Synthesis of pyrrolizidine, indolizidine, and quinolizidine derivatives using ruthenium-catalyzed ring-opening metathesis and ring-closing metathesis of cycloalkene-ynes

Article abstract of DOI:10.1002/adsc.200600539

Ring-opening metathesis and ring-closing metathesis (ROM-RCM) of a cyclopentene-yne having an ester moiety was demonstrated using first- and second-generation Grubbs' catalysts. When the reaction of cycloalkene-yne was carried out in the presence of 5 mol

Full text of DOI:10.1002/adsc.200600539

FULL PAPERS
DOI: 10.1002/adsc.200600539
Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine
Derivatives Using Ruthenium-Catalyzed Ring-Opening
Metathesis and Ring-Closing Metathesis of Cycloalkene-ynes
Hideaki Wakamatsu,a Yoshihiro Sato,b Reiko Fujita,a and Miwako Moric,*
a
Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Health Sciences Universityof Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
b
c
Phone/Fax: (+81)-1-1787-6045; e-mail: mori@pharm.hokudai.ac.jp
Received: October 17, 2006
Abstract: Ring-opening metathesis and ring-closing complex, pyrrolizidine and indolizidine derivatives
metathesis (ROM-RCM) of
having an ester moietywas demonstrated using first-
and second-generation Grubbsꢀ catalysts. When the alkyne. When azabicyclo
a
cyclopentene-yne were obtained in good yields. The distribution of
these products depends on the substituents on the
[2.2.1]heptene-ynes bearing
AHCTREUNG
reaction of cycloalkene-yne was carried out in the large substituents on the alkyne were treated with
presence of 5 mol% of a ruthenium carbene com- ruthenium catalyst 1b, a pyrrolizidine derivative was
plex under an ethylene atmosphere at room temper- obtained as the major product. ROM-RCM of
ature, ROM-RCM proceeded smoothlyto give a pyr-
azabicyclo[2.2.2]octene-ynes with 1b afforded quino-
A
rolidine derivative in good yield, which could be con- lizidine derivative 20, although the yield was moder-
verted to a pyrrolizidine derivative. Furthermore, ate.
ROM-RCM of azabicyclo[2.2.1]heptene-ynes using
A
the second-generation Grubbsꢀ catalyst was investi-
gated. When an azabicycloheptene derivative was ex- Keywords: enyne metathesis; ethylene; indolizidine;
posed to a catalytic amount of a ruthenium carbene pyrrolizidine; ROM-RCM; ruthenium
Introduction
applications.[3] We have alreadyreported various
enyne metathesis reactions catalyzed by ruthenium
Since the development of Grubbsꢀ ruthenium-based carbene complex 1a or 1b,[4] including the effect of
carbene complexes (1a, 1b; Figure 1),[1] the olefin ethylene for the RCM[4c] and CM (cross metathesis)
metathesis reaction plays an important role as a of alkynes, which is an effective synthetic method for
carbon-carbon bond forming reaction in the field of 2,3-disubstituted-1,3-dienes.[4b,d,e] Recently, the ROM-
synthetic organic chemistry.[2]
RCM[5] of cycloalkene-ynes under an ethylene atmos-
[4f–h]
It is also well known that the ruthenium-catalyzed phere was reported byour group (Scheme 1).
metathesis reaction is applicable to the synthesis of When cycloalkene I having substituent at the C-3 po-
natural products as a keystep. Ennye metathesis,
sition was reacted with ruthenium carbene complex
which takes place between a double bond and a triple 1a under an ethylene atmosphere, a pyrrolidine deriv-
bond to afford a diene derivative, is a synthetically ative was obtained in high yield. In this reaction, the
useful transformation with a large number of recent double bonds of the cycloalkene and ethylene were
Scheme 1. ROM-RCM of a cycloalkene having a substituent
at the C-3 position.
Figure 1. Ruthenium catalysts for metathesis.
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Hideaki Wakamatsu et al.
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cleaved, and each alkylidene part was recombined
with an alkyne moiety to afford a new cyclic com-
pound having a triene moiety.
On the other hand, when cycloalkene III having a
substituent at the C-1 position was reacted with 1b, a
bicyclic compound was formed in high yield. In this
reaction, the double bond of the cycloalkene was
cleaved and carbon-carbon bonds were formed be-
tween the double bond of the cycloalkene and the
triple bond to provide a bicyclic compound having a
diene moiety(Scheme 2).
Scheme 4. Synthesis of substrate 2a. Ns=o-nitrobenzenesul-
fonyl.
When a CH2Cl2 solution of 2a and 10 mol% of 1a
was stirred under an ethylene atmosphere at room
temperature for 40 h, pyrrolidine derivative 3a was
obtained in 17% yield and the starting material 2a
was recovered in 55% yield (Scheme 5).
Scheme 2. ROM-RCM of a cycloalkene having a substituent
at the C-1 position.
We have alreadyapplied this method to synthesis
of isoquinoline derivatives from cyclobutene deriva-
tives having an alkyne side chain.[4i]
We described herein concise synthesis of pyrrolizi-
dine derivatives using ROM-RCM as a keyreaction
and the syntheses of pyrrolizidine, indolizidine and
quinolizidine derivatives using ROM-RCM of azabi-
cycloalkene-ynes.
Scheme 5. ROM-RCM of a cyclopentene-yne.
Although the yield of pyrrolidine derivative 3a was
low, the result indicated that the desired ROM-RCM
of the cycloalkene-yne occurred to give 3a. The possi-
ble reaction course for the formation of pyrrolidine
derivative 3 from cyclopentene derivative 2 is shown
in Scheme 6.
Results and Discussion
Synthesis of a Pyrrolizidine Derivative using ROM-
RCM of a Cycloalkene-yne
To improve the yield of 3a, the reaction was carried
out under the various conditions (Table 1). When a
We planned the synthesis of pyrrolizidine derivative 3 CH2Cl2 solution of 2a and 1a was refluxed, the result
from cyclopentene derivative 2 having an alkyne was unsatisfactory(entry2). On the other hand, when
moietyin the side chain using ROM-RCM
(Scheme 3).
the second-generation ruthenium carbene complex 1b
was used at room temperature for this reaction, the
For the synthesis of the substrate 2a, commercially ROM-RCM proceeded smoothlyto give 3a in 75%
available 4 was reacted with thionyl chloride in yield (entry 3). It is generally accepted that catalyst
MeOH[6] followed bytreatment with NsCl and Et N
3
in CH2Cl2 at 08C to afford cyclopentene derivative 5
in 98% yield (Scheme 4). Introduction of an alkyne
side chain to 5 was achieved bythe Mitsunobu reac-
tion[7] with propargyl alcohol to afford substrate 2a in
68% yield.
Scheme 3. Plan for the synthesis of a pyrrolizidine deriva-
tive.
Scheme 6. Possible reaction course for ROM-RCM.
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Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine Derivatives
FULL PAPERS
Table 1. ROM-RCM of cyclopentene-yne 2a.
Entsrty(Cmaotal%ly )
Temperature
Time [h]
Yield of
3a [%]
Recoveryof 2a [%]
1
2
3
4
5
1a (10)
1a (10)
1b (10)
1b (10)
1b (5)
r.t.
reflux
r.t.
reflux
r.t.
40
6
2
2
6
17
5
75
34
76
55
69
0
25
0
1b is used under a higher reaction temperature, how-
ever, poor yield and incomplete conversion were
shown in this reaction (entry4). Even upon lowering
the use of 1b to 5 mol%, 3a was obtained in high
yield (entry 5).
Subsequently, we tried to synthesize pyrrolizidine
derivative 7 from triene 3a under several sets of reac-
tion conditions.[8] Although the nosyl group of 3a
could be removed bytreatment with 2-mercaptoetha-
nol and DBU in DMF, cyclization did not proceed at
room temperature. Thus, the DMF solution was
warmed at 408C to give pyrrolizidine derivative 7 in
78% yield (Scheme 7).[9]
Scheme 7. Synthesis of pyrrolizidine derivative 7.
Scheme 8. Plan for one-step synthesis of bicyclic heterocy-
cles.
