3 or
silicon atom (Scheme 4). On the other hand, the
epoxydation of an olefin moiety of 1 could not be
achieved (Scheme 5). The oxidation of 1a with m-
CPBA [8] gave the complex mixture including desi-
lylated compounds that was observed by NMR spec-
tra. So, the protection of the silylcarbonyl group with
ethylene glycol [9] and the following oxidation with
m-CPBA was examined. Although the correspond-
ing epoxide derivative was provided in good yield,
the deprotection with protic acid also gave the desi-
lylated complex mixture. As a consequence, 2,3-anti-
dihydroxyacylsilane 3a has not yet been obtained.
The nucleophilic addition of organometallic
reagents to 2a proceeded to afford the correspond-
ing 1,2,3-triol derivatives in low yields. Furthermore,
in these reactions, high diastereoselectivity observed
in the similar reaction using β-alkoxyacylsilanes [3]
was not accomplished. The representative results are
shown in Table 1. The reaction of 2a with alkyl-
lithium gave the diastereomeric mixture with a slight
preference for 1,2-syn isomers 4; however, that with
trimethylaluminum proceeded with a little stereose-
lectivity. Meanwhile, 1,2-anti isomer 5 was preferen-
tially yielded by the reaction with MeLi in the pres-
ence of titanium tetrachloride as an additive [10].
Since these low yield and stereoselectivity were
attributed to undesirable chelation of a nucleophilic
reagent with free hydroxyl groups on C-2 of 2, the
protection of two hydroxyl groups of 2 with ace-
tone ketal in the presence of p-TsOH was performed
[11], and then the corresponding dioxolanylacylsi-
lane derivatives 6 were obtained in moderate-to-
good yields (Scheme 6).
The nucleophilic addition of organometallic
reagents to the silyl carbonyl group of 6 was carried
out. The results are shown in Table 2. In all cases,
the corresponding diastereomeric mixtures of silyl
alcohol derivatives 7 and 8 were obtained. The reac-
tion with methyllithium or phenyllithium in diethyl
ether proceeded smoothly to afford 7 predominantly
independent of the kind of the substituent on C-3 or
silicon atom (entries 1–4). Similarly, high diastere-
oselectivity was observed in the reaction of 6a with
the Grignard reagent (entry 5). It should be noted
SCHEME 5 Approaches to the synthesis of 2,3-anti-2,3-dihydroxyacylsilane.
Heteroatom Chemistry DOI 10.1002/hc

568 Honda et al.
SCHEME 6 Protection of 2,3-dihydroxyacylsilanes.
TABLE 2 Nucleophilic Addition to Dioxolanylacylsilanes
SCHEME 7 Plausible mechanism of a reaction with organo-
lithium or Grignard reagent.
Entry
6
Nucleophile Solvent Yield (%)a Products 7/8b
1
2
3
4
5
6
7
8
6a MeLi
Et2O
Et2O
Et2O
Et2O
96
70
88
97
79
91
85
98
7a, 8a 93: 7
7b, 8b 93: 7
7c, 8c 95: 5
7d, 8d 99: 1
7a, 8a 98: 2
7a, 8a 5:95
7b, 8b 5:95
7c, 8c 7:93
6b MeLi
6c MeLi
6a PhLic
6a MeMgBrc
6a Me3AI
6b Me3AI
6c Me3AI
Et2O
Toluene
Toluene
Toluene
Molar ratio; 6/RLi = 1:2, 6/MeMgBr = 1:3, 6/Me3AI = 1:5.
aIsolated yield.
bDetermined by 1H NMR analysis.
cThe reaction was carried out at –78°C.
SCHEME 8 Plausible mechanism of reaction with trimethla-
luminum.
that the other stereoisomeric products 8 were pre-
dominantly yielded in the reactions with trimethyla-
luminum as a nucleophilic reagent (entries 6–8). In
these nucleophilic additions, the silyl group would
act as a directing group for the synthesis of silylalco-
hols with high stereoselectivity, as mentioned above
[3a].
It appears that these reactions proceeded as
follows: In the reaction of 6 with organolithium
reagents or Grignard reagent (Scheme 7), the 1,3-
chelation model seems to be favored compared to
the 1,2-chelation model by the less strain between
silyl group and the substituent R group on C-3. The
attack of nucleophile occurs from a less-hindered
site to afford the silyl alcohol derivatives 7. On the
other hand, the reaction with trimethylaluminum
proceeds via six-membered ring transition states
(Scheme 8). In this case, the 1,2-chelation model
seems to be favored compared to the 1,3-chelation
model by the less strain between the six-membered
ring and dioxolanyl ring. Then the silyl alcohol
derivatives 8 are exclusively yielded.
The deprotection of a cyclic ketal moiety of the
resulting silyl alcohols 7a and 8a was successfully
achieved to give the silylated triol derivatives 4a
and 5a by the treatment with hydrochloric acid in
methanol under reflux (Scheme 9) [12]. It is known
that the protodesilylation of α-silylalcohols proceeds
with complete retention of the configuration [4].
Thus, the protodesilylation of 4a and 5a with tetra-
butylammonium fluoride was carried out and gave
the corresponding 1,2,3-triols 9a and 10a in good
yields, respectively. Consequently, two diastereoiso-
mers (9 and 10) of 1,2,3-triol derivatives having the
three contiguous stereogenic centers among four
possible diastereomeric products were yielded with
high stereoselectivity by a series of reactions starting
from α,β-unsaturated acylsilanes.
Next, we tried out the other route to 1,2,3-
triol. That is, the nucleophilic addition reaction to
α,β-unsaturated acylsilanes and the following dihy-
droxylation of the resulting α-silylated allyl alcohols
were studied.
Heteroatom Chemistry DOI 10.1002/hc

Stereoselective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated Acylsilanes 569
SCHEME 9 Deprotection and following protodesilylation to 1,2,3-triols.
TABLE 3 Nucleophilic Addition to α,β-Unsaturated Acylsi-
lane
SCHEME 10 Oxidation of α-silylated allyl alcohols with m-
CPBA.
Entry Nucleophile Temperature (°C) Product Yield(%)a
1
2
3
4
MeLi
MeLi
MeMgl
MeCeCI2
0
−78
−78
−78
12a
11a
11a
11a
62
51
94
99
To obtain the desired 2,3-anti triol deriva-
tives, stereoselective epoxydation of the resulting α-
silylated allyl alcohols 11 with several oxidants and
the following hydrolysis reaction were carried out
[15]. The treatment of α-silylated allyl alcohols 11
possessing various substituents and silyl groups with
m-CPBA did not give the corresponding epoxides,
but afforded the silyl-migrated compounds 13 with
excellent 2,3-anti selectivity in quantitative yields
(Scheme 10) [16]. In addition, the desired epox-
ides as the precursor compounds of 2,3-anti triol
derivatives were not obtained at all by using the
epoxidation reaction of 11a with other oxidants,
Sharpless–Katsuki asymmetric epoxidation reagents
[17], OxoneꢀR [18], hydrogen peroxide [19], sodium
peroxide [20]. In these reactions, silyl-migrated or
silyl-eliminated derivatives 13–16 were, respectively,
yielded (Scheme 11).
In conclusion, the stereoselective synthesis of
1,2,3-triol derivatives having the three contiguous
stereogenic centers from α,β-unsaturated acylsi-
lanes has been investigated. The two isomers of
possible four stereoisomers of 1,2,3-triol derivatives
were synthesized by using the characteristic features
of the silyl group with high stereoselectivity. How-
ever, synthetic routes to the other two isomers have
not been established yet. Further studies are aimed
at the synthesis of the other two isomers using α,β-
unsaturated acylsilanes in our laboratory.
Molar ratio; 1a/MeLi = 1:2, 1 a/MeMgl = 1:4, 1a/MeCeCI2 = 1:6.
aIsolated yield.
