Study of the Lewis acid-promoted rearrangement of 2-aryl-2,3-epoxy acylates

Article abstract of DOI:10.1016/S0040-4020(00)01041-3

The reaction of 2-aryl-2,3-epoxy acylates with Lewis acids was examined in detail. Cyclic 2-aryl-2,3-epoxy acylates afforded the rearranged products via C2-carbocation intermediates. On the other hand, acyclic ones gave the rearranged products via phenonium ion intermediates obtained by C3-cleavage of oxirane rings. The method was also applied to the synthesis of the optically active benzylic quaternary carbon center.

Full text of DOI:10.1016/S0040-4020(00)01041-3

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 815±825
Study of the Lewis acid-promoted rearrangement
of 2-aryl-2,3-epoxy acylates
Yasuyuki Kita,p Akihiro Furukawa, Junko Futamura, Kazuhiro Higuchi, Koichiro Ueda and
Hiromichi Fujioka
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
Received 6 May 2000; accepted 31 August 2000
AbstractÐThe reaction of 2-aryl-2,3-epoxy acylates with Lewis acids was examined in detail. Cyclic 2-aryl-2,3-epoxy acylates afforded the
rearranged products via the C2-carbocation intermediates obtained by the C2-cleavage of the oxirane rings. On the other hand, acyclic 2-aryl-
2,3-epoxy acylates gave the rearranged products via the phenonium ion intermediates obtained by the C3-cleavage of the oxirane rings. The
method was also applied to the synthesis of the optically active benzylic quaternary carbon center. q 2001 Elsevier Science Ltd. All rights
reserved.
1. Introduction
the C3-cleavage of oxiranes by diversifying the bulkiness
and electron-withdrawing nature of the acyloxy group (Eq.
(1)).3 On the other hand, in our synthesis of fredericamycin
A, which has the 2-aryl substituted 2,3-epoxy acylate
moiety, the rearrangement proceeded via the C2-cleavage
of the oxirane ring.4 Therefore, aryl and acyloxyalkyl
groups showed the opposite nature for the cleavage of the
oxirane ring. We then examined the Lewis acid-catalyzed
reactions of various cyclic 2-aryl-2,3-epoxy acylates which
were recently communicated. In these cases, every
rearrangement reaction proceeded via the C2-cleavage of
the oxirane ring and it proved that the carbocation stabili-
zing ability of the aryl group is stronger than the electron
withdrawing nature of the acyloxyalkyl group (Eq. (2)).5 We
now examined the reactions of the acyclic 2-aryl-2,3-epoxy
acylates and suprisingly found that the rearrangement
proceeds via the C3-cleavage of the oxirane ring (Eq. (3)).
In this paper, we present the full details of the study
concerning the rearrangement of the 2-aryl-2,3-epoxy
acylates in both cyclic and acyclic systems.
The rearrangement of epoxides is one of the well known
carbon skeleton constructions and a very useful method for
the synthesis of carbonyl compounds.1 In the rearrangement
reactions of epoxides, the control of the regio- and stereo-
chemistries is very important in order to make them more
useful. Many techniques have been developed so far. In
these cases, neighboring groups such as hydroxyl, its alkyl
or silyl ether,2a phenyl,2b vinyl,2c silyl,2d and carbonyl
groups2e can often help to control the regio- and stereo-
chemistries.
Recently, we reported the Lewis acid-catalyzed rearrange-
ment of 2,3-epoxy acylates with alkyl substituents in the C2-
and C3-positions. Although the acyloxy group is recognized
as one of the most popular functional groups causing
neighboring group participation, we succeeded in control-
ling the regiochemistry of the Lewis acid-catalyzed
rearrangement of alkyl substituted 2,3-epoxy acylates via
Keywords: Lewis acid; phenyl group; epoxy acylates.
* Corresponding author. Tel.: 181-6-6879-8225; fax: 181-6-6879-8229
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01041-3

816
Y. Kita et al. / Tetrahedron 57 (2001) 815±825
ꢀ1†
ꢀ2†
ꢀ3†
2. Results and discussion
mediates (A) might be formed by neighboring group
participation of the acyloxy groups. The p-nitrobenzoate,
trans-1c, did not show such a reaction. The difference
between these tendencies must depend on the electron-with-
drawing strength, because the p-nitrobenzoyl group has a
very strong electron-withdrawing nature and does not show
any neighboring group participation (Scheme 1). Effect of
Lewis acid was also examined using 1c as a substrate and
BF3´Et2O proved to be the most effective Lewis acid (Table
1).
2.1. The rearrangement of the epoxy acylates6 in cyclic
system
2.1.1. The epoxy acylates6 with phenyl group. For the
reaction of the ®ve-membered epoxy acylates, the trans-
epoxy acylates (trans-1a±c) afforded high yields of the
corresponding rearrangement products (trans-2a±c) via
the C2-cleavage of the oxirane ring by BF3´Et2O treatment.7
The reactivity, however, depended on the acyloxy group.
That is, the benzoyloxy and pivaloyloxy compounds
required longer reaction times than that of the p-nitro-
benzoyloxy compound. During the reactions, the formation
of the intermediates was observed using TLC for trans-1a,b.
The structures of the intermediates were found to be the
dioxenium cations (A) by trapping them using allyl-
trimethylsilane leading to the allylates 3a,b. The inter-
The tendency observed in the trans-epoxy acylate systems
was also obtained with the cis-epoxy acylates (cis-1a±c).
Thus, cis-epoxy pivalate (cis-1a) and cis-epoxy benzoate
(cis-1b) rearranged to give the corresponding 3-oxo-
acylates (cis-2a and cis-2b) in low yields accompanied
with orthoesters 4a,b formed by neighboring group partici-
pation followed by the attack of the oxygen atom to the
Scheme 1.
Table 1. Effect of Lewis acid on rearrangement of 1c in CH2Cl2
resulting dioxenium cations (B). p-Nitrobenzoate (cis-1c)
was also produced cis-2c in moderate yield, but the by-
product was the enone 5, not the orthoester. The formation
of 5 was rationalized as follows. The carbocation is formed
®rst via the C2-cleavage of the oxirane ring, then 1,2-hy-
dride migration and 1,5-acyl migration followed by b-elimi-
nation. The change in the p-nitrobenzoyl group to
Lewis acid
Time (h)
Yield of 2c
BF3´Et2O
SnCl4
TMSOTf
TiCl4
3
4
1
1
90%
82%
Trace
Trace

Y. Kita et al. / Tetrahedron 57 (2001) 815±825
817
Scheme 2.
2-nitrobenzoyl (cis-1d) or 2-methyl-6-nitrobenzoyl (cis-1e)
does not have much of an effect. Thus, the Lewis acid-cata-
lyzed reactions of the cis- and trans-2-phenyl-2,3-epoxy
acylates proceeded via the C2-cleavage of the oxirane ring
(Scheme 2).
ment via benzylic cation intermediates, because the
benzylic group prolongs the lifetime of the cation and the
rearrangement proceeds in a non-concerted way.8 However,
we rationalized that our result must be due to the more stable
conformation of the cation intermediate ii than the inter-
mediate i ®rst formed by cleavage of the oxirane ring due
to the long life of the cation. In fact, the PM3 calculation
shows that intermediate ii is 3.2 kcal/mol more stable than
intermediate i (Scheme 3).
Rearrangement via the C2-cleavage of the oxirane ring was
also observed in the six-membered ring. That is, 2-phenyl
trans-epoxy p-nitrobenzoate 6 afforded the ring-contracted
®ve-membered product 7 via the C2-cleavage of the oxirane
ring followed by ring-methylene unit rearrangement. The
structure of 7 was unambiguously determined by X-ray
analysis. The con®guration of the quaternary carbon center
of 7 proved to be opposite to the con®guration predicted by
the concerted rearrangement. Quite recently, Neef et al.
reported that it is very dif®cult to predict the con®guration
of the quaternary carbon center produced by the rearrange-
2.1.2. The epoxy acylates6 with p-methoxyphenyl group.
The stabilization ability of the benzylic cation by the
p-methoxyphenyl group is usually recognized as being
much stronger than that of the phenyl group. We then
tried the reactions of the 2,3-epoxy acylates with the
p-methoxyphenyl group at the C2-position (Scheme 4). As
expected, the reactions of 8 and 10 proceeded very smoothly
Scheme 3.