Plan for One-Step Synthesis of Bicyclic Heterocycles
nacyclobutene intermediate VIII. Ring opening of
Next, we tried the one-step synthesis of bicyclic het- VIII gives ruthenium carbene complex IX. If the re-
erocycles from 2-azabicyclo[2.2.1]hepten-3-one action is carried out under an ethylene atmosphere,
having an alkyne moiety on the nitrogen. the generated ruthenium carbene of IX should react
Our plan is shown in Scheme 8. When compound 8 with ethylene to provide bicyclic compound X.
is reacted with ruthenium carbene complex 1b, bicy- During the course of our investigation of this proj-
a
ACHTREUNG
clic heterocycle X should be formed. The ruthenium ect, Arjona, Plumet and co-workers reported the
methylidene carbene complex should react with an same ROM-RCM of an azabicycloheptene derivative
alkene moietyof the azabicycloheptene derivative
8
8a (Scheme 9).[10] Theyobtained indolizidine deriva-
to afford the ruthenium carbene complex VII, which tive 10a from 8a in nearlyquantitative yield when a
reacts with an alkyne moiety of VII to give the ruthe- CH2Cl2 solution of 8a and 1b was heated in a sealed
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Hideaki Wakamatsu et al.
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dine derivative 10a, not pyrrolizidine derivative 9a, is
formed as a major product in the reaction of 8a.
Subsequently, we examined the substituent effect
on the alkyne. When the reaction of 8b (R=Me) was
carried out under our optimized reaction conditions
(in toluene at 808C), pyrrolizidine derivative 9b was
obtained in 30% yield along with indolizidine deriva-
tive 10b in 40% yield (Table 2, entry 1). It was inter-
esting that ethylene is required for this reaction be-
cause compound 8b did not provide the desired prod-
ucts under argon atmosphere although the starting
material 8b was consumed (entry2). [11] The ratio of
pyrrolizidine to indolizidine was changed when com-
pound 8c having the phenyl group on the alkyne was
used for this reaction, and pyrrolizidine derivative 9c
was obtained as a major product. To examine the
Scheme 9. ROM-RCM reported byArjona, Plumet and co-
workers.
tube. We have obtained compound 10a along with a electronic effect of the substituent on the alkyne,
fair amount of pyrrolizidine derivative 9a when the compound 8d or 8e was subjected to the reaction. But
reaction was carried out in toluene upon heating. The the ratio of 9d to 10d is almost same as that of 9e to
result is interesting because the pyrrolizidine deriva- 10e, and in each case, pyrrolizidine derivative, 9d or
tive is formed along with indolizidine derivatives. 9e, was obtained as the major product (entries 3 and
Thus, we decided to conduct a further investigation of 4). In the case of 8d, tetraene 11d was obtained in
this reaction, especially, the product distribution in 12% yield (entry 4). When 11d was re-exposed to
regard to the substituent on the alkyne.
Grubbsꢀ catalyst 1b under the same reaction condi-
tions, RCM did not proceed and 11d was recovered in
82% yield. This means that 9d and 10d were not
formed from 11d. A TMS group was also effective for
the formation of pyrrolizidine derivative 9f (entry6).
ROM-RCM of Azabicyclo[2.2.1]heptene-ynes
A
When a CH2Cl2 solution of 8a was stirred in the pres- To explore the steric effect on the alkyne, the bulky
ence of 1a or 1b under an ethylene atmosphere at TIPS (triisopropylsilyl) group was introduced on the
room temperature, none of the product was obtained. terminal alkyne. Interestingly, 8g gave pyrrolizidine
Thus, a CH2Cl2 solution of 8a and 1b was refluxed for derivative 9g in 31% yield along with ring-opening
5 h under ethylene gas, but the result was unsatisfac- product 12g in 36% yield.
tory. The solvent was changed to toluene for use of a
When a toluene solution of 12g was treated with 20
higher reaction temperature. When a toluene solution mol% of 1b at 808C for 4.5 h under ethylene atmos-
of 8a was stirred in the presence of 10 mol% of the phere, a mixture of 9g and 9g’ (an olefin of 9g’ conju-
second-generation ruthenium carbene complex 1b gated with the carbonyl group) was obtained in 37%
under an ethylene atmosphere at 808C for 0.5 h, indo- yield, and the starting material 12g and 12g’ (olefin
lizidine derivative 10a was obtained in 50% yield isomer of 12g) was recovered in 49% yield
along with pyrrolizidine derivative 9a in 18% yield (Scheme 11). In this case, formation of indolizidine
(Scheme 10). It is not clear at this stage whyindolizi-
derivative 10g was also not observed. Furthermore,
the TIPS group of 12g was removed bytreatment
with TBAF and the resultant 12a’ was treated in a
similar manner. As a result, pyrrolizidine derivative 7
and indolizidine derivative 10a’ were obtained in
60% and 21% yields, respectively. It is noteworthy
that pyrrolizidine derivative 7 was formed as a major
product in this case although the reaction of 8a gave
indolizidine derivative 10a as the major product. Fur-
thermore, the reaction of 12c’, which was obtained by
Sonogashira coupling reaction of 12a’ and phenyl
iodide, preferred the formation of pyrrolizidine deriv-
ative 9c’ other that of indolizidine derivative 10c’.
This result is similar to that of 8c.
When a toluene solution of 13 having a one-carbon
elongated side chain and 10 mol% of 1b was warmed
at 808C for 1 h, the metathesis products were not ob-
Scheme 10. ROM-RCM of azabicyclo[2.2.1]heptene-yne 8a.
A
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FULL PAPERS
Table 2. Synthesis of bicyclic heterocycles.
EntryR
Atmosphere
9 (%)[a]
10 (%)[a]
1
2
Me (8b)
Me (8b)
H2C=CH2
Ar
30
0
40
0
3
Ph (8c)
H2C=CH2
H2C=CH2
H2C=CH2
H2C=CH2
H2C=CH2
56
40
34
51
31[d]
15
21
18
23
-
4[b]
5
C6H4-p-OMe (8d)
C6H4-p-CO2Et (8e)
TMS (8f)
6
7[c]
TIPS (8g)
[a]
Isolated yields.
11d was obtained in 12% yield.
12g was obtained in 36% yield.
1:1 mixture of 9g and 9g’.
[b]
[c]
[d]
tained although the spot of the starting material 13 terminal alkyne, was subjected to the same reaction
disappeared on TLC (Scheme 12). However, when conditions, ROM-CM with ethylene proceeded to
compound 14, which possessed a TIPS group on the give 15 in 41% yield. The removal of the TIPS group
Scheme 11. Effect of alkyne TIPS-substitution on ROM-RCM product distribution.
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XIV.[10] However, RCM of complex XII or XIII
should be faster than CM with ethylene in our case
because of the higher reaction temperature. Ethylene
is required for the formation of 9 and 10 from ruthe-
nium carbene complexes XI, VII and IX. If the reac-
tion proceeds through this reaction mechanism, an in-
dolizidine derivative would be formed from complex
XII. Since the bulkysubstituents on the alkyne would
disturb the formation of XII from 12, the formation
of pyrrolizidine derivative 9 via IX or XIII would be
taken precedence.
ROM-RCM of Azabicyclo
ACHTREUNG
ROM-RCM of azabicyclo
AHCTREUNG
ried out. When a CH2Cl2 solution of 19a was refluxed
in the presence of 10 mol% of 1b under an ethylene
atmosphere, 19a was recovered in 73% yield (Table 3,
entry1). Ethylene gas was important for this reaction
and starting material 19a was recovered in only39%
yield when the reaction was carried out under argon
atmosphere (entry2). When a toluene solution of 19a
and 10 mol% of 1b was stirred at 808C for 0.5 h, qui-
nolizidine derivative 20a was obtained in 27% yield
along with triene 21a, which was provided bycross
enyne metathesis of 19a and ethylene, in 42% yield
(entry3). The higher reaction temperature led to a
slight change of the products ratio (entry4). In the
Scheme 12. Synthesis of indolizidine derivative 17.
of 15 gave 16, which was subjected to the metathesis case of 19b, cross metathesis product 21b was ob-
conditions to afford onlyindolizidine derivative 17 in tained in 78% yield (entry 5). This means that the
74% yield, and bicyclic compound 18, containing a 7- bulkysubstituent of TMS group on the alknye dis-
membered ring was not formed.
turbs the formation of quinolizidine derivative 20b,
and only CM of the alkyne part with ethylene pro-
ceeded.