At first, the nucleophilic addition to α,β-
unsaturated acylsilane was investigated. These re-
sults are shown in Table 3. The reaction of α,β-
unsaturated acylsilane 1a with methyllithium at 0°C
proceeded to give β-silyl ketone derivative 12a, and
the desired silyl alcohol 11a was not produced at all.
It has been known that the nucleophilic addition of
vinyllithium to acylsilanes affords the β-silyl ketones
via the Brook rearrangement of the corresponding
alkoxide intermediate and the following migration of
the silyl group to β-position [13]. Because the reac-
tion of 1a with alkyllithium gave the similar alkoxide
intermediate, the β-silyl ketone 12a would be yielded
via the Brook rearrangement of the above interme-
diate. In contrast, the exclusive formation of 11a
was achieved by the reaction at –78°C with methyl-
lithium. The Brook rearrangement of the alkoxide
intermediate would be prevented under low temper-
ature. The yield was, however, remained moderate.
On the other hand, the use of the Grignard reagent
or organo cerium reagent [13,14] made it feasible to
generate 11a quantitatively.
Heteroatom Chemistry DOI 10.1002/hc

570 Honda et al.
SCHEME 11 Oxidation of α-silylated allyl alcohol.
EXPERIMENTAL
General Procedures
A Typical Procedure for the Preparation of
α,β-Unsaturated Acylsilanes 1
To a stirred solution of titanium tetrachloride
(10.4 g, 55 mmol) in dichloromethane (150 mL)
at –78°C, a solution of acetal (55 mmol) in
dichloromethane was added slowly. The resulting re-
action mixture was stirred, and then acylsilane silyl
enol ether (55 mmol) in dichloromethane was added.
After stirring for 2 h, methanol (10 mL) was added
and the reaction mixture was allowed to warm to
ambient temperature and then poured into saturated
aq. NaHCO3. The aqueous layer was extracted with
hexane for three times. The combined organic lay-
ers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography on a silica gel
20:1 hexane–ethyl acetate as the eluent to give β-
methoxyacylsilane derivatives in 70–81% yields as
pale yellow oil.
IR spectra were recorded on a Horiba FTIR-720
or Shimadzu FTIR- 8300 infrared spectrometer.
1H and 13C NMR spectra were recorded on a
JEOL JNM EX-270, LA-400 or ECA-500 spectrom-
eter. Chemical shifts of 1H NMR were expressed
in parts per million downfield from tetramethyl-
silane (TMS) with reference to internal residual
CHCl3 (δ = 7.26) in CDCl3. Chemical shifts of 13C
NMR were expressed in parts per million down-
field from CDCl3 (δ = 77.0) as an internal stan-
dard. Coupling constants (J) were reported in hertz
(Hz). Following abbreviations were used to desig-
nate the multiplicities: s = singlet, d = doublet,
t = triplet, q = quartet, quin = quintet, sext =
sextet, br = broad, m = multiplet. Mass spectra
were recorded on a JEOL JMS-700 or JMS-SX102A
mass spectrometer. Melting points were measured
on a Yanaco MP-J3 and were uncorrected. Analyti-
cal thin layer chromatography (TLC) was performed
3-Methoxy-3-phenyl-1-trimethylsilyl-1-propanone.
IR (neat) 3086, 3063, 3029, 2955, 2926, 1644, 1453,
1248, 1105, 842 cm−1. 1H NMR (270 MHz, CDCl3): δ
7.26–7.35 (m, 5H), 4.67 (dd, J = 8.6 Hz, 4.3 Hz, 1H),
3.24 (dd, J = 16.2 Hz, 8.6 Hz, 1H), 3.17 (s, 3H), 2.67
(dd, J = 16.2 Hz, 4.3 Hz, 1H), 0.12 (s, 9H). 13C NMR
(68 MHz, CDCl3): δ 240.5, 138.9, 132.2, 128.8, 126.5,
82.3, 56.6, 55.0, –2.7. HRMS calcd for C13H20O2Si
(M+) 236.1233, found 236.1230.
on precoated glass plates (Merck Kieselgel 60 F254
,
layer thickness 0.25 mm). Visualization was accom-
plished with UV light (254 nm) and molybdophos-
phoric acid. Flash column chromatography was car-
ried out using Kanto Chemical silica gel 60 N (40–
50 mm). Preparative HPLC was performed on a JAI
LC-908 and LC-918 chromatograph equipped with
JAIGEL-1H and -2H and JAIGEL-SIL. GC analysis
was performed on a Shimadzu GC-14B equipped
with a CBP1-M25-O20 column (Shimadzu, 25 m ×
0.22 mm, detector = FID) with a helium gas as a car-
rier. Unless otherwise noted, commercially available
reagents were used without purification. All the sol-
vents were distilled and stored over a drying agent.
Methyllithium (1.3 M solution in diethylether), n-
butyllithium (1.6 M solution in hexane), phenyl-
lithium (1.1 M solution in cyclohexane), methyl mag-
nesium bromide (1.0 M solution in tetrahydrofuran),
and trimethylaluminum (1.0 M solution in hexane)
were purchased from Kanto Chemical. All reactions
were carried out under an argon atmosphere in dried
glassware.
3-Cyclohexyl-3-methoxy-1-trimethylsilyl-1-propa-
none. IR (neat) 2926, 2853, 1643, 1456, 1250, 1096,
1
847 cm−1. H NMR (270 MHz, CDCl3): δ 3.56 (ddd,
J = 7.9 Hz, 4.1 Hz, 4.1 Hz, 1H), 3.25 (s, 3H), 2.90
(dd, J = 16.2 Hz, 7.9 Hz, 1H), 2.51 (dd, J = 16.2 Hz,
4.0 Hz, 1H), 1.73–0.99 (m, 11H), 0.21 (s, 9H). 13C
NMR (100 MHz, CDCl3): δ 247.1, 79.9, 57.3, 49.2,
41.2, 28.2, 28.0, 26.2, 26.0, 25.9, –3.6. HRMS calcd
for C13H26O2Si (M+) 242.1702, found 242.1705.
3-Methoxy-1-dimethylphenylsilyl-1-butanone. IR
(neat) 2970, 2930, 1643, 1460, 1429, 1373, 1250,
1194, 1111, 1088 cm−1. 1H NMR (270 MHz, CDCl3):
Heteroatom Chemistry DOI 10.1002/hc

Stereoselective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated Acylsilanes 571
δ 7.56–7.38 (m, 5H), 3.74 (m, 1H), 2.94 (dd, J =
General Procedure for the Dihydroxylation of
α,β-Unsaturated Acylsilanes 1
16.3 Hz, 5.9 Hz, 1H), 2.51 (dd, J = 16.3 Hz, 4.0 Hz,
1H), 1.04 (d, J = 6.2 Hz, 3H), 0.49 (s, 3H), 0.48 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 245.6, 134.2,
133.9, 129.8, 128.1, 72.1, 55.9, 55.0, 19.3, –4.9, –5.0.
HRMS calcd for C13H20O2Si (M+) 236.1233, found
236.1241.
To a solution of α,β-unsaturated acylsilane (5 mmol)
in pyridine (25 mL) at room temperature, osmium
tetroxide (1.4 g, 5.5 mmol) was added slowly. Af-
ter stirring for 1 h, water (25 mL), sodium hydro-
gen sulfite (2.4 g, 23 mmol), and pyridine (25 mL)
was added and the reaction mixture was stirred for
1 h, and then the aqueous layer was extracted with
diethyl ether for three times. The combined organic
layers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography on a silica gel
using 2:1 hexane–ethyl acetate as the eluent to give
2,3-syn-dihydroxyacylsilane derivatives 2 in 79–87%
yields as pale yellow oil.
