Neighboring group effect of five-membered heteroaromatic rings for π-facial selectivity in the reactions of fused isopropylidenenorbornene systems with electrophilic reagents

Article abstract of DOI:10.1016/S0040-4020(01)00916-4

The electrophilic reactions of novel isopropylidenenorbornadienes and isopropylidenenorbornenes fused with a furan, pyrrole, thiophene, and pyrazole ring with 1,2,4-triazole-3,5-(4H)-dione, m-chloroperbenzoic acid, dichlorocarbene, and N-bromosuccinimide

Full text of DOI:10.1016/S0040-4020(01)00916-4

TETRAHEDRON
Pergamon
Tetrahedron 57 *2001) 9073±9085
Neighboring group effect of ®ve-membered heteroaromatic rings
for p-facial selectivity in the reactions of fused isopropyl-
idenenorbornene systems with electrophilic reagents
Tomoshige Kobayashi,p Takeo Tsuzuki, Yoko Tayama and Yosuke Uchiyama
Department of Chemistry, Faculty of Science, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan
Received 27 August 2001; accepted 11 September 2001
AbstractÐThe electrophilic reactions of novel isopropylidenenorbornadienes and isopropylidenenorbornenes fused with a furan, pyrrole,
thiophene, and pyrazole ring with 1,2,4-triazole-3,5-*4H)-dione, m-chloroperbenzoic acid, dichlorocarbene, and N-bromosuccinimide *NBS)
indicated that the neighboring group effect of the ®ve-membered heteroaromatic rings was, unexpectedly, almost similar to that of a benzene
ring except for the reaction with NBS. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Although numerous experimental and theoretical studies on
the p-facial stereoselectivity have been reported,1 essen-
tially no attention has been paid to the possible control of
p-facial selectivity by a neighboring heteroaromatic ring.
Recently, we reported the electrophilic reactions of iso-
propylidenenorbornadienes 3 and 5, and isopropylidene-
norbornenes 4 and 6, fused with six-membered hetero-
aromatic rings such as pyridazine and pyrazine.2 In these
reactions, the predominant syn selectivity, which can not be
attained by the benzene-fused congeners 1 and 2,3 was
realized probably due to the positive electrostatic potential
®eld over the electron-de®cient heteroaromatic rings. On the
other hand, ®ve-membered heteroaromatics are generally
recognized to be electron-excessive, and the higher anti
preference than the benzene-fused congeners might be
expected in the electrophilic reactions of isopropylidene-
norbornenes fused with these rings. In due course of our
studies on the neighboring group participation of hetero-
aromatic rings,4±11 we wish to describe here the syntheses
of isopropylidenenorbornadienes and isopropylidene-
norbornenes 7±16 fused with a furan, pyrrole, thiophene,
and pyrazole ring, and the reactions of them with 4-phenyl-
1,2,4-triazole-3,5*4H)-dione *PTAD), m-chloroperbenzoic
acid *MCPBA), dichlorocarbene, and N-bromosuccinimide
*NBS), in order to clarify the neighboring group effect of the
®ve-membered heteroaromatics for the p-facial selectivity
*Scheme 1).
Keywords: p-facial selectivity; neighboring group effect; electrophilic reac-
tion; isopropylidenenorbornene; heteroaromatic ring.
p
Corresponding author. Fax: 181-263-37-2470;
e-mail: tkobaya@gipac.shinshu-u.ac.jp
Scheme 1.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020*01)00916-4

9074
T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
be promising for the synthesis of the isopropylidene-
norbornene derivatives.
Our initial attempt to synthesize the furan 18 by treatment of
the aldehyde 17 with sodium borohydride, followed by the
acid-induced cyclization with Amberlyst-15, resulted in the
1
formation of a trace amount of oil. The H NMR spectrum
of the oil exhibiting dˆ1.50 *6H, s), 4.28 *2H, t, Jˆ2 Hz),
6.76 *2H, t, Jˆ2 Hz), and 7.01 *2H, s) seemed to be assign-
able to 18, but we could not obtain enough amount of 18
for the full characterization. Thus, we turned to the synthesis
of the diphenyl-substituted furan 7. The reductive cycli-
zation of 2,3-dibenzoyl-7-*1-methylethylidene) bicyclo-
[2.2.1]hepta-2,5-diene *19) in the presence of triethyl
phosphite provided the fused diphenylfuran 7 in 26%
yield. A similar treatment of 20 with triethyl phosphite
gave 8 in 69% yield *Scheme 2).
For the synthesis of the fused pyrroles 9 and 10, the alde-
hyde 17 was treated with p-toluidine to give the imine 21.
The reduction of 21 with sodium borohydride, and the
subsequent treatment with silica gel in benzene at room
temperature successfully provided the pyrrole 9 in 11%
overall yield from 21. On the other hand, the initial hydro-
genation of 21 in the presence of Pd/C, and the successive
treatments with sodium borohydride and silica gel afforded
the fused isopropylidenenorbornene 10 in 41% overall yield
from 21. In these reactions, we encountered dif®culty in
puri®cation of the intermediates 22±24, and we used them
to the next step without puri®cation.
Scheme 2. Reagents and conditions: *i) NaBH4, EtOH, rt; Amberlyst-15,
CH2Cl2, rt; *ii) P*OEt)3, o-dichlorobenzene, re¯ux.
1.1. Synthesis of the fused isopropylidenenorbornene
derivatives
The thiophene-fused isopropylidenenorbornadiene 11 *17%)
and isopropylidenenorbornene 12 *19%) were, respec-
tively, prepared by the double-Wittig reactions of the
We have reported the synthesis of the norbornadienes
fused with furans, pyrroles, thiophenes,8±10 and pyra-
zoles.11 Thus, the analogous synthetic pathways would
Scheme 3. Reagents and conditions: *i) p-toluidine, MgSO4, CH2Cl2, rt; *ii) NaBH4, EtOH, rt; *iii) SiO2, PhH, rt; *iv) H2, Pd/C, AcOEt, rt; *v) *Ph3P1CH2)2S
2Cl2 *27), BuLi, Et2O, 2788C to rt.

T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
9075
Scheme 4. Reagents and conditions: *i) PhH, re¯ux; *ii) CH2N2, Et2O±CH2Cl2, 08C; *iii) NaH, THF, 08C; *iv) NaH, MeI, THF, rt; *v) H2, Pd/C, AcOEt, rt.
isopropylidenenorbornene-2,3-dione 25 and isopropyl-
idenenorbornane-2,3-dione 26 with the ylide, which was
derived from dimethyl thioether-a,a0-bisphosphonium
dichloride *27) *Scheme 3).
provided the ene-reaction products 34 and 35, where
PTAD attacks exclusively from the syn face with respect
to the heteroaromatic rings. Although isopropylidenebenzo-
norbornadiene 1 was reported to give a single ene-reaction
product on treatment with PTAD, the stereochemistry was
ambiguous.12 In contrast, the stereochemistry of the ene-
reaction products 34 and 35 was clearly determined as
being syn by the observations of NOEs between the ole®nic
protons at the 5- and 6-positions and the methyl group by the
NOE differential spectroscopy.
The pyrazole-fused isopropylidenenorbornadiene 13 was
synthesized by a sequence of the Diels±Alder reaction of
6,6-dimethylfulvene *28) and ethynyl p-tolyl sulfone *29)
giving 30, the 1,3-dipolar cycloaddition reaction of 30 with
diazomethane, and the elimination of toluenesulfenic acid
from 31 with sodium hydride in THF. When the fused
pyrazole 13 was treated with sodium hydride and methyl
iodide, the 2-methyl isomer 15 and the 1-methyl isomer 32
were obtained in 41 and 31% yields, respectively. The
hydrogenation of 13 or 15 in the presence of Pd/C
underwent the selective reduction of the endocyclic double
bond to give 14 or 16 *Scheme 4).
The exclusive syn preference of these reactions was
assumed to be due to the existence of the endocyclic double
bond, that would stabilize a transition state of the reaction
by bishomoaromatic interaction of the p-systems. Thus, the
reactions of the fused isopropylidenenorbornenes 8 and 12,
where the endocyclic double bond potentially involved in
such stabilization is absent, were investigated. In these
reactions, a mixture of syn and anti products 36 and 37, or
38 and 39 was obtained with anti preference as expected.
Assignments of syn and anti con®guration of the products
were determined by the NOE measurements. Unfortunately,
the reaction of the fused pyrroles 9 and 10 with PTAD gave
the substitution products 40 and 41, respectively, and
no ene-reaction was observed. Similar reactions of the
pyrazole-fused isopropylidenenorbornadienes 13 and 15
with PTAD gave only syn isomers 42 and 43, while the
fused isopropylidenenorbornene 16 gave a mixture of syn
and anti isomers 44 and 45 in a ratio of 9:91 with anti
1.2. Electrophilic reactions of fused isopropylidene-
norbornene derivatives
The reactions of the fused isopropylidenenorbornene
derivatives with PTAD, MCPBA, dichlorocarbene, and
NBSwere investigated. The products and the ratios of syn
and anti isomers in these reactions are summarized in Table
1.
On treatment with PTAD, the furan- and thiophene-fused
isopropylidenenorbornadiene
7 and 11, respectively,
Table 1. Products and ratios of the syn and anti isomers in the electrophilic reactions of the fused isopropylidenenorbornenes
Substrates
Products
MCPBA *syn/anti)
PTAD *syn/anti)
CCl2 *syn/anti)
NBS* syn/anti)
7
8
9
10
11
12
13
15
1644
23
34 *100:0)
36137 *21:79)
40
46
47148 *14:86)
±
±
49
51152 *18:82)
±
±
±
17:83
±
±
±
±
58 *0:100)
±
60
±
59 *0:100)
±
41
±
53154 *61:39)
55156 *62:38)
±
35 *100:0)
38139 *28:72)
42 *100:0)
43 *100:0)
145 *9:91)
19:81
±
±
±
65:35
±
19:81

