Lewis acid catalyzed stereoselective hydrosilylation of ketones under the control of σ-π chelation

Article abstract of DOI:10.1016/S0040-4020(02)00968-7

Hydrosilylation of 2-methyl-1-phenyl-pentan-1-one with Et₃SiH in the presence of catalytic amounts of B(C₆F₅)₃ gave the anti-product with slight predominance over syn-product (syn/anti=1:1.5). In contrast, the s

Full text of DOI:10.1016/S0040-4020(02)00968-7

Tetrahedron 58 (2002) 8195–8203
Lewis acid catalyzed stereoselective hydrosilylation of ketones
under the control of s–p chelation
*
Naoki Asao, Takeshi Ohishi, Kenichiro Sato and Yoshinori Yamamoto
Department of Chemistry, Graduate School of Science, Tohoku University, 980-8578 Sendai, Japan
Received 16 April 2002; accepted 1 May 2002
Abstract—Hydrosilylation of 2-methyl-1-phenyl-pentan-1-one with Et3SiH in the presence of catalytic amounts of B(C6F5)3 gave the anti-
product with slight predominance over syn-product (syn/anti¼1:1.5). In contrast, the syn-product was obtained stereoselectively in the
reaction of 2-methyl-1-phenyl-pent-4-yn-1-one bearing an ethynyl group at the b-position (syn/anti¼7:1). The syn-selectivities were also
observed in the B(C6F5)3-catalyzed reactions of other related ketones, such as a-methyl-b-alkynyl aryl ketones and a-methyl-b-alkynyl
alkyl ketones. The moderate anti-selectivity observed in the former case can be explained by the ordinary Felkin–Anh model. On the other
hand, the unusual syn-selectivity in the latter cases can be accounted for by the s–p chelation by R3Siþ, in which both the lone pair (s) of the
carbonyl group and the p-electrons of the alkyne coordinate to the silylium ion. The s–p chelation control was also effective for the 1,3-
asymmetric induction. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
communicated the unprecedented s–p chelation-controlled
stereoselective hydrosilylation of ketones using B(C6F5)3
catalyst.5,6 Herein, we wish to report the full detail on the
B(C6F5)3-catalyzed 1,2 and 1,3-stereoselective hydrosilyl-
ation of ketones (Scheme 1).
Since Cram’s pioneering work on chelation control in
Grignard-type addition to chiral alkoxy carbonyl sub-
strates,1 a number of studies on related subjects have
appeared.2 Among them, the Lewis acid-mediated chelation
control is one of the most fundamental and practically
important concepts in modern organic chemistry.3 It is well
accepted that the chelating controlled reaction proceeds
through the s-coordination of a lone pair of heteroatoms,
such as an oxygen of alkoxy groups and a nitrogen of amino
groups, to a Lewis acid (s–s chelation). Recently, we
reported the first example of chelation controlled regio- and
chemoselective reaction through the s-coordination of
carbonyl oxygen and p-coordination of triple bond to a
Lewis acid (s–p chelation).4 Based on this finding, we next
2. Results and discussion
2.1. 1,2-Stereoselective hydrosilylation
We examined the stereoselective hydrosilylation of various
ketones using R3SiH-B(C6F5)3 as a reducing agent.7 The
reaction of 2-methyl-1-phenyl-pentan-1-one 1 with Et3SiH
in the presence of catalytic amounts of B(C6F5)3 proceeded
smoothly to give a mixture of the hydrosilylated products 2
and 3 in 98% yield (Eq. (1)). Slightly predominant
formation of the anti-product 3 over syn-product 2 was
observed: the ratio of 2/3 was 1:1.5. We next examined the
hydrosilylation of 2-methyl-1-phenyl-pent-4-yn-1-one 4a
(R1¼Ph, R2¼H) under the same reaction conditions as
above. Interestingly, the syn-product 5a was afforded as the
major product (5a/6a¼7:1) (Eq. (2)). This result prompted
us to examine the hydrosilylation of 4a and related ketones
4b–h to clarify the generality of this unusual diastereo-
selectivity. The results are summarized in Table 1.
Scheme 1.
ð1Þ
Keywords: chelation; stereocontrol; alkynes; ketones.
*
Corresponding author. Tel.: þ81-22-217-6581; fax: þ81-22-217-6784;
e-mail: yoshi@yamamoto1.chem.tohoku.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00968-7

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N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
Table 1. s–p chelation-controlled hydrosilylation of 4
Entry
Substrate 4
R1 R2
R3SiH
Yield 5 and 6 (%)a Ratio 5/6
Figure 1.
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Et
c-C6H11
o-MePh
tBu
H
H
Me
Ph
4a Et3SiH 90
4a Ph2MeSiH 99
7.0:1
6.8:1
5.0:1
3.0:1
7.7:1
4.4:1
5.0:1
15:1
1
structures of 5b–g and 6b–g were assigned by their H
NMR spectra on the analogy of those of 5a, 6a, and 5h.
4b Et3SiH
4c Et3SiH
Quant
Quant
Quant
Quant
93
TMS 4d Et3SiH
The difference of the diastereoselectivities between Eqs. (1)
and (2) clearly shows that the acetylenic bond of 4 exerts a
crucial role upon the observed syn-selectivity. Piers et al.
proposed the interesting silane activation mechanism in the
B(C6F5)3 catalyzed hydrosilylation of aldehydes and
ketones; the ordinary mechanism, in which the carbonyl
oxygen of the electrophiles coordinates to B(C6F5)3 and thus
carbonyl substrates are activated, is not operative in the
B(C6F5)3 catalyzed reduction.7 Their extensive mechanistic
studies clarify that B(C6F5)3 activates the silane via hydride
abstraction to form the incipient silylium species which
enhances the electrophilicity of carbonyl group, facilitating
the reduction by [HB(C6F5)3]2 or R3SiH (Fig. 1).
H
H
H
H
4e Et3SiH
4f Et3SiH
4g Et3SiH
4h Et3SiH
94
Quant
.30:1
Reaction was performed with R3SiH (1 equiv.) and B(C6F5)3 (2 mol%) in
toluene at 08C within 1 h.
Isolated yield.
a
ð2Þ
The predominant formation of the syn-product was also
observed in the reaction of 4a with other silanes such as
Ph2MeSiH (entry 2). The reactions of 4b–d, bearing Me,
Ph, and TMS groups at the terminal position of alkyne,
respectively, also gave syn-selectivities (entries 3–5). Not
only aromatic ketones but also aliphatic ketones 4e, 4f, and
4h produced syn-products selectively (entries 6, 7, and 9).
Interestingly, stereoselectivities increased from 4.4:1
(R1¼Et) to .30:1 (R1¼tBu) as the substituents at R1
position became bulkier. These results clearly indicate that
the syn diastereoselectivity is widely observed in the
B(C6F5)3 catalyzed reduction of 4 with hydrosilanes.
Most probably, a silylium species is generated here also, and
the s–p coordination of this species is operative in the
reaction of 4. The anti diastereoselectivity in the reaction of
1 can be accounted for by the ordinary Felkin–Anh model.
The propyl group at the a-position is regarded as the largest
group and the Me as the medium size (model 11).
Accordingly, anti-3 is produced with slight preference,
and the observed low stereoselectivity is due to the small
steric difference between propyl and methyl group at the
a-position. On the contrary, in the reaction of 4, the
reduction would proceed through the s–p chelation of
R3Siþ (model 12): the hydride attack takes place from the
less hindered side to produce the syn-isomer 5. If the
ordinary Felkin–Anh model is involved also in the case of
4, the anti-diastereomer 6 should be produced predomi-
nantly, since a propargyl group is sterically larger than a Me
group. Indeed, the anti-selectivity was observed with slight
predominance when the reduction of 4a was carried out
using DIBAL-H, in which the ratio of 13/14 was 49:51.
The stereostructures of 5a and 6a were unambiguously
determined by converting 5a and 6a to 9a and 10,
respectively, as shown in Scheme 2. The treatment of a
mixture of 5a and 6a (4.9:1) with TBAF, followed by the
protection of the resulting alcohols by MPMCl under basic
condition gave 7 in 88% yield. The alkynyl part of 7 was
converted to a carboxylic acid by hydroboration-oxidative
work-up, which was subsequently esterified to give 8 in
47% yield. Deprotection of the MPM group of 8 by CAN
gave a mixture of the lactones 9a and 10 in a ratio of 4.6:1 in
1
87% yield. The H NMR spectrum of 9a was identical to
that of the known compound.8 The stereostructure of 5h,
which was obtained from the aliphatic ketone 4h, was also
determined by converting 5h to cis-6-tert-butyl-5-methyl-
tetrahydro-pyran-2-one (9b) via similar routes. The stereo-
The stereoselectivities decreased as the substituents R2 of 4
became bulky (entries 1, 3, and 4). Presumably, a bulky R2
group would make it difficult to form strong s–p chelation
in 12. Higher selectivity obtained in the case of 4d may be
explained by the well-known b-silyl effect, which would
make the chelation more stronger.9 The proposed chelation
model also can explain the reason the syn-selectivity was
obtained very predominantly or exclusively in the reaction
Scheme 2.