To a stirred solution of β-methoxyacylsilane
(1 mmol) in THF (10 mL) at 25–40°C, an aqueous so-
lution of HCl (1.0 M, 2.5 mL) was added slowly. The
resulting reaction mixture was stirred, and then acyl-
silane silyl enol ether (55 mmol) in dichloromethane
was added. After completion of the reaction evi-
denced by GC (usually after being stirred for 3–44 h),
brine was then added, and the resulting mixture was
separated. The aqueous layer was extracted with di-
ethyl ether for three times. The combined organic
layers were washed with saturated aq. NaHCO3 and
brine for three times, dried over anhydrous Na2SO4,
and concentrated in vacuo. The residue was pu-
rified by column chromatography on a silica gel
10:1 hexane–ethyl acetate as the eluent to give α,β-
unsaturated acylsilane derivatives in 63–95% yields
as pale yellow oil.
2,3-syn-2,3-Dihydroxy-3-Phenyl-1-trimethylsilyl-
1-propanone (2a). IR (neat) 3438, 2950, 2901, 1703,
1
1643, 1593, 1495, 1452, 1248 cm−1. H NMR (270
MHz, CDCl3): δ 7.39–7.29 (m, 5H), 5.20 (d, J = 2.0
Hz, 1H), 4.50 (d, J = 2.0 Hz, 1H), 0.30 (s, 9H). 13C
NMR (68 MHz, CDCl3): δ 244.5, 141.0, 128.8, 128.2,
126.4, 84.1, 72.0, 2.8. HRMS calcd for C12H18O3Si
(M+) 238.1025, found 238.1029.
(E)-3-Phenyl-1-trimethylsilyl-2-propen-1-one (1a).
IR (neat) 3028, 2958, 2900, 1703, 1639, 1622, 1579,
1562, 1494, 1250 cm−1. 1H NMR (270 MHz, CDCl3):
δ 7.38–7.25 (m, 6H), 6.90 (d, J = 16.5 Hz, 1H), 0.32
(s, 9H). 13C NMR (68 MHz, CDCl3): δ 235.9, 142.7,
134.6, 131.0, 130.2, 128.7, 128.0, –2.2. HRMS calcd
for C12H16OSi (M+) 204.0970, found 204.0971.
2,3-syn-3-Cyclohexyl-2,3-dihydroxy-1-trimethyl-
silyl-1-propanone (2b). IR (neat) 3369, 2903, 2855,
1638, 1389, 1250, 1115, 849 cm−1 1H NMR (270
.
MHz, CDCl3): δ 4.44 (dd, J = 3.8 Hz, 1.1 Hz,
1H), 4.07 (d, J = 3.8 Hz, 1H), 3.77 (t, J = 9.4 Hz,
1H), 2.05–0.99 (m, 11H), 0.29 (s, 9H). 13C NMR
(68 MHz, CDCl3): δ 244.2, 81.0, 74.4, 29.6, 29.4,
26.3, 25.9, 25.8, –2.7. HRMS calcd for C12H24O3Si
(M+) 244.1495, found 244.1503.
(E)-3-Cyclohexyl-1-trimethylsilyl-2-propen-1-one
2,3-syn-2,3-Dihydroxy -1-dimethylphenylsilyl-1-
(1b). IR (neat) 2928, 2853, 1638, 1593, 1448, 1250,
butanone (2c). IR (neat) 3433, 3070, 2974, 1639,
1
980, 845 cm−1. H NMR (270 MHz, CDCl3): δ 6.68
1429, 1379, 1252, 1111, 1088, 989, 912 cm−1 1H
.
(dd, J = 16.3 Hz, 6.6 Hz, 1H), 6.16 (dd, J = 16.3 Hz,
1.3 Hz, 1H), 1.79–1.14 (m, 11H), 0.25 (s, 9H). 13C
NMR (68 MHz, CDCl3): δ 236.9, 153.9, 133.7, 40.7,
31.7, 25.8, 25.6, –1.9. HRMS calcd for C12H22OSi
(M+) 210.1440, found 210.1440.
NMR (270 MHz, CDCl3): δ 7.58–7.40 (m, 5H), 4.16
(dq, J = 6.4 Hz, 1.6 Hz, 1H), 4.09 (d, J = 1.8 Hz, 1H),
1.19 (d, J = 6.5 Hz, 3H), 0.58 (s, 3H), 0.55 (s, 3H). 13C
NMR (68 MHz, CDCl3): δ 243.5, 134.0, 133.5, 130.1,
128.2, 84.4, 66.2, 20.1, –4.3, –4.6. HRMS calcd for
C12H18O3Si (M+) 238.1025, found 238.1021.
(E)-1-dimethylphenylsilyl-2-buten-1-one
IR (neat) 3069, 2966, 1639, 1585, 1429, 1283, 1248,
1186, 1111, 970, 837 cm−1 1H NMR (270 MHz,
(1c).
General Procedure for the Nucleophilic Reaction
to Dihydroxyacylsilanes 2a
.
CDCl3): δ 7.56–7.37 (m, 5H), 6.6 (m, 1H), 6.24 (dt, J =
8.4 Hz, 1.6 Hz, 1H), 1.73 (m, 3H), 0.49 (s, 3H), 0.48
(s, 3H). 13C NMR (68 MHz, CDCl3): δ 233.9, 144.5,
137.8, 135.4, 133.8, 129.6, 128.0, 18.4, –3.7. HRMS
calcd for C12H16OSi (M+) 204.0970, found 204.0961.
To a solution of dihydroxyacylsilane 2 (0.5 mmol)
in a solvent (10 mL) at -–78°C, a solution of nu-
cleophilic reagent was added slowly. After stirring
for 1 h, methanol (1 mL) was added and the re-
action mixture was allowed to warm to ambient
Heteroatom Chemistry DOI 10.1002/hc

572 Honda et al.
temperature and then poured into brine. The aque-
ous layer was extracted with diethyl ether for three
times. The combined organic layer was then washed
with brine, dried over anhydrous Na2SO4, and con-
centrated in vacuo. The residue was purified by col-
umn chromatography on a silica gel 10:1 hexane–
ethyl acetate as the eluent to give silyltriol derivatives
4 and 5 in 13–60% yields as pale yellow oil.
tion (200 mL). The organic layers were washed with
brine, dried over anhydrous potassium carbonate,
and concentrated in vacuo. The residue was puri-
fied by recrystallization from t-butyl alcohol to give
1,3-dioxane derivative in 55% yield as a white solid.
(E)-2-Styryl-1-trimethylsilyl-1,3-dioxolane. Mp
115.6°C. IR (neat) 3028, 2962, 2891, 1248, 1122, 987
1
cm−1. H NMR (270 MHz, CDCl3): δ 7.40–7.23 (m,
1-Phenyl-3-trimethylsilylbutane-1,2,3-triol (4a,
5a). Compound 4a: IR (neat) 3313, 3065, 3020,
5H), 6.56 (d, J = 16.0 Hz, 1H), 6.10 (d, J = 16.0 Hz,
1H), 3.93 (ddd, J = 6.3 Hz, 3.1 Hz, 1.9 Hz, 2H), 3.86
(ddd, J = 6.4 Hz, 3.1 Hz, 1.9 Hz, 2H), 0.10 (s, 9H).
13C NMR (68 MHz, CDCl3): δ 136.6, 129.6, 129.3,
128.4, 127.4, 126.4, 108.4, 64.5, –4.1. HRMS calcd
for C14H20O2Si (M+) 248.1233, found 248.1238.
1
2959, 1605, 1495, 1452, 1249 cm−1. H NMR (270
MHz, CDCl3): δ 7.39–7.25 (m, 5H), 5.09 (s, 1H), 3.72
(s, 1H), 3.59 (d, J = 6.1 Hz, 1H), 2.29 (d, J = 6.1 Hz,
1H), 1.98 (s, 1H), 1.31 (s, 3H), 0.21 (s, 9H). 13C NMR
(68 MHz, CDCl3): δ 141.6, 128.5, 127.6, 125.8, 77.5,
75.0, 70.8, 22.5, –3.0. HRMS calcd for C13H22O2Si
(M+) 254.1338, found 254.1332.