9076
T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
Scheme 5.
preference. Stereochemical assignment for the inseparable
mixture of 44 and 45 was based on the 1H chemical shifts of
the methyl and methylene protons at isopropenyl group: the
chemical shifts of the methyl *dˆ1.74) and the methylene
*dˆ4.92 and 5.06) groups in the anti isomer 45 are shielded
compared to those of the syn isomer 44 *dˆ1.90 for CH3
and dˆ5.18 and 5.22 for vCH2) due to the shielding effect
of the aromatic pyrazole ring *Scheme 5).
a ratio of 14:86 albeit in low yield *26%). In these reactions,
we could not isolate any other products, but a by-product
bearing benzoyl groups seemed to be formed possibly by an
oxidative ring-cleavage of the furan ring. Epoxidation of the
thiophene 12 with MCPBA provided a mixture of syn and
anti epoxides 51 and 52 with anti preference. The stereo-
1
chemistry of the epoxides was based on the H chemical
shifts of the methyl group: an epoxide bearing the shielded
methyl group *dˆ1.30) was assigned to be the anti epoxide
52, with respect to the syn epoxide 51 *dˆ1.37 for CH3). To
our surprise, the reaction of the thiophene-fused isopropyl-
idenenorbornadiene 11 with MCPBA unexpectedly
produced the thiophene S,S-dioxide 49 and no epoxidation
at the isopropylidene moiety was observed. We also
Although the epoxidation reaction of the furan 7 with
MCPBA gave the epoxide 46 as a single stereoisomer, the
yield was very low *11%) and the stereochemistry of 46
could not be determined. Treatment of 8 with MCPBA
provided a mixture of syn and anti epoxides 47 and 48 in

T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
9077
Scheme 7.
of the fused furan 8 and thiophene 12 with NBSexclusively
produced the anti ene-reaction products 58 and 59, respec-
tively. The NOE measurements of 58 or 59 exhibited no
NOE between the methyl group and the proton at the
5-position, in contrast to the fact that the NOEs are clearly
observed for most of the syn isomers formed by other
reactions. Furthermore, the 1H chemical shifts of the methyl
group *dˆ1.79 for 58 and dˆ1.75 for 59) are almost
identical to those of the anti isomers of the ene-reaction
products with PTAD *dˆ1.79 for 37 and dˆ1.71 for 39).
These results are suggestive of the anti con®guration of the
products. We again observed the formation of the substi-
tution product 60 on treatment of the fused pyrrole 10 with
NBS*Scheme 7).
The variations in syn and anti ratios depending on the fused
heteroaromatic rings and the electrophilic reagents would be
attributed to the relative stability of the corresponding tran-
sition states. The anti ratios for the reactions of 8 and 12
with PTAD as well as that of 12 with MCPBA are approxi-
mately equal or slightly less compared to those of the
benzene-fused analog 2 *Table 1). The anti preference of
the reactions with PTAD and MCPBA would be ascribed to
the neighboring group effect of ®ve-membered hetero-
aromatic rings stabilizing the transition states by the bis-
homoaromatic interaction *61 and 62).2,3 The pyrazole
ring of 16 seems to be most effective for the formation of
the anti isomer.
Scheme 6.
obtained a solid, the structure of which could be assigned to
the thiophene S-oxide 50 judging from the H NMR and
1
mass spectra. However, the compound 50 is thermally labile
as generally recognized for thiophene S-oxides,13,14 and the
reproducibility of 50 was rather low. Thus, we could not
make a full characterization for 50. The thiophenes 11 and
12 reacted with dichlorocarbene, which was generated by
the thermolysis of sodium trichloroacetate, to give the syn
isomers 53 and 55 as major components, respectively. Since
no isomerization between syn and anti adducts was
observed under the reaction conditions, the major syn
adducts are considered to be kinetically controlled products
*Scheme 6).
The addition reactions of dichlorocarbene would take place
by a HOMO±LUMO interaction *64). At the same time, an
electrostatic interaction between the electron-de®cient
carbon center of the carbene and the electron-rich thiophene
ring would account for syn preference of the reactions *65).3
Our calculations on the fused thiophene 12 and the fused
benzene 2 by the PM3 method indicated no signi®cant
difference of the electrostatic potential ®elds between
these compounds,15 which would account for a similar
syn/anti selectivity of the reactions.
In contrast to these reactions described above, the reactions

9078
T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
Scheme 8.
The exclusive anti preference in the reactions with NBScan
be explained as follows: the bromine±nitrogen bond in the
transition state 63 is almost dissociated and the developed
cationic charge on the bromine atom would be effectively
stabilized by ®ve-membered heteroaromatic rings. The
effect seems to be rather stronger than that of a benzene
ring, due to the electron-excessive heteroaromatic rings
*Scheme 8).
One index to evaluate the through-space interaction
between heteroaromatic rings and the isopropylidene
moiety at the ground state as depicted in 66 is the difference
in the 13C chemical shifts of the ole®nic carbons at iso-
propylidene group.16±19 *Fig. 1) The chemical shift differ-
ences of the fused furan 8 and thiophene 12 are slightly
smaller than that observed for 2, whereas those of the
fused pyrrole 10 and pyrazole 16 show larger values. Unfor-
tunately, we could not clarify the p-facial selectivity of the
fused pyrroles, but the trend in the difference of the 13C
chemical shifts is qualitatively comparable with that of the
p-facial selectivity observed in the reaction with PTAD,
probably because the transition state in the reactions with
PTAD would resemble to the nature of the ground state.
Previously, the neighboring group participation of ®ve-
membered heteroaromatic rings has been demonstrated
rather effective for the electrophilic addition reactions of
fused norbonradienes.10,11 Therefore, we had presumed, in
the beginning, that the increasing anti selectivity in the
electrophilic reactions of fused isopropylidenenorbornene
derivatives could be expected for the fused ®ve-membered
heteroaromatics compared to that of the benzene-fused
congener. However, the neighboring group effect of ®ve-
membered heteroaromatic rings for the p-facial selectivity
was found to be almost similar to that of a benzene ring,
except for the reaction with NBS. Further studies would be
necessary to clarify the reason why the effect of the ®ve-
membered rings is comparable.
2. Experimental
2.1. General
All mps were determined with a Yanagimoto hot-stage
apparatus. IR spectra were obtained with a JEOL
Diamond-20 spectrometer. NMR spectra were recorded
Figure 1. 13C Chemical shifts of the exocyclic double bonds in the fused
isopropylidenenorbornene derivatives 1, 2, and 7±16.

