Acid-catalyzed rearrangement of α-hydroxytrialkylsilanes

Article abstract of DOI:10.1016/S0040-4020(03)00952-9

Cationic rearrangement of several α-hydroxysilanes is described. Treatment of both (1R,1′R,2′S)-α-hydroxycyclopropylsilane syn-9 and (1S,1′R,2′S)-anti-9 under aqueous H₂SO₄ underwent rearrangement via a common α-silyl cation intermediate A to give a mixture of the ring-opened (R)-vinylsilane 13, the tandem [1,2]-CC bond migration product (1R,2S,1′R)-14, and its 1′S isomer 15. On the other hand, the acidic treatment of (R,E)-α-hydroxyalkenylsilane 8 or (R,Z)-8 was each accompanied with partial racemization to give an enantiomeric isomer of allylic alcohol 23 via a preferential syn-facial S_N2′ reaction, respectively. Both α-hydroxyalkynylsilane 6 and α-hydroxyalkylsilane 12 were inert to the acidic conditions; however, treatment of (R)-α-mesyloxyalkynylsilane 26 under aqueous H₂SO₄ gave a mixture of the optically active rearranged allene 27, α,β-unsaturated ketone 28, and (S)-α-hydroxyalkynylsilane 6 with partial racemization. Comparisons of the reactivities of these α-hydroxysilanes under acidic conditions are also disclosed.

Full text of DOI:10.1016/S0040-4020(03)00952-9

Tetrahedron 59 (2003) 6647–6658
Acid-catalyzed rearrangement of a-hydroxytrialkylsilanes
*
Kazuhiko Sakaguchi, Masato Higashino and Yasufumi Ohfune
*
Department of Material Science, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
Received 13 May 2003; accepted 12 June 2003
0
0
Abstract—Cationic rearrangement of several a-hydroxysilanes is described. Treatment of both (1R,1 R,2 S)-a-hydroxycyclopropylsilane
0
0
2 4
syn-9 and (1S,1 R,2 S)-anti-9 under aqueous H SO underwent rearrangement via a common a-silyl cation intermediate A to give a mixture
of the ring-opened (R)-vinylsilane 13, the tandem [1,2]-CC bond migration product (1R,2S,1 R)-14, and its 1 S isomer 15. On the other hand,
the acidic treatment of (R,E)-a-hydroxyalkenylsilane 8 or (R,Z)-8 was each accompanied with partial racemization to give an enantiomeric
2 reaction, respectively. Both a-hydroxyalkynylsilane 6 and a-
hydroxyalkylsilane 12 were inert to the acidic conditions; however, treatment of (R)-a-mesyloxyalkynylsilane 26 under aqueous H SO
0
0
0
isomer of allylic alcohol 23 via a preferential syn-facial S
N
2
4
gave a mixture of the optically active rearranged allene 27, a,b-unsaturated ketone 28, and (S)-a-hydroxyalkynylsilane 6 with partial
racemization. Comparisons of the reactivities of these a-hydroxysilanes under acidic conditions are also disclosed.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
catalyzed rearrangement of several a-substituted a-
hydroxysilanes.
It is well-known that carbocation b to silicon is stabilized by
s-p hyperconjugation (the b-effect), and various synthetic
1
applications have been provided (Scheme 1). On the
2. Results and discussion
contrary to the b-silyl cation, carbocation a to silicon (a-
silyl cation) has not been well investigated because of its
presumed chemical instability which is indicated by MP2/6-
2.1. Preparation of a-hydroxysilanes
3
is 18.3 kcal/mol less stable than the corresponding carbo-
1G*//3-21G calculations; a carbocation a to the SiH group
Since in the previous studies difficulty was incurred in
handling the TMS-substituted a-hydroxysilanes during its
preparation and the product analysis due to its instability
against acidic conditions, a chemically more stable tert-
butyldimethylsilyl (TBDMS) group was used for the present
study. Preparation of the enantiomers and diastereomers of
a-hydroxysilanes 6, 8, 9 and 12 are summarized in Scheme
4 where racemic 6, prepared from 2-butyn-1-ol (5) in one
3
2
cation a to a methyl group. To date, no systematic
investigations regarding the generation of the a-silyl cation
1
a,3
and its synthetic applications have been reported.
During
the course of our recent studies regarding syntheses and
reactions using optically active a-hydroxysilane, we found
that the a-hydroxycyclopropylsilane 1 underwent acid-
catalyzed rearrangement via a putative a-silyl cation
intermediate to give a mixture of products, which were
composed of the ring-opened vinyl silane 2, silylcyclopro-
5
,6
pot (86%), was used as the common synthetic precursor
except for (R,E)-8. Jones oxidation of 6 gave silyl ketone 7
whose enantioselective reduction with (2)-B-chloro diiso-
0
4
7
pane 3, and its C1 -diastereomer 4 (Scheme 2). Since the
previous work dealt preliminarily with only one diaster-
eomer of a-hydroxycyclopropylsilane (syn form), the
stereochemical outcome from the other diastereomer (anti
form) remained to be examined. Furthermore, it is of
interest to investigate acid-catalyzed reactions of a-hydro-
xysilanes having an a-alkenyl, an a-alkynyl or an a-alkyl
group to establish whether the a-silyl cation can be
generated (Scheme 3). Herein, we wish to report acid-
pinocamphenylborane (DIP-Cl) afforded optically active
8
a-hydroxyalkynylsilane (R)-6 (86% yield, .95% ee). Z-a-
Hydroxyalkenylsilane (R,Z)-8 was prepared from (R)-6 by
hydrogenation using the Lindlar catalyst (81%). Stereo-
selective cyclopropanation of (R,Z)-8 was performed using
0
0
Et Zn–CH I to give (1R,1 R,2 S)-a-hydroxycyclopropyl-
2
2 2
9
silane syn-9. Its 1S isomer anti-9 was prepared by the
following two-step reaction: (1) PDC oxidation of syn-9
(72%) and (2) reduction with DIBAL-H (76%, anti/syn¼20/
8
1). a-Hydroxyalkenylsilane (R,E)-8 (90% ee) was prepared
from (E)-silyl ketone 11 by enantioselective reduction
1
0
Keywords: a-hydroxysilane; a-silyl cation; acid-catalyzed rearrangement;
tandem [1,2] shift.
1
1
using (2)-DIP-Cl (63%). An a-hydroxysilane (R)-12
having an alkyl group was prepared from (R)-6 by
*
Corresponding authors. Tel.: þ81-6-6605-2571; fax: þ81-6-6605-3153;
1
2
e-mail: sakaguch@sci.osaka-cu.ac.jp
hydrogenation using the Willkinson catalyst.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00952-9

6648
K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
Scheme 1.
Scheme 2.
Scheme 3.
2.2. Acid-catalyzed rearrangement of a-hyroxycyclo-
propylsilanes
not only the same rearrangement products as those from
syn-9 but also their product ratios were almost similar to that
of each diastereomer. Interconversion between the
rearranged products (R)-13, 14 and 15 was not observed
To test the effect of the sterically bulky TBDMS group
under the cationic rearrangement, syn-9 (.95% ee) which is
the same diastereomer as the TMS substrate, syn-1, was
subjected to acidic conditions (Scheme 5). The reaction
using 10% H SO (THF, rt, 1 h) gave a mixture of (R)-
1
4
under the reaction conditions.
These results suggest that the reactions of both syn- and
anti-9 proceed via the common a-silyl cation intermediate
A having a stable anti conformation as compared with an
2
4
1
3
vinylsilane 13 (Julia-type rearrangement product, 38%),
(
0
0
eomer 15 (14%) whose composition was almost identical
0
1R,2S,1 R)-silylcyclopropane 14 (16%) and its 1 S diaster-
unfavorable eclipsed conformation A to give the rearrange-
ment products as shown in Scheme 6. The formation of the
vinylsilane (R)-13 would be a stereospecific process via the
transition state structure C where the positive charge is
4
with that of products from syn-1. The optical purity of the
starting syn-9 was completely retained in the rearranged
8
0
products (.95% ee). A trace amount of the primary
located at the more substituted C2 (secondary carbocation,
0
carbocation, path b). Thus, the reaction proceeded via
alcohol 16 was a by-product which would be produced by a
nucleophilic attack of 1,4-butanediol derived from THF. On
the other hand, the hydroxy diastereomer, anti-9 (.95%
ee), was completely consumed within 4 h to give a mixture
of (R)-13 (39%), 14 (20%) and 15 (26%) in an optically
path a) than the less substituted C3 in B (primary
0
path a in an S 2 manner to give (R)-13. On the other hand,
N
the formation of a mixture of diastereomeric 14 and 15
would be attributed to the tandem [1,2]-CC bond migration
from the a-silyl cation A via a putative cyclobutyl cation
8
active form (.95% ee). Thus, it was found that anti-9 gave