Compound 5a: IR (neat) 3365, 3020, 2961, 1647,
1541, 1508, 1248 cm−1. 1H NMR (270 MHz, CDCl3):
δ 7.36–7.25 (m, 5H), 5.02 (brs, 1H), 3.91 (brs, 1H),
3.52 (brs, 1H), 1.29 (s, 3H), 0.19 (s, 9H). 13C NMR
(68 MHz, CDCl3): δ 141.3, 128.4, 127.5, 125.9, 77.6,
73.4, 72.0, 21.2, –2.9. HRMS calcd for C13H22O2Si
(M+) 254.1338, found 254.1333.
Epoxydation of (E)-2-Styryl-1-trimethylsilyl-1,3-
dioxolane
To a stirred solution of (E)-2-styryl-1-trimethylsilyl-
1,3-dioxolane (248 mg, 1 mmol) in dichloromethane
(15 mL), - m-chloroperbenzoic acid (259 mg,
1.5 mmol) dissolved in dichloromethane was added.
After stirring at room temperature for 13 h, the
reaction mixture was poured into 10% solution of
sodium sulfite to destroy any excess peroxide. The
organic layer was then washed with saturated aq.
NaHCO3 and brine for three times, dried over an-
hydrous Na2SO4, and concentrated in vacuo. The
residue was purified by column chromatography on
a silica gel 5:1 hexane–ethyl acetate as the eluent to
give 1,3-dioxane derivative in 94% yield as pale yel-
low oil.
1-Phenyl-3-trimethylsilylheptane-1,2,3-triol (4b,
5b). Compound 4b: IR (neat) 3371, 3063, 3028,
1
2957, 2934, 2903, 2872, 1452, 1249 cm−1. H NMR
(270 MHz, CDCl3): δ 7.40–7.27 (m, 5H), 5.12 (s, 1H),
4.02 (s, 1H), 3.75 (d, J = 6.6 Hz, 1H), 2.21 (d, J = 6.6
Hz, 1H), 1.94 (s, 1H), 1.29–1.23 (m, 6H), 0.89 (t, J =
6.8 Hz, 3H), 0.26 (s, 9H). 13C NMR (68 MHz, CDCl3):
δ 141.5, 128.4, 127.6, 125.7, 77.5, 74.3, 74.2, 37.6,
27.0, 23.5, 14.0, –1.8. HRMS calcd for C16H28O2Si
(M+) 296.1808, found 296.1818.
2-(3-Phenyloxiran-2-yl)-2-trimethylsilyl-1,3-dioxo-
lane. IR (neat) 3031, 2964, 2895, 1654, 1560, 1252,
1
Compound 5b: IR (neat) 3420, 3028, 2957,
993 cm−1. H NMR (270 MHz, CDCl3): δ 7.45–7.32
1
2932, 2901, 2862, 1452, 1248 cm−1. H NMR (270
(m, 5H), 4.21–4.14 (m, 2H), 4.02–3.86 (m, 3H), 3.14
(d, J = 2.0 Hz, 1H), 0.22 (s, 9H). 13C NMR (68 MHz,
CDCl3): δ 136.9, 128.3, 127.8, 125.2, 105.3, 66.5,
65.5, 64.8, 55.0, –4.0. HRMS calcd for C14H20O3Si
(M+) 264.1182, found 264.1179.
MHz, CDCl3): δ 7.39–7.26 (m, 5H), 5.23 (s, 1H), 3.91
(brs, 1H), 3.72 (d, J = 6.3 Hz, 1H), 2.36 (d, J =
6.4 Hz, 1H), 1.44–1.25 (m, 6H), 0.97 (t, J = 6.9 Hz,
3H), 0.13 (s, 9H). 13C NMR (68 MHz, CDCl3): δ
141.3, 128.5, 127.5, 125.8, 75.8, 74.9, 73.3, 36.7,
27.0, 23.7, 14.0, –1.9. HRMS calcd for C16H28O2Si
(M+) 296.1808, found 296.1807.
General Procedure for the Protection of Hydroxy
Groups of Dihydroxyacylsilanes 2
To a solution of dihydroxyacylsilane 2 (5.8 mmol)
in acetone (50 mL), 2,2-dimethoxypropane (5.2 g,
51 mmol) and p-TsOH (128 mg, 0.75 mmol) were
added. After stirring at room temperature for 21 h,
the reaction mixture was poured into cooled satu-
rated aq. NaHCO3. The mixture was extracted with
diethyl ether for three times. The organic layer was
then washed with brine, dried over potassium car-
bonate, and concentrated in vacuo. The residue was
Protection of the Carbonyl Group of
α,β-Unsaturated Acylsilane 1a
To a stirred solution of acylsilane 1a (8.16 g,
40 mmol) in benzene (100 mL), - ethylene glycol
(2.73 g, 44 mmol) and p-TsOH (83 mg, 0.46 mmol)
were added. After stirring under reflux for 6 h, the
reaction mixture was cooled to ambient tempera-
ture and extracted with 10% sodium hydroxide solu-
Heteroatom Chemistry DOI 10.1002/hc

Stereoselective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated Acylsilanes 573
purified by column chromatography on a silica gel
Method for Using Trimethylaluminum as a Nu-
cleophilic Reagent. To a solution of dioxolanylacyl-
silanes 6 (0.4 mmol) in toluene (10 mL) at -0°C, a
1.0 M solution of trimethylaluminum (2 mL,
2 mmol) in hexane was added slowly. After stirring
for 1 h, the reaction mixture was poured into sat-
urated aq. NH4Cl. The aqueous layer was extracted
with diethyl ether for three times. The combined or-
ganic layer was then washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. The
residue was purified by column chromatography on
a silica gel 10:1 hexane–ethyl acetate as the eluent
to give silyl alcohol derivatives 7 and 8 in 85–98%
yields as pale yellow oil.
10:1 hexane–ethyl acetate as the eluent to give diox-
olanylacylsilane derivatives 6 in 65–84% yields as
pale yellow oil.
4,5-anti-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yltrimethylsilylmethanone (6a). IR (neat) 3029,
2988, 2901, 1651, 1496, 1452, 1380, 1249, 1068
1
cm−1. H NMR (270 MHz, CDCl3): δ 7.40–7.27 (m,
5H), 5.00 (d, J = 7.6 Hz, 1H), 4.21 (d, J = 7.6 Hz,
1H), 1.55 (s, 3H), 1.53 (s, 3H), 0.26 (s, 9H). 13C NMR
(68 MHz, CDCl3): δ 245.1, 138.7, 128.3, 127.8, 126.3,
110.3, 91.4, 78.0, 26.6, 26.4, –1.9. HRMS calcd for
C15H22O3Si (M+) 278.1338, found 278.1342.
4,5-anti-5-Cyclohexyl-2,2-dimethyl-1,3-dioxolan-
1-(2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-yl)-1-
trimethylsilylethan-1-ol (7a, 8a). Compound 7a: IR
(neat) 3503, 3031, 2986, 1460, 1456, 1371, 1246,
4-yltrimethylsilylmethanone (6b). IR (neat) 2988,
1
2928, 2855, 1649, 1450, 1381, 1248, 1211 cm−1. H
NMR (270 MHz, CDCl3): δ 4.07 (d, J = 3.8 Hz, 1H),
3.77 (dd, J = 5.6 Hz, 3.8 Hz, 1H), 2.05–0.99 (m,
11H), 0.29 (s, 9H). 13C NMR (68 MHz, CDCl3): δ
264.1, 109.4, 87.9, 80.6, 41.1, 29.5, 28.3, 26.7, 26.5,
26.3, 26.0, 25.8, –2.3. HRMS calcd for C15H28O3Si
(M+) 284.1808, found 284.1799.
1169, 1059 cm−1 1H NMR (270 MHz, CDCl3): δ
.
