Diastereoselective alkylation and reduction of β-alkoxyacylsilanes: Stereoselective construction of three contiguous stereogenic centers

Article abstract of DOI:10.1016/j.tet.2003.08.050

The nucleophilic addition reaction to acylsilanes, having stereogenic centers at the α and β positions, derived from the aldol reaction of dimethyl acetals and acylsilane silyl enol ethers gives the corresponding α-silylalcohols in high yields with excellent diastereoselectivity. The protiodesilylation of α-silylalcohols proceeds with complete retention of the configuration. In addition, the reduction of acylsilanes having stereogenic centers at the α and β positions affords the corresponding α-silylalcohols in good yields with high diastereoselectivity similarly to the nucleophilic addition. And the treatment of acylsilanes having a phenyl group on silicon atom with fluoride ion results in the formation of phenyl carbinol derivatives via migration of the phenyl group with high diastereoselectivity.

Full text of DOI:10.1016/j.tet.2003.08.050

Tetrahedron 59 (2003) 8203–8212
Diastereoselective alkylation and reduction of
b-alkoxyacylsilanes: stereoselective construction of three
contiguous stereogenic centers
*
Mitsunori Honda, Naoto Ohkura, Shin-ichi Saisyo, Masahito Segi and Tadashi Nakajima
Department of Chemistry and Chemical Engineering, Faculty of Engineering, Kanazawa University, 2-40-20 Kodatsuno,
Kanazawa 920-8667, Japan
Received 12 June 2003; accepted 19 August 2003
Abstract—The nucleophilic addition reaction to acylsilanes, having stereogenic centers at the a and b positions, derived from the aldol
reaction of dimethyl acetals and acylsilane silyl enol ethers gives the corresponding a-silylalcohols in high yields with excellent
diastereoselectivity. The protiodesilylation of a-silylalcohols proceeds with complete retention of the configuration. In addition, the
reduction of acylsilanes having stereogenic centers at the a and b positions affords the corresponding a-silylalcohols in good yields with high
diastereoselectivity similarly to the nucleophilic addition. And the treatment of acylsilanes having a phenyl group on silicon atom with
fluoride ion results in the formation of phenyl carbinol derivatives via migration of the phenyl group with high diastereoselectivity.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
above obtained acylsilanes with nucleophiles. The purpose
of this paper is to report the results of our experiments on the
nucleophilic addition reaction to the carbonyl group of the
acylsilanes having stereogenic centers at the a and b
positions and the subsequent protiodesilylation of the
resulting silylcarbinols8 to lead to the construction of
three contiguous stereogenic centers.
Acylsilanes are an useful class of compounds in organic
synthesis,1,2 and several procedures using acylsilanes have
been developed for the asymmetric synthesis.2,3 In particu-
lar, the important utility of acylsilanes is their ability to
function as aldehyde equivalents in stereoselective nucleo-
philic addition reactions.4,5 For these reasons, the stereo-
controlled nucleophilic addition to a- or b-chiral acylsilanes
has been studied.4–6 The works of Ohno4a,b and Panek4c
et al. on the reaction of a- or b-chiral acylsilanes with
nucleophiles demonstrate the synthetic potential of 1,2- or
1,3-asymmetric induction in chiral acylsilanes. The stereo-
chemistry of these reactions is respectively explained by
open-chain pathway (Felkin-Anh-type) or Cram-type
chelation model.
Furthermore, the reduction9,10 and the protiodesilyla-
tion11–13 of acylsilanes having stereogenic centers at the
a and b positions are also described in this article. The
reduction of simple acylsilanes (e.g. acetylsilane and
benzoylsilane) has already been published,10 however, no
other detailed study has been reported on the reduction of
acylsilanes having stereogenic centers at the a and b
positions. On the other hand, only a few reports have been
published for the protiodesilylation of acylsilanes having
stereogenic centers at the a and b positions.12
On the other hand, we recently found that TiCl4 mediated
aldol reaction of silyl enol ethers of simple acylsilanes with
acetals gives the corresponding b-alkoxyacylsilanes which
have two stereogenic centers at the a and b positions with
high diastereoselectivity.7 The stereoselectivity of the
nucleophilic addition to acylsilanes having two stereogenic
centers at the a and b positions has not been clarified. Thus,
our interest focused on efficient and stereoselective
formation of multiple stereogenic centers via reaction of
2. Results and discussion
2.1. Preparation of acylsilanes 1–4
Acylsilanes having stereogenic centers at the a and b
positions 1–4 were employed in this study. a-Substituted-
b-methoxyacylsilanes 1 and 2 were prepared by the aldol
reaction of acylsilane silyl enol ethers with simple acetals in
the presence of TiCl4.7,14 Aldol adducts containing three
contiguous stereogenic centers 3 and 4 were obtained by
Keywords: addition reactions; aldols; diastereoselection; reduction, silicon
and compounds.
*
Corresponding author. Tel.: þ81-76-234-4789; fax: þ81-76-234-4800;
e-mail: honda@t.kanazawa-u.ac.jp
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.050

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M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
condensation of acylsilane silyl enol ethers with 2-phenyl-
propionaldehyde dimethyl acetal15 in the presence of TiCl4
(Scheme 1). In this reaction, it has been reported that the
aldol adducts 3 and 4 are formed with complete Cram-type
(3,4-syn) selectivity.7
positions of starting acylsilanes and of the kind of
organometallic reagents.
The reaction of 1 or 2 having an aliphatic group at the a
position with several nucleophiles was carried out under
similar conditions as above. The results are shown in
Table 2. In all cases, the corresponding diastereomeric
mixture of 3-methoxysilylalcohols 5–8 was obtained in
good yields with preference of 1,2-syn isomer 5 or 7. It was
found that the reaction of 1 with alkyllithium reagents
(entries 1 and 3) exhibited higher diastereoselectivity than
that of 2 (entries 2 and 6). The stereoselectivity increased
with the bulkiness of the a-substituent of 1 or 2. The
reaction with Grignard reagent resulted in the selective
formation of 1,2-syn isomer (entries 4 and 8).
Table 2. Substituent effect of b-methoxyacylsilanes 1 and 2 in nucleophilic
addition
Scheme 1. Synthesis of b-methoxyacylsilane having stereogenic centers at
the a and b positions.
The pure 2,3-anti and 2,3-syn isomers as a starting
acylsilane are required to study the stereoselectivity of
nucleophilic addition reaction or reduction, but the products
obtained under the above conditions were a mixture of the
2,3-anti and 2,3-syn isomers in most cases. These
diastereomers were separated completely by column
chromatography on silica gel and then used.
