An auxiliary induced asymmetric synthesis of functionalized cyclobutanes by means of catalytic (2+2)-cycloaddition reaction

Article abstract of DOI:10.1016/j.tet.2003.12.054

A new entry to optically active hydroxycyclobutanes is described. Treatment of silyl enol ether and (-)-8-phenylmenthyl acrylate in the presence of a catalytic amount of EtAlCl₂ affords enantiomerically enriched multi-substituted cyclobutane compounds in a good yield and diastereofacial selectivity.

Full text of DOI:10.1016/j.tet.2003.12.054

Tetrahedron 60 (2004) 2071–2078
An auxiliary induced asymmetric synthesis of functionalized
cyclobutanes by means of catalytic (212)-cycloaddition reaction
*
Kiyosei Takasu, Satoshi Nagao, Megumi Ueno and Masataka Ihara
*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan
Received 5 December 2003; revised 24 December 2003; accepted 25 December 2003
Abstract—A new entry to optically active hydroxycyclobutanes is described. Treatment of silyl enol ether and (2)-8-phenylmenthyl
acrylate in the presence of a catalytic amount of EtAlCl2 affords enantiomerically enriched multi-substituted cyclobutane compounds in a
good yield and diastereofacial selectivity.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
induces new asymmetric centers with excellent diastereo-
selectivity in case of the intramolecular Michael–aldol
reaction using a stoichiometric amount of trimethylsilyl
iodide and hexamethyldisilazane.5 Here we wish to report
asymmetric catalytic intermolecular (2þ2)-cycloaddition
with 8-phenylmenthyl acrylate to afford enantiomerically
enriched cyclobutanes.
Previous work in our laboratory has demonstrated EtAlCl2
catalyzed (2þ2)-cycloaddition of silyl enol ether with a,b-
unsaturated ester.1 This process concisely provides siloxy-
cyclobutane carboxylate in a high yield with an excellent
stereoselectivity. Further studies revealed the reaction
proceeds via a stepwise pathway, like a sequential Michael
addition and aldol reaction. Chiral substances possessing a
hydroxycyclobutane skeleton are found often in nature
(Fig. 1)2 and serve as key intermediates3 in routes to
biologically and medicinally important synthetic targets.
However, stereocontrolled construction of the multi-
substituted cyclobutanes remains a difficult task in prepara-
tive organic chemistry.4–9 Recently we have demonstrated
that chiral auxiliary such as phenylmenthol effectively
2. Results and discussions
2.1. Asymmetric (212)-cycloaddition
Based on the results of our previous studies,1 reaction was
conducted using 1 equiv. of (2)-8-phenylmenthyl acrylate
(2a) and 1.2 equiv. of silyl enol ether 1 in the presence of
20 mol% of EtAlCl2 catalyst at 278 8C in CH2Cl2
(Scheme 1). Theoretically, eight disatereomeric isomers
could be produced by this reaction since three stereogenic
centers are generated on cyclobutane ring. The results of the
(2þ2)-cycloaddtion are summarized in Table 1. In the
reaction of t-butyldimethylsiloxy-1-cyclohexene (1a) with
2a, production of two diastereomers trans-3a and cis-3a in
51 and 33% yield, respectively, was observed (entry 1).
These diastereomeic products can be separated by silica gel
chromatography. Both trans-3a and cis-3a were analytically
pure stereoisomeric compounds in 1H and 13C NMR
spectroscopies. Except for siloxyethylene 1i (entry 9), the
resulting cyclobutane adducts were obtained in moderate to
high yield from cyclic and acyclic substrates possessing
TBS or TIPS moiety. However, only small amounts of
cycloadducts were observed in the reaction of less stable
TES enol ether 1c (entry 3). The low yield of cycloadducts 3
was originated from decomposition of silyl enol ether into
the corresponding ketone or dimeric aldol-adduct 4 (entries
Figure 1. Examples of natural substances possessing functionalized
cyclobutane ring.
Keywords: Hydroxycyclobutanes; (2þ2)-Cycloadditions; Stereoselectivity;
Chiral auxiliary; Asymmetric induction.
*
Corresponding authors. Tel.: þ81-22-217-6887; fax: þ81-22-217-6877
(M.I.); e-mail address: mihara@mail.pharm.tohoku.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.12.054

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K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
Scheme 1.
3, 4, 5 and 9). Interestingly, trans-3 was exclusively
furnished in an excellent yield using TBS enol ethers 1f or
1k as a substrate (entries 6 and 11).
Phenylmenthyl methacrylate (2b) also affords (2þ2)-adduct
trans-3l in 42% yield along with cis-3l (3% yield) by the
reaction with 1f (Scheme 2). On the contrary, crotonate 2c
furnished cycloadducts in only 6% yield as a mixture of two
diastereomers even using 100 mol% of a Lewis acid at the
elevated temperature.
To our surprise, it was observed a TIPS enol ether gives
cyclobutane 3 with the higher cis-selectivity compared with
the corresponding TBS enol ether (entry 1 vs. 2, 4 vs. 5, or 6
vs. 7). The selectivity in this asymmetric reaction is a
complementary result against the one using achiral
substrates.1 We have reported that the trans-selectivity is
enhanced in the reaction with achiral acrylate when more
sterically bulky silyl enol ethers are employed as substrates.
It has been proved no decomposition nor isomerization of
cyclobutane products occurs under the (2þ2)-cycloaddition
conditions and work-up process. Although the detailed
conformation of the transition state in this (2þ2)-cyclo-
addition remains to be clarified, we assume an additional
steric and/or stereoelectronic effect between triisopropyl-
silyl group and phenylmenthyl moiety causes the preferred
production of cis-isomer.
2.2. Stereochemical study of (212)-cycloaddition
product
The absolute configuration of trans-3a, whose single
crystals (colorless prisms) were prepared from a mixed
solvent system of AcOH and MeOH, was determined by
X-ray crystallography (Fig. 2). It reveals that trans-3a has
the (1R,6S,8R)-bicyclo[4.2.0]octane skeleton.
The stereochemistry of cis-3a was determined by chemical
transformation as shown in Scheme 3. Both diastereomers
trans- and cis-3a were, separately, reduced with DIBAL-H
into alcohols trans- and cis-5a, respectively. Since those
Table 1. Asymmetric (2þ2)-cycloaddion reaction
Entry
Silyl enol ether
Product
trans-3
Yield (de) (%)
cis-3
Yield (de) (%)
1
2
3
1a (R¼TBS)
51 (.99)
23 (.99)
5 (.99)
33 (.99)
41 (.99)
1 (.99)
1b (R¼TIPS)
1c (R¼TES)
4
5
1d (R¼TBS)
1e (R¼TIPS)
28 (.99)
26 (.99)
5 (.99)
16 (.99)
6
7
1f (R¼TBS)
1g (R¼TIPS)
89 (.99)
54 (.99)
0 (—)
16 (.99)
8
1h
74 (.99)
10 (.99)
9
1i
1j
0 (—)
0 (—)
10
62 (.99)
25 (.99)
11
1k
91 (.99)
0 (—)

K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
2073
exo-olefine (þ)-7a, whose specific rotation ([a]D in CHCl3)
is þ10.4. In accordance with the above procedure, trans-5a
was converted into (2)-7a ([a]D¼29.8 in CHCl3), whose
spectral data except for chiroptical sense were consistent
with (þ)-7a. Consequently, it has been made clear that cis-
3a possesses the (1S,6R,8R)-bicyclo[4.2.0]octane
framework.