7.45–7.32 (m, 5H), 4.93 (d, J = 8.4 Hz, 1H), 4.10
(d, J = 8.4 Hz, 1H), 1.51 (s, 3H), 1.48 (s, 3H), 1.19
(s, 3H), 0.06 (s, 9H). 13C NMR (68 MHz, CDCl3):
δ 138.6, 128.4, 128.1, 127.6, 108.2, 88.1, 78.3, 66.3,
27.3, 27.2, 20.8, –3.1. HRMS calcd for C16H26O3Si
(M+) 294.1651, found 294.1644.
4,5-anti-2,2,5-Trimethyl-1,3-dioxolan-4-yldime-
thylphenylsilylmethanone (6c). IR (neat) 3068,
2986, 2934, 1645, 1429, 1379, 1248, 1173, 1096,
Compound 8a: IR (neat) 3464, 3035, 2984, 1427,
1
1377, 1250, 1215, 1175, 1117, 1061 cm−1. H NMR
(270 MHz, CDCl3): δ 7.45–7.29 (m, 5H), 5.11 (d, J =
8.4 Hz, 1H), 4.04 (d, J = 8.4 Hz, 1H), 1.51 (s, 3H),
1.48 (s, 3H), 0.85 (s, 3H), 0.06 (s, 9H). 13C NMR
(68 MHz, CDCl3): δ 139.0, 128.3, 128.1, 127.9, 107.8,
87.1, 77.0, 65.0, 27.4, 27.2, 19.6, –3.3. HRMS calcd
for C16H26O3Si (M+) 294.1651, found 294.1657.
1061, 839 cm−1 1H NMR (270 MHz, CDCl3): δ
.
7.58–7.37 (m, 5H), 4.16 (dq, J = 4.5 Hz, 1.8 Hz,
1H), 4.09 (d, J = 1.8 Hz, 1H), 1.37 (s, 3H), 1.27–1.25
(m, 3H), 1.19 (s, 3H), 0.58 (s, 9H), 0.58 (s, 9H). 13C
NMR (68 MHz, CDCl3): δ 243.8, 134.2, 134.2, 129.7,
127.8, 109.4, 91.3, 72.9, 27.0, 26.1, 18.2, –3.7, –4.4.
HRMS calcd for C15H22O3Si (M+) 278.1338, found
278.1330.
1-(5-Cyclohexyl-2,2-dimethyl-1,3-dioxolan-4-yl)-
1-trimethylsilylethan-1-ol (7b, 8b). Compound 7b:
IR (neat) 3490, 2983, 1457, 1373, 1247, 1170, 1071
cm−1
.
1H NMR (270 MHz, CDCl3): δ 3.93 (d, J =
General Procedure for the Nucleophilic Reaction
to Dioxolanylacylsilane Derivatives 6
7.6 Hz, 1H), 3.76 (dd, J = 7.6 Hz, 4.0 Hz, 1H),
1.79–1.18 (m, 11H), 1.38 (s, 3H), 1.35 (s, 3H), 1.23
(s, 3H), 0.10 (s, 9H). 13C NMR (68 MHz, CDCl3):
δ 107.5, 83.1, 80.5, 66.1, 40.2, 31.4, 27.6, 27.5,
26.8, 26.7, 26.5, 26.3, 21.2, –3.1. HRMS calcd for
C16H32O3Si (M+) 300.2121, found 300.2120.
Method for Using the Organolithium Reagent or
Grignard Reagent as a Nucleophilic Reagent. To a so-
lution of dioxolanylacylsilanes 6 (0.4 mmol) in ether
(10 mL) at -0°C, a solution of nucleophilic reagent
was added slowly. After stirring for 1 h, methanol
(1 mL) was added and the reaction mixture was al-
lowed to warm to ambient temperature and then
poured into brine. The aqueous layer was extracted
with diethyl ether for three times. The combined or-
ganic layer was then washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. The
residue was purified by column chromatography on
a silica gel 10:1 hexane-ethyl acetate as the eluent
to give silyl alcohol derivatives 7 and 8 in 70–97%
yields as pale yellow oil.
Compound 8b: IR (neat) 3482, 2986, 1451, 1372,
1251, 1171, 1082 cm−1. 1H NMR (270 MHz, CDCl3):
δ 3.97 (dd, J = 6.9 Hz, 4.1 Hz, 1H), 3.90 (d, J =
7.1 Hz, 1H), 1.77–1.18 (m, 11H), 1.39 (s, 3H), 1.34
(s, 3H), 1.08 (s, 3H), 0.08 (s, 9H). 13C NMR (68 MHz,
CDCl3): δ 107.6, 82.8, 79.2 65.7, 41.2, 31.6, 27.8, 27.5,
26.9, 26.8, 26.5, 26.3, 19.8, –3.0. HRMS calcd for
C16H32O3Si (M+) 300.2121, found 300.2125.
1-(2,2,5-Trimethyl-1,3-dioxolan-4-yl)-1-dimethyl-
phenylsilylethan-1-ol (7c, 8c). Compound 7c: IR
Heteroatom Chemistry DOI 10.1002/hc

574 Honda et al.
(neat) 3483, 3053, 2984, 1456, 1369, 1248, 1171,
Protodesilylation of Silyltriol Derivatives 4a and
5a
1059, 918 cm−1 1H NMR (270 MHz, CDCl3): δ
.
7.63–7.34 (m, 5H), 3.98 (dq, J = 8.1 Hz, 5.9 Hz, 1H),
3.60 (d, J = 8.1 Hz, 1H), 1.38 (s, 3H), 1.36 (s, 3H),
1.23–1.06 (m, 3H), 0.41 (s, 3H), 0.40 (s, 3H). 13C
NMR (68 MHz, CDCl3): δ 136.1, 134.5, 129.2, 127.6,
107.4, 87.4, 72.3, 66.1, 27.1, 20.9, 19.9, 0.10, –4.6.
HRMS calcd for C16H26O3Si (M+) 294.1651, found
294.1656.
To a stirred solution of trimethylsilyltriol 4a or 5a
(127 mg, 0.5 mmol) in DMF (10 mL), tetrabuty-
lammonium fluoride (653 mg, 2.5 mmol) was added
slowly. After stirring for 24 h, the reaction mixture
was poured into brine. The aqueous layer was ex-
tracted with diethyl ether for three times. The com-
bined organic layers were washed with brine, dried
over anhydrous Na2SO4, and concentrated in vacuo.
The residue was purified by column chromatography
on a silica gel using 2:1 hexane–ethyl acetate as the
eluent to give triol derivatives 9a or 10a in 92–97%
yields as pale yellow oil.
Compound 8c: IR (neat) 3462, 3049, 2984, 1458,
1427, 1377, 1250, 1175, 1117, 1061, 980, 868 cm−1
.
1H NMR (270 MHz, CDCl3): δ 7.61–7.34 (m, 5H),
4.20 (dq, J = 7.8 Hz, 5.9 Hz, 1H), 3.50 (d, J = 7.8 Hz,
1H), 1.36 (s, 3H), 1.34 (s, 3H), 1.23 (d, J = 5.9 Hz,
1H), 1.06 (s, 3H), 0.40 (s, 3H), 0.39 (s, 3H). 13C NMR
(68 MHz, CDCl3): δ 136.1, 134.5, 129.2, 127.0.41 (s,
3H), 0.40 (s, 3H). 13C NMR (68 MHz, CDCl3): δ 136.3,
134.3, 129.1, 127.4, 107.2, 87.1, 70.6, 64.7, 27.1, 20.8,
19.5, –4.6, –5.0. HRMS calcd for C16H26O3Si (M+)
294.1651, found 294.1655.
3-Methyl-1-phenylbutane-1,2,3-triol (9a, 10a).