N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
Table 2. s–p chelation-controlled 1,3-hydrosilylation of 25
8197
Entry
Substrate 25
R2
Yield 26 and 27 (%)a
Ratio anti-26/syn-27
R1
R3
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
c-C6H11
tBu
Me
TMS
TMS
TMS
Ph
Me
H
Ph
Ph
TMS
TMS
25a
25a
25a
25b
25c
25d
25e
25f
Quant
90
Quant
90
Quant
85
Quant
Quant
83
6.5:1
4.2:1
4.2:1
6.5:1
4.8:1
3.3:1
12:1
18:1
3.6:1
20:1
2b
3c
4
5
6
7
8
9
10
c-C6H11
tBu
25g
25h
Me
77
Reaction was performed with Ph2MeSiH (1 equiv.) and B(C6F5)3 (2 mol%) in toluene at 08C within 1 h unless otherwise indicated.
Isolated yield.
a
b
Et3SiH was used instead of Ph2MeSiH.
PhMe2SiH was used instead of Ph2MeSiH.
c
of 4g and 4h having bulky R1 groups (entries 8 and 9). There
is a possibility that hydride may attack from the bottom side
of carbonyl group in the conformer 15, which produces the
anti-isomer 6. On the other hand, the axially oriented methyl
group prevents the hydride attack from the bottom side in
the conformer 16. The conformer 16 is more favored with
the bulkier R1 group because of the increased steric
repulsion between R1 and Me in 15.10
attempted the (C6F5)3B catalyzed hydrosilylation of
3-methyl-1-phenyl-5-trimethylsilyl-pentan-1-one 22a with
Ph2MeSiH (Eq. (5)). The reaction proceeded smoothly to
give a mixture of the reduced products 23a and 24a
quantitatively, however, no selectivity was observed
(23a/24a¼1:1). While the anti-product 23b was obtained
t
predominantly in the reaction of 22b bearing Bu group at
the b-position, the selectivity was not high
(23b/24b¼2.3:1). On the other hand, high anti-selectivities
were observed in the reaction of 25 bearing alkynyl moieties
(Eq. (6)) and the results are summarized in Table 2.
ð5Þ
The B(C6F5)3-catalyzed hydrosilylation of 17 with Et3SiH
afforded the syn-isomer 18 as a sole product in 99% yield
(Eq. (3)). Both the s–p chelation and Felkin–Anh model
leads to the syn-isomer, since isopropyl group at the
a-position of 17 is sterically larger than propargyl group.
On the other hand, the syn-selectivity was decreased (syn-
20/anti-21¼98:2) in the hydrosilylation of 19, bearing a
saturated propyl group instead of a propargyl group at the
a-position, under the same reaction condition (Eq. (4)).
These results clearly imply the s–p chelation can be used
not only for reversing the Felkin–Anh selectivity but also
for increasing it by choosing the substituent at the
a-position of carbonyl compounds.
ð6Þ
The reaction of the alkynyl ketone 25a with Ph2MeSiH gave
the anti-product 26a stereoselectively (26a/27a¼6.5:1)
(entry 1). The anti-selectivities were also observed in the
reactions using other silanes although the selectivities
slightly decreased (entries 2 and 3). Interestingly, stereo-
selectivities increased from 6.5:1 (R2¼Me) to 18:1
(R2¼tBu) as the substituent at R2 position became bulkier
(entries 4, 7, and 8). Not only aromatic ketones but also the
aliphatic ketones 25g and 25h produced the corresponding
anti-products selectively (entries 9 and 10). These results
clearly indicate that the anti diastereoselectivity is widely
observed in the B(C6F5)3 catalyzed reduction of 25 with
hydrosilanes.
ð3Þ
ð4Þ
The stereostructure of 26a was unambiguously determined
by converting 26a to cis-4-Methyl-6-phenyl-tetrahydro-
pyran-2-one 32a11 via a similar route to that shown in
Scheme 2. The stereostructures of 26h and 27h, which were
obtained from the aliphatic ketone 25h, were also
determined by converting an 11:1 mixture of 26h and 27h
to the 6-membered lactones 32h and 33h, as shown in
Scheme 3. To remove the silyl group at the terminus
position of alkyne, a mixture of 26h and 27h (11:1) was
treated with KOH in MeOH–THF. The reaction gave the
desired product 28 (anti/syn¼4.5:1) in 47% yield together
2.2. 1,3-Stereoselective hydrosilylation
The 1,2-asymmetric induction via the s–p chelation
control could be extended to the 1,3-system. First, we

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N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
37 was produced preferentially over 38 (Eq. (8)). Therefore,
the reactivity difference in the present reaction is not due to
the inductive effect but due to the coordinating effect of
alkyne leading to formation of the s–p chelation complex
34.
ð7Þ
ð8Þ
Scheme 3.
with the anti-alcohol 29 as a single diastereomer in 47%
yield. This result indicates that the desilylation of TMS and
Ph2MeSi group of the anti-isomer 26h proceeded more
readily than that of the syn-isomer 27h. Hydrogenation of
the alkynyl part of 28 with Pd–BaSO4 in the presence of
quinoline gave 30 in 80% yield and the resulting alkene 30
was converted to the corresponding alcohol 31 in 42% yield
by hydroboration-oxidative work-up. Deprotection of the
Ph2MeSi group of 31 by TBAF gave diol, which was
subsequently oxidized with NaClO in the presence of a
catalytic amount of TEMPO to give the lactones 32h and
33h in a ratio of 4.0:1 in 30% yield. Irradiation of the methyl
group at the 4-position of pyran ring of 33h enhanced the
signal of the proton at the 6-position (2.6% NOE), whereas
no enhancement was observed in the case of 32h.
Now it is clear that the s–p chelation is operative not only
in the 1,2- but also in the 1,3-asymmetric induction of
certain acetylenic ketones. The syn-diastereoisomers
obtained either exclusively or predominantly in the reaction
of 4 or the anti-isomer in the reaction of 25 can be
converted, upon reduction of the triple bond, to the anti-
Felkin–Anh products which are not easily available through
the ordinary reducing methods. We are now in a position to
apply the s–p coordination concept along with the well-
known s–s chelation in order to control stereoselectivities.
The anti-stereoselectivity in the reaction of 25 can be
accounted for by the s–p chelation model 34, which
involves hydride attack on the less hindered face of a
conformationally locked, internally chelated intermediate.2a
The stereoselectivities decreased as the silanes became
small (entries 1–3 in Table 2). Presumably, when the
sterically less-hindered silanes work as reducing agents
(M2H in 34), they would have smaller steric interactions
with the chiral center rather than that in the 1,2-system since
the chiral center in the present system is remote from the
reaction center.
3. Experimental
3.1. General procedures
All reactions sensitive to air or moisture were carried out
under argon atmosphere in dry solvents purchased from
Wako or Kanto chemicals. Analytical thin-layer chroma-
tography (TLC) was performed using E. Merck Silica gel 60
F254 plates. Column chromatography was performed using
Kanto Chemical silica gel 60N (spherical, neutral; 40–
50 mm). IR spectra were recorded on a Shimazu FTIR-
8200A spectrometer. 1H and 13C NMR spectra were
recorded on a JEOL JNM-AL 300 spectrometer, and
chemical shift values are reported in ppm (d) downfield
from tetramethylsilane with reference to internal residual
CHCl3 (1H NMR, 7.26; 13C NMR, 77.0). Coupling
constants (J) are reported in hertz (Hz). Low- and high-
resolution mass spectra (MS, HRMS) were recorded on a
Hitachi M-2500S spectrometer.
The proposed formation of s–p chelation is supported not
only by the 1,3-anti stereoselectivity observed in the
reduction of 25, but also by the chemoselectivity mentioned
below. The competitive reaction of a 1:1 mixture of 22b and
25f with 1 equiv. of Ph2MeSiH in the presence of catalytic
amounts of B(C6F5)3 gave selectively 36 over 35 in a ratio
of 8:1 (Eq. (7)). The observed chemoselectivity suggested
that the reactivity of 25f would be enhanced by the
formation of s–p chelation.4,12 We next examined the
hydrosilylation of an equimolar mixture of 25i and 25j. If
the electron-withdrawing effect of the alkyne is responsible
for the enhanced reactivity of 25f, 25j would be more
reactive than 25i due to the presence of an electron-
withdrawing CF3 group at the para position, and therefore
predominant formation of 38 should be observed. However,
3.2. General procedure for hydrosilylation
The preparation of 5h is representative. To a stirred solution
of 4h (152 mg, 1 mmol) and Et3SiH (0.16 mL, 1 mmol) in
toluene (3 mL) was added a 0.05 M solution of B(C6F5)3 in
toluene (0.40 mL, 2 mol%) at 08C. After the mixture was
stirred for 60 min, the resulting solution was filtered
through a short column chromatography of silica gel. The
solvent was removed under reduced pressures to give a
crude product, which was purified by silica gel column

N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
8199
chromatography using hexane/Et2O¼9/1 as eluent to give
5h as a colorless oil (268 mg, 1 mmol) in nearly 100% yield.