T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
9079
with a JEOL JNM-LA400 *1H: 400 MHz, 13C: 100 MHz)
spectrometer using TMSas internal standard. J values are
mixture was concentrated and the residue was separated by
column chromatography *alumina, hexane±ethyl acetate
5/1) to give 21 *0.87 g, 49%): a slightly yellow solid
*from hexane); mp 100.5±101.58C; IR *KBr) 2974, 2925,
2914, 2881, 1624, 1572, 1504, 1336, 1281, 1180, 1122,
1
given in Hz. Assignments of the H and 13C signals are
based on DEPT, H±H COSY, and C±H COSY measure-
ments. Mass spectra were measured with a Shimadzu
GCMS-QP1000EX spectrometer operating in the electron
impact mode *70 eV). Elemental analyses were performed
with a Perkin±Elmer Model 240 apparatus. High-resolution
mass spectra *HR-MS) were taken with a JEOL DX-300
spectrometer. MPLC separations were carried out by a
YAMAZEN YFLC-600-10V system with a YAMZEN
Ultra Packw Column *Si-40B, silica gel). Solvents were
dried and puri®ed by standards methods. Yields are based
on the isolated products with suf®cient purity.
1
1092, 1053, 1022 cm21; H NMR *CDCl3) dˆ1.21 *3H, t,
Jˆ7 Hz, CH3), 1.22 *3H, t, Jˆ7 Hz, CH3), 1.50 *3H, s,
CH3), 1.53 *3H, s, CH3), 2.34 *3H, s, CH3), 3.42±3.60
*4H, m, OCH2), 4.26 *1H, t, Jˆ2.5 Hz, 4-H), 4.81 *1H, t,
Jˆ2.5 Hz, 1-H), 5.45 *1H, s, CH), 6.91 *1H, m, 5-H), 7.02
*2H, m, 6-H), 7.06 *2H, d, Jˆ8.5 Hz), 7.15 *2H, d, Jˆ
8.5 Hz), 8.66 *1H, S, CHvN); 13C NMR *CDCl3) dˆ15.2
*CH3), 18.4 *CH3), 18.7 *CH3), 21.0 *CH3), 50.2 *C-1), 52.5
*C-4), 61.1 *OCH2), 61.2 *OCH2), 98.7 *C), 99.1 *CH),
121.0, 129.7, 135.4, 141.9 *C-5), 142.6 *C-6), 150.2,
151.1, 154.2 *CHvN), 159.7, 161.1; MS m/z *rel intensity)
351 *17, M1), 322 *100, M2Et), 306 *18, M2OEt), 118
*32, CHvN-tolyl). Found: C, 78.57; H, 8.61; N, 4.00%.
Calcd for C23H29NO2: C, 78.60; H, 8.32; N, 3.98%.
2.1.1. 4,7-Dihydro-8-.1-methylethylidene)-1,3-diphenyl-
4,7-methanoisobenzofuran .7). A solution of 2,3-diben-
zoyl-7-*1-methylethylidene)bicyclo[2.2.1]hepta-2,5-diene2
*19) *170 mg, 0.5 mmol) and triethyl phosphite *0.25 cm3,
1.5 mmol) in o-dichlorobenzene *5 cm3) was re¯uxed for
30 min under a nitrogen atmosphere. The mixture was
concentrated and the residue was separated by TLC *silica
gel, hexane±ethyl acetate 5/1) to give 7 *42 mg, 26%):
orange prisms *from ethanol); mp 168.5±169.58C; IR
2.1.4.
4,7-Dihydro-8-.1-methylethylidene)-2-.p-tolyl)-
4,7-methano-2H-isoindole .9). To a solution of the imine
21 *0.53 g, 1.5 mmol) in ethanol *20 cm3) was added
sodium borohydride *0.08 g, 2 mmol), and the mixture
was stirred at room temperature for 30 min. The mixture
was concentrated and benzene *30 cm3) was added to the
residue. The organic phase was washed with water and brine
prior to drying with Na2SO4. Insoluble materials were
removed by ®ltration, and the ®ltrate was stirred at room
temperature for 1 h in the presence of silica gel *1.5 g). After
removal of the solvent, the residue was separated by column
chromatography *silica gel, dichloromethane) to give 9
*0.20 g, 11%): colorless plates *from ethanol); mp 136±
*KBr) 3008, 2974, 1601, 1493, 1444 cm21 1H NMR
;
*CDCl3) dˆ1.62 *6H, s, CH3), 4.57 *2H, s, 4-H and 7-H),
6.89 *2H, s, 5-H and 6-H), 7.23 *2H, m), 7.40 *4H, m), 7.72
*4H, m); 13C NMR *CDCl3) dˆ19.5 *CH3), 44.7 *C-4 and
C-7), 105.1 *C-9), 124.0, 126.7, 128.6, 131.4, 134.0 *C-3a
and C-7a), 141.2 *C-1 and C-3), 141.4 *C-5 and C-6), 156.7
*C-8); MS m/z *rel intensity) 324 *100, M1), 309 *15,
M2CH3), 105 *39, COPH), 77 *51, Ph). Found: C, 88.92;
H, 6.35%. Calcd for C24H20O: C, 88.85; H, 6.21%.
1
1378C; IR *KBr) 3008, 2974, 1601, 1493, 1444 cm21; H
2.1.2. 4,5,6,7-Tetrahydro-8-.1-methylethylidene)-1,3-di-
phenyl-4,7-methanoisobenzofuran .8). A solution of
2,3-dibenzoyl-7-*1-methylethylidene)bicyclo[2.2.1]hept-2-
ene2 *20) *340 mg, 1 mmol) and triethyl phosphite *0.5 cm3,
3 mmol) in o-dichlorobenzene *10 cm3) was re¯uxed for 1 h
under a nitrogen atmosphere. The mixture was concentrated
and the residue was passed through a short column *silica
gel, benzene). The eluent was concentrated and the resulting
solid was collected by suction to give 8 *230 mg, 69%): a
white solid *from methanol); mp 184±1858C; IR *KBr)
NMR *CDCl3) dˆ1.59 *6H, s, CH3), 2.32 *3H, s, CH3), 4.32
*2H, t, Jˆ2 Hz, 4-H and 7-H), 6.77 *2H, s, 1-H and 3-H),
6.87 *2H, t, Jˆ2 Hz, 5-H and 6-H), 7.12 *2H, d, Jˆ8.5 Hz,
tolyl), 7.17 *2H, d, Jˆ8.5 Hz, tolyl); 13C NMR *CDCl3)
dˆ19.3 *CH3), 20.8 *CH3), 44.7 *C-4 and C-7), 101.5
*C-9), 109.9 *C-1 and C-3), 119.7, 129.8, 133.7 *C-3a and
C-7a), 136.2, 139.1, 143.0 *C-5 and C-6), 159.2 *C-8); MS
m/z *rel intensity) 261 *100, M1), 91 *31, C7H7). Found: C,
87.54; H, 7.40; N, 5.19%. Calcd for C19H19N: C, 87.31; H,
7.33; N, 5.36%.
1
2997, 2966, 1603, 1493, 1444, 1109, 1061 cm21; H NMR
*CDCl3) dˆ1.52 *2H, dm, Jˆ7 Hz, 5-Hendo and 6-Hendo),
1.68 *6H, s, CH3), 2.02 *2H, dm, Jˆ7 Hz, 5-Hexo and
6-Hexo), 4.05 *2H, t, Jˆ2 Hz, 4-H and 7-H), 7.22 *2H, m),
7.40 *4H, m), 7.72 *4H, m); 13C NMR *CDCl3) dˆ20.3
*CH3), 22.7 *C-5 and C-6), 38.8 *C-4 and C-7), 112.6
*C-9), 124.0, 126.4, 128.6, 131.7, 132.0, 140.5 *C-1 and
C-3), 147.4 *C-8); MS m/z *rel intensity) 326 *100, M1),
311 *15, M2CH3), 298 *97, M2CH2CH2), 105 *21, COPh),
77 *34, Ph). Found: C, 88.35; H, 6.78%. Calcd for C24H22O:
C, 88.31; H, 6.79%.
2.1.5. 4,5,6,7-Tetrahydro-8-.1-methylethylidene)-2-.p-
tolyl)-4,7-methano-2H-isoindole .10). Under a hydrogen
atmosphere, a mixture of the imine 21 *1.05 g, 3 mmol)
and Pd/C *10%, 25 mg) in ethyl acetate *40 cm3) was stirred
at room temperature for 4 h. Insoluble materials were
removed by ®ltration through celite, and the ®ltrate was
concentrated to give the imine 23 as a yellow oil; 1H
NMR *CDCl3) dˆ1.22 *3H, t, Jˆ7 Hz), 1.23 *3H, t, Jˆ
7 Hz), 1.33 *2H, m), 1.58 *3H, s), 1.61 *3H, s), 1.82 *2H,
m), 2.32 *3H, a), 3.49±3.69 *5H, m), 4.08 *1H, m), 5.41 *1H,
s), 7.04 *2H, d, Jˆ8 Hz), 7.13 *2H, d, Jˆ8 Hz), 8.60 *1H, s);
13C NMR *CDCl3) dˆ14.9, 15.0, 19.1, 19.4, 20.7, 25.7,
26.6, 42.3, 44.7, 60.4, 61.4, 98.3, 109.2, 120.7, 129.3,
134.0, 144.9, 145.3, 150.2, 152.7, 154.1; MS m/z *rel
intensity) 353 *3, M1), 296 [100, M2CH3±C*CH3)2], 250
[70, M2CH*OEt)2].
2.1.3. N-[3-.Diethoxymethyl)-7-.1-methylethylidene)bi-
cyclo[2.2.1]hepta-2,5-dien-2-yl]methylidene-N-.p-tolyl)-
amine .21). A mixture of 3-*diethoxymethyl)-7-*1-methyl-
ethylidene)bicyclo[2.2.1]hepta-2,5-diene-2-carbaldehyde2
*17) *1.31 g, 5 mmol), p-toluidine *0.54 g, 5 mmol), and
anhydrous magnesium sulfate *0.5 g) in chloroform
*10 cm3) was stirred at room temperature for 30 min. The
To the crude 23 was added ethanol *40 cm3) and sodium