Compound 9a: IR (neat) 3367, 3018, 2931, 2859,
1
1495, 1454, 1379, 1197, 1056, 1011 cm−1. H NMR
(500 MHz, CDCl3): δ 7.35–7.24 (m, 5H), 4.71 (d,
J = 5.9 Hz, 1H), 3.65 (dq, J = 6.5 Hz, 2.7 Hz, 1H),
3.40 (dd, J = 5.9 Hz, 2.7 Hz, 1H), 1.14 (d, J =
6.2 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ
140.5, 128.5, 127.3, 126.1, 76.9, 75.5, 71.5, 22.6.
HRMS calcd for C11H16O3Si (M+) 196.1099, found
196.1101.
2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
ylphenyltrimethylsilylmethanol
(7d). IR
(neat)
3539, 3032, 2977, 1590, 1483, 1445, 1371, 1246,
1
1069, 1026, 843 cm−1. H NMR (270 MHz, CDCl3):
Compound 10a: IR (neat) 3362, 3021, 2933,
δ 7.53–7.25 (m, 10H), 4.63 (d, J = 8.4 Hz, 1H), 4.39
(d, J = 8.4 Hz, 1H), 1.55 (s, 3H), 1.52 (s, 3H), 0.06
(s, 9H). 13C NMR (68 MHz, CDCl3): δ 143.5, 141.1,
138.1, 128.7, 128.6, 128.4, 127.7, 127.2, 127.1, 127.0,
125.7, 124.8, 108.2, 87.4, 78.6, 71.3, 27.3, 27.0, –3.3.
HRMS calcd for C21H28O3Si (M+) 356.1808, found
356.1811.
1
2860, 1458, 1380, 1196, 1055 cm−1. H NMR (270
MHz, CDCl3): δ 7.33–7.16 (m, 5H), 4.96 (d, J =
3.2 Hz, 1H), 3.93 (m, 1H), 3.66 (m, 1H), 1.20 (d, J =
6.1 Hz, 3H). 13C NMR (68 MHz, CDCl3): δ
140.9, 128.6, 127.8, 126.2, 76.9, 73.9, 73.3, 22.7.
HRMS calcd for C11H16O3Si (M+) 196.1099, found
196.1097.
General Procedure for the Nucleophilic Reaction
to α,β-Unsaturated Acylsilane 1a
Deprotection of Silyl Alcohol Derivatives 7a and
8a
To a solution of acylsilane 1a (0.5 mmol) in THF
(10 mL), a solution of a nucleophilic reagent was
added slowly. After stirring for 1 h, methanol (1 mL)
was added and the reaction mixture was allowed to
warm to ambient temperature and then poured into
brine. The aqueous layer was extracted with diethyl
ether for three times. The combined organic layer
was then washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography on a silica gel
10:1 hexane–ethyl acetate as the eluent to give silyl
alcohol derivative 11a in 51–99% yields or β-silyl
ketone derivative 12a in 62% yield as pale yellow oil.
To a stirred solution of trimethylsilylethanol 7a or
8a (147 mg, 0.5 mmol) in methanol (16 mL), an
aqueous solution of HCl (1.0 M, 2.5 mL) was added
slowly. The resulting mixture was heated to reflux.
Acetone and methanol were slowly distilled. Addi-
tional methanol (2 mL) and an aqueous solution
of HCl (0.5 M, 1.1 mL) were added, and the mix-
ture was stirred at room temperature for 5 h. The
mixture was diluted with saturated sodium bicar-
bonate solution and extracted with ether for three
times. The organic layer was then washed with brine
for three times, dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified by
column chromatography on a silica gel 2:1 hexane–
ethyl acetate as the eluent to give silyl substituted
triol derivatives 4a or 5a in 71–77% yields as pale
yellow oil.
4-Phenyl-2-trimethylsilyl-3-buten-1-ol (11a). IR
(neat) 3443, 3026, 2957, 2899, 1599, 1493, 1448,
1248, 1059 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.38–
7.19 (m, 5H), 6.41 (d, J = 16.2 Hz, 1H), 6.37 (d,
Heteroatom Chemistry DOI 10.1002/hc

Stereoselective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated Acylsilanes 575
J = 16.2 Hz, 1H), 1.40 (s, 3H), 0.08 (s, 9H). 13C NMR
for three times. The combined organic layers were
washed with saturated sodium bicarbonate solu-
tion and brine, dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified
by column chromatography on a silica gel using
10:1 hexane–ethyl acetate as the eluent to give 3–
hydroxy-2-silylpropan-1-one derivatives 13 in quan-
titative yield as pale yellow oil.
(100 MHz, CDCl3): δ 137.5, 136.6, 128.4, 126.7, 126.0,
125.0, 69.0, 24.8, –4.4. HRMS calcd for C13H20OSi
(M+) 220.1283, found 220.1281.
4-Phenyl-2-dimethylphenylsilyl-2-propen-1-ol
(11b),
4-Phenyl-2-triisopropylsilyl-3-buten-1-ol
(11c), and 1,3-diphenyl-1-trimethylsilyl-3-buten-1-
ol (11d) were synthesized in a manner similar to
those for 11a described above, in the yield of 81, 84,
and 74%, respectively, as pale yellow oil.
3-Hydroxy-4-phenyl-3-trimethylsilylbutan-2-one
(13a). IR (neat) 3429, 3030, 2957, 2899, 1692,
Compound 11b: IR (neat) 3439, 3025, 2961,
1
1454, 1420, 1252, 1057 cm−1. H NMR (270 MHz,
1
1599, 1577, 1492, 1448, 1248, 1115 cm−1. H NMR
CDCl3): δ 7.32–7.19 (m, 5H), 4.96 (d, J = 5.7 Hz, 1H),
3.04 (d, J = 5.7 Hz, 1H), 1.99 (s, 3H), 0.03 (s, 9H).
13C NMR (68 MHz, CDCl3): δ 212.4, 144.1, 128.4,
127.3, 125.7, 73.7, 56.5, 31.4, –1.7. HRMS calcd for
C13H20O2Si (M+) 236.1233, found 236.1234.
(400 MHz, CDCl3): δ 7.59–7.19 (m, 10H), 6.36 (d, J =
16.0 Hz, 1H), 6.31 (d, J = 16.0 Hz, 1H), 1.36 (s, 3H),
0.38 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 137.2,
135.9, 135.5, 134.2, 129.4, 128.2, 127.4, 126.5, 125.8,
125.1, 68.9, 24.8, –6.1. HRMS calcd for C18H22OSi
(M+) 282.1440, found 282.1442.
3-Hydroxy-4-phenyl-3-dimethylphenylsilylbutan-
Compound 11c: IR (neat) 3450, 3026, 2945,
1
2866, 1600, 1493, 1448, 1252, 1115 cm−1. H NMR
2-one (13b). IR (neat) 3379, 3048, 2900, 1669,
1
1611, 1577, 1495, 1450, 1256, 1119, 1058 cm−1. H
(400 MHz, CDCl3): δ 7.37–7.16 (m, 5H), 6.48 (d,
J = 15.8 Hz, 1H), 6.44 (d, J = 15.8 Hz, 1H), 1.50
(s, 3H), 1.37–1.05 (m, 21H). 13C NMR (100 MHz,
CDCl3): δ 138.9, 137.6, 128.5, 126.7, 126.0, 123.7,
71.8, 28.3, 19.2, 11.0. HRMS calcd for C19H32OSi
(M+) 304.2222, found 304.2225.
NMR (270 MHz, CDCl3): δ 7.54–7.20 (m, 10H), 4.96
(brs, 1H), 4.23 (brd, 1H), 3.23 (d, J = 4.6 Hz, 1H),
1.72 (s, 3H), 0.45 (s, 3H), 0.40 (s, 9H). 13C NMR (68
MHz, CDCl3): δ 197.5, 142.6, 132.1, 129.6, 128.4,
127.8, 127.4, 127.2, 126.2, 72.9, 55.5, 26.5, 0.0.
HRMS calcd for C18H22O2Si (M+) 298.1389, found
298.1392.
