Intramolecular Friedel-Crafts type reaction of vinyloxiranes linked to an ester group

Article abstract of DOI:10.1016/j.tet.2009.09.037

The 7-endo Friedel-Crafts cyclization of arylpropyl vinyloxiranes was found to proceed regio- and stereoselectively to afford polyfunctional seven-membered carbocycles in excellent yields.

Full text of DOI:10.1016/j.tet.2009.09.037

Tetrahedron 65 (2009) 9884–9896
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Intramolecular Friedel–Crafts type reaction of vinyloxiranes linked
to an ester group
,
b
b
b
b
Shinji Nagumo a , Toshie Miura , Megumi Mizukami , Irie Miyoshi , Masanori Imai ,
*
Norio Kawahara b, Hiroyuki Akita c
a Department of Applied Chemistry, Kogakuin University, Nakano 2665-1, Hachioji, Tokyo 192-0015, Japan
b Hokkaido Pharmaceutical University, School of Pharmacy, Katsuraoka 7-1, Otaru 047-0264, Japan
c School of Pharmaceutical Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 May 2009
Received in revised form 7 September 2009
Accepted 8 September 2009
Available online 12 September 2009
The 7-endo Friedel–Crafts cyclization of arylpropyl vinyloxiranes was found to proceed regio- and ster-
eoselectively to afford polyfunctional seven-membered carbocycles in excellent yields.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
O
OH
SnCl4
Ring opening reaction of epoxide with various nucleophiles
continues to be used for the synthesis of many natural products.
Epoxide can react in either of two directions distinct from other
functional groups. Consequently, it is important to control the re-
action site of the substitution. The regioselectivity of epoxides is
mainly determined by a steric factor, stereoelectronic requirement,
and/or the fractional positive charge of the carbon center in the
transition state. An intramolecular reaction of epoxides is also
regulated by ring size of products in addition to the above factors.
Taylor et al. investigated an intramolecular Friedel–Crafts (FC) re-
action of arylalkyl epoxides mediated by various acids.1–3 Their
study indicated that six-membered FC cyclization was favored over
five- and seven-membered FC cyclization. Furthermore, 6-exo cy-
clization seemed to be more facile than 6-endo cyclization. Sec-
ondary epoxide 1 undertook 6-endo cyclization to give alcohol 2 in
moderate yield (Scheme 1). On the other hand, an excellent yield
was obtained from the 6-exo cyclization of 3. Cyclization of epoxide
5 having a substituent at the C30-position resulted in the formation
of para- and ortho-substitution products 6 and 7 with a ratio of ca.
1.6:1. Homologous epoxide 8 underwent seven-membered cycli-
zation to form 9 in moderate yield. It is of good synthetic potential
because there are many natural and medicinal compounds con-
taining a seven-membered carbocycle with a polyfunctional group.
However, seven-membered cylization of simple epoxide is limited
to exo mode. Our attention has thus been directed to the de-
velopment of a facile method of 7-endo-selective FC cyclization.
57%
1
2
CH2OH
O
SnCl4
91%
3
4
CH2OH
OMe CH2OH
O
SnCl4
95%
+
MeO3'
MeO
1'
6 : 7 = ca. 1.6 : 1
5
6
7
OH
OH
O
SnCl4
+
65%
9 : 10 = ca. 3 : 1
8
9
10
Scheme 1.
Linkage of a functional group exerting a resonance effect is known
to be useful for controlling the reaction site of epoxide.4,5 Akita et al.
reported intermolecular FC reaction of g,d-epoxy-a,b-unsaturated
ester 11 with arene derivatives upon treatment with BF3$Et2O
(Scheme 2).6 In their research, arene derivatives selectively
attacked the epoxide carbon linked to the vinyl group. Such
* Corresponding author.
E-mail address: bt13071@ns.kogakuin.ac.jp (S. Nagumo).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.037

S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
9885
a resonance effect would make 7-endo FC cyclization of epoxides
2. Results
more advantageous than 6-exo FC cyclization. We report here 7-
endo-selective FC cyclization of arylalkyl vinyloxiranes.7
2.1. Synthesis of vinyloxiranes
OMe
OMe
Vinyloxiranes 16a–d, 20b, and 24b–f were synthesized from the
corresponding aldehydes 14a–f (Scheme 3). Horner–Emmons re-
action of 14a with (EtO)2POCH2CH]CHCOOMe gave ester 15,
which was converted into 16a by epoxidation with MCPBA. Wittig
reaction of 14b–f with Ph3P]CHCOOMe or Ph3P]CMeCOOEt
produced conjugate esters 17b–d or 21b–f, respectively. Reduction
of 17b–d and 21b–f with DIBAL-H afforded the corresponding
allylalcohols 18b–d and 22b–f, which were subjected to epoxida-
tion with MCPBA to give epoxyalcohols 19b–d and 23b–f. Finally,
.
BF3 Et2O
CH2Cl2
-78 ºC
OMe
OMe
+
COOMe
COOMe
O
77%
OH
11
12
13
Scheme 2.
MeOOC
MeOOC
O
OHC
a
b
O
e, f
16a
14a
15
MeOOC
MeO
20b
HO
HO
O
b
d
R2
R2
R1
MeOOC
R2
R1
R2
R1
e, c
O
R1
c
17b-d
18b-d
19b-d
R2
R1
OHC
16b-d
COOMe
O
g
HO
HO
COOEt
14b (R1=OMe, R2=H)
14c (R1=R2=OMe)
14d (R1=H, R2=OMe)
14e (R1=H, R2=Me)
O
b
e, c
d
R2
R1
R2
R2
R1
R2
R1
R1
21b-e
22b-e
23b-e
24b-e
COOMe
O
HO
HO
COOEt
O
e, c
d
b
g
CHO
21f
14f
22f
23f
24f
COOMe
COOMe
O
a
b
CHO
COOMe
O
27a
25a
26
HO
HO
COOMe
O
e, c
d
b
R2
R1
R2
R1
R2
R1
R2
R1
c
28b-d
29b-d
30b-d
27b-d
R2
CHO
COOMe
g
R1
HO
HO
EtOOC
25b (R1=OMe, R2=H)
25c (R1=R2=OMe)
25d (R1=H, R2=OMe)
e, c
d
b
O
O
MeO
MeO
MeO
MeO
31b
32b
33b
34b
Scheme 3. (a) (EtO)2POCH2CH]CHCOOMe, LDA, THF; (b) MCPBA, CH2Cl2; (c) Ph3P]CHCOOMe, THF; (d) DIBAL-H, toluene, ꢀ78 ꢁC; (e) Dess–Martin periodinane, CH2Cl2; (f)
Ph3PCH3Br, KHMDS, THF, ꢀ20 ꢁC, (g) Ph3P]CMeCOOEt, THF.

9886
S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
.
19b–d and 23b–f were converted into 20b, 16b–d and 24b–f by the
BF3 Et2O
O
OH
sequence of Dess–Martin oxidation and Wittig reaction. Conversion
of 25a–d into 27a–d and 34b was also carried out in a manner
similar to that described above.
CH2Cl2
MeO
MeO
-30 ºC
20b
35b (85%)
MeOOC
MeOOC
2.2. 7-endo-Selective cyclization of vinyloxiranes
.
BF3 Et2O
O
OH
CH2Cl2
As the start of this research, we performed FC cyclization of
vinyloxirane 20b, in which 7-endo versus 6-exo cyclization can
competitively occur (Scheme 4). As was expected, the regiochem-
ical outcome was guided by the vinyl group and 7-endo cyclization
was favored over 6-exo cyclization. Treatment of vinyloxirane 20b
with 0.5 equiv of BF3$Et2O in CH2Cl2 at ꢀ30 ꢁC afforded seven-
membered carbocycle 35b in 85% yield as an epimeric mixture. In
contrast to the above reaction, selective 7-endo cyclization of
vinyloxirane 16a with an ester group proceeded stereoselectively to
afford only trans isomer 36a, but its yield was very low. Sub-
stitution of a simple epoxide is known to proceed with inversion of
configuration. Such a special stereochemistry of epoxide can be
ascribed to the neighboring effect of epoxide-oxygen on the re-
action center in an intermediate or a transition state.1 However, the
cyclization of 20b can be considered to proceed via an almost open
cation that is not subjected to the neighboring effect. The SN1-like
mechanism depends on the strong resonance effect by vinyl
groups. Ester group in 16a should moderately decrease the reso-
nance effect of the vinyl group toward epoxide. Activation by
methoxy group made the 7-endo cyclization more facile. Vinyl-
oxiranes 16b and 16c underwent facile 7-endo cyclizations at only
60-positions to produce 36b and 36c, respectively, in excellent yield.
On the other hand, vinyloxirane 16d having only a methoxy group
at the 40-position was surprisingly transformed into the spiro-cyclic
-30 ºC
16a
MeOOC
36a (25%)
MeOOC
.
BF3 Et2O
CH2Cl2
O
OH
36b (97%)
OH
4'
3'
6'
MeO
MeO
-30 ºC
16b
MeOOC
MeOOC
.
BF3 Et2O
O
O
4'
MeO
MeO
6'
CH2Cl2
3'
MeO
MeO
-30 ºC
16c
36c (95%)
COOMe
O
MeOOC
COOMe
.
BF3 Et2O
O
O
4'
MeO
OH
CH2Cl2
+
-30 ºC
37d (70%)
38d (9%)
16d
Scheme 4.
MeOOC
MeO
MeOOC
MeOOC
.
BF3 Et2O
CH2Cl2
O
OH
OH
+
3'
MeO
MeO
-30 ºC
39b (44%)
40b (4%)
24b
COOMe
COOMe
MeOOC
OH
O
F
CHO
+
+
MeO
MeO
MeO
41b (36%)
42b (4%)
43b (7%)
MeOOC
MeOOC
.
BF3 Et2O
O
OH
4'
MeO
MeO
MeO
CH2Cl2
3'
MeO
-30 ºC
24c
39c (87%)
COOMe
COOMe
MeOOC
MeOOC
.
BF3 Et2O
O
R
OH
R
R
R
4'
CH2Cl2
O
F
CHO
+
+
-30 ºC
41d (9%)
41e (48%)
42d (6%)
42e (23%)
43d (73%)
43e (9%)
24d (R = OMe)
24e (R = Me)
COOMe
COOMe
MeOOC
MeOOC
.
BF3 Et2O
O
OH
O
CH2Cl2
F
CHO
+
+
-30 ºC
41f (54%)
42f (22%)
43f (7%)
24f
Scheme 5.

S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
9887
product 37d and its intramolecular 1,4-adduct 38d under acidic
conditions.
simple epoxide 5 proceeded at both C20 and C60-positions. We
considered that it would be instructive to conduct 6-endo FC cy-
clization of 4,5-epoxy-7-aryl-2-heptenoates. Treatment of vinyl-
oxirane 27a with 0.5 equiv of BF3$Et2O in CH2Cl2 at ꢀ30 ꢁC resulted
in 6-endo cyclization yielding tetrahydro-2-naphthol 44a in mod-
erate yield (Scheme 6). The 6-endo cyclization of vinyloxirane 27b
proceeded at both the 20 and 60-positions to afford 44b and 45b in
combined yield of 100% and a ratio of ca. 2:1. Also, cyclization of 27c
proceeded smoothly at both the 20 and 60-positions to produce 44c
and 45c with a ratio of ca. 5:1. Interestingly, 27d possessing only
a methoxy group at the C40-position afforded fused ring compound
44d in contrast to the result for 16d. When trisubstituted epoxide
34b with a 30-methoxy group was treated with BF3$Et2O, 46b and
47b were obtained in combined yield of 90% and a ratio of ca. 2:3.
We next turned our attention to explore the behavior of tri-
substituted epoxides linked to conjugate ester under acidic condi-
tions (Scheme 5). It is well-known that trisubstituted epoxides
undergo facile 1,2-alkyl or 1,2-hydride migration upon treatment
with Lewis acids.8 Treatment of vinyloxirane 24b with BF3$Et2O
afforded two regioisomers 39b and 40b in 44% and 4% yields along
with fluorohydrin 41b (36%),9 aldehyde 42b (4%), and ketone 43b
(7%).10 The unsatisfactory result could be modified by introduction of
a further methoxy group at the C40-position. Upon treatment with
BF3$Et2O, 24c was converted into seven-membered carbocycle 39c in
high yield. As well as cyclization of the secondary vinyloxirane,
a methoxy group at the C30-position was found to be essential for
smooth 7-endo cyclization. Treatment of 24d having a methoxygroup
at the C40-position with BF3$Et2O produced only undesired com-
pounds: fluorohydrin 41d (9%), aldehyde 42d (6%), and ketone 43d
(73%).10 It was noteworthy that the yield of ketone 43d was higher
than that of fluorohydrin 41d in contrast to the result for 24b. In order
to clarify the reason for the difference, we performed BF3$Et2O-me-
diated reaction of vinyloxirane 24e having a methyl group at the C40-
position and 24f without a benzene ring. Interestingly, the ratio of
fluorohydrins 41e,f, aldehydes 42e,f, and ketones 43e,f10 turned out
to be comparable to that shown by the reaction of 24b.
3. Discussion
As we expected, 7-endo cyclization of vinyloxirane was favored
over 6-exo cyclization due to resonance control by the vinyl group.
The endo-selective cyclization was also applicable to six-membered
cyclization. Several differences between 6-endo and 7-endo cycli-
zations should be considered. Vinyloxirane 27d having a methoxy
group at the C40-position undergoes FC cyclization to afford 44d in
excellent yield (Scheme 6), whereas 16d undergoes ipso-cyclization
and the subsequent demethylation of the resulting spiro-benze-
nium ion A to afford spiro-cyclic products 37d and 38d (Schemes 4
and 7). It is also noteworthy that trisubstituted epoxides 24e,f give
mainly fluorohydrins 41e,f and aldehydes 42e,f, whereas 24d
having a methoxy group at the C40-position gives ketone 43d as
2.3. 6-endo Cyclization of vinyloxiranes
It should be noted that vinyloxiranes 16b underwent cyclization
at the C60-position specifically, since six-membered cyclization of
COOMe
O
COOMe
.
BF3 Et2O
OH
CH2Cl2
-30 ºC
27a
44a (65%)
COOMe
COOMe
COOMe
.
MeO
BF3 Et2O
CH2Cl2
O
OH
OH
6'
+
+
3'
MeO
MeO
-30 ºC
2'
27b
44b (65%)
45b (35%)
COOMe
O
COOMe
COOMe
.
MeO
BF3 Et2O
4'
3'
MeO
MeO
MeO
MeO
OH
MeO
OH
CH2Cl2
-30 ºC
27c
44c (84%)
45c (16%)
COOMe
COOMe
.
BF3 Et2O
O
4'
MeO
MeO
OH
CH2Cl2
-30 ºC
27d
44d (98%)
COOMe
COOMe
COOMe
OH
.
MeO
BF3 Et2O
O
OH
CH2Cl2
-30 ºC
+
3'
MeO
MeO
34b
46b (34%)
47b (56%)
Scheme 6.