IR (neat); 3065, 3028, 2957, 2910, 2878, 2174, 1454, 1379,
1250, 1134, 843, 743 cm21. MS (EI) m/z 331 (Mþ2C2H5,
3). Anal. calcd for C21H36OSi: C, 69.93; H, 10.06, found: C,
70.16; H, 10.33.
3.2.1. 2-Methyl-1-phenyl-1-triethylsilyloxy-pentane
(213). Colorless oil; 1H NMR (CDCl3, 300 MHz) d
7.20–7.36 (m, 5H), 4.45 (d, J¼5.4 Hz, 1H, 2), 4.37 (d,
J¼6.3 Hz, 1H, 3), 0.43–1.74 (m, 26H). IR (neat); 3086,
3065, 3028, 2957, 2912, 1495, 1454, 1379, 1238, 1082,
1067, 1006, 743 cm21. MS (EI) m/z 291 (Mþ2H, 0.1).
HRMS calcd for C18H31OSi (Mþ2H) 291.2143, found
291.2117.
3.2.7. 4-Methyl-5-phenyl-5-triethylsilyloxy-hept-1-yne
1
(5e16e). Colorless oil; H NMR (C6D6, 300 MHz) d 3.22
(dt, J¼3.6, 6.6 Hz, 1H, 5e), 3.14 (q, J¼5.4 Hz, 1H, 6e),
1.35–1.94 (m, 4H), 0.93–1.02 (m, 2H), 0.40–1.02 (m,
15H), 0.17 (q, J¼8.1 Hz, 6H). IR (neat); 2961, 2912, 2878,
1458, 1416, 1240, 1136, 1094, 1011, 841, 743 cm21. MS
(EI) m/z 211 (Mþ2C2H5, 42). HRMS calcd for C12H23OSi
(Mþ2C2H5) 211.1518, found 211.1504.
3.2.2. 4-Methyl-5-phenyl-5-triethylsilyloxy-pent-1-yne
(5a16a). Colorless oil; 1H NMR (CDCl3, 300 MHz) d
7.20–7.30 (m, 5H), 4.69 (d, J¼5.1 Hz, 1H, 5a), 4.47 (d,
J¼7.2 Hz, 1H, 6a), 2.20–2.30 (m, 1H), 1.85–2.00 (m, 3H),
0.97 (d, J¼6.6 Hz, 3H, 5a), 0.87 (t, J¼7.8 Hz, 9H), 0.51 (q,
J¼7.8 Hz, 6H). IR (neat); 2957, 2912, 2878, 1454, 1414,
1240, 1134, 1088, 1069, 826, 743, 702 cm21. MS (EI) m/z
259 (Mþ2C2H5, 16). HRMS calcd for C16H23OSi
(Mþ2C2H5) 259.1518, found 259.1529.
3.2.8. 5-Cyclohexyl-4-methyl-5-triethylsilyloxy-pent-1-
1
yne (5f16f). Colorless oil; H NMR (CDCl3, 300 MHz) d
3.46 (dd, J¼3.2, 6.5 Hz, 1H, 5f), 3.29 (m, 1H, 6f), 2.03–
2.36 (m, 2H), 1.95 (t, J¼2.6 Hz, 1H, 5f), 1.93 (t, J¼2.6 Hz,
1H, 6f), 1.60–1.93 (m, 6H), 0.86–1.43 (m, 12H), 0.62 (q,
J¼7.9 Hz, 6H). IR (neat); 2955, 2930, 1458, 1450, 1109,
1076, 1009, 738 cm21. MS (EI) m/z 265 (Mþ2C2H5, 26).
HRMS calcd for C16H29OSi (Mþ2C2H5) 265.2013, found:
265.1976.
3.2.3. 4-Methyl-5-phenyl-5-diphenylmethylsilyloxy-
1
pent-1-yne (5aa16aa). Colorless oil; H NMR (CDCl3,
300 MHz) d 7.17–7.61 (m, 15H), 4.71 (d, J¼5.4 Hz, 1H,
5aa), 4.52 (d, J¼7.2 Hz, 1H, 6aa), 1.83–2.32 (m, 4H), 1.03
(d, J¼6.9 Hz, 3H, 5aa), 0.78 (d, J¼6.9 Hz, 3H, 6aa), 0.44,
(s, Si-Me, 3H, 5aa), 0.39 (s, Si-Me, 3H, 6aa). IR (neat)
3069, 3026, 2963, 2910, 2874, 1454, 1429, 1256, 1119,
1088, 854, 739 cm21. MS (EI) m/z 330 (Mþ2C3H4, 0.4).
HRMS calcd for C22H22OSi (Mþ2C3H4) 330.1440, found
330.1435.
3.2.9. 4-Methyl-5-o-methylphenyl-5-triethylsilyloxy-
pent-1-yne (5g16g). Colorless oil; 1H NMR (CDCl3,
300 MHz) d 7.07–7.43 (m, 4H), 5.06 (d, J¼3.9 Hz, 1H,
5g), 4.71 (d, J¼6.6 Hz, 1H, 6g), 2.32 (s, 3H), 1.85–2.36 (m,
4H), 0.81–0.96 (m, 12H), 0.51 (q, J¼8.1 Hz, 6H). IR (neat);
3067, 3024, 2957, 2912, 2878, 1460, 1414, 1240, 1136,
1076, 837, 746 cm21. MS (EI) m/z 302 (Mþ, 0.1). Anal.
calcd for C19H30OSi: C, 75.43; H, 10.00, found: C, 75.08; H,
10.26.
3.2.4. 5-Methyl-6-phenyl-6-triethylsilyloxy-hex-2-yne
(5b16b). Colorless oil; 1H NMR (CDCl3, 300 MHz) d
7.20–7.29 (m, 5H), 4.69 (d, J¼4.8 Hz, 1H, 5b), 4.47 (d,
J¼7.2 Hz, 1H, 6b), 2.16–2.20 (m, 1H), 1.27–1.91 (m, 5H),
0.92 (d, J¼6.6 Hz, 3H, 5b), 0.87 (t, J¼8.1 Hz, 9H), 0.78 (d,
J¼6.9 Hz, 3H, 6b), 0.51 (q, J¼8.1 Hz, 6H). IR (neat); 3063,
3028, 2957, 2912, 2876, 1454, 1414, 1240, 1134, 1086, 831,
742 cm21. MS (EI) m/z 273 (Mþ2C2H5, 8). Anal. calcd for
C19H30OSi: C, 75.43; H, 10.00. found: C, 75.44; H, 10.30.
3.2.10. (4R p,5S p)-4,6,6-Trimethyl-5-phenyl-5-triethyl-
silyloxy-hept-1-yne (5h). Colorless oil; H NMR (CDCl3,
1
300 MHz) d 3.22 (d, J¼1.6 Hz, 1H), 2.40–2.48 (m, 1H),
1.83–2.01 (m, 3H), 1.11 (d, J¼6.5 Hz, 3H), 0.97 (t,
J¼7.8 Hz, 9H), 0.88 (s, 9H), 0.62 (q, J¼7.8 Hz, 6H). 13C
NMR (CDCl3, 75 MHz) d 85.3, 84.1, 68.4, 36.6, 34.7, 26.7,
21.1, 21.0, 7.3, 5.7. IR (neat); 2957, 2912, 2878, 1458, 1418,
1238, 1128, 1099, 1034, 849, 808, 737 cm21. MS (EI) m/z
267 (Mþ2H, 0.1). HRMS calcd for C16H31OSi (Mþ2H)
267.2143, found 267.2134.
3.2.5. 4-Methyl-1-phenyl-5-phenyl-5-triethylsilyloxy-
pent-1-yne (5c16c). Colorless oil; 1H NMR (CDCl3,
300 MHz) d 7.21–7.42 (m, 10H), 4.78 (d, J¼5.1 Hz, 1H,
5c), 4.55 (d, J¼7.5 Hz, 1H, 6c), 2.54 (d, J¼6.0 Hz, 2H, 6c),
2.46 (dd, J¼13.5, 6.6 Hz, 1H, 5c), 2.16 (dd, J¼16.5, 6.9 Hz,
1H, 5c), 1.93–2.04 (m, 1H), 0.83–1.05 (m, 12H), 0.45–
0.57 (m, 6H). IR (neat); 3063, 3030, 2957, 2910, 2876,
1454, 1414, 1240, 1132, 1088, 827, 754 cm21. MS (EI) m/z
364 (Mþ, 0.1). HRMS calcd for C24H32OSi (Mþ) 364.2222,
found 364.2234. Anal. calcd for C24H32OSi: C, 79.06; H,
8.85, found: C, 78.72; H, 9.21.