Consideration of the Reaction Mechanism of
Azabicyclo[2.2.1]heptene-ynes
These results are summarized as follows: (1) initial
reaction would proceed via CM of the alkyne part
and ethylene; (2) because of the slow reaction rate of
A
The possible reaction course for the formation of in- a cyclohexene part with ruthenium carbene of XV or
dolizidine and quinolizidine derivatives is shown in XVI generated on the side chain, the yield of quinoli-
Scheme 13 on the basis of the preceding results. The zidine derivative 20 is low; (3) due to the bulkysub-
cycloaddition and subsequent cycloreversion of the stituent on the alkyne, the formation of XVI is sup-
ruthenium methylidene complex to the double bond pressed; (4) indolizidine derivative 22 could not be
of cycloalkene 8 provide XI and VII, which would be obtained in this reaction, because of the low reactivity
converted to 12 under an ethylene atmosphere. If the of the cyclohexene part to ROM. From these results,
ruthenium carbene of VII reacts with the alkyne part the reaction mechanism of azabicyclo
A
intramolecularly, IX would be formed via ruthenacy- ynes should be different from that of azabicyclo-
clobutene VIII, and IX reacts with ethylene to afford
pyrrolizidine derivative 9. The ruthenium carbene of
XI would not react with the alkyne moiety due to the
A
ring strain of formed ruthenacyclobutene. On the Conclusions
other hand, if the ruthenium methylidene complex
reacts with the alkyne moiety in 12, complexes XIII A simple construction method for a pyrrolizidine
and XII would be formed, giving pyrrolizidine deriva- skeleton via ROM-RCM of cyclopentene-yne cata-
tive 9 and indolizidine derivative 10 byintramolecular
lyzed by the ruthenium carbene complex 1b, and one-
reaction. It is also possible that these complexes (XII step synthesis of bicyclic heterocycles by ROM-RCM
and XIII) can react with ethylene to provide tetraene of azabicycloalkene-ynes were investigated. In the
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Scheme 13. Possible reaction course for the formation of pyrrolizidine and indolizidine derivatives.
Table 3. ROM-RCM of azabicyclo[2.2.2]octene-ynes 19.
G
EntryR
Temperature [
8C]
Time [h]
20 [%][a]
21 [%][a]
Recoveryof 19 [%][b]
1[c]
2[d]
3
4
5
H (19a)
H (19a)
H (19a)
H (19a)
TMS (19b)
reflux
80
80
reflux
80
21
3
0.5
0.5
0.5
-
-
27
22
-
-
-
73
39
-
-
-
42
50
78[b]
[a]
1
Yield was determined by H NMR using (E)-stilbene as an internal standard.
Isolated yield.
In CH2Cl2.
[b]
[c]
[d]
Under an argon atmosphere.
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Scheme 14. Plausible reaction course for the reaction of 19.
Methyl 4-(2-Nitrobenzenesulfonylamino)-cyclopent-2-
enecarboxylate (5)
former case, ROM-RCM of cyclopentene-ynes pro-
ceeded smoothlyat room temperature to give pyrroli-
dines derivative having a triene moietyin good yield,
which were converted into pyrrolizidine derivatives
bysimple treatment. In the latter case, pyrrolizidine
and indolizidine derivatives were obtained in only
To a solution of 4 (504.5 mg, 4.62 mmol) in MeOH (24 mL)
was added SOCl2 (0.6 mL, 8.23 mmol) at 08C, and the mix-
ture was stirred at room temperature for 3 h. The volatiles
were removed under reduce pressure, and the residue was
dissolved in CH2Cl2 (23 mL). To this solution were added
Et3N (1.9 mL, 13.87 mmol) and NsCl (1.54 g, 6.93 mmol) at
08C, and the solution was stirred for 1.5 h. Saturated NH4Cl
solution was added, and the mixture was extracted with
AcOEt. The organic phase was washed with saturated NaCl
solution, dried over MgSO4, and concentrated. The residue
was purified bycolumn chromatographyon silica gel
(hexane/AcOEt, 2:1) to afford 5; yield: 1.47 g (98%). IR
one step from azabicyclo[2.2.1]heptene-ynes, and the
A
ratio of the pyrrolizidine and the indolizidine deriva-
tives was affected bythe substituent on the alkyne.
When azabicyclo[2.2.1]heptene-ynes bearing large
R
substituents on the alkyne were treated with rutheni-
um catalyst 1b, a pyrrolizidine derivative was ob-
tained as the major product. From azabicyclo-
A
(neat): n=1714 (s), 1545 (s), 1364 (s), 1167 (s) cmÀ1
;
1H NMR (270 MHz, CDCl3): d=1.89 (ddd, J=3.0, 3.5,
14.1 Hz, 1H), 2.33 (ddd, J=7.9, 8.6, 14.1 Hz, 1H), 3.44
(dddd, J=2.0, 2.5, 3.5, 8.6 Hz, 1H), 3.71 (s, 3H), 4.67
(ddddd, J=1.4, 2.3, 3.0, 7.9, 8.5 Hz, 1H), 5.72 (ddd, J=2.0,
2.3, 5.6 Hz, 1H), 5.85 (br, 1H), 5.90 (ddd, J=1.4, 2.5,
5.6 Hz, 1H), 7.71–7.78 (m, 2H), 7.84–7.89 (m, 1H), 8.16–
8.20 (m, 1H); 13C NMR (67.8 MHz, CDCl3): d=34.3, 49.3,
52.5, 59.6, 125.2, 130.4, 132.7, 132.8, 133.1, 133.4, 135.1,
147.8, 173.8; EI-LR-MS: m/z=326 (M+), 295, 267, 186, 140,
108, 80.
tained although the yield was moderate.
Experimental Section
General Remarks
The metathesis reactions were carried out under an atmos-
phere of ethylene (1 atm) unless otherwise mentioned. All
other manipulations were carried out under an atmosphere
of argon unless otherwise mentioned. Ruthenium complexes
were purchased from Aldrich Chemical Company. All other
solvents and reagents were purified when necessaryusing
standard procedure. Column chromatographywas per-
formed on silica gel 60 N (spherical, neutral, 40–60 mm,
Kanto Chemical Co.).
Methyl 4-[(2-Nitrobenzenesulfonyl)-prop-2-ynyl-
amino]-cyclopent-2-enecarboxylate (2a)
To a solution of 5 (315.1 mg, 0.97 mmol), PPh3 (303.9 mg,
1.16 mmol), and propargyl alcohol (0.07 mL, 1.16 mmol) in
THF (10 mL) was added DEAD (0.53 mL, 1.16 mmol, 40%
toluene solution) at 08C. The solution was stirred at room
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Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine Derivatives
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temperature for 32 h, and the volatiles were removed under
reduce pressure. The residue was purified bycolumn chro-
matographyon silica gel (hexane/AcOEt, 2:1) to afford 2a;
yield: 237.5 mg (68%). IR (neat): n=2124 (w), 1734 (s),
117.3, 128.6, 129.0, 130.3, 134.0, 141.9, 172.0; EI-LR-MS:
m/z=175 (M+), 160, 148, 132, 118, 106, 93; EI-HR-MS:
m/z=175.0979, calcd. for C11H13ON (M+): 175.09970.