K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
6649
Scheme 4. Conditions. (a) (one-pot) (1) n-BuLi (1.05 equiv.), TBDMSCl (1.05 equiv.), THF, 08C, 2 h. (2) n-BuLi (1.2 equiv.), THF, 2458C, 1.5 h, then AcOH,
2
788C, 86%. (b) Jones oxidation, 91%. (c) (2)-DIP-Cl (1.5 equiv.), THF, 2408C, 2 h, 86%. (d) H
CH Cl , 2208C, 3 h, 75%. (f) PDC, CH Cl , rt, 1 h, 72%. (g) DIBAL-H, CH Cl , 2788C, 30 min, 88%. (h) (2)-DIP-Cl (1.5 equiv.), THF, rt, 2 h, 63%. (i) H
PPh RhCl, benzene, rt, 1 h, 69%.
2
, Lindlar cat., AcOEt, rt, 1 h, 81%. (e) Et
2
Zn, CH
2
I
2
2
,
,
2
2
2
2
2
2
(
3 3
)
1
5
D (path c), which immediately rearranged to a stable
cyclopropylcarbinyl cation F. H O attacks the cationic
The fact that anti-9 required longer reaction time (4 h) than
syn-9 (1 h) would be attributed to the ease of protonation to
the hydroxy group of 9. Conformation analysis of syn-9 and
2
center from the re- or si-face in a non-stereoselective
manner to give a mixture of 14 and 15. Since none of the
rearranged products derived from the primary cation G
1
anti-9 using H NMR revealed that the hydroxy group of
anti-9 was sterically more hindered (JHc–Hd¼12.3 Hz) than
(
path d) was obtained, path c to form D would be the favored
that of syn-9 (JHa–Hb¼11.2 Hz). Therefore, elimination of
rearrangement process. As the result, the reaction proceeded
in a competitive manner between the hydroxy attack to the
H O to produce A in anti-9 would be slower than that of
2
syn-9.
0
path c).
C2 position (path a) and the CC bond migration from A
(
Next, we examined the mode of rearrangement using a
Scheme 5.

6650
K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
Scheme 6.
Lewis acid in an aprotic solvent. The reaction of syn-9 with
BF OEt (0.1 equiv.) in CH Cl was completed within 2 h
slowly to give after 3.5 h a mixture of cyclopropane 20 (a
mixture of diastereomers at the hydroxy group) and homoallyl
alcohols 21 and 22 and unreacted starting material 19 [19: 20:
(21þ22)¼2:1.1:1.1]. Uponstandingthereactionfor72 h,both
19 and 20 disappeared to give a mixture of 21 (35%) and 22
3
2
2
2
at 2788C to give a mixture of (R)-13 (4%, .95% ee), 14
8%, .95% ee), 15 (16%, .95% ee), and the dimeric
(
products 17 (9%) and 18 (21% as a mixture of three
diastereomers) (Scheme 7). The fact that the reaction gave
the same rearranged products 13–15 in optically active
form as those from sulfuric acid indicates that the
rearrangement proceeded in the same manner as that using
aqueous sulfuric acid. Presumably, dimeric products 17 and
1
6
(35%, E/Z¼66/34). From these results, it was clearly
understood that (1) tandem [1,2] CC-shift occurs in both the
a-silyl and the a-methyl substrates, (2) the rate of the
rearrangement of a-hydroxysilanes 1 and 9 is 10–70 times
faster than that of the methyl derivative 19, and (3) the
rearranged cyclopropylcarbinol having a trialkylsilyl group is
18 were derived from 13 and a mixture of 14 and 15,
respectively.
1
4
stable under the reaction conditions for 20 h, while the
methyl derivative undergoes rapid ring-opening to give the
homoallyl alcohols.
The remaining question is whether the present rearrangement
is specific to the a-trialkylsilylcyclopropyl system. Thus, we
examined the reaction of an analogous substrate 19 having a
methyl group instead of a trialkylsilyl group (Scheme 8). The
reaction of 19 with 10% H SO in THF at room temperature
2.3. Acid-catalyzed rearrangement of a-hyroxy-
alkenylsilanes
2
4
1
was monitored using H NMR and was found to proceed
Next, we turned our attention to the acid-catalyzed
Scheme 7.

K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
6651
Scheme 8.
Table 1. Reactions of a-hydroxyalkenylsilanes and their analogs under acidic conditions
a
Entry
Substrate
Method
Condition
Results
1
A
rt, 21 h
2
A
rt, 23 h
Recovery of (R,Z)-8 85%, 94% ee
3
4
(R,Z)-8 .95% ee
(R,Z)-8 .95% ee
A
B
458C, 41 h
rt, 8 h
(R)-23 19%, 48% ee þ recovery of (R,Z)-8 57%, 93% ee
5
A
rt, 22 h
a
2 4 3 2 2 2
(a) Method A: 10% H SO aq. (20 equiv.) in THF; method B: BF ·OEt (1.5 equiv.) in CH Cl .
Scheme 9.
rearrangement of optically active a-hydroxyalkenylsilanes
Table 1). Treatment of a-hydroxysilane (R,E)-8 (90% ee)
with 10% H SO in THF at room temperature for 21 h gave
The same acidic treatment of the Z-isomer, (R,Z)-8 (.95%
ee), asabovewasveryslowandnoneoftherearrangedproduct
was produced (entry 2). Since the ee of the recovered (R,Z)-8
was 94%, no racemization was observed in (R,Z)-8. On the
other hand, upon warming to 458C the reaction gradually
proceeded to give, after 41 h, a mixture of vinylsilane (R)-23
(
2
4
a mixture of trans-vinylsilane (S)-23 (10%) and the starting
(
(
R,E)-8 (86%) (entry 1). The optical purity of the recovered
R,E)-8 was the same as that of the starting 8, while the
8
optical purity of the rearranged (S)-23 was 29% ee where the
ee of the starting 8 was much decreased. Treatment of (S)-23
(45% yield, 27% ee ) and the starting (R,Z)-8 (44% yield, 57%
8
ee ) (entry 3). Since 23 is optically stable under the warm-up
(
28% ee) under warm-up conditions (458C, 17 h) resulted in
conditions, partial racemization occurred at the a position of
the Z-isomer 8. Lewis acid treatment (BF , CH Cl , room
temperature, 8 h) of (R,Z)-8 afforded a mixture of the
the exclusive recovery of (S)-23 whose ee was the same as
that of the starting 23.
3
2
2

Table 2. Reactions of a-hydroxyalkynylsilanes, a-hydroxyalkylsilanes, and their analogs under acidic conditions
a
Entry
Substrate
Method
Condition
Results
1
A
Reflux, 19 h
Recovery of (R)-6 88% .95% ee
2
(R)-6>95% ee
B
rt, 2 h
3
A
Reflux, 21 h
4
5
A
B
Reflux, 18 h
Reflux, 24 h
Recovery of (R)-12 96% .95% ee
(R)-12 .95% ee
6
7
8
A
A
A
Reflux, 18 h
Reflux, 21 h
Recovery of (S)-32 73% 87% ee
Recovery of (R)-33 73% 87% ee
Reflux, 21 h
Reflux, 19 h
9
A
a
(a) Method A: 10% H
2
SO
4
aq. (20 equiv.) in THF; method B: BF
2
·OEt
2
2 2
(0.1 equiv.) in CH Cl .