Compound 11d: IR (neat) 3433, 3028, 2959,
1
1599, 1578, 1493, 1248, 1067 cm−1. H NMR (400
MHz, CDCl3): δ 7.51–7.13 (m, 10H), 6.93 (d, J =
15.6 Hz, 1H), 6.60 (d, J = 15.6 Hz, 1H), 0.01 (s, 9H).
13C NMR (100 MHz, CDCl3): δ 145.2, 137.6, 134.3,
128.5, 128.4, 128.3, 127.0, 126.6, 125.9, 124.2, 75.0,
–4.1. HRMS calcd for C18H22OSi (M+) 282.1440,
found 282.1443.
3-Hydroxy-4-phenyl-3-triisopropylsilylbutan-2-
one (13c). IR (neat) 3447, 3026, 2945 2868, 1670,
1
1601, 1582, 1493, 1450, 1234, 1163, 1057 cm−1. H
NMR (270 MHz, CDCl3): δ 7.38–7.17 (m, 5H), 5.29
(d, J = 10.5 Hz, 1H), 4.97 (d, J = 10.5 Hz, 1H), 3.24
(s, 1H), 1.92 (s, 3H), 1.41–1.34 (m, 3H), 1.25–1.13
(m, 18H). 13C NMR (68 MHz, CDCl3): δ 215.0, 145.5,
128.1, 126.7, 124.8, 72.4, 50.6, 34.1, 18.7, 11.9.
HRMS calcd for C19H32O2Si (M+) 320.2172, found
320.2170.
4-Phenyl-4-trimethylsilylbutan-2-one (12a). IR
(neat) 3024, 2955, 2897, 1717, 1601, 1578, 1495,
1450, 1248, 1115 cm−1. 1H NMR (400 MHz, CDCl3):
δ 7.26–7.00 (m, 5H), 2.97–2.91 (m, 1H), 2.74–2.62
(m, 2H), 2.03 (s, 3H), 0.06 (s, 9H). 13C NMR (100
MHz, CDCl3): δ 208.0, 142.5, 128.1, 127.2, 124.6,
43.8, 31.5, 29.7, –3.2. HRMS calcd for C13H20OSi
(M+) 220.1283, found 220.1287.
3-Hydroxy-1,3-diphenyl-2-trimethylsilylpropan-2-
one (13d). IR (neat) 3452, 3029, 2947, 2901, 1689,
1
1491, 1450, 1257, 1056 cm−1. H NMR (270 MHz,
CDCl3): δ 7.77–7.19 (m, 10H), 5.21 (d, J = 4.6 Hz,
1H), 3.94 (d, J = 4.6 Hz, 1H), 0.01 (s, 9H). 13C
NMR (68 MHz, CDCl3): δ 205.2, 144.8, 138.9, 132.7,
128.6, 128.1, 127.6, 126.0, 125.6, 74.1, 50.4, –1.5.
HRMS calcd for C18H22O2Si (M+) 298.1389, found
298.1392.
General Procedure for the Reaction of Silyl
Alcohols 11 with m-CPBA
To
a solution of silyl alcohol (1 mmol) in
dichloromethane (15 mL) at room temperature, m-
CPBA (336 mg, 1.5 mmol) was added. After com-
pletion of the reaction evidenced by GC (usually af-
ter being stirred for 1.5–24 h), a saturated sodium
hydrogen carbonate solution was added, and then
the aqueous layer was extracted with diethyl ether
General Procedure for the Oxidation of Silyl
Alcohol 11a
Method for using OxoneꢀR as an oxidant. To a so-
lution of silyl alcohol 11a (220 mg, 1 mmol) in ethyl
Heteroatom Chemistry DOI 10.1002/hc

576 Honda et al.
acetate (5 mL) at room temperature, a sodium bicar-
bonate solution (420 mg, 5 mmol, 5 mL) was added.
Then an aqueous oxone solution (oxone 923 mg,
1.5 mmol, 6.4 mL) and acetone (732 μL, 10 mmol)
were added. After stirring for 1 h, the reaction mix-
ture was separated and then the aqueous layer was
extracted with diethyl ether for three times. The
combined organic layer was then washed with brine,
dried over anhydrous Na2SO4, and concentrated in
vacuo. The residue was purified by column chro-
matography on a silica gel 10:1 hexane–ethyl acetate
as the eluent to give hydroxysilylpropanone deriva-
tive 13a in quantitative yield.
Method for Using Sodium Peroxide as an Oxidant.
To a solution of silyl alcohol 11a (220 mg, 1 mmol)
in ethanol (10 mL) at room temperature, sodium
peroxide (312 mg, 4 mmol) was added. After stirring
at 45°C for 40 min, the reaction mixture was allowed
to cool to 35°C and stirred for 1 h. Then 0.01 M
hydrochloric acid solution was added at ambience
temperature, the reaction mixture was separated and
then the aqueous layer was extracted with diethyl
ether for three times. The combined organic layer
was then washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was
purified by column chromatography on a silica gel
10:1 hexane–ethyl acetate as the eluent to give 4-
phenylbutan-2-one 16a in 89% yield as pale yellow
oil.
Method for Using Hydrogen Peroxide as an Ox-
idant. To a solution of silyl alcohol 11a (220 mg,
1 mmol) in methanol (10 mL) at room temper-
ature, acetonitrile (165 mg, 4 mmol), 30% hy-
drogen peroxide (456 mg, 4 mmol), and phos-
phate buffer (8.7 mmol KH2PO4 and 30.4 mmol
Na2HPO4/kg·H2O, 250 μL) were added. After stir-
ring for 24 h, the reaction mixture was added brine
and then extracted with diethyl ether for three times.
The combined organic layer was then washed with
brine, dried over anhydrous Na2SO4, and concen-
trated in vacuo. The residue was purified by column
chromatography on a silica gel 10:1 hexane–ethyl ac-
etate as the eluent to give β-hydroxy ketone deriva-
tive 14a in 56% yield as pale yellow oil.
REFERENCES
[1] For recent reviews on synthesis and reaction of
acylsilanes, see (a) Brook, M. A. Silicon in Or-
ganic, Organometallic, and Polymer Chemistry; Wi-
ley: New York, 2000; (b) Page, P. C. B.; McKen-
zie, M. J. Product Subclass 25: Acylsilanes. In Sci-
ence of Synthesis; Fleming, I., Ed.; Thieme: Stuttgart,
Germany, 2001; Vol. 4, pp. 513–568; (c) Bonini, B.
F.; Comes-Franchini, M.; Fochi, M.; Mazzanti, G.;
Ricci, A. J Organomet Chem 1998, 567, 181–189;
(d) Qi, H.; Curran, D. P. In Acyl Silicon, Germa-
nium, or Boron Functions. Comprehensive Organic
Functional Group Transformations: Synthesis: Car-
bon with Two Attached Heteroatoms with at Least
One Carbon-to-Heteroatom Multiple Link, Katrizky,
A. R., Meth-Cohn, O., Rees, C. W., Moody, C. J.,
(Eds.); Pergamon: Oxford, UK, 1995; Vol. 5, pp. 409–
433, Ch. 5.09; (e) Cirillo, P. F.; Panek, J. S. Org Prep
Proced Int 1992, 24, 553–582.
[2] (a) Page, P. C. B.; McKenzie, M. J.; Klair, S. S.;
Rosenthal, S. In The Chemistry of Organic Silicon
Compounds; Rappoport, Z., Apeloig, Y., (Eds.); Wi-
ley: New York, 1998; Vol. 2, pp. 1599–1665, Ch. 27;
(b) Tsubouchi, A.; Sasaki, N.; Enatsu, S.; Takeda, T.
Tetrahedron Lett 2013, 54, 1264–1267; (c) Sasaki,
M.; Oyamada, K.; Takeda, K. J Org Chem 2010, 75,
3941–3943; (d) Takeda, K. Yakugaku Zasshi 2007,
127, 1399–1418; (e) Takeda, K.; Nakatani, J.; Naka-
mura, H.; Sako, K.; Yoshii, E.; Yamaguchi, K. Synlett
1993, 841–843; (f) Takeda, K.; Fujisawa, M.; Makino,
T.; Yoshii, E. J Am Chem Soc 1993, 115, 9351–9352.