The above stereochemical studies reveal that trans-3a and
cis-3a possess the same (R)-configuration at the a-carbon of
ester function. Thus, silyl enol ether 1a would selectively
approach to the enoate moiety from one side with complete
diastereofacial recognition; the diastereofacial selection
favoring 3a is controlled by p-stacking interaction of the
aromatic ring of phenylmenthol moiety (Fig. 3).11 When
TBS enol ether 3a was reacted with phenylisomenthyl
acrylate (2d),12 which would not be expected for good
conformational fixation by p-stacking interaction, under the
same conditions, non-selective formation of four consider-
able diastereomers was observed (Scheme 4). It has been,
thus, made clear that 8-phenylmenthyl moiety works as an
effective chiral auxiliary in the EtAlCl2 catalyzed (2þ2)-
cycloaddition of silyl enol ether with a,b-unsaturated ester.
Scheme 2. Rp¼8-phenylmenthyl.
Figure 2. ORTEP drawing of trans-3a.
Figure 3. Proposed transition state models for the production of trans-3a
(left) and cis-3a (right).
Scheme 4.
For the bicyclic compounds, trans- and cis-3b–h,l, their
relative configurations around the cyclobutane ring were
1
assigned based on analogy in H and 13C NMR spectro-
scopies. On the other hand, the relative stereochemistries of
trans-3j, cis-3j and trans-3k were confirmed by NOESY
experiment after transformation into the corresponding
alcohols trans-5j, cis-5j and trans-5k, respectively (Fig. 4).
The absolute configuration of all the product was presumed
based on the mechanism described as above.
Scheme 3.
spectral data are not identical, the stereochemistry of
cyclobutane skeleton of cis-3a corresponds to (1R,6S,8S)
or its enantiomeric (1S,6R,8R). In order to remove the
chirality at C(8) position, cis-5a was conducted to Grieco’s
dehydration reaction.10 Namely, by treatment with o-
nitrophenylselenyl cyanide in the presence of tributylpho-
sphine cis-5a was transformed into selenoether cis-6a.
Exposure of cis-6a under the oxidation conditions furnished
Figure 4.

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K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
3. Conclusion
1H, J¼4.4, 10.7, 10.7 Hz), 2.77 (dd, 1H, J¼8.8, 9.9 Hz),
2.18–1.82 (m, 3H), 1.76–1.16 (m, 10H), 1.32 (s, 3H), 1.22
(s, 3H), 1.08–0.72 (m, 9H), 0.17 (s, 3H), 0.14 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 171.1, 151.4, 128.0, 125.6, 125.2,
76.4, 74.3, 50.2, 41.9, 40.5, 39.9, 34.5, 32.1, 31.3, 27.2,
26.8, 26.0, 25.6, 23.4, 21.7, 21.4, 20.3, 19.2, 17.9, 22.92,
22.98; LRMS m/z 441 (Mþ257). Anal. calcd for
C31H50O3Si: C, 74.64; H, 10.10, found C, 74.60; H, 10.02.
In summary, we have developed a versatile, convenient and
stereoselective method for the formation of optically active
hydroxycyclobutanes using EtAlCl2 catalyzed (2þ2)-
cycloaddition reaction. The reaction provides optically
active multi-substituted cyclobutane compounds from
readily available silyl enol ethers and 8-phenylmenthyl
acrylate. The relative and absolute stereochemistries of
cyclobutane products were assigned on the basis of X-ray
crystallographic analysis and their chemical transformation.
4.2.2. (1S,6R,8R)-1-(tert-Butyldimethylsiloxy)-8-
[(1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclo-
hexyloxycarbonyl]bicyclo[4.2.0]octane (cis-3a). Colorless
oil; [a]2D8 (c 0.94, CHCl3) 26.1; IR (neat) 2928, 2855, 1718,
1472, 1250, 1082, 835, 733, 699, 668 cm21 1H NMR
;
4. Experimental
4.1. General
(300 MHz, CDCl3) d 7.29–7.21 (m, 4H), 7.19–7.11 (m,
1H), 4.86 (ddd, 1H, J¼4.4, 10.7, 10.7 Hz), 2.73 (dd, 1H,
J¼7.6, 7.6 Hz), 2.20 (m, 1H), 2.08–1.81 (m, 4H), 1.63–
0.74 (m, 17H), 1.34 (s, 3H), 1.22 (s, 3H), 0.86 (s, 9H), 0.11
(s, 3H), 0.079 (s, 3H); 13C NMR (75 MHz, CDCl3) d 171.1,
151.7, 127.9, 125.6, 125.1, 79.1, 74.0, 50.4, 46.9, 42.1, 39.9,
36.1, 34.5, 31.2, 28.9, 27.0, 26.8, 26.2, 25.9, 24.3, 22.8,
22.3, 21.6, 18.1, 22.28, 22.51; LRMS m/z 498 (Mþ);
HRMS calcd for C31H50O3Si 498.3529, found 498.3529.
All reactions were carried out under an inert atmosphere.
Anhydrous THF and CH2Cl2 were purchased from the
Kanto Chemical Co., Inc. Unless otherwise described, other
materials were obtained from commercial suppliers and
used without further purification. Organic extracts were
dried over MgSO4 or Na2SO4, filtered and concentrated
under reduced pressure using an evaporator. Column
chromatography was performed on Merck silica gel 60 N
(230–400 mesh), and flash column chromatography was
performed on Cica silica gel 60 (spherical/40–100 mm).
Reactions and chromatography fractions were analysed
employing precoated silica gel plate (Merck silica gel
60F254). All melting points were determined on Yanaco
micro melting point apparatus and are uncorrected. IR
spectra were measured on JASCO IR Report-100 spectro-
4.2.3. (1R,6S,8R)-1-Triisopropylsiloxy-8-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[4.2.0]octane (trans-3b). Colorless prisms,
mp 54–55 8C (from AcOEt–MeOH); [a]2D8 (c 0.50, CHCl3)
238.0; IR (KBr) 2943, 2924, 2866, 1732, 1207, 1184, 1138,
1
1103 cm21; H NMR (400 MHz, CDCl3) d 7.26–7.23 (m,
4H), 7.15–7.11 (m, 1H), 4.82 (ddd, 1H, J¼10.7, 10.7,
4.4 Hz), 2.60 (dd, 1H, J¼9.4, 9.4 Hz), 2.16–2.08 (m, 1H),
2.05–1.93 (m, 1H), 1.90–1.84 (m, 1H), 1.80–1.73 (m, 1H),
1.60–0.80 (m, 18H), 1.31 (s, 3H), 1.20 (s, 3H), 1.08–0.94
(m, 18H), 0.87–0.85 (m, 3H); 13C NMR (100 MHz, CDCl3)
d 170.6, 151.3, 127.8, 125.4, 125.0, 76.0, 74.3, 50.8, 50.3,
42.0, 41.0, 40.0, 34.6, 32.9, 31.4, 27.1, 27.0, 26.4, 23.5,
21.9, 21.6, 20.6, 19.1, 18.4, 13.3; LRMS m/z 540 (Mþ).