Entry Substrate
R1
RM
Product Yield 1,2-syn/1,2-antib
(%)a
1
2
3
4
5
6
7
8
1b
2b
1c
1c
2c
2c
2d
2d
Chxc MeLi
Chxc MeLi
i-Pr
i-Pr
i-Pr
i-Pr
Et
5j, 6j
7j, 8j
5k, 6k
99
97
98
79
85
99
84
77
98/2
74/26
88/12
.99/1
76/24
77/23
67/33
96/4
BuLi
MeMgBr 5l, 6l
MeLi
BuLi
MeLi
2.2. Nucleophilic addition reaction to
b-methoxyacylsilanes
7l, 8l
7k, 8k
7m, 8m
Acylsilanes 1a and 2a, derived from benzaldehyde dimethyl
acetal and silyl enol ether of benzyl silyl ketone, were
treated with organolithium reagents or methylmagnesium
bromide at 2788C in THF. The results are summarized in
Table 1. In all cases, the reaction proceeded smoothly to
afford the corresponding 1,2-syn-3-methoxysilylalcohols 5
and 7 (syn refers to the relationship between the phenyl
group at b position and the hydroxy group on the zig zag
main chain containing the silyl group) having the three
contiguous stereogenic centers in high yields with excellent
diastereoselectivity. This 1,2-syn stereoselectivity was
independent of the relative configuration at the 2 and 3
Et
MeMgBr 7m, 8m
Molar ratio; 1 or 2/RLi¼1:2, 1 or 2/MeMgBr¼1:4.
a
Isolated yield.
Determined by H NMR analysis.
Chx¼Cyclohexyl.
b
c
1
In order to examine the construction of the four contiguous
stereogenic centers, b-methoxyacylsilanes 3 and 4 were also
used as the substrate. The reaction with methyllithium
proceeded smoothly to afford the corresponding 3-methoxy-
silylalcohols 9–12 in high yields (Scheme 2). As men-
tioned above, high 1,2-syn selectivity was observed in the
reaction using acylsilanes 3a and 4a having a phenyl group
at the a position, independent of the stereochemistry in C-2,
C-3 and C-4 of the starting acylsilanes. However, the
Table 1. Nucleophilic addition of organometallic reagents to b-methoxy-
acylsilanes 1 and 2
Entry Substrate
RM
Product Yield (%)a 1,2-syn/1,2-antib
1
2
3
4
5
6
1a
2a
2a
2a
2a
2a
MeLi
MeLi
5f, 6f
7f, 8f
MeMgBr 7f, 8f
99
95
59
99
97
74
.99/1
.99/1
.99/1
.99/1
.99/1
.99/1
BuLi
s-BuLi
PhLi
7g, 8g
7h, 8h
7i, 8i
Molar ratio; 1a or 2a/RLi¼1:2, 1a or 2a/MeMgBr¼1:4.
a
Isolated yield.
Scheme 2. Nucleophilic addition of methyllithium to b-methoxyacylsi-
lanes 3 and 4.
Determined by 1H NMR analysis.
b

M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
Table 4. Reduction of 2,3-syn-3-methoxyacylsilanes 1 with LiAlH4
8205
diastereoselectivity in the reaction of 3b or 3c having an
aliphatic group at the a position was decreased.
2.3. Reduction of b-methoxyacylsilanes
The hydride reduction of 2a with various reducing agents
was carried out. In this study, lithium aluminum hydride,
sodium borohydride, diisobutylaluminum hydride and
borane were employed as reducing agents. The results are
summarized in Table 3. Using lithium aluminum hydride as
a reducing agent, the reaction proceeded smoothly to afford
the corresponding two diastereomers of 3-methoxysilylal-
cohols 13a and 14a in quantitative yields with preference of
13a. The diastereoselectivity in the reaction was increased
with lowering the reaction temperature (entries 1–3). The
reduction using sodium borohydride also gave the silylal-
cohols in excellent yields at 08C (entry 5), but the
stereoselectivity was low. In the reaction at 2788C (entry
4), the stereoselectivity was improved, but the product was
obtained in low yield. The reduction using diisobutylalu-
minum hydride gave high yield, but the stereoselectivity
was relatively low (entries 6 and 7). The reaction using
borane as a reducing agent gave low yield and poor
diastereoselectivity (entries 8 and 9). Since the mechanism
of reaction with diisobutylaluminum hydride or borane is
different from that of reaction with lithium aluminum
hydride or sodium borohydride, the decrease in the
diastereoselectivity was observed.16 Among the reducing
agents examined, best results were obtained by using
lithium aluminum hydride at low temperature, and hence
all of the following reductions were carried out using
lithium aluminum hydride in THF at 2788C for 0.5 h.
Entry
Substrate
R1
R2
Product
Yield (%)a
15/16b
1
2
3
4
1a
1b
1d
1e
Ph
Ph
Ph
Ph
i-Pr
15a, 16a
15b, 16b
15d, 16d
15e, 16e
89
98
96
99
.99/1
93/7
91/9
Chxc
Et
Ph
.99/1
Molar ratio; 1/LiAlH4¼1:0.5.
a
Isolated yield of a mixture of 15 and 16.
Determined by 1H NMR analysis.
Chx¼Cyclohexyl.
b
c
Table 5. Reduction of 2,3-anti-3-methoxyacylsilanes 2 with LiAlH4
Entry
Substrate
R1
R2
Product
Yield (%)a
13/14b
1
2
3
4
2a
2b
2d
2e
Ph
Ph
Ph
Ph
i-Pr
13a, 14a
13b, 14b
13d, 14d
13e, 14e
99
98
96
96
96/4
Chxc
Et
77/23
45/55
92/8
Ph
Molar ratio; 2/LiAlH4¼1:0.5.
a
Isolated yield of a mixture of 13 and 14.
Determined by 1H NMR analysis.
Chx¼Cyclohexyl.
b
c
Table 3. Reaction of b-methoxyacylsilane 2a with various reducing agents
diastereoselectivity of the reduction was influenced by the
stereochemistry of the starting acylsilanes and the bulkiness
of a-substituent (R1). In the reaction of 1, high stereo-
selectivity was observed in most cases independent of the
bulkiness of R1 (Table 4). On the other hand, high
diastereoselectivity was observed when acylsilanes 2 having
a phenyl group at the a position were employed (Table 5,
entries 1 and 4), while lower selectivity was observed when
the a-substituent was a cyclohexyl or an ethyl group (entries
2 and 3). In other words, the stereoselectivity in the reaction
of 2 increased with increasing the bulkiness of R1.