K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
6653
8
rearrangement product (R)-23 (19%, 48% ee ) and the starting
8
are summarized in Table 2. The reaction of a-hydroxyalk-
ynylsilane (R)-6 with 10% H SO in THF at room temperature
(
R,Z)-8 (57%, 93% ee ) (entry 4).
2
4
did not proceed at all and even under reflux for 19 h resulted in
complete recovery of the starting material (entry 1). On the
other hand, treatment of its mesylate (R)-26 under the same
conditions gave a mixture of the optically active allene 27
From these results, acid-catalyzed rearrangement of a-
hydroxyalkenylsilane is summarized by the following
points. (1) Both (R,E)-8 and (R,Z)-8 are optically stable
alcohols under the reaction conditions at room tempera-
ture, since the recovered 8 showed the same ee values,
respectively (entries 1, 2, and 4). (2) Under the warm-up
conditions, the ee of 23 was completely retained. (3) The
1
8
2
6
19
{22%, [a] ¼2141.0 (c 1.68, CHCl )}, the unsaturated
D
3
8
ketone 28 (24%) and a-hydroxysilane (S)-6 (36%, 22% ee )
(entry 3). The allenyl mesylate 27 would be produced via [3,3]
sigmatropic rearrangement of (R)-26. The ketone 28 would be
0
(
R,E)-isomer gave (S)-23 containing 36% of its R-isomer,
formed by a nucleophilic attack of H O (S 2 ). The
2
N
and the (R,Z)-isomer gave (R)-23 containing 37% of the
corresponding S-isomer while the reaction of the Z-
isomer was much slower than that of the E-isomer
hydrolyzed product (S)-6 showed 22% ee suggesting that
competitive hydrolysis of the mesyl group and nucleophilic
substitution with H O occurred. Lewis acidic treatment of (R)-
2
(entries 1 and 2). (4) None of the rearranged Z-
vinylsilane was produced in all cases. (5) Partial
racemization occurred upon warming (R,Z)-8 to 458C
6 (BF OEt ) afforded a mixture of unsaturated ketone 30 (9%,
3
2
E/Z¼1/2.1) and the starting material (R)-6 (49%, .95% ee)
(entry 2). The formation of 30 would be the result of a [1,2]-
silyl shift. Silyl migration similar to that of 30 has been
(
(
entry 3). (6) Aprotic conditions using BF gave the same
3
R)-23 in 48% ee (entry 5).
6
reported by Schaumann et al.
These experimental results led us to propose the following
reaction pathway (Scheme 9): (1) A trigonal a silyl cation
which gives a completely racemized product did not form
except under the warm-up conditions of (R,Z)-8 where
formation of a delocalized allylic cation is also possible. (2)
The reaction proceeded from conformer H with the least
allylic strain among other conformers where the hydroxy
group locates perpendicular to the CC double bond plane.
Conformer I would be eliminated due to the fact that the Z-
Treatment of the a-hydroxyalkylsilane (R)-12 (10%
H SO , THF, reflux, 18 h) resulted in complete recovery
2
4
of the starting material without loss of its ee (entry 4). Its
mesylate gave a small amount of a hydrolyzed product
(entry 6). On the other hand, treatment of (R)-12 (.95%
ee) with BF OEt afforded dimerized product 31 in 37%
3
2
2
7
yield which showed [a] ¼29.9 (c 3.25 CHCl ).
D
3
Although its ee could not be estimated, 31 would contain
a significant amount of the optically active (R,R)-
enantiomer, i.e., the a-silyl cation from 12 would be
attacked by the hydroxy group of (R)-12 in an SN1
vinylsilane was not obtained. (3) Based on this assumption,
syn-S 2 reaction would be the major pathway to produce
0
S)-23 from (R,E)-8 or (R)-23 from (R,Z)-8. The reaction
N
(
also involved an anti-S 2 reaction that contributes to a
manner, since S 2 reaction would give the (R,S)-
N
enantiomer which is a mesomeric form (entry 5).
0
N
decrease in ee of the product. However, we have not reached
a conclusion regarding the preference of the syn attack over
the anti attack. (4) Lewis acid-catalyzed reaction of (R,Z)-8
would involve internal migration of the hydroxy group that
gives (R)-23, since the product ee (48%) was higher than
that obtained using protic conditions.
We, next, examined the acidic treatment of analogous
substrates having a methyl group instead of the TBDMS
2
0
group. Treatment of (R)-3-octyn-2-ol (32, .95% ee)
(10% H SO , THF, reflux, 21 h) resulted in recovery of (R)-
32 in 73% yield, but its optical purity was reduced to 87%
2
4
8
21
ee (entry 7). Treatment of (R)-2-octanol (33, .95% ee)
under the same conditions also resulted in recovery of
Next, we examined acid-catalyzed rearrangement of the a
1
7
8
methyl substrate, (S,Z)-3-octen-2-ol (24, .95% ee), to
compare the results obtained by the use of the TBDMS
substrate 8. Treatment of (S,Z)-24 using 10% H SO , THF,
partially racemized (R)-33 (entry 8, 73% yield, 87% ee ).
2
2
On the contrary to this, the reaction of the mesylate (R)-34
(10% H SO , THF, reflux, 19 h) gave (S)-2-octanol in 46%
yield with .95% ee (S 2 reaction) (entry 9). These results
2
4
2
4
room temperature, 24 h gave an unidentifiable mixture of
products which contained only trace amounts of (E)-24, 25
and the starting (Z)-24. The product mixture was analyzed
N
indicate that a-hydroxyalkynylsilane 6, a-hydroxyalkylsi-
lane 12 or its mesylate 29 is each much less reactive than the
corresponding methyl-substituted analog 32, 33 or 34 under
acidic conditions (10% H SO ), respectively.
1
by H NMR indicating that the ratio of (E)-24:25:(Z)-24 was
0:8:100. Because the reaction is sluggish and only trace
2
2
4
amounts of the products mixture were isolated, the ee values
of the products could not be obtained. However, we found
that the reaction involves allylic rearrangement together
with double bond isomerization. From these results, it is
seen that a-hydroxyalkenylsilane 8 gradually rearranges to
the trans-vinylsilane 23; however, 8 is much less reactive
than its methyl-substituted analog contrary to the case of the
a cyclopropyl substrates 9 and 19.
3. Conclusion
Systematic studies of the acid-catalyzed reactions of
a-hydroxycyclopropylsilane 9, a-hydroxyalkenylsilane 8,
a-hydroxyalkynylsilane 6, a-mesyloxyalkynylsilane 26, a-
hydroxyalkylsilane 12, and a-mesyloxyalkylsilane 29 were
performed for the first time. From the mode of rearrange-
ment using a-hydroxycyclopropylsilane it was well under-
2.4. Acid-catalyzed rearrangement of a-alkynyl and
a-alkyl a-hyroxysilanes
0
stood that the rearrangement involves an S 2 cyclopropyl
N
ring-opening and a tandem CC-migration reaction in a
competitive manner. The alkenylsilanes 8 gave the allylic
rearrangement product. Inspection of the products ee
Next, we examined acid-catalyzed rearrangement of a-
alkynyl or a-alkyl substituted a-hydroxysilanes. These results