9888
S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
COOMe
O
COOMe
COOMe
OH
Me
O
O
MeO
MeO
OH
38d
37d
16d
A
COOMe
O
COOMe
MeO
OH
H
43d
24d
B
Scheme 7.
a major product (Scheme 5). Selective formation of 43d might be
ascribed to the temporary formation of spiro-benzenium ion B
(Scheme 7) and its 1,2-hydride migration concomitant with
aromatization.
afford 6 and 7 with a ratio of ca. 1.6:1. Interestingly, the ratio is close
to that of 44b and 45b, which were obtained in FC cyclization of
vinyloxirane 27b. The similarity of their ratios suggests that 6-endo
cyclization of vinyloxirane 27b also prefers direct routes (Scheme 8,
paths a and b). Of course, also 7-endo cyclization of 16b should be
considered to proceed via a direct route (Scheme 8, path c). How-
ever, strange to say for this mechanistic insight is that the direct
cyclization at the C20-position does not occur in contrast to the 6-
endo cyclization. We thus think that it is difficult to rule out the
following possibility. As well as the reaction of 16d and 24d (Scheme
7), 16b might undergo ipso-cyclization to generate a spiro-benze-
nium ion (Scheme 8, path d). In contrast with A and B (Scheme 7),
the cation C contains a methoxy group at the C30-position. Electron-
releasing by the substituent may induce the subsequent skeletal
rearrangement to afford the ion D, which is converted into seven-
membered carbocycle 36b. If so, the complete regioselectivity on
the benzene ring for the cyclization of 16b would be ascribed to
selective migration of the C4–C10 bond to the C4–C60 bond. Al-
though the reason for this remains unclear, a similar selectivity of
migration was reported by Pigge et al. in a skeletal rearrangement of
azaspiro cyclohexadienyl ruthenium complex 50 concomitant with
a demetalation (Scheme 9).11 On the other hand, the demetalation of
48 underwent demethylation concomitantly to produce the spiro-
cyclic compound 49 as well as BF3$Et2O-promoted reaction of 16d.
Interestingly, positional selectivity on the benzene ring shows
a remarkable difference between 6-endo cyclization and 7-endo
cyclization. Thus, 6-endo cylizations of 27b,c provide C60-cyclized
products 44b,c and C20-cyclized products 45b,c, whereas 7-endo
cyclizations of 16b,c proceed regioselectively to afford only C60-
cyclized products 36b,c in excellent yield (Schemes 4 and 6). Gen-
erally, two pathways are possible for intramolecular FC cyclization
of various electrophilic functional groups: direct cyclization at the
position ortho to the alkyl side chain and a sequential mechanismvia
a spiro-benzenium ion. A kinetic study by Taylor et al. revealed that
6-exo cyclization of simple epoxide 3 and its derivatives occurred
almost completely via a direct route (Scheme 1).1–3 Among of the
derivatives, epoxide 5 possessing a methoxy group at the C30-po-
sition underwent cyclization at both the C20 and C60-positions to
COOMe
H
OH
path a
path b
COOMe
O
44b
MeO
a
6'
COOMe
OH
O
O
3'
MeO
2'
MeO
MeO
O
MeO
b
CuCl2
99%
H
NMe
NMe
45b
27b
MeO
RuCp
48
49
MeOOC
MeOOC
O
OH
c
H
path c
O
MeO
d
36b
MeO
CpRu
CuCl2
MeO
MeO
O
NMe
16b
55%
NMe
MeO
path d
OMe
MeOOC
H
COOMe
50
51
6'
1'
Scheme 9.
OH
4
OH
5
3'
MeO
4. Conclusion
8
MeO
C
D
In conclusion, we have developed a facile 7-endo-selective FC
cyclization of vinyloxiranes mediated by BF3$Et2O. Each cyclization
Scheme 8.

S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
9889
exhibited excellent stereoselectivity. This novel method was also
applicable to a six-membered cyclization. The positional selectivity
on the benzene ring showed a remarkable difference between 6-
endo cyclization and 7-endo cyclization. Thus, 6-endo cyclization of
27b,c provide two regiochemical isomers, whereas 7-endo cycli-
zations of 16b,c proceed regioselectively. Seven-membered prod-
ucts obtained from 7-endo-selective FC cyclization of vinyloxiranes
should be useful for synthetic applications because they have
polyfunctional groups.
5.3.1. Methyl (4R
72% (colorless oil); IR (neat) 1729, 1661 cmꢀ1
CDCl3)
*
,5R
*
,2E)-4,5-epoxy-8-phenyl-2-octenoate (16a). Yield
;
1H NMR (270 MHz,
d
7.38–7.13 (5H, m), 6.67 (1H, dd, J¼15.5, 7.2 Hz), 6.11 (1H, d,
J¼15.5 Hz), 3.74 (3H, s), 3.20 (1H, d, J¼7.2, 2.0 Hz), 2.90 (1H, td, J¼5.6,
2.0 Hz), 2.67 (2H, t, J¼7.6 Hz), 1.89–1.56 (4H, m); 13C NMR (68 MHz,
CDCl3)
d 166.00, 144.91, 141.56, 128.30 (4C), 125.86, 123.03, 61.17,
56.07, 51.61, 35.34, 31.25, 27.38; EIMS m/z 246 (Mþ), 228, 214, 187,
169, 149, 131, 117, 104, 92; HRMS (EI) m/z 246.1245 (calcd for
C15H18O3: 246.1255).
5. Experimental
5.3.2. Methyl (4R
Yield 72% (colorless oil); IR (neat) 1725, 1661, 1605 cmꢀ1
(270 MHz, CDCl3)
*
,5R
*
,2E)-4,5-epoxy-7-phenyl-2-heptenoate (27a).
;
1H NMR
5.1. General methods
d
7.33–7.14 (5H, m), 6.63 (1H, dd, J¼15.8, 6.9 Hz),
6.05 (1H, dd, J¼15.8, 0.7 Hz), 3.74 (3H, s), 3.13 (1H, dd, J¼6.9,
The melting points were determined on a Yanako micro melting
point apparatus and were uncorrected. IR spectra were recorded on
a JASCO IRA-102 or a JASCO FT-IR-7000 spectrometer. NMR spectra
were recorded on a JEOL GX-270 and a JEOL AL-400 spectrometer
using tetramethylsilane as an internal standard. Chemical shifts are
given in parts per million. The following abbreviations are used:
s, singlet; d, doublet; t, triplet; q, quartet; br, broad. MS spectra were
measured on a Hitachi M-2000 instrument. Elemental analyses were
performed using a Perkin Elmer 2400II. Column chromatography was
carried out on Merck’s Silica gel 60 (70–230 mesh ASTM).
1.8 Hz), 2.91 (1H, td, J¼5.6, 1.8 Hz), 2.88–2.67 (2H, m), 2.04–1.82
(2H, m); 13C NMR (68 MHz, CDCl3)
d 165.98, 144.76, 140.68, 128.45
(2C), 128.29 (2C), 126.12, 123.08, 60.61, 56.37, 51.61, 33.62, 31.94;
EIMS m/z 232 (Mþ), 201, 173, 141, 128, 117, 105; HRMS (EI) m/z
232.1078 (calcd for C14H16O3: 232.1099).
5.4. Wittig reaction of arylalkanal with Ph3P]CHCOOMe
To
a solution of aldehyde 14 or 25 in THF was added
Ph3P]CHCOOMe or Ph3P]CMeCOOEt (1.5 equiv) at room tem-
perature under an argon atmosphere. After being stirred at room
temperature for 12–15 h, a large amount of hexane was added to
the reaction mixture. The precipitate was removed by filtration. The
filtrate was concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel eluted with hex-
ane/AcOEt (20–10/1) to give conjugate ester 17, 21, 28 or 31.
5.2. Horner–Emmons reaction of 14a and 25a
To a solution of (EtO)2POCH2CH]CHCOOMe (1.1 equiv) in THF
was added dropwise LDA (1.1 equiv) in THF at ꢀ78 ꢁC under an ar-
gon atmosphere. After being stirred for 10 min, a solution of 14a or
25a in THF was added to the mixture. After 1 h, the reaction mixture
was quenched with saturated aqueous NH4Cl and extracted with
Et2O. The extract was washed with saturated aqueous NaCl, dried
over MgSO4, and concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel eluted with
hexane/AcOEt (30/1) to give diene conjugate ester 15 or 26.
5.4.1. Methyl (2E)-6-(3-methoxyphenyl)-2-hexenoate (17b). Yield
89% (colorless oil); IR (neat) 1723, 1659 cmꢀ1 1H NMR (270 MHz,
;
CDCl3)
d
7.20 (1H, t, J¼7.8 Hz), 6.98 (1H, dt, J¼15.9, 7.3 Hz), 6.80–
6.70 (3H, m), 5.84 (1H, dt, J¼15.9, 1.5 Hz), 3.79 (3H, s), 3.73 (3H, s),
2.62 (2H, t, J¼7.3 Hz), 2.33 (2H, qd, J¼7.3, 1.5 Hz), 1.79 (2H, quintet,
J¼7.3 Hz); 13C NMR (68 MHz, CDCl3)
d 167.07,159.68,149.06,143.30,
5.2.1. Methyl(2E,4E)-8-phenylocta-2,4-dienoate (15). Yield 59% (color-
129.33, 121.26, 120.82, 114.22, 111.16, 55.13, 51.39, 35.23, 31.58,
29.47; EIMS m/z 234 (Mþ), 203, 174, 161; HRMS (EI) m/z 234.1245
(calcd for C14H18O3: 234.1255).
less oil); IR (neat) 1717, 1644 cmꢀ1; 1H NMR (270 MHz, CDCl3)
d 7.35–
7.15 (6H, m), 6.25–6.05 (2H, m), 5.79 (1H, d, J¼15.5 Hz), 3.74 (3H, s),
2.63 (2H, t, J¼7.6 Hz), 2.21 (2H, q, J¼7.6 Hz), 1.76 (2H, quintet,
J¼7.6 Hz); 13C NMR (68 MHz, CDCl3)
d
167.60, 145.12, 144.08, 141.84,
5.4.2. Methyl (2E)-6-(3,4-dimethoxyphenyl)-2-hexenoate (17c). Yield
128.67, 128.35 (2C), 128.89 (2C), 125.81, 118.88, 51.37, 35.25, 32.36,
30.26; EIMS m/z 230 (Mþ), 199, 170, 147; HRMS (EI) m/z 230.1313
(calcd for C15H18O2: 230.1306).
78% (colorless oil); IR (neat) 1723, 1659 cmꢀ1 1H NMR (270 MHz,
;
CDCl3)
d
6.99 (1H, dt, J¼15.6, 7.1 Hz), 6.80 (1H, d, J¼8.6 Hz), 6.73–6.67
(2H, m), 5.84 (1H, dt, J¼15.6, 1.6 Hz), 3.87 (3H, s), 3.86 (3H, s), 3.73
(3H, s), 2.59 (2H, t, J¼7.7 Hz), 2.25 (2H, qd, J¼7.1, 1.6 Hz), 1.77 (2H,
5.2.2. Methyl (2E,4E)-7-phenylhepta-2,4-dienoate (26). Yield 56%
(white solid); mp 48–49 ꢁC (hexane). Anal. Calcd for C14H16O2: C,
77.78; H, 7.46. Found: C, 77.98; H 7.57. IR (neat) 1715, 1647 cmꢀ1; 1H
quintet, J¼7.7 Hz); 13C NMR (68 MHz, CDCl3)
d 166.90,148.99,147.75,
147.15, 134.17, 121.12, 120.09, 111.62, 111.16, 55.77, 55.68, 51.22, 34.64,
31.44, 29.66; EIMS m/z 264 (Mþ), 233, 204, 191; HRMS (EI) m/z
264.1331 (calcd for C15H20O4: 264.1360).
NMR (270 MHz, CDCl3)
d
7.38 (1H, dd, J¼15.5,10.8 Hz), 7.18–7.02 (3H,
m), 6.98–6.90 (2H, m), 5.86–5.72 (2H, m), 5.62 (1H, dt, J¼15.5, 7.6 Hz),
3.44 (3H, s), 2.37 (2H, t, J¼7.6 Hz), 2.06 (2H, q, J¼7.6 Hz); 13C NMR
5.4.3. Methyl (2E)-6-(4-methoxyphenyl)-2-hexenoate (17d). Yield
(68 MHz, CDCl3)
d
167.44, 144.90, 143.19, 140.93, 128.76, 128.29 (2C),
96% (colorless oil); IR (neat) 1721, 1659, 1613 cmꢀ1 1H NMR
;
128.25 (2C), 125.94, 119.09, 51.27, 34.93, 34.56; EIMS m/z 216 (Mþ),
185, 175, 149; HRMS (EI) m/z 216.1140 (calcd for C14H16O2: 216.1149).
(270 MHz, CDCl3)
d
7.08 (2H, d, J¼8.6 Hz), 6.98 (1H, dt, J¼15.5,
6.9 Hz), 6.83 (2H, d, J¼8.6 Hz), 5.83 (1H, dt, J¼15.5, 1.3 Hz), 3.79 (3H,
s), 3.73 (3H, s), 2.58 (2H, t, J¼7.6 Hz), 2.22 (2H, qd, J¼7.6,1.3 Hz),1.75
5.3. Epoxidation of arylalkyldienoates
(2H, quintet, J¼7.6 Hz); 13C NMR (68 MHz, CDCl3)
d 167.09, 157.82,
149.20, 133.70, 129.27 (2C), 121.16, 113.77 (2C), 55.22, 51.38, 34.25,
31.53, 29.81; EIMS m/z 234 (Mþ), 134, 121; HRMS (EI) m/z 234.1229
(calcd for C14H18O3: 234.1255).
To a solution of 15 or 26 in CH2Cl2 was added m-chloro-
perbenzoic acid (1.5 equiv) at 0 ꢁC. The mixture was stirred at room
temperature for 1 h and then quenched with saturated aqueous
Na2S2O3 and extracted with Et2O. The extract was washed with
saturated aqueous NaCl, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by column chroma-
tography on silica gel eluted with hexane/AcOEt (10/1) to give
epoxy conjugate ester 16a or 27a.
5.4.4. Ethyl (2E)-6-(3-methoxyphenyl)-2-methyl-2-hexenoate (21b).
Yield 45% (colorless oil); IR (neat) 1711, 1653 cmꢀ1 1H NMR
;
(270 MHz, CDCl3) d 7.24–7.16 (1H, m), 6.82–6.70 (4H, m), 4.19 (2H, q,
J¼7.3 Hz), 3.80 (3H, s), 2.62 (2H, t, J¼7.3 Hz), 2.20 (2H, q, J¼7.3 Hz),
1.81 (3H, d,1.5 Hz),1.78 (2H, quintet, J¼7.3 Hz),1.29 (3H, t, J¼7.3 Hz);