Anal. calcd for C34H56O3Si: C, 75.50; H, 10.44, found C,
75.40; H, 10.37.
1
photometer or Shimadzu FTIR-8300 spectrometer. The H
and 13C NMR spectra were recorded at Varian Gemini 2000
(300 and 75 MHz), JEOL AL 400 (400 and 100 MHz) as
CDCl3 solutions, respectively, and were reported in ppm
downfield from TMS (d¼0) for the 1H NMR and relative to
the central CDCl3 resonance (d¼77.00) for the 13C NMR.
Mass spectra were recorded on JEOL DX-303 or AX-500
spectrometer. Elemental analyses were performed on
Yanagimoto MT-3 or YANACO CHN CORDER MT-6,
and the results (C, H) were within^0.4% of theoretical
values.
4.2.4. (1S,6R,8R)-1-Triisopropylsiloxy-8-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl] bicyclo[4.2.0]octane (cis-3b). Colorless oil; [a]2D8 (c
0.53, CHCl3) 21.0; IR (neat) 2943, 2866, 1724, 1462, 1242,
4.2. General procedure for (212)-cycloaddition reaction
1115, 1088, 413 cm21 1H NMR (400 MHz, CDCl3) d
;
7.27–7.23 (m, 4H), 7.15–7.11 (m, 1H), 4.85 (ddd, 1H,
J¼10.7, 10.7, 4.4 Hz), 2.78 (dd, 1H, J¼8.5, 8.5 Hz), 2.24–
2.17 (m, 1H), 2.04–1.96 (m, 4H), 1.69–0.81 (m, 17H), 1.30
(s, 3H), 1.22 (s, 3H), 1.05 (d, 18H, J¼7.6 Hz), 0.90–0.81
(m, 3H); 13C NMR (100 MHz, CDCl3) d 170.7, 151.5,
127.8, 125.4, 125.0, 80.7, 73.7, 50.4, 45.2, 42.2, 40.0, 35.3,
34.6, 31.3, 30.6, 27.1, 26.9, 26.8, 26.3, 23.5, 22.8, 21.8,
18.6, 18.2; LRMS m/z 540 (Mþ). Anal. calcd for
C34H56O3Si: C, 75.50; H, 10.44, found C, 75.52; H, 10.39.
To a solution of phenylmenthyl ester 2 (0.23 mmol) and
silyl enol ether 1 (0.28 mmol) in CH2Cl2 (2 mL) was slowly
added EtAlCl2 (0. 46 mmol; 0.9 M solution in hexane) at
278 8C. After being stirred for 50 min, the resulting mixture
was quenched with sat. NaHCO3, and then was extracted
with Et2O three times. The organic layer was washed with
brine, dried and concentrated. The residue was purified by
column chromatography on silica gel with 2% Et2O/hexane
to give 3.
4.2.5. (1R,6S,8R)-1-Triethylsiloxy-8-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[4.2.0]octane (trans-3c). Pale yellow oil;
[a]2D7 (c 0.54, CHCl3) 247.1; IR (neat) 2953, 2928, 2874,
4.2.1. (1R,6S,8R)-1-(tert-Butyldimethylsiloxy)-8-
[(1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclo-
hexyloxycarbonyl]bicyclo[4.2.0]octane (trans-3a). Color-
less prisms, mp 108–110 8C (from AcOEt–MeOH); [a]D27
(c 0.94, CHCl3) 236.6; IR (KBr) 2927, 2856, 1717, 1249,
1184, 1101, 836, 768, 699, 668 cm21; 1H NMR (300 MHz,
CDCl3) d 7.37–7.22 (m, 4H), 7.21–7.12 (m, 1H), 4.83 (ddd,
1
1715, 1238, 1186, 1101, 1078, 1018, 700 cm21; H NMR
(400 MHz, CDCl3) d 7.28–7.24 (m, 4H), 7.17–7.12 (m,
1H), 4.80 (ddd, 1H, J¼10.7, 10.7, 4.1 Hz), 2.59 (dd, 1H,

K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
2075
J¼9.4, 9.4 Hz), 2.19–2.08 (m, 1H), 2.00–1.85 (m, 2H),
1.71–1.64 (m, 1H), 1.61–0.75 (m, 15H), 1.34 (s, 3H), 1.22
(s, 3H), 0.97 (t, 9H J¼7.8 Hz), 0.64 (q, 6H, J¼7.8 Hz); 13C
NMR (100 MHz, CDCl3) d 170.9, 151.2, 127.8, 125.4,
125.0, 76.3, 74.5, 50.5, 50.4, 42.0, 40.7, 40.1, 34.6, 32.4,
31.4, 28.0, 27.1, 25.7, 23.5, 21.9, 21.5, 20.5, 19.1, 7.1, 6.2;
LRMS m/z 498 (Mþ); HRMS calcd for C34H56O3Si,
498.3529, found 498.3564.
J¼10.0, 10.0 Hz), 2.46–2.36 (m, 1H), 2.11–1.86 (m, 3H),
1.81–1.66 (m, 4H), 1.60–0.75 (m, 12H), 1.32 (s, 3H), 1.22
(s, 3H), 1.06 (s, 21H); 13C NMR (100 MHz, CDCl3) d 171.3,
151.2, 127.8, 125.4, 125.0, 86.7, 74.5, 50.5, 49.6, 44.8, 42.0,
40.1, 37.8, 34.6, 31.6, 31.4, 27.7, 25.9, 24.5, 21.9, 19.8,
18.3, 13.2; LRMS m/z 526 (Mþ). Anal. calcd for
C33H54O3Si: C, 75.23; H, 10.33, found C, 75.42; H, 10.27.