6654
K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
Scheme 10.
0
suggested that the rearrangement involves a syn-SN2
reaction as the major pathway. On the other hand, the
reactions of alkynyl and alkyl substituted derivatives 6, 12,
and 29 were inert under the reaction conditions, while the
alkynyl mesylate 26 gave the rearranged products including
optically active allene. The reactivity profile of the a-
hydroxysilanes is depicted in Scheme 10. These results
suggest that the putative a-silyl cation generated from the a-
hydroxy or mesyloxy group is a short-lived species which
rapidly migrates to the more stable cyclopropylcarbinyl,
allyl, or allenyl cation to give the rearrangement product in
all cases tested which is consistent with the calculation of
were determined with a Yanaco MP-21 melting point
apparatus and were uncorrected. Optical rotations ([a] )
D
1
were taken on a Perkin–Elmer 241 polarimeter. H NMR
1
3
and C NMR spectra were recorded on one of the following
instruments: Varian Unity plus 500, JEOL JNM-LA400,
JEOL JNM-GX-400 or JEOL JNM-LA300. Chemical shifts
1
of H NMR were reported as d values in ppm relative to
CHCl (7.26) in CDCl , CH OH (3.30) in CD OD or HDO
3
3
3
3
1
3
(4.80) in D O. Chemical shifts of C NMR were reported as
2
d values in ppm relative to CDCl3 (77.00) in CDCl3,
CH OH (49.00) in CD OD or dioxane (68.90) in D
2-
3
3
O. Infrared spectra (IR) were measured on either a Hitachi
270-30 or a JASCO FT/IR-420 spectrophotometer. High-
resolution mass spectra (HRMS) were obtained on either a
JEOL JMS-D300 or a JEOL JMS-AX500 spectrometer for
electron ionization (EI), chemical ionization (CI) or fast
atom bombardment ionization (FAB).
2
the a-silyl cation.
4. Experimental
4
.1. General
4.1.1. (dl)-1-t-Butyldimethylsilyl-2-butyn-1-ol (rac-6). To
All reagents and solvents were purchased from either
Aldrich Chemical Company, Inc., Merck & Co., Inc.,
Nacalai Tesque Company, Ltd, Peptide Institute, Tokyo
Kasei Kogyo Co., Ltd, or Wako Pure Chemical Industries,
Ltd, and used without further purification unless otherwise
indicated. Tetrahydrofuran (THF) was distilled under an
argon atmosphere from sodium/benzophenone ketyl.
Dichloromethane (CH Cl ) was distilled from phosphoric
a solution of 2-butyn-1-ol (5, 15.0 g, 214 mmol) in THF
(180 mL) was added n-BuLi in n-hexane (1.60 M solution;
161 mL, 257 mmol) at 2788C, and the mixture was stirred
at 08C for 30 min. To the solution was added a solution of
TBDMSCl (35.48 g, 235 mmol) in THF (80 mL) at 2788C.
After stirring at rt for 4 h, n-BuLi in n-hexane (1.60 M
solution; 174 mL, 278 mmol) was added dropwise to the
solution at 2788C, and the mixture stirred at 2458C for 2 h.
The reaction was quenched by 10% AcOH in THF at
2
2
pentaoxide (P O ). Methanol (MeOH) was distilled from
2
5
magnesium turnings and iodine. Diethyl ether (Et O) of
2
2788C. The mixture was extracted with Et O, and the
2
anhydrous grade was used.
organic layer was washed with saturated NaHCO3 and
brine, dried over MgSO . The solvent was evaporated in
4
All reactions were monitored by thin layer chromatography
TLC), carried out on 2£5 cm precoated TLC plates (Merck
vacuo. The residue was purified by flash column chroma-
tography on silica gel (n-hexane/Et O¼30/1) to give rac-6
(
Kieselgel gel 60F-254; layer thickness, 0.25 mm), with UV
2
1
(34.86 g, 88%) as pale yellow oil: H NMR (400 MHz,
light (254 nm), KMnO solution (0.5 g dissolved in 100 mL
4
CDCl
1.34 (br, 1H, exchangeable with D O), 0.97 (s, 9H), 0.09 (s,
3H), 0.07 (s, 3H); C NMR (100 MHz, CDCl ) d 84.0,
3
80.2, 55.1, 26.9, 16.9, 3.8, 28.0, 28.6; IR (neat) 3448,
2960, 2900, 2864, 2310, 1696, 1590, 1466, 1250, 976, 838,
3
) d 4.17 (q, J¼2.7 Hz, 1H), 1.87 (d, J¼3.0 Hz, 3H),
of water), ninhydrin solution (TCI N-094) and/or phospho-
molybdic acid solution (10 g dissolved in 150 mL of EtOH).
Silica gel (DAISO-GEL IR-60-63/210W or IR-60-40/63W)
was used for column chromatography. Melting points (mp)
2
1
3

K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
6655
82 cm2 ; HRMS (EI) m/z calcd for C H OSi (M)
84.1283, found 184.1264.
1
þ
0 0
(1R,1 R,2 S)-syn-9 (1.32 g, 75%) as pale yellow oil:
7
1
1
0 20
1
7
1
[a] ¼þ29.4 (c 1.43, CHCl , .95% ee); H NMR
D
3
(
400 MHz, CDCl ) d 3.05 (d, J¼11.3 Hz, 1H), 1.58 (br,
3
4.1.2. 1-t-Butyldimethylsilyl-2-butynone (7). To a solution
of rac-6 (32.00 g, 86.8 mmol) in acetone (100 mL) was
1H), 1.07 (d, J¼5.1 Hz, 3H), 1.03 (m, 1H), 0.97 (s, 9H),
0.87 (m, 1H), 0.73 (m, 1H), 0.07 (s, 3H), 0.03 (s, 3H), 0.02
(m, 1H); C NMR (100 MHz, CDCl ) d 63.5, 26.9, 21.7,
1
3
added dropwise Jones reagent (110 mL, 27% solution) at
0
3
8C until the reaction mixture became red. To the mixture
16.8, 14.3, 12.4, 11.2, 27.2, 29.0; IR (neat) 3456, 2956,
2936, 2888, 2860, 1464, 1392, 1364, 1250, 1027, 1010, 984,
was added isopropyl alcohol at 08C until the reaction
mixture became green. After removal of the solvent in
vacuo, the reaction mixture was exposed to aqueous
2
1
940, 838, 802, 774 cm ; HRMS (FAB) m/z calcd for
þ
C H OSi (M2H) 199.1518, found 199.1529.
11 23
NaHCO3 (350 mL) and was extracted with Et O. The
2
organic layer was washed with brine and dried over MgSO4.
The solvent was evaporated in vacuo. The residue was
purified by flash column chromatography on silica gel (n-
4.1.6. (1R,2S)-2-Methylcyclopropyl t-butyldimethylsilyl