818
Y. Kita et al. / Tetrahedron 57 (2001) 815±825
Scheme 4.
to give the rearranged products 9 and 11, respectively (Runs
1 and 3). The reaction times were very short, and the yields
were very high by just using BF3´Et2O. The effect of the
p-methoxyphenyl group was clari®ed in the catalytic
version. That is, the reactivity of the epoxides was
examined using 0.1 equiv. of BF3´Et2O. The reaction
times and the yields of the rearranged products from the
2,3-epoxy acylates with the p-methoxyphenyl group 8, 10
are the same as those obtained using 1 equiv. of BF3´Et2O
(Runs 2 and 4).9
via the C2-cleavage of the oxirane rings due to the stronger
carbocation stabilizing ability of the aryl groups in com-
parison with the C2-carbocation destabilization ability of
the acyloxy group.
However, the results obtained by the reaction of the 2-aryl-
2,3-epoxy acylates in an acyclic system are completely
different from those in the cyclic systems (Scheme 5).
First, we examined 3,3-dimethyl epoxy p-nitrobenzoate
12. In this case, to our surprise, 12 afforded the phenyl
migrated product 13 in a quantitative yield through the
C3-cleavage of the oxirane ring. We rationalized the forma-
tion of 13 as follows. Although there are three possible
cationic intermediates v, vi, and vii to give 13, the C3-cation
intermediate v is unfavorable in this case because we
already recognize that in more conformationary ®xed cyclic
2.2. The rearrangement of the epoxy acylates6 in an
acyclic system
As mentioned above, we found that the rearrangements of
the 2-aryl-2,3-epoxy acylates in the cyclic system proceeded
Scheme 5.

Y. Kita et al. / Tetrahedron 57 (2001) 815±825
819
Scheme 6.
compounds, the formation of the C3-cation intermediates
cannot be observed. Therefore, we think that 13 was
obtained via a neighboring group, like the ester and phenyl
group participation. (The dioxenium ion (vi) formation by
neighboring participation of the ester group is not clear for
p-nitrobenzoate compounds. We can't see any product
which exempli®es the formation of vi on TLC though
such a product from the reaction of the intermediate and
water on TLC was observed in the case of benzoate in
place of p-nitrobenzoate.) The formation of the phenonium
ion intermediate (vii) is well recognized in the rearrange-
ment reaction of the phenyl group. The difference in the
results between the cyclic and acyclic systems must be
due to the ¯exibility of the starting epoxides. In the acyclic
system, the structure of the starting material is more ¯exible.
The phenyl group can work as a good b-cation stabilizer by
forming a phenonium ion. The same reaction was also
observed for the cyclohexyl epoxy p-nitrobenzoate 14.
That is, the treatment of 14 with BF3´Et2O afforded 15 in
92% yield.
3. Conclusion
As mentioned above, the rearrangements of the 2-aryl-2,3-
epoxy acylate systems are governed by the ¯exibility of the
conformations of the intermediates. Aryl groups in these
systems intrinsically work as neighboring group partici-
pating functions to cause the C3-cleavage of the oxirane
rings because the acyloxy groups also assist in the cleavage
of the oxirane rings at the C3-positions. However, when the
conformations of the intermediates are ®xed like cyclic
systems and neighboring group participation is dif®cult,
aryl groups work as benzylic cation (C2-carbocation)
stabilizing groups and their aptitudes are stronger than the
C2-carbocation destabilizing aptitudes of the acyloxy
groups. The method was also applied to the asymmetric
construction of benzylic quaternary carbon centers found
in many natural products.
4. Experimental
All melting points are uncorrected. The NMR spectra were
measured using 270 and 300 MHz spectrometers with
CDCl3 as the solvent and SiMe4 as the internal standard.
Infrared (IR) absorption spectra were recorded as a KBr
pellet. All solvents were distilled and dried according to
standard procedures.
2.3. Application to the construction of a chiral benzylic
quaternary carbon center in an optically active form
Rearrangement reactions are usually divided into two
categories. One is a concerted rearrangement and the other
is a stepwise rearrangement depending on the lifetime of the
cation intermediates. The stepwise rearrangement some-
times loses stereoselectivity. Although our reaction is a
stepwise reaction, the rearrangement proceeds in a dia-
stereoselective manner as mentioned above. We then
applied our method to the asymmetric synthesis of benzylic
quaternary carbon centers.
4.1. Synthesis of the starting epoxides (cf. Scheme 6)
4.1.1. Synthesis of (^)-trans-epoxy acylates in Scheme 1.
trans-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-yl 2,2-
dimethylpropanoate (trans-1a). DIBAH (n-hexane solu.
7.5 mL, 7.05 mmol) was added dropwise to a solution
of the enone, 3-methyl-2-phenyl-2-cyclopenten-1-one,13
(1.01 g, 5.86 mmol) in CH2Cl2 (30 mL) at 08C under N2
and the resulting mixture was stirred for 20 min at the
same temperature. The reaction mixture was quenched by
the addition of MeOH and then extracted with Et2O. The
organic layer was washed with brine, dried over MgSO4,
and evaporated in vacuo to give the crude allyl alcohol. A
solution of t-BuOOH (60% solu., dried over Na2SO4, 2.10 g,
15.8 mmol) in benzene (10 mL) was added dropwise to a
solution of a cat. amount of VO(acac)2 and the above crude
allyl alcohol in benzene (20 mL) at rt under N2. The mixture
was stirred for 1.5 h. Sat. aq. Na2S2O3 was then added to the
mixture. The resulting solution was extracted with AcOEt.
The organic layer was washed with brine, dried over
The reduction of the enone 16 by Corey's method10 afforded
the (R)-allyl alcohol 17 in 90% ee. The ee value of 17 was
determined by HPLC analysis. Epoxidation of 17 with
11
t-BuOOH/VO(acac)2 stereoselectively gave the epoxy
alcohol 18 in 87% yield. The Mitsunobu reaction12 of 18
with p-nitrobenzoic acid gave the trans-epoxy p-nitrobenzo-
ate (1)-8 in 90% yield. The reactions proceeded without
losing chiral integrity during the conversions of 17 to (1)-8.
The treatment of epoxy p-nitrobenzoates (1)-8 with
BF3´Et2O afforded the optically active product (1)-9 with
the same ee values as the starting epoxy acylates. This
experiment showed that the reaction stereospeci®cally
proceeded during the rearrangements (Scheme 6).

820
Y. Kita et al. / Tetrahedron 57 (2001) 815±825
Na2SO4, and evaporated in vacuo. The residue was puri®ed
by SiO2 column chromatography using hexane±AcOEt
(9/1) as the eluent to give the cis-epoxy alcohol (1.04 g,
93% in 2 steps). Pivalic acid (449 mg, 4.40 mmol) and
Ph3P (1.12 g, 4.26 mmol) were added to a solution of the
above cis-epoxy alcohol (405 mg, 2.13 mmol) in toluene
(10 mL) at 08C under N2. Diethyl azadicarboxylate (toluene
solu., 1.90 mL, 4.36 mmol) was added dropwise to the
resulting solution. The mixture was stirred overnight, then
treated with sat. aq. NaHCO3. The resulting solution was
extracted with AcOEt. The organic layer was washed with
brine, dried over Na2SO4, and evaporated in vacuo. The
residue was puri®ed by SiO2 column chromatography
using hexane±AcOEt (9/1) as the eluent to give trans-1a
(524 mg, 90%). Colorless oil; IR (KBr) 1732, 1279,
and evaporated in vacuo. The residue was puri®ed by SiO2
column chromatography using hexane±AcOEt (7/1) as the
eluent to give cis-1a (575 mg, 99%). Colorless crystals mp
69±718C (hexane±EtOAc); IR (KBr) 1728, 1283,
1
1161 cm21; H NMR (CDCl3) d 1.03 (s, 9H), 1.21 (s,
3H), 1.40±1.57 (m, 1H), 1.75±1.87 (m, 1H), 2.04±2.21
(m, 2H), 5.67 (t, 1H, Jˆ8.1 Hz), 7.26±7.37 (m, 5H); 13C
NMR (CDCl3) d 15.3, 24.5, 26.9, 30.5, 38.6, 68.1, 71.2,
75.9, 126.8, 127.6, 128.0, 133.7, 178.4; Anal. Calcd for
C17H22O3: C, 74.42; H, 8.08. Found: C, 74.28; H, 8.05.