1546 (s), 1372 (s), 1166 (s) cmÀ1 1H NMR (270 MHz,
;
2-Prop-2-ynyl-2-azabicyclo[2.2.1]hept-5-en-3-one (8a)
A
CDCl3): d=2.07 (t, J=2.5 Hz, 1H), 2.20 (ddd, J=5.6, 6.3,
15.3 Hz, 1H), 2.61 (ddd, J=8.4, 9.2, 15.3 Hz, 1H), 3.51
(ddddd, J=1.5, 2.1, 2.1, 6.3, 9.2 Hz, 1H), 3.72 (s, 3H), 4.10
(d, J=2.5 Hz, 2H), 5.21 (ddddd, J=1.5, 2.1, 2.1, 5.6, 8.4 Hz,
1H), 5.87 (ddd, J=2.1, 2.1, 5.6 Hz, 1H), 6.00 (ddd, J=2.1,
2.1, 5.6 Hz, 1H), 7.65–7.73 (m, 3H), 8.17–8.20 (m, 1H);
13C NMR (67.8 MHz, CDCl3): d=30.8, 32.8, 48.9, 52.2, 64.2,
72.6, 79.5, 124.1, 131.4, 131.6, 132.2, 133.4, 133.5, 133.6,
147.8, 173.6.
To a suspension of NaH (98.3 mg, 2.46 mmol) in DMF
(5.5 mL) was added 2-azabicyclo[2.2.1]hept-5-en-3-one
AHCTREUNG
(223.4 mg, 2.05 mmol) in DMF (4.5 mL) at 08C, and the
mixture stirred at room temperature for 1 h. To this suspen-
sion was added propargyl bromide (0.23 mL, 3.07 mmol) at
08C, and stirred at room temperature for 1 h. Saturated
NH4Cl solution was added, and the mixture was extracted
with AcOEt. The organic phase was washed with H2O and
saturated NaCl solution, dried with MgSO4, and concentrat-
ed. The residue was purified bycolumn chromatographyon
silica gel (hexane/AcOEt, 3:2) to afford 8a; yield: 245.3 mg
Typical Procedure for the Metathesis Reaction of 2a
(Table 1, entry 3)
(81%). IR (neat): n=2118 (w), 1707 (s), 1560 (w) cmÀ1
;
1H NMR (270 MHz, CDCl3): d=2.15 (ddd, J=1.5, 1.6,
7.7 Hz, 1H), 2.23 (t, J=2.6 Hz, 1H), 2.31 (ddd, J=1.5, 1.6,
7.7 Hz, 1H), 3.37 (ddt, J=0.5, 3.3, 1.5 Hz, 1H), 3.74 (dd, J=
2.6, 17.6 Hz, 1H), 4.00 (dd, J=2.6, 17.6 Hz, 1H), 4.33 (ddt,
J=1.5, 2.0, 1.6 Hz, 1H), 6.58 (ddd, J=1.5, 3.3, 5.3 Hz, 1H),
6.92 (ddd, J=0.5, 2.0, 5.3 Hz, 1H); 13C NMR (67.8 MHz,
CDCl3): d=33.0, 53.2, 57.4, 62.6, 72.7, 76.5, 136.0, 139.1,
178.9; EI-LR-MS: m/z=147 (M+), 88, 66; EI-HR-MS:
m/z=147.0672, calcd. for C9H9ON (M+): 147.0684.
To a solution of ruthenium carbene complex 1b (9.3 mg,
11.01 mmol, 10 mol%) in CH2Cl2 (2 mL) was added 2a
(40.1 mg, 0.11 mmol) in CH2Cl2 (2 mL) at 08C, and the solu-
tion was stirred at room temperature for 2 h. A few drops of
ethyl vinyl ether were added to the mixture, and the vola-
tiles were removed under reduce pressure. The residue was
purified bycolumn chromatographyon silica gel (hexane/
AcOEt, 3:2) to afford methyl 2-[1-(2-nitrobenzenesulfonyl)-
4-vinyl-2,5-dihydro-1H-pyrrol-2-ylmethyl]-but-3-enoate (3a);
yield: 32.3 mg (75%). IR (neat): n=1735 (s), 1640 (w), 1546
1
(s), 1372 (s), 1170 (s) cmÀ1; H NMR (270 MHz, CDCl3): d=
Typical Procedure for the Metathesis Reaction of 8
(Scheme 10)
2.04 (ddd, J=4.7, 6.0, 13.7 Hz, 1H), 2.33 (ddd, J=2.5, 8.7,
13.7 Hz, 1H), 3.20 (ddd, J=4.7, 8.0, 8.7 Hz, 1H), 3.62 (s,
3H), 4.28 (ddd, J=1.2, 4.5, 13.8 Hz, 1H), 4.32 (ddd, J=1.1,
2.0, 13.8 Hz, 1H), 4.88 (m, 1H), 5.05–5.25 (m, 4H), 5.56
(ddd, J=1.1, 1.2, 1.8 Hz, 1H), 5.75 (ddd, J=8.0, 9.9,
17.3 Hz, 1H), 6.37 (dd, J=10.2, 15.0 Hz, 1H), 7.61–7.73 (m,
3H), 7.92–7.96 (m, 1H); 13C NMR (67.8 MHz, CDCl3): d=
37.4, 45.6, 52.0, 54.5, 66.1, 117.1, 117.6, 124.2, 126.7, 129.3,
130.1, 131.5, 131.8, 133.6, 135.4, 137.0, 148.4, 173.9; EI-LR-
MS: m/z=392 (M+), 361, 279, 206, 186, 106, 93; EI-HR-MS:
m/z=392.1051, calcd. for C18H20O6N2S (M+): 392.1042.
To a solution of ruthenium carbene complex 1b (9.9 mg,
11.62 mmol, 10 mol%) in toluene (3 mL) was added 8a
(17.1 mg, 0.12 mmol) in toluene (3 mL) at 08C, and the solu-
tion was stirred at 808C for 0.5 h. A few drops of ethyl vinyl
ether were added to the mixture, and the volatiles were re-
moved under reduced pressure. The residue was purified by
column chromatographyon silica gel (hexane/AcOEt, 3:2)
to afford 9a and 10a.
2,6-Divinyl-1,2,5,7a-tetrahydropyrrolizin-3-one (9a): yield:
3.7 mg (18%); IR (neat): n=1704 (s), 1641 (m) cmÀ1
;
1H NMR (270 MHz, CDCl3): d=1.76 (ddd, J=9.7, 9.7,
12.2 Hz, 1H), 2.60 (ddd, J=6.1, 7.3, 12.2 Hz, 1H), 3.48 (ddd,
J=6.1, 6.8, 9.7 Hz, 1H), 3.81 (m, 1H), 4.56 (m, 1H), 4.66
(m, 1H), 5.12–5.25 (m, 4H), 5.80 (m, 1H), 5.94 (ddd, J=6.8,
10.4, 17.1 Hz, 1H), 6.48 (dd, J=10.9, 17.6 Hz, 1H);
13C NMR (67.8 MHz, CDCl3): d=36.4, 48.4, 48.8, 65.2,
117.1, 117.4, 127.8, 130.2, 134.6, 140.5, 176.7; EI-LR-MS:
m/z=175 (M+), 160, 146, 132, 117, 106, 93; EI-HR-MS:
m/z=175.0979, calcd. for C11H13ON (M+): 175.09970.
2-Ethylidene-6-vinyl-1,2,5,7a-tetrahydropyrrolizin-3-
one (7)
To a solution of 3a (10.1 mg, 0.03 mmol) in DMF (0.5 mL)
was added DBU (38 mL, 0.26 mmol) and HSCH2CH2OH
(18 mL, 0.26 mmol) at 08C. The resultant solution was stirred
at room temperature for 2 h, and then at 408C for 14 h. Sa-
turated NaHCO3 solution was added at 08C, and the mix-
ture was extracted with AcOEt. The organic phase was
washed with saturated NH4Cl solution and saturated NaCl
solution, dried with MgSO4, and concentrated. The residue
was purified bycolumn chromatographyon silica gel
(hexane/AcOEt, 1:1) to afford 7; yield: 3.5 mg (78%). IR
6-Methylene-2-vinyl-1,5,6,8a-tetrahydro-2H-indolizin-3-
one (10a): yield: 10.1 mg (50%); IR (neat): n=1689 (s),
1642 (m) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.56 (m,
;
1H), 2.52 (m, 1H), 3.23 (ddd, J=6.8, 6.9, 7.1 Hz, 1H), 3.60
(d, J=15.6 Hz, 1H), 4.19 (m, 1H), 4.73 (d, J=15.6 Hz, 1H),
4.98 (s, 2H), 5.18 (d, J=17.1 Hz, 1H), 5.21 (d, J=9.6 Hz,
1H), 5.78 (d, J=9.8 Hz, 1H), 5.92 (ddd, J=6.8, 9.6, 17.1 Hz,
1H), 6.22 (d, J=9.8 Hz, 1H); 13C NMR (67.8 MHz, CDCl3):
d=32.9, 42.0, 46.7, 52.7, 113.2, 117.5, 127.2, 128.9, 134.8,
136.7, 172.1; EI-LR-MS: m/z=175 (M+), 160, 146, 132, 117,
106, 93; EI-HR-MS: m/z=175.0985, calcd. for C11H13ON
(M+): 175.09970.