9890
S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
13C NMR (68 MHz, CDCl3)
128.18, 120.84, 114.22, 111.14, 60.41, 55.14, 35.49, 30.02, 28.14, 14.29,
12.40; EIMS m/z 262 (Mþ), 216, 161; HRMS (EI) m/z 262.1547 (calcd
for C16H22O3: 262.1568).
d
168.22, 159.68, 143.52, 141.69, 129.29,
6.8 Hz), 6.83 (2H, d, J¼8.3 Hz), 5.83 (1H, d, J¼15.6 Hz), 3.79 (3H, s),
3.72 (3H, s), 2.72 (2H, t, J¼6.8 Hz), 2.49 (2H, q, J¼6.8 Hz); 13C NMR
(68 MHz, CDCl3) d 166.90, 157.91, 148.41, 132.70, 129.15 (2C), 121.31,
113.79 (2C), 55.13, 51.32, 34.06, 33.35; EIMS m/z 220 (Mþ), 151, 121,
91; HRMS (EI) m/z 220.1070 (calcd for C13H16O3: 220.1099).
5.4.5. Ethyl (2E)-6-(3,4-dimethoxyphenyl)-2-methyl-2-hexenoate (21c).
Yield 100% (colorless oil); IR (neat) 1711, 1651, 1607 cmꢀ1
;
1H NMR
5.4.12. Ethyl (2E)-5-(3-methoxyphenyl)-2-methyl-2-pentenoate (31b).
(270 MHz, CDCl3)
d
6.84–6.67 (4H, m), 4.19 (2H, q, J¼7.1 Hz), 3.87 (3H,
Yield 91% (colorless oil); IR (neat) 1711, 1653 cmꢀ1 1H NMR
;
s), 3.86 (3H, s), 2.59 (2H, t, J¼7.6 Hz), 2.20 (2H, q, J¼7.6 Hz), 1.81 (3H, d,
(270 MHz, CDCl3) d 7.24–7.16 (1H, m), 6.84–6.71 (4H, m), 4.21 (2H, q,
J¼1.2 Hz), 1.76 (2H, quintet, J¼7.6 Hz), 1.30 (3H, t, J¼7.1 Hz); 13C NMR
J¼7.3 Hz), 3.80 (3H, s), 2.73 (2H, t, J¼7.6 Hz), 2.48 (2H, q, J¼7.6 Hz),
(68 MHz, CDCl3) d 168.07, 148.73, 147.12, 141.63, 134.39, 127.99, 120.11,
1.79 (3H, d, J¼1.3 Hz),1.29 (3H, t, J¼7.3 Hz); 13C NMR (68 MHz, CDCl3)
111.64,111.14, 60.28, 55.79, 55.69, 34.90, 30.21, 27.97,14.16,12.29; EIMS
m/z 292 (Mþ), 247, 218, 191; HRMS (EI) m/z 292.1643 (calcd for
C17H24O4: 292.1673).
d 168.05,159.63,142.82,140.80,129.35,128.39,120.66,114.08,111.29,
60.36, 55.07, 34.71, 30.40, 14.22, 12.28; EIMS m/z 248 (Mþ), 202, 174;
HRMS (EI) m/z 248.1382 (calcd for C15H20O3: 248.1412).
5.4.6. Ethyl (2E)-6-(4-methoxyphenyl)-2-methyl-2-hexenoate (21d).
5.5. Reduction of arylalkenoates with DIBAL-H
Yield 100% (colorless oil); IR (neat) 1711, 1651 cmꢀ1 1H NMR
;
(270 MHz, CDCl3)
d
7.08 (2H, d, J¼8.8 Hz), 6.82 (2H, d, J¼8.8 Hz),
To a solution of 17, 21, 28 or 31 in toluene was added dropwise
diisobutylaluminium hydride (toluene solution, 2.5 equiv) at
ꢀ78 ꢁC under an argon atmosphere. The mixture was stirred at
ꢀ78 ꢁC for 0.5–1 h and then quenched with H2O. The precipitate
was removed by filtration. The filtrate was dried over MgSO4 and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel eluted with hexane/AcOEt (2/
1) to give allyl alcohol 18, 22, 29 or 32.
6.83–6.72 (1H, m), 4.19 (2H, q, J¼7.3 Hz), 3.79 (3H, s), 2.59 (2H, t,
J¼7.6 Hz), 2.18 (2H, q, J¼7.6 Hz), 1.80 (3H, d, J¼1.3 Hz), 1.74 (2H,
quintet, J¼7.6 Hz), 1.29 (3H, t, J¼7.3 Hz); 13C NMR (68 MHz, CDCl3)
d
167.82, 157.59, 141.53, 133.57, 128.99 (2C), 127.79, 113.48 (2C),
60.07, 54.81, 34.25, 30.13, 27.79,14.01,12.10; EIMS m/z 262 (Mþ),188,
160; HRMS (EI) m/z 262.1540 (calcd for C16H22O3: 262.1568).
5.4.7. Ethyl (2E)-2-methyl-6-(4-methylphenyl)-2-hexenoate (21e).
Yield 83% (colorless oil); IR (neat) 1711, 1653 cmꢀ1
;
1H NMR
5.5.1. (2E)-6-(3-Methoxyphenyl)-2-hexen-1-ol (18b). Yield 100%
(400 MHz, CDCl3)
d
7.09 (2H, d, J¼8.1 Hz), 7.06 (2H, d, J¼8.1 Hz), 6.77
(colorless oil); IR (neat) 3350, 1671 cmꢀ1 1H NMR (270 MHz,
;
(1H, t, J¼7.3 Hz), 4.19 (2H, q, J¼7.1 Hz), 2.60 (2H, t, J¼7.3 Hz), 2.32 (3H,
CDCl3)
d
7.19 (1H, dd, J¼8.9, 7.5 Hz), 6.80–6.70 (3H, m), 5.77–5.58
s), 2.19 (2H, q, J¼7.3 Hz),1.81 (3H, s),1.76 (2H, quintet, J¼7.3 Hz),1.29
(2H, m), 4.09 (2H, br), 3.79 (3H, s), 2.60 (2H, t, J¼7.6 Hz), 2.09 (2H,
(3H, t, J¼7.1 Hz); 13C NMR (100 MHz, CDCl3)
d 167.86, 141.57, 138.50,
q, J¼7.6 Hz), 1.72 (2H, quintet, J¼7.6 Hz), 1.26 (1H, br); 13C NMR
134.96, 128.80 (2C), 128.06 (2C), 127.87, 60.11, 34.79, 30.07, 27.90,
20.73, 14.07, 12.15; EIMS m/z 246 (Mþ), 201, 172; HRMS (EI) m/z
246.1606 (calcd for C16H22O2: 246.1619).
(68 MHz, CDCl3) d 159.48, 143.85, 132.44, 129.34, 129.10, 120.78,
114.15, 110.86, 63.45, 54.98, 35.26, 31.60, 30.52; EIMS m/z 206
(Mþ), 188, 161, 147, 107; HRMS (EI) m/z 206.1282 (calcd for
C13H18O2: 206.1306).
5.4.8. Ethyl (2E)-2-methyl-2-octenoate (21f). Yield 93% (colorless
oil); IR (neat) 1715,1653 cmꢀ1; 1H NMR (270 MHz, CDCl3)
d
6.76 (1H,
5.5.2. (2E)-6-(3,4-Dimethoxyphenyl)-2-hexen-1-ol (18c). Yield 88%
tq, J¼7.6, 1.3 Hz), 4.19 (2H, q, J¼7.3 Hz), 2.16 (2H, q, J¼7.6 Hz), 1.83
(colorless oil); IR (neat) 3398, 1593, 1518 cmꢀ1 1H NMR (270 MHz,
;
(3H, d, J¼1.3 Hz),1.52–1.20 (6H, m),1.30 (3H, t, J¼7.3 Hz), 0.90 (3H, t,
CDCl3)
d
6.79 (1H, d, J¼8.5 Hz), 6.74–6.68 (2H, m), 5.79–5.59 (2H, m),
J¼6.9 Hz); 13C NMR (68 MHz, CDCl3)
d
167.97, 142.12, 127.49, 60.08,
4.10 (2H, br), 3.87 (3H, s), 3.86 (3H, s), 2.57 (2H, t, J¼7.6 Hz), 2.09 (2H,
31.38, 28.44, 28.11, 22.31,14.06,13.73,12.05; EIMS m/z 184 (Mþ),141,
109, 97, 83; HRMS (EI) m/z 184.1468 (calcd for C11H20O2: 184.1462).
q, J¼7.6 Hz), 1.70 (2H, quintet, J¼7.6 Hz), 1.30 (1H, br); 13C NMR
(68 MHz, CDCl3) d 148.71,147.04,134.91,132.63,129.29,120.13,111.75,
111.16, 63.58, 55.84, 55.73, 34.85, 31.62, 30.87; EIMS m/z 236 (Mþ),
218,191, 177; HRMS (EI) m/z 236.1426 (calcd for C14H20O3: 236.1411).
5.4.9. Methyl (2E)-5-(3-methoxyphenyl)-2-pentenoate (28b). Yield
72% (colorless oil); IR (neat) 1725, 1659, 1603 cmꢀ1 1H NMR
;
(270 MHz, CDCl3)
d
7.21 (1H, t, J¼7.8 Hz), 7.00 (1H, dt, J¼15.8, 6.8 Hz),
5.5.3. (2E)-6-(4-Methoxyphenyl)-2-hexen-1-ol (18d). Yield 99%
6.80–6.70 (3H, m), 5.85 (1H, dt, J¼15.8,1.6 Hz), 3.79 (3H, s), 3.71 (3H,
(colorless oil); IR (neat) 3390, 1667, 1615 cmꢀ1; 1H NMR (270 MHz,
s), 2.75 (2H, t, J¼7.7 Hz), 2.59–2.47 (2H, m); 13C NMR (68 MHz,
CDCl3)
d
7.08 (2H, d, J¼8.9 Hz), 6.82 (2H, d, J¼8.9 Hz), 5.77–5.58 (2H,
CDCl3)
d
166.92, 159.68, 148.25, 142.31, 129.40, 121.41, 120.66, 114.11,
m), 4.09 (2H, t, J¼5.6 Hz), 3.78 (3H, s), 2.56 (2H, t, J¼7.9 Hz), 2.08 (2H,
111.38, 55.09, 51.37, 34.31, 33.69; EIMS m/z 220 (Mþ), 189, 160, 147,
121, 84; HRMS (EI) m/z 220.1080 (calcd for C13H16O3: 220.1099).
q, J¼7.9 Hz), 1.68 (2H, quintet, J¼7.9 Hz), 1.22 (1H, t, J¼5.6 Hz); 13C
NMR (68 MHz, CDCl3)
d 157.49, 134.24, 132.40, 129.23, 129.12 (2C),
113.53 (2C), 63.35, 55.03, 34.24, 31.50, 30.85; EIMS m/z 206 (Mþ),
147, 134; HRMS (EI) m/z 206.1332 (calcd for C13H18O2: 206.1306).
5.4.10. Methyl (2E)-5-(3,4-dimethoxyphenyl)-2-pentenoate (28c).
Yield 78% (colorless oil); IR (neat) 1721, 1657 cmꢀ1 1H NMR
;
(270 MHz, CDCl3)
d
7.00 (1H, dt, J¼15.5, 6.8 Hz), 6.80 (1H, d,
5.5.4. (2E)-6-(3-Methoxyphenyl)-2-methyl-2-hexen-1-ol (22b). Yield
J¼8.2 Hz), 6.75 (1H, dd, J¼8.2, 2.0 Hz), 6.69 (1H, d, J¼2.0 Hz), 5.84
(1H, dt, J¼15.5, 1.6 Hz), 3.87 (3H, s), 3.86 (3H, s), 3.72 (3H, s), 2.73
(2H, t, J¼6.8 Hz), 2.51 (2H, q, J¼6.8 Hz); 13C NMR (68 MHz, CDCl3)
100% (colorless oil); IR (neat) 3374, 1603 cmꢀ1 1H NMR (270 MHz,
;
CDCl3)
d
7.24–7.15 (1H, m), 6.82–6.69 (3H, m), 5.43 (1H, tq, J¼5.8,
1.2 Hz), 4.00 (2H, s), 3.80 (3H, s), 2.60 (2H, t, J¼7.6 Hz), 2.08 (2H, q,
d
166.62, 148.59, 148.12, 147.15, 133.05, 121.14, 119.90, 111.42,
J¼7.6 Hz), 1.70 (2H, quintet, J¼7.6 Hz), 1.65 (3H, s), 1.30 (1H, br); 13C
111.03, 55.59, 55.51, 51.08, 33.79, 33.64; EIMS m/z 250 (Mþ), 219,
151, 107, 78, HRMS (EI) m/z 250.1198 (calcd for C14H18O4:
250.1204).
NMR (68 MHz, CDCl3) d 159.60, 144.07, 135.11, 129.18, 125.92, 120.86,
114.22, 110.94, 68.95, 55.13, 35.54, 30.98, 27.18, 13.71; EIMS m/z 220
(Mþ), 202, 192; HRMS (EI) m/z 220.1489 (calcd for C14H20O2:
220.1462).
5.4.11. Methyl (2E)-5-(4-methoxyphenyl)-2-pentenoate (28d). Yield
87% (colorless oil); IR (neat) 1717, 1655, 1615 cmꢀ1
;
1H NMR
5.5.5. (2E)-6-(3,4-Dimethoxyphenyl)-2-methyl-2-hexen-1-ol (22c).
(400 MHz, CDCl3)
d
7.08 (2H, d, J¼8.3 Hz), 6.99 (1H, dt, J¼15.6,
Yield 98% (colorless oil); IR (neat) 3424, 1673, 1593 cmꢀ1 1H NMR
;