4.2.2. cis-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-yl
benzoate (cis-1b). In the same procedure for cis-1a, cis-
1b (763 mg, 98%) was obtained from the cis-epoxy alcohol
(503 mg, 2.64 mmol), benzoyl chloride (460 mL, 3.96
mmol), and pyridine (5.0 mL). Colorless crystals; mp 74±
808C (hexane±AcOEt); IR (KBr) 1717, 1451, 1271, 1120,
1099 cm21; 1H NMR (CDCl3) d 1.23 (s, 3H), 1.59±1.67 (m,
1H), 1.83±1.91 (m, 1H), 2.19±2.32 (m, 2H), 5.94 (t, 1H, Jˆ
8.1 Hz), 7.28±7.52 (m, 8H), 7.96 (dd, 2H, Jˆ8.5, 1.5 Hz);
13C NMR (CDCl3) d 15.3, 24.9, 30.5, 68.3, 71.1, 76.9,
126.8, 127.7, 128.1, 128.2, 129.7, 129.8, 132.9, 133.7,
166.3; Anal. Calcd for C19H18O3: C, 77.53; H, 6.16.
Found: C, 77.29; H, 6.18.
1151 cm21 1H NMR (CDCl3) d 1.12 (s, 9H), 1.31 (s,
;
3H), 1.57±1.65 (m, 1H), 1.92±2.07 (m, 3H), 5.34 (d, 1H,
Jˆ5.2 Hz), 7.29±7.43 (m, 5H); 13C NMR (CDCl3) d 16.1,
27.0, 28.3, 30.7, 38.7, 70.0, 70.8, 77.6, 127.8, 128.0, 128.6,
133.6, 177.2; HRMS (FAB) Calcd for C17H23O3 (M11H):
275.1647. Found: 275.1647.
4.1.2. trans-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-
yl benzoate (trans-1b). In the same procedure for trans-1a,
trans-1b (489 mg, 60%) was obtained from the cis-epoxy
alcohol (525 mg, 2.76 mmol), benzoic acid (867 mg,
7.10 mmol), Ph3P (1.81 g, 6.91 mmol), diethyl aza-
dicarboxylate (toluene solu., 3.0 mL, 6.89 mmol), and
toluene (10 mL). Colorless needles; mp 69±728C (hexane±
4.2.3. cis-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-yl
4-nitrobenzoate (cis-1c). In the same procedure for cis-
1a, cis-1c (633 mg, 88%) was obtained from the cis-epoxy
alcohol (404 mg, 2.12 mmol), p-nitrobenzoyl chloride
(593 mg, 3.20 mmol), and pyridine (5.0 mL). Colorless
EtOAc); IR (KBr) 1723, 1271, 1113 cm21 1H NMR
;
oil; IR (KBr) 1728, 1537, 1273, 1123, 1101 cm21 1H
;
(CDCl3) d 1.34 (s, 3H), 1.81±1.84 (m, 1H), 2.05±2.14 (m,
3H), 5.63 (d, 1H, Jˆ4.9 Hz), 7.25±7.31 (m, 3H), 7.42±7.59
(m, 5H), 7.99 (d, 2H, Jˆ 8.2 Hz); 13C NMR (CDCl3) d 15.9,
28.3, 30.7, 70.2, 70.7, 78.5, 128.0, 128.2, 128.3, 129.4,
130.2, 132.9, 133.6, 165.3; Anal. Calcd for C19H18O3: C,
77.53; H, 6.16. Found: C, 77.43; H, 6.21.
NMR (CDCl3) d 1.24 (s, 3H), 1.60±1.73 (m, 1H), 1.85±
1.97 (m, 1H), 2.21±2.38 (m, 2H), 5.95 (t, 1H, Jˆ8.0 Hz),
7.28±7.44 (m, 5H), 8.11 (d, 2H, Jˆ8.9 Hz), 8.21 (d, 2H,
Jˆ8.9 Hz); 13C NMR (CDCl3) d 15.2, 24.9, 30.5, 68.6, 70.9,
78.1, 123.3, 126.7, 127.9, 128.3, 130.7, 133.3, 135.1, 150.4,
164.4; HRMS (FAB) Calcd for C19H18NO5 (M11H):
340.1185. Found: 340.1183.
4.1.3. trans-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-
yl 4-nitrobenzoate (trans-1c). In the same procedure for
trans-1a, trans-1c (519 mg, 72%) was obtained from the
cis-epoxy alcohol (406 mg, 2.13 mmol), p-nitrobenzoic
acid (709 mg, 4.24 mmol), Ph3P (1.12 g, 4.25 mmol),
diethyl azadicarboxylate (toluene solu., 1.90 mL, 4.36
mmol), and toluene (10 mL). Yellowish crystals; mp 98±
1008C (hexane±EtOAc); IR (KBr) 1728, 1532, 1271, 1177,
1117 cm21; 1H NMR (CDCl3) d 1.36 (s, 3H), 1.84±1.87 (m,
1H), 2.08±2.19 (m, 3H), 5.65 (d, 1H, Jˆ5.1 Hz), 7.27±7.44
(m, 5H), 8.12 (d, 2H, Jˆ9.0 Hz), 8.28 (d, 2H, Jˆ9.0 Hz);