Entry
M–H
Solvent Temperature.(8C)
Product
Yield (%)a 13a/14ab
1
2
3
LiAlH4
NaBH4
THF
278
rt
Reflux
99
99
99
96/4
76/24
71/29
2.4. Mechanistic considerations
4
5
MeOH
278
0
13
99
89/11
81/19
In general, the stereoselection of reduction of carbonyl
compounds having a b-methoxy group is understood by
assuming the Cram-chelate model.17 Thus, the following
mechanism for the reduction of 1 or 2 is proposed
(Scheme 3). First, the metal ion coordinates to two oxygen
atoms of carbonyl group and methoxy group to give
chelation models A (from 1) and B (from 2). The illustrated
two models are favorable as the steric interaction between a
bulky silyl group and R1. In the reaction of 1, the attack of
hydride occurs from the less-hindered site in A, giving the
1,2-syn products 15. On the other hand, the stereochemical
outcome for the hydride reduction of 2 depended on the
bulkiness of R1 (Table 5). That is, when R1 is a bulky group
in chelating model B, the attack of hydride occurs
preferentially from the opposite side of the R1 to avoid the
steric repulsion between incoming hydride and R1 leading to
6
7
DIBAL-H Toluene 278
Reflux
91
99
61/39
84/16
8
9
BH3
THF
rt
Reflux
13
40
53/47
64/36
a
Isolated yield of a mixture of 13 and 14.
Determined by 1H NMR analysis.
b
The reduction of b-methoxyacylsilanes 1 and 2 having
various substituent groups at the a and b positions using
lithium aluminum hydride was carried out. The results of the
reaction using 1 and 2 are, respectively, summarized in
Tables 4 and 5. In all cases, the corresponding diastereo-
meric mixtures of 3-methoxysilylalcohols 13–16 were
obtained quantitatively. In analogy with the reaction of 1
or 2 with organometallic reagents (Tables 1 and 2), the

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M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
2.6. Treatment of b-methoxyacylsilanes with
tetrabutylammonium fluoride (TBAF)
It has been reported that the treatment of acylsilane having
one or more phenyl groups on silicon atom with base such as
alkoxide or fluoride ion gives phenyl carbinol derivative via
migration of a phenyl group.12,13 The aldol adducts 20
having a dimethylphenylsilyl group were prepared, and then
the reaction with TBAF in THF was examined. The reaction
proceeded smoothly at room temperature to afford the
corresponding phenyl carbinols 19 having the three
contiguous stereogenic centers with excellent 1,2-anti
selectivity. The results are summarized in Table 6. When
the a-substituent of 20 was an aliphatic group, the reaction
with TBAF afforded the products 19 in good yields
regardless of amounts of TBAF or reaction temperature
(entries1–4). Indeed, the reaction proceeded efficiently for
1 h even at 2308C with 0.2 equiv. of TBAF (entry 3).
However, in the reaction of 20 having a phenyl group as the
a-substituent, the yield was lowered and stilbene was
formed as the byproduct (entry 5).
Scheme 3.
the 1,2-syn products 13. On the other hand, when R1 is a
small group such as ethyl group, due to the steric repulsion
between R2 at C-3 and incoming hydride, the attack of
hydride from the same side of R1 to lead to the 1,2-anti
products 14 also becomes a significant route (dotted arrow
in B), which results in a low stereoselectivity. In addition,
the stereoselectivity of the nucleophilic addition reaction of
organometallic reagents to 1 or 2 would also be explained
according to similar models as above.
Table 6. Treatment of b-methoxyacylsilanes 20 with TBAF
Entry Substrate R1
TBAF Temperature Product Yield d.e.
(%)a (%)b
(equiv.)
(8C)
2.5. Protiodesilylation of 3-methoxysilylalcohols
1
2
3
4
5
20d
20d
20d
20c
20a
Et
Et
Et
i-Pr
Ph
1
rt
rt
230
rt
19d
19d
19d
19c
19a
99
99
99
78
.99
.99
.99
.99
The protiodesilylation of a-silylalcohols proceeds with
complete retention of the configuration.8 Treatment of
3-methoxysilylalcohols 9 or 11 with tetrabutylammo-
nium fluoride (TBAF) at room temperature for 24 h in
N,N-dimethylformamide (DMF) gave the corresponding
protiodesilylated compounds 17 or 18, respectively. The
results are shown in Scheme 4. In all cases the products 17
and 18 having the four contiguous stereogenic centers were
quantitatively obtained with a high diastereomeric purity
independent of the stereochemistry of the starting silyl-
alcohols and the kind of b-substituent.
0.2
0.2
0.2
0.2
rt
20c .99
a
b
c
Isolated yield.
Determined by H NMR analysis.
Stilbene was formed as the byproduct.
1
The following mechanism for the stereoselective formation
of 19 is proposed (Scheme 5). At the first step of the
reaction, fluoride ion attacks silicon atom of acylsilane 20 to
generate a pentacoordinate silicon anionic intermediate 20.
The migration of phenyl group from silicon to carbonyl
carbon may occur to produce an alkoxide ion 21, subsequent
Brook rearrangement of silyl group from carbon to oxygen
affords a carbanion intermediate 22. The conformational
structure of 22 would be pseudo six-membered ring (C) by
the coordination of silicon atom to methoxy group at C-3
owing to Lewis acidity of silicon group. In this chelating
model C, the attack of proton from the less-hindered side of
Scheme 4. Protiodesilylation of 3-methoxysilylalcohols 9 and 11.
Scheme 5.

M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
8207
carbanion gives (3-methoxypropoxy)silane derivatives,
followed by hydrolysis, could ultimately result in formation
of rearranged 1,2-anti alcohol 19 with a high selectivity.
Therefore, we could obtain the protiodesilylated compounds
having three or four contiguous stereogenic centers with
high diastereomeric purity. In addition, reduction of the
acylsilanes afforded the corresponding a-silylalcohols in
high yields with a high diastereoselectivity similarly to the
nucleophilic reaction. Treatment of the acylsilanes having a
dimethylphenylsilyl group with fluoride ion resulted in the
formation of the corresponding phenyl carbinol derivatives
via migration of a phenyl group in a high stereoselectivity.
Further application and the efficient stereoselective con-
struction of multiple stereogenic centers using these
reactions are now in progress. The results will be reported
in due course.
Additionally, the product 19a derived from the reaction of
20a with TBAF was identical with the one obtained from the
nucleophilic addition reaction of phenyllithium to 2a
followed by treatment of TBAF (Scheme 6).
Scheme 6.
4. Experimental
4.1. General
2.7. Stereochemical assignment
IR spectra were recorded on a JASCO A-202 or
SHIMADZU FTIR-8300 infrared spectrometer. 1H and
13C NMR spectra were recorded on a JEOL JNM FX-100s,
EX-270 or LA-400 spectrometer, and tetramethylsilane
(TMS) served as the internal standard. Mass spectra were
recorded on a JEOL JMS-SX102A, JMS-AM50 or Hitachi
M-80 mass spectrometer.
Stereochemical assignment of the resulting 3-methoxysilyl-
alcohol 7f was performed by conversion into the corre-
sponding dimethoxypropane derivative (Scheme 7). The
protiodesilylation of 7f with TBAF in DMF gave the
corresponding 3-methoxyalcohol derivative 23 with reten-
tion of the configuration8 as mentioned above. Treatment of
23 with sodium hydride followed by methylation with
iodomethane gave dimethoxypropane derivative 24. The
stereochemistry of 24 has already been reported,18 and
the vicinal coupling constant of 7.9 Hz observed between
the protons on C-1 and C-2 in the 1H NMR spectrum
indicates the 1,2-anti configuration, which is correlated to
the 1,2-syn configuration in 3-methoxysilylalcohol 7f.