3.3. Determination of stereostructure of 5a and 6a
To a solution of 5a and 6a (1.44 g, 5 mmol, 5a/6a¼4.9:1) in
THF (10 mL) was added 1 M solution of TBAF in THF
(10.2 mL, 10.2 mmol) at 08C. The resulting mixture was
stirred for 1 h at rt, and then H2O was added. The mixture
was extracted with ether several times. The combined
extracts were dried (Na2SO4) and evaporated to leave a
crude product, which was purified by column chromato-
graphy (silica gel, hexane/ether¼2/1 eluent) to give
2-methyl-1-phenyl-4-pentyn-1-ol (826 mg, 4.7 mmol) in
95% yield. To a suspension of NaH (150 mg, 6.3 mmol)
in THF (10 mL) was added 2-methyl-1-phenyl-4-pentyn-1-
ol (826 mg, 4.8 mmol) at rt. After the mixture was stirred for
10 min, p-methoxybenzyl chloride (0.8 mL, 6 mmol) and
TBAI (184 mg, 0.5 mmol) were added. The resulting
mixture was stirred for 2 h at 508C, and then H20 was
added. The mixture was extracted with ether several times.
3.2.6. 4-Methyl-5-phenyl-5-triethylsilyloxy-1-trimethyl-
silyl-pent-1-yne (5d16d). Colorless oil; 1H NMR
(CDCl3, 300 MHz) d 7.19–7.29 (m, 5H), 4.75 (d,
J¼4.8 Hz, 1H, 5d), 4.51 (d, J¼7.2 Hz, 1H, 6d), 2.33 (m,
2H, 6d), 2.27 (dd, J¼16.5, 6.3 Hz, 1H, 5d), 1.99 (dd,
J¼16.6, 6.8 Hz, 1H, 5d), 1.84–1.90 (m, 1H), 0.94 (d,
J¼6.6 Hz, 3H, 5d), 0.89 (t, J¼4.1 Hz, 9H), 0.79 (d,
J¼6.6 Hz, 3H, 6d), 0.51 (q, J¼8.1 Hz, 6H), 0.17 (s, 9H).

8200
N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
The combined extracts were dried (Na2SO4) and evaporated
to leave a crude product, which was purified by column
chromatography (silica gel, hexane/ether¼19/1 eluent) to
give 5-p-methoxybenzyloxy-4-methyl-5-phenyl-1-pentyne
(7) (1.3 g, 4.4 mmol) in 93% yield. To a solution of 7
(885 mg, 3.0 mmol) in THF (5 mL) was added a 1 M
solution of BH3·THF in THF (3 mL, 3.0 mmol) at 08C. The
mixture was stirred for 2 h at 08C, then excess hydride was
decomposed by adding 0.5 mL of MeOH. To the resulting
solution was added a solution of mCPBA (1.7 g, 10 mmol)
in THF (10 mL) at 08C and the mixture was stirred for 2 h at
rt. The reaction was quenched by adding H2O, and then the
mixture was extracted with ether several times. The
combined extracts were dried (Na2SO4) and evaporated to
leave a crude product. The crude product was treated with
K2CO3 (0.76 g) and Me2SO4 (1.7 mL, 18 mmol) in acetone
(20 mL) at rt. After the mixture was stirred for 2 h at 658C,
the reaction mixture was filtered through a pad of celite. The
solvent was removed under the reduced pressure to give a
crude product, which was purified by column chromato-
graphy (silica gel, hexane/ether¼9/1 eluent) to give methyl
5-p-methoxybenzyloxy-4-methyl-5-phenyl-pentanoate (8)
(479 mg, 1.4 mmol) in 47% yield by three steps. To a
solution of 8 (72 mg, 0.21 mmol) in CH3CN (2.0 mL) and
H2O (1.0 mL) was added CAN (230 mg, 0.42 mmol) at 08C.
After the mixture was stirred for 2 h at rt, the mixture was
extracted with ether several times. The combined extracts
were dried (Na2SO4) and evaporated to leave a crude
product, which was purified by column chromatography
(silica gel, hexane/ether¼1/1 eluent) to give a mixture of
4-methyl-6-phenyl-tetrahydro-pyran-2-one (9a/1054.6:1)
(35 mg, 0.18 mmol) in 87% yield.
IR (neat); 3030, 2957, 2912, 1456, 1238, 1099, 1070, 825,
731, 702 cm21. MS (EI) m/z 287 (Mþ2C2H5, 5). HRMS
calcd for C18H27OSi (Mþ2C2H5) 287.1830, found:
287.1848.
3.3.4. (1R p,2R p)-2-Isopropyl-1-phenyl-1-triethylsilyl-
oxy-pentane (20). Colorless oil; 1H NMR (CDCl3,
300 MHz) d 7.2–7.3 (m, 5H), 4.55 (d, J¼6.6 Hz, 1H),
2.07 (m, 1H), 1.3–1.4 (m, 1H), 0.8–1.1 (m, 19H), 0.71 (t,
J¼6.9 Hz, 3H), 0.43 (q, J¼8.1 Hz, 6H). 13C NMR (CDCl3,
75 MHz) d 145.1, 127.6, 127.0, 126.7, 77.0, 51.5, 27.7, 26.4,
22.3, 22.0, 17.2, 14.4, 6.8, 4.9. IR (neat); 3028, 2957, 2876,
1454, 1414, 1130, 1084, 827 cm21. MS (EI) m/z 291
(Mþ2C2H5, 2). HRMS calcd for C18H31OSi (Mþ2C2H5)
291.2144, found: 291.2176.
3.3.5. 1-Diphenylmethylsilyloxy-3-methyl-1-phenyl-5-
trimethylsilyl-pentane (23a124a). Colorless oil; 1H
NMR (CDCl3, 300 MHz) d 7.55–7.20 (m, 15H), 4.74 (m,
1H, 22), 4.71 (m, 21), 1.92 (ddd, J¼4.2, 9.0, 13.4 Hz, 1H,
21), 1.69 (t, J¼6.9 Hz, 1H, 22), 1.65–0.86 (m, 4H), 0.81 (d,
J¼6.1 Hz, 3H, 22), 0.73 (d, J¼6.1 Hz, 3H, 21), 0.44 (s, 3H,
22), 0.43 (s, 3H, 21), 0.40–0.20 (m, 2H), 20.04 (s, 9H, 21),
20.10 (s, 9H, 22). IR (neat); 3068, 2952, 1429, 1248, 1119,
698 cm21. MS (EI) m/z 446 (Mþ, 0.06). HRMS calcd for
C28H38OSi2 (Mþ) 446.2459, found 446.2484.
3.3.6. 3-tert-Butyl-1-diphenylmethylsilyloxy-1,5-di-
phenyl-pentane (23b124b). Colorless oil; 1H NMR
(CDCl3, 300 MHz) d 7.57 (m, 4H), 7.29 (m, 14H), 7.07
(d, J¼6.9 Hz, 2H), 4.67 (dd, J¼6.6, 7.7 Hz, 1H), 2.77 (ddd,
J¼5.1, 11.4, 13.5 Hz, 1H), 2.46 (ddd, J¼5.4, 11.4, 13.8 Hz,
1H), 1.91 (ddd, J¼4.2, 6.6, 14.1 Hz, 1H), 1.72 (m, 2H), 1.24
(m, 2H), 0.69 (s, 9H), 0.41 (s, 3H). IR (neat); 3069, 3026,
2961, 2868, 1494, 1454, 1429, 1367, 1253, 1119, 1065, 791,
698 cm21. MS (EI) m/z 492 (Mþ, 0.01). HRMS calcd for
C34H40OSi 492.2848, found: 492.2816.
3.3.1. 5-Methyl-6-phenyl-tetrahydro-pyran-2-one
(9a110). Colorless oil; 1H NMR (CDCl3, 300 MHz) d
7.26–7.41 (m, 5H), 5.50 (d, J¼3.3 Hz, 1H, 9a), 4.85 (d,
J¼9.6 Hz, 1H, 10), 2.64–2.76 (m, 2H), 2.01–2.40 (m, 2H),
1.73–1.83 (m, 1H), 0.87 (d, J¼6.3 Hz, 3H, 10), 0.78 (d,
J¼7.2 Hz, 3H, 9a). IR (neat); 3063, 3032, 2964, 2936, 2880,
1454, 1383, 1236, 1200, 1065, 748, 702 cm21. MS (EI) m/z
190 (Mþ, 22). HRMS calcd for C12H14O2 (Mþ) 190.0994,
found 190.0996.