4.2.10. (1S,5R,7R)-1-Triisopropylsiloxy-7-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[3.2.0]heptane (cis-3e). Colorless oil; [a]D28
(c 1.01, CHCl3) 211.1; IR (neat) 2947, 2866, 1732, 1231,
4.2.6. (1S,6R,8R)-1-Triethylsiloxy-8-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[4.2.0]octane (cis-3c). Colorless oil; [a]2D7 (c
0.58, CHCl3) 23.1; IR (neat) 2951, 2936, 2874, 1715, 1182,
1161, 1084, 741, 698 cm21; 1H NMR (400 MHz, CDCl3) d
7.30–7.18 (m, 4H), 7.15–7.09 (m, 1H), 4.88 (ddd, 1H,
J¼4.0, 10.6, 10.6 Hz), 2.72 (dd, 1H, J¼7.0, 7.0 Hz), 2.24–
2.20 (m, 1H), 2.03–1.92 (m, 4H), 1.90–1.73 (m, 3H), 1.66–
0.82 (m, 16H), 1.33 (s, 3H), 1.22 (s, 3H), 0.93 (t, 9H
J¼7.6 Hz), 0.65–0.52 (m, 6H); 13C NMR (100 MHz,
CDCl3) d 170.9, 151.5, 127.8, 125.4, 125.0, 78.4, 74.0,
50.5, 48.3, 42.1, 40.7, 40.0, 36.4, 34.7, 31.4, 28.0, 27.0,
26.4, 23.0, 22.7, 22.2, 21.8, 7.2, 6.6; LRMS m/z 498 (Mþ);
HRMS calcd for C34H56O3Si, 498.3529, found 498.3518.
1163, 1103, 883, 700, 681 cm21 1H NMR (400 MHz,
;
CDCl3) d 7.28–7.22 (m, 4H), 7.16–7.08 (m, 1H), 4.84 (ddd,
1H, J¼10.6, 10.6, 4.1 Hz), 2.75 (dd, 1H, J¼8.5, 8.5 Hz),
2.48–2.38 (m, 1H), 2.35–2.20 (m, 1H), 2.11–2.02 (m, 1H),
2.00–1.90 (m, 1H), 1.90–1.67 (m, 4H), 1.67–0.74 (m,
12H), 1.34 (s, 3H), 1.22 (s, 3H), 1.05 (s, 21H); 13C NMR
(100 MHz, CDCl3) d 170.3, 151.4, 127.8, 125.4, 125.0,
86.6, 74.5, 50.6, 48.7, 43.8, 42.0, 41.6, 40.2, 34.6, 31.3,
28.2, 27.1, 25.2, 24.3, 22.0, 21.8, 18.4, 18.3, 13.5; LRMS
m/z 526 (Mþ); HRMS calcd for C33H54O3Si, 526.3842,
found 526.3888.
4.2.7. (1R,5S,7R)-1-tert-Butyldimethylsiloxy-7-
[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclo-
hexyloxycarbonyl]bicyclo[3.2.0]heptane (trans-3d). Pale
yellow oil; [a]2D9 (c 0.66, CHCl3) 233.5; IR (neat) 2953,
4.2.11. (1R,7S,9R)-1-tert-Butyldimethylsiloxy-9-
[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclo-
hexyloxycarbonyl]bicyclo[5.2.0]nonane (trans-3f). Color-
less prisms, mp 86–88 8C (from AcOEt–MeOH); [a]2D8 (c
0.54, CHCl3) 231.4; IR (KBr) 2924, 2855, 1728, 1254,
2928, 2855, 1717, 1258, 1225, 1096, 837, 775, 700 cm21
;
1H NMR (400 MHz, CDCl3) d 7.27–7.20 (m, 4H), 7.18–
7.10 (m, 1H), 4.83 (ddd, 1H, J¼4.4, 10.7, 10.7 Hz), 2.93
(dd, 1H, J¼10.1, 10.1 Hz), 2.44–2.36 (m, 1H), 2.05–1.88
(m, 4H), 1.82–1.65 (m, 5H), 1.60–0.70 (m, 10H), 1.33 (s,
3H), 1.23 (s, 3H), 0.86 (s, 9H), 0.12 (s, 3H), 0.10 (s, 3H); 13C
NMR (100 MHz, CDCl3) d 171.4, 151.1, 127.8, 125.4,
125.1, 86.7, 74.5, 50.5, 49.0, 44.4, 42.0, 40.1, 37.6, 34.6,
31.4, 31.4, 27.9, 27.0, 25.8, 24.8, 21.9, 20.0, 17.9, 22.88,
22.95; LRMS m/z 484 (Mþ). Anal. calcd for C30H48O3Si:
C, 74.33; H, 9.98, found C, 74.32; H, 9.83.
1150, 1126, 1065, 837, 775 cm21; H NMR (400 MHz,
1
CDCl3) d 7.25–7.24 (m, 4H), 7.15–7.13 (m, 1H), 4.83 (ddd,
1H, J¼4.4, 10.7, 10.7 Hz), 2.73 (dd, 1H, J¼9.8, 9.8 Hz),
2.14 (m, 1H), 1.99 (m, 1H), 1.91–1.84 (m, 2H), 1.79–0.81
(m, 20H), 1.30 (s, 3H), 1.20 (s, 3H), 0.90 (s, 9H), 0.20 (s,
3H), 0.16 (s, 3H); 13C NMR (100 MHz, CDCl3) d 170.7,
151.2, 127.8, 125.3, 125.0, 82.3, 74.4, 74.1, 50.3, 48.7, 46.7,
40.0, 34.7, 32.7, 31.4, 26.9, 26.7, 26.5, 26.1, 25.9, 23.7,
22.5, 22.0, 21.8, 18.2, 22.67, 22.84; LRMS m/z 455
(Mþ257). Anal. calcd for C32H52O3Si: C, 74.94; H, 10.22,
found C, 75.00; H, 10.11.
4.2.8. (1S,5R,7R)-1-tert-Butyldimethylsiloxy-7-
[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclo-
hexyloxycarbonyl]bicyclo[3.2.0]heptane (cis-3d). Pale
yellow oil; [a]2D9 (c 0.34, CHCl3) 213.7; IR (neat) 2951,
2930, 2856, 1732, 1173, 1161, 1097, 905, 835, 775,
4.2.12. (1R,7S,9R)-1-Triisopropylsiloxy-9-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[5.2.0]nonane (trans-3g). Colorless needles,
mp 87–88 8C (from AcOEt–MeOH); [a]2D8 (c 0.44, CHCl3)
227.9; IR (KBr) 2926, 2866, 1728, 1460, 1252, 1225, 1205,
1
700 cm21; H NMR (400 MHz, CDCl3) d 7.29–7.23 (m,
4H), 7.18–7.10 (m, 1H), 4.78 (ddd, 1H, J¼4.1, 10.5,
10.5 Hz), 2.77 (dd, 1H, J¼8.3, 8.3 Hz), 2.54–2.46 (m, 1H),
2.45–2.34 (m, 1H), 2.18–2.08 (m, 1H), 1.87–1.75 (m, 5H),
1.60–0.70 (m, 12H), 1.38 (s, 3H), 1.25 (s, 3H), 0.90 (s, 9H),
0.11 (s, 3H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3) d
171.0, 151.5, 127.8, 125.5, 125.0, 86.2, 74.9, 50.6, 48.3,
43.1, 42.0, 41.6, 40.4, 34.7, 31.5, 31.3, 29.5, 27.2, 25.9,
24.0, 21.8, 21.8, 18.2, 22.47, 22.87; LRMS m/z 484 (Mþ);
HRMS calcd for C30H48O3Si, 484.3373, found 484.3403.