9080
T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
borohydride *0.15 g, 4 mmol), and the mixture was stirred at
room temperature for 1 h. The mixture was concentrated
and benzene *50 cm3) was added to the residue. The organic
phase was washed with water and brine prior to drying with
Na2SO4. Insoluble materials were removed by ®ltration, and
the ®ltrate was stirred at room temperature for 14 h in the
presence of silica gel *12 g). After removal of the solvent,
the residue was separated by column chromatography *silica
gel, benzene) to give 10 *0.32 g, 41% from 21): colorless
plates *from methanol); mp 122±122.58C; IR *KBr) 2991,
phase was separated. The aqueous layer was extracted with
ether, and the combined organic phases were washed with
water prior to drying with Na2SO4. After removal of the
solvent, the residue was separated by MPLC *hexane) and
the resulting oil was distilled *bath temperature 1008C,
0.5 Torr) with a Kugelrohr apparatus to give 12 *0.11 g,
19%): colorless rods; mp 56±588C; IR *KBr) 3005, 2962,
2933, 2861, 1369, 1358, 1286 cm21; 1H NMR *CDCl3) dˆ
1.31 *2H, dm, Jˆ7 Hz, 5-Hendo and 6-Hendo), 1.61 *6H, s,
CH3), 1.88 *2H, dm, Jˆ7 Hz, 5-Hexo and 6-Hexo), 3.76 *2H, t,
Jˆ2.5 Hz, 4-H and 7-H), 6.71 *2H, s, 1-H and 3-H); 13C
NMR *CDCl3) dˆ20.1 *CH3), 28.1 *C-5 and C-6), 41.3 *C-4
and C-7), 110.5 *C-1 and C-3), 112.2 *C-9), 147.7 *C-8),
149.3 *C-3a and C-7a); MS m/z *rel intensity) 190 *41, M1),
175 *100, M2CH3), 162 *80, M2CH2CH2). Found: C,
75.96; H, 7.62%. Calcd for C12H14S: C, 75.74; H, 7.41%.
2968, 2931, 2863, 1523, 1338, 1028 cm21 1H NMR
;
*CDCl3) dˆ1.32 *2H, dm, Jˆ6.5 Hz, 5-Hendo and 6-Hendo),
1.64 *6H, s, CH3), 1.88 *2H, dm, Jˆ6.5 Hz, 5-Hexo and
6-Hexo), 2.32 *3H, s, CH3), 3.76 *2H, m, 4-H and 7-H),
6.70 *2H, s, 1-H and 3-H), 7.14 *2H, d, Jˆ8.5 Hz, tolyl),
7.19 *2H, d, Jˆ8.5 Hz, tolyl); 13C NMR *CDCl3) dˆ20.2
*CH3), 20.8 *CH3), 29.1 *C-5 and C-6), 38.7 *C-4 and C-7),
108.2 *C-1 and C-3), 109.9 *C-9), 119.9, 129.9, 133.8, 134.2
*C-3a and C-7a), 139.2, 149.4 *C-8); MS m/z *rel intensity)
263 *35, M1), 248 *52, M2CH3), 235 *100, M2CH2CH2).
Found: C, 86.82; H, 7.95; N, 5.29%. Calcd for C19H21N: C,
86.65; H, 8.04; N, 5.32%.
2.1.8. 7-.1-Methylethylidene)-2-.p-tolylsulfonyl)bicyclo-
[2.2.1]hepta-2,5-diene .30). A solution of 6,6-dimethyl-
fulvene23 *28) *0.75 g, 7 mmol) and ethynyl p-tolyl
sulfone24 *29) *0.90 g, 5 mmol) in benzene *20 cm3) was
re¯uxed for 48 h. After removal of the solvent, the residue
was separated by column chromatography *silica gel,
CH2Cl2). The resulting solid was collected by suction and
washed with hexane to give 30 *1.02 g, 71%): colorless
needles *from hexane±ethyl acetate 1/1); mp 108±1098C;
IR *KBr) 3027, 2979, 2911, 2854, 1546, 1311, 1297, 1174,
2.1.6. 4,7-Dihydro-8-.1-methylethylidene)-4,7-methano-
2-benzothiophene .11). To
a mixture of dimethyl
thioether-a,a0-bis*triphenylphosphonium) dichloride20 *27)
*3.93 g, 6 mmol) in ether *840 cm3) was added butyl lithium
*1.63 M hexane solution, 7.4 cm3, 12 mmol) during 10 min
at room temperature under a nitrogen atmosphere, and the
mixture was stirred at room temperature for 4 h. The
mixture was cooled to 2788C, and a solution of 7-*1-methyl-
ethylidene)bicyclo[2.2.1]hept-5-ene-2,3-dione21 *25) *0.97
g, 6 mmol) in ether *25 cm3) was added. The mixture was
warmed up to room temperature and further stirred for 60 h.
The reaction mixture was poured into water and the organic
phase was separated. The aqueous layer was extracted with
ether, and the combined organic phases were washed with
water prior to drying with Na2SO4. After removal of the
solvent, the residue was separated by MPLC *hexane±
dichloromethane 10/1) to give 11 *0.19 g, 17%): colorless
needles *from methanol); mp 87.5±888C; IR *KBr) 3091,
3066, 3012, 2968, 2925, 2908, 1369, 1346, 1290, 1219
1
1149 cm21; H NMR *CDCl3) dˆ1.32 *3H, s, CH3), 1.42
*3H, s, CH3), 2.43 *3H, s, CH3), 4.15 *1H, m, 1-H), 4.27 *1H,
m, 4-H), 6.74 *2H, m, 5-H and 6-H), 7.31 *2H, d, Jˆ8 Hz),
7.51 *1H, dd, Jˆ3 and 1 Hz, 3-H), 7.69 *2H, d, Jˆ8 Hz); 13C
NMR *CDCl3) dˆ18.2 *CH3), 18.4 *CH3), 21.6 *CH3), 50.6
*C-1), 51.8 *C-4), 99.4 *C-8), 127.8, 129.7, 136.2, 141.0
*C-5 or C-6), 142.2 *C-6 or C-5), 144.1, 151.6 *C-3),
156.8 *C-2), 162.2 *C-7); MS m/z *rel intensity) 286 *40,
M1), 271 *17, M2CH3), 131 *44, M2Ts), 106 *13, 28), 91
*100, C7H7), 65 *31, C5H5). Found: C, 71.41; H, 6.28%.
Calcd for C17H18O2S: C, 71.30; H, 6.34%.
2.1.9. 4,7-Dihydro-8-.1-methylethylidene)-4,7-methano-
2H-indazole .13). A solution of diazomethane in Et2O
*30 cm3), prepared from N-methyl-N-nitrosourea *2.06 g,
20 mmol), was added to a solution of 30 *858 mg,
3 mmol) in dichloromethane *100 cm3) at 08C. The mixture
was stirred at room temperature for 1 h. A small amount of
acetic acid was added to destroy excess diazomethane. The
mixture was concentrated, and the resulting solid was
collected by suction and washed with methanol to give the
1
cm21; H NMR *CDCl3) dˆ1.56 *6H, s, CH3), 4.22 *2H,
t, Jˆ2 Hz, 4-H and 7-H), 6.66 *2H, s, 1-H and 3-H), 6.79
*2H, t, Jˆ2 Hz, 5-H and 6-H); 13C NMR *CDCl3) dˆ19.2
*CH3), 46.8 *C-4 and C-7), 105.3 *C-9), 110.8 *C-1 and
C-3), 142.2 *C-5 and C-6), 151.6 *C-3a and C-7a), 157.3
*C-8); MS m/z *rel intensity) 188 *100, M1), 173 *60,
M2CH3), 134 *22, 2-benzothiophene). Found: C, 76.25;
H, 6.56%. Calcd for C12H12S: C, 76.55; H, 6.42%.
1
crude adduct 31 *728 mg): a tan solid; mp 148±1508C; H
NMR *CDCl3) dˆ1.34 *3H, s, CH3), 1.49 *3H, s, CH3), 2.48
*3H, s, CH3), 2.75 *1H, dd, Jˆ8 and 2 Hz, 3a-H), 3.26 *1H,
m, 4-H or 7-H), 3.75 *1H, m, 7-H or 4-H), 4.19 *1H, dd,
Jˆ19 and 3 Hz, 3-Hexo), 4.33 *1H, dd, Jˆ19 and 8 Hz,
3-Hendo), 6.46 *2H, t, Jˆ2 Hz, 5-H and 6-H), 7.40 *2H, d,
Jˆ8 Hz), 7.83 *2H, d, Jˆ8 Hz); 13C NMR *CDCl3) dˆ19.8
*CH3), 19.9 *CH3), 21.8 *CH3), 42.8 *C-3a), 48.7 *C-4 or
C-7), 49.2 *C-7 or C-4), 80.4 *C-3), 116.1 *C-7a), 123.2
*C-9), 129.6, 129.8, 133.1 *C-5 or C-6), 134.7, 138.2 *C-6
or C-5), 141.2 *C-8), 145.3; MS m/z *rel intensity) 328 *5,
M1), 313 *5, M2CH3), 300 *3, M2N2), 286 *3, M2
CH2N2), 222 *16, M228), 106 *45, 28), 91 *100, C7H7).
2.1.7.
4,5,6,7-Tetrahydro-8-.1-methylethylidene)-4,7-
methano-2-benzothiophene .12). To a mixture of dimethyl
thioether-a,a0-bis*triphenylphosphonium) dichloride *27)
*2.26 g, 3.5 mmol) in ether *700 cm3) was added butyl
lithium *1.63 M hexane solution, 4.3 cm3, 7 mmol) during
10 min at room temperature under a nitrogen atmosphere,
and the mixture was stirred at room temperature for 6 h. The
mixture was cooled to 2788C, and a solution of 7-*1-methyl-
ethylidene)bicyclo[2.2.1]heptane-2,3-dione22 *26) *0.57 g,
3.5 mmol) in ether *50 cm3) was added. The mixture was
warmed up to room temperature and further stirred for 36 h.
The reaction mixture was poured into water and the organic
A mixture of the crude adduct 31 *728 mg) and sodium

T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
9081
hydride *60%, 196 mg, 5 mmol) in THF *3 cm3) was stirred
at 08C for 2 h. Aqueous ammonium chloride *10 cm3) was
added and the product was extracted with dichloromethane.
The organic phase was washed with water and brine prior to
drying with Na2SO4. After removal of the solvent, the
resulting solid was collected by suction to give 13
*314 mg, 61% from 30): colorless needles *from diethyl
ether); mp 152±1538C; IR *KBr) 3166 *NH), 3068, 3014,
2997, 2908, 2852, 1577, 1560, 1479, 1438, 1396, 1369,
1286, 1272, 1211, 1166, 1157, 1141, 1083, 1076, 1020
methano-2H-indazole .14). A mixture of 13 *52 mg,
0.3 mmol) and Pd/C *10%, 2 mg) in ethyl acetate *15 cm3)
was stirred under a hydrogen atmosphere at room tempera-
ture for 24 h. Insoluble materials were removed by ®ltration
through celite, and the ®ltrate was concentrated. Recrystal-
lization of the resulting solid from ether provided 14
*22 mg, 42%) as colorless needles: mp 150±1518C; IR
*KBr) 3139 *NH), 3039, 2997, 2865, 1581, 1471, 1461,
1407, 1371, 1298, 1272, 1160, 1147, 1114, 1079,
1022 cm21
;
1H NMR *CDCl3) dˆ1.26 *2H, m, 5-Hendo
1
cm21; H NMR *CDCl3) dˆ1.56 *6H, s, CH3), 4.34 *1H,
and 6-Hendo), 1.62 *3H, s, CH3), 1.63 *3H, s, CH3), 1.90
*2H, m, 5-Hexo and 6-Hexo), 3.83 *1H, d, Jˆ3 Hz, 4-H or
7-H), 3.89 *1H, d, Jˆ3 Hz, 7-H or 4-H), 7.11 *1H, s,
3-H), 9.66 *1H, br, NH); 13C NMR *CDCl3) dˆ19.9
*CH3), 20.1 *CH3), 27.3 *C-5 or C-6), 28.7 *C-6 or C-5),
38.2 *C-4 or C-7), 39.1 *C-7 or C-4), 111.1 *C-9), 118.8
*C-3), 126.4 *C-3a), 148.6 *C-8), 162.6 *C-7a); MS m/z
*rel intensity) 174 *21, M1), 159 *53, M2CH3), 146 *100,
M2CH2CH2). Found: C, 75.65; H, 8.40; N, 16.29%. Calcd
for C11H14N2: C, 75.82; H, 8.10; N, 16.08%.
d, Jˆ3 Hz, 4-H or 7-H), 4.36 *1H, d, Jˆ3 Hz, 7-H or 4-H),
6.89 *1H, dd, Jˆ5.5 and 3 Hz, 5-H or 6-H), 6.92 *1H, dd,
Jˆ5.5 and 3 Hz, 6-H or 5-H), 7.26 *1H, s, 3-H); 13C NMR
*CDCl3) dˆ19.0 *CH3), 19.2 *CH3), 43.8 *C-4 or C-7), 45.2
*C-7 or C-4), 102.6 *C-9), 118.7 *C-3), 129.8 *C-3a), 142.4
*C-5 or C-6), 144.6 *C-6 or C-5), 159.7 *C-8), 168.2 *C-7a);
MS m/z *rel intensity) 172 *74, M1), 157 *100, M2CH3),
144 *32, M2N2). Found: C, 76.57; H, 6.97; N, 16.10%.
Calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.27%.
2.1.10. N-Methylation reaction of 13. To a mixture of
sodium hydride *60%, 106 mg, 2.6 mmol) in THF *7 cm3)
was added a solution of 13 *278 mg, 1.6 mmol) in THF
*7 cm3) and the mixture was stirred at room temperature
for 20 min. Methyl iodide *572 mg, 4 mmol) was added
and the mixture was stirred at room temperature for 6 h.
Water was added and the products were extracted with
dichloromethane. The organic phase was washed with
water and brine prior to drying with Na2SO4. After removal
of the solvent, the residue was separated by column
chromatography *silica gel, benzene±ethyl acetate 1/2)
to give 4,7-dihydro-2-methyl-8-*1-methylethylidene)-4,7-
methano-2H-indazole *15) *123 mg, 41%) and 4,7-di-
hydro-1-methyl-8-*1-methylethylidene)-4,7-methano-1H-
indazole *32) *94 mg, 31%).
2.1.12. 4,5,6,7-Tetrahydro-2-methyl-8-.1-methylethyl-
idene)-4,7-methano-2H-indazole .16). By a similar pro-
cedure to that described for 14, treatment of 15 *174 mg,
1 mmol) with Pd/C *10%, 6 mg) in ethyl acetate *25 cm3)
under a hydrogen atmosphere provided 16 *89 mg, 50%): a
white solid *from ether): mp 83±838C; IR *KBr) 3014, 2972,
2863, 1571, 1461, 1384, 1376, 1371, 1282, 1176, 1155,
1116 cm21
;
1H NMR *CDCl3) dˆ1.23 *2H, m, 5-Hendo
and 6-Hendo), 1.59 *6H, s, CH3), 1.90 *2H, m, 5-Hexo and
6-Hexo), 3.77 *4H, m, N±CH3 and 4-H or 7-H), 3.81 *1H,
d, Jˆ3 Hz, 7-H or 4-H), 6.88 *1H, s, 3-H); 13C NMR
*CDCl3) dˆ19.8 *CH3), 20.0 *CH3), 27.4 *C-5 or C-6),
28.8 *C-6 or C-5), 38.2 *N±CH3), 38.4 *C-4 or C-7), 39.2
*C-7 or C-4), 110.6 *C-9), 120.6 *C-3), 126.9 *C-3a), 148.5
*C-8), 162.5 *C-7a); MS m/z *rel intensity) 188 *27, M1),
173 *53, M2CH3), 160 *100, M2CH2CH2). Found: C,
76.39; H, 8.50; N, 14.92%. Calcd for C12H16N2: C, 76.55;
H, 8.57; N, 14.88%.
15: a colorless liquid; bp 1308C *bath temperature, 5 Torr),
IR *neat) 3010, 2975, 2869, 1570, 1455, 1446, 1373,
1
1290 cm21; H NMR *CDCl3) dˆ1.56 *6H, s, CH3), 3.74
*3H, s, N-CH3), 4.30 *1H, m, 4-H or 7-H), 4.32 *1H, m, 7-H
or 4-H), 6.88 *1H, m, 5-H or 6-H), 6.92 *1H, m, 6-H or 5-H);
13C NMR *CDCl3) dˆ19.0 *CH3), 19.2 *CH3), 38.1
*N±CH3), 44.1 *C-4 or C-7), 45.4 *C-7 or C-4), 101.9
*C-9), 121.2 *C-3), 130.2 *C-3a), 142.7 *C-5 or C-6),
144.8 *C-6 or C-5), 159.8 *C-8), 167.7 *C-7a); MS m/z
*rel intensity) 186 *100, M1), 185 *59, M2H), 171 *85,
M2CH3). Found: C, 77.41; H, 7.83; N, 15.30%. Calcd for
C12H14N2: C, 77.38; H, 7.58; N, 15.04%.
2.1.13. Reaction of 7 with 4-phenyl-1,2,4-triazole-
3,5.4H)-dione .33, PTAD). A solution of 7 *81 mg,
0.25 mmol) and 4-phenyl-1,2,4-triazole-3,5*4H)-dione25
*33) *66 mg, 0.38 mmol) in dichloromethane *10 cm3) was
stirred at room temperature for 30 min. After removal of the
solvent, the residue was separated by TLC *silica gel,
benzene) to give 34 *53 mg, 17%): a slightly tan solid
*from hexane±ether 1/1); mp 243.5±244.58C; IR *KBr)
3167, 3080, 3053, 2966, 2945, 2916, 2848, 1765, 1703,
1
1691, 1599, 1502, 1493, 1427 cm21; H NMR *CDCl3)
32: a white solid *from hexane); mp 111.5±1168C; IR *KBr)
dˆ1.92 *3H, s, CH3), 4.79 *2H, br s, 4-H and 7-H), 5.03
*1H, s, vCH2), 5.24 *1H, s, vCH2), 6.60 *2H, t, Jˆ2 Hz,
5-H and 6-H), 7.19±7.45 *11H, m, Ph), 7.72 *4H, m, Ph),
8.42 *1H, br, NH), NOE observed between CH3 and 5-H;
13C NMR *CDCl3) dˆ23.5 *CH3), 50.0 *C-4 and C-7), 96.5
*C-8), 116.5 *vCH2), 124.2, 125.6, 127.2, 128.2, 128.7,
129.1, 130.6, 131.1, 131.4, 137.7 *C-5 and C-6), 141.2,
143.9, 152.1 *CO), 153.6 *CO); MS m/z *rel intensity) 499
*75, M1), 323 *100, M233±H), 105 *41, COPh). Found: C,
76.73; H, 5.33; N, 8.24%. Calcd for C32H25N3O3: C, 76.94;
H, 5.04; N, 8.41%.
3012, 2977, 2933, 2908, 1540, 1440 cm21 1H NMR
;
*CDCl3) dˆ1.54 *6H, s, CH3), 3.85 *3H, s, N±CH3), 4.31
*2H, m, 4-H and 7-H), 6.88 *1H, m, 5-H or 6-H), 7.07 *1H,
m, 6-H or 5-H), 7.11 *1H, s, 3-H); 13C NMR *CDCl3) dˆ
18.8 *CH3), 19.0 *CH3), 37.4 *N±CH3), 45.0 *C-4 or C-7),
45.4 *C-7 or C-4), 99.9 *C-9), 130.2 *C-3), 133.8 *C-3a),
141.9 *C-5 or C-6), 147.2 *C-6 or C-5), 159.0 *C-8), 161.4
*C-7a); MS m/z *rel intensity) 186 *67, M1), 185 *50,
M2H), 171 *100, M2CH3). Found: C, 77.61; H, 7.73; N,
15.18%. Calcd for C12H14N2: C, 77.38; H, 7.58; N, 15.04%.
2.1.11. 4,5,6,7-Tetrahydro-8-.1-methylethylidene)-4,7-
2.1.14. Reaction of 11 with PTAD 33. A solution of 11