3.3.7. (3R p,5R p)-5-Diphenymethylsilyloxy-3-methyl-5-
phenyl-1-trimethylsilyl-pent-1-yne (26a). Colorless oil;
1H NMR (CDCl3, 300 MHz) d 7.51 (m, 4H), 7.40–7.20 (m,
11H), 4.88 (dd, J¼5.7, 7.6 Hz, 1H), 2.18 (ddq, J¼5.8, 6.4,
8.7 Hz, 1H), 2.08 (ddd, J¼5.7, 8.7, 12.6 Hz, 1H), 1.76 (ddd,
J¼5.8, 7.6, 12.6 Hz, 1H), 1.02 (d, J¼6.4 Hz, 3H), 0.46 (s,
3H), 0.09 (s, 9H). 13CNMR (CDCl3, 75 MHz) d 144.7,
136.3, 136.2, 134.4, 134.3, 129.5, 129.4, 128.0, 127.6,
127.4, 127.3, 126.4, 111.4, 85.0, 74.4, 48.3, 24.3, 21.3, 0.4,
22.5. IR (neat); 3069, 2961, 2168, 1429, 1250, 1119, 1082,
843, 698 cm21. MS (EI) m/z 442 (Mþ, 2). HRMS calcd for
C28H34OSi2 (Mþ) 442.2146, found 442.2133.
3.3.2. cis-6-tert-Butyl-5-methyl-tetrahydro-pyran-2-one
1
(9b). Colorless oil; H NMR (CDCl3, 300 MHz) d 3.72 (d,
J¼7.2 Hz, 1H), 2.47 (ddd, J¼4.8, 8.1, 16.8 Hz, 1H), 2.32
(ddd, J¼4.5, 8.4, 17.1 Hz, 1H), 2.02 (sex, J¼6.7 Hz, 1H),
1.85 (dddd, J¼4.6, 5.6, 8.7, 13.1 Hz, 1H), 1.58 (dddd,
J¼4.8,7.5, 8.5, 13.3 Hz, 1H), 1.12 (d, J¼6.6 Hz, 3H), 1.00
(s, 9H). 13C NMR (CDCl3, 75 MHz) d 173.1, 92.5, 36.2,
28.7, 27.8, 27.7, 26.0, 21.4. IR (neat); 2961, 2874, 1740,
1464, 1244, 1082, 1061, 1005, 920, 733 cm21. MS (EI) m/z
170 (Mþ, 1). HRMS calcd for C10H18O2 (Mþ) 170.1307,
found 170.1287.
3.3.8. (3R p,5S p)-5-Diphenymethylsilyloxy-3-methyl-5-
phenyl-1-trimethylsilyl-pent-1-yne (27a). Colorless oil;
1H NMR (CDCl3, 300 MHz) d 7.60–7.20 (m, 15H), 5.00
(dd, J¼2.3, 9.6 Hz, 1H), 2.80 (ddq, J¼4.0, 7.0, 11.0 Hz,
1H), 1.91 (ddd, J¼4.0, 9.6, 13.4 Hz, 1H), 1.62 (ddd, J¼2.3,
11.0, 13.4 Hz, 1H), 1.16 (d, J¼7.0 Hz, 3H), 0.54 (s, 3H),
0.15 (s, 9H). IR (neat); 3080, 2963, 2166, 1429, 1250, 1119,
1057, 843, 698 cm21. MS (EI) m/z 442 (Mþ, 2). HRMS
calcd for C28H34OSi2 (Mþ) 442.2146, found 442.2161.
3.3.3. (4R p,5R p)-4-Isopropyl-5-phenyl-5-triethylsilyl-
oxy-pent-1-yne (18). Colorless oil; 1H NMR (CDCl3,
300 MHz) d 7.1–7.3 (m, 5H), 4.96 (d, J¼5.4 Hz, 1H),
2.23 (ddd, J¼2.6, 7.9, 16.9 Hz, 1H), 2.04 (ddd, J¼2.7, 5.0,
16.9 Hz, 1H), 1.93 (t, J¼2.7 Hz, 1H), 1.65–1.72 (m, 1H),
0.95 (d, J¼6.9 Hz, 3H), 0.87 (m, 12H), 0.51 (q, J¼7.8 Hz,
6H). 13C NMR (CDCl3, 75 MHz) d 144.3, 127.8, 126.9,
126.6, 84.5, 75.6, 69.3, 51.1, 26.1, 22.5, 18.1, 15.6, 6.8, 4.8.
3.3.9. 3-Methyl-5-phenyl-5-triethylsilyloxy-1-trimethyl-
silyl-pent-1-yne (26aa127aa). Colorless oil; 1H NMR

N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
8201
(CDCl3, 300 MHz) d 7.20 (m, 5H), 4.92 (dd, J¼2.4, 9.8 Hz,
1H, 27aa), 4.85 (dd, J¼5.6, 8.6 Hz, 1H, 26aa), 2.15 (ddq,
J¼6.6, 6.8, 9.2 Hz,1H), 1.95 (ddd, J¼5.6, 9.2, 12.0 Hz, 1H)
1.67 (ddd, J¼6.8, 8.6,12.0 Hz, 1H), 1.16 (d, J¼6.7 Hz, 3H,
27aa), 1.11 (d, J¼6.6 Hz, 3H, 26aa), 0.87 (t, J¼8.0 Hz,
9H), 0.52 (dq, J¼3.6, 8.0 Hz,6H), 0.19 (s, 9H, 27aa), 0.18
(s, 9H, 26aa). IR (neat); 2957, 2878, 2168, 1493, 1456,
1416, 1250, 1086, 1057, 1005, 881, 758, 665 cm21. MS (EI)
m/z 360 (Mþ, 2). HRMS calcd for C21H36OSi2 360.2305,
found: 360.2320.
Anal. calcd for C25H26OSi: C, 81.03; H, 7.07. Found: C,
80.97; H, 7.23.
3.3.14. (3R p,5S p)-5-Diphenylmethylsilyloxy-3-methyl-5-
1
phenyl-pent-1-yne (27d). Colorless oil; H NMR (CDCl3,
300 MHz) d 7.51 (m, 4H), 7.31 (m, 11H), 4.96 (dd, J¼2.7,
9.9 Hz, 1H), 2.78 (ddq, J¼3.9, 7.2, 9.2 Hz, 1H), 1.99 (d,
J¼1.2 Hz, 1H), 1.91 (ddd, J¼3.9, 9.9, 13.2 Hz, 1H), 1.63
(ddd, J¼2.7, 9.2, 13.2 Hz, 1H), 1.17 (d, J¼7.2 Hz, 3H), 0.48
(s, 3H.). 13C NMR (CDCl3, 75 MHz) d 144.6, 136.4, 136.2,
134.6, 134.4, 129.6, 129.5, 128.1, 127.7, 127.6, 127.2,
126.2, 88.4, 74.0, 69.0, 48.0, 22.9, 21.2, 22.6. IR (neat);
3304, 3069, 3026, 2968, 2936, 1456, 1429, 1254, 1119,
1053, 847, 791, 734, 698 cm21. MS (EI) m/z 370 (Mþ, 0.5).
Anal. calcd for C25H26OSi: C, 81.03; H, 7.07, found: C,
80.88; H, 7.41.
3.3.10. 5-Dimethyphenylsilyloxy-3-methyl-5-phenyl-1-
trimethylsilyl-pent-1-yne (26aaa127aaa). Colorless oil;
1H NMR (CDCl3, 300 MHz) d 7.48 (m, 2H), 7.29 (m, 8H),
4.95 (dd, J¼2.4, 9.8 Hz, 1H, 27aaa), 4.80 (dd, J¼6.2,
7.3 Hz,1H, 26aaa), 2.19 (ddq, J¼5.8, 6.9, 8.3 Hz, 1H), 1.97
(ddd, J¼6.2, 8.3, 2.3 Hz, 1H), 1.77 (ddd, J¼4.1, 9.8,
12.9 Hz, 27aaa), 1.66 (ddd, J¼5.8, 7.3, 12.3 Hz, 1H,
26aaa), 1.13 (d, J¼6.9 Hz, 3H, 27aaa), 1.03 (d,
J¼6.9 Hz, 3H, 26aaa), 0.24 (d, J¼9.0 Hz, 6H), 0.16 (s,
9H, 27aaa), 0.11 (s, 9H, 26aaa). IR (neat); 3069, 3028,
2961, 2899, 2168, 1454, 1427, 1250, 1117, 1084, 841,
700 cm21. MS (EI) m/z 380 (Mþ, 0.3). HRMS calcd for
C23H32OSi2 380.1992, found: 380.1985.