S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
9891
(400 MHz, CDCl3)
d
6.79 (1H, d, J¼8.8 Hz), 6.71 (1H, d, J¼8.8 Hz),
(270 MHz, CDCl3)
d
7.19 (1H, dd, J¼8.6, 7.3 Hz), 6.82–6.70 (3H,
6.70 (1H, s), 5.44 (1H, t, J¼7.3 Hz), 4.01 (2H, d, J¼5.6 Hz), 3.87 (3H,
s), 3.86 (3H, s), 2.57 (2H, t, J¼7.3 Hz), 2.08 (2H, q, J¼7.3 Hz), 1.68
(2H, quintet, J¼7.3 Hz), 1.65 (3H, s), 1.28 (1H, t, J¼5.6 Hz); 13C NMR
m), 5.45 (1H, t, J¼7.3 Hz), 4.00 (2H, d, J¼5.9 Hz), 3.80 (3H, s),
2.65 (2H, t, J¼7.3 Hz), 2.36 (2H, q, J¼7.3 Hz), 1.63 (3H, s), 1.30
(1H, t, J¼5.9 Hz); 13C NMR (68 MHz, CDCl3)
d 159.50, 143.58,
(68 MHz, CDCl3)
d
148.68, 146.99, 135.00, 134.96, 125.72, 120.09,
135.43, 129.18, 125.06, 120.79, 114.22, 110.94, 68.70, 55.06, 35.66,
29.31, 13.57; EIMS m/z 206 (Mþ), 178, 149; HRMS (EI) m/z
206.1329 (calcd for C13H18O2: 206.1307).
111.69, 111.12, 68.75, 55.82, 55.69, 34.97, 31.22, 27.05, 13.61; EIMS
m/z 250 (Mþ), 232, 217, 191; HRMS (EI) m/z 250.1538 (calcd for
C15H22O3: 250.1568).
5.6. Epoxidation of aryl-2-alken-1-ol
5.5.6. (2E)-6-(4-Methoxyphenyl)-2-methyl-2-hexen-1-ol (22d). Yield
100% (colorless oil); IR (neat) 3386, 1613, 1514 cmꢀ1
;
1H NMR
Epoxidation of 18, 22, 29, and 32 was performed according to
that of 15.
(400 MHz, CDCl3)
d
7.09 (2H, d, J¼8.8 Hz), 6.82 (2H, d, J¼8.8 Hz), 5.43
(1H, tq, J¼7.3, 1.5 Hz), 4.01 (2H, d, J¼5.3 Hz), 3.79 (3H, s), 2.56 (2H, t,
J¼7.3 Hz), 2.05 (2H, q, J¼7.3 Hz), 1.66 (2H, quintet, J¼7.3 Hz), 1.64
5.6.1. (2R
(19b). Yield 91% (colorless oil); IR (neat) 3420, 1154 cmꢀ1; 1H NMR
(270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-6-(3-methoxyphenyl)-1-hexanol
(3H, s), 1.24 (1H, t, J¼5.3 Hz); 13C NMR (100 MHz, CDCl3)
d 157.48,
134.87, 134.37, 129.10 (2C), 125.62, 113.52 (2C), 68.55, 55.04, 34.40,
31.24, 26.96, 13.52; EIMS m/z 220 (Mþ), 147, 134; HRMS (EI) m/z
220.1437 (calcd for C14H20O2: 220.1462).
d
7.20 (1H, dd, J¼9.1, 7.5 Hz), 6.81–6.71 (3H, m),
3.89 (1H, ddd, J¼12.5, 5.5, 2.5 Hz), 3.80 (3H, s), 3.62 (1H, ddd,
J¼12.5, 7.3, 4.3 Hz), 3.00–2.87 (2H, m), 2.65 (2H, t, J¼7.6 Hz), 1.88–
1.50 (5H, m); 13C NMR (68 MHz, CDCl3)
d 159.64, 143.49, 129.29,
5.5.7. (2E)-2-Methyl-6-(4-Methylphenyl)-2-hexen-1-ol (22e). Yield
120.79, 114.20, 111.09, 61.62, 58.33, 55.75, 55.11, 35.52, 31.01, 27.49;
EIMS m/z 222 (Mþ), 191, 173, 161; HRMS (EI) m/z 222.1282 (calcd for
C13H18O3: 222.1255).
85% (colorless oil); IR (neat) 3332, 1673 cmꢀ1 1H NMR (400 MHz,
;
CDCl3)
d
7.09 (2H, d, J¼9.3 Hz), 7.06 (2H, d, J¼9.3 Hz), 5.42 (1H, t,
J¼7.6 Hz), 4.00 (2H, s), 2.58 (2H, t, J¼7.6 Hz), 2.32 (3H, s), 2.07 (2H,
q, J¼7.6 Hz), 1.68 (2H, quintet, J¼7.6 Hz), 1.65 (3H, s), 1.26 (1H, br);
5.6.2. (2R
(19c). Yield 80% (colorless oil); IR (neat) 3442, 1593, 1518 cmꢀ1; 1H
NMR (270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-6-(3,4-dimethoxyphenyl)-1-hexanol
13C NMR (100 MHz, CDCl3)
d 139.20, 134.88 (2C), 128.82 (2C), 128.16
(2C), 125.62, 68.48, 34.92, 31.17, 27.06, 20.84, 13.55; EIMS m/z 204
(Mþ), 186, 171; HRMS (EI) m/z 204.1521 (calcd for C14H20O:
204.1513).
d
6.79 (1H, d, J¼8.8 Hz), 6.75–6.69 (2H, m),
3.93 (1H, d, J¼2.7 Hz), 3.87 (3H, s), 3.86 (3H, s), 3.62 (1H, dd, J¼12.5,
4.2 Hz), 3.02–2.95 (1H, m), 2.94–2.89 (1H, m), 2.62 (2H, t, J¼7.5 Hz),
1.90–1.50 (5H, m); 13C NMR (68 MHz, CDCl3)
d 148.69, 147.06,
5.5.8. (2E)-2-Methyl-2-octen-1-ol (22f). Yield 72% (colorless oil); IR
134.41, 120.05, 111.62, 111.14, 61.60, 58.33, 55.79, 55.68 (2C), 34.96,
30.89, 27.71; EIMS m/z 252 (Mþ), 191, 177, 164; HRMS (EI) m/z
252.1371 (calcd for C14H20O4: 252.1360).
(neat) 3318, 1462 cmꢀ1 1H NMR (270 MHz, CDCl3)
; d 5.41 (1H, tq,
J¼7.3, 1.3 Hz), 4.00 (2H, d, J¼5.6 Hz), 2.02 (2H, q, J¼6.9 Hz), 1.66 (3H,
s), 1.44–1.19 (7H, m), 0.89 (3H, t, J¼6.9 Hz); 13C NMR (68 MHz,
CDCl3)
d
134.52, 126.66, 69.06, 31.53, 29.18, 27.55, 22.56, 14.03,
5.6.3. (2R
(19d). Yield 86% (colorless oil); IR (neat) 3450, 1613, 1584,
1516 cmꢀ1; 1H NMR (270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-6-(4-methoxyphenyl)-1-hexanol
13.61; EIMS m/z 142 (Mþ), 121, 100; HRMS (EI) m/z 142.1362 (calcd
for C9H18O: 142.1357).
d
7.09 (2H, d, J¼8.6 Hz), 6.82
(2H, d, J¼8.6 Hz), 3.89 (1H, ddd, J¼12.5, 5.5, 2.5 Hz), 3.79 (3H, s),
3.62 (1H, ddd, J¼12.5, 7.3, 4.3 Hz), 2.97 (1H, td, J¼5.5, 2.3 Hz), 2.93–
2.88 (1H, m), 2.61 (2H, t, J¼7.6 Hz), 1.85–1.48 (5H, m); 13C NMR
5.5.9. (2E)-5-(3-Methoxyphenyl)-2-penten-1-ol (29b). Yield 86%
(colorless oil); IR (neat) 3370, 1671, 1603 cmꢀ1; 1H NMR (270 MHz,
CDCl3)
(2H, m), 4.07 (2H, br d, J¼4.6 Hz), 3.79 (3H, s), 2.68 (2H, t, J¼7.8 Hz),
2.45–2.30 (2H, m), 1.50 (1H, br); 13C NMR (68 MHz, CDCl3)
159.57,
d
7.20 (1H, dd, J¼8.9, 7.5 Hz), 6.85–6.70 (3H, m), 5.80–5.55
(68 MHz, CDCl3) d 157.79, 133.92, 129.25 (2C), 113.76 (2C), 61.67,
58.36, 55.79, 55.24, 34.58, 30.98, 27.87; EIMS m/z 222 (Mþ),173,161,
147, 134, 121, 103, 91; HRMS (EI) m/z 222.1278 (calcd for C13H18O3
222.1255).
d
143.30, 132.10, 129.61, 129.22, 120.80, 114.24, 111.05, 63.58, 55.09,
35.52, 33.78; EIMS m/z 192 (Mþ), 121, 84; HRMS (EI) m/z 192.1158
(calcd for C12H16O2: 192.1149).
5.6.4. (2R
anol (23b). Yield 90% (colorless oil); IR (neat) 3426 cmꢀ1; 1H NMR
(270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-6-(3-methoxyphenyl)-2-methyl-1-hex-
5.5.10. (2E)-5-(3,4-Dimethoxyphenyl)-2-penten-1-ol (29c). Yield 85%
d
7.20 (1H, dd, J¼8.9, 7.5 Hz), 6.82–6.69 (3H, m),
(colorless oil); IR (neat) 3496, 1671, 1593, 1516 cmꢀ1
;
1H NMR
3.80 (3H, s), 3.72–3.50 (2H, m), 3.06 (1H, t, J¼6.1 Hz), 2.73–2.59 (2H,
(270 MHz, CDCl3)
d
6.82–6.68 (3H, m), 5.80–5.61 (2H, m), 4.09 (2H, t,
m), 1.94–1.52 (5H, m), 1.26 (3H, s); 13C NMR (68 MHz, CDCl3)
J¼4.8 Hz), 3.87 (3H, s), 3.86 (3H, s), 2.66 (2H, t, J¼7.8 Hz), 2.41–2.30
d 159.60, 143.54, 129.31, 120.80, 114.22, 111.16, 65.30, 60.72, 59.93,
(2H, m), 1.27 (1H, br t, J¼4.8 Hz); 13C NMR (68 MHz, CDCl3)
d
148.27,
55.14, 35.62, 28.10, 27.77, 14.24; EIMS m/z 236 (Mþ), 178, 161; HRMS
(EI) m/z 236.1434 (calcd for C14H20O3: 236.1411).
146.68, 133.99, 131.14, 129.27, 119.76, 111.38, 110.84, 62.74, 55.40,
55.31, 34.67, 33.74; EIMS m/z 222 (Mþ), 151, 120, 107, 87, HRMS (EI)
m/z 222.1253 (calcd for C13H18O3: 222.1255).
5.6.5. (2R
hexanol (23c). Yield 88% (colorless oil); IR (neat) 3472 cmꢀ1
NMR (400 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-6-(3,4-dimethoxyphenyl)-2-methyl-1-
;
1H
5.5.11. (2E)-5-(4-Methoxyphenyl)-2-penten-1-ol (29d). Yield 82%
d
6.80 (1H, dd, J¼6.8, 2.0 Hz), 6.73 (1H, dd,
(colorless oil); IR (neat) 3350, 1613, 1514 cmꢀ1; 1H NMR (270 MHz,
J¼6.8, 2.0 Hz), 6.72 (1H, d, J¼2.0 Hz), 3.88 (3H, s), 3.86 (3H, s), 3.68
(1H, dd, J¼12.2, 4.4 Hz), 3.58 (1H, dd, J¼12.2, 8.8 Hz), 3.07 (1H, t,
J¼6.2 Hz), 2.72–2.57 (2H, m), 1.92–1.68 (5H, m), 1.26 (3H, s); 13C
CDCl3)
d
7.09 (2H, d, J¼8.6 Hz), 6.83 (2H, d, J¼8.6 Hz), 5.79–5.57 (2H,
m), 4.08 (2H, t, J¼4.9 Hz), 3.79 (3H, s), 2.60 (2H, t, J¼8.0 Hz), 2.38–
2.29 (2H, m), 1.26 (1H, t, J¼4.9 Hz); 13C NMR (68 MHz, CDCl3)
NMR (68 MHz, CDCl3) d 148.75, 147.14, 134.47, 120.09, 111.66, 111.18,
d
157.70, 133.74, 132.22, 129.47, 129.23 (2C), 113.66 (2C), 63.58,
65.28, 60.75, 59.91, 55.82, 55.73, 35.05, 28.32, 27.60,14.13; EIMS m/z
266 (Mþ), 248, 208; HRMS (EI) m/z 266.1524 (calcd for C15H22O4:
266.1517).
55.18, 34.55, 34.15; EIMS m/z 192 (Mþ), 151, 121, 83; HRMS (EI) m/z
192.1177 (calcd for C12H16O2 192.1149).
5.5.12. (2E)-5-(3-Methoxyphenyl)-2-methyl-2-penten-1-ol (32b).
5.6.6. (2R
*
,3R
*
)-2,3-Epoxy-6-(4-methoxyphenyl)-2-methyl-1-hex-
Yield 76% (colorless oil); IR (neat) 3374, 1603 cmꢀ1 1H NMR
;
anol (23d). Yield 86% (colorless oil); IR (neat) 3428 cmꢀ1; 1H NMR