ketone (10). To a solution of (1R,1 R,2 S)-syn-9 (3.6 g,
0
18.1 mmol) in CH Cl (20 mL) were added PDC (6.8 g,
0
2
2
hexane/ethyl acetate¼50/1) to give 7 (27.22 g, 86%) as
18.1 mmol) at rt for 30 min. The mixture was filtrated and
the solvent was evaporated in vacuo. The residue was
purified by flash column chromatography on silica gel (n-
hexane/ethyl acetate¼40/1) to give 10 (2.6 g, 72%) as
1
yellow oil: H NMR (400 MHz, CDCl ) d 2.09 (s, 3H), 0.96
3
1
3
(
s, 9H), 0.21 (s, 6H); C NMR (100 MHz, CDCl ) d 226.0,
3
9
2
8
8.5, 85.0, 26.3, 16.8, 4.4, 27.5; IR (neat) 2960, 2936,
892, 2864, 2280, 2192, 1594, 1466, 1252, 1142, 840, 820,
1
4
1
yellow oil: [a] ¼þ11.3 (c 1.19, CHCl ); H NMR
D
3
2
1
04, 780 cm ; HRMS (CI) m/z calcd for C H OSi
1
(500 MHz, CDCl ) d 2.60 (ddd, J¼8.8, 7.6, 5.6 Hz, 1H),
0
19
3
þ
(
MþH) 183.1205, found 183.1203.
1.49 (m, 1H), 1.16 (ddd, J¼7.1, 5.4, 3.7 Hz, 1H), 0.97 (d,
J¼6.1 Hz, 3H), 0.93 (s, 9H), 0.86 (ddd, J¼15.5, 7.9, 4.9 Hz,
1
3
4
.1.3. (R)-1-t-Butyldimethylsilyl-2-butyn-1-ol {(R)-6}. To
1H), 0.19 (s, 3H), 0.16 (s, 3H); C NMR (125 MHz,
CDCl ) d 246.2, 32.4, 26.5, 21.2, 16.8, 15.1, 11.8, 27.1,
a solution of (2)-DIP-Cl (8.2 g, 26.3 mmol) in THF
25 mL) was added a solution of 7 (3.0 g, 16.5 mmol) in
3
(
27.3; IR (neat) 2964, 2936, 2864, 1732, 1616, 1460, 1368,
2
1
THF (20 mL) at 2788C under an argon atmosphere, and the
reaction mixture was stirred at 2358C for 5 h. To the
reaction mixture was added diethanolamine (6.5 g,
1250, 1214 cm ; HRMS (EI) m/z calcd for C H OSi
11 22
þ
(M) 198.1440, found 198.1423.
0 0 0
4.1.7. (1S,1 R,2 S)-2 -Methylcyclopropyl t-butyldimethyl-
silyl methanol {(1S,1 R,2 S)-anti-9}. To a solution of 10
7
1
4.3 mmol), and the reaction mixture was stirred at rt for
6 h. After addition of Et O, the mixture was filtrated, and
0
0
2
the filtrate was dried over MgSO . The solvent was
4
(450 mg, 2.3 mmol) in CH Cl (14 mL) was added DIBAL
2
2
evaporated in vacuo. The residue was purified by flash
column chromatography on silica gel (n-hexane/
AcOEt¼100/1, then 50/1) to give (R)-6 (2.5 g, 82%) as
in n-hexane (0.96 mol/l, 2.8 mL) at 2788C under an argon
atmosphere. The reaction mixture was stirred at 2788C.
After 0.5 h, the reaction was quenched by saturated NH Cl.
The mixture was extracted with Et O, and organic layer was
2
washed with brine, dried over MgSO . The solvent was
4
4
1
7
pale yellow oil: [a] þ77.7 (c 1.02, CHCl , .95% ee).
D
3
4.1.4. (R,Z)-1-t-Butyldimethylsilyl-2-buten-1-ol {(R,Z)-8}.
A suspension of (R)-6 (200 mg, 1.08 mmol) and Lindlar
evaporated in vacuo. The residue was purified by flash
column chromatography on silica gel (n-hexane/ethyl
0
0
catalyst (10 mg, 0.11 mmol) in AcOEt (10 mL) was stirred
under H at rt for 3 h. The mixture was filtrated, and the filtrate
acetate¼50/1) to give (1S,1 R,2 S)-anti-9 (279 mg, 61%)
D 3
1
4
as pale yellow oil: [a] ¼þ18.4 (c 0.81, CHCl , .95% ee);
2
1
was concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel (n-hexane/ethyl
acetate¼35/1) to give (R,Z)-8 (190 mg, 95%) as colorless
H NMR (400 MHz, CDCl ) d 3.11 (d, J¼11.7 Hz, 1H),
3
1.29 (br s, 1H, exchangeable with D O), 1.18 (d, J¼6.1 Hz,
2
3H), 1.08–0.99 (2H), 0.97 (s, 9H), 0.77 (m, 1H), 0.07 (s,
3H), 0.00 (s, 3H), 20.07 (m, 1H); C NMR (100 MHz,
CDCl ) d 65.5, 27.0, 20.6, 16.8, 12.8, 12.6, 10.3, 27.1,
1
5
1
13
oil: [a] ¼þ49.3 (c 1.05, CHCl ); H NMR (400 MHz,
D
3
CDCl ) d 5.56 (ddq, J¼10.6, 10.6, 1.7 Hz, 1H), 5.45 (dqd,
3
3
J¼10.6, 6.9, 1.2 Hz, 1H), 4.47 (d, J¼10.5 Hz, 1H), 1.63 (dd,
28.5; IR (neat) 3480, 3064, 2996, 2956, 2932, 2888, 2860,
1466, 1450, 1394, 1364, 1250, 1032, 1018, 982, 836, 778,
J¼6.8, 1.7 Hz, 3H), 1.57 (br s, 1H, exchangeable with D O),
2
1
3
21
þ
0.96 (s, 9H), 0.36 (s, 3H), 20.06 (s, 3H); C NMR (100 MHz,
CDCl ) d 127.0, 123.1, 65.7, 26.8, 17.8, 17.0, 27.8, 28.3; IR
656 cm ; HRMS (CI) m/z calcd for C H OSi (M)
1
1 24
200.1596, found 200.1591.
3
(
9
1
neat) 3370, 2930, 2859, 1722, 1523, 1464, 1351, 1251, 1168,
59, 841 cm2 ; HRMS (CI) m/z calcd for C H OSi (M)
86.1440, found 186.1444.
1
þ
4.1.8. (R)-1-t-Butyldimethylsilyl-1-butanol {(R)-12}. A
solution of (R)-6 (1.00 g, 5.4 mmol) and Wilkinson catalyst
1
0 22
(700 mg, 0.76 mmol) in benzene (40 mL) was stirred under
H at rt for 1 h. The solvent was evaporated in vacuo. The
0
0
0
4
.1.5. (1R,1 R,2 S)-2 -Methylcyclopropyl t-butyldimethyl-
2
0
0
silyl methanol {(1R,1 R,2 S)-syn-9}. To a solution of (R,Z)-
(1.64 g, 8.82 mmol) in CH Cl (50 mL) were added ZnEt
2
56.7 mL, 56.7 mmol) and CH I (4.6 mL, 56.7 mmol) at
2
2108C under an argon atmosphere. After stirring for 3 h, the
reaction was quenched by saturated NH Cl. The mixture
was extracted with Et O, and organic layer was washed with
2
brine, dried over MgSO . The solvent was evaporated in
4
vacuo. The residue was purified by flash column chroma-
tography on silica gel (n-hexane/ethyl acetate¼50/1) to give
residue was purified by flash column chromatography on
silica gel (n-hexane/ethyl acetate¼30/1) to give (R)-12
8
(
2
2
2
4
(703 mg, 69%) as a colorless oil: [a] ¼27.89 (c 1.47,
2
D
1
CHCl , .95% ee); H NMR (400 MHz, CDCl ) d 3.5 (dd,
3
3
J¼10.6, 2.6 Hz, 1H), 1.63 (br s, 1H, exchangeable with
4
D O), 1.67–1.43 (3H), 1.37–1.28 (m, 1H), 0.95–0.94 (3H),
2
1
3
0.94 (s, 9H), 0.01 (s, 3H), 20.05 (s, 3H); C NMR
(100 MHz, CDCl ) d 64.1, 36.5, 27.0, 19.9, 16.8, 13.9,
27.6, 28.7; IR (neat) 3421, 2956, 2929, 2857, 1465, 1362,
3