13C NMR (CDCl3) d 16.0, 28.2, 30.7, 70.2, 70.6, 79.5,
123.6, 128.1, 128.2, 128.3, 130.5, 133.2, 135.5, 150.5,
163.5; Anal. Calcd for C19H17NO5: C, 67.25; H, 5.05; N,
4.13. Found: C, 66.98; H, 5.19; N, 4.12.
4.2.4. cis-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-yl
2-nitrobenzoate (cis-1d). In the same procedure for cis-
1a, cis-1d (178.5 mg, 99%) was obtained from the cis-
epoxy alcohol (101.2 mg, 0.532 mmol), o-nitrobenzoyl
chloride (100 mL, 0.757 mmol), and pyridine±CH2Cl2
(1:1, 2.0 mL). Colorless crystals; mp 76±788C (hexane±
AcOEt); IR (KBr) 1732, 1539, 1352, 1289, 1132,
1
1075 cm21; H NMR (CDCl3) d 1.23 (s, 3H), 1.60±1.93
(m, 2H), 2.20±2.39 (m, 2H), 5.97 (t, 1H, Jˆ7.9 Hz),
7.30±7.59 (m, 8H), 7.84±7.87 (m, 1H); 13C NMR
(CDCl3) d 15.2, 24.4, 30.5, 68.8, 70.8, 78.4, 123.8, 126.8,
127.5, 127.9, 128.3, 129.6, 131.6, 132.8, 133.3, 147.7,
165.3; Anal. Calcd for C19H17NO5: C, 67.25; H, 5.05; N,
4.13. Found: C, 67.35; H, 5.16; N, 4.15.
4.2. Synthesis of (^)-cis-epoxy acylates in Scheme 2
4.2.5. cis-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-yl
2-methyl-6-nitrobenzoate (cis-1e). In the same procedure
for cis-1a, cis-1e (76.9 mg, 40%) was obtained from the
cis-epoxy alcohol (104.0 mg, 0.547 mmol), 2-methyl-4-
nitrobenzoyl chloride (204 mg, 1.02 mmol), and pyridine±
CH2Cl2 (1:1, 4.0 mL). Light yellowish crystals; mp 143±
1458C (hexane±AcOEt); IR (KBr) 1738, 1538, 1271, 1121,
1076 cm21; 1H NMR (CDCl3) d 1.23 (s, 3H), 1.71±1.93 (m,
2H), 1.98 (s, 3H), 2.21±2.40 (m, 2H), 6.13 (t, 1H,
4.2.1. cis-5-Methyl-1-phenyl-6-oxabicyclo[3.1.0]hex-2-yl
2,2-dimethylpropanoate (cis-1a). Pivaloyl chloride
(390 mL, 3.17 mmol) was added dropwise to a solution of
the cis-epoxy alcohol (the same one used in the synthesis of
1a, 403 mg, 2.12 mmol) in pyridine (5.0 mL) at 08C under
N2. The mixture was stirred for 3 h at rt, then treated with
H2O. The resulting solution was extracted with AcOEt. The
organic layer was washed with brine, dried over Na2SO4,

Y. Kita et al. / Tetrahedron 57 (2001) 815±825
821
Jˆ8.1 Hz), 7.30±7.47 (m, 7H), 7.91±7.95 (m, 1H); 13C
NMR (CDCl3) d 15.2, 18.4, 24.1, 30.6, 69.0, 71.0, 77.7,
121.6, 126.9, 127.9, 128.3, 129.4, 129.5, 133.2, 135.9,
137.3, 145.6, 166.4; Anal. Calcd for C20H19NO5: C, 67.98;
H, 5.42; N, 3.96. Found: C, 67.79; H, 5.48; N, 3.95.
boxylate (toluene solu., 1.05 mL, 2.41 mmol), and toluene
(10 mL). Colorless needles; mp 105±1078C (hexane±
AcOEt); IR (KBr) 1728, 1526, 1271, 1250, 1117,
1
1103 cm21; H NMR (CDCl3) d 1.36 (s, 3H), 1.81±2.16
(m, 4H), 3.77 (s, 3H), 5.62 (d, 1H, Jˆ4.9 Hz), 6.83 (dd,
2H, Jˆ6.8, 1.8 Hz), 7.33 (dd, 2H, Jˆ6.8, 1.8 Hz), 8.12 (d,
2H, Jˆ7.0 Hz), 8.29 (d, 2H, Jˆ7.0 Hz); 13C NMR (CDCl3)
d 16.0, 28.1, 30.7, 55.2, 70.1, 70.4, 79.6, 113.6, 123.6,
125.2, 129.4, 130.6, 135.6, 150.5, 159.4, 163.6; Anal.
Calcd for C20H19NO6: C, 65.03; H, 5.18; N, 3.79. Found:
C, 64.81; H, 5.26; N, 3.76.
4.3. Synthesis of (^)-trans-6-methyl-1-phenyl-7-oxa-
bicyclo[4.1.0]hept-2-yl 4-nitrobenzoate (6) in Scheme 3
DIBAH (n-hexane solu. 1.40 mL, 1.33 mmol) was added
dropwise to a solution of 3-methyl-2-phenyl-2-cyclo-
hexen-1-one14 (202 mg, 1.08 mmol) in CH2Cl2 (11 mL) at
08C under N2 and the resulting mixture was stirred for
20 min at the same temperature. The reaction mixture was
quenched by addition of MeOH and extracted with Et2O.
The organic layer was washed with brine, dried over
MgSO4, and evaporated in vacuo to give the crude allyl
alcohol. A solution of tert-BuOOH (68% solu., dried over
MgSO4, 430 mg, 3.24 mmol) in benzene (3.0 mL) was
added dropwise to a solution of cat. amount of VO(acac)2
and the above crude allyl alcohol in benzene (7.0 mL) at rt
under N2. The mixture was stirred for 1.5 h. Sat. aq.
Na2S2O3 was added to the mixture. The resulting solution
was extracted with AcOEt. The organic layer was washed
with water and brine, dried over Na2SO4, and evaporated in
vacuo. The residue was puri®ed by SiO2 column chroma-
tography using hexane±AcOEt (2/1) as the eluent to give
the cis-epoxy alcohol (209 mg, 94% in 2 steps). p-Nitro-
benzoic acid (341 mg, 2.04 mmol) and Ph3P (536 mg,
2.04 mmol) were added to a solution of the above cis-
epoxy alcohol (209 mg, 1.02 mmol) in toluene (10 mL) at
08C under N2. Diethyl azadicarboxylate (toluene solu.,
890 mL, 2.04 mmol) was added dropwise to the resulting
solution. The mixture was stirred for 2.5 h, then treated
with sat. aq. NaHCO3. The resulting solution was extracted
with AcOEt. The organic layer was washed with brine, dried
over Na2SO4, and evaporated in vacuo. The residue was
puri®ed by SiO2 column chromatography using hexane±
AcOEt (9/1) as the eluent to give trans-epoxy p-nitrobenzo-
ate 6 (327 mg, 90%). Colorless crystals; mp 123±1248C
4.4.2. trans-6-Methyl-1-[4-(methyloxy)phenyl]-7-oxabi-
cyclo[4.1.0]hept-2-yl 4-nitrobenzoate (10). In the same
procedure for 6, 10 was prepared. Reduction of 3-methyl-
2-[4-(methyloxy)phenyl]-2-cyclohexen-1-one (704 mg, 3.25
mmol) with DIBAH (4.15 mL, 3.91 mmol) in CH2Cl2
(33 mL) gave the allyl alcohol (692 mg, 98%). Epoxy
alcohol (682 mg, 94%) was obtained from the allyl alcohol
(674 mg, 3.09 mmol), VO(acac)2 (cat. amount), tert-
BuOOH (1.50 g, 11.3 mmol), and benzene (10±4 mL).
Epoxy p-nitrobenzoate 10 (513 mg, 90%) was obtained
from epoxy alcohol (351 mg, 1.49 mmol), Ph3P (862 mg,
3.29 mmol), p-nitrobenzoic acid (550 mg, 3.29 mmol),
diethyl azadicarboxylate (toluene solu., 1.50 mL, 3.45
mmol), and toluene (15 mL). Colorless crystals; mp 85±
888C (hexane±AcOEt); IR (KBr) 1728, 1538, 1273, 1119,
1102 cm21; 1H NMR (CDCl3) d 1.10 (s, 3H), 1.60±1.72 (m,
3H), 1.92±2.16 (m, 3H), 3.71 (s, 3H), 5.50 (t, 1H, Jˆ
5.0 Hz), 6.76 (d, 2H, Jˆ8.5 Hz), 7.25 (d, 2H, Jˆ8.5 Hz),
8.02 (d, 2H, Jˆ8.8 Hz), 8.23 (d, 2H, Jˆ8.8 Hz); 13C NMR
(CDCl3) d 15.9, 22.1, 26.4, 29.6, 55.1, 64.4, 66.2, 73.3,
113.2, 123.4, 128.7, 128.8, 130.4, 135.5, 150.3, 158.9,
163.3; Anal. Calcd for C21H21NO6: C, 65.79; H, 5.52; N,
3.65. Found: C, 65.74; H, 5.59; N, 3.63.
4.5. Synthesis of acyclic epoxy p-nitrobenzoates in
Scheme 5
4.5.1. (3,3-Dimethyl-2-phenyloxiran-2-yl)methyl 4-nitro-
benzoate (12). Light yellowish crystals; IR (KBr) 1732,
1
(hexane±AcOEt); IR (KBr) 1728, 1530, 1271 cm21; H
1
NMR (CDCl3) d 1.10 (s, 3H), 1.57±1.73 (m, 3H), 1.93±
2.16 (m, 3H), 5.51 (t, 1H, Jˆ5.3 Hz), 7.18±7.36 (m, 5H),
7.98 (d, 2H, Jˆ8.5 Hz), 8.22 (d, H, Jˆ8.5 Hz); 13C NMR
(CDCl3) d 15.9, 22.1, 26.5, 29.6, 64.2, 66.6, 73.0, 123.3,
127.6, 127.7, 127.8, 130.4, 135.4, 136.6, 150.3, 163.2; Anal.