Thin layer chromatography and flash column chromato-
graphy were performed by the use of silica gel 60F 254
(Merck) and silica gel BW-127ZH (Fuji Silysia),
respectively.
All the solvents were distilled and stored over a drying
agent. n-Buthyllithium (1.6 M solution in hexane) was
purchased from Aldrich Chemical Co., Inc.
All reactions were carried out under an argon atmosphere in
dried glassware.
Scheme 7.
Acylsilanes were prepared according to the literature
procedures.1
Thus, the stereochemistry of other silylalcohols 5–12 was
predicted by comparing with the chemical shift and
3J(H2,H3) coupling constant of 7f. On the other hand, the
stereochemistry of silylalcohols 13–16 derived from the
reduction of b-methoxyacylsilanes 1 and 2 was considered
in a similar manner as above.
4.2. A typical procedure for the preparation of
b-methoxyacylsilane (1–4)7
A 300 ml, four-necked, round-bottomed flask equipped with
argon inlet adapter, rubber septum, thermometer, drop funnel
and magnetic stirring bar was charged with 50 ml of
dichloromethane and 5 mmol of titanium tetrachloride. This
solution was cooled to 2788C and acetal solution (5 mmol in
10 ml of dichloromethane) was added dropwise to the stirred
solution. After 5 min, a solution of acylsilane silyl enol ether
(5 mmol in 1 ml of dichloromethane) was added to the
mixture. After completion of the reaction monitered by GC
(usuallyafter beingstirredfor 1 h at2788C). AsaturatedNaCl
solution was then added, and the resulting mixture was
separated. The aqueous layer was extracted with diethyl ether.
The combined organic layers were washed with a saturated
NaCl solution, and dried over Na2SO4, filtered, concentrated.
The crude product was purified and the diastereomers of
b-methoxyacylsilane were separated by column chromato-
graphy (silica gel, benzene) to afford the pure 2,3-anti and
2,3-syn isomers as pale yellow oils.
3. Conclusion
In summary, stereoselective construction of multiple
stereogenic centers using b-methoxyacylsilanes derived
from the aldol reaction of dimethyl acetals and acylsilane
silyl enol ethers has been described. The acylsilanes having
stereogenic centers at the a and b positions were treated
with organometallic reagents such as alkyllithium, phenyl-
lithium or methylmagnesium bromide to afford the
corresponding silylalcohols in high yields with an excellent
diastereoselectivity. The stereoselectivity was influenced by
bulkiness of substituent at the a position of acylsilanes. The
protiodesilylation of above obtained a-silylalcohols pro-
ceeded with complete retention of the configuration.

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M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
4.3. Reaction of b-methoxyacylsilane with nucleophile
J¼10.4 Hz, 1H), 4.65 (s, 1H), 3.48 (d, J¼10.4 Hz, 1H),
3.12 (s, 1H), 1.63–1.32 (m, 1H), 1.03 (d, J¼6.8 Hz, 3H),
0.87–0.70 (m, 2H), 0.65 (t, J¼6.8 Hz, 3H), 0.28 (s, 9H).
A 30 ml, three-necked, round-bottomed flask equipped with
argon inlet adapter, rubber septum, thermometer and
magnetic stirring bar was charged with 5 ml of THF and
0.5 mmol of b-methoxyacylsilane. This solution was cooled
to 2788C and either organolithium reagent solution
(1 mmol in hexane) or Grignard reagent solution (2 mmol
in THF) was added slowly via syringe. After completion of
the reaction monitered by GC (usually after being stirred for
5 min at 2788C), 5 ml of methanol was added to quench,
and the resulting mixture was partitioned between H2O and
diethyl ether. The aqueous layer was extracted with diethyl
ether. The combined organic phases were washed with a
saturated NaCl solution, and dried over Na2SO4, filtered,
concentrated. Column chromatography on silica gel
afforded a-silylalcohol as pale yellow oils.
4.3.4. 3-Methoxy-1,2,3-triphenyl-1-silyl-1-propanol (7i).
IR (neat) 3450, 3095, 3060, 3045, 2960, 2910, 2835, 1605,
1495, 1455, 1445, 1340, 1245, 1100, 1075, 835 cm21
.
HRMS calcd for C25H30O2Si (Mþ) 390.2015, found
390.2035.
1H NMR (CDCl3) d 7.43–6.65 (m, 15H), 5.04 (s, 1H), 4.37
(d, J¼10.5 Hz, 1H), 3.78 (d, J¼10.5 Hz, 1H), 3.06 (s, 1H),
20.13 (s, 9H).
4.3.5. 3-Cyclohexyl-4-methoxy-4-phenyl-2-trimethylsilyl-
2-butanol (5j, 7j and 8j). Compound 5j. IR (neat) 3450, 3040,
2940, 2850, 1445, 1365, 1245, 1095, 1075, 865, 840 cm21
.
4.3.1. 4-Methoxy-3,4-diphenyl-2-trimethylsilyl-2-butanol
(5f,7f).Compound5f. IR(neat)3470, 3055, 3040, 2955, 2900,
HRMS calcd for C19H30OSi ([M2CH3OH]þ) 302.2066,
found 302.2065.
2810, 1600, 1495, 1455, 1245, 1105, 1085, 875, 835 cm21
.
HRMS calcd for C19H24OSi ([M2CH3OH]þ) 296.1596,
found 296.1603.
1H NMR (CDCl3) d 7.62–7.08 (m, 5H), 4.55 (d, J¼4.6 Hz,
1H), 4.26 (br, 1H), 3.25 (s, 3H), 2.22–0.57 (m, 12H), 1.18
(s, 3H), 0.08 (s, 9H).
1H NMR (CDCl3) d 7.49–6.72 (m, 10H), 5.23 (d, J¼3.1 Hz,
1H), 4.10 (s, 1H), 3.31 (s, 3H), 2.63 (d, J¼3.1 Hz, 1H), 1.62
(s, 3H), 20.29 (s, 9H).
Compound 7j. HRMS calcd for C19H30OSi
([M2CH3OH]þ) 302.2066, found 302.2062.
13C NMR (CDCl3) d 140.2, 138.3, 131.8, 127.7, 127.6,
127.5, 127.3, 126.5, 87.2, 69.7, 63.7, 55.9, 24.8.
1H NMR (CDCl3) d 7.54–7.02 (m, 5H), 4.61 (d, J¼6.6 Hz,
1H), 3.14 (s, 3H), 2.01–0.62 (m, 12H), 1.35 (s, 3H), 0.10 (s,
9H).