6656
K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
1
0
1
HRMS (FAB) m/z calcd for C H OSi (M2H) 187.1518,
found 187.1518.
254, 1050, 1006, 953, 806, 774, 655, 572, 419 cm2
;
4.3.2. (1R,2S,1 R)-1-(2-t-Butyldimethylsilylcyclopropy-
11
þ
l)ethanol (14). [a] ¼þ26.9 (c 0.98, CHCl , .95% ee);
1
0
23
D
3
1
H NMR (400 MHz, CDCl ) d 3.16 (ddd, J¼13.9, 6.3,
3
6
.3 Hz, 1H), 1.42 (br, 1H, exchangeable with D O), 1.28 (d,
2
4
8
.1.9. (R,E)-1-t-Butyldimethylsilyl-2-buten-1-ol {(R,E)-
}. To a solution of (2)-DIP-Cl (3.79 g, 12.2 mmol) in
J¼6.2 Hz, 3H), 0.93 (s, 9H), 0.81 (m, 1H), 0.49–0.38 (2H),
20.13 (s, 3H), 20.19 (s, 3H), 20.39 (ddd, J¼10.1, 6.6,
1
3
THF (15 mL) was added a solution of 11 (1.41 g, 7.7 mmol)
in THF (15 mL) at 2788C under an argon atmosphere, and
the reaction mixture was stirred at rt for 52 h. To the
reaction mixture was added diethanolamine (3.04 g,
6.6 Hz, 1H); C NMR (100 MHz, CDCl ) d 74.2, 27.3,
3
24.1, 23.2, 17.8, 6.9, 0.0, 26.5, 27.2; IR (neat) 3876, 3388,
2
1
3060, 2956, 2932, 2884, 2856, 1252, 832, 808, 768 cm
þ
;
HRMS (EI) m/z calcd for C H OSi (M) 200.1596, found
1
1 24
3
1
4.7 mmol), and the reaction mixture was stirred at rt for
4 h. After Et O was added the mixture was filtrated, and
200.1604.
2
0
the filtrate was dried over MgSO . The solvent was
4
4.3.3. (1R,2S,1 S)-1-(2-t-Butyldimethylsilylcyclopropy-
1
1
D
evaporated in vacuo to give a crude residue, which was
purified by flash column chromatography on silica gel (n-
hexane/AcOEt, 80/1) to give (R,E)-8 (0.90 g, 4.9 mmol) as
l)ethanol (15). [a] ¼þ20.3 (c 1.19, CHCl , .95% ee);
3
1
H NMR (400 MHz, CDCl ) d 3.05 (ddd, J¼12.4, 8.3,
3
6.3 Hz, 1H), 1.69 (br, 1H, exchangeable with D O), 1.28 (d,
2
2
2
1
pale yellow oil: [a] ¼þ33.1 (c 1.02, CHCl , 90% ee); H
J¼6.1 Hz, 3H), 0.91 (s, 9H), 0.80 (m, 1H), 0.52 (ddd,
J¼10.2, 4.2, 4.2 Hz, 1H), 0.42 (ddd, J¼7.1, 7.1, 3.9 Hz,
1H), 20.16 (s, 3H), 20.19 (s, 3H), 20.50 (ddd, J¼10.3, 6.6,
D
3
NMR (400 MHz, CDCl ) d 5.56 (ddq, J¼15.6, 7.2, 1.5 Hz,
3
1
H), 5.50 (dqd, J¼15.0, 6.4, 1.5 Hz, 1H), 4.05 (dt, J¼7.2,
.5 Hz, 1H), 1.71 (dt, J¼6.4, 1.5 Hz, 3H), 1.35 (br, 1H,
1
3
1
exchangeable with D O), 0.94 (s, 9H), 0.00 (s, 3H), 20.06
6.6 Hz, 1H); C NMR (100 MHz, CDCl ) d 74.4, 26.7,
3
23.3, 22.8, 17.1, 7.3, 21.3, 27.3, 27.7; IR (neat) 3912,
3804, 3592, 3368, 3060, 2956, 2932, 2888, 2856, 1472,
2
1
3
(
s, 3H); C NMR (100 MHz, CDCl ) d 133.3, 122.3, 67.0,
3
2
1
2
1
1
7.0, 17.9, 17.0, 27.7, 28.9; IR (neat) 3370, 2932, 2854,
716, 1635, 1578, 1464, 1365, 1341, 1251, 1224, 1095,
1466, 1254, 1104, 960, 826, 766 cm ; HRMS (EI) m/z
þ
calcd for C H Osi (M) 200.1596, found 200.1590.
11 24
2
1
005, 969, 828, 741 cm ; HRMS (EI) m/z calcd for
þ
C H OSi (M) 186.1440, found 186.1434.
0 22
4.3.4. (E)-1,4-Butanediol mono-2-(5-t-butyldimethylsi-
1
1
lylpent-4-enyl)ether (16). H NMR (300 MHz, CDCl ) d
3
4.2. General procedure for acid-catalyzed
rearrangement reaction of a-hydroxysilane with H SO
6.01 (dd, J¼18.6, 6.6 Hz, 1H), 5.69 (d, J¼18.6 Hz, 1H),
3.68–3.58 (m, 2H), 3.56–3.36 (m, 3H), 2.48–2.14 (m, 2H),
2
4
1
.90 (br, 1H), 1.68–1.48 (m, 6H), 1.14 (d, J¼6.24 Hz, 3H),
To a solution of a-hydroxysilane (1.0 equiv.) in THF was
added aqueous 10% H SO (20 equiv.) at rt, and the reaction
0.86 (s, 9H), 0.00 (s, 6H); HRMS (CI) m/z calcd for
C H O Si (MþH) 273.2250, found 273.2254.
þ
2
4
15 33 2
mixture was stirred under the reaction condition. The
reaction was quenched by saturated NaHCO , and the
mixture was extracted with Et O. The organic layer was
2
p
0
(19). H NMR (300 MHz, CDCl ) d 3.37 (m, 1H), 1.60 (br s,
p
0
p
0
4.3.5. (1R ,1 R ,2 R )-1-(2 -n-Butylcyclopropyl)ethanol
1
3
3
washed with brine and dried over MgSO . The solvent was
4
evaporated in vacuo. The residue was purified by flash
column chromatography on silica gel.
1H), 1.54–1.26 (6H), 1.30 (d, J¼5.9 Hz, 3H), 1.07 (m, 1H),
0.90 (t, J¼7.1 Hz, 3H), 0.85 (m, 1H), 0.70 (m, 1H), 0.04 (q,
J¼4.7 Hz, 1H).
1
4.3. General procedure for acid-catalyzed
rearrangement reaction of a-hydroxysilane with
4.3.6. (E)-2-Nonen-5-ol (21). H NMR (500 MHz, CDCl )
3
d 5.53 (dqt, J¼15.1, 6.1, 1.5 Hz, 1H), 5.42 (dtq, J¼15.1, 7.7,
BF OEt
3
1.2 Hz, 1H), 3.56 (m, 1H), 2.20 (m, 1H), 2.04 (m, 1H), 1.67
2
(
dd, J¼6.1, 1.2 Hz, 1H), 1.52 (br s, 1H, exchangeable with
1
3
To a solution of a-hydroxysilane in CH Cl was added
2
D O), 1.49–1.25 (4H), 0.89 (t, 3H); C NMR (125 MHz,
2
2
BF OEt at reaction condition. The mixture was stirred under
3
CDCl ) d 128.8, 127.2, 71.0, 40.7, 36..5, 27.9, 22.7, 18.0, 14.0.
3
the reaction condition. The reaction was quenched by
saturated NaHCO , and the mixture was extracted with
Et O. The organic layer was washed with brine and dried
2
1
4.3.7. 4-Nonen-2-ol (22, E/Z mixture). H NMR
(500 MHz, CDCl ) d 5.56–5.49 (1H), 5.42–5.34 (1H),
3
3
over MgSO . The solvent was evaporated in vacuo. The
4
residue was purified by flash column chromatography on
silica gel.
3.80–3.73 (1H), 2.26–2.14 (1H), 2.10–1.99 (3H), 1.56 (br
s, 1H, exchangeable with D O), 1.36–1.24 (4H), 1.18 (d,
2
J¼6.3 Hz, 1.02H), 1.16 (d, J¼6.1 Hz, 1.98H), 0.89–0.86
1
3
(
3H); C NMR (125 MHz, CDCl ) d 134.7, 133.4, 125.8,
3
4
1
.3.1. (R,E)-5-t-Butyldimethylsilyl-4-penten-2-ol {(R)-
1
125.0, 67.8, 67.3, 42.6, 37.2, 32.3, 31.9, 31.7, 27.1, 22.8,
22.6, 22.3, 22.2, 13.9, 13.8.
1
D
1
3}. [a] ¼27.2 (c 0.92, CHCl , .95% ee); H NMR
3
(
400 MHz, CDCl ) d 6.03 (dt, J¼18.5, 6.4 Hz, 1H), 5.76 (d,
3
J¼18.4 Hz, 1H), 3.87 (ddq, J¼6.3, 6.2 Hz, 1H), 2.30 (2H),
4.3.8. (R,E)-4-t-Butyldimethylsilyl-3-buten-2-ol {(R)-23}.
1
6
1
1
3
.56 (br, 1H, exchangeable with D O), 1.20 (d, J¼6.2 Hz,
[a] ¼þ4.3 (c 1.31, CHCl , 48% ee); H NMR (400 MHz,
2
D
3
1
3
H), 0.87 (s, 9H), 0.02 (s, 6H); C NMR (100 MHz,
CDCl ) d 6.10 (dd, J¼18.8, 5.1 Hz, 1H), 5.82 (dd, J¼18.8,
3
CDCl ) d 143.9, 131.7, 66.8, 46.9, 26.4, 22.7, 16.4, 26.1,
3
2
1
6
2
1.5 Hz, 1H), 4.29 (m, 1H), 1.61 (br s, 1H, exchangeable with
1
3
6.2; IR (neat) 3740, 3688, 3352, 2956, 2932, 2896, 2856,
620, 1472, 1466, 1250, 1120, 1078, 992, 828, 812, 780,
D O), 1.26 (d, J¼6.3 Hz, 3H), 0.86 (s, 9H), 0.02 (s, 6H); C
NMR (100 MHz, CDCl ) d 151.1, 125.2, 70.6, 26.4, 23.1,
2
3
2
1
þ
56 cm ; HRMS (EI) m/z calcd for C H OSi (M)
1
16.4, 26.2; IR (neat) 3341, 2953, 2927, 2883, 2857, 1717,
1619, 1471, 1463, 1362, 1248, 1130, 1060, 990, 939, 830,
1 24
00.1596, found 200.1596.