3.3.15. 3-Cyclohexyl-1,5-diphenyl-5-diphenylmethyl-
silyloxy-pent-1-yne (26e127e). Colorless oil; 1H NMR
(CDCl3, 300 MHz) d 7.54 (d, J¼6.3 Hz, 4H), 7.32 (m, 16H),
5.01 (t, J¼6.0 Hz, 1H), 2.14 (m, 2H), 1.93 (t, J¼8.4 Hz,
1H), 1.71–1.54 (m, 5H), 1.26–1.11 (m, 6H), 0.46 (S, 3H).
IR (neat); 2926, 2853, 1489, 1450, 1429, 1254, 1119, 1078,
1026, 854, 791 cm21. MS (EI) m/z 514 (Mþ, 2). HRMS
calcd for C18H38OSi 514.2692, found: 514.2675.
3.3.11. 5-Diphenylmethylsilyloxy-3-methyl-1,5-diphenyl-
1
pent-1-yne (26b127b). Colorless oil; H NMR (CDCl3,
3.3.16. 3-tert-Butyl-1,5-diphenyl-5-diphenylmethylsily-
oxy-pent-1-yne (26f127f). Colorless oil; 1H NMR
(CDCl3, 300 MHz) d 7.53 (dd, J¼1.5, 7.8 Hz, 4H), 7.28
(m, 16H), 5.09 (t, J¼7.4 Hz, 1H), 2.04 (m, 2H), 1.74 (ddd,
J¼2.8, 5.8, 10.1 Hz, 1H), 0.88 (s, 9H), 0.47 (s, 3H). IR
(neat); 3069, 2963, 2868, 1489, 1456, 1429, 1367, 1254,
1119, 1074, 1053, 885, 792, 737, 698 cm21. MS (EI) m/z
448 (Mþ, 1). HRMS calcd for C34H36OSi 488.2535, found:
488.2525.
300 MHz) d 7.52 (m,4H), 7.32 (m,16H), 5.05 (dd, J¼2.5,
9.6 Hz, 1H, 26b), 4.97 (dd, J¼5.9, 8.0 Hz, 1H, 27b), 2.38
(ddq, J¼5.6, 6.9, 8.6 Hz, 1H), 2.17 (ddd, J¼5.9, 8.6,
12.6 Hz, 1H, 26b), 2.00 (ddd, J¼3.9, 9.6, 13.0 Hz, 1H, 27b),
1.84 (ddd, J¼5.6, 8.0, 12.6 Hz, 1H, 26b), 1.72 (ddd, J¼2.5,
10.1, 13.0 Hz, 1H, 27b), 1.26 (d, J¼7.2 Hz, 3H, 27b), 1.12
(d, J¼6.9 Hz, 3H, 26b), 0.50 (s, 3H, 27b), 0.46 (s, 3H, 26b).
IR (neat); 3069, 2966, 2361, 2443, 1489, 1456, 1429, 1256,
1119, 1082, 1053, 997, 835, 793, 698, 665 cm21. MS (EI)
m/z 446 (Mþ, 5). HRMS calcd for C31H30OSi 446.2066,
found: 446.2072.
3.3.17. 5-Cyclohexyl-5-diphenylmethylsilyloxy-3-
methyl-1-trimethylsilyl-pent-1-yne (26g127g). Colorless
1
oil; H NMR (CDCl3, 300 MHz) d 7.58 (m, 4H), 7.38 (m,
3.3.12. 6-Diphenylmethylsilyloxy-4-methyl-6-phenyl-
hex-2-yne (26c127c). Colorless oil; 1H NMR(CDCl3,
300 MHz) d 7.54 (m, 6H), 7.35 (m, 9H), 4.97 (dd, J¼3.0,
9.9 Hz, 1H, 27c), 4.90 (dd, J¼6.0, 7.5 Hz, 1H, 26c) 2.77 (m,
1H), 2.15 (m, 1H), 2.07 (ddd, J¼6, 8.9, 12.9 Hz, 1H), 1.91
(ddd, J¼4.2, 9.9.13.8 Hz, 1H), 1.76 (d, J¼2.4 Hz, 3H, 27c),
1.74 (d, J¼2.1 Hz, 3H, 26c), 1.71 (m, 1H), 1.59 (ddd,
J¼3.0, 10.8, 13.5 Hz, 1H), 1.15 (d, J¼6.9 Hz, 3H, 27c),
1.02 (d, J¼6.6 Hz, 3H, 26c), 0.50 (s, 3H, 27c), 0.48 (s, 3H,
26c). IR (neat); 3069, 3049, 2964, 2918, 1429, 1119, 1088,
1069, 716, 793 cm21. MS (EI) m/z 384 (Mþ, 3). HRMS
calcd for C26H28OSi 384.1909, found: 384.1901.
6H), 3.95 (dt, J¼3.0, 9.9 Hz, 1H, 27g), 3.76 (dt, J¼3.6,
9.9 Hz, 1H, 26g), 2.5 (tq, J¼6.9, 13.8 Hz, 1H) 1.70–1.43
(m, 8H) 1.21–1.04 (m, 5H), 1.09 (d, J¼6.9 Hz, 3H, 27g),
0.97 (d, J¼6.9 Hz, 3H, 26g), 0.71 (s, 3H, 27g),0.66 (s, 3H,
26g), 0.15 (s, 9H, 27g) 0.13 (s, 9H, 26g). IR (neat); 2959,
2928, 2853, 2164, 1450, 1429, 1250 cm21. MS (EI) m/z 448
(Mþ, 0.4). HRMS calcd for C18H40OSi2 448.2618, found:
448.2598.
3.3.18. (3R p,5R p)-5-Diphenylmethylsilyloxy-3,6,6,-tri-
methyl-1-trimethylsilyl-hept-1-yne (26h). White crystals;
1
mp 36–36.58C; H NMR (CDCl3, 300 MHz) d 7.58 (m,
4H), 7.37 (m, 6H), 3.38 (dd, J¼2.6, 8.5 Hz, 1H), 2.37 (ddq,
J¼2.1, 4.3, 9.8 Hz, 1H), 1.79 (ddd, J¼4.3, 8.5, 13.1 Hz,
1H), 1.55 (ddd, J¼2.6, 9.8, 13.1 Hz, 1H), 0.86 (s, 9H), 0.83
(d, J¼2.1 Hz, 3H), 0.66 (s, 3H), 0.144 (s, 9H). 13C NMR
(CDCl3, 75 MHz) d 136.8, 134.6, 129.5, 127.7, 112.7, 79.0,
77.2, 40.5, 35.6, 26.3, 23.4, 19.7, 0.3, 21.7. IR (KBr); 2168,
3.3.13. (3R p,5R p)-5-Diphenylmethylsilyloxy-3-methyl-5-
phenyl-pent-1-yne (26d). Colorless oil; H NMR (CDCl3,
1
300 MHz) d 7.52 (m, 4H), 7.32 (m, 11H), 4.88 (dd, J¼6.0,
7.6 Hz, 1H), 2.21 (ddq, J¼5.8, 6.6, 8.8 Hz, 1H), 2.10 (ddd,
J¼6.0, 8.8, 12.9 Hz, 1H), 1.97 (d, J¼2.4 Hz, 1H), 1.74 (ddd,
J¼5.8, 7.6, 12.9 Hz, 1H), 1.04 (d, J¼6.6 Hz, 3H), 0.45 (s,
3H). 13C NMR (CDCl3, 75 MHz) d 143.9, 136.3, 136.1,
134.4, 134.3, 129.7, 129.6, 128.1, 127.7, 127.4, 126.4, 88.6,
73.8, 68.6, 47.2, 22.2, 20.6, 22.5. IR (neat); 3302, 3069,
3026, 2970, 2936, 2853, 2343, 1454, 1429, 1254, 1119,
1055, 858, 791, 739, 700 cm21. MS (EI) m/z 370 (Mþ, 0.3).
2959, 2872, 1429, 1250, 1117, 1092, 1028, 860, 841 cm21
.
MS (EI) m/z 407 (Mþ2CH3, 0.7). Anal. calcd for
C26H38OSi2: C, 73.87; H, 9.06. Found: C, 73.62; H, 9.12.
3.3.19. (3R p,5S p)-5-Diphenylmethylsilyloxy-3,6,6-tri-
methyl-1-trimethylsilyl-hept-1-yne (27h). Colorless oil;

8202
N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
1H NMR (CDCl3, 300 MHz) d 7.59 (m, 4H), 7.35 (m, 6H),
3.76 (dd, J¼0.9, 9.0 Hz, 1H), 2.31 (ddq, J¼3.6, 6.9,
12.0 Hz, 1H), 1,56 (ddd, J¼0.9 12.0 13.3 Hz, 1H), 1.45
(ddd, J¼3.6, 9.0, 13.3 Hz, 1H), 0.98 (d, J¼6.9 Hz, 3H), 0.81
(s, 9H), 0.74 (s, 3H), 0.16 (s, 9H). IR (neat); 2961, 2870,
2168, 1479, 1429, 1250, 1117, 1090, 841 cm21. MS (EI)
m/z 407 (Mþ2CH3, 2). Anal. calcd for C26H38OSi2: C,
73.87; H, 9.06, found: C, 73.68; H, 9.20.
give cis-4-methyl-6-phenyl-tetrahydro-pyran-2-one (32a)
(61 mg, 0.32 mmol) in 89% yield.