(neat): n=1747 (s), 1706 (s) cmÀ1 1H NMR (270 MHz,
;
CDCl3): d=1.77 (ddd, J=1.3, 2.3, 7.1 Hz, 3H), 2.49 (dddq,
J=3.3, 5.6, 16.1, 2.3 Hz, 1H), 3.04 (dddq, J=2.1, 7.9, 16.1,
1.3 Hz, 1H), 3.90 (ddd, J=2.0, 3.8, 14.5 Hz, 1H), 4.63 (ddd,
J=1.5, 3.0, 14.5 Hz, 1H), 4.70 (m, 1H), 5.17 (d, J=17.5 Hz,
1H), 5.21 (d, J=10.6 Hz, 1H), 5.84 (m, 1H), 6.49 (dd, J=
10.6, 17.5 Hz, 1H), 6.53 (ddq, J=2.1, 3.3, 7.1 Hz, 1H);
13C NMR (67.8 MHz, CDCl3): d=14.9, 30.4, 50.1, 64.1,
Adv. Synth. Catal. 2007, 349, 1231 – 1246
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1239

Hideaki Wakamatsu et al.
FULL PAPERS
2-But-2-ynyl-2-azabicyclo
A
2-(3-Phenyl-prop-2-ynyl)-2-azabicyclo
en-3-one (8c)
G
To a suspension of NaH (160.0 mg, 4.00 mmol) in DMF
(8 mL) was added 2-aza-bicyclo[2.2.1]hept-5-en-3-one
To the solution of 8a (145.4 mg, 0.99 mmol), CuI (9.4 mg,
49.40 mmol), Pd(PPh3)4 (57.1 mg, 49.40 mmol) and Et3N
(363.7 mg, 3.33 mmol) in DMF (10 mL) at 08C, and stirred
at room temperature for 1 h. To this suspension was added
1-bromo-2-butyne (0.44 mL, 5.00 mmol) at 08C, and stirred
at room temperature for 1 h. Saturated NH4Cl solution was
added, and the mixture was extracted with AcOEt. The or-
ganic phase was washed with H2O and saturated NaCl solu-
tion, dried with MgSO4, and concentrated. The residue was
purified bycolumn chromatographyon silica gel (hexane/
AcOEt, 1:1) to afford 8b; yield: 418.1 mg (78%). IR (neat):
AHCTREUNG
(2.5 mL) in benzene (1 mL) was added PhI (0.12 mL,
1.04 mmol) at room temperature, and stirred for 14 h. The
volatiles were removed under reduce pressure, and the resi-
due was purified bycolumn chromatographyon silica gel
(hexane/AcOEt, 3:2) to afford 8c; yield: 181.3 mg (82%).
IR (neat): n=2243 (w), 1710 (s), 1599 (w), 1560 (w), 757 (s)
1
cmÀ1; H NMR (270 MHz, CDCl3): d=2.15 (ddd, J=1.5, 1.6,
7.7 Hz, 1H), 2.34 (ddd, J=1.6, 1.8, 7.7 Hz, 1H), 3.39 (m,
1H), 4.02 (d, J=17.6 Hz, 1H), 4.18 (d, J=17.6 Hz, 1H),
4.37 (m, 1H), 6.59 (ddd, J=1.5, 3.3, 5.2 Hz, 1H), 6.96 (ddd,
J=0.5, 2.0, 5.2 Hz, 1H), 7.28–7.44 (m, 5H); 13C NMR
(67.8 MHz, CDCl3): d=33.5, 53.0, 57.0, 62.4, 82.4, 84.2,
121.9, 127.7, 127.8, 131.0, 135.7, 139.1, 178.9; EI-LR-MS:
m/z=223 (M+), 194, 167, 129, 115, 66; EI-HR-MS: m/z=
223.0990, calcd. for C15H13ON (M+): 223.0997.
n=2228 (w), 1712 (s), 1559 (w) cmÀ1; H NMR (270 MHz,
CDCl3): d=1.81 (t, J=2.5 Hz, 3H), 2.12 (dt, J=7.7, 1.5 Hz,
1H), 2.31 (dt, J=7.7, 1.5 Hz, 1H), 3.36 (m, 1H), 3.68 (dq,
J=17.2, 2.5 Hz, 1H), 3.94 (dq, J=17.2, 2.5 Hz, 1H), 4.31
(ddd, J=1.5, 1.6, 1.8 Hz, 1H), 6.56 (ddd, J=1.5, 3.1, 5.3 Hz,
1H), 6.92 (dd, J=2.1, 5.3 Hz, 1H); 13C NMR (67.8 MHz,
CDCl3): d=3.5 (CH3), 33.8 (CH2), 53.7 (CH), 57.7(CH2),
62.8 (CH), 72.8 (C), 80.7 (C), 136.5 (CH), 139.7 (CH), 179.6
(C); EI-LR-MS: m/z=161 (M+), 88, 66; EI-HR-MS: m/z=
161.0810, calcd. for C10H11ON (M+): 161.0841.
6-(1-Phenylvinyl)-2-vinyl-1,2,5,7a-tetrahydropyrrolizin-
3-one (9c) and 6-Methylene-7-phenyl-2-vinyl-1,5,6,8a-
tetrahydro-2H-indolizin-3-one (10c)
6-Isopropenyl-2-vinyl-1,2,5,7a-tetrahydropyrrolizin-3-
one (9b) and 7-Methyl-6-methylene-2-vinyl-1,5,6,8a-
tetrahydro-2H-indolizin-3-one (10b)
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 8c (30.8 mg, 0.14 mmol) and 1b
(11.7 mg, 13.79 mmol) in toluene (7 mL) was stirred at 808C
for 0.5 h to afford 9c and 10c.
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 8b (48.5 mg, 0.30 mmol) and 1b
(25.5 mg, 0.03 mmol) in toluene (15 mL) was stirred at 808C
for 0.5 h to afford 9b and 10b.
9c: yield: 19.3 mg (56%); IR (neat): n=1737 (m), 1699
1
(s), 1644 (m), 756 (s) cmÀ1; H NMR (270 MHz, CDCl3): d=
1.75 (ddd, J=9.6, 11.7, 12.4 Hz, 1H), 2.57 (ddd, J=5.9, 7.3,
11.7 Hz, 1H), 3.48 (m, 1H), 3.97 (m, 1H), 4.64–4.74 (m,
2H), 5.15 (dt, J=17.3, 1.5 Hz, 1H), 5.18–5.25 (m, 3H), 5.69
(d, J=1.2 Hz, 1H), 5.96 (ddd, J=6.8, 10.6, 17.3 Hz, 1H),
7.25–7.39 (m, 5H); 13C NMR (67.8 MHz, CDCl3): d=36.4,
48.3, 50.0, 65.7, 116.5, 117.5, 127.7, 128.2, 128.3, 128.5, 134.7,
140.5, 141.5, 143.4, 176.9; EI-LR-MS: m/z=251 (M+), 169,
148; EI-HR-MS: m/z=251.1331, calcd. for C17H17ON (M+):
251.1310.