K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
6657
77, 662 cm2 ; HRMS (EI) m/z calcd for C H O Si (M)
86.1440, found 186.1466.
1
þ
4.3.14. (Z)-2-t-Butyldimethylsilyl-2-butenal (E-30).
NMR (300 MHz, CDCl ) d 9.53 (s, 1H), 7.31 (q,
1
H
7
1
1
0 22 2
3
J¼7.15 Hz, 1H), 2.12 (d, J¼7.15 Hz, 3H), 0.88 (s, 9H), 0.23
1
21
4
.3.9. (Z)-3-Octen-2-ol (24). H NMR (400 MHz, CDCl ) d
3
(s, 6H);IR(neat) 2955, 2927, 2856, 1250, 836, 668, 419 cm
.
5
.46–5.40 (2H), 4.64 (dq, J¼6.4, 6.4 Hz, 1H), 2.11–1.99
1
(
2H), 1.69 (br s, 1H, exchangeable with D O), 1.39–1.28
2
4.3.15. (E)-2-t-Butyldimethylsilyl-2-butenal (E-30).
NMR (300 MHz, CDCl ) d 10.34 (s, 1H), 6.92 (q,
H
(
4H), 1.24 (d, J¼6.4 Hz, 3H), 0.89 (t, J¼7.0 Hz, 3H).
3
J¼7.34 Hz, 1H), 2.18 (d, J¼7.34 Hz, 3H), 0.85 (s, 9H),
4.3.10. 1-t-Butyldimethylsilyl-1-mesyloxy-2-butyne (26).
To a solution of (R)-6 (1.0 g, 5.43 mmol) in CH Cl
0.11 (s, 6H); IR (neat) 2955, 2927, 2856, 1250, 836, 668,
.
419 cm2
1
2
2
(
30 mL) added pyridine (3.1 mL, 38 mmol) at rt for
1
1
0 min. To the solution was added MsCl (1.3 mL,
6.3 mmol) at rt. After stirring at rt for 2.5 h, the reaction
4.3.16.
2
Bis(1-t-butyldimethylsilyl-butyl)oxide
1
(31).
[a] ¼29.94 (c 3.25, CHCl ); H NMR (400 MHz,
7
D
3
was quenched by 1N HCl. The mixture was extracted with
Et O, and organic layer was washed with saturated NaHCO
and brine, dried over MgSO . The solvent was evaporated in
CDCl ) d 4.06 (dd, J¼9.64, 2.81 Hz, 2H), 1.61–1.40
3
(6H), 1.35–1.20 (2H), 0.93–0.89 (6H), 0.91 (s, 18H),
2
3
1
3
20.04 (s, 6H), 20.05 (s, 6H); C NMR (100 MHz, CDCl3)
d 64.1, 36.6, 27.3, 20.0, 16.9, 14.0, 27.2, 27.5; IR (neat)
3198, 2956, 2928, 2857, 2360, 2343, 1464, 1398, 1365,
4
vacuo. The residue was purified by flash column chroma-
tography on silica gel (n-hexane/ethyl acetate¼30/1) to give
2
7
2
2
5
3
6 (795 mg, 56%) as pale yellow oil: [a] ¼þ128.9 (c
1308, 1247, 1119, 1076, 1052, 1008, 959, 937, 830, 808,
21
D
1
.132, CHCl , .95% ee); H NMR (400 MHz, CDCl ) d
3
781, 661, 574 cm
.
3
.05 (q, J¼2.44 Hz, 1H), 3.11 (s, 3H), 1.91 (d, J¼2.44 Hz,
1
3
H), 0.98 (s, 9H), 0.15 (s, 3H), 0.12 (s, 3H); C NMR
4.3.17. (S)-3-Octyn-2-ol {(S)-32}. To a solution of rac-32
(2 g, 15.9 mmol) in n-hexane was added MS4A and vinyl
acetate (4.5 g, 52.4 mmol) and Lipase AK (1 g, 50 wt%)
at rt. After stirring at rt for 5 h, the reaction mixture was
filtrated. The solvent was evaporated in vacuo. The
residue was purified by flash column chromatography on
silica gel (n-hexane/ethyl acetate¼40/1) to give (R)-2-
acetoxy-3-octyne (1.53 g, 58%) and (S)-32 (0.57 g, 29%,
(
100 MHz, CDCl ) d 88.3, 74.8, 66.3, 39.4, 26.7, 17.0, 3.9,
3
2
7.8, 28.3; IR (neat) 2953, 2930, 2860, 1472, 1359, 1252,
2
1
1
for C H O SSi (M2Me) 247.0824, found 247.0818.
174, 974, 911, 820, 553, 520 cm ; HRMS (CI) m/z calcd
þ
10 19 3
4
.3.11. 1-t-Butyldimethylsilyl-3-mesyloxy-1,2-butadiene
2
6
D
1
(
27). [a] ¼2141.0 (c 1.68, CHCl ); H NMR (400 MHz,
3
2
7
CDCl ) d 5.87 (ddd, J¼4.15 Hz, 1H), 3.03 (s, 3H), 2.05 (d,
.95% ee) as colorless oil: [a] ¼230.1 (c 1.73, CHCl ,
3
D
3
1
3
1
J¼4.15 Hz, 3H), 0.91 (s, 9H), 0.10 (s, 6H); C NMR
.95% ee); H NMR (300 MHz, CDCl ) d 4.49 (ddq,
3
(
100 MHz, CDCl ) d 204.7, 121.4, 98.6, 37.9, 26.1, 18.5,
3
J¼2.0, 2.0, 6.6 Hz, 1H), 2.18 (ddd, J¼1.8, 7.0, 7.0 Hz,
1
1
7
6.8, 26.0, 26.1; IR (neat) 2952, 2929, 2885, 2858, 1959,
471, 1416, 1366, 1251, 1186, 1108, 965, 856, 838, 822,
2H), 1.98 (br, 1H), 1.40 (d, J¼6.4 Hz, 3H), 1.33–1.55
1
3
(4H), 0.89 (t, J¼7.1 Hz, 3H); C NMR (75 MHz, CDCl )
3
2
1
84, 707, 604, 542, 523 cm ; HRMS (CI) m/z calcd for
þ
d 84.58, 82.19, 58.52, 30.67, 24.70, 21.86, 18.27, 13.53;
IR (neat) 3400, 2936, 1464, 1372, 1330, 1156, 1078,
C H O SSi (M2Me) 247.0824, found 247.0813.
10 19 3
010, 968 cm2
1
.
1
1
4
.3.12. (E)-4-t-Butyldimethylsilyl-3-buten-2-one (28). H
NMR (400 MHz, CDCl ) d 7.03 (d, J¼19.27 Hz, 1H), 6.46
4.3.18. 2-Mesyloxy-octane {(R)-34}. To a solution of (R)-2-
octanol ((R)-33, 556 mg, 4.27 mmol) in CH Cl (15 mL)
added pyridine (2.4 mL, 29.9 mmol) at rt for 10 min. To the
solution was added MsCl (0.7 mL, 8.55 mmol) at rt. After
stirring at rt for 2.5 h, the reaction was quenched by 1N HCl.
3
(d, J¼19.27 Hz, 1H), 2.27 (s, 3H), 0.89 (s, 9H), 0.09 (s, 6H);
IR (neat) 2927, 2856, 1680, 1464, 1362, 1251, 1219, 997,
2
2
2
1
8
30, 530 cm ; HRMS (CI) m/z calcd for C H OSi
10 21
þ
(
MþH) 185.1362, found 185.1362.
The mixture was extracted with Et O, and organic layer was
2
4.3.13. 1-t-Butyldimethylsilyl-1-mesyloxy-butane (29).
To a solution of rac-12 (1.649 g, 8.76 mmol) in CH Cl
washed with saturated NaHCO3 and brine, dried over
MgSO . The solvent was evaporated in vacuo. The residue
2
2
4
(
1
1
40 mL) added pyridine (5 mL, 61.3 mmol) at rt for
0 min. To the solution was added MsCl (1.4 mL,
7.5 mmol) at rt. After stirring at rt for 4 h, the reaction
was purified by flash column chromatography on silica gel
(n-hexane/ethyl acetate¼15/1) to give (R)-34 (890 mg,
2
6
quant) as pale yellow oil: [a] ¼29.80 (c 1.66, CHCl ,
D
3
1
was quenched by 1N HCl. The mixture was extracted
with Et O, and organic layer was washed with saturated
NaHCO and brine, dried over MgSO . The solvent was
4
evaporated in vacuo. The residue was purified by flash
column chromatography on silica gel (n-hexane/ethyl
.95% ee); H NMR (300 MHz, CDCl ) d 4.77 (m, 1H),
3
2.97 (s, 3H), 1.77–1.52 (2H), 1.40 (d, J¼6.24 Hz, 3H),
2
1
3
1.37–1.19 (8H), 0.87 (t, J¼6.79 Hz, 3H); C NMR
3
(75 MHz, CDCl ) d 80.4, 38.6, 36.6, 31.6, 28.9, 25.0,
3
22.5, 21.1, 14.0; IR (neat) 2933, 2859, 1467, 1353, 1176,
2
21 3
1
acetate¼30/1) to give 29 (1.507 g, 65%) as pale yellow
972, 918, 531 cm ; HRMS (FAB) m/z calcd for C H O S
9
1
þ
oil: H NMR (400 MHz, CDCl ) d 4.78 (dd, J¼7.44,
(MþH) 209.1211, found 209.1185.
3
5
1
0
3
2
8
.00 Hz, 1H), 2.99 (s, 3H), 1.77 (m, 2H), 1.55 (m, 1H),
.45 (m, 1H), 0.95–0.94 (3H), 0.95 (s, 9H), 0.09 (s, 3H),
1
4.3.19. t-Butyldimethylsilyl propyl ketone (35). H NMR
(300 MHz, CDCl ) d 2.57 (t, J¼7.16 Hz, 2H), 1.53 (qt,
1
3
.06 (s, 3H); C NMR (100 MHz, CDCl ) d 77.9, 39.0,
3
3
5.3, 26.8, 20.3, 16.8, 13.9, 27.0, 27.2; IR (neat) 2959,
932, 2903, 2859, 1466, 1341, 1252, 1172, 971, 915, 879,
J¼7.43, 7.16 Hz, 2H), 0.92 (s, 9H), 0.87 (t, J¼7.43 Hz, 3H),
1
3
0.17 (s, 6H); C NMR (75 MHz, CDCl ) d 247.7, 52.2,
3
2
1
38, 824, 809, 778, 522 cm ; HRMS (EI) m/z calcd for
þ
26.4, 16.4, 15.3, 13.8, 27.0; IR (neat) 2958, 2930, 2859,
21
C H O SSi (M2t-Bu) 209.0668, found 209.0669.
7 17 3
1641, 1464, 1363, 1250, 837, 824, 806, 774, 419 cm
.