[3] (a) Honda, M.; Mikami, Y.; Sanjyo, T.; Segi, M.; Naka-
jima, T. Chem Lett 2005, 34, 1432–1433; (b) Honda,
M.; Ohkura, N.; Saisyo, S.-I.; Segi, M.; Nakajima,
T. Tetrahedron 2003, 59, 8203–8212; (c) Honda, M.;
Nakajima, T.; Okada, M.; Ymaguchi, K.; Suda, M.;
Kunimoto, K.-K.; Segi, M. Tetrahedron Lett 2011, 52,
3740–3742; (d) Honda, M. and Segi, M. J Synth Org
Chem Jpn 2010, 68, 601–613; (e) Honda, M.; Mita,
T.; Nishizawa, T.; Sano, T.; Segi, M. and Nakajima,
T. TetrahedronLett 2006, 47, 5751–5754; (f) Honda,
M.; Naitou, T.; Hoshino, H.; Takagi, S.; Segi, M. and
Nakajima, T. Tetrahedron Lett 2005, 46, 7345–7348;
(g) Honda, M.; Yamamoto, Y.; Tsuchida, H.; Segi,
Method for Sharpless–Katsuki Asymmetric Epox-
idation Reagents as an Oxidant. To a solution of ti-
tanium isopropoxide (355μL, 1.2 mmol) at -–18°C,
diethyl-L-tartarate (248 mg, 1.2 mmol) was added.
After stirring for 5 min, the reaction mixture was
added silyl alcohol 11a (220 mg, 1 mmol) and tert-
butyl hydroperoxide(219 μL, 1.2 mmol) and then
stirred at ambience temperature for 1 h. Then 10%
tartaric acid solution was added and stirred for
30 min. The reaction mixture was separated, and
then the aqueous layer was extracted with diethyl
ether for three times. The combined organic layer
was then washed with brine, and concentrated in
vacuo. The residue was added diethyl ether (10 mL)
and 1 N sodium hydroxide solution at 0°C. After
stirring for 30 min, a saturated ammonium chlo-
ride solution was added, and then the aqueous layer
was extracted with diethyl ether for three times. The
combined organic layer was then washed with brine,
dried over anhydrous Na2SO4, and concentrated in
vacuo. The residue was purified by column chro-
matography on a silica gel 10:1 hexane–ethyl acetate
as the eluent to give the mixture of 13a, 14a, and
4-phenyl-3-buten-2-one 15a (13:26:61) in 66% yield
as pale yellow oil.
Heteroatom Chemistry DOI 10.1002/hc

Stereoselective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated Acylsilanes 577
M.; Nakajima, T. Tetrahedron Lett 2005, 46, 6465–
[11] Huber, P.; Bratovanov, S.; Bienz, S.; Syldatk, C.;
Pietzsch, M. Tetrahedron: Asymmetry 1996, 7, 69–
78.
[12] Mash, E. A.; Nelson, K. A.; Deusen, S. V.; Hemperly,
S. B. Org Synth Coll, Vol. VIII, 1993, 155–
161.
[13] (a) Enda, J.; Kuwajima, I. J Am Chem Soc 1985, 107,
5495–5501; (b) Kato, M.; Mori, A.; Oshino, H.; Enda,
J.; Kobayashi, K.; Kuwajima, I. J Am Chem Soc 1984,
106, 1773–1778; (c) Bonini, B. F.; Comes-Franchini,
M.; Fochi, M.; Mazzanti, G.; Ricci, A.; Varchi, G. Syn-
lett 2000, 1688–1690.
[14] Imamoto, T.; Suguira, Y.; Takiyama, N. Tetrahedron
Lett 1984, 25, 4233–4236.
[15] For review on directed epoxidation of allylic alcohols,
see Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem Rev
1993, 93, 1307–1370.
[16] Fa¨ssler, J.; Enev, V.; Bienz, S. Helv Chim Acta 1999,
82, 561–587.
[17] For reviews on Sharpless-Katsuki asymmetric epox-
idation, see (a) Johnson, R. A.; Sharpless, K. B.
In Comprehensive Organic Synthesis, Trost, B. M.;
Fleming, I., (Eds.); Pergamon Press: New York, 1991;
Vol. 7, pp. 389–436; (b) Johnson, R. A.; Sharpless,
K. B. In Catalytic Asymmetric Synthesis, Ojima, I.,
(Ed.); VCH: New York, 1993; pp. 103–158; (c) Kat-
suki, T.; Martin, V. S. Org React 1996, 48, 1–300.
[18] For report on epoxidation of olefins using oxone, see
Hashimoto, N.; Kanda, A. Org Proc Res Dev 2002, 6,
405–406.
6468; (h) Honda, M.; Iwamoto, R.; Nogami, Y.; Segi,
M. Chem Lett 2005, 3x4, 466–467; (i) Honda, M.;
Oguchi, W.; Segi, M.; Nakajima, T. Tetrahedron 2002,
58, 6815–6823.
[4] For reports on protodesilylation of α-silylalcohols
with complete retention of the configuration, see (a)
Nakada, M.; Urano, Y.; Kobayashi, S.; Ohno, M. J
Am Chem Soc 1988, 110, 4826–4827; (b) Nakada, M.;
Urano, Y.; Kobayashi, S.; Ohno, M. Tetrahedron Lett
1994, 35, 741–744.
[5] For recent examples of synthesis of 1,2,3-triol deriva-
tives, but they are not stereocontrolled synthesis, see
(a) Mukerjee, P.; Abid, M.; Schroeder, F. C. Org Lett
2010, 12, 3986–3989; (b) Alp, C.; Atmaca, U.; C¸ elik,
M.; Gu¨ltekin, M. S. Synlett 2009, 2765–2768; (c) Dun-
lap, N. K.; Drake, J.; Ward, A.; Salyard, T. L. J.; Mar-
tin, L. J Org Chem 2007, 73, 2928–2930; (d) Fujino,
A.; Asano, M.; Yamaguchi, H.; Shirasaka, N.; Sakoda,
A.; Ikunaka, M.; Obata, R.; Nishiyama, S.; Sugai, T.
Tetrahedron Lett 2007, 48, 979–983.
[6] (a) Honda, M.; Oguchi, W.; Segi, M.; Nakajima, T.
Tetrahedron 2002, 58, 6815–6823; (b) Sato, T.; Arai,
M.; Kuwajima, I. J Am Chem Soc 1977, 99, 5827–
5828.
[7] For reviews on osmylation reaction, see (a) Franc¸ais,
A.; Bedel, O.; Haudrechy, A. Tetrahedron 2008, 64,
2495–2524; (b) Donohoe, T. J. Oxidation and Reduc-
tion in Organic Synthesis; Oxford University Press:
New York, 2000.
[8] Valente, V. R.; Wolfhagen, J. L. J Org Chem 1966, 31,
2509–2512.
[9] Daignault, R. A.; Eliel, E. L. Org Synth Coll. Vol. V,
1973, 303–305.
[10] Fujisawa, T.; Ukaji, Y.; Funabora, M.; Yamashita, M.;
Sato, T. Bull Chem Soc Jpn 1990, 63, 1894–1897.
[19] For report on epoxidation with H2O2 in buffer, see
Ogata, Y.; Sawaki, Y. Tetrahedron 1964, 20, 2065–
2068.
[20] Yamashita, M.; Reddy, K. V.; Rao, L. N.; Haritha, B.;
Maeda, M.; Suzuki, K.; Totsuka, H.; Takahashi, M.;
Oshikawa, T. Tetrahedron Lett 2003, 44, 2339–2341.
Heteroatom Chemistry DOI 10.1002/hc