Calcd for C20H19NO5: C, 67.98; H, 5.42; N, 3.96. Found: C,
67.87; H, 5.49; N, 3.92.
1532, 1273, 1118 cm21; H NMR (CDCl3) d 1.07 (s, 3H),
1.60 (s, 3H), 4.57 (d, 1H, Jˆ11.9 Hz), 4.97 (d, 1H,
Jˆ11.9 Hz), 7.29±7.40 (m, 5H), 8.00 (d, 2H, Jˆ9.0 Hz),
8.22 (d, 2H, Jˆ9.0 Hz); 13C NMR (CDCl3) d 20.5, 21.8,
63.7, 66.7, 68.1, 123.4, 126.7, 127.6, 128.1, 130.5, 135.0,
137.2, 150.4, 164.1; Anal. Calcd for C18H17NO5: C, 66.05;
H, 5.23; N, 4.28. Found: C, 65.99; H, 5.23; N, 4.27.
4.5.2. (2-Phenyl-1-oxaspiro[2.5]oct-2-yl)methyl 4-nitro-
benzoate (14). Light yellowish crystals; IR (KBr) 1730,
4.4. Synthesis of (^)-epoxy p-nitrobenzoates in Scheme 4
1529, 1273 cm21 1H NMR (CDCl3) d 1.19±1.88 (m,
;
4.4.1. trans-5-Methyl-1-[4-(methyloxy)phenyl]-6-oxabi-
cyclo[3.1.0]hex-2-yl 4-nitrobenzoate (8). In the same
procedure for trans-1a, 8 was obtained. Reduction of 3-
methyl-2-[4-(methyloxy)phenyl]-2-cyclopenten-1-one (257
mg, 1.27 mmol) with DIBAH (1.60 mL, 1.52 mmol) in
CH2Cl2 (10 mL) gave the allyl alcohol (247 mg, 95%).
cis-Epoxy alcohol (266 mg, quant.) was obtained from the
allyl alcohol (247 mg, 1.21 mmol), VO(acac)2, tert-BuOOH
(68%, 480 mg, 3.62 mmol), and benzene (7±3 mL). Epoxy
p-nitrobenzoate 8 (420 mg, 94%) was obtained from epoxy
alcohol (266 mg, 1.21 mmol), Ph3P (638 mg, 2.43 mmol),
p-nitrobenzoic acid (411 mg, 2.46 mmol), diethyl azadicar-
10H), 4.59 (d, 1H, Jˆ11.9 Hz), 4.98 (d, 1H, Jˆ11.9 Hz),
7.28±7.42 (m, 5H), 7.99 (d, 2H, Jˆ8.9 Hz), 8.22 (d, 2H,
Jˆ8.9 Hz); 13C NMR (CDCl3) d 24.5, 25.4, 25.5, 30.8, 31.6,
67.6, 68.0, 68.3, 123.5, 126.8, 127.6, 128.2, 130.6, 135.1,
137.1, 150.5, 164.3; Anal. Calcd for C21H21NO5: C, 68.65;
H, 5.76; N, 3.81. Found: C, 68.74; H, 5.77; N, 3.81.
4.6. Lewis acid treatment of the epoxides
4.6.1. General procedure of the reaction of epoxy
acylates and Lewis acid. Lewis acid (0.3 mmol) was

822
Y. Kita et al. / Tetrahedron 57 (2001) 815±825
Reactions in Scheme 1
Entry
Substrate
Lewis acid
CH2Cl2 (mL)
Product yield
1
2
3
trans-1a 108.9 mg (0.397 mmol)
trans-1b 95.4 mg (0.324 mmol)
trans-1c 101.3 mg (0.299 mmol)
BF3´Et2O 50 mL (0.407 mmol)
BF3´Et2O 40 mL (0.325 mmol)
BF3´Et2O 40 mL (0.325 mmol)
4.0
3.2
3.0
trans-2a 91.1 mg (84%)
trans-2b 64.1 mg (67%)
trans-2c 91.2 mg (90%)
added dropwise to a solution of epoxy acylate (0.3 mmol) in
CH2Cl2 (3 mL) at 08C under N2 and the resulting mixture
was stirred at 08C or rt. After completion of the reaction
(TLC check), sat. aq. NaHCO3 was added to the mixture.
The resulting solution was extracted with CH2Cl2. The
organic layer was washed with brine, dried over Na2SO4,
and evaporated in vacuo. The residue was puri®ed by SiO2
column chromatography using hexane±AcOEt as the
eluent.
140.0, 150.7, 163.9, 217.1; Anal. Calcd for C19H17NO5: C,
67.25; H, 5.05; N, 4.13. Found: C, 67.01; H, 5.12; N, 4.09.
4.6.5. cis-2-Methyl-3-oxo-2-phenylcyclopentyl 2,2-di-
methylpropanoate (cis-2a). Colorless needles; mp 129±
1338C (hexane±AcOEt); IR (KBr) 1738, 1717, 1285,
1
1167 cm21; H NMR (CDCl3) d 0.84 (s, 9H), 1.48 (s,
3H), 2.03±2.11 (m, 1H), 2.31±2.42 (m, 1H), 2.56±2.62
(m, 2H), 5.43 (dd, 1H, Jˆ4.3, 2.1 Hz), 7.19±7.30 (m,
5H); 13C NMR (CDCl3) d 23.2, 25.8, 26.6, 35.8, 38.5,
56.7, 79.6, 126.7, 127.6, 128.0, 138.8, 177.1, 217.9; Anal.
Calcd for C17H22O3: C, 74.42; H, 8.08. Found: C, 74.27; H,
8.04.
4.6.2. trans-2-Methyl-3-oxo-2-phenylcyclopentyl 2,2-
dimethylpropanoate (trans-2a). Colorless oil; IR (KBr)
1
1748, 1732, 1283, 1146 cm21; H NMR (CDCl3) d 1.22
(s, 9H), 1.35 (s, 3H), 1.92±2.14 (m, 2H), 2.40±2.48 (m,
2H), 5.75 (t, 1H, Jˆ3.5 Hz), 7.24±7.36 (m, 5H); 13C
NMR (CDCl3) d 19.4, 25.1, 27.0, 34.4, 38.9, 58.0, 79.1,
126.2, 127.2, 128.9, 140.5, 177.5, 217.7; HRMS
(FAB) Calcd for C17H23O3 (M11H): 275.1647. Found:
275.1674.
4.6.6. 1-(1,1-Dimethylethyl)-3-methyl-6-phenyl-2,7,8-tri-
oxatricyclo[3.2.1.03,6]octane (4a). Colorless crystals; mp
56±598C (hexane±AcOEt); IR (KBr) 1489, 1455, 1402,
1
1163, 1063 cm21; H NMR (CDCl3) d 0.95 (s, 3H), 1.26
(s, 9H), 1.82±1.93 (m, 1H), 2.17±2.25 (m, 3H), 4.21 (dd,
1H, Jˆ2.1, 1.8 Hz), 7.25±7.42 (m, 5H); 13C NMR (CDCl3)
d 19.8, 25.4, 28.5, 32.8, 33.0, 82.9, 88.8, 94.0, 122.3, 125.4,
128.1, 128.5, 133.4; Anal. Calcd for C17H22O3: C, 74.42; H,
8.08. Found: C, 74.28; H, 8.04.
4.6.3. trans-2-Methyl-3-oxo-2-phenylcyclopentyl benzo-
ate (trans-2b). Colorless oil; IR (KBr) 1748, 1722, 1273,
1111 cm21; 1H NMR (CDCl3) d 1.44 (s, 3H), 2.18±2.23 (m,
2H), 2.49±2.59 (m, 2H), 6.05 (t, 1H, Jˆ3.7 Hz), 7.28±7.62
(m, 8H), 8.03 (d, 2H, Jˆ7.6 Hz); 13C NMR (CDCl3) d 19.7,
25.2, 34.5, 58.3, 80.0, 126.2, 127.3, 128.5, 129.0, 129.5,
129.7, 133.3, 140.4, 165.7, 217.7; HRMS (FAB) Calcd for
C19H19O3 (M11H): 295.1334. Found: 295.1344.