9b: yield: 16.9 mg (30%); IR (neat): n=1701 (s), 1644
(m) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.77 (ddd, J=
;
9.7, 9.7, 12.2 Hz, 1H), 1.93 (s, 3H), 2.61 (ddd, J=5.6, 6.2,
12.2 Hz, 1H), 3.48 (m, 1H), 3.85 (ddd, J=2.0, 2.6, 14.5 Hz,
1H), 4.58 (ddd, J=1.5, 3.5, 14.5 Hz, 1H), 4.69 (m, 1H), 4.91
(s, 1H), 5.04 (s, 1H), 5.15 (ddd, J=1.3, 1.3, 17.3 Hz, 1H),
5.21 (ddd, J=1.3, 1.3, 10.6 Hz, 1H), 5.81 (d, J=1.6 Hz, 1H),
5.95 (ddd, J=6.8, 10.6, 17.3 Hz, 1H); 13C NMR (67.8 MHz,
CDCl3): d=20.2 (CH3), 36.4 (CH2), 48.4 (CH), 49.7 (CH2),
65.6 (CH), 115.0 (CH2), 117.4 (CH2), 125.1 (CH), 134.8
(CH), 136.9 (C), 142.4 (C), 176.8 (C); EI-LR-MS: m/z=189
(M+), 174, 148, 107, 88; EI-HR-MS: m/z=189.1179, calcd.
for C12H15ON (M+): 189.1154.
10c: yield: 5.1 mg (15%); IR (neat): n=1674 (s), 1644
(m), 776 (s) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.67
;
(ddd, J=10.0, 11.7, 12.2 Hz, 1H), 2.58 (ddd, J=6.5, 7.9,
12.2 Hz, 1H), 3.28 (m, 1H), 3.74 (m, 1H), 4.36 (m, 1H),
4.82 (d, J=15.0 Hz, 1H), 4.94 (m, 1H), 5.14 (m, 1H), 5.21
(ddd, J=1.3, 1.5, 17.1 Hz, 1H), 5.25 (ddd, J=1.3, 1.5,
10.5 Hz, 1H), 5.74 (br, 1H), 5.98 (ddd, J=6.8, 10.5, 17.1 Hz,
1H), 7.23–7.39 (m, 5H); EI-LR-MS: m/z=251 (M+), 222,
174, 128, 115; EI-HR-MS: m/z=251.1333, calcd. for
C17H17ON (M+): 251.1310.
10b: yield: 22.8 mg (40%); IR (neat): n=1691 (s), 1643
(m) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.55 (ddd, J=
;
9.7, 9.7, 12.2 Hz, 1H), 1.87 (s, 3H), 2.49 (ddd, J=6.4, 7.9,
12.2 Hz, 1H), 3.21 (m, 1H), 3.59 (dd, J=1.8, 15.3 Hz, 1H),
4.18 (m, 1H), 4.70 (d, J=15.3 Hz, 1H), 4.99 (s, 1H), 5.09 (d,
J=1.5 Hz, 1H), 5.17 (ddd, J=1.3, 1.5, 17.1 Hz, 1H), 5.21
(ddd, J=1.3, 1.5, 10.6 Hz, 1H), 5.63 (s, 1H), 5.92 (ddd, J=
6.8, 10.6, 17.1 Hz, 1H); 13C NMR (67.8 MHz, CDCl3): d=
19.1 (CH3), 33.2 (CH2), 42.9 (CH2), 46.5 (CH), 53.3 (CH),
110.6 (CH2), 117.5 (CH2), 126.8 (CH), 131.4 (C), 135.1
(CH), 138.4 (C), 172.2 (C); EI-LR-MS: m/z=189 (M+), 174,
149, 88; EI-HR-MS: m/z=189.1149, calcd. for C12H15ON
(M+): 189.1154.
2-[3-(p-Methoxyphenyl)-prop-2-ynyl]-2-azabicyclo-
A
To the solution of 8a (203.9 mg, 1.39 mmol), CuI (13.2 mg,
69.27 mmol), Pd(PPh3)4 (80.0 mg, 69.27 mmol) and Et3N
AHCTREUNG
(4 mL) in benzene (3 mL) was added 1-iodo-4-methoxy-ben-
zene (340.5 mg, 1.45 mmol) at room temperature, and stirred
for 36 h. The volatiles were removed under reduced pres-
sure, and the residue was purified bycolumn chromatogra-
phyon silica gel (hexane/AcOEt, 3:2) to afford 8d; yield:
123.3 mg (35%); IR (neat): n=2241 (w), 1710 (s), 1607 (m),
1568 (w), 1249 (s), 1033 (m), 756 (s) cmÀ1
;
1H NMR
1240
asc.wiley-vch.de
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1231 – 1246

Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine Derivatives
FULL PAPERS
(270 MHz, CDCl3): d=2.14 (ddd, J=1.5, 1.5, 7.7 Hz, 1H),
2.33 (ddd, J=1.5, 1.8, 7.7 Hz, 1H), 3.39 (m, 1H), 3.81 (s,
3H), 4.01 (d, J=17.6 Hz, 1H), 4.17 (d, J=17.6 Hz, 1H),
4.37 (m, 1H), 6.58 (ddd, J=1.5, 3.3, 5.3 Hz, 1H), 6.84 (d, J=
8.9 Hz, 2H), 6.94 (ddd, J=0.5, 2.0, 5.3 Hz, 1H), 7.35 (d, J=
8.9 Hz, 2H); 13C NMR (67.8 MHz, CDCl3): d=34.0 (CH2),
53.4 (CH), 55.0 (CH3), 57.4 (CH2), 62.7 (CH), 81.3 (C), 84.5
(C), 113.7 (CH), 114.4 (C), 132.8 (CH), 136.0 (CH), 139.6
(CH), 159.5 (C), 179.3 (C); EI-LR-MS: m/z=253 (M+), 187,
159, 145, 132, 102, 66; EI-HR-MS: m/z=253.1100, calcd. for
C16H15O2N (M+): 253.1103.
Ethyl 4-[3-(3-Oxo-2-azabicyclo
prop-1-ynyl]-benzoate (8e)
A
To the solution of 8a (225.1 mg, 1.53 mmol), CuI (14.6 mg,
76.48 mmol), Pd(PPh3)4 (88.4 mg, 76.48 mmol) and Et3N
AHCTREUNG
(4 mL) in benzene (3 mL) was added ethyl 4-iodobenzoate
(0.27 mL, 1.61 mmol) at room temperature, and stirred for
14 h. The volatiles were removed under reduced pressure,
and the residue was purified bycolumn chromatographyon
silica gel (hexane/AcOEt, 3:2) to afford 8e; yield: 418.7 mg
(93%). IR (neat): n=2245 (w), 1715 (s), 1606 (m), 1560 (w),
756 (s) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.40 (t, J=
;
7.1 Hz, 3H), 2.17 (ddd, J=1.5, 1.5, 7.7 Hz, 1H), 2.35 (ddd,
J=1.6, 1.6, 7.7 Hz, 1H), 3.41 (m, 1H), 4.05 (d, J=17.8 Hz,
1H), 4.20 (d, J=17.8 Hz, 1H), 4.38 (m, 1H), 4.38 (q, J=
7.1 Hz, 2H), 6.60 (ddd, J=1.5, 3.1, 4.9 Hz, 1H), 6.95 (ddd,
J=0.5, 1.6, 4.9 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.99 (d, J=
8.4 Hz, 2H); 13C NMR (67.8 MHz, CDCl3): d=13.8 (CH3),
33.7 (CH2), 53.1 (CH), 57.1 (CH2), 60.6 (CH2), 62.6 (CH),
83.6 (C), 85.8 (C), 126.6 (C), 129.0 (CH), 129.6 (C), 131.0
(CH), 135.9 (CH), 139.2 (CH), 165.3 (C), 179.0 (C); EI-LR-
MS: m/z=295 (M+), 266, 250, 230, 222, 202, 184, 159, 114,
101, 66; EI-HR-MS: m/z=295.1193, calcd. for C18H17O3N
(M+): 295.1208.
6-[1-(p-Methoxyphenyl)-vinyl]-2-vinyl-1,2,5,7a-tetra-
hydropyrrolizin-3-one (9d), 7-(p-Methoxyphenyl)-6-
methylene-2-vinyl-1,5,6,8a-tetrahydro-2H-indolizin-3-
one (10d) and 1-[3-(p-Methoxyphenyl)-2-methylene-
but-3-enyl]-3,5-divinylpyrrolidin-2-one (11d)
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 8d (42.5 mg, 0.17 mmol) and 1b
(14.2 mg, 16.78 mmol) in toluene (8.5 mL) was stirred at
808C for 0.5 h to afford 9d, 10d and 11d.