9892
S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
(400 MHz, CDCl3)
d
7.10 (2H, d, J¼8.6 Hz), 6.83 (2H, d, J¼8.6 Hz),
222 (Mþ), 204, 191; HRMS (EI) m/z 222.1267 (calcd for C13H18O3:
222.1256).
3.79 (3H, s), 3.67 (1H, d, J¼12.2 Hz), 3.57 (1H, d, J¼12.2 Hz), 3.05
(1H, t, J¼6.3 Hz), 2.70–2.56 (2H, m), 1.88–1.55 (5H, m), 1.25 (3H, s);
13C NMR (68 MHz, CDCl3)
d
157.53, 133.72, 129.00 (2C), 113.51 (2C),
5.7. (3R
*
,4R )-3,4-Epoxy-7-(3-Methoxyphenyl)-
*
65.41, 60.91, 60.01, 54.93, 34.37, 28.19, 27.40, 13.88; EIMS m/z 236
(Mþ), 178, 161; HRMS (EI) m/z 236.1440 (calcd for C14H20O3:
236.1411).
1-heptene (20b)
To a solution of 19b (422 mg, 1.90 mmol) in CH2Cl2 (70 ml) was
added Dess–Martin periodinane (1.61 g, 3.80 mmol) at 0 ꢁC under
an argon atmosphere. The mixture was stirred at room temperature
for 1 h and then quenched with saturated aqueous NaHCO3 and
extracted with Et2O. The extract was washed with saturated
aqueous NaHCO3 and NaCl, dried over MgSO4, and concentrated
under reduced pressure to give aldehyde. To a suspension of
methyltriphenylphosphonium bromide (1.32 g, 2.85 mmol) in THF
(10 ml) was added dropwise potassium bis(trimethylsilyl)amide
(0.5 M in toluene 4.9 ml, 2.47 mmol) at 0 ꢁC under an argon at-
mosphere. After being stirred for 30 min, a solution of the aldehyde
in THF (10 ml) was added to the mixture at ꢀ20 ꢁC. After being
stirred for 1 h at ꢀ20 ꢁC, the reaction was quenched with H2O at
0 ꢁC and extracted with Et2O. The extract was dried over MgSO4 and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel eluted with hexane/AcOEt
(10/1) to give 20b (361 mg, 1.66 mmol, 89%) as a colorless oil: IR
5.6.7. (2R
(23e). Yield 100% (colorless oil); IR (neat) 3426 cmꢀ1
(400 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-2-methyl-6-(4-methylphenyl)-1-hexanol
;
1H NMR
d
7.10 (2H, d, J¼8.6 Hz), 7.07 (2H, d, J¼8.6 Hz),
3.67 (1H, d, J¼12.2 Hz), 3.56 (1H, d, J¼12.2 Hz), 3.05 (1H, t,
J¼6.1 Hz), 2.72–2.57 (2H, m), 2.32 (3H, s), 1.89–1.53 (5H, m), 1.26
(3H, s); 13C NMR (68 MHz, CDCl3)
d 138.42, 134.76, 128.63 (2C),
127.88 (2C), 65.41, 60.85, 59.95, 34.73, 27.96, 27.35, 20.60, 13.74;
EIMS m/z 220 (Mþ), 202, 171; HRMS (EI) m/z 220.1457 (calcd for
C14H20O2: 220.1462).
5.6.8. (2R
*
,3R
*
)-2,3-Epoxy-2-methyl-1-octanol (23f). Yield 77% (col-
orless oil); IR (neat) 3422, 2928 cmꢀ1
;
1H NMR (270 MHz, CDCl3)
d
3.69 (1H, dd, J¼12.2, 4.6 Hz), 3.58 (1H, dd, J¼12.2, 8.6 Hz), 3.04 (1H,
t, J¼6.1 Hz), 1.72–1.30 (9H, m), 1.28 (3H, s), 0.90 (3H, t, J¼7.1 Hz); 13C
NMR (68 MHz, CDCl3) d 65.51, 61.05, 60.33, 31.45, 27.94, 25.95, 22.38,
13.95, 13.77; EIMS m/z 158 (Mþ), 139, 83; HRMS (EI) m/z 158.1303
(neat) 1603, 1586 cmꢀ1 1H NMR (270 MHz, CDCl3)
; d 7.19 (1H, t,
(calcd for C9H18O2: 158.1306).
J¼7.6 Hz), 6.82–6.67 (3H, m), 5.57 (1H, ddd, J¼17.1, 9.9, 7.3 Hz), 5.44
(1H, dd, J¼17.1, 2.0 Hz), 5.25 (1H, dd, J¼9.9, 1.6 Hz), 3.80 (3H, s), 3.09
(1H, dd, J¼7.2, 2.0 Hz), 2.89–2.79 (1H, m), 2.65 (2H, t, J¼7.6 Hz),
5.6.9. (2R
(30b). Yield 91% (colorless oil); IR (neat) 3442, 1603 cmꢀ1
NMR (270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-5-(3-methoxylphenyl)-1-pentanol
;
1H
1.92–1.46 (4H, m); 13C NMR (68 MHz, CDCl3)
d 159.55, 143.41,
d
7.21 (1H, dd, J¼8.9, 7.6 Hz), 6.81–6.72
135.72, 129.17, 120.68, 118.78, 114.08, 110.99, 60.05, 58.41, 54.94,
35.44, 31.30, 27.38; EIMS m/z 218 (Mþ), 200, 177, 161; HRMS (EI) m/z
218.1331 (calcd for C14H18O2: 218.1306).
(3H, m), 3.85 (1H, ddd, J¼12.5, 5.6, 2.6 Hz), 3.79 (3H, s), 3.57 (1H,
ddd, J¼12.5, 7.6, 4.3 Hz), 2.99 (1H, td, J¼5.6, 2.3 Hz), 2.86 (1H, dt,
J¼5.6, 2.3 Hz), 2.85–2.64 (2H, m), 1.95–1.84 (2H, m), 1.72–1.61(1H,
m); 13C NMR (68 MHz, CDCl3)
d
159.70, 142.64, 129.42, 120.73,
5.8. Preparation of 16b–d, 24b–f, 27b–d, and 34b
114.19, 111.31, 61.62, 58.61, 55.33, 55.11, 33.20, 32.19; EIMS m/z 208
(Mþ), 147, 134, 119, 84; HRMS (EI) m/z 208.1098 (calcd for
C12H16O3: 208.1099).
Dess–Martin oxidation of 19, 23, 30, and 33 was carried out
according to that of 19b (see Section 5.7). Wittig reaction of the
aldehydes obtained by the oxidation was carried out according to
that of 14b–d.
5.6.10. (2R
(30c). Yield 80% (colorless oil); IR (neat) 3472, 1593, 1518 cmꢀ1; 1H
NMR (270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-5-(3,4-dimethoxylphenyl)-1-pentanol
d
6.80 (1H, d, J¼8.2 Hz), 6.73 (1H, dd, J¼8.2,
5.8.1. Methyl (4R
ate (16b). Yield 77% (colorless oil); IR (neat) 1725, 1661 cmꢀ1
NMR (270 MHz, CDCl3)
*
,5R
*
,2E)-4,5-epoxy-8-(3-methoxyphenyl)-2-octeno-
2.0 Hz), 6.71 (1H, d, J¼2.0 Hz), 3.91–3.80 (1H, m), 3.87 (3H, s), 3.86
(3H, s), 3.64–3.52 (1H, m), 3.00 (1H, td, J¼5.9, 2.3 Hz), 2.90–2.85
(1H, m), 2.84–2.61 (2H, m), 1.93–1.83 (2H, m), 1.69 (1H, br); 13C
;
1H
d
7.20 (1H, td, J¼7.6, 1.4 Hz), 6.80–6.70 (3H,
m), 6.67 (1H, dd, J¼15.6, 7.0 Hz), 6.12 (1H, d, J¼15.6 Hz), 3.80 (3H, s),
3.74 (3H, s), 3.19 (1H, dd, J¼7.0, 1.9 Hz), 2.89 (1H, td, J¼6.5, 1.9 Hz),
2.64 (2H, t, J¼7.4 Hz), 1.88–1.57 (4H, m); 13C NMR (68 MHz, CDCl3)
NMR (68 MHz, CDCl3) d 148.48,146.94,133.36,119.85,111.37,110.98,
61.47, 58.56, 55.53, 55.45, 55.13, 33.21, 31.39; EIMS m/z 238 (Mþ),
220, 207, 194, 177, 164, 151, HRMS (EI) m/z 238.1206 (calcd for
C13H18O4: 238.1204).
d
166.09, 159.68, 144.95, 143.27, 129.35, 123.13, 120.79, 114.24, 111.14,
61.25, 56.15, 55.13, 51.70, 35.45, 31.33, 27.33; EIMS m/z 276 (Mþ),199,
177, 161; HRMS (EI) m/z 276.1390 (calcd for C16H20O4: 276.1360).
5.6.11. (2R
(30d). Yield 96% (colorless oil); IR (neat) 3420, 1613, 1584,
1516 cmꢀ1; 1H NMR (270 MHz, CDCl3)
*
,3R
*
)-2,3-Epoxy-5-(4-methoxylphenyl)-1-pentanol
5.8.2. Methyl
octenoate (16c). Yield 82% (colorless oil); IR (neat) 1723,1659 cmꢀ1
1H NMR (270 MHz, CDCl3)
(4R
*
,5R ,2E)-4,5-epoxy-8-(3,4-dimethoxyphenyl)-2-
*
d
7.11 (2H, d, J¼8.9 Hz), 6.83
;
(2H, d, J¼8.9 Hz), 3.85 (1H, dd, J¼12.5, 2.5 Hz), 3.79 (3H, s), 3.57 (1H,
dd, J¼12.5, 4.0 Hz), 2.98 (1H, td, J¼4.0, 2.5 Hz), 2.90–2.82 (1H, m),
2.82–2.60 (2H, m), 2.00–1.75 (2H, m), 1.66 (1H, br); 13C NMR
d
6.79 (1H, d, J¼8.5 Hz), 6.75–6.63 (3H,
m), 6.12 (1H, d, J¼15.6 Hz), 3.87 (3H, s), 3.86 (3H, s), 3.74 (3H, s), 3.20
(1H, dd, J¼7.0, 1.6 Hz), 2.90 (1H, ddd, J¼6.4, 4.9, 1.6 Hz), 2.62 (2H, t,
(68 MHz, CDCl3)
d
157.83, 133.01, 129.18 (2C), 113.77 (2C), 61.64,
J¼7.5 Hz), 1.90–1.52 (4H, m); 13C NMR (68 MHz, CDCl3)
d 165.94,
58.71, 55.34, 55.14, 33.47, 31.16; EIMS m/z 208 (Mþ), 159, 147, 134,
121; HRMS (EI) m/z 208.1123 (calcd for C12H16O2: 208.1099).
148.72, 147.13, 144.85, 134.17, 122.98, 120.05, 111.55, 111.11, 61.14,
56.03, 55.77, 55.68, 51.56, 34.90, 31.20, 27.54; EIMS m/z 306 (Mþ),
274, 191; HRMS (EI) m/z 306.1487 (calcd for C17H22O5: 306.1466).
5.6.12. (2R
tanol (33b). Yield 82% (colorless oil); IR (neat) 3446, 1603 cmꢀ1
1H NMR (270 MHz, CDCl3)
*
,3R )-2,3-Epoxy-5-(3-methoxylphenyl)-2-methyl-1-pen-
*
;
5.8.3. Methyl (4R
noate (16d). Yield 63% (colorless oil); IR (neat) 1734, 1661,
1613 cmꢀ1; 1H NMR (270 MHz, CDCl3)
*
,5R ,2E)-4,5-epoxy-8-(4-methoxyphenyl)-2-octe-
*
d
7.21 (1H, dd, J¼8.9, 7.6 Hz), 6.84–
6.72 (3H, m), 3.80 (3H, s), 3.64 (1H, dd, J¼12.2, 4.5 Hz), 3.53 (1H,
dd, J¼12.2, 8.6 Hz), 3.09 (1H, t, J¼6.3 Hz), 2.90–2.64 (2H, m),
2.03–1.77 (2H, m), 1.66 (1H, dd, J¼8.6, 4.5 Hz), 1.15 (3H, s); 13C
d
7.08 (2H, d, J¼8.4 Hz), 6.82
(2H, d, J¼8.4 Hz), 6.67 (1H, dd, J¼15.5, 6.9 Hz), 6.11 (1H, d,
J¼15.5 Hz), 3.78 (3H, s), 3.74 (3H, s), 3.19 (1H, dd, J¼6.9, 1.6 Hz), 2.89
(1H, td, J¼5.4, 1.6 Hz), 2.68 (2H, t, J¼7.4 Hz), 1.88–1.50 (4H, m); 13C
NMR (68 MHz, CDCl3)
d 159.62, 142.69, 129.36, 120.74, 114.20,
111.26, 65.30, 61.21, 59.57, 55.07, 32.65, 29.89, 14.02; EIMS m/z
NMR (68 MHz, CDCl3) d 166.06, 157.81, 144.97, 133.66, 129.21 (2C),

S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
9893
123.05, 113.75 (2C), 61.26, 56.14, 55.19, 51.66, 34.46, 31.24, 27.63;
EIMS m/z 276 (Mþ), 199, 177, 162; HRMS (EI) m/z 276.1337 (calcd for
C16H20O4: 276.1360).
1661 cmꢀ1; 1H NMR (270 MHz, CDCl3)
d
6.80 (1H, d, J¼8.1 Hz), 6.74–
6.70 (2H, m), 6.65 (1H, dd, J¼15.5, 7.0 Hz), 6.07 (1H, d, J¼15.5 Hz),
3.86 (6H, s), 3.74 (3H, s), 3.16 (1H, dd, J¼7.0, 1.9 Hz), 2.91 (1H, td,
J¼5.7, 1.9 Hz), 2.85–2.62 (2H, m), 1.97–1.86 (2H, m); 13C NMR
5.8.4. Methyl (4R
2-octenoate (24b). Yield 69% (colorless oil); IR (neat) 1723, 1655,
1603 cmꢀ1; 1H NMR (270 MHz, CDCl3)
*
,5R
*
,2E)-4,5-epoxy-8-(3-methoxyphenyl)-4-methyl-
(68 MHz, CDCl3) d 166.02, 148.95, 147.45, 144.81, 133.33, 123.15,
120.20, 111.64, 111.33, 60.72, 56.40, 55.91, 55.80, 51.66, 33.85, 31.62;
EIMS m/z 292 (Mþ), 164, 151; HRMS (EI) m/z 292.1325 (calcd for
C16H20O5: 292.1310).
d
7.20 (1H, dd, J¼8.9, 7.4 Hz),
6.80–6.71 (3H, m), 6.75 (1H, d, J¼15.8 Hz), 6.00 (1H, d, J¼15.8 Hz),
3.79 (3H, s), 3.73 (3H, s), 2.85 (1H, t, J¼6.1 Hz), 2.75–2.56 (2H, m),
1.94–1.52 (4H, m), 1.40 (3H, s); 13C NMR (68 MHz, CDCl3)
d
166.53,
5.8.11. Methyl (4R
*
,5R ,2E)-4,5-epoxy-7-(4-methoxyphenyl)-2-hepte-
*
159.68, 150.12, 143.28, 129.33, 121.01, 120.77, 114.20, 111.18, 65.72,
58.37, 55.13, 51.64, 35.51, 28.04, 27.90,15.17; EIMS m/z 290 (Mþ), 231,
177; HRMS (EI) m/z 290.1506 (calcd for C17H22O4: 290.1517).
noate (27d). Yield 89% (white needles); mp 59 ꢁC (hexane/tol-
uene¼10/1). Anal. Calcd for C15H18O4: C, 68.69; H, 6.92. Found: C,
68.58; H, 6.93. IR (neat) 1717, 1661 cmꢀ1; 1H NMR (270 MHz, CDCl3)
d
7.10 (2H, d, J¼8.6 Hz), 6.83 (2H, d, J¼8.6 Hz), 6.64 (1H, dd, J¼15.8,
5.8.5. Methyl (4R
thyl-2-octenoate (24c). Yield 77% (colorless oil); IR (neat) 1725, 1657,
1607 cmꢀ1; 1H NMR (400 MHz, CDCl3)
6.81–6.71 (3H, m), 6.77 (1H,
*
,5R
*
,2E)-4,5-epoxy-8-(3,4-dimethoxyphenyl)-4-me-
7.0 Hz), 6.06 (1H, d, J¼15.8 Hz), 3.79 (3H, s), 3.74 (3H, s), 3.13 (1H, dd,
J¼7.0, 1.5 Hz), 2.90 (1H, td, J¼5.7, 1.5 Hz), 2.84–2.66 (2H, m), 2.00–
d
1.77 (2H, m); 13C NMR (68 MHz, CDCl3)
d 165.95, 157.89, 144.80,
d, J¼15.7 Hz), 6.02 (1H, d, J¼15.7 Hz), 3.87 (3H, s), 3.86 (3H, s), 3.74
132.66, 129.16 (2C), 122.99, 113.80 (2C), 60.62, 56.30, 55.10, 51.56,
33.78, 30.99; EIMS m/z 262 (Mþ), 244, 148; HRMS (EI) m/z 262.1177
(calcd for C15H18O4: 262.1204).
(3H, s), 2.86 (1H, t, J¼6.0 Hz), 2.70–2.56 (2H, m), 1.90–1.60 (4H, m),
1.41 (3H, s); 13C NMR (68 MHz, CDCl3)
d 166.50, 150.08, 148.82,
147.25, 134.28, 120.95, 120.14, 111.67, 111.23, 65.71, 58.33, 55.88,
55.79, 51.61, 35.01, 28.17, 27.95, 15.13; EIMS m/z 320 (Mþ), 191, 177;
HRMS (EI) m/z 320.1622 (calcd for C18H24O5: 320.1634).
5.8.12. Methyl (4R
2-heptenoate (34b). Yield 90% (colorless oil); IR (neat) 1729,
1653 cmꢀ1 1H NMR (270 MHz, CDCl3)
*
,5R ,2E)-4,5-epoxy-7-(3-methoxyphenyl)-4-methyl-
*
;
d
7.21 (1H, t, J¼7.7 Hz),
5.8.6. Methyl (4R
2-octenoate (24d). Yield 88% (colorless oil); IR (neat) 1714, 1653,
1613 cmꢀ1; 1H NMR (400 MHz, CDCl3)
*
,5R
*
,2E)-4,5-epoxy-8-(4-methoxyphenyl)-4-methyl-
6.78–6.71 (3H, m), 6.72 (1H, d, J¼15.5 Hz), 5.96 (1H, d, J¼15.5 Hz),
3.79 (3H, s), 3.74 (3H, s), 2.88 (1H, t, J¼6.3 Hz), 2.84–2.62 (2H, m),
2.06–1.78 (2H, m), 1.28 (3H, s); 13C NMR (68 MHz, CDCl3)
d
7.09 (2H, d, J¼8.3 Hz), 6.83
(2H, d, J¼8.3 Hz), 6.75 (1H, d, J¼15.6 Hz), 6.00 (1H, d, J¼15.6 Hz),
3.79 (3H, s), 3.74 (3H, s), 2.85 (1H, t, J¼6.1 Hz), 2.70–2.55 (2H, m),
d 166.46, 159.64, 149.98, 142.35, 129.42, 121.00, 120.73, 114.18,
111.37, 65.15, 58.71, 55.04, 51.60, 32.46, 30.22, 14.96; EIMS m/z
276 (Mþ), 217, 147, 83; HRMS (EI) m/z 276.1336 (calcd for
C16H20O4: 276.1360).
1.89–1.59 (4H, m), 1.40 (3H, s); 13C NMR (68 MHz, CDCl3)
d 166.51,
157.80, 150.15, 133.67, 129.19 (2C), 120.93, 113.74 (2C), 65.72, 58.34,
55.17, 51.61, 34.50, 28.19, 27.92, 15.10; EIMS m/z 290 (Mþ), 177, 162;
HRMS (EI) m/z 290.1536 (calcd for C17H22O4: 290.1517).
5.9. BF3$Et2O-promoted reaction of vinyloxiranes 16, 20, 24,
27 or 34
5.8.7. Methyl (4R
2-octenoate (24e). Yield 72% (colorless oil); IR (neat) 1723,
1657 cmꢀ1; 1H NMR (400 MHz, CDCl3)
*
,5R
*
,2E)-4,5-epoxy-4-methyl-8-(4-methylphenyl)-
As a representative example, the reaction of 16b was performed
in the following manner. To a solution of 16b (150 mg, 0.543 mmol)
in CH2Cl2 (20 ml) was added BF3$Et2O (34 ml, 0.269 mmol) at
d
7.10 (2H, d, J¼8.1 Hz), 7.07
(2H, d, J¼8.1 Hz), 6.75 (1H, d, J¼15.6 Hz), 6.01 (1H, d, J¼15.8 Hz),
3.74 (3H, s), 2.85 (1H, t, J¼5.9 Hz), 2.71–2.56 (2H, m), 2.32 (3H, s),
ꢀ30 ꢁC under an argon atmosphere. The mixture was stirred at
ꢀ30 ꢁC for 10 min, then quenched with saturated aqueous NaHCO3
and extracted with Et2O. The extract was washed with saturated
aqueous NaCl, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel to give 36b (145 mg, 0.525 mmol, 97%). Spectroscopic data
are shown in Section 5.9.3.
1.90–1.54 (4H, m), 1.40 (3H, s); 13C NMR (68 MHz, CDCl3)
d 166.36,
150.07, 138.42, 135.18, 128.91 (2C), 128.09 (2C), 120.82, 65.61, 58.21,
51.47, 34.89, 27.97, 27.89, 20.83, 15.01; EIMS m/z 274 (Mþ), 242, 215;
HRMS (EI) m/z 274.1576 (calcd for C17H22O4: 274.1568).
5.8.8. Methyl (4R
Yield 57% (colorless oil); IR (neat) 1725, 1657 cmꢀ1
(270 MHz, CDCl3)
*
,5R
*
,2E)-4,5-epoxy-4-methyl-2-decenoate (24f)
;
1H NMR
d
6.77 (1H, dd, J¼15.7 Hz), 6.02 (1H, d,
5.9.1. 5-Ethenyl-6,7,8,9-tetrahydro-2-methoxy-5H-benzocyclo-
hepten-6-ol (35b). Cyclized product 35b was obtained in 85% yield
as as epimeric mixture with a ratio of 1.6/1. A part of the epimers
was separated by flash column chromatography. For less polar: IR
J¼15.7 Hz), 3.74 (3H, s), 2.84 (1H, t, J¼6.0 Hz), 1.70–1.24 (8H, m),
1.43 (3H, s), 0.90 (3H, t, J¼6.9 Hz); 13C NMR (68 MHz, CDCl3)
d
166.39, 150.21, 120.72, 65.84, 58.22, 51.45, 31.40, 28.32, 25.84,
22.38, 15.01, 13.78; EIMS m/z 212 (Mþ), 181, 154; HRMS (EI) m/z
(neat) 3404, 1609 cmꢀ1 1H NMR (270 MHz, CDCl3)
; d 7.09 (1H, d,
212.1402 (calcd for C12H20O3: 212.1411).
J¼7.8 Hz), 6.72–6.64 (2H, m), 6.31 (1H, ddd, J¼17.3, 10.5, 6.8 Hz),
5.21 (1H, dt, J¼10.5, 1.5 Hz), 5.03 (1H, dt, J¼17.3, 1.5 Hz), 3.98–3.88
(1H, m), 3.78 (3H, s), 3.71 (1H, d, J¼7.1 Hz), 2.84 (1H, dd, J¼12.7,
10.5 Hz), 2.66 (1H, dd, J¼12.7, 7.8 Hz), 2.10–1.75 (2H, m), 1.74–1.51
5.8.9. Methyl (4R
noate (27b). Yield 64% (colorless oil); IR (neat) 1717, 1661 cmꢀ1
1H NMR (270 MHz, CDCl3)
*
,5R ,2E)-4,5-epoxy-7-(3-methoxyphenyl)-2-hepte-
*
;
d
7.21 (1H, t, J¼7.7 Hz), 6.79–6.73 (3H,
(2H, m), 1.44 (1H, d, J¼7.1 Hz); 13C NMR (68 MHz, CDCl3)
d 158.39,
m), 6.63 (1H, dd, J¼15.6, 7.0 Hz), 6.05 (1H, d, J¼15.6 Hz), 3.79 (3H,
s), 3.74 (3H, s), 3.13 (1H, dd, J¼7.0, 2.0 Hz), 2.91 (1H, td, J¼5.7,
2.0 Hz), 2.88–2.64 (2H, m), 2.05–1.80 (2H, m); 13C NMR (68 MHz,
144.24, 136.90, 131.75, 130.17, 116.70, 116.17, 110.79, 72.03, 55.88,
55.16, 36.75, 35.82, 24.78; EIMS m/z 218 (Mþ), 174, 161; HRMS (EI)
m/z 218.1279 (calcd for C14H18O2: 218.1306). For more polar: IR
CDCl3)
d
166.06, 159.77, 144.81, 142.37, 129.50, 123.19, 120.73,
(neat) 3422, 1609 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 7.08 (1H, d,
114.24, 111.40, 60.66, 56.46, 55.13, 51.68, 33.58, 32.06; EIMS m/z
262 (Mþ), 244, 148; HRMS (EI) m/z 262.1178 (calcd for C15H18O4:
262.1204).
J¼7.8 Hz), 6.73–6.64 (2H, m), 6.09 (1H, ddd, J¼17.1, 10.3, 6.3 Hz),
5.18 (1H, d, J¼10.3 Hz), 4.94 (1H, d, J¼17.1 Hz), 4.01 (1H, br), 3.79
(3H, s), 3.72 (1H, t, J¼6.3 Hz), 2.92–2.81 (1H, m), 2.71–2.61 (1H, m),
2.05–1.85 (2H, m),1.80–1.63 (2H, m),1.51 (1H, d, J¼7.3 Hz); 13C NMR
5.8.10. Methyl (4R
*
,5R
*
,2E)-4,5-epoxy-7-(3,4-dimethoxyphenyl)-2-
(68 MHz, CDCl3) d 158.60, 144.15, 137.41, 132.48, 129.46, 116.52,
heptenoate (27c). Yield 40% (colorless oil); IR (CHCl3) 1729,
116.20, 110.72, 71.12, 56.54, 55.12, 35.68, 34.44, 22.01; EIMS m/z 218