1192, 1130, 772, 700, 683 cm21 1H NMR (400 MHz,
;
CDCl3) d 7.25–7.23 (m, 4H), 7.15–7.10 (m, 1H), 4.84 (ddd,
1H, J¼4.1, 10.5, 10.5 Hz), 2.76 (dd, 1H, J¼10.0, 10.0 Hz),
2.25–2.17 (m, 1H), 2.04–1.97 (m, 1H), 1.90–0.81 (m,
22H), 1.29 (s, 3H), 1.19 (s, 3H), 1.10 (s, 18H), 0.88–0.86
(m, 3H); 13C NMR (100 MHz, CDCl3) d 170.5, 151.3,
127.8, 125.3, 125.0, 82.3, 74.2, 50.3, 49.4, 47.1, 41.9, 40.0,
36.3, 34.6, 34.3, 33.6, 32.2, 31.4, 26.9, 26.7, 26.5, 23.7,
22.1, 21.9, 18.5, 13.4; LRMS m/z 554 (Mþ). Anal. calcd for
C32H52O3Si: C, 74.94; H, 10.22, found C, 75.00; H, 10.11.
4.2.9. (1R,5S,7R)-1-Triisopropylsiloxy-7-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[3.2.0]heptane (trans-3e). Pale yellow oil;
[a]2D9 (c 1.83, CHCl3) 230.5; IR (neat) 2951, 2889, 2866,
4.2.13. (1S,7R,9R)-1-Triisopropylsiloxy-9-[(1R,2S,5R)-5-
methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]bicyclo[5.2.0]nonane (cis-3g). Colorless oil; [a]2D8 (c
0.87, CHCl3) 29.0; IR (neat) 2924, 2866, 1722, 1454, 1240,
1
1719, 1223, 1194, 1121, 1105, 881, 700 cm21; H NMR
1
(400 MHz, CDCl3) d 7.27–7.22 (m, 4H), 7.18–7.10 (m,
1H), 4.84 (ddd, 1H, J¼4.4, 10.7, 10.7 Hz), 2.98 (dd, 1H,
1092, 762, 700, 677 cm21; H NMR (400 MHz, CDCl3) d
7.27–7.25 (m, 4H), 7.15–7.10 (m, 1H), 4.84 (ddd, 1H,

2076
K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
J¼4.4, 10.5, 10.5 Hz), 2.87 (dd, 1H, J¼8.8, 8.8 Hz), 2.41
(br, 1H), 2.12 (dd, 1H, J¼10.5, 20.0 Hz), 2.04–1.94 (m,
1H), 1.92–1.85 (m, 1H), 1.80–1.71 (m, 1H), 1.70–0.80 (m,
19H), 1.32 (s, 3H), 1.20 (s, 3H), 1.05 (s, 18H), 0.86–0.80
(m, 3H); 13C NMR (100 MHz, CDCl3) d 170.3, 151.5,
127.8, 125.4, 125.0, 84.3, 73.9, 50.5, 46.6, 45.9, 42.1, 40.9,
40.0, 34.6, 31.8, 31.3, 30.2, 26.9, 26.8, 26.6, 25.6, 24.9,
21.8, 21.5, 18.6, 13.8; LRMS m/z 554 (Mþ); HRMS calcd
for C32H52O3Si, 554.4155, found 554.4156.
CDCl3) d 7.60–7.52 (m, 2H), 7.35–7.18 (m, 7H), 7.13–
7.05 (m, 1H), 4.92 (ddd, 1H, J¼4.4, 10.7, 10.7 Hz), 2.95
(dd, 1H, J¼7.8, 7.8 Hz), 2.67–2.55 (m, 1H), 2.32 (ddd, 1H,
J¼5.4, 10.7, 10.7 Hz), 2.14–1.96 (m, 3H), 1.63–0.70 (m,
10H), 1.35 (s, 3H), 1.23 (s, 3H), 0.80 (s, 9H), 20.13 (s, 3H),
20.42 (s, 3H); 13C NMR (100 MHz, CDCl3) d 170.3, 151.4,
145.7, 127.9, 127.8, 127.2, 126.4, 125.4, 125.0, 80.7, 74.5,
53.3, 50.4, 42.3, 40.1, 34.6, 31.9, 31.4, 27.3, 27.0, 26.0,
21.8, 18.2, 17.7, 22.94, 23.37; LRMS m/z 520 (Mþ);
HRMS calcd for C32H48O3Si, 520.3373, found 520.3378.
4.2.14. (1R,8S,10R)-1-tert-Butyldimethylsiloxy-9-
[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclo-
hexyloxycarbonyl]bicyclo[6.2.0]decane (trans-3h). Color-
less oil; [a]2D7 (c 0.76, CHCl3) 214.2; IR (neat) 2927, 2855,
1713, 1240, 1165, 1136, 1005, 833, 812, 766, 700 cm21; 1H
NMR (400 MHz, CDCl3) d 7.29–7.22 (m, 4H), 7.16–7.10
(m, 1H), 4.84 (ddd, 1H, J¼4.4, 10.7, 10.7 Hz), 2.85 (dd, 1H,
J¼10.0, 10.0 Hz), 2.03–1.78 (m, 3H), 1.68–0.80 (m, 23H),
1.29 (s, 3H), 1.20 (s, 3H), 0.91 (s, 9H), 0.22 (s, 3H), 0.20 (s,
3H); 13C NMR (100 MHz, CDCl3) d 170.6, 151.2, 127.8,
125.3, 125.1, 81.7, 74.2, 50.3, 49.8, 46.5, 42.0, 40.0, 34.6,
31.4, 30.5, 28.9, 27.1, 26.9, 26.8, 26.7, 26.1, 24.9, 24.3,
24.1, 21.9, 21.4, 18.5, 22.34, 22.75; LRMS m/z 526 (Mþ);
HRMS calcd for C33H54O3Si: 526.3842, found 526.3854.
4.2.18. (1S,4R)-1-tert-Butyldimethylsiloxy-1-isopropyl-
2,2-dimethyl-4-[(1R,2S,5R)-5-methyl-2-(1-methyl-1-
phenylethyl)cyclohexyloxycarbonyl]cyclobutane (trans-
3k). Colorless oil; [a]D26 (c 0.85, CHCl3) 27.4; IR (neat)
2959, 2928, 2856, 1715, 1254, 1070, 764, 700, 669 cm21
;
1H NMR (400 MHz, CDCl3) d 7.27–7.23 (m, 4H), 7.16–
7.11 (m, 1H), 4.85 (ddd, 1H, J¼4.4, 10.7, 10.7 Hz), 2.78
(dd, 1H, J¼6.4, 10.0 Hz), 2.31–2.20 (m, 1H), 2.05–1.95
(m, 1H), 1.94–1.84 (m, 1H), 1.62–0.78 (m, 17H), 1.32 (s,
3H), 1.21 (s, 3H), 1.13 (s, 3H), 0.98 (s, 3H), 0.93 (s, 9H,),
0.22 (s, 3H), 0.20 (s, 3H); 13C NMR (100 MHz, CDCl3) d
172.4, 151.3, 127.9, 125.4, 125.2, 74.3, 50.3, 47.4, 42.9,
41.4, 39.9, 34.5, 32.6, 31.4, 26.9, 26.2, 24.7, 21.8, 19.1,
17.7, 17.5, 22.28, 22.51; LRMS m/z 457 (Mþ257);
HRMS calcd for C32H48O3Si: 457.3138, found 457.3156.