9082
T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
*47 mg, 0.25 mmol) and 33 *44 mg, 0.25 mmol) in dichloro-
methane *10 cm3) was stirred at room temperature for
30 min. After the removal of the solvent, the residue was
separated by TLC *silica gel, dichloromethane) to give 35
*53 mg, 58%): a white solid *from methanol); mp 236±
237.58C; IR *KBr) 3157, 3062, 2916, 2852, 1766, 1693,
separated by TLC *silica gel, dichloromethane±hexane 1/1)
to give 38 *23 mg, 25%) and 39 *60 mg, 65%).
38: a white powder *from hexane); mp 229±2308C; IR
*KBr) 3159, 3068, 2976, 2949, 2870, 1768, 1691, 1502,
1429 cm21
;
1H NMR *CDCl3) dˆ1.34 *2H, dm, Jˆ
1
1502, 1433 cm21; H NMR *CDCl3) dˆ1.86 *3H, s, CH3),
7.5 Hz, 5-Hendo and 6-Hendo), 1.90 *3H, s, CH3), 2.02 *2H,
d, Jˆ7.5 Hz, 5-Hexo and 6-Hexo), 3.99 *2H, s, 4-H and 7-H),
5.16 *1H, t, Jˆ1.5 Hz, vCH2), 5.19 *1H, br s, vCH2), 6.80
*2H, s, 1-H and 3-H), 7.33±7.47 *5H, m, Ph), 8.57 *1H, br,
4.39 *2H, br s, 4-H and 7-H), 5.06 *1H, br s, vCH2), 5.15
*1H, br s, vCH2), 6.55 *2H, t, Jˆ2 Hz, 5-H and 6-H), 6.75
*2H, s, 1-H and 3-H), 7.35±7.49 *5H, m, Ph), 9,11 *1H, br,
NH), NOE observed between CH3 and 5-H; 13C NMR
*CDCl3) dˆ23.3 *CH3), 51.7 *C-4 and C-7), 96.4 *C-8),
114.8 *C-1 and C-3), 116.2 *vCH2), 125.6, 128.3, 129.0,
131.1, 138.7 *C-5 and C-6), 141.3, 149.1, 151.5 *CO), 154.1
*CO); MS m/z *rel intensity) 363 *3, M1), 187 *100, M233±
H), 134 *27, 2-benzothiophene), 119 *16, PhNCO). Found:
C, 65.94; H, 4.98; N, 11.85%. Calcd for C20H17N3O2S : C,
66.10; H, 4.71; N, 11.56%.
NH), NOE observed between CH3 and 5-Hexo;
13C NMR
*CDCl3) dˆ19.6 *CH3), 26.0 *C-5 and C-6), 46.0 *C-4 and
C-7), 87.2 *C-8), 114.0 *C-1 and C-3), 117.0 *vCH2),
125.6, 128.1, 129.0, 131.2, 138.5, 146.8, 150.9 *CO),
153.9 *CO); MS m/z *rel intensity) 365 *3, M1), 189 *100,
M233±H). Found: C, 65.94; H, 5.38; N, 11.46%. Calcd for
C20H19N3O2S: C, 65.73; H, 5.24; N, 11.50%.
39: a white powder *from hexane); mp 245.5±2478C; IR
*KBr) 3174, 2929, 2868, 1778, 1710, 1502, 1414, 1354
2.1.15. Reaction of 8 with PTAD 33. A solution of 8
*82 mg, 0.25 mmol) and PTAD *53 mg, 0.3 mmol) in
dichloromethane *10 cm3) was stirred at room temperature
for 40 min. After removal of the solvent, the residue was
separated by TLC *silica gel, benzene) to give 36 *10 mg,
8%) and 37 *38 mg, 30%).
1
cm21; H NMR *CDCl3, 808C) dˆ1.45 *2H, d, Jˆ8 Hz,
5-Hendo and 6-Hendo), 1.71 *3H, s, CH3), 2.28 *2H, d, Jˆ
8 Hz, 5-Hexo and 6-Hexo), 4.02 *2H, br s, 4-H and 7-H),
4.88 *1H, s, vCH2), 4.98 *1H, s, vCH2), 6.77 *2H, s,
1-H and 3-H), 7.34±7.55 *5H, m, Ph), 8.33 *1H, br, NH);
13C NMR *CDCl3) dˆ21.8 *CH3), 27.1 *C-5 and C-6), 46.7
*C-4 and C-7), 83.8 *C-8), 113.7 *C-1 and C-3), 117.6
*vCH2), 125.8, 128.5, 129.3, 131.4, 140.4, 151.5 *CO),
154.0 *CO), 1C missing; MS m/z *rel intensity) 365 *2,
M1), 189 *100, M233-H). Found: C, 65.92; H, 5.18; N,
11.23%. Calcd for C20H19N3O2S: C, 65.73; H, 5.24; N,
11.50%.
36: a white powder *from hexane±ether 1/1); mp 288.5±
289.58C; IR *KBr) 3176, 3084, 3049, 3033, 2993, 2931,
1
2868, 1763, 1703, 1689, 1599, 1502, 1493, 1427 cm21; H
NMR *CDCl3) dˆ1.52 *2H, dm, Jˆ7.5 Hz, 5-Hendo and
6-Hendo), 1.96 *3H, s, CH3), 2.14 *2H, br d, Jˆ7.5 Hz,
5-Hexo and 6-Hexo), 4.37 *2H, br s, 4-H and 7-H), 5.20
*1H, br s, vCH2), 5.27 *1H, br s, vCH2), 7.18±7.44
*11H, m, Ph), 7.72 *4H, m, Ph), 8.45 *1H, br, NH), NOE
2.1.17. Reaction of 9 with PTAD 33. A solution of 9
*65 mg, 0.25 mol) and 33 *53 mg, 0.3 mmol) in dichloro-
methane *10 cm3) was stirred at room temperature for
30 min. The mixture was concentrated and the residue
was separated by TLC *silica gel, hexane±ethyl acetate
1/1) to give 40 *46 mg, 42%): a white solid *from
hexane±ether 9/1); mp 138±1408C; IR *KBr) 3490, 3006,
2920, 2854, 1778, 1722, 1711, 1516, 1502, 1408, 1336
observed between CH3 and 5-Hexo;
13C NMR *CDCl3)
dˆ19.7 *CH3), 25.9 *C-5 and C-6), 44.2 *C-4 and C-7),
87.7 *C-8), 117.4 *vCH2), 124.1, 125.6, 127.0, 128.1,
128.8, 129.0, 129.6, 130.9, 131.3, 138.4, 142.7, 151.3
*CO), 153.3 *CO); MS m/z *rel intensity) 501 *100, M1),
325 *10, M233±H), 105 *78, COPh), 77 *38, Ph). Found: C,
76.66; H, 5.65; N, 8.08%. Calcd for C32H27N3O3: C, 76.63;
H, 5.43; N, 8.38%.
1
cm21; H NMR *CDCl3) dˆ1.53 *3H, s, CH3), 1.57 *3H,
s, CH3), 2.32 *3H, s, CH3), 4.29 *1H, br s, 4-H or 7-H), 4.32
*1H, br s, 7-H or 4-H), 6.52 *1H, s, 3-H), 6.84 *2H, m, 5-H
and 6-H), 7.12±7.47 *9H, m); 13C NMR *CDCl3) dˆ19.2
*2C, CH3), 21.0 *CH3), 44.7 *C-4 or C-7), 45.0 *C-7 or C-4),
102.4 *C-9), 113.1, 113.2 *C-3), 125.1, 125.8, 128.4, 129.1,
130.0, 131.1, 134.8, 134.9, 136.1, 137.0, 142.4 *C-5 or C-6),
143.5 *C-6 or C-5), 151.1 *CO), 153.0 *CO), 158.9 *C-8);
MS m/z *rel intensity) 436 *100, M1), 259 *84, M233±2H),
119 *17, PhNCO), 91 *54, C7H7). Found: C, 74.51; H, 5.46;
N, 12.91%. Calcd for C27H24N4O2: C, 74.29; H, 5.54; N,
12.84%.
37: a white powder *from hexane); mp 300.5±3028C; IR
*KBr) 3172, 3055, 3033, 2997, 2945, 2854, 1765, 1703,
1
1691, 1597, 1493, 1433 cm21; H NMR *CDCl3, 608C)
dˆ1.67 *2H, d, Jˆ8.5 Hz, 5-Hendo and 6-Hendo), 1.79 *3H,
s, CH3), 2.43 *2H, br s, 5-Hexo and 6-Hexo), 4.40 *2H, br s,
4-H and 7-H), 4.91 *1H, s, vCH2), 5.11 *1H, s, vCH2),
7.21±7.25 *2H, m, Ph), 7.34±7.52 *7H, m, Ph), 7.64 *6H, m,
Ph), 9.62 *1H, br, NH); 13C NMR *CDCl3) dˆ22.0 *CH3),
26.7 *C-5 and C-6), 44.6 *C-4 and C-7), 84.8 *C-8),
117.3 *vCH2), 123.8, 125.3, 126.9, 128.2, 128.8, 129.1,
131.0, 136.3, 140.2, 142.2, 151.1 *CO), 153.5 *CO), 1C
missing; MS m/z *rel intensity) 501 *100, M1), 325 *16,
M233±H), 105 *60, COPh), 77 *35, Ph). Found: C, 76.86;
H, 5.67; N, 8.32%. Calcd for C32H27N3O3: C, 76.63; H, 5.43;
N, 8.38%.
2.1.18. Reaction of 10 with PTAD 33. A solution of 10
*66 mg, 0.25 mmol) and 33 *53 mg, 0.3 mmol) in dichloro-
methane *10 cm3) was stirred at room temperature for
30 min. The mixture was concentrated and the residue
was separated by TLC *silica gel, hexane±ethyl acetate
1/1) to give 41 *84 mg, 76%): a light tan solid *from
hexane); mp 180±1828C; IR *KBr) 3492, 3174, 2929,
2.1.16. Reaction of 12 with PTAD 33. A solution of 12
*48 mg, 0.25 mmol) and PTAD *50 mg, 0.29 mmol) in
dichloromethane *10 cm3) was stirred at room temperature
for 30 min. After removal of the solvent, the residue was
2862, 1778, 1711, 1502, 1414, 1354 cm21
;
1H NMR
*CDCl3) dˆ1.36 *2H, m, 5-Hendo and 6-Hendo), 1.60 *3H, s,