9894
S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
(Mþ), 174, 166, 147; HRMS (EI) m/z 218.1290 (calcd for C14H18O2:
218.1306).
44% (colorless oil); IR (neat) 3506, 1717 cmꢀ1
CDCl3)
;
1H NMR (270 MHz,
7.29 (1H, d, J¼8.7 Hz), 7.21 (1H, d, J¼15.9 Hz), 6.74 (1H, dd,
d
J¼8.7, 2.9 Hz), 6.69 (1H, d, J¼2.9 Hz), 5.41 (1H, d, J¼15.9 Hz), 3.98–
3.87 (1H, m), 3.80 (3H, s), 3.70 (3H, s), 2.88 (1H, t, J¼12.3 Hz), 2.59
(1H, dd, J¼14.0, 5.7 Hz), 2.08–2.00 (2H, m), 1.78–1.45 (2H, m), 1.61
5.9.2. (5R
dro-5H-benzocyclohepten-6-ol (36a). Yield 25% (colorless oil); IR
(neat) 3454, 1723, 1653 cmꢀ1; 1H NMR (270 MHz, C6D6)
7.27 (1H,
*
,6R
*
)-5-(Methoxycarbonyl-(E)-ethenyl)-6,7,8,9-tetrahy-
d
(3H, s), 1.20 (1H, br d, J¼9.0 Hz); 13C NMR (68 MHz, CDCl3)
d 166.27,
dd, J¼15.8, 6.3 Hz), 7.04–6.83 (4H, m), 5.68 (1H, dd, J¼15.8, 1.8 Hz),
3.74 (1H, br), 3.53 (1H, td, J¼6.3, 1.8 Hz), 3.38 (3H, s), 2.61–2.48 (1H,
m), 2.41–2.29 (1H, m), 1.70–1.42 (3H, m), 1.40–1.22 (1H, m), 0.98
158.72, 154.49, 144.82, 131.24, 130.05, 118.99, 117.39, 110.68, 75.39,
55.13, 51.48, 51.33, 37.07, 35.08, 27.79, 21.46; EIMS m/z 290 (Mþ),
258, 187; HRMS (EI) m/z 290.1490 (calcd for C17H22O4: 290.1517).
(1H, br); 13C NMR (68 MHz, CDCl3)
d 166.80, 147.45, 142.45, 135.96,
131.87, 130.38, 127.79, 126.61, 122.06, 70.58, 56.05, 51.51, 35.51,
34.79, 21.59. EIMS m/z 246 (Mþ), 214, 186, 170, 157, 128, 115; HRMS
(EI) m/z 246.1242 (calcd for C15H18O3: 246.1255).
5.9.8. (5R
methyl-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ol
4% (colorless oil); 1H NMR (270 MHz, CDCl3)
*
,6R )-4-Methoxy-5-(methoxycarbonyl-(E)-ethenyl)-5-
*
(40b). Yield
d
7.28 (1H, d,
J¼16.1 Hz), 7.07 (1H, t, J¼7.8 Hz), 6.76–6.67 (2H, m), 5.66 (1H, d,
J¼16.1 Hz), 4.24 (1H, m), 3.72 (3H, s), 3.66 (3H, s), 3.11 (1H, dd,
J¼15.4, 12.5 Hz), 2.71 (1H, dd, J¼15.4, 7.0 Hz), 2.20–1.49 (5H, m),
1.60 (3H, s); EIMS m/z 290 (Mþ), 258, 187, 83; HRMS (EI) m/z
290.1491 (calcd for C17H22O4: 290.1517).
5.9.3. (5R
6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ol (36b). Yield 97% (col-
orless oil); IR (neat) 3462, 1721, 1649 cmꢀ1 1H NMR (270 MHz,
CDCl3)
*
,6R )-2-Methoxy-5-(methoxycarbonyl-(E)-ethenyl)-
*
;
d
7.20 (1H, dd, J¼15.6, 5.9 Hz), 7.04 (1H, d, J¼9.3 Hz), 6.73–
6.67 (2H, m), 5.60 (1H, dd, J¼15.6, 2.0 Hz), 4.20 (1H, br), 3.88 (1H, td,
J¼5.9, 2.0 Hz), 3.79 (3H, s), 3.71 (3H, s), 2.79 (1H, ddd, J¼14.1, 9.3,
3.4 Hz), 2.64 (1H, ddd, J¼14.1, 5.9, 2.4 Hz), 2.04–1.87 (2H, m), 1.77–
5.9.9. Methyl (2E)-4-fluoro-5-hydroxy-8-(3-methoxyphenyl)-4-meth-
yl-2-octenoate (41b). Yield 36% (colorless oil); IR (neat) 3482,
1.64 (2H, m), 1.58 (1H, br); 13C NMR (68 MHz, CDCl3)
d
166.86,
1717 cmꢀ1; 1H NMR (270 MHz, CDCl3)
d
7.19 (1H, dd, J¼8.5, 7.6 Hz),
159.09, 147.80, 144.07, 133.33, 127.57, 122.00, 116.59, 111.07, 70.55,
55.40, 55.18, 51.51, 35.84, 34.70, 21.63; EIMS m/z 276 (Mþ), 258, 244,
216; HRMS (EI) m/z 276.1386 (calcd for C16H20O4: 276.1360).
6.93 (1H, dd, J¼21.1, 15.7 Hz), 6.79–6.70 (3H, m), 6.11 (1H, d,
J¼15.7 Hz), 3.79 (3H, s), 3.76 (3H, s), 3.65 (1H, tdd, J¼10.7, 8.3,
2.5 Hz), 2.69–2.52 (2H, m), 2.04–1.83 (2H, m),1.80–1.29 (3H, m), 1.45
(3H, d, J¼22.5 Hz); 13C NMR (68 MHz, CDCl3)
d 166.67, 159.96,146.82
5.9.4. (5R
*
,6R
*
)-2,3-Dimethoxy-5-(methoxycarbonyl-(E)-ethenyl)-
(d, J¼19.9 Hz), 143.94, 129.58, 121.29 (d, J¼9.9 Hz), 121.07, 114.42,
111.45, 97.90 (d, J¼175.6 Hz), 76.04 (d, J¼24.9 Hz), 55.41, 52.07, 35.96,
31.02 (d, J¼3.7 Hz), 28.11, 20.55 (d, J¼23.7 Hz); EIMS m/z 310 (Mþ),
179, 161; HRMS (EI) m/z 310.1570 (calcd for C17H23O4F: 310.1579).
6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ol
(36c). Yield
95%
(white needles); mp 144 ꢁC (toluene). Anal. Calcd for C17H22O5: C,
66.65; H, 7.24. Found: C, 66.71; H, 7.37. IR (neat) 3498, 1717,
1653 cmꢀ1; 1H NMR (270 MHz, C6D6)
d
7.30 (1H, dd, J¼15.8, 5.6 Hz),
6.47 (1H, s), 6.40 (1H, s), 5.77 (1H, dd, J¼15.8, 2.0 Hz), 3.87 (1H, q,
J¼5.6 Hz), 3.52 (1H, td, J¼5.6, 2.0 Hz), 3.42 (3H, s), 3.40 (6H, s), 2.58
(1H, dd, J¼14.5, 10.2 Hz), 2.27 (1H, dd, J¼14.5, 5.6 Hz), 1.82–1.30
5.9.10. Methyl (2E)-4-formyl-7-(3-methoxyphenyl)-4-methyl-2-hep-
tenoate (42b). Yield 4% (colorless oil); IR (neat) 1725, 1653,
1603 cmꢀ1 1H NMR (270 MHz, CDCl3)
; d 9.42 (1H, s), 7.20 (1H, t,
(4H, m), 1.16 (1H, d, J¼7.5 Hz); 13C NMR (68 MHz, CDCl3)
d
166.82,
J¼7.9 Hz), 6.96 (1H, d, J¼16.1 Hz), 6.80–6.67 (3H, m), 5.85 (1H, d,
147.79, 147.40, 147.01, 134.93, 127.34, 121.91, 115.85, 114.13, 70.43,
55.94 (2C), 55.84, 51.47, 35.25, 34.48, 21.59; EIMS m/z 306 (Mþ),
288, 274; HRMS (EI) m/z 306.1445 (calcd for C17H22O5: 306.1466).
J¼16.1 Hz), 3.80 (3H, s), 3.75 (3H, s), 2.59 (2H, t, J¼7.4 Hz), 1.76–1.45
(4H, m), 1.23 (3H, s); 13C NMR (68 MHz, CDCl3)
d 200.85, 166.32,
159.74, 148.10, 143.06, 129.41, 122.21, 120.76, 114.23, 111.24, 55.17,
52.53, 51.74, 36.12, 35.17, 25.63,18.06; EIMS m/z 290 (Mþ), 262, 230;
HRMS (EI) m/z 290.1507 (calcd for C17H22O4: 290.1517).
5.9.5. (10R
*
,20R )-3-(20-Hydroxy-90-oxospiro[5.5]undeca-70,100-dien-
*
10-yl)-2E-propenoic acid methyl ester (37d). Yield 70% (white nee-
dles); mp 146–147 ꢁC (toluene). Anal. Calcd for C15H18O4: C, 68.69;
H, 6.92. Found: C, 68.97; H, 7.02. IR (CHCl3) 3452, 3024, 1721,
5.9.11. Methyl (3E)-8-(3-methoxyphenyl)-4-methyl-5-oxooct-3-eno-
ate (43b). Yield 7% (colorless oil); IR (neat) 1742, 1671 cmꢀ1 1H
;
1665 cmꢀ1
;
1H NMR (270 MHz, CDCl3)
d
7.16 (1H, dd, J¼10.6,
NMR (270 MHz, CDCl3)
d
7.20 (1H, dd, J¼8.8, 7.6 Hz), 6.82–6.69 (4H,
3.0 Hz), 6.61 (1H, dd, J¼10.2, 3.0 Hz), 6.46 (1H, dd, J¼15.6, 9.9 Hz),
6.42 (1H, dd, J¼10.5, 2.0 Hz), 6.23 (1H, dd, J¼9.9, 2.0 Hz), 5.87 (1H,
d, J¼15.6 Hz), 3.87 (1H, td, J¼10.5, 4.6 Hz), 3.69 (3H, s), 2.31–2.20
m), 3.80 (3H, s), 3.74 (3H, s), 3.28 (2H, d, J¼6.8 Hz), 2.72 (2H, t,
J¼7.3 Hz), 2.62 (2H, t, J¼7.3 Hz), 1.95 (2H, quintet, J¼7.3 Hz), 1.78
(3H, s); 13C NMR (68 MHz, CDCl3)
d 201.59, 171.39, 160.14, 143.87,
(2H, m), 1.97–1.38 (6H, m); 13C NMR (68 MHz, CDCl3)
d
185.62,
139.97, 132.92, 129.75, 121.35, 114.61, 111.75, 55.58, 52.61, 36.99,
35.74, 34.63, 26.41, 12.20; EIMS m/z 290 (Mþ), 259, 217; HRMS (EI)
m/z 290.1499 (calcd for C17H22O4: 290.1517).
165.82, 155.22, 148.32, 144.43, 131.08, 128.98, 125.43, 68.07, 55.40,
51.55, 45.79, 35.90, 33.91, 20.54; EIMS m/z 262 (Mþ), 244, 230;
HRMS (EI) m/z 262.1216 (calcd for C15H18O4: 262.1204).
5.9.12. (5R
5-methyl-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ol (39c). Yield
87% (colorless oil); IR (neat) 3512, 1715, 1647 cmꢀ1 1H NMR
(400 MHz, CDCl3)
*
,6R
*
)-2,3-Dimethoxy-5-(methoxycarbonyl-(E)-ethenyl)-
5.9.6. 3-(2,11-Epoxy-9-oxospiro[5.5]undeca-7-en-1-yl)-2E-prope-
noic acid methyl ester (38d). Yield 9% (colorless oil); IR (neat) 1717,
;
1620 cmꢀ1
;
1H NMR (270 MHz, CDCl3)
d
7.16 (1H, dd, J¼15.5,
d
7.20 (1H, d, J¼16.1 Hz), 6.91 (1H, s), 6.65 (1H, s),
9.4 Hz), 6.45 (1H, d, J¼10.1 Hz), 6.00 (1H, d, J¼15.5 Hz), 5.96 (1H, d,
J¼10.1 Hz), 4.50 (1H, dd, J¼10.9, 6.9 Hz), 4.46 (1H, m), 3.78 (3H, s),
3.13 (1H, dd, J¼9.4, 5.6 Hz), 2.89 (1H, dd, J¼16.2, 6.9 Hz), 2.55 (1H,
dd, J¼16.2, 10.9 Hz), 2.02–1.70 (5H, m), 1.41 (1H, br d, J¼7.3 Hz); 13C
5.42 (1H, d, J¼16.1 Hz), 3.93 (1H, dt, J¼9.8, 3.9 Hz), 3.88 (6H, s), 3.71
(3H, s), 2.85 (1H, dd, J¼14.7, 12.7 Hz), 2.56 (1H, dd, J¼14.7, 5.9 Hz),
2.08–2.01 (2H, m), 1.74–1.54 (2H, m), 1.63 (3H, s), 1.22 (1H, d,
J¼9.8 Hz); 13C NMR (68 MHz, CDCl3)
d 167.28, 154.11, 147.61, 146.74,
NMR (68 MHz, CDCl3)
d
197.29, 166.01, 149.73, 141.89, 128.39,
136.05, 129.98, 119.07, 114.91, 114.29, 75.46, 56.12, 55.82, 51.61,
51.53, 36.48, 35.10, 27.88, 21.56; EIMS m/z 320 (Mþ), 288, 249, 231;
HRMS (EI) m/z 320.1640 (calcd for C18H24O5: 320.1622).
125.61, 80.15, 80.12, 51.75, 49.87, 47.29, 43.92, 30.16, 25.38, 17.44;
EIMS m/z 262 (Mþ), 230, 217; HRMS (EI) m/z 262.1227 (calcd for
C15H18O4: 262.1204).
5.9.13. Methyl (2E)-4-fluoro-5-hydroxy-8-(4-methoxyphenyl)-4-met-
5.9.7. (5R
*
,6R
*
)-2-Methoxy-5-(methoxycarbonyl-(E)-ethenyl)-5-
(39b). Yield
hyl-2-octenoate (41d). Yield 9% (colorless oil); IR (neat) 3492,
methyl-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ol
1729 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d
7.08 (2H, d, J¼8.3 Hz), 6.93