4.2.15. (1S,8R,10R)-1-tert-Butyldimethylsiloxy-9-
[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclo-
hexyloxycarbonyl]bicyclo[6.2.0]decane (cis-3h). Color-
less oil; [a]2D6 (c 0.28, CHCl3)þ22.2; IR (neat) 2926,
2855, 1722, 1445, 1259, 1165, 1094, 1022, 835, 810, 764,
4.2.19. (1R,7S,9R)-1-(tert-Butyldimethylsiloxy)-9-
methyl-9-[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-
ethyl)cyclohexyloxycarbonyl]bicyclo[5.2.0]nonane
(trans-3l). Colorless oil; [a]2D7 (c 0.47, CHCl3) 24.5; IR
1
700 cm21; H NMR (400 MHz, CDCl3) d 7.28–7.19 (m,
4H), 7.15–7.09 (m, 1H), 4.91 (ddd, 1H, J¼4.4, 10.7,
10.7 Hz), 2.39 (dd, 1H, J¼9.5, 9.5 Hz), 2.03–1.89 (m, 2H),
1.83–0.82 (m, 24H), 1.31 (s, 3H), 1.19 (s, 3H), 0.89 (s, 9H),
0.11 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3);d
171.6, 151.3, 127.8, 125.3, 125.0, 81.2, 73.8, 50.6, 49.3,
47.2, 42.6, 39.8, 34.5, 31.9, 31.4, 29.1, 27.1, 26.7, 26.1,
26.0, 25.3, 24.9, 24.4, 24.3, 22.0, 21.0, 18.5, 22.10, 22.42;
LRMS m/z 526 (Mþ); HRMS calcd for C33H54O3Si:
526.3842, found 526.3854.
(neat) 2926, 2855, 1715, 1456, 1076, 835, 773, 700 cm21
;
1H NMR (400 MHz, CDCl3) d 7.28–7.23 (m, 4H), 7.17–
7.11 (m, 1H), 4.79 (ddd, 1H, J¼4.1, 10.6, 10.6 Hz), 2.43–
2.30 (m, 1H), 2.05–1.93 (m, 2H), 1.81–0.72 (m, 21H), 1.32
(s, 3H), 1.29 (s, 3H), 1.20 (s, 3H), 0.89 (s, 9H), 0.19 (s, 3H),
0.14 (s, 3H); 13C NMR (100 MHz, CDCl3) d 174.5, 151.1,
127.9, 125.4, 1251, 83.6, 75.1, 50.7, 50.3, 43.8, 41.8, 40.2,
34.7, 31.5, 31.4, 29.0, 28.2, 27.3, 26.2, 24.9, 23.4, 21.9,
21.9, 21.8, 18.8, 0.09, 21.63, 21.72; LRMS m/z 526 (Mþ);
HRMS calcd for C33H54O3Si, 526.3842, found 526.3861.
4.2.16. (1R,2R)-1-tert-Butyldimethylsiloxy-2-
[(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclo-
4.3. X-ray crystallography13
hexyloxycarbonyl]-1-phenylcyclobutane
(trans-3j).
Colorless oil; [a]2D7 (c 1.17, CHCl3) 248.0; IR (neat)
Prismatic crystals of trans-3a suitable for X-ray crystal-
lography were grown by slow crystallization from AcOH–
MeOH. A Colorless prism crystal of trans-3a having
approximate dimensions of 0.20£0.20£0.20 mm was
mounted on a glass fiber. All measurements were made on
a Rigaku/MSC Mercury CCD diffractometer with graphite
monochromated Mo Ka radiation. The data were collected
at a temperature of 2100^1 8C to a maximum 2u value of
55.08. The structure was solved using the programs in
teXsan; the compound trans-3a belongs to the monoclinic
2928, 2856, 1715, 1256, 1005, 833, 698 cm21; H NMR
1
(400 MHz, CDCl3) d 7.44–7.39 (m, 2H), 7.30–7.15 (m,
7H), 7.15–7.09 (m, 1H), 4.49 (ddd, 1H, J¼4.4, 10.6,
10.6 Hz), 3.22 (dd, 1H, J¼9.4, 9.4 Hz), 2.64–2.56 (m, 1H),
2.25 (q, 4H, J¼10.6 Hz), 1.79–1.62 (m, 3H), 1.47–1.35 (m,
2H), 1.24 (s, 3H), 1.11 (s, 3H), 0.90 (s, 9H), 0.94–0.55 (m,
7H), 0.15 (q, 1H, J¼12.0 Hz), 20.02 (s, 3H), 20.23 (s, 3H);
13C NMR (100 MHz, CDCl3) d 169.7, 151.3, 142.2, 127.7,
127.6, 127.3, 126.3, 125.3, 125.0, 80.6, 73.9, 55.3, 50.1,
40.5, 39.9, 34.4, 33.9, 31.0, 26.8, 26.3, 25.9, 21.6, 18.1,
15.4, 22.83, 22.93; LRMS m/z 520 (Mþ). Anal. calcd for
C32H48O3Si: C, 76.10; H, 9.29, found C, 75.89; H, 8.97.
˚
˚
space group P21 (#4) with a¼10.168(2) A, b¼11.027(2) A,
3
˚
˚
c¼13.583(3) A, b¼91.139(4)8, V¼1522.6(5) A , Z¼2, and
D¼1.088 g/cm3. R¼0.034, and Rw¼0.036 for 3644 unique
reflections. GOF¼0.92.
4.2.17. (1S,2R)-1-tert-Butyldimethylsiloxy-2-[(1R,2S,5R)-
5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyloxycar-
bonyl]-1-phenylcyclobutane (cis-3j). Colorless oil; [a]D27
(c 1.17, CHCl3) 237.3; IR (neat) 2928, 2856, 1722, 1229,
4.4. General procedure for reduction of ester 3 into
alcohol 5
1124, 980, 835, 764, 700 cm21
;
1H NMR (400 MHz,
To a solution of 3 (1.0 equiv.) in CH2Cl2 (0.1 M) was

K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
2077
gradually added DIBAL-H (7.0 equiv., 1 M hexane sol-
ution) at 278 8C. The mixture was stirred for 70 min at the
same temperature, and then was quenched with MeOH. The
resulting mixture was filtered through Celitew and the
filtrate was concentrated in vacuo. The residue was
chromatographed on silica gel (12% AcOEt/hexane) to
afford alcohol 5.