9d: yield: 18.9 mg (40%); IR (neat): n=1693 (s), 1608 (s),
1249 (s), 1033 (m), 755 (s) cmÀ1 1H NMR (270 MHz,
;
CDCl3): d=1.76 (ddd, J=9.6, 11.9, 12.2 Hz, 1H), 2.57 (ddd,
J=5.8, 7.3, 11.9 Hz, 1H), 3.48 (m, 1H), 3.83 (s, 3H), 3.96
(m, 1H), 4.63–4.74 (m, 2H), 5.11–5.25 (m, 4H), 5.71 (br,
1H), 5.96 (ddd, J=6.8, 10.4, 17.1 Hz, 1H), 6.89 (d, J=
8.8 Hz, 2H), 7.23 (d, J=8.8 Hz, 2H); 13C NMR (67.8 MHz,
CDCl3): d=36.4 (CH2), 48.3 (CH), 50.1 (CH2), 55.3 (CH3),
65.6 (CH), 113.6 (CH), 115.8 (CH2), 117.5 (CH2), 128.3
(CH), 129.4 (CH), 132.9 (C), 134.7 (CH), 141.7 (C), 142.8
(C), 159.2 (C), 176.9 (C); EI-LR-MS: m/z=281 (M+), 199,
184, 148, 133; EI-HR-MS: m/z=281.1445, calcd. for
C18H19O2N (M+): 281.1416.
Ethyl 4-[1-(5-Oxo-6-vinyl-5,6,7,7a-tetrahydro-3H-
pyrrolizin-2-yl)-vinyl]-benzoate (9e) and Ethyl 4-(6-
Methylene-3-oxo-2-vinyl-1,2,3,5,6,8a-hexahydro-
indolizin-7-yl)-benzoate (10e)
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 8e (89.1 mg, 0.30 mmol) and 1b
(25.6 mg, 30.17 mmol) in toluene (15 mL) was stirred at
808C for 0.5 h to afford 9e and 10e.
9e: yield: 32.8 mg (34%); IR (neat): n=1713 (s), 1609
10d: yield: 9.8 mg (21%); IR (neat): n=1690 (s), 1609 (s),
1
(m), 756 (s) cmÀ1; H NMR (270 MHz, CDCl3): d=1.41 (t,
1247 (s), 1032 (m), 755 (s) cmÀ1 1H NMR (270 MHz,
;
J=7.1 Hz, 3H), 1.76 (ddd, J=9.6, 11.9, 12.2 Hz, 1H), 2.58
(ddd, J=5.9, 7.3, 11.9 Hz, 1H), 3.49 (m, 1H), 3.98 (m, 1H),
4.40 (q, J=7.1 Hz, 2H), 4.65–4.76 (m, 2H), 5.16 (ddd, J=
1.2, 1.3, 17.3 Hz, 1H), 5.22 (ddd, J=1.0, 1.3, 10.4 Hz, 1H),
5.27 (s, 1H), 5.28 (s, 1H), 5.66 (br, 1H), 5.97 (ddd, J=6.8,
10.4, 17.3 Hz, 1H), 7.37 (d, J=8.1 Hz, 2H), 8.04 (d, J=
8.1 Hz, 2H); 13C NMR (67.8 MHz, CDCl3): d=14.3 (CH3),
36.2 (CH2), 48.2 (CH), 49.9 (CH2), 61.0 (CH2), 65.6 (CH),
117.2 (CH2), 117.5 (CH2), 128.3 (CH), 128.8 (CH), 129.5
(CH), 129.8 (C), 134.6 (CH), 140.9 (C), 142.6 (C), 144.9 (C),
166.2 (C), 176.9 (C); EI-LR-MS: m/z=323 (M+), 294, 278,
250, 241, 167, 148; EI-HR-MS: m/z=323.1507, calcd. for
C20H21O3N (M+): 323.1522.
CDCl3): d=1.66 (ddd, J=10.1, 11.4, 12.0 Hz, 1H), 2.57
(ddd, J=6.4, 7.7, 12.0 Hz, 1H), 3.27 (m, 1H), 3.72 (dd, J=
1.8, 15.0 Hz, 1H), 3.83 (s, 3H), 4.35 (m, 1H), 4.80 (d, J=
15.0 Hz, 1H), 4.96 (d, J=0.8 Hz, 1H), 5.13 (d, J=0.8 Hz,
1H), 5.21 (ddd, J=1.5, 1.5, 17.1 Hz, 1H), 5.24 (ddd, J=1.3,
1.5, 10.6 Hz, 1H), 5.71 (br, 1H), 5.98 (ddd, J=6.8, 10.6,
17.1 Hz, 1H), 6.88 (d, J=8.8 Hz, 2H), 7.18 (d, J=8.8 Hz,
2H); 13C NMR (67.8 MHz, CDCl3): d=33.4 (CH2), 43.4
(CH2), 46.6 (CH), 53.7 (CH), 55.3 (CH3), 113.6 (CH), 114.7
(CH2), 117.6 (CH2), 127.5 (CH), 130.0 (CH), 131.6 (C),
135.0 (CH), 137.8 (C), 138.3 (C), 159.1 (C), 172.2 (C); EI-
LR-MS: m/z=281 (M+), 266, 250, 198, 174, 115; EI-HR-
MS: m/z=281.1446, calcd. for C18H19O2N (M+): 281.1416.
11d: yield: 6.0 mg (12%); IR (neat): n=1693 (s), 1642
10e: yield: 17.5 mg (18%); IR (neat): n=1713 (s), 1695
1
(s), 1608 (m), 753 (m) cmÀ1; H NMR (270 MHz, CDCl3):
(w), 1608 (s), 1248 (s), 1033 (m), 755 (s) cmÀ1 1H NMR
;
d=1.41 (t, J=7.1 Hz, 3H), 1.69 (ddd, J=10.1, 11.7, 12.2 Hz,
1H), 2.60 (ddd, J=6.6, 7.9, 12.2 Hz, 1H), 3.29 (m, 1H), 3.74
(dd, J=1.7, 15.1 Hz, 1H), 4.37 (m, 1H), 4.39 (q, J=7.1 Hz,
1H), 4.83 (d, J=15.1 Hz, 1H), 4.89 (br, 1H), 5.16 (br, 1H),
5.22 (ddd, J=1.5, 1.5, 17.1 Hz, 1H), 5.25 (ddd, J=1.3, 1.5,
10.4 Hz, 1H), 5.79 (br, 1H), 5.98 (ddd, J=6.6, 10.4, 17.1 Hz,
1H), 7.33 (d, J=8.6 Hz, 2H), 8.03 (d, J=8.6 Hz, 2H); EI-
LR-MS: m/z=323 (M+), 294, 278, 250, 174; EI-HR-MS:
m/z=323.1505, calcd. for C20H21O3N (M+): 323.1522.
(270 MHz, CDCl3): d=1.69 (ddd, J=7.6, 9.4, 13.0 Hz, 1H),
2.44 (ddd, J=7.3, 8.9, 13.0 Hz, 1H), 3.10 (m, 1H), 3.65 (d,
J=15.7 Hz, 1H), 3.82 (s, 3H), 4.01 (m, 1H), 4.50 (d, J=
15.7 Hz, 1H), 5.09 (br, 1H), 5.11 (br, 1H), 5.16–5.28 (m,
6H), 5.63 (ddd, J=8.7, 9.7, 17.3 Hz, 1H), 5.96 (ddd, J=6.6,
9.9, 17.8 Hz, 1H), 6.86 (d, J=8.9 Hz, 2H), 7.24 (d, J=
8.9 Hz, 2H); EI-LR-MS: m/z=309 (M+), 294, 281, 266, 226,
186, 173, 159; EI-HR-MS: m/z=309.1713, calcd. for
C20H23O2N (M+): 309.1729.