4.6.7. cis-2-Methyl-3-oxo-2-phenylcyclopentyl benzoate
(cis-2b). Colorless crystals; mp 101±1028C (hexane±
AcOEt)); IR (KBr) 1748, 1717, 1279, 1113 cm21 1H
;
NMR (CDCl3) d 1.56 (s, 3H), 2.24±2.29 (m, 1H), 2.45±
2.72 (m, 3H), 5.62 (t, 1H, Jˆ4.0 Hz), 7.14±7.50 (m, 8H),
7.65 (dd, 2H, Jˆ8.5, 1.4 Hz); 13C NMR (CDCl3) d 22.8
25.8, 35.8, 57.1, 80.6, 127.0, 127.8, 128.1, 128.2, 129.4,
129.8, 133.0, 138.7, 165.5, 217.9.
4.6.4. trans-2-Methyl-3-oxo-2-phenylcyclopentyl 4-nitro-
benzoate (trans-2c). Light yellowish crystals; mp 119±
1218C (hexane±EtOAc); IR (KBr) 1748, 1728, 1532,
1
1273, 1117, 1103 cm21; H NMR (CDCl3) d 1.44 (s, 3H),
2.17±2.30 (m, 2H), 2.52±2.60 (m, 2H), 6.08 (t, 1H,
Jˆ3.6 Hz), 7.29±7.40 (m, 5H), 8.20 (d, 2H, Jˆ9.0 Hz),
8.31 (d, 2H, Jˆ9.0 Hz); 13C NMR (CDCl3) d 19.6, 25.2,
34.4, 58.3, 81.2, 123.7, 126.2, 127.6, 129.2, 130.7, 135.0,
4.6.8. 3-Methyl-1,6-diphenyl-2,7,8-trioxatricyclo[3.2.1.03,6]-
octane (4b). Colorless oil; IR (KBr) 1453, 1387, 1317,
1
1078, 1053 cm21; H NMR (CDCl3) d 1.11 (s, 3H), 1.97±
2.04 (m, 1H), 2.30±2.45 (m, 3H), 4.45 (d, 1H, Jˆ4.3 Hz),
Reactions in Scheme 2
Entry
1
Substrate
Lewis acid
CH2Cl2 (mL)
3.8
Product yield
cis-1a 103.1 mg
(0.376 mmol)
cis-1b 103.3 mg
(0.351 mmol)
cis-1c 103.9 mg
(0.306 mmol)
cis-1d 93.6 mg
(0.276 mmol)
cis-1e 58.2 mg
(0.165 mmol)
BF3´Et2O 50 mL
(0.407 mmol)
BF3´Et2O 45 mL
(0.366 mmol)
BF3´Et2O 40 mL
(0.326 mmol)
BF3´Et2O 35 mL
(0.285 mmol)
BF3´Et2O 20 mL
(0.163 mmol)
cis-2a 25.7 mg (25%)
4a 49.4 mg (48%)
cis-2b 28.1 mg (27%)
4b 45.2 mg (43%)
cis-2c 51.5 mg (50%)
5 16.5 mg (31%)
cis-2d 53.9 mg (58%)
5 11.9 mg (25%)
cis-2e 30.6 mg (53%)
5 5.6 mg (20%)
2
3
4
5
3.5
3.0
2.8
1.7

Y. Kita et al. / Tetrahedron 57 (2001) 815±825
823
Reactions in Scheme 4
Entry
Substrate
Lewis acid
CH2Cl2 (mL)
Product yield
1
2
3
4
8 101.1 mg (0.273 mmol)
8 42.6 mg (0.115 mmol)
10 91.4 mg (0.238 mmol)
10 58.4 mg (0.152 mmol)
BF3´Et2O 35 mL (0.285 mmol)
BF3´Et2O 2 mL (0.016 mmol)
BF3´Et2O 30 mL (0.244 mmol)
BF3´Et2O 2 mL (0.016 mmol)
2.8
1.2
2.4
1.5
9 97.9 mg (97%)
9 39.6 mg (93%)
11 87.6 mg (94%)
11 54.1 mg (93%)
7.34±7.45 (m, 8H), 7.79±7.83 (m, 2H); 13C NMR (CDCl3)
d 20.2, 28.3, 33.1, 83.5, 89.8, 95.1, 117.0, 125.3, 127.0,
128.2, 128.4, 128.6, 130.1, 131.2, 132.7; HRMS (FAB)
Calcd for C19H19O3 (M11H): 295.1334. Found: 295.1325.
ate (7). 7 (49.8 mg, 62%) was obtained from 6 (80.9 mg,
0.229 mmol), BF3´Et2O (30 mL, 0.244 mmol), and CH2Cl2
(2.3 mL). Colorless crystals; mp 149±1518C (hexane±
1
AcOEt); IR (KBr) 1725, 1715, 1530, 1277 cm21; H NMR
(CDCl3) d 1.57±1.62 (m, 1H), 1.86±1.98 (m, 2H), 1.91 (s,
3H), 2.20±2.37 (m, 2H), 2.71±2.83 (m, 1H), 6.17 (d, 1H,
Jˆ5.2 Hz), 7.30±7.43 (m, 5H), 8.14 (d, 2H, Jˆ9.1 Hz), 8.30
(d, 2H, Jˆ9.1 Hz); 13C NMR (CDCl3) d 20.6, 27.3, 31.6,
33.2, 68.5, 81.2, 123.7, 126.3, 127.7, 129.2, 130.7, 135.3,
138.8, 150.7, 163.9, 205.7; Anal. Calcd for C20H19NO5:
C, 67.98; H, 5.42; N, 3.96. Found: C, 67.97; H, 5.39; N,
3.98.
4.6.9. cis-2-Methyl-3-oxo-2-phenylcyclopentyl 4-nitro-
benzoate (cis-2c). Light yellowish needles; mp 125±
1278C (hexane±AcOEt); IR (KBr) 1748, 1725, 1531,
1
1277, 1116, 1103 cm21; H NMR (CDCl3) d 1.59 (s, 3H),
2.27±2.33 (m, 1H), 2.50±2.74 (m, 3H), 5.66 (dd, 1H, Jˆ4.6,
2.7 Hz), 7.16±7.32 (m, 5H), 7.75 (d, 2H, Jˆ8.9 Hz), 8.15 (d,
2H, Jˆ8.9 Hz); 13C NMR (CDCl3) d 22.7, 25.7, 35.8, 57.2,
81.7, 123.3, 127.1, 127.6, 128.2, 130.4, 135.1, 138.4, 150.4,
163.5, 217.4; Anal. Calcd for C19H17NO5: C, 67.25; H, 5.05;
N, 4.13. Found: C, 67.18; H, 5.12; N, 4.09.
4.6.14. trans-2-Methyl-2-[4-(methyloxy)phenyl]-3-oxo-
cyclopentyl 4-nitrobenzoate (9). Yellowish crystals; mp
167±1698C (hexane±AcOEt); IR (KBr) 1746, 1723, 1520,
1277, 1253, 1117, 1105 cm21; 1H NMR (CDCl3) d 1.41 (s,
3H), 2.17±2.59 (m, 4H), 3.80 (s, 3H), 6.05 (t, 1H,
Jˆ3.5 Hz), 6.90 (d, 2H, Jˆ9.0 Hz), 7.22 (d, 2H, Jˆ
9.0 Hz), 8.19 (d, 2H, Jˆ9.0 Hz), 8.31 (d, 2H, Jˆ9.0 Hz);
13C NMR (CDCl3) d 19.7, 25.2, 34.4, 55.3, 57.7, 81.3,
114.6, 123.7, 127.4, 130.8, 131.8, 135.2, 150.8, 158.9,
164.0, 217.2; Anal. Calcd for C20H19NO6: C, 65.03; H,
5.18; N, 3.79. Found: C, 64.89; H, 5.22; N, 3.83.