3.5. Determination of stereostructure of 26h and 27h
To a solution of 26h and 27h (2.32 g, 5.50 mmol,
26h/27h¼11:1) in MeOH (10 mL) and THF (1.5 mL) was
added a 1 M solution of KOH in MeOH (6.6 mL, 6.6 mmol)
at 2108C. The resulting mixture was stirred for 2.5 h at 08C,
and then H2O was added. The mixture was extracted with
ether several times. The combined extracts were dried
(MgSO4) and evaporated to leave a crude product, which
was purified by column chromatography (silica gel,
hexane/ether¼30/1 eluent) to give 28 (898 mg,
2.57 mmol, anti/syn¼4.5:1) in 47% yield together with
(3R p,5R p)-2,2,5-Trimethyl-hept-6-yn-3-ol 29 (399 mg,
2.59 mmol) in 47% yield. To a solution of 28 (854 mg,
2.44 mmol, anti/syn¼4.5:1) in AcOEt (5 mL) was added
Pd–BaSO4 which was poisoned with quinoline. The
resulting mixture was stirred for 1 h at rt under hydrogen
atmosphere, then it was filtrated through a pad of celite and
evaporated to leave a crude product, which was purified by
column chromatography (silica gel, hexane/ether¼30/1
eluent) to give 5-diphenylmethylsilyloxy-3,6,6-trimethyl-
hept-1-ene 30 (686 mg, 1.95 mmol, anti/syn¼4.9:1) in 80%
yield. To a solution of 30 (651 mg, 1.85 mmol) in THF
(5 mL) was added BH3 –Me2S complex (17.5 mL,
1.85 mmol) at 08C. The resulting mixture was stirred for
50 min at 08C, and then H2O was added. To the mixture was
added 3 M solution of aqueous NaOH (2.47 mL,
7.40 mmol) and 30% H2O2 (1 mL, 8.80 mmol) at 08C,
successively. The resulting mixture was stirred for 1 h at rt,
and then it was extracted with ether several times. The
combined extracts were dried (MgSO4) and evaporated to
leave a crude product, which was purified by column
chromatography (silica gel, hexane/ether¼3/1 eluent) to
give 5-diphenylmethylsilyloxy-3,6,6-trimethyl-heptan-1-ol
31 (287 mg, 0.78 mmol, anti/syn¼5.3:1) in 42% yield. To a
solution of 31 (256 mg, 0.75 mmol) in THF (3 mL) was
added a 1 M solution of TBAF in THF (0.75 mL,
0.75 mmol) at 08C. The resulting mixture was stirred for
1 h at rt, then H2O was added. The mixture was extracted
with ether several times. The combined extracts were dried
(MgSO4) and evaporated to leave a crude product, which
was purified by column chromatography (silica gel,
hexane/ether¼1/1 eluent) to give 3,6,6-trimethyl-heptane-
1,5-diol (130 mg, 0.75 mmol, anti/syn¼6.4:1) quanti-
tatively. To a solution of 3,6,6-trimethyl-heptane-1,5-diol
(100 mg, 0.60 mmol) in CH2Cl2 (2 mL) was added a 1 M
solution of aqueous KBr (0.05 mL, 0.05 mmol), TEMPO
reagent (1.6 mg, 0.01 mmol), and 0.3 M solution of aqueous
NaClO (2 mL, 0.60 mmol) at 08C, successively. The
resulting mixture was stirred for 1 h at rt, then it was
extracted with ether several times. The combined extracts
were dried (MgSO4) and evaporated to leave a crude
product, which was purified by column chromatography
(silica gel, hexane/ether¼2/1 eluent) to give a mixture of
32h and 33h (31 mg, 0.18 mmol, anti/syn¼4.0:1) in 30 %
yield.
3.4. Determination of stereostructure of 26a
To a solution of 26a (2.2 g, 5.0 mmol) in THF (10 mL) was
added a 1 M solution of TBAF in THF (10.2 mL,
10.2 mmol) at 08C. The resulting mixture was stirred for
0.5 h at 08C, and then H2O was added. The mixture was
extracted with ether several times. The combined extracts
were dried (Na2SO4) and evaporated to leave a crude
product, which was purified by column chromatography
(silica gel, hexane/ether¼4/1 eluent) to give 3-methyl-1-
phenyl-4-pentyn-1-ol (870 mg, 5.0 mmol) quantitatively.
To a suspension of NaH (100 mg, 4.2 mmol) in DMF
(5 mL) was added 3-methyl-1-phenyl-4-pentyn-1-ol
(354 mg, 2.0 mmol) at rt. After the mixture was stirred for
1 h, p-methoxybenzyl chloride (0.4 mL, 3.0 mmol) was
added. The resulting mixture was stirred for 3 h, and then
NH4Cl was added. The mixture was extracted with ether
several times. The combined extracts were dried (Na2SO4)
and evaporated to leave a crude product, which was purified
by column chromatography (silica gel, CH2Cl2 eluent) to
give 5-p-methoxybenzyloxy-3-methyl-5-phenyl-1-pentyne
(532 mg, 1.8 mmol) in 90% yield. To a solution of 5-p-
methoxybenzyloxy-3-methyl-5-phenyl-1-pentyne (294 mg,
1.0 mmol) in THF (3 mL) was added BH3·SMe2 (0.1 mL,
1.0 mmol) at 2158C. The mixture was stirred for 3 h at 08C,
then excess hydride was decomposed by adding 0.2 mL of
MeOH. To the resulting solution was added a solution of
mCPBA (580 mg, 3.0 mmol) in THF (3.0 mL) at 2788C.
The mixture was allowed to warm to rt and it was stirred for
2 h. The reaction was quenched by adding NH4Cl, and then
the mixture was extracted with ether several times. The
combined extracts were dried (Na2SO4) and evaporated to
leave a crude product, which was treated by sodium chlorite
(325 mg, 3.6 mmol) in the presence of 2-methyl-2-butene
(0.5 mL, 4.7 mmol) and NaH2PO4 (125 mg, 1.0 mmol) in
tBuOH (7.5 mL) and H2O (2 mL) to give crude 5-p-
methoxybenzyl-3-methyl-5-phenyl-pentanoic acid. The
crude product was treated with K2CO3 (1 g) and MeI
(0.62 mL, 10 mmol) at rt. After the mixture was stirred for
2 h, the reaction was quenched with H2O. The mixture was
extracted with ether several times. The combined extracts
were dried (Na2SO4) and evaporated to leave a crude
product, which was purified by column chromatography
(silica gel, hexane/ether¼5/1 eluent) to give methyl 5-p-
methoxybenzyloxy-3-methyl-5-phenyl-pentanoate
(125 mg, 0.37 mmol) in 37% yield by four steps. To a
solution of methyl 5-p-methoxybenzyloxy-3-methyl-5-
phenyl-pentanoate (124 mg, 0.36 mmol) in CH3CN
(1.5 mL) and H2O (1.5 mL) was added CAN (394 mg,
0.72 mmol) at rt. After the mixture was stirred for 2 h, the
mixture was extracted with ether several times. The
combined extracts were dried (Na2SO4) and evaporated to
leave a crude product, which was purified by column
chromatography (silica gel, hexane/ether¼1/1 eluent) to
3.5.1. 5-Diphenylmethylsilyloxy-3,6,6-trimethyl-hept-1-
yne (28). Colorless oil; 1H NMR (CDCl3, 300 MHz) d
7.59 (m, 4H), 7.45 (m, 6H), 3.74 (dd, J¼1.4, 9.2 Hz, 1H,

N. Asao et al. / Tetrahedron 58 (2002) 8195–8203
8203
28b), 3.40 (dd, J¼2.4, 8.4 Hz, 1H, 28a), 2.33 (dddq, J¼2.4,
3.9, 6.6, 10.2 Hz, 1H,), 2.01 (d, J¼2.1 Hz, 1H, 28b), 1.98 (d,
J¼2.4 Hz, 1H, 28a), 1.82 (ddd, J¼3.9, 8.4, 13.2 Hz, 1H),
1.58 (ddd, J¼2.4, 10.2, 13.2 Hz, 1H), 1.02 (d, J¼6.9 Hz,
3H, 28b), 0.85 (d, J¼6.6 Hz, 3H, 28a), 0.74 (s, 9H, 28b),
0.68 (s, 9H, 28a). IR (neat); 3308, 3071, 2959, 2872, 1429,
1254, 1117, 1090, 791, 737 cm21. MS (EI) m/z 350 (Mþ,
0.1). HRMS calcd for C23H30OSi 350.2066, found:
350.2033.