6658
K. Sakaguchi et al. / Tetrahedron 59 (2003) 6647–6658
4
.3.20. (E)-1-t-Butyldimethylsilyl-3-chloro-1-butene
1
I. Tetrahedron Lett. 1990, 31, 4677–4680. (b) Dahr, R. K.
Aldrichimica Acta 1994, 27, 43–51.
(
6
36). H NMR (400 MHz, CDCl ) d 6.58 (dd, J¼18.42,
3
.96 Hz, 1H), 5.86 (dd, J¼18.54, 0.73 Hz, 1H), 4.51 (ddq,
8. The optical purity and absolute configuration of chiral
secondary alcohols in this work were determined by the
J¼7.32, 6.83, 0.73 Hz, 1H), 1.59 (d, J¼6.59 Hz, 3H), 0.87
1
3
1
modified Mosher method using H NMR: Ohtani, I.; Kusumi,
(s, 9H), 0.05 (s, 3H), 0.04 (s, 3H); C NMR (100 MHz,
CDCl ) d 147.77, 128.19, 59.86, 29.70, 26.34, 24.74,
3
T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113,
4092–4093.
2
6.28, 26.30; IR (neat) 2954, 2927, 2856, 1726, 1464,
2
1
1
C H ClSi (M) 204.1101, found 204.1120.
362, 1255, 1173, 837, 668 cm ; HRMS (CI) m/z calcd for
þ
9. Sakaguchi, K.; Mano, H.; Ohfune, Y. Tetrahedron Lett. 1998,
39, 4311–4312.
1
0 21
1
0. (a) Danheiser, R. L.; Fink, D. M.; Okano, K.; Tsai, Y.-M.;
Szczepanski, S. W. J. Org. Chem. 1985, 50, 5393–5396. (b)
Scheller, M. E.; Frei, B. Helv. Chim. Acta 1985, 68, 44–52.
1. Sakaguchi, K.; Suzuki, H.; Ohfune, Y. Chirality 2001, 13,
1
4
.3.21. 2-Chloro-3-octyne (37). H NMR (300 MHz,
CDCl ) d 4.66 (qd, J¼6.79, 2.09 Hz, 1H), 2.23 (td,
3
J¼6.97, 2.09 Hz, 2H), 1.72 (d, J¼4.22 Hz, 3H), 1.57–
1
1
1
1
1
.34 (4H), 0.91 (t, J¼7.15 Hz, 3H).
3
57–365.
2. Hydrogenation of (R)-6 using 10% Pd–C afforded the silyl
ketone 35 in good yield.
3. Julia, M.; Julia, S.; Guegan, R. Bull. Soc. Chim. Fr. 1960,
Acknowledgements
1
072.
This study was financially supported by a Grant-in-Aid (No.
3680674) from the Ministry of Education, Science, Sports,
and Culture, Japan, and by a Grant from Suntory Institute
for Bioorganic Research (SUNBOR).
4. Acidic treatment of 15 with 10% H
2 4
SO (20 equiv.) in THF at
1
rt for more than 20 h resulted in a recovery of 15 accompanied
with a trace amount of 14.
1
5. The carbocationic rearrangement such as the ring expansion of
a cyclopropylacylsilane to a cyclobutanone has been reported.
(
a) Danheiser, R. L.; Fink, D. Tetrahedron Lett. 1985, 26,
513–2516. (b) Nakajima, T.; Segi, M.; Mitsuoka, T.; Fukute,
Y.; Honda, M.; Naitou, K. Tetrahedron Lett. 1995, 36,
667–1670.
References
2
1
. (a) Brook, M. A. Silicon in Organic Organometallic, and
Polymer Chemistry; Wiley-Interscience: New York, 2000; pp
1
1
6. Two alcohols E- and Z-22 were inseparable by the column
chromatography on silica gel. Their E/Z ratio was estimated by
4
80–510, Chapter 14. (b) Siehl, H.-U.; Mueller, T. The
Chemistry of Organic Silicon Compounds; Rappoport, Z.,
Apeloig, Y., Eds.; Wiley: Chichester, UK, 1998; vol. 2, p 595
Chapter 12. (c) Fleming, I.; Barbeto, A.; Walter, D. Chem.
Rev. 1997, 97, 2063–2192. (d) Colvin, E. W. Silicon in
Organic Synthesis; Butterworth: London, 1981.
1
H NMR.
1
7. The alcohol (S,Z)-24 was prepared from a-hydroxyalkynylsi-
lane (S)-32 by hydrogenation using the Lindlar catalyst.
1
8. The mesylate (R)-26 was prepared from a-hydroxyalkynylsi-
lane (R)-6 {MsCl (3 equiv.), pyridine (7 equiv.), CH
2 2
Cl , rt,
2
3
. The stability of the a-silyl cation was estimated by the
solvolysis and the calculation studies: Apeloig, Y.; Stanger, A.
J. Am. Chem. Soc. 1985, 107, 2806–2807.
2
.5 h, 56%} On the other hand, the reaction of a-hydroxyalk-
enylsilane (R,Z)-8 under the same conditions did not give its
mesylate but gave the allylic alcohol (R)-23 (26% yield, 56%
. Several studies on the stability of a-silyl cation, see: (a)
Apeloig, Y.; Biton, R.; bu-Freih, A. J. Am. Chem. Soc. 1993,
8
ee) and the allylic chloride 36 (32%).
1
2
2
2
9. The absolute configuration of the allene 27 was not
determined.
115, 2522–2523. (b) Soderquist, J. A.; Hassner, A. Tetra-
hedron Lett. 1988, 29, 1899–1902.
. Sakaguchi, K.; Fujita, M.; Ohfune, Y. Tetrahedron Lett. 1998,
0. Burgess, K.; Jennings, L. D. J. Am. Chem. Soc. 1991, 113,
6
4
5
6
129–6139.
39, 4313–4316.
1. (R)-2-Octanol (.95% ee) is commercially available from
Kawaken Fine Chemicals Co. Ltd.
. Sakaguchi, K.; Fujita, M.; Suzuki, H.; Higashino, M.; Ohfune,
Y. Tetrahedron Lett. 2000, 41, 6589–6592.
2
6
2. The mesylate (R)-34 {[a] ¼29.8 (c 1.66, CHCl ), .95% ee}
. Reverse Brook rearrangement of 2-alkynyl trialkylsilyl ether
was originally reported in the syntheses of a,b-bis-silylated
enals and enones: Mergardt, B.; Weber, K.; Adiwidjaja, G.;
Schaumann, E. Angew. Chem. Int. Ed. Engl. 1991, 30,
D
3
was prepared from (R)-33 {MsCl (2 equiv.), pyridine
7 equiv.), CH Cl , rt, 2.5 h, quant} On the other hand, the
(
2
2
reaction of the propargylic alcohol (S)-32 under the same
conditions did not give its mesylate but gave the propargylic
chloride 37 (68%).
1687–1688.
7
. (a) Sonderquist, E. J.; Anderson, C. L.; Miranda, E. I.; Rivera,