S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
9895
(1H, dd, J¼21.5, 16.1 Hz), 6.82 (2H, d, J¼8.3 Hz), 6.10 (1H, d,
J¼16.1 Hz), 3.78 (3H, s), 3.76 (3H, s), 3.64 (1H, t, J¼9.2 Hz), 2.66–2.48
(2H, m), 2.03 (1H, br), 1.96–1.80 (1H, m), 1.70–1.29 (3H, m), 1.44 (3H,
(68 MHz, CDCl3)
d
166.96, 147.31 (d, J¼19.6 Hz), 121.10 (d, J¼11.2 Hz),
98.08 (d, J¼175.8 Hz), 76.34 (d, J¼25.2 Hz), 52.17, 32.04, 31.52 (d,
J¼3.9 Hz), 26.22, 22.95, 20.85 (d, J¼24.1 Hz), 14.38; EIMS m/z 231
(Mþ), 201, 149, 133; HRMS (EI) m/z 231.1414 (calcd for C12H20FO3:
231.1395).
d, J¼22.4 Hz); 13C NMR (68 MHz, CDCl3)
d 166.42, 157.79, 146.60 (d,
J¼20.1 Hz), 134.10, 129.24 (2C), 120.98 (d, J¼10.9 Hz), 113.80 (2C),
97.60 (1H, d, J¼175.6), 75.76 (d, J¼14.7 Hz), 55.26, 51.81, 34.68, 30.65
(d, J¼3.8 Hz), 28.15, 20.24 (d, J¼24.2 Hz); EIMS m/z 310 (Mþ), 178,
161; HRMS (EI) m/z 310.1550 (calcd for C17H23O4F: 310.1579).
5.9.20. Methyl (2E)-4-formyl-4-methyl-2-nonenoate (42f). Yield
22% (colorless oil); IR (neat) 1729, 1653 cmꢀ1 1H NMR (270 MHz,
;
CDCl3)
d
9.44 (1H, s), 6.99 (1H, d, J¼16.2 Hz), 5.87 (1H, d, J¼16.2 Hz),
5.9.14. Methyl (2E)-4-formyl-7-(4-methoxyphenyl)-4-methyl-2-hep-
3.76 (3H, s), 1.70–1.57 (2H, m), 1.39–1.15 (6H, m), 1.23 (3H, s), 0.88
tenoate (42d). Yield 6% (colorless oil); IR (neat) 1725, 1653 cmꢀ1
;
(3H, t, J¼6.8 Hz); 13C NMR (68 MHz, CDCl3)
d 201.15, 166.43, 148.42,
1H NMR (270 MHz, CDCl3)
d
9.40 (1H, s), 7.06 (2H, d, J¼8.6 Hz), 6.96
121.93, 52.64, 51.73, 35.75, 32.17, 23.63, 22.38,17.99,13.94; EIMS m/z
212 (Mþ), 196, 184; HRMS (EI) m/z 212.1431 (calcd for C12H20O3:
212.1411).
(1H, d, J¼16.2 Hz), 6.82 (2H, d, J¼8.6 Hz), 5.84 (1H, d, J¼16.2 Hz),
3.79 (3H, s), 3.75 (3H, s), 2.55 (2H, t, J¼7.3 Hz), 1.90–1.46 (4H, m),
1.22 (3H, s); EIMS m/z 290 (Mþ), 278, 258; HRMS (EI) m/z 290.1503
(calcd for C17H22O4: 290.1517).
5.9.21. Methyl (3E)-4-methyl-5-oxodec-3-enoate (43f). Yield 7%
(colorless oil); IR (neat) 1744, 1673 cmꢀ1; 1H NMR (270 MHz, CDCl3)
5.9.15. Methyl (3E)-8-(4-methoxyphenyl)-4-methyl-5-oxooct-3-enoate
d
6.79 (1H, tq, J¼6.9, 1.3 Hz), 3.74 (3H, s), 3.29 (2H, d, J¼6.9 Hz), 2.69
(43d). Yield 73% (colorless oil); IR (neat) 1742, 1671 cmꢀ1
;
1H NMR
(2H, t, J¼7.5 Hz), 1.79 (3H, d, J¼1.3 Hz), 1.67–1.54 (2H, m), 1.41–1.18
(270 MHz, CDCl3)
d
7.10 (2H, d, J¼8.6 Hz), 6.82 (2H, d, J¼8.6 Hz), 6.73
(4H, m), 0.89 (3H, t, J¼6.8 Hz); 13C NMR (68 MHz, CDCl3)
d 201.72,
(1H, tq, J¼6.9, 1.3 Hz), 3.78 (3H, s), 3.73 (3H, s), 3.27 (2H, d, J¼6.9 Hz),
2.70 (2H, t, J¼7.5 Hz), 2.58 (2H, t, J¼7.5 Hz), 1.92 (2H, quintet,
171.04, 139.50, 132.34, 52.16, 37.31, 34.15, 31.51, 24.43, 22.48, 13.93,
11.75; EIMS m/z 212 (Mþ), 196, 184; HRMS (EI) m/z 212.1441 (calcd
for C12H20O3: 212.1411).
J¼7.5 Hz), 1.78 (3H, d, J¼1.3 Hz); 13C NMR (68 MHz, CDCl3)
d 201.23,
170.94, 157.78, 139.45, 133.80, 132.44, 129.31 (2C), 113.73 (2C), 55.21,
52.13, 36.45, 34.28, 34.11, 26.31, 11.72; EIMS m/z 290 (Mþ), 177, 134;
HRMS (EI) m/z 290.1524 (calcd for C17H22O4: 290.1517).
5.9.22. (1R
dronaphthalen-2-ol (44a). Yield 65% (colorless oil); IR (neat) 3436,
1725, 1655 cmꢀ1 1H NMR (270 MHz, CDCl3)
7.20–7.10 (3H, m),
*
,2R
*
)-1-(Methoxycarbonyl-(E)-ethenyl)-1,2,3,4-tetrahy-
;
d
5.9.16. Methyl (2E)-4-fluoro-5-hydroxy-4-methyl-8-(4-methylphenyl)-
2-octenoate (41e). Yield 48% (white needles); mp 53–54 ꢁC (hexane).
Anal. Calcd for C17H23O3F: C, 69.36; H, 7.88. Found: C, 69.30; H, 7.92.
7.06–7.00 (1H, m), 6.92 (1H, dd, J¼15.5, 9.2 Hz), 6.00 (1H, dd, J¼15.5,
1.0 Hz), 3.94 (1H, ddd, J¼9.2, 6.3, 3.0 Hz), 3.76 (3H, s), 3.55 (1H, t,
J¼8.1 Hz), 3.03–2.82 (2H, m), 2.20–2.09 (1H, m), 1.94–1.79 (2H, m);
IR (CHCl3) 3618, 1721, 1665 cmꢀ1
;
1H NMR (270 MHz, CDCl3)
d
7.09
13C NMR (68 MHz, CDCl3)
d 166.59, 149.35, 135.50, 134.02, 129.56,
(2H, d, J¼8.4 Hz), 7.05 (2H, d, J¼8.4 Hz), 6.92 (1H, dd, J¼21.1, 15.8 Hz),
6.10 (1H, d, J¼15.8 Hz), 3.77 (3H, s), 3.65 (1H, tdd, J¼10.6, 4.9, 2.3 Hz),
2.64–2.54 (2H, m), 2.31 (3H, s), 1.96–1.80 (1H, m), 1.92 (1H, dt, J¼4.9,
1.3 Hz), 1.74–1.26 (3H, m), 1.45 (3H, d, J¼22.3 Hz); 13C NMR (68 MHz,
128.86, 126.82, 126.12, 124.29, 69.97, 51.56, 51.38, 29.04, 26.84;
EIMS m/z 232 (Mþ), 214, 200, 181, 156, 128, 115; HRMS (EI) m/z
232.1107 (calcd for C14H16O3 232.1099).
CDCl3)
d
166.40, 146.60 (d, J¼19.6 Hz), 138.88, 135.21, 129.00 (2C),
5.9.23. (1R
*
,2R )-6-Methoxy-1-(methoxycarbonyl-(E)-ethenyl)-
*
128.20 (2C), 120.91 (d, J¼10.9 Hz), 97.60 (d, J¼176.0 Hz), 75.71 (d,
J¼24.7 Hz), 51.77, 35.11, 30.67 (d, J¼3.8 Hz), 27.99, 20.94, 20.24 (d,
J¼24.2 Hz); EIMS m/z 294 (Mþ), 274, 197, 161; HRMS (EI) m/z
294.1645 (calcd for C17H23O3F: 294.1630).
1,2,3,4-tetrahydronaphthalen-2-ol (44b). Yield 65% (white needles);
mp 88 ꢁC (hexane/toluene¼2/1). Anal. Calcd for C15H18O4: C, 68.69;
H, 6.92. Found: C, 68.55; H, 6.98. IR (CHCl3) 3442, 1719, 1655 cmꢀ1
;
1H NMR (270 MHz, CDCl3)
d
6.94 (1H, d, J¼8.5 Hz), 6.90 (1H, dd,
J¼15.5, 9.2 Hz), 6.72 (1H, dd, J¼8.5, 2.7 Hz), 6.66 (1H, d, J¼2.7 Hz),
5.97 (1H, d, J¼15.5 Hz), 3.94–3.83 (1H, m), 3.78 (3H, s), 3.75 (3H, s),
3.49 (1H, t, J¼8.2 Hz), 3.00–2.78 (2H, m), 2.18–2.06 (1H, m), 1.99–
5.9.17. Methyl (2E)-4-formyl-4-methyl-7-(4-methylphenyl)-2-hepte-
noate (42e). Yield 23% (colorless oil); IR (neat) 1727, 1649 cmꢀ1; 1H
NMR (270 MHz, CDCl3)
d
9.41 (1H, s), 7.09 (2H, d, J¼7.8 Hz), 7.03
1.78 (2H, m); 13C NMR (68 MHz, CDCl3)
d 166.58, 158.47, 149.56,
(2H, d, J¼7.8 Hz), 6.96 (1H, d, J¼16.4 Hz), 5.84 (1H, d, J¼16.4 Hz),
136.81, 130.67, 126.09, 124.23, 113.51, 112.55, 70.25, 55.24, 51.59,
50.93, 29.02, 27.15; EIMS m/z 262 (Mþ), 244, 230, 159; HRMS (EI) m/
z 262.1224 (calcd for C15H18O4: 262.1204).
3.75 (3H, s), 2.57 (2H, t, J¼7.8 Hz), 2.31 (3H, s), 1.75–1.48 (4H, m),
1.22 (3H, s); 13C NMR (68 MHz, CDCl3)
d 200.88, 166.34, 148.13,
138.29, 135.50, 129.10 (2C), 128.20 (2C), 122.11, 52.54, 51.74, 35.61,
35.16, 25.85, 20.97, 17.98; EIMS m/z 274 (Mþ), 256, 171; HRMS (EI)
m/z 274.1597 (calcd for C17H22O3: 274.1568).
5.9.24. (1R
*
,2R )-8-Methoxy-1-(methoxycarbonyl-(E)-ethenyl)-
*
1,2,3,4-tetrahydronaphthalen-2-ol (45b). Yield 35% (white needles);
mp 117 ꢁC (hexane/toluene¼1:1). Anal. Calcd for C15H18O4: C,
68.69; H, 6.92. Found: C, 68.74; H, 6.99. IR (CHCl3) 3442, 1719,
5.9.18. Methyl (3E)-4-methyl-8-(4-methylphenyl)-5-oxooct-3-enoate
(43e). Yield 9% (colorless oil); IR (neat) 1717, 1653 cmꢀ1
;
1H NMR
1655 cmꢀ1; 1H NMR (270 MHz, CDCl3)
d
7.16 (1H, t, J¼7.9 Hz), 6.98
(270 MHz, CDCl3)
d
7.10 (2H, d, J¼8.8 Hz), 7.06 (2H, d, J¼8.8 Hz), 6.73
(1H, dd, J¼15.7, 6.6 Hz), 6.76 (1H, d, J¼7.9 Hz), 6.69 (1H, d, J¼7.9 Hz),
5.58 (1H, dd, J¼15.7, 1.6 Hz), 4.25–4.18 (1H, m), 3.95–3.88 (1H, m),
3.75 (3H, s), 3.70 (3H, s), 2.98 (1H, ddd, J¼17.6, 10.0, 7.6 Hz), 2.76
(1H, ddd, J¼17.6, 5.9, 3.9 Hz), 2.05–1.88 (2H, m), 1.65 (1H, d,
(1H, tq, J¼6.6, 1.0 Hz), 3.75 (3H, s), 3.27 (2H, d, J¼6.6 Hz), 2.71 (2H, t,
J¼7.6 Hz), 2.60 (2H, t, J¼7.6 Hz), 2.32 (3H, s), 1.93 (2H, quintet,
J¼7.6 Hz), 1.78 (3H, d, J¼1.0 Hz); 13C NMR (68 MHz, CDCl3)
d 201.27,
170.99, 139.53, 138.69, 135.32, 132.44, 129.04 (2C), 128.36 (2C),
52.19, 36.57, 34.80, 34.18, 26.20, 21.00, 11.77; EIMS m/z 274 (Mþ),
248, 201; HRMS (EI) m/z 274.1576 (calcd for C17H22O3: 274.1568).
J¼5.4 Hz); 13C NMR (68 MHz, CDCl3)
d 167.23, 158.17, 149.55, 137.03,
127.57, 121.98, 121.63, 121.28, 107.80, 68.51, 55.25, 51.42, 43.87,
25.17, 23.62; EIMS m/z 262 (Mþ), 244, 230, 159; HRMS (EI) m/z
262.1183 (calcd for C15H18O4: 262.1204).
5.9.19. Methyl (2E)-4-fluoro-5-hydroxy-4-methyl-2-decenoate (41f).
Yield 54% (colorless oil); IR (CHCl3) 3470, 1729, 1665 cmꢀ1; 1H NMR
5.9.25. (1R
1,2,3,4-tetrahydronaphthalen-2-ol (44c). Yield 84% (colorless oil); IR
(neat) 3496, 1723, 1653 cmꢀ1; 1H NMR (270 MHz, CDCl3)
6.92 (1H,
dd, J¼15.6, 9.0 Hz), 6.61 (1H, s), 6.48 (1H, s), 5.97 (1H, dd, J¼15.6,
*
,2R
*
)-6,7-Dimethoxy-1-(methoxycarbonyl-(E)-ethenyl)-
(270 MHz, CDCl3)
J¼15.7 Hz), 3.77(3H, s), 3.68–3.56(1H, m),1.97 (1H, d,J¼4.6 Hz),1.65–
d
6.95 (1H, dd, J¼21.1, 15.7 Hz), 6.11 (1H, d,
d
1.20 (8H, m), 1.46 (3H, d, J¼22.5 Hz), 0.89 (3H, t, J¼6.8 Hz); 13C NMR