T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
9083
CH3), 1.63 *3H, s, CH3), 1.86 *2H, m, 5-Hexo and 6-Hexo),
2.33 *3H, s, CH3), 3.75 *1H, br d, Jˆ3 Hz, 4-H or 7-H), 3.77
*1H, br d, Jˆ3 Hz, 7-H or 4-H), 6.49 *1H, s, 3-H), 7.13±7.24
*4H, m), 7.34±7.47 *5H, m), 8.50 *1H, br, NH); 13C NMR
*CDCl3) dˆ20.1 *CH3), 20.2 *CH3), 21.0 *CH3), 28.1 *C-5
or C-6), 28.8 *C-6 or C-5), 38.6 *C-4 or C-7), 38.9 *C-7 or
C-4), 111.0 *C-1 or C-9), 111.6 *C-9 or C-1), 112.0 *C-3),
125.2, 125.8, 128.3, 129.1, 129.9, 131.1, 131.9, 132.3,
136.2, 137.1, 148.7 *C-8), 151.3 *CO), 153.0 *CO); MS
m/z *rel intensity) 438 *3, M1), 247 *16, M233±CH4),
119 *100, PhNCO), 91 *74, C7H7). Found: C, 73.71; H,
5.74; N, 12.73%. Calcd for C27H26N4O2: C, 73.95; H,
5.98; N, 12.78%.
*5 cm3) was stirred at room temperature for 1 h. After
removal of the solvent, and the resulting solid was collected
by suction and washed with ether to give a mixture of 44 and
45 *9:91, 71 mg, 68%): a white powder *from methanol);
decomp 2788C; IR *KBr) 3240 *NH), 1770, 1708, 1423,
1
1390 cm21; H NMR *CDCl3) dˆ1.25±1.44 *2H, m, 5-
Hendo and 6-Hendo), 1.73 *2.73H, s, 45 CH3), 1.90 *0.27H,
s, 44 CH3), 2.04 *0.18H, m, 44 5-Hexo and 6-Hexo), 2.28
*1.82H, m, 45 5-Hexo and 6-Hexo), 3.80 *2.73H, s, 45
N±CH3), 3.83 *0.27H, s, 44 N±CH3), 4.03 *0.18H, br s,
44 4-H and 5-H), 4.18 *1.92H, br s, 45 4-H and 5-H), 4.89
*0.91H, s, 45 vCH2), 5.05 *0.91H, s, 45 vCH2), 5.15
*0.09H, s, 44 vCH2), 5.21 *0.09H, s, 44 vCH2), 6.91
*0.91H, s, 45 3-H), 6.98 *0.09H, s, 44 3-H), 7.25±7.54
*5H, m, Ph), 9.46 *1H, br, NH); 13C NMR *CDCl3) dˆ
19.3 *44, CH3), 22.1 *45 CH3), 25.5 *44 C-5 or C-6), 26.5
*45 C-5 or C-6), 27.0 *44, C-6 or C-5), 28.0 *45 C-6 or C-5),
38.5 *N±CH3), 43.9 *44 C-4 or C-7), 44.3 *45 C-4 or C-7),
45.0 *44 C-7 or C-4), 45.5 *45 C-7 or C-4), 85.2 *45 C-8),
88.7 *44 C-8), 116.9 *44 vCH2), 117.2 *45 vCH2), 122.3,
123.3, 124.1, 125.0, 125.5, 125.7, 127.9, 128.2, 128.9,
129.1, 131.6, 131.8, 138.9, 140.9, 151.2, 151.8, 153.4,
153.7, 160.0, 161.2; MS m/z *rel intensity) 363 *2, M1),
188 *15, M233), 187 *100, M233±H). Found: C, 66.13;
H, 5.92; N, 19.23%. Calcd for C20H21N5O2: C, 66.10; H,
5.82; N, 19.27%.
2.1.19. Reaction of 13 with PTAD 33. A solution of 13
*52 mg, 0.3 mmol) and 33 *70 mg, 0.4 mmol) in dichloro-
methane *5 cm3) was stirred at room temperature for
30 min. After removal of the solvent, the residue was
separated by column chromatography *silica gel, ben-
zene±hexane 1/10) to give 42 *36 mg, 35%): a white
powder *from ethyl acetate); mp 168±1708C; IR *KBr)
3213, 3068, 2947, 2918, 2852, 1765, 1720, 1711, 1691,
1682, 1645, 1597, 1502, 1427, 1357, 1276, 1203, 1182,
1
1139, 1041, 1025 cm21; H NMR *CDCl3) dˆ1.95 *3H, s,
CH3), 4.38 *1H, d, Jˆ3 Hz, 4-H or 7-H), 4.94 *1H, d, Jˆ
3 Hz, 7-H or 4-H), 5.10 *1H, br s, vCH2), 5.28 *1H, br s,
vCH2), 6.79 *1H, dd, Jˆ5 and 3 Hz, 5-H or 6-H), 6.86 *1H,
dd, Jˆ5 and 3 Hz, 6-H or 5-H), 7.19 *1H, s, 3-H), 7.32 *1H,
m), 7.43 *4H, m), 11.10 *1H, br, NH), 11.90 *1H, br, NH),
NOE observed between CH3 and 5-H; 13C NMR *CDCl3)
dˆ23.7 *CH3), 49.3 *C-4 or C-7), 51.0 *C-7 or C-4), 99.8
*C-8), 116.1 *vCH2), 121.5 *C-3), 125.3, 128.0, 128.8
*C-3a), 129.0, 131.2, 137.5 *C-5 or C-6), 141.3 *vCMe),
142.9 *C-6 or C-5), 151.5 *CO), 154.6 *CO), 165.4 *C-7a);
MS m/z *rel intensity) 347 *39, M1), 303 *7, M2CONH2),
172 *27, M233), 171 *78, M233±H), 119 *100, PHNCO).
Found: C, 65.94; H, 4.84; N, 19.98%. Calcd for
C19H17N5O2: C, 65.70; H, 4.93; N, 20.16%.
2.1.22. Reaction of 7 with MCPBA. A solution of 7
*81 mg, 0.25 mmol) and MCPBA *70%, 62 mg, 0.25
mmol) in dichloromethane *15 cm3) was stirred at room
temperature for 1 h. The mixture was washed with aqueous
sodium sul®te, aqueous sodium carbonate, and brine prior to
drying with Na2SO4. After removal of the solvent, the
residue was separated by TLC *silica gel, benzene) to give
46 *9 mg, 11%); a white solid *from methanol); mp 140±
1428C; IR *KBr) 3080, 3060, 3010, 2960, 2920, 2850, 1597,
1
1493, 1440, 1057 cm21; H NMR *CDCl3) dˆ1.31 *6H, s,
CH3), 3.93 *2H, t, Jˆ2 Hz, 4-H and 7-H), 6.83 *2H, t, Jˆ
2 Hz, 5-H and 6-H), 7.26 *2H, m), 7.41 *4H, m), 7.71 *4H,
m); 13C NMR *CDCl3) dˆ20.7 *CH3), 46.1 *C-4 and C-7),
65.3 *CMe2), 98.5 *C-8), 124.0, 127.0, 128.8, 129.8, 131.0,
138.0 *C-5 and C-6), 142.1 *C-1 and C-3); MS m/z *rel
intensity) 340 *11, M1), 270 *100, M2acetone±CH2), 105
*10, COPh). HR-MS*FAB 1) Found: 341.1557. Calcd for
C24H22O21H: 341.1542.
2.1.20. Reaction of 15 with 33. A solution of 15 *99 mg,
0.5 mmol) and 33 *147 mmol, 0.8 mmol) in dichloro-
methane *5 cm3) was stirred at room temperature for 5 h.
After removal of the solvent, the resulting solid was recrys-
tallized from benzene to give 43 *89 mg, 46%): a white solid
*from benzene); mp 139±1408C; IR *KBr) 3220, 2983,
1
2948, 2819, 1770, 1720, 1710, 1496, 1427, 1382 cm21; H
NMR *CDCl3) dˆ1.88 *3H, s, CH3), 3.81 *3H, s, N±CH3),
4.35 *1H, br s, 4-H or 7-H), 4.58 *1H, br s, 7-H or 4-H), 5.07
*1H, br s, vCH2), 5.18 *1H, br s, vCH2), 6.67 *1H, m, 5-H
or 6-H), 6.72 *1H, m, 6-H or 5-H), 7.00 *1H, s, 3-H), 7.26±
7.44 *5H, m), 8.84 *1H, br, NH), NOE observed between
CH3 and 5-H; 13C NMR *CDCl3) dˆ23.3 *CH3), 38.3 *N±
CH3), 49.7 *C-4 or C-7), 50.9 *C-7 or C-4), 99.8 *C-8), 116.0
*vCH2), 124.0 *C-3), 125.4, 127.9, 128.4 *C-3a), 129.9,
131.3, 138.7 *C-5 or C-6), 141.6 *vCMe), 141.8 *C-6 or
C-5), 152.0 *CO), 153.3 *CO), 166.4 *C-7a); MS m/z *rel
intensity) 361 *8, M1), 317 *6, M2CONH2), 186 *19,
M233), 185 *100, M233±H), 119 *33, PhNCO). Found:
C, 66.45; H, 5.60; N, 19.48%. Calcd for C20H19N5O2: C,
66.47; H, 5.30; N, 19.38%.
2.1.23. Reaction of 8 with MCPBA. A solution of 8
*82 mg, 0.25 mmol) and MCPBA *70%, 62 mg, 0.25
mmol) in dichloromethane *15 cm3) was stirred at room
temperature for 1 h. The mixture was washed with aqueous
sodium sul®te, aqueous sodium carbonate, and brine prior to
drying with Na2SO4. After removal of the solvent, the
residue was separated by TLC *silica gel, benzene) to give
a mixture of 47 and 48 *22 mg, 26%, 47±48ˆ14:86): a
white solid *from methanol); mp 161±1628C; IR *KBr)
3080, 3060, 3035, 3024, 2999, 2976, 2937, 2860, 1599,
1
1493, 1446 cm21; H NMR *CDCl3) dˆ1.35 *5.16H, s,
48 CH3), 1.44 *0.84H, s, 47 CH3), 1.59 *2H, m, 5-Hendo
and 6-Hendo), 2.12 *0.28H, dm Jˆ7.5 Hz, 47 5-Hexo and
6-Hexo), 2.37 *1.72H, dm Jˆ7.5 Hz, 48 5-Hexo and 6-Hexo),
3.24 *2H, m, 4-H and 7-H), 7.18±7.26 *2H, m), 7.35±7.43
*4H, m), 7.69±7.72 *4H, m); 13C NMR *CDCl3) dˆ20.8 *47
CH3), 21.7 *48 CH3), 25.3 *47 C-5 and C-6), 26.2 *48 C-5
2.1.21. Reaction of 16and 33. A solution of 16 *53 mg,
0.3 mmol) and 33 *71 mg, 0.4 mmol) in dichloromethane