Anal. calcd for C20H28O2Si: C, 73.12; H, 8.59. Found: C,
73.27; H, 8.47.
Compound 8j. 1H NMR (CDCl3) d 4.99 (d, J¼3.4 Hz, 1H),
3.38 (s, 3H), 0.14 (s, 9H).
Compound 7f. HRMS calcd for C19H24OSi
([M2CH3OH]þ) 296.1596, found 296.1592.
4.3.6. 6-Isopropyl-7-methoxy-7-phenyl-5-trimethylsilyl-
5-heptanol (5k, 6k, 7k and 8k). Compound 5k. IR (neat)
3570, 3500, 3070, 3030, 2960, 2880, 1455, 1365, 1250,
1H NMR (CDCl3) d 7.18–6.88 (m, 10H), 6.71 (d,
J¼10.5 Hz, 1H), 3.52 (s, 1H), 3.24 (d, J¼10.5 Hz, 1H),
3.14 (s, 3H), 1.16 (s, 3H), 0.14 (s, 9H).
1090, 1075, 835 cm21
.
HRMS calcd for C19H32OSi ([M2CH3OH]þ) 304.2222,
found 304.2229.
4.3.2. 7-Methoxy-6,7-diphenyl-5-trimethylsilyl-5-heptanol
(7g). IR (neat) 3470, 3080, 3065, 3045, 2960, 2910, 2880,
1605, 1595, 1465, 1455, 1377, 1355, 1255, 1200, 1100, 980,
1H NMR (CDCl3) d 7.45–7.08 (m, 5H), 4.58 (d, J¼2.5 Hz,
1H), 4.38 (br, 1H), 3.36 (s, 3H), 1.20 (d, J¼6.8 Hz, 3H),
1.03 (d, J¼6.8 Hz, 3H), 2.40–0.60 (m, 11H), 0.08 (s, 9H).
885, 835 cm21
.
HRMS calcd for C22H30OSi ([M2CH3OH]þ) 338.2066,
found 338.2066.
Compound 6k. 1H NMR (CDCl3) d 3.01 (s, 3H), 0.13 (s, 9H).
1H NMR (CDCl3) d 7.39–6.68 (m, 10H), 4.70 (d,
J¼10.3 Hz, 1H), 3.42 (d, J¼10.3 Hz, 1H), 3.30 (s, 1H),
3.14 (s, 3H), 1.79–1.05 (m, 6H), 0.86 (t, J¼6.1 Hz, 3H),
0.16 (s, 9H).
Compound 7k. HRMS calcd for C19H32OSi
([M2CH3OH]þ) 304.2222, found 304.2219.
1H NMR (CDCl3) d 7.55–7.10 (m, 5H), 4.79 (d, J¼4.6 Hz,
1H), 3.25 (s 1H), 2.85 (br, 1H), 2.24–0.93 (m, 8H), 1.26 (d,
J¼7.1 Hz, 3H), 1.11 (d, J¼7.3 Hz, 3H), 0.84 (t, J¼7.3 Hz,
3H), 0.19 (s, 9H).
4.3.3. 6-Methoxy-2-methyl-5,6-diphenyl-4-trimethylsilyl-
4-hexanol (7h). IR (neat) 3455, 3055, 3030, 2955, 2900,
1495, 1450,1245, 1095, 840 cm21
.
Compound 8k. 1H NMR (CDCl3) d 4.94 (d, J¼3.7 Hz, 1H),
HRMS calcd for C22H30OSi ([M2CH3OH]þ) 338.2066,
found 338.2050.
3.39 (s, 3H), 0.13 (s, 9H).
4.3.7. 3-Isopropyl-4-methoxy-4-phenyl-2-trimethylsilyl-
2-butanol (5l, 7l, 8l). Compound 5l. IR (neat) 3595, 3500,
1H NMR (CDCl3) d 7.49–6.79 (m, 10H), 4.73 (d,

M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
8209
3105, 3090, 3045, 2980, 2910, 2840, 1500, 1455, 1375,
1255, 1205, 1105, 1085, 1065, 860, 835 cm21
HRMS calcd for C21H34OSi ([M2CH3OH]þ) 330.2379,
found 330.2370.
.
HRMS calcd for C16H26OSi ([M2CH3OH]þ) 262.1753,
found 262.1753.
1H NMR (CDCl3) d 7.48–6.98 (m, 5H), 3.70 (dd, J¼8.1,
2.1 Hz, 1H), 3.50 (s, 3H), 3.32–3.09 (m, 1H), 1.98–0.71 (m,
12H), 1.38 (d, J¼7.1 Hz, 3H), 1.16 (s, 3H), 20.12 (s, 9H).
1H NMR (CDCl3) d 7.54–7.07 (m, 5H), 4.50 (d, J¼4.6 Hz,
1H), 3.26 (s, 3H), 2.23–2.02 (m, 1H), 1.88 (dd, J¼4.6 Hz,
1.6 Hz, 1H), 1.19 (s, 3H), 1.11 (d, J¼7.1 Hz, 3H), 0.88 (d,
J¼7.1 Hz, 3H), 0.07 (s, 9H).
4.3.11. 3-Isopropyl-4-methoxy-5-phenyl-2-trimethylsilyl-
2-hexanol (9c). IR (neat) 3510, 3470, 3080, 3025, 2935, 2835,
1495, 1455, 1250, 1100, 1080, 840 cm21
.
Compound 7l. HRMS calcd for C16H26OSi
([M2CH3OH]þ) 262.1753, found 262.1742.
HRMS calcd for C18H30OSi ([M2CH3OH]þ) 290.2066,
found 290.2057.
1H NMR (CDCl3) d 7.50–7.09 (m, 5H), 4.65 (d, J¼6.1 Hz,
1H), 3.16 (s, 3H), 2.08 (dd, J¼6.1 Hz, 1.2 Hz, 1H), 1.83–
1.56 (m, 1H), 1.35 (s, 3H), 1.05 (d, J¼7.1 Hz, 3H), 1.03 (d,
J¼7.1 Hz, 3H), 0.10 (s, 9H).
1H NMR (CDCl3) d 7.42–6.96 (m, 5H), 3.71 (dd, J¼8.0,
2.0 Hz, 1H), 3.48 (s, 3H), 3.26–3.04 (m, 1H), 2.54–2.35
(m, 1H), 1.67–1.48 (m, 1H), 1.38 (d, J¼7.1 Hz, 3H), 1.24
(d, J¼7.1 Hz, 3H), 1.19 (d, J¼7.1 Hz, 3H), 1.13 (s, 3H),
20.13 (s, 9H).
1
Compound 8l. H NMR (CDCl3) d4.99 (d, J¼4.1 Hz, 1H),
3.37 (s, 3H), 0.12 (s, 9H).