9896
S. Nagumo et al. / Tetrahedron 65 (2009) 9884–9896
0.9 Hz), 3.96–3.88 (1H, m), 3.85 (3H, s), 3.81 (3H, s), 3.76 (3H, s),
3.55–3.45 (1H, m), 2.95–2.73 (2H, m), 2.16–2.04 (1H, m), 1.93–1.77
1.44 (3H, s); 13C NMR (68 MHz, CDCl3)
d 167.57,158.23,158.13,136.51,
129.81, 127.53,121.59,117.93,109.18, 72.65, 55.08, 51.35, 45.13, 28.66,
25.63, 16.58; EIMS m/z 276 (Mþ), 244, 187, 173; HRMS (EI) m/z
276.1354 (calcd for C16H20O4: 276.1360).
(2H, m); 13C NMR (68 MHz, CDCl3)
d 166.55, 149.59, 148.11, 147.59,
127.66, 125.57, 124.18, 112.30, 111.51, 70.09, 56.02, 55.86, 51.62,
51.05, 28.85, 26.28; EIMS m/z 292 (Mþ), 274, 189; HRMS (EI) m/z
292.1290 (calcd for C16H20O5: 292.1310).
Acknowledgements
5.9.26. (1R
1,2,3,4-tetrahydronaphthalen-2-ol (45c). Yield 16% (colorless oil); IR
(neat) 3448, 1723, 1653 cmꢀ1; 1H NMR (270 MHz, CDCl3)
7.01 (1H,
*
,2R
*
)-7,8-Dimethoxy-1-(methoxycarbonyl-(E)-ethenyl)-
This work was supported by a Grant-in-Aid for Scientific Re-
search (C) (15590017 to S.N.).
d
dd, J¼15.6, 7.1 Hz), 6.86 (1H, d, J¼8.4 Hz), 6.81 (1H, d, J¼8.4 Hz),
5.64 (1H, dd, J¼15.6, 1.5 Hz), 4.21–4.12 (1H, m), 3.95–3.88 (1H, m),
3.83 (3H, s), 3.76 (3H, s), 3.69 (3H, s), 2.91 (1H, ddd, J¼17.0, 10.0,
6.8 Hz), 2.72 (1H, ddd, J¼17.0, 6.1, 4.3 Hz), 2.01–1.79 (2H, m), 1.74
References and notes
1. Taylor, S. K.; Hockerman, G. H.; Karrick, G. L.; Lyle, S. B.; Schramm, S. B. J. Org.
Chem. 1983, 48, 2449.
(1H, br); 13C NMR (68 MHz, CDCl3)
d 167.04, 150.68, 149.77, 147.84,
128.57, 127.62, 124.10, 122.06, 111.98, 68.69, 60.42, 55.87, 51.47,
44.79, 25.65, 23.23; EIMS m/z 292 (Mþ), 274, 189; HRMS (EI) m/z
292.1287 (calcd for C16H20O5: 292.1310).
2. Taylor, S. K.; Davisson, M. E.; Hissom, B. R., Jr.; Brown, S. L.; Pristach, H. A.;
Schramm, S. B.; Harvey, S. M. J. Org. Chem. 1987, 52, 425.
3. Taylor, S. K.; Blankespoor, C. L.; Harvey, S. M.; Richardson, L. J. J. Org. Chem. 1988,
53, 3309.
4. Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang, C.-K. J. Am. Chem. Soc.
1989, 111, 5330 5335.
5.9.27. (1R
1,2,3,4-tetrahydronaphthalen-2-ol (44d). Yield 98% (colorless oil);
IR (neat) 3440, 1723, 1649 cmꢀ1 1H NMR (400 MHz, CDCl3)
7.05
*
,2R )-7-Methoxy-1-(methoxycarbonyl-(E)-ethenyl)-
*
5. Stork, G.; Kobayashi, Y.; Suzuki, T.; Zhao, K. J. Am. Chem. Soc. 1990, 112, 1661.
6. (a) Akita, H.; Umezawa, I.; Takano, M.; Matsukura, H.; Oishi, T. Chem. Pharm.
Bull. 1991, 39, 3094; (b) Ono, M.; Todoriki, R.; Yamamoto, Y.; Akita, H. Chem.
Pharm. Bull. 1994, 42, 1590; (c) Ono, M.; Yamamoto, Y.; Todoriki, R.; Akita, H.
Heterocycles 1994, 37, 181; (d) Ono, M.; Yamamoto, Y.; Akita, H. Chem. Pharm.
Bull. 1995, 43, 553.
;
d
(1H, d, J¼8.4 Hz), 6.91 (1H, dd, J¼15.5, 8.6 Hz), 6.74 (1H, dd, J¼8.4,
2.5 Hz), 6.55 (1H, d, J¼2.5 Hz), 5.99 (1H, d, J¼15.5 Hz), 3.96–3.88
(1H, m), 3.75 (6H, s), 3.52 (1H, t, J¼8.6 Hz), 2.95–2.77 (2H, m), 2.18–
7. For preliminary report from our lab, see: Nagumo, S.; Miyoshi, I.; Akita, H.;
Kawahara, N. Tetrahedron Lett. 2002, 43, 2223.
2.08 (1H, m), 1.91–1.79 (2H, m); 13C NMR (68 MHz, CDCl3)
d 166.53,
8. House, H. O. J. Am. Chem. Soc. 1956, 78, 2298; (b) House, H. O.; Wasson, R. L.
J. Am. Chem. Soc. 1956, 78, 4394; (c) House, H. O.; Ryerson, G. D. J. Am. Chem.
Soc. 1961, 83, 979; (d) Maruoka, K.; Hasegawa, M.; Yamamoto, H.; Suzuki, K.;
Shimazaki, M.; Tsuchihashi, G. J. Am. Chem. Soc. 1986, 108, 3827; (e) Suzuki,
K.; Miyazawa, M.; Tsuchihashi, G. Tetrahedron Lett. 1987, 28, 3515; (f)
Maruoka, K.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1989, 111, 6431; (g)
Maruoka, K.; Nagahara, S.; Ooi, T.; Yamamoto, H. Tetrahedron Lett. 1989, 30,
5607; (h) Enev, V. S.; Tsankova, E. T. Tetrahedron 1991, 47, 6399; (i) Maruoka,
K.; Ooi, T.; Nagahara, S.; Yamamoto, H. Tetrahedron 1991, 47, 6983; (j)
Maruoka, K.; Ooi, T.; Yamamoto, H. Tetrahedron 1992, 48, 3303; (k) Jung, M.
E.; Da´mico, D. C. J. Am. Chem. Soc. 1995, 117, 7379; (l) Takanami, T.; Hirabe,
R.; Ueno, M.; Hino, F.; Suda, K. Chem. Lett. 1996, 1031; (m) Suda, K.; Baba, K.;
Nakajima, S.; Takanami, T. Tetrahedron Lett. 1999, 40, 7243; (n) Hara, N.;
Mochizuki, A.; Tatara, A.; Fujimoto, Y. Tetrahedron: Asymmetry 2000, 11,
1859; (o) Kita, Y.; Furukawa, A.; Futamura, J.; Higuchi, K.; Ueda, K.; Fujioka,
H. Tetrahedron 2001, 57, 815; (p) Suda, K.; Baba, K.; Nakajima, S.; Takanami,
T. Chem. Commun. 2002, 2570; (q) Suda, K.; Kikkawa, T.; Nakajima, S.; Ta-
kanami, T. J. Am. Chem. Soc. 2004, 126, 9554.
9. For the formation of fluorohydrin from epoxide with BF3$Et2O, see: (a) Gold-
smith, D. J. J. Am. Chem. Soc. 1962, 84, 3913; (b) Berti, G.; Macchia, B.; Macchia,
F.; Monti, L. J. Chem. Soc. C 1971, 3371; (c) Barili, P. L.; Belluci, G.; Berti, G.;
Macchia, B.; Macchia, F. J. Chem. Soc., Perkin Trans. 1 1974, 477; (d) Takaishi, N.;
Takahashi, H.; Inamoto, Y. Tetrahedron Lett. 1985, 26, 2361; (e) Duhamel, P.;
Leblond, B.; Poirier, J.-M. J. Chem. Soc., Chem. Commun. 1993, 476.
10. Formation of conjugated ketones 43b, 43d, 43e, and 43f includes migration of
double bond. The rearrangement occurs when the corresponding reaction
mixture is purified by column chromatography with silica gel.
157.86, 149.15, 135.17, 129.81, 127.54, 124.38, 114.51, 112.91, 70.05,
55.25 (2C), 51.57, 29.24, 25.98; EIMS m/z 262 (Mþ), 244, 159; HRMS
(EI) m/z 262.1224 (calcd for C15H18O4: 262.1204).
5.9.28. (1R
methyl-1,2,3,4-tetrahydronaphthalen-2-ol (46b). Yield 34% (color-
less oil); IR (neat) 3484, 1723 cmꢀ1 1H NMR (270 MHz, CDCl3)
*
,2R
*
)-6-Methoxy-1-(methoxycarbonyl-(E)-ethenyl)-1-
;
d
7.01 (1H, d, J¼15.8 Hz), 6.96 (1H, d, J¼8.5 Hz), 6.72 (1H, dd, J¼8.5,
2.9 Hz), 6.63 (1H, d, J¼2.9 Hz), 5.84 (1H, d, J¼15.8 Hz), 3.92 (1H, dd,
J¼8.9, 4.0 Hz), 3.77 (3H, s), 3.74 (3H, s), 3.02–2.80 (2H, m), 2.05–1.88
(2H, m), 1.57 (1H, br), 1.39 (3H, s); 13C NMR (68 MHz, CDCl3)
d
167.06, 158.13, 156.06, 136.05, 131.76, 129.77, 121.23, 113.29, 112.71,
72.86, 55.15, 51.55, 46.40, 27.32, 26.09, 20.99; EIMS m/z 276 (Mþ),
244, 187, 173; HRMS (EI) m/z 276.1336 (calcd for C16H20O4:
276.1360).
5.9.29. (1R
methyl-1,2,3,4-tetrahydronaphthalen-2-ol (47b). Yield 56% (colorless
oil); IR (neat) 3472,1717,1647 cmꢀ1; 1H NMR (270 MHz, CDCl3)
7.14
*
,2R
*
)-8-Methoxy-1-(methoxycarbonyl-(E)-ethenyl)-1-
d
(1H, d, J¼16.0 Hz), 7.13 (1H, t, J¼7.9 Hz), 6.72 (1H, dd, J¼7.9, 0.8 Hz),
6.68 (1H, d, J¼7.9 Hz), 5.85 (1H, d, J¼16.0 Hz), 3.86–3.71 (1H, m), 3.74
(3H, s), 3.69 (3H, s), 2.91 (2H, dd, J¼8.4, 4.8 Hz), 2.09–1.82 (3H, m),
11. (a) Pigge, F. C.; Coniglio, J. J.; Rath, N. P. Org. Lett. 2003, 5, 2011; (b) Pegge, F. C.;
Coniglio, J. J.; Rath, N. P. J. Org. Chem. 2004, 69, 1161.