NMR (100 MHz, CDCl3) d 145.7, 128.2, 127.3, 126.3, 79.7,
64.3, 50.2, 31.9, 25.8, 17.9, 14.9, 23.14, 23.69; LRMS m/z
292 (Mþ); HRMS calcd for C17H28O2Si, 292.1859, found
292.1871.
4.4.5. (1S,4S)-1-tert-Butyldimethylsiloxy-4-hydroxy-
methyl-1-isopropyl-2,2-dimethylcyclobutane (trans-5k).
Compound trans-5k was obtained from trans-3k (65 mg,
0.13 mmol) in 61% yield (22 mg). Colorless needles, mp
60–61 8C (from AcOEt–hexane); [a]2D6 (c 0.78,
CHCl3)þ6.4; IR (neat) 3317, 2934, 2860, 1462, 1256,
4.4.1. (1R,6S,8S)-1-tert-Butyldimethylsiloxy-8-hydroxy-
methylbicyclo[4.2.0]octane (trans-5a). Compound trans-
5a was obtained from trans-3a (252 mg, 0.51 mmol) in 73%
yield (100 mg). Colorless needles, mp 72–73 8C (from
AcOEt–hexane); [a]D28 (c 0.27, CHCl3) 232.9; IR (CHCl3)
1
1067, 862, 835, 770 cm21; H NMR (400 MHz, CDCl3) d
4.09–3.96 (m, 1H), 3.71 (dd, 1H, J¼10.3, 10.3 Hz), 2.49–
2.37 (m, 1H), 2.01–1.84 (m, 2H), 1.32 (dd, 1H, J¼4.4,
11.7 Hz), 1.17 (s, 3H), 1.03 (s, 3H), 0.94 (s, 9H), 0.85 (d,
6H, J¼7.1 Hz), 0.23 (s, 3H), 0.16 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 85.4, 64.4 45.5, 42.2, 34.0, 31.0, 26.8,
26.3, 25.8, 19.2, 17.3, 21.58, 21.85; LRMS m/z 228
(Mþ258); HRMS calcd for C13H28OSi: 228.1909, found
228.1889.
3683, 3607, 3032, 3013, 1234, 1200, 802, 706, 679 cm21
;
1H NMR (400 MHz, CDCl3) d 3.78–3.73 (m, 1H), 3.60–
3.54 (m, 1H), 2.30–2.17 (m, 2H), 1.73–1.22 (m, 9H), 1.08
(d, 1H, J¼10.2 Hz), 1.03 (d, 1H, J¼10.5 Hz), 0.85 (s, 9H),
0.12 (s, 3H), 0.10 (s, 3H); 13C NMR (100 MHz, CDCl3) d
100.5, 62.9, 48.6, 40.8, 31.1, 25.8, 23.7, 21.8, 20.4, 18.0,
22.36, 22.40; LRMS m/z 213 (Mþ257). Anal. calcd for
C15H30O2Si: C, 66.61; H, 11.18, found C, 66.43; H, 10.84.
4.5. Transformation into exo-olefin 7a
4.4.2. (1S,6R,8S)-1-tert-Butyldimethylsiloxy-8-hydroxy-
methylbicyclo[4.2.0]octane (cis-5a). Compound cis-5a
was obtained from cis-3a (35 mg, 0.070 mmol) in 77%
yield (13 mg). Colorless oil; [a]2D7 (c 0.49, CHCl3)þ6.1; IR
(neat) 3354, 2930, 2856, 1462, 1252, 1180, 1076, 881, 835,
4.5.1. (1S,6R,8R)-1-tert-Butyldimethylsiloxy-8-o-nitro-
phenylselanylmethylbicyclo[4.2.0]octane (cis-6a). To a
solution of cis-5a (74 mg, 0.27 mmol) and o-nitrophenyl-
selenocyanide (75 mg, 0.33 mmol) in THF (4.0 mL) was
slowly added tributylphosphine (85 mL, 0.34 mmol) at
ambient temperature, and the resulting solution was stirred
for 22.5 h at 50–55 8C. After removal of solvent, the residue
was purified by column chromatography on silica gel with
2% AcOEt/hexane to give cis-6a (100 mg, 80%) as
yellowish prisms, mp 63–65 8C (from AcOEt–hexane);
[a]2D8 (c 0.37, CHCl3) 21.6; IR (KBr) 2928, 2855, 1512,
1
772, 667 cm21; H NMR (400 MHz, CDCl3) d 3.92–3.86
(m, 1H), 3.68–3.59 (m, 1H), 2.53–2.40 (m, 2H), 2.37–2.25
(m, 1H), 1.88–1.81 (m, 1H), 1.76–1.66 (m, 2H), 1.52–1.34
(m, 7H), 0.89 (s, 9H), 0.18 (s, 3H), 0.14 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 63.9, 45.7, 40.0, 37.6, 25.9, 25.6, 21.4,
21.1, 20.0, 18.1, 22.24, 22.40; LRMS m/z 213 (Mþ257);
HRMS m/z calcd for C15H30O2Si (Mþ257): 213.1311,
found 213.1321.
1
1329, 1304, 1067, 835, 733 cm21; H NMR (400 MHz,
CDCl3) d 8.30–8.25 (m, 1H), 7.56–7.46 (m, 2H), 7.31–
7.25 (m, 1H), 3.22 (dd, 1H, J¼5.5, 11.2 Hz), 2.98 (dd, 1H,
J¼10.6, 10.6 Hz), 2.52–2.33 (m, 2H), 1.84–1.21 (m, 10H),
0.93 (s, 9H), 0.16 (s, 3H), 0.14 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 134.5, 133.3, 129.1, 126.3, 125.0, 76.6, 41.6, 40.1,
36.7, 27.7, 27.2, 26.7, 26.0, 22.3, 22.1, 18.4, 22.23; LRMS
m/z 398 (Mþ257). Anal. calcd for C21H33NO3SeSi: C,
55.49; H, 7.32; N, 3.08, found C, 55.67; H, 7.15; N, 2.92.
4.4.3. (1R,2S)-1-tert-Butyldimethylsiloxy-2-hydroxy-
methyl-1-phenylcyclobutane
(trans-5j).
Compound
trans-5j was obtained from trans-3j (63 mg, 0.12 mmol)
in 83% yield (29 mg). Colorless oil; [a]2D8 (c 1.17, CHCl3)
224.6; IR (neat) 3329 2953, 2930, 2856, 1254, 775,
1
700 cm21; H NMR (400 MHz, CDCl3) d 7.50–7.45 (m,
2H), 7.39–7.33 (m, 2H), 7.29–7.26 (m, 1H), 3.21 (ddd, 1H,
J¼6.3, 6.8, 11.4 Hz), 3.13 (ddd, 1H, J¼5.8, 6.1, 11.6 Hz),
2.85–2.76 (m, 1H), 2.70 (ddd, 1H, J¼2.7, 8.7, 11.6 Hz),
2.38–2.28 (m, 1H), 2.03–1.93 (m, 1H), 1.48–1.36 (m, 1H),
0.91 (s, 9H), 0.75 (dd, 1H, J¼5.8, 6.3 Hz), 20.01 (s, 3H),
20.22 (s, 3H); 13C NMR (100 MHz, CDCl3) d 142.7, 128.1,
127.2, 126.2, 79.4, 63.3, 52.2, 33.3, 25.9, 18.0, 16.4, 22.86,
22.97; LRMS m/z 292 (Mþ); HRMS calcd for C17H28O2Si,
292.1859, found 292.1883.