1H, 38a), 2.12 (ddd, J¼6.0, 8.9, 13.2 Hz, 1H, 38a), 1.96
(ddd, J¼4.1, 10.1, 13.4 Hz, 1H, 38b), 1.79 (ddd, J¼5.5, 7.8,
13.2 Hz, 1H, 38a), 1.67 (ddd, J¼3.0, 10.8, 13.4 Hz, 1H,
38b), 1,21 (d, J¼6.9 Hz, 3H, 38b), 1.07 (d, J¼6.9 Hz, 3H,
38a), 0.41 (s, 3H, 38b), 0.39 (s, 3H, 38a). IR (neat); 3071,
1614, 1429, 1323, 1256, 1167, 1121, 1067, 700, 665 cm21
.
MS (EI) m/z 514 (Mþ, 5). Anal. calcd for C32H29F3OSi: C,
74.68; H, 5.68, found: C, 74.39; H, 5.68.
3.5.2. (3R p,5R p)-2,2,5-Trimethyl-hept-6-yn-3-ol (29).
1
Colorless oil; H NMR (CDCl3, 300 MHz) d 3.33 (ddd,
References
J¼2.1, 4.5, 9.6 Hz, 1H), 2.62 (m,1H), 2.14 (d, J¼2.4 Hz,
1H), 2.06 (d, J¼4.5 Hz, 1H), 1.66 (ddd, J¼2.1, 7.5, 12.9 Hz,
1H), 1.53 (ddd, J¼7.3, 9.6, 12.9 Hz, 1H), 1.22 (d, J¼6.9 Hz,
3H), 0.89 (s, 9H). 13C NMR (CDCl3, 75 MHz) d 89.7, 78.2,
69.0, 38.8, 34.8, 25.6, 23.7, 20.6. IR (neat); 3404, 3312,
2957, 2906, 2872, 2112, 1479, 1466, 1394, 1466, 1188,
980 cm21. MS (EI) m/z 154 (Mþ, 5). HRMS calcd for
C10H18O 154.1358, found: 154.1345.
1. (a) Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81,
2748. (b) Leitereg, T. J.; Cram, D. J. J. Am. Chem. Soc. 1968,
90, 4019.
2. (a) Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191–1223.
(b) In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley–
VCH: Weinheim, 2000.
3. (a) Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.;
Wiley–VCH: Weinheim, 2000; Vols. 1–2. (b) In Lewis Acid
Reagents; Yamamoto, H., Ed.; Oxford University: New York,
1999. (c) Mahrwald, R. Chem. Rev. 1999, 99, 1095–1120.
(d) Santelli, M.; Pons, J. M. Lewis Acids and Selectivity in
Organic Synthesis; CRC: Boca Raton, 1996. (e) Shambayati,
S.; Schreiber, S. L. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 1, pp
283–324. (f) Yamaguchi, M. Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol. 1, pp 325–353.
3.5.3. cis-4-Methyl-6-phenyl-tetrahydro-pyran-2-one
1
(32a). H NMR (CDCl3, 300 MHz) d 7.40–7.30 (m, 5H),
5.32 (dd, J¼2.9, 11.6 Hz, 1H), 2.82 (m, 1H), 2.32–2.12 (m,
3H), 1.53 (ddd, J¼11.6, 13.2, 13.5 Hz, 1H), 1.09 (d,
J¼5.8 Hz, 3H). MS (EI) m/z 190 (Mþ, 25). IR (neat); 1722,
1496, 1266, 1244, 995 cm21. HRMS calcd for C12H14O2
(Mþ) 190.0993, found 190.0993.
3.5.4. 6-tert-Butyl-4-methyl-tetrahydro-pyran-2-one
(32h133h). White crystals; mp 24–258C; 1H NMR
(CDCl3, 300 MHz) d 3.98 (dd, J¼2.1, 7.1 Hz, 1H, 33h),
3.95 (dd, J¼1.8, 7.2 Hz, 1H, 32h), 2.66 (ddd, J¼1.2, 6.3,
13.5 Hz, 1H, 32h), 2.51 (dd, J¼5.4, 11.4 Hz, 1H, 33h), 2.19
(m, 2H, 33h), 1.99 (m, 2H, 32h), 1.87 (m, 1H, 32h), 1.82
(ddd, J¼4.4, 7.1, 8.4 Hz, 1H, 33h), 1.50 (ddt, J¼0.6, 2.4,
8.4 Hz, 1H, 33h), 1.18 (ddd, J¼0.9, 7.2, 14.1 Hz, 1H, 32h),
1.10 (d, J¼3.9 Hz, 1H, 33h), 1.04 (d, J¼3.9 Hz, 1H). IR
(KBr); 2959, 2874, 1481, 1458, 1367, 1242, 1207, 1074,
1003 cm21. MS (EI) m/z 170 (Mþ, 0.01). HRMS calcd for
C10H18O, found: 170.1341.
4. Asao, N.; Asano, T.; Ohishi, T.; Yamamoto, Y. J. Am. Chem.
Soc. 2000, 122, 4817–4818.
5. Asao, N.; Ohishi, T.; Sato, K.; Yamamoto, Y. J. Am. Chem.
Soc. 2001, 123, 6931–6932.
6. There are several examples of s–p chelation in the transition
metal complexes by using tethered olefin-phosphine ligands,
see Yamazaki, A.; Nishihara, Y.; Nakajima, K.; Hara, R.;
Takahashi, T. Organometallics 1999, 18, 3105–3108, and
references cited therein.
7. Piers and his co-workers found that B(C6F5)3 catalyzed
hydrosilylation of carbonyl functions, such as aldehydes,
ketones and esters, proceeded very smoothly to give the
corresponding reduced compounds in high yields. (a) Parks,
D. J.; Piers, W. E. J. Am. Chem. Soc. 1996, 118, 9440–9441.
(b) Parks, D. J.; Blackwell, J. M.; Piers, W. E. J. Org. Chem.
2000, 65, 3090–3098.
3.5.5. 5-Diphenylmethylsilyloxy-3-methyl-5-phenyl-1-p-
tolyl-pent-1-yne (37). Colorless oil; 1H NMR (CDCl3,
300 MHz) d 7.53 (m, 6H), 7.34 (m, 9H), 7.15 (d, J¼7.8 Hz,
2H), 7.07 (d, J¼7.8 Hz, 2H), 5.05 (dd, J¼3.0, 9.9 Hz, 1H,
37b), 4.97 (dd, J¼6.0, 8.1 Hz, 1H, 37a), 2.36 (s, 3H), 2.35
(m, 1H), 2.34 (s, 3H), 2.16 (ddd, J¼6.0, 9.3, 13.2 Hz, 1H),
1.83 (ddd, J¼5.7, 8.1, 13.2 Hz, 1H), 1.24 (d, J¼6.9 Hz, 3H),
1.11 (d, J¼6.6 Hz, 3H), 0.50 (s, 3H, 37b), 0.45 (s, 3H, 37a).
IR (neat); 3049, 3026, 2966, 1510, 1454, 1254, 1119, 1082,
797, 791 cm21. MS (EI) m/z 460 (Mþ, 8). Anal. calcd for
C32H32OSi: C, 83.43; H, 7.00, found: C, 83.17; H, 7.06.
8. Oshima, M.; Yamazaki, H.; Shimizu, I.; Nisar, M.; Tsuji, J.
J. Am. Chem. Soc. 1989, 111, 6280–6287.
9. For reviews, see: (a) Lambert, J. B. Tetrahedron 1988, 46,
2677–2689. (b) Apeloig, Y. In The Chemistry of Organic
Silicon Compounds; Patai, S., Rappoport, Z., Eds.; Wiley-
Interscience: New York, 1989; pp 57–225. (c) Fleming, I.
CHEMTRACTS Org. Chem. 1993, 6, 113–116.
10. Sarko, C. R.; Guch, I. C.; DiMare, M. J. Org. Chem. 1994, 59,
705–706.
3.5.6. 5-Diphenylmethylsilyloxy-3-methyl-5-phenyl-1-(4-
trifluoromethylphenyl)-pent-1-yne (38). Colorless oil; 1H
NMR (CDCl3, 300 MHz) d 7.48 (m, 6H), 7.27 (m, 13H),
4.95 (dd, J¼3, 10.1 Hz, 1H, 36b), 4.87 (dd, J¼6.0, 7.8 Hz,
1H, 36a), 2.48 (m, 1H, 38b), 2.37 (ddq, J¼5.5, 6.9, 8.9 Hz,
11. Barbero, A.; Blakemore, D. C.; Fleming, I.; Wesley, R. N.
J. Chem. Soc., Perkin Trans. 1 1997, 1329–1352.
12. Reetz, M. T.; Maus, S. Tetrahedron 1984, 43, 101–108.