4.6.10. 3-Methyl-2-phenylcyclopent-2-en-1-one (5). Color-
less oil; IR (KBr) 1696, 1379, 1134 cm21; 1H NMR (CDCl3)
d 2.19 (s, 3H), 2.54±2.67 (m, 4H), 7.27±7.44 (m, 5H).
4.6.11. cis-2-Methyl-3-oxo-2-phenylcyclopentyl 2-nitro-
benzoate (cis-2d). Colorless oil; IR (KBr) 1738, 1732,
1
1538, 1352, 1288, 1129, 1075 cm21; H NMR (CDCl3) d
1.56 (s, 3H), 2.37±2.68 (m, 4H), 5.74 (dd, 1H, Jˆ4.3,
2.1 Hz), 6.77 (dd, 1H, Jˆ7.6, 1.8 Hz), 7.23±7.37 (m, 5H),
7.45±7.56 (m, 2H), 7.87 (d, 1H, Jˆ7.9 Hz); 13C NMR
(CDCl3) d 22.8, 25.2, 35.7, 57.1, 81.9, 123.8, 126.9,
127.9, 128.1, 129.2, 131.4, 132.9, 138.5, 164.2, 217.5;
HRMS (FAB) Calcd for C19H18NO5 (M11H): 340.1185.
Found: 340.1204.
4.6.15. trans-2-Acetyl-2-[4-(methyloxy)phenyl]cyclopentyl
4-nitrobenzoate (11). Colorless oil; IR (KBr) 1728, 1722,
1531, 1516, 1277, 1255, 1121, 1105 cm21 1H NMR
;
(CDCl3) d 1.65±2.05 (m, 3H), 1.99 (s, 3H), 2.35±2.54 (m,
3H), 3.74 (s, 3H), 6.19 (d, 1H, Jˆ4.9 Hz), 6.84 (d, 2H, Jˆ
8.3 Hz), 7.22 (d, 2H, Jˆ8.3 Hz), 7.71 (d, 2H, Jˆ9.2 Hz),
8.12 (d, 2H, Jˆ9.2 Hz); 13C NMR (CDCl3) d 21.3, 24.9,
31.3, 31.5, 55.1, 68.7, 79.6, 114.0, 123.2, 128.5, 129.2,
130.2, 135.8, 150.1, 158.8, 163.6, 207.6; HRMS (FAB)
Calcd for C21H22NO6 (M11H): 384.1448. Found:
384.1450.
4.6.12. cis-2-Methyl-3-oxo-2-phenylcyclopentyl 2-methyl-
6-nitrobenzoate (cis-2e). Colorless needles; mp 146±
1498C (hexane±AcOEt); IR (KBr) 1740, 1725, 1545,
1
1285, 1273, 1116 cm21; H NMR (CDCl3) d 1.55 (s, 3H),
1.63 (s, 3H), 2.46±2.62 (m, 4H), 5.71 (dd, 1H, Jˆ2.9,
1.8 Hz), 7.19±7.41 (m, 7H), 7.91 (dd, 1H, Jˆ7.3, 2.2 Hz);
13C NMR (CDCl3) d 18.1, 23.0, 24.7, 35.4, 55.6, 82.4,
121.6, 127.0, 127.9, 128.1, 128.9, 129.7, 135.9, 137.7,
138.6, 145.8, 165.2, 217.1; Anal. Calcd for C20H19NO5: C,
67.98; H, 5.42; N, 3.96. Found: C, 67.88; H, 5.50; N, 3.98.
4.6.16. (3-Methyl-2-oxo-3-phenylbutyl 4-nitrobenzoate
(13). Colorless needles; IR (KBr) 1738, 1716, 1539, 1279,
1128, 1105 cm21; 1H NMR (CDCl3) d 1.61 (s, 6H), 4.85 (s,
2H), 7.32±7.44 (m, 5H), 8.20 (d, 2H, Jˆ9.0 Hz), 8.28 (d,
2H, Jˆ9.0 Hz); 13C NMR (CDCl3) d 25.3, 50.6, 65.9, 123.5,
126.2, 127.5, 129.1, 131.0, 134.8, 142.5, 150.7, 164.0,
205.0; Anal. Calcd for C18H17NO5: C, 66.05; H, 5.23; N,
4.28. Found: C, 66.17; H, 5.27; N, 4.31.
Reactions in Scheme 3
4.6.13. trans-2-Acetyl-2-phenylcyclopentyl 4-nitrobenzo-
Reactions in Scheme 5
Entry
Substrate
Lewis acid
CH2Cl2 (mL)
Product yield
1
2
12 36.2 mg (0.111 mmol)
14 75.1 mg (0.204 mmol)
BF3´Et2O 15 mL (0.122 mmol)
BF3´Et2O 25 mL (0.203 mmol)
1.1
2.0
13 36.1 mg (quant)
15 69.4 mg (92%)

824
Y. Kita et al. / Tetrahedron 57 (2001) 815±825
4.6.17. 2-Oxo-2-(1-phenylcyclohexyl)ethyl 4-nitrobenzo-
ate (15). Colorless needles IR (KBr) 1738, 1723, 1532,
(c 0.47, CHCl3); HPLC analysis: 90% ee. (CHIRALCEL
OD; hexane/iPrOHˆ98/2; ¯ow rate, 1.0 mL/min).
1275 cm21 1H NMR (CDCl3) d 1.25±1.65 (m, 6H),
;
4.6.21. (1)-(1S,2R)-2-Methyl-2-[4-(methyloxy)phenyl]-
3-oxocyclopentyl 4-nitrobenzoate ((1)-9). (1)-9
(123 mg, 93%) was obtained from (1)-8 (131.5 mg,
0.355 mmol), BF3´Et2O (4 mL, 0.032 mmol), CH2Cl2
1.92±2.00 (m, 2H), 2.37±2.42 (m, 2H), 4.85 (s, 2H),
7.28±7.44 (m, 5H), 8.19 (d, 2H, Jˆ9.0 Hz), 8.27 (d, 2H,
Jˆ9.0 Hz); 13C NMR (CDCl3) d 22.8, 25.7, 33.5, 54.7, 66.1,
123.5, 126.6, 127.7, 129.1, 131.0, 134.9, 141.3, 150.6,
164.1, 203.9; Anal. Calcd for C21H21NO5: C, 68.65; H,
5.76; N, 3.81. Found: C, 68.83; H, 5.77; N, 3.81.
20
(3.6 mL). Yellowish crystals; [a]D ˆ172.6 (c 2.53,
CHCl3); HPLC analysis: 90% ee. (CHIRALCEL OD;
hexane/iPrOHˆ97/3; ¯ow rate, 1.0 mL/min).
Reactions in Scheme 6
4.6.18. (1R)-3-Methyl-2-[4-(methyloxy)phenyl]cyclopent-
2-en-1-ol (17). BH3´Me2S (2 M in THF, 400 mL,
0.80 mmol) was added dropwise to a solution of (S)-5,5-
diphenyl-2-methyl-3,4-propan-1,3,2-oxazaborodine (167
mg, 0.602 mmol) in THF (7.0 mL) at 08C under N2. After
being stirred for 30min, a solution of 3-methyl-2-phenyl-2-
cyclopentan-1-one (100 mg, 0.502 mmol) in THF (8 mL)
was added slowly to the resulting mixture. After being stir-
red for 30 min, MeOH was added to the mixture. The
solvent was removed in vacuo. The residue was puri®ed
by SiO2 column chromatography using hexane±AcOEt
(3/1) as the eluent to give 17 (103 mg, quant.). Colorless
References
1. For reviews on the Lewis acid-mediated rearrangement of
epoxides, see: (a) Parker R. E.; Isaacs, N. S. Chem. Rev.