4.4. Reduction of b-methoxyacylsilanes with lithium
aluminum hydride
4.3.8. 3-Ethyl-4-methoxy-4-phenyl-2-trimethylsilyl-2-
butanol (7m, 8m). Compound 7m. IR (neat) 3465, 3060,
A 30 ml, three-necked, round-bottomed flask equipped with
argon inlet adapter, rubber septum, thermometer and
magnetic stirring bar was charged with 5 ml of THF and
0.5 mmol of b-methoxyacylsilane. This solution was cooled
to 2788C and lithium aluminum hydride solution (2 mmol
in THF) was added slowly via syringe. After completion of
the reaction monitered by GC (usually after being stirred for
30 min at 2788C), 5 ml of methanol was added to quench,
and the resulting mixture was partitioned between H2O and
diethyl ether. The aqueous layer was extracted with diethyl
ether. The combined organic phases were washed with a
saturated NaCl solution, and dried over Na2SO4, filtered,
concentrated. Column chromatography on silica gel
afforded a-silylalcohol as pale yellow oils.
3025, 2950, 2865, 1495, 1455, 1250, 1080, 835 cm21
.
HRMS calcd for C15H24OSi ([M2CH3OH]þ) 248.1596,
found 248.1587.
1H NMR (CDCl3) d 7.49–7.12 (m, 5H), 4.85 (br, 1H), 4.15
(d, J¼10.5 Hz, 1H), 3.03 (s, 3H), 1.83–0.68 (m, 6H), 1.25
(t, J¼7.3 Hz, 3H), 0.15 (s, 9H).
Compound 8m. 1H NMR (CDCl3) d 5.39 (br, 1H), 4.34 (d,
J¼10.0 Hz, 1H), 3.10 (s, 3H), 0.10 (s, 9H).
4.3.9. 4-Methoxy-3,5-diphenyl-2-trimethylsilyl-2-hexanol
(9a, 11a). Compound 9a. IR (neat) 3412, 3061, 3028, 2932,
2833, 1709, 1493, 1452, 1248, 1096, 1063 cm21
.
4.4.1. 3-Methoxy-2,3-diphenyl-1-trimethylsilylpropanol
(13a–15a). Compound 13a. IR (neat) 3460, 3090, 3070,
3045, 2960, 2910, 2825, 1495, 1455, 1250, 1105, 865,
840 cm21
.
HRMS calcd for C21H28OSi ([M2CH3OH]þ) 324.1909,
found 324.1922.
1H NMR (CDCl3) d 7.56–6.88 (m, 10H), 4.26 (dd, J¼9.5,
2.4 Hz, 1H), 3.73 (s, 3H), 3.47 (br, 1H), 2.54 (dq, J¼7.1,
2.4 Hz, 1H), 2.40 (d, J¼2.4 Hz, 1H), 1.39 (s, 3H), 1.20 (d,
J¼7.1 Hz, 3H), 20.42 (s, 9H).
HRMS calcd for C18H22OSi ([M2CH3OH]þ) 282.1440,
found 282.1440.
1H NMR (CDCl3) d 7.33–6.84 (m, 10H), 4.63 (d, J¼8.1 Hz,
1H), 4.23 (br, 1H), 3.24 (s, 3H), 2.84 (dd, J¼8.1, 2.8 Hz,
1H), 2.36 (br, 1H), 20.25 (s, 9H).
Anal. calcd for C22H32O2Si: C, 74.10; H, 9.05. Found: C,
74.31; H, 8.97.
13C NMR (CDCl3) d 140.5, 140.4, 129.8, 127.9, 127.8,
127.2, 127.1, 126.5, 85.8, 65.2, 57.0, 55.6, 23.4.
Compound 11a. HRMS calcd for C21H28OSi
([M2CH3OH]þ) 324.1909, found 324.1905.
Anal. calcd for C19H26O2Si: C, 72.56; H, 8.33. Found: C,
72.40; H, 8.34.
1H NMR (CDCl3) d 7.48–6.85 (m, 10H), 4.06 (dd, J¼8.3,
3.9 Hz, 1H), 3.17 (s, 3H), 2.96 (d, J¼8.3 Hz, 1H), 2.86 (m,
1H), 1.60 (br, 1H), 1.31 (s, 3H), 1.27 (d, J¼8.1 Hz, 3H),
20.12 (s, 9H).
1
Compound 14a. H NMR (CDCl3) d 7.25–6.83 (m, 10H),
5.13 (s, 1H), 4.62 (d, J¼9.5 Hz, 1H), 4.05 (dd, J¼10.6,
1.1 Hz, 1H), 3.23 (s, 3H), 3.14 (dd, J¼10.6, 9.5 Hz, 1H),
20.29 (s, 9H).
4.3.10. 3-Cyclohexyl-4-methoxy-5-phenyl-2-trimethylsilyl-
2-hexanol (9b). IR (neat) 3515, 3450, 3090, 3060, 3035, 2970,
2905, 2840, 1495, 1455, 1385, 1365, 1250, 1110, 1085, 860,
Compound 15a. HRMS calcd for C18H22OSi
([M2CH3OH]þ) 282.1440, found 282.1436.
840 cm21
.

8210
M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
1H NMR (CDCl3) d 7.37–6.85 (m, 10H), 4.77 (d, J¼6.7 Hz,
1H), 3.65 (d, J¼3.3 Hz, 1H), 3.13 (s, 3H), 2.87 (dd, J¼6.7,
3.3 Hz, 1H), 20.25 (s, 9H).
3.4 Hz, 1H), 3.48 (dd, J¼5.9, 5.9 Hz, 1H), 3.30 (s, 3H), 2.85
(dd, J¼5.9, 3.4 Hz, 1H), 2.60 (d, J¼3.6 Hz, 1H), 1.91–1.83
(m, 1H), 0.92 (d, J¼6.8 Hz, 3H), 0.85 (d, J¼6.8 Hz, 3H),
20.19 (s, 9H).
4.4.2. 2-Cyclohexyl-3-methoxy-3-phenyl-1-trimethylsilyl-
propanol (13b–16b). Compound 15b. IR (neat) 3450, 3040,
Compound 13e. HRMS calcd for C15H24OSi
([M2CH3OH]þ) 248.1596, found s248.1584.
2940, 2850, 1445, 1365, 1245, 1095, 1075, 865, 840 cm21
.
HRMS calcd for C18H28OSi ([M2CH3OH]þ) 288.1909,
found 280.1904.
1H NMR (CDCl3) d 7.41–7.21 (m, 5H), 4.03 (dd, J¼6.6,
2.2 Hz, 1H), 3.54 (s, 3H), 3.52 (dd, J¼8.3, 4.4 Hz, 1H), 2.72
(dd, J¼8.3, 2.2 Hz, 1H), 1.97 (d, J¼6.6 Hz, 1H), 1.63–1.56
(m, 1H), 0.95 (d, J¼6.8 Hz, 3H), 0.83 (d, J¼6.6 Hz, 3H),
20.25 (s, 9H).