9084
T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
and C-6), 39.0 *47 C-4 and C-7), 39.2 *48 C-4 and C-7), 62.3
*47 CMe2), 63.0 *48 CMe2), 86.6 *48 C-8), 89.7 *47 C-8),
123.9, 124.0, 126.6, 126.8, 128.2, 128.6, 128.7, 128.8,
131.3, 131.4, 141.9 *48 C-1 and C-3), 142.3 *47 C-1 and
C-3); MS m/z *rel intensity) 342 *58, M1), 271 *100,
M2acetone±CH), 105 *68, COPh). Found: C, 84.28; H,
6.60%. Calcd for C24H22O2: C, 84.18; H, 6.48%.
duced into the mixture in every 10 min and a total amount
*920 mg, 5 mmol) of the sodium trichloroacetate was added.
Water was added and the mixture was extracted three times
with ether. The combined organic layers were washed with
aqueous sodium sul®te, aqueous ammonium chloride, and
brine prior to drying with Na2SO4. After removal of the
solvent, the residue was separated by TLC *silica gel,
hexane) to give 53 *24 mg, 35%) and 54 *15 mg, 22%).
2.1.24. Reaction of 11 with MCPBA. A solution of 11
*47 mg, 0.25 mmol) and MCPBA *62 mg, 0.25 mmol) in
dichloromethane *10 cm3) was stirred at room temperature
for 1 h. The mixture was washed with aqueous sodium sul-
®te, aqueous sodium carbonate, and brine prior to drying
with Na2SO4. After removal of the solvent, the residue was
puri®ed by TLC *silica gel, benzene) to give 49 *10 mg,
20%): a white solid *from pentane); mp 205.5±206.58C;
IR *KBr) 3159, 3111, 3091, 3062, 3014, 2981, 2918,
2854, 1606, 1452, 1373, 1281, 1176, 1146, 1099, 1058
53: a white powder *from methanol); mp 99±1018C; IR
*KBr) 3089, 3074, 3026, 3012, 3003, 2996, 2968, 2929,
2873, 1375, 1350, 1288, 1144, 1126 cm21 1H NMR
;
*CDCl3) dˆ1.12 *6H, s, CH3), 3.65 *2H, t, Jˆ2 Hz, 4-H
and 7-H), 6.72 *2H, s, 1-H and 3-H), 6.81 *2H, t, Jˆ2 Hz,
5-H and 6-H), NOE observed between CH3 and 5-Hexo;
13C
NMR *CDCl3) dˆ19.0 *CH3), 30.9 *CMe2), 48.2 *C-4 and
C-7), 69.2 *C-8), 76.0 *CCl2), 112.1 *C-1 and C-3), 140.7
*C-5 and C-6), 150.2 *C-3a and C-7a); MS m/z *rel intensity)
270/272/274 *1.2/0.8/0.2, M1), 235/237 *100/39, M2Cl),
134 *44, 2-benzothiophene). Found: C, 57.64; H, 4.26%.
Calcd for C13H12Cl2S: C, 57.57; H, 4.46%.
1
cm21; H NMR *CDCl3) dˆ1.64 *6H, s, CH3), 4.22 *2H,
t, Jˆ2 Hz, 4-H and 7-H), 6.15 *2H, s, 1-H and 3-H), 6.39
*2H, t, Jˆ2 Hz, 5-H and 6-H); 13C NMR *CDCl3) dˆ20.2
*CH3), 44.8 *C-4 and C-7), 115.3 *C-5 and C-6), 119.4
*C-9), 136.6 *C-1 and C-3), 140.5 *C-8), 146.0 *C-3a and
C-7a); MS m/z *rel intensity) 220 *36, M1), 172 *65,
M22O±CH4), 91 *100, C7H7). Found: C, 65.19; H,
5.60%. Calcd for C12H12O2S: C, 65.43; H, 5.49%.
54: a white powder *from methanol); mp 146.5±148.58C; IR
*KBr) 2993, 2958, 2925, 2852, 1373 cm21 1H NMR
;
*CDCl3) dˆ1.29 *6H, s, CH3), 3.60 *2H, t, Jˆ2 Hz, 4-H
and 7-H), 6.71 *2H, t, Jˆ2 Hz, 5-H and 6-H), 6.79 *2H, s,
1-H and 3-H); 13C NMR *CDCl3) dˆ20.2 *CH3), 30.0
*CMe2), 48.3 *C-4 and C-7), 70.4 *C-8), 75.7 *CCl2),
112.5 *C-1 and C-3), 140.8 *C-5 and C-6), 150.1 *C-3a
and C-7a); MS m/z *rel intensity) 270/272/274 *4/2/0.5,
M1), 235/237 *100/38, M2Cl), 134 *57, 2-benzo-
thiophene). Found: C, 57.49; H, 4.34%. Calcd for
C13H12Cl2S: C, 57.57; H, 4.46%.
A small amount of a white solid which could be assignable
to 50 was also obtained; 1H NMR *CDCl3) dˆ1.72 *6H, s),
3.92 *2H, t, Jˆ2 Hz), 6.70 *2H, s), 6.76 *2H, t, Jˆ2 Hz); MS
m/z *rel intensity) 204 *21, M1), 175 *100, M2C2H5). HR-
MS*FAB 1) found: 205.0713. Calcd for C12H12OS1H:
205.0687.
2.1.25. Reaction of 12 with MCPBA. A solution of 12
*48 mg, 0.25 mmol) and MCPBA *70%, 87 mg, 0.35
mmol) in dichloromethane *10 cm3) was stirred at room
temperature for 1 h. The mixture was washed with aqueous
sodium sul®te, aqueous sodium carbonate, and brine prior to
drying with Na2SO4. After removal of the solvent, the
residue was puri®ed by TLC *silica gel, hexane) to give a
mixture of 51 and 52 *42 mg, 81%, 51±52ˆ18:82): a white
powder *from methanol); mp 121±1228C; IR *KBr) 3006,
2.1.27. Reaction of 12 with sodium trichloroacetate. By a
similar procedure to that described above, the reaction of 12
*48 mg, 0.25 mmol) and sodium trichloroacetate *920 mg,
5 mmol) provided 55 *35 mg, 51%) and 56 *21 mg, 30%).
55: a white powder *from methanol); mp 145±1468C; IR
*KBr) 2966, 2951, 2937, 2866, 1464, 1452, 1371, 1363,
1
1162, 1103 cm21; H NMR *CDCl3) dˆ1.30 *6H, s, CH3),
1.46 *2H, dm, Jˆ7.5 Hz, 5-Hendo and 6-Hendo), 1.98 *2H, dm,
Jˆ7.5 Hz, 5-Hexo and 6-Hexo), 3.15 *2H, t, Jˆ2 Hz, 4-H and
7-H), 6.82 *2H, s, 1-H and 3-H), NOE observed between
1
2993, 2979, 2933, 2868, 1375, 1360, 1117 cm21; H NMR
*CDCl3) dˆ1.30 *4.92H, s, 52 CH3), 1.37 *3.08H, m,
5-Hendo, 6-Hendo, and 51 CH3), 2.01 *0.36H, dm, Jˆ7 Hz,
51 5-Hexo and 6-Hexo), 2.23 *1.64H, dm, Jˆ7 Hz, 52 5-Hexo
and 6-Hexo), 2.99 *2H, m, 4-H and 7-H), 6.85 *1.64H, s, 52
1-H and 3-H), 6.87 *0.36H, s, 51 1-H and 3-H); 13C NMR
*CDCl3) dˆ20.7 *51 CH3), 21.7 *52 CH3), 25.5 *51 C-5 and
C-6), 26.5 *52 C-5 and C-6), 41.2 *51 C-4 and C-7), 41.6 *52
C-4 and C-7), 62.3 *51 CMe2), 62.9 *52 CMe2), 85.7 *52
C-8), 89.5 *51 C-8), 112.6 *52 C-1 and C-3), 113.2 *51 C-1
and C-3), 145.3 *52 C-3a and C-7a), 147.3 *51 C-3a and
C-7a); MS m/z *rel intensity) 206 *4, M1), 178 *13,
M2C2H4), 137 *100, M2C2H4±C3H5). Found: C, 69.80;
H, 6.90%. Calcd for C12H14OS: C, 69.86; H, 6.84%.
CH3 and 5-Hexo
;
13C NMR *CDCl3) dˆ19.0 *CH3), 28.5
*C-5 and C-6), 29.5 *CMe2), 43.6 *C-4 and C-7), 62.9
*C-8), 77.2 *CCl2), 112.1 *C-1 and C-3), 148.2 *C-3a and
C-7a); MS m/z *rel intensity) 272/274/276 *25/17/4, M1),
237/239 *100/38, M2Cl), 135 *83, 2-benzothiophene1H).
Found: C, 56.99; H, 5.23%. Calcd for C13H14Cl2S: C, 57.15;
H, 5.16%.
56: a white powder *from methanol); mp 73±748C; IR
*KBr) 2976, 2954, 2939, 2868, 1462, 1441, 1381, 1371,
1
1363, 1151, 1097 cm21; H NMR *CDCl3) dˆ1.15 *6H, s,
CH3), 1.43 *2H, dm, Jˆ7.5 Hz, 5-Hendo and 6-Hendo), 2.25
*2H, dm, Jˆ7.5 Hz, 5-Hexo and 6-Hexo), 3.12 *2H, t, Jˆ2 Hz,
4-H and 7-H), 6.75 *2H, s, 1-H and 3-H); 13C NMR *CDCl3)
dˆ19.9 *CH3), 27.6 *C-5 and C-6), 29.2 *CMe2), 43.1 *C-4
and C-7), 61.2 *C-8), 111.7 *C-1 and C-3), 148.3 *C-3a
and C-7a), 1C missing; MS m/z *rel intensity) 272/274/
276 *14/10/3, M1), 237/239 *81/31, M2Cl), 135 *100,
2.1.26. Reaction of 11 with sodium trichloroacetate. To a
solution of 11 *47 mg, 0.25 mmol) in a mixture of tetra-
chloroethylene *5 cm3) and diglyme *5 cm3) was added
sodium trichloroacetate *46 mg, 0.25 mmol) under re¯ux.
Sodium trichloroacetate *46 mg, 0.25 mmol) was intro-