1959, 59, 737±799. (b) Rickborn, B. In Comprehensive
Organic Synthesis, Carbon±Carbon s-Bond Formation,
Pattenden, G., Ed., Pergamon: Oxford, 1991; Vol. 3, pp
733±775 (Chapter 3.3).
2. (a) Maruoka, K.; Hasegawa, M.; Yamamoto, H.; Suzuki, K.;
Shimazaki, M.; Tsuchihashi, G. J. Am. Chem. Soc. 1986, 108,
3827±3382. Suzuki, K.; Miyazawa, M.; Tsuchihashi, G.
Tetrahedron Lett. 1987, 28, 3515±3518. Shimazaki, M.;
Hara, H.; Suzuki, K.; Tsuchihashi, G. Tetrahedron Lett.
1987, 28, 5891±5894. (b) Ranu, B. C.; Jana, V. J. Org.
Chem. 1998, 63, 8212±8216. (c) Jung, M. E.; D'Amico, D. C.
J. Am. Chem. Soc. 1995, 117, 7379±7388. (d) Muchowski, J.
M.; Naef, R.; Maddox, M. L. Tetrahedron Lett. 1985, 26,
5375±5378. (e) Bach, R. D.; Klix, R. C. J. Org. Chem.
1985, 50, 5438±5440. Bach, R. D.; Tubergen, M. W.;
Klix, R. C. Tetrahedron Lett. 1986, 27, 3565±3568.
Obuchi, K.; Hayashibe, S.; Asaoka, M.; Takei, H. Bull.
Chem. Soc. Japan. 1992, 65, 3206±3208. Okada, K.;
Katsura, T.; Tanino, H.; Kakoi, H.; Inoue, S. Chem. Lett.
1994, 65, 157±160.
20
oil; [a]D ˆ175.9 (c 1.05, CHCl3); IR (KBr) 3400±3200,
1
1512, 1248 cm21; H NMR (CDCl3) d 1.75±1.80 (m, 1H),
1.83 (s, 3H), 2.28±2.37 (m, 2H), 2.60±2.68 (m, 1H), 3.82 (s,
3H), 5.11 (brs, 1H), 6.91 (d, 2H, Jˆ8.7 Hz), 7.30 (d, 2H,
Jˆ8.7 Hz); HPLC analysis: 90% ee. (CHIRALCEL OD;
hexane/iPrOHˆ95/5; ¯ow rate, 1.0 mL/min).
4.6.19. (1R,2R,5S)-5-Methyl-1-[4-(methyloxy)phenyl]-6-
oxabicyclo[3.1.0]hexane-2-ol (18). A solution of tert-
BuOOH (dried over MgSO4 before use, 68%, 440 mg,
3.32 mmol) in benzene (4 mL) was added dropwise to a
solution of 17 (114 mg, 0.558 mmol) and cat. amount of
VO(acac)2 in benzene (4 mL) at rt under N2. After being
stirred for 1.5 h at rt, sat. aq. Na2S2O3 was added to the
mixture. The resulting solution was extracted with AcOEt.
Organic layer was washed with water and brine, dried
over Na2SO4, and evaporated in vacuo. The residue was
puri®ed by SiO2 column chromatography using hexane±
AcOEt (1/1) as the eluent to give 18 (107 mg, 87%).
3. (a) Fujioka, H.; Kitagaki, S.; Imai, R.; Kondo, M.;
Okamoto, S.; Yoshida, Y.; Akai, S.; Kita, Y. Tetrahedron
Lett. 1995, 36, 3219±3222. (b) Kita, Y.; Kitagaki, S.;
Yoshida, Y.; Mihara, S.; Fang, D.-F.; Fujioka, H. Tetrahedron
Lett. 1997, 38, 1061±1064. (c) Kita, Y.; Kitagaki, S.;
Yoshida, Y.; Mihara, S.; Fang, D.-F.; Kondo, M.;
Okamoto, S.; Imai, R.; Akai, S.; Fujioka, H. J. Org. Chem.
1997, 62, 4991±4997. (d) Kita, Y.; Yoshida, Y.; Kitagaki, S.;
Mihara, S.; Fang, D.-F.; Furukawa, A.; Higuchi, K.;
Fujioka, H. Tetrahedron 1999, 55, 4979±4998.
20
Colorless crystals; [a]D ˆ254.2 (c 1.01, CHCl3); 1H
NMR (CDCl3) d 1.18 (s, 3H), 1.41±1.51 (m, 1H),
1.67±1.79 (m, 1H), 2.03±2.15 (m, 2H), 3.82 (s, 3H), 4.65
(q, 1H, Jˆ8.2 Hz), 6.93 (d, 2H, Jˆ9.0 Hz), 7.33 (d, 2H,
Jˆ9.0 Hz).
4. (a) Kita, Y.; Kitagaki, S.; Imai, R.; Okamoto, S.; Mihara, S.;
Yoshida, Y.; Akai, S.; Fujioka, H. Tetrahedron Lett. 1996, 37,
1817±1820. (b) Kita, Y.; Higuchi, K.; Yoshida, Y.; Iio, K.;
Kitagaki, S.; Akai, S.; Fujioka, H. Angew. Chem., Int. Ed.
Engl. 1999, 38, 683±686.
4.6.20. (1)-(1R,2S,5S)-5-Methyl-1-[4-(methyloxy)phenyl]-
6-oxabicyclo[3.1.0]hex-2-yl 4-nitrobenzoate ((1)-8). p-
Nitrobenzoic acid (162 mg, 0.969 mmol) and Ph3P
(255 mg, 0.972 mmol) were added to a solution of 18
(107 mg, 0.486 mmol) in toluene (5 mL) at 08C under N2.
Diethyl azadicarboxylate (toluene solu., 420 mL,
0.965 mmol) was added dropwise to the resulting solution.
The mixture was stirred for 0.5 h, then treated with sat. aq.
NaHCO3. The resulting solution was extracted with AcOEt.
The organic layer was washed with brine, dried over
Na2SO4, and evaporated in vacuo. The residue was puri®ed
by SiO2 column chromatography using hexane±AcOEt
(6/1) as the eluent to give trans-epoxy p-nitrobenzoate
5. Kita, Y.; Furukawa, A.; Futamura, J.; Higuchi, K.; Ueda, K.;
Fujioka, H. Tetrahedron Lett. 2000, 41, 2133±2136.
6. Racemic epoxy acylates were used in these experiments.
7. The con®gurations of the quaternary carbon centers of new
compounds from 5-membered epoxy acylates were tentatively
determined by supposing the stereoselective rearrangement of
the starting epoxy acylates.
8. After ®nishing our work (Ref. 5), the result of Neef et al. has
appeared in preliminary form. They examined the rearrange-
ment of the epoxy benzyl ether with the C3-aryl substituent
and discussed the lifetime of the benzylic cation. However,
their study is only on the epoxides from carvone and very
20
(1)-8 (162 mg, 90%). Colorless needles; [a]D ˆ12195

Y. Kita et al. / Tetrahedron 57 (2001) 815±825
825
limited. Neef, G.; Baesler, S.; Depke, G.; Vierhufe, H.
Tetrahedron Lett. 1999, 40, 7969±7973.
11. Sharpless, K. B.; Michaelson, R. C. J. Am. Chem. Soc. 1973,
95, 6136±6137.
9. Treatment of trans-1c with a catalytic amount of BF3´Et2O
(0.1 equiv.) required longer reaction time (5 h) and the yield
decreased (58% yield).
12. Mitsunobu, O.; Kimura, J.; Iiizumi, K.; Yanagida, N. Bull.
Chem. Soc. Jpn. 1976, 49, 510±513.
13. Grob, C. A.; Wenk, P. Tetrahedron Lett. 1976, 4195±4198.
14. Sato, T.; Hayase, K. Bull. Chem. Soc. Jpn. 1991, 64, 3384±
3389.
10. Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh,
V. K. J. Am. Chem. Soc. 1987, 109, 7925±7926. Absolute
con®guration of 17 was deduced by referring to the literature.