1H NMR (CDCl3) d 7.37–7.23 (m, 5H), 4.66 (d, J¼1.6 Hz,
1H), 3.82 (s, 1H), 3.46 (d, J¼1.6 Hz, 1H), 3.25 (s, 3H),
2.29–1.17 (m, 12H), 20.07 (s, 9H).
4.5. Protiodesilylation of a-silylalcohol
1
Compound 16b. H NMR (CDCl3) d 4.33 (dd, J¼10.0,
2.7 Hz, 1H), 3.05 (s, 3H).
A 30 ml, three-necked, round-bottomed flask equipped with
argon inlet adapter, rubber septum, thermometer and
magnetic stirring bar was placed in a water bath (308C)
and charged with 10 ml of DMF, 0.5 mmol of a-silylalcohol
and tetrabuthylammonium fluoride solution (2.5 mmol in
DMF). After 24 h, a saturated NaCl solution was added, and
the resulting mixture was partitioned between H2O and
diethyl ether. The aqueous layer was extracted with diethyl
ether. The combined organic phases were washed with a
saturated NaCl solution, and dried over Na2SO4, filtered,
and concentrated. Column chromatography on silica gel
afforded the corresponding alcohols as pale yellow oils.
Compound 13b. HRMS calcd for C18H28OSi
([M2CH3OH]þ) 288.1909, found 280.1905.
1H NMR (CDCl3) d 7.39–7.25 (m, 5H), 4.41 (d, J¼9.3 Hz,
1H), 3.13 (s, 3H), 3.10 (s, 1H), 1.99 (d, J¼12.4 Hz, 1H),
1.79–0.90 (m, 12H), 20.02 (s, 9H).
1
Compound 14b. H NMR (CDCl3) d 4.76 (d, J¼2.7 Hz,
1H), 3.81 (dd, J¼5.3, 2.7 Hz, 1H), 3.53 (d, J¼5.3 Hz, 1H),
3.24 (s, 3H), 2.19 (d, J¼12.2 Hz, 1H), 0.15 (s, 9H).
4.4.3. 2-Ethyl-3-methoxy-3-phenyl-1-trimethylsilyl-
propanol (13d–16d). Compound 15d. IR (neat) 3450,
3040, 2940, 2850, 1445, 1365, 1245, 1095, 1075, 865,
4.5.1. 4-Methoxy-3,5-diphenyl-2-hexanol (17a, 18a).
Compound 17a. IR (neat) 3474, 3061, 3026, 2970, 2930,
2882, 2837, 1493, 1452, 1408, 0369, 1136, 1086 cm21
.
840 cm21
.
HRMS calcd for C19H24O2 (Mþ) 284.1776, found
284.1783.
HRMS calcd for C14H22OSi ([M2CH3OH]þ) 234.1440,
found 234.1436.
1H NMR (CDCl3) d 7.56–6.91 (m, 10H), 4.20 (dq, J¼9.8,
6.1 Hz, 1H), 4.08 (dd, J¼10.1, 2.5 Hz, 1H), 3.73 (s, 3H),
2.45 (dq, J¼10.1, 6.8 Hz, 1H), 2.24 (dd, J¼9.8, 2.5 Hz, 1H),
1.58 (br, 1H), 1.26 (d, J¼6.8 Hz, 3H), 0.87 (d, J¼6.1 Hz,
3H).
1H NMR (CDCl3) d 7.38–7.23 (m, 5H), 4.63 (d, J¼2.0 Hz,
1H), 3.84 (br, 1H), 3.38 (br, 1H), 3.26 (s, 3H), 1.65–1.37
(m, 2H), 0.60 (t, J¼7.1 Hz, 3H), 0.06 (s, 9H).
Compound 16d. 1H NMR (CDCl3) 0.17 (s, 9H).
13C NMR (CDCl3) d 145.0, 140.8, 128.8, 128.4, 128.2,
127.7, 126.9, 126.1, 93.4, 71.3, 61.2, 56.8, 40.9, 21.8, 11.7.
Compound 13d. HRMS calcd for C14H22OSi
([M2CH3OH]þ) 234.1440, found 234.1452.
Anal. calcd for C19H24O2: C, 80.24; H, 8.51. Found: C,
80.38; H, 8.59.
1H NMR (CDCl3) d d 7.38–7.26 (m, 5H), 4.20 (d,
J¼9.5 Hz, 1H), 3.66–3.61 (m, 1H), 3.30–3.20 (m, 1H),
3.09 (s, 3H), 1.95–1.91 (m, 1H), 1.26–1.01 (m, 2H), 0.67 (t,
J¼7.6 Hz, 3H), 0.00 (s, 9H).
Compound 18a. HRMS calcd for C19H24O2 (Mþ) 284.1776,
found 284.1777.
1
Compound 14d. H NMR (CDCl3) d 3.23 (s, 3H), 0.12 (s,
9H).
1H NMR (CDCl3) d 7.54–6.84 (m, 10H), 4.63 (br, 1H), 4.18
(dq, J¼8.6, 6.1 Hz, 1H), 3.85 (dd, J¼9.8, 2.5 Hz, 1H), 3.14
(s, 3H), 2.76 (dd, J¼9.8, 8.6 Hz, 1H), 2.69 (dq, J¼7.2,
2.5 Hz, 1H), 1.29 (d, J¼7.2 Hz, 3H), 0.84 (d, J¼6.1 Hz,
3H).
4.4.4. 3-Methoxy-4-methyl-2-phenyl-1-trimethylsilyl-
propanol (13e, 15e). Compound 15e. IR (neat) 3460,
3090, 3070, 3045, 2960, 2910, 2825, 1495, 1455, 1250,
1105, 865, 840 cm21
.
4.5.2. 3-Cyclohexyl-4-methoxy-5-phenyl-2-hexanol
(17b). IR (neat) 3449, 3061, 3026, 2926, 2851, 1493,
1450, 1375, 1094 cm21
.
HRMS calcd for C15H24OSi ([M2CH3OH]þ) 248.1596,
found s248.1594.
HRMS calcd for C19H30O2 (Mþ) 290.2246, found
290.2253.
1H NMR (CDCl3) d 7.41–7.20 (m, 5H), 3.82 (dd, J¼3.6,

M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
8211
1H NMR (CDCl3) d 7.57–6.92 (m, 5H), 4.11–3.91 (m, 1H),
3.71 (dd, J¼8.1, 2.2 Hz, 1H), 3.49 (s, 3H), 3.17–2.95 (m,
1H), 2.06–0.72 (m, 12H), 1.38 (d, J¼6.8 Hz, 3H), 1.03 (d,
J¼6.4 Hz, 3H).
Anal. calcd for C22H22O2: C, 82.99; H, 6.96. Found: C,
82.95; H, 6.87.