T. Kobayashi et al. / Tetrahedron 57 .2001) 9073±9085
9085
2-benzothiophene1H). Found: C, 57.23; H, 5.10%. Calcd
for C13H14Cl2S: C, 57.15; H, 5.16%.
*CDCl3) dˆ20.3 *CH3), 28.0 *C-5 and C-6), 49.8 *C-4 and
C-7), 81.7 *C-8), 112.9 *C-1 and C-3), 114.5 *vCH2),
144.6, 144.8 *C-3a and C-7a); MS m/z *rel intensity) 268/
270 *28/29, M1), 189 *100, M2Br), 175 *34, M2Br±CH2).
HR-MS*FAB) found: 269.9904. Calcd for C 12H1381BrS: C,
269.9901.
2.1.28. Reaction of 8 with NBS. A solution of 8 *82 mg,
0.25 mmol) and NBS*53 mg, 0.3 mmol) in dichloro-
methane *10 cm3) was stirred at room temperature for
20 min. Aqueous sodium sul®te was added to the mixture,
and the organic phase was separated. The organic phase was
washed with water and brine prior to drying with Na2SO4.
After removal of the solvent, the resulting solid was
collected by suction to give 58 *98 mg, 96%): a white
powder *form hexane±ether 10/1); mp 177±1798C; IR
*KBr) 3060, 3022, 2993, 2979, 2945, 2868, 1595, 1493,
Acknowledgements
We are grateful to Professor Makoto Nitta *Waseda Uni-
versity, Japan) for the measurement of the high-resolution
mass spectra.
1
1446, 1127, 1061 cm21; H NMR *CDCl3) dˆ1.62 *2H,
dm, Jˆ8 Hz, 5-Hendo and 6-Hendo), 1.79 *3H, s, CH3), 2.63
*2H, d, Jˆ8 Hz, 5-Hexo and 6-Hexo), 3.88 *2H, m, 4-H and
7-H), 4.71 *1H, s, vCH2), 4.97 *1H, s, vCH2), 7.23 *2H,
m), 7.40 *4H, m), 7.70 *4H, m); 13C NMR *CDCl3) dˆ20.7
*CH3), 27.7 *C-5 and C-6), 47.7 *C-4 and C-7), 82.7 *C-8),
114.3 *vCH2), 123.8, 126.9, 128.0, 128.8, 131.0, 141.9,
144.6; MS m/z *rel intensity) 404/406 *81/84, M1), 326
*32, M2Br), 105 *100, COPh), 77 *55, Ph). Found: C,
71.21; H, 5.09%. Calcd for C24H21BrO: C, 71.12; H. 5.22%.
References
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2.1.29. Reaction of 10 with NBS. A solution of 10 *27 mg,
0.1 mmol) and NBS*45 mg, 0.25 mmol) in dichloro-
methane *10 cm3) was stirred at room temperature for 1 h.
Aqueous sodium sul®te was added to the mixture, and the
organic layer was separated. The organic layer was washed
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*silica gel, hexane) to give 60 *23 mg, 53%): a slightly
yellow solid *from hexane); mp 130±1328C; IR *KBr)
2968, 2939, 2924, 2854, 1514, 1371, 1338, 1228, 1115,
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1020 cm21
;
1H NMR *CDCl3) dˆ1.36 *2H, dm, Jˆ
6.5 Hz, 5-Hendo and 6-Hendo), 1.66 *6H, s, CH3), 1.87 *2H,
dm, Jˆ6.5 Hz, 5-Hexo and 6-Hexo), 2.41 *3H, s, CH3), 3.75
*2H, m, 4-H and 7-H), 7.08 *2H, br s),7.23 *2H, br s); 13C
NMR *CDCl3) dˆ20.2 *CH3), 21.3 *CH3), 28.1 *C-5 and
C-6), 39.5 *C-4 and C-7), 92.9 *C-1 and C-3), 111.5 *C-9),
129.9, 133.8 *C-3a and C-7a), 135.3, 138.3, 147.3 *C-8), 1C
missing; MS m/z *rel intensity) 419/421/423 *11/21/10,
M1), 404/406/408 *9/15/10, M2CH3), 366/368/370 *32/
100/44, M2C4H5). HR-MS*FAB) found: 418.9839. Calcd
for C19H1979Br2N: 418.9885.
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1999, 72, 1597.
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È
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2.1.30. Reaction of 12 with NBS. A solution of 12 *48 mg,
0.25 mmol) and NBS*53 mg, 0.3 mmol) in dichloro-
methane *10 cm3) was stirred at room temperature for
20 min. Aqueous sodium sul®te was added to the mixture,
and the organic phase was separated. The organic phase was
washed with water and brine prior to drying with Na2SO4.
After removal of the solvent, the resulting solid was
collected by suction to give 59 *98 mg, 97%): a white
powder; mp 628C; IR *KBr) 3089, 2997, 2976, 2922,
20. Dimroth, K.; Follmann, H.; Pohl, G. Chem. Ber. 1966, 99, 642.
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2871, 1639, 1444, 1373, 1360, 1109 cm21 1H NMR
;
*CDCl3) dˆ1.42 *2H, dm, Jˆ7.5 Hz, 5-Hendo and 6-Hendo),
1.75 *3H, s, CH3), 2.50 *2H, dm, Jˆ7.5 Hz, 5-Hexo and
6-Hexo), 3.61 *2H, m, 4-H and 7-H), 4.71 *1H, s, vCH2),
4.88 *1H, s, vCH2), 6.76 *2H, s, 1-H and 3-H); 13C NMR
25. Cookson, R. C.; Gupte, S. S.; Stevens, I. D. R.; Watts, C. T.
Organic Syntheses Collected Volume; VI; Wiley: New York,
1988; p 936.