4.5.2. (1S,6R)-1-tert-Butyldimethylsiloxy-8-methylidene-
bicyclo[4.2.0]octane ((1)-7a). To a solution of cis-6a
(72 mg, 0.16 mmol) in THF (3.2 mL) was added H2O2 (31%
v/v; 300 mL) at 0 8C, and the mixture was stirred for 17.5 h
at ambient temperature. The resulting mixture was extracted
with Et2O twice, dried, and concentrated. The residue was
chromatographed on silica gel (hexane) to furnish (þ)-7a
(31 mg, 78%) as colorless oil, [a]2D7 (c 1.75, CHCl3)þ10.4;
IR (neat) 2930, 2856, 1680, 1252, 1142, 1088, 835,
4.4.4. (1S,2S)-1-tert-Butyldimethylsiloxy-2-hydroxy-
methyl-1-phenylcyclobutane (cis-5j). Compound cis-5j
was obtained from cis-3j (26 mg, 0.050 mmol) in 66%
yield (10 mg). Colorless oil; [a]2D7 (c 0.39, CHCl3) 22.9; IR
(neat) 3420, 2953, 2930, 2856, 1252, 1126, 835, 777,
1
773 cm21; H NMR (400 MHz, CDCl3) d 4.91–4.86 (m,
1H), 4.69–4.63 (m, 1H), 2.42–2.25 (m, 2H), 2.20–2.10 (m,
1H), 1.78–1.18 (m, 8H), 0.88 (s, 9H), 0.09 (s, 6H); 13C
NMR (100 MHz, CDCl3) d 155.7, 101.2 77.6, 39.9, 35.8,
28.5 25.8, 24.2, 21.3 20.8 18.2, 22.40, 22.44; LRMS m/z
252 (Mþ); HRMS m/z calcd for C15H28OSi (Mþ): 252.1909,
found 252.1916.
1
669 cm21; H NMR (400 MHz, CDCl3) d 7.51–7.47 (m,
2H), 7.39–7.34 (m, 2H), 7.30–7.25 (m, 1H), 4.15 (ddd, 1H,
J¼3.2, 11.2, 11.2 Hz), 3.79 (ddd, 1H, J¼4.6, 9.8, 11.5 Hz),
3.22 (dd, 1H, J¼3.2, 9.8 Hz), 2.88–2.80 (m, 1H), 2.70–2.60
(m, 1H), 2.49–2.39 (m, 1H), 1.73–1.62 (m, 1H), 1.55–1.46
(m, 1H), 0.87 (s, 9H), 20.01 (s, 3H), 20.45 (s, 3H); 13C
4.5.3. (1R,6S,8R)-1-tert-Butyldimethylsiloxy-8-o-nitro-
phenylselenylmethylbicyclo[4.2.0]octane (trans-6a). To

2078
K. Takasu et al. / Tetrahedron 60 (2004) 2071–2078
2. (a) Kepler, J. A.; Wall, M. E.; Mason, J. E.; Basset, C.;
McPhail, A. T.; Sim, G. A. J. Am. Chem. Soc. 1967, 89,
1260–1261. (b) Wilson, B. J.; Wilson, C. H.; Hayes, A. W.
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a solution of trans-5a (95 mg, 0.35 mmol) and o-nitro-
phenylselenocyanide (96 mg, 0.42 mmol) in THF (4.0 mL)
was slowly added tributylphosphine (105 mL, 0.42 mmol) at
ambient temperature, and the resulting solution was stirred
for 17 h at the same temperature and additional 5.5 h at
50 8C. After removal of solvent, the residue was purified by
column chromatography on silica gel with 2% AcOEt/
hexane to give trans-6a. (140 mg, 88%) as yellowish
prisms, mp 91–93 8C (from AcOEt–hexane); [a]2D8 (c
0.36, CHCl3) 254.8; IR (KBr) 2928, 2855, 1508, 1333,
1252, 1094, 773, 741 cm21; 1H NMR (400 MHz, CDCl3) d
8.29 (d, 1H, J¼7.8 Hz), 7.52–7.48 (m, 2H), 7.33–7.27 (m,
1H), 3.10 (dd, 1H, J¼5.9, 11.0 Hz), 2.84 (dd, 1H, J¼9.8,
9.8 Hz), 2.38–2.27 (m, 1H), 2.26–2.16 (m, 1H), 1.84 (dd,
1H, J¼8.5, 8.5 Hz), 1.76–1.20 (m, 8H), 1.15 (d, 1H,
J¼10.3 Hz), 1.09 (d, 1H, J¼10.5 Hz), 0.89 (s, 9H), 0.11 (s,
3H), 0.11 (s, 3H); 13C NMR (100 MHz, CDCl3) d 134.2,
133.4, 128.9, 126.4, 125.1, 75.8, 44.7, 40.6, 31.1, 26.0, 25.8,
23.8, 23.6, 21.8, 20.4, 18.0, 22.24, 22.34; LRMS m/z 398
(Mþ257). Anal. calcd for C21H33NO3SeSi: C, 55.49; H,
7.32; N, 3.08, found C, 55.34; H, 7.10; N, 2.92.
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4.5.4. (1R,6S)-1-tert-Butyldimethylsiloxy-8-methylidene-
bicyclo[4.2.0]octane ((2)-7a). To a solution of trans-6a
(118 mg, 0.26 mmol) in THF (5.2 mL) was added H2O2
(31% v/v; 430 mL) at 0 8C, and the mixture was stirred for
21 h at ambient temperature. The resulting mixture was
extracted with Et2O twice, dried, and concentrated. The
residue was chromatographed on silica gel (hexane) to
furnish (2)-7a (16 mg, 25%) as colorless oil, [a]2D6 (c 0.75,
CHCl3) 29.8. All spectral data were identical with (þ)-7.
6. (a) Takasu, K.; Misawa, K.; Yamada, M.; Furuta, Y.;
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Acknowledgements
We thank Dr. Chizuko Kabuto (Instrumental Analysis
Center for Chemistry, Faculty of Science, Tohoku
University) for doing the X-ray analysis. This work was
supported in part by Fujisawa Pharmaceutical Company
Award in Synthetic Organic Chemistry, Japan, and a Grant-
in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
10. Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976,
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13. Crystallographic data for compound trans-3a has been
deposited with Cambridge Crystallographic Data Center as
supplementary publication number CCDC 227495.
References and notes
1. Takasu, K.; Ueno, M.; Inanaga, K.; Ihara, M. J. Org. Chem.
2004, 69, 517–521.