4.6.2. 2-(Methoxyphenylmethyl)-3-methyl-1-phenyl-1-
butanol (19c). IR (neat) 3430, 3080, 3070, 3015, 2945,
2830, 1220 cm21
.
4.5.3. 3-Isopropyl-4-methoxy-5-phenyl-2-hexanol (17c).
IR (neat) 3450, 3061, 3026, 2963, 2932, 2876, 2831, 1495,
1454, 1371, 1092, 1020 cm21
.
HRMS calcd for C18H20O ([M2CH3OH]þ) 252.1514,
found 252.1509.
HRMS calcd for C16H26O2 (Mþ) 250.1933, found
250.1936.
1H NMR (CDCl3) d 7.47–7.14 (m, 10H), 4.93 (d, J¼7.1 Hz,
1H), 4.45 (d, J¼7.3 Hz, 1H), 4.45–4.19 (m, 1H), 3.20 (s,
3H), 2.25 (ddd, J¼7.2, 6.8, 2.5 Hz, 1H), 1.60–1.35 (m, 1H),
0.75 (d, J¼7.1 Hz, 3H), 0.75 (d, J¼7.1 Hz, 3H).
1H NMR (CDCl3) d 7.57–6.93 (m, 5H), 4.13–3.89 (m, 1H),
3.72 (dd, J¼8.1, 2.0 Hz, 1H), 3.50 (s, 3H), 3.14–2.99 (m,
1H), 2.07–2.01 (m, 1H), 1.39 (d, J¼6.8 Hz, 3H), 1.37–1.32
(m, 1H), 1.03 (d, J¼6.4 Hz, 6H), 0.85 (d, J¼7.1 Hz, 3H).
4.6.3. 2-(Methoxyphenylmethyl)-1-phenyl-1-butanol
(19d). IR (neat) 3440, 3085, 3065, 3040, 2970, 2935,
2880, 2830, 1085 cm21
.
4.5.4. 4-Methoxy-3,4-diphenyl-2-butanol (23). According
to the general procedure, the protiodesililation of 7f afforded
23 in 94% yield. IR (neat) 3490, 3100, 3080, 3060, 2960,
2940, 2840, 1500, 1460, 1420, 1375, 1295, 1135, 1090,
HRMS calcd for C17H18O ([M2CH3OH]þ) 238.1358,
found 238.1357.
1035, 975 cm21
.
1H NMR (CDCl3) d 7.41–7.19 (m, 10H), 4.98 (br, 1H), 4.29
(br, 1H), 4.28 (d, J¼5.5 Hz, 1H), 3.29 (s, 3H), 1.90–1.84
(m, 1H), 1.36–1.29 (m, 1H), 1.27–1.18 (m, 1H), 0.84 (t,
J¼7.5 Hz, 3H).
HRMS calcd for C16H16O ([M2CH3OH]þ) 224.1201,
found 224.1205.
1H NMR (CDCl3) d 7.28–6.80 (m, 10H), 5.07 (s, 1H),
4.56 (d, J¼10.1 Hz, 1H), 4.41 (dq, J¼9.1, 6.1 Hz, 1H), 3.23
(s, 3H), 2.86 (dd, J¼10.1, 9.1 Hz, 1H), 0.92 (d, J¼6.1 Hz,
3H).
4.6.4. 1,3-Dimethoxy-1,2-diphenylbutane (24). A 30 ml,
three-necked, round-bottomed flask equipped with argon
inlet adapter, rubber septum, reflux condenser and mag-
netic stirring bar was placed and charged with 15 ml of
THF, 1.4 mmol of 4-methoxy-3,4-diphenyl-2-butanol 23
and sodium hydride (2.8 mmol). Then iodomethane
(11.2 mmol) was added slowly via syringe. This mixture
was stirred under reflux. After 6 h, water was added, and the
resulting mixture was partitioned between H2O and diethyl
ether. The aqueous layer was extracted with diethyl ether.
The combined organic phases were washed with a saturated
NaCl solution, and dried over Na2SO4, filtered, concen-
trated. Column chromatography on silica gel afforded the
corresponding dimethoxybutane 24 in 87% yield.
13C NMR (CDCl3) d 139.6, 139.2, 128.8, 128.0, 127.7,
127.4, 127.3, 126.3, 90.3, 71.8, 60.3, 56.4, 21.9.
Anal. calcd for C17H20O2: C, 79.59; H, 7.86. Found: C,
79.65; H, 7.98.
4.6. Treatment of b-methoxyacylsilane 20 with
tetrabutylammonium fluoride (TBAF)
A 30 ml, three-necked, round-bottomed flask equipped with
argon inlet adapter, rubber septum, thermometer and
magnetic stirring bar was placed in a water bath (258C)
and charged with 10 ml of THF, 0.5 mmol of acylsilane and
tetrabuthylammonium fluoride solution (0.1 mmol in THF).
After 1 h, a saturated NaCl solution was added, and the
resulting mixture was partitioned between H2O and diethyl
ether. The aqueous layer was extracted with diethyl ether.
The combined organic phases were washed with a saturated
NaCl solution, and dried over Na2SO4, filtered, concen-
trated. Column chromatography on silica gel afforded the
corresponding alcohols as pale yellow oils.
IR (neat) 3090, 3070, 3040, 2985, 2940, 2910, 2820, 1490,
1455, 1370, 1185, 1145, 1095, 1075 cm21
.
HRMS calcd for C18H22O2 (Mþ) 270.1620, found
270.1617.
1H NMR (CDCl3) d 7.25–6.81 (m, 10H), 4.76 (d, J¼6.1 Hz,
1H), 3.67 (dq, J¼7.9, 6.1 Hz, 1H), 3.41 (s, 3H), 3.29 (dd,
J¼7.9, 6.1 Hz, 1H), 3.22 (s, 3H), 1.03 (d, J¼6.1 Hz, 3H).
13C NMR (CDCl3) d 139.4, 138.2, 130.2, 128.0, 127.5,
127.3, 127.2, 126.3, 83.5, 76.6, 57.0, 56.7, 55.7, 16.4.
4.6.1. 3-Methoxy-1,2,3-triphenyl-1-propanol (19a). IR
(neat) 3450, 3095, 3070, 3040, 2945, 2825, 1495, 1450,
1100, 1085, 1060, 1025 cm21
.
HRMS calcd for C21H18O ([M2CH3OH]þ) 286.1358,
found 286.1359.
Acknowledgements
This work was partially supported by the Saneyoshi
Scholarship Foundation and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports
and Culture, Japan.
1H NMR (CDCl3) d 7.58–6.77 (m, 15H), 5.38 (d, J¼2.7 Hz,
1H), 4.71 (d, J¼7.7 Hz, 1H), 3.32 (s, 3H), 3.27 (dd, J¼7.7,
2.7 Hz, 1H).

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M. Honda et al. / Tetrahedron 59 (2003) 8203–8212
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