Adv. Synth. Catal. 2007, 349, 1231 – 1246
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1241

Hideaki Wakamatsu et al.
FULL PAPERS
was extracted with AcOEt. The organic phase was washed
with saturated NaCl solution, dried with MgSO4, and con-
centrated. The residue was purified bycolumn chromatogra-
phyon silica gel (hexane/AcOEt, 3:1) to afford 8g; yield:
185.0 mg (16%). IR (neat): n=2175 (w), 1714 (s), 1561 (w)
2-[3-(Trimethylsilyl)-prop-2-ynyl]-2-azabicyclo
hept-5-en-3-one (8f)
[2.2.1]-
To a solution of 8a (83.9 mg, 0.57 mmol) in THF (6 mL) was
added BuLi (0.44 mL, 0.68 mmol, 1.57M hexane solution) at
À788C, and stirred for 1 h. To the resultant solution was
added TMSCl (0.14 mL, 1.14 mmol), and stirred for 1 h. Sa-
turated NH4Cl solution was added, and the mixture was ex-
tracted with AcOEt. The organic phase was washed with sa-
turated NaCl solution, dried with MgSO4, and concentrated.
The residue was purified bycolumn chromatographyon
silica gel (hexane/AcOEt, 3:2) to afford 8f; yield: 97.3 mg
1
cmÀ1; H NMR (270 MHz, CDCl3): d=1.01–1.07 (m, 21H),
2.13 (ddd, J=1.5, 1.6, 7.7 Hz, 1H), 2.30 (ddd, J=1.5, 1.8,
7.7 Hz, 1H), 3.35 (m, 1H), 3.83 (d, J=17.8 Hz, 1H), 4.03 (d,
J=17.8 Hz, 1H), 4.34 (m, 1H), 6.56 (ddd, J=1.5, 3.3,
5.3 Hz, 1H), 6.92 (ddd, J=0.5, 2.0, 5.3 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3): d=11.0 (CH), 18.4 (CH3), 34.1 (CH2),
53.5 (CH), 57.8 (CH2), 62.7 (CH), 85.7 (C), 100.8 (C), 136.4
(CH), 139.6 (CH), 179.1 (C); EI-LR-MS: m/z=303 (M+),
260, 237, 194, 166, 138, 100; EI-HR-MS: m/z=303.2035,
calcd. for C18H29ONSi (M+): 303.2018.
(78%). IR (neat): n=2178 (w), 1716 (s), 1560 (w) cmÀ1
;
1H NMR (270 MHz, CDCl3): d=0.14 (s, 9H), 2.11 (d, J=
7.6 Hz, 1H), 2.27 (d, J=7.6 Hz, 1H), 3.33 (br, 1H), 3.77 (d,
J=17.6 Hz, 1H), 3.94 (d, J=17.6 Hz, 1H), 4.29 (dd, J=1.8,
3.6 Hz, 1H), 6.52 (ddd, J=1.8, 3.6, 5.1 Hz, 1H), 6.88 (dd,
J=1.8, 5.1 Hz, 1H); 13C NMR (67.8 MHz, CDCl3): d=À0.3,
34.2, 53.5, 57.5, 62.7, 89.7, 99.3, 136.1, 139.5, 179.2; EI-
LRMS: m/z=219 (M+), 204, 176, 161, 88; EI-HR-MS: m/
z=219.1092, calcd. for C12H17ONSi (M+): 219.1079.
6-[1-(Triisopropylsilyl)-vinyl]-2-vinyl-1,2,5,7a-tetra-
hydropyrrolizin-3-one (9g), 1-[3-(Triisopropylsilyl)-
prop-2-ynyl]-3,5-divinylpyrrolidin-2-one (12g) and
2-Ethylidene-6-[1-(triisopropylsilyl)-vinyl]-1,2,5,7a-
tetrahydropyrrolizin-3-one (9g’)
6-[1-(Trimethylsilyl)-vinyl]-2-vinyl-1,2,5,7a-tetrahydro-
pyrrolizin-3-one (9f) and 6-Methylene-7-(trimethyl-
silyl)-2-vinyl-1,5,6,8a-tetrahydro-2H-indolizin-3-one
(10f)
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 8g (26.9 mg, 0.09 mmol) and 1b
(7.5 mg, 8.86 mmol) in toluene (4.4 mL) was stirred at 808C
for 0.5 h to afford the mixture of 9g and 9g’ (yield: 9.0 mg,
31%, 1:1) and 12g. After the ratio of 9g and 9g’ had been
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 8f (35.2 mg, 0.16 mmol) and 1b
(13.6 mg, 16.05 mmol) in toluene (8 mL) was stirred at 808C
for 0.5 h to afford 9f and 10f.
1
determined by H NMR, the CH2Cl2 solution of 9g and 9g’
was stirred with silica gel at room temperature for 3 h. The
volatiles were removed under reduced pressure, and the res-
idue was purified bycolumn chromatographyon silica gel to
afford 9g’ as a sole product.
9f: yield: 21.0 mg (53%); IR (neat): n=1705 (s), 1644
1
(m) cmÀ1; H NMR (270 MHz, CDCl3): d=0.18 (s, 9H), 1.75
12g: yield: 10.7 mg (36%); IR (neat): n=2176 (w), 1704
(ddd, J=9.6, 12.2, 12.2 Hz, 1H), 2.61 (ddd, J=5.6, 6.1,
12.2 Hz, 1H), 3.47 (m, 1H), 3.83 (m, 1H), 4.57 (ddd, J=1.6,
1.6, 14.6 Hz, 1H), 4.68 (m, 1H), 5.15 (ddd, J=1.3, 1.4,
17.1 Hz, 1H), 5.21 (ddd, J=1.3, 1.4, 10.4 Hz, 1H), 5.53 (d,
J=2.1 Hz, 1H), 5.67 (d, J=2.1 Hz, 1H), 5.82 (d, J=1.6 Hz,
1H), 5.96 (ddd, J=6.7, 10.4, 17.1 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3): d=À0.8, 36.6, 48.4, 50.2, 65.7, 117.4,
126.5, 127.4, 134.8, 142.9, 143.8, 176.8; EI-LR-MS: m/z=247
(M+), 232, 148, 106; EI-HR-MS: m/z=247.1394, calcd. for
C14H21ONSi (M+): 247.1392.
(s), 1644 (w) cmÀ1 1H NMR (270 MHz, CDCl3): d=0.98–
;
1.12 (m, 21H), 1.68 (ddd, J=8.2, 9.9, 12.9 Hz, 1H), 2.48
(ddd, J=6.9, 8.7, 12.9 Hz, 1H), 3.10 (dddt, J=6.6, 6.9, 8.2,
1.5 Hz, 1H), 3.60 (d, J=17.5 Hz, 1H), 4.17 (ddd, J=8.7, 8.7,
9.9 Hz, 1H), 4.61 (d, J=17.5 Hz, 1H), 5.20 (ddd, J=1.3, 1.5,
17.8 Hz, 1H), 5.21 (ddd, J=1.3, 1.5, 9.9 Hz, 1H), 5.29 (dd,
J=1.3, 9.9 Hz, 1H), 5.39 (dd, J=1.3, 17.0 Hz, 1H), 5.63
(ddd, J=8.7, 9.9, 17.0 Hz, 1H), 5.93 (ddd, J=6.6, 9.9,
17.8 Hz, 1H); 13C NMR (67.8 MHz, CDCl3): d=11.1 (CH),
18.5 (CH3), 31.3 (CH2), 31.9 (CH2), 45.8 (CH), 58.8 (CH),
84.8 (C), 101.1 (C), 117.3 (CH2), 119.7 (CH2), 135.2 (CH),
137.2 (CH), 174.0 (C); EI-LR-MS: m/z=331 (M+), 288, 260,
138, 109; EI-HR-MS: m/z=331.2320, calcd. for C20H33ONSi
(M+): 331.2332.
10f: yield: 9.2 mg (23%); IR (neat): n=1695 (s), 1621 (w)
cmÀ1 1H NMR (270 MHz, CDCl3): d=0.19 (s, 9H), 1.54
;
(ddd, J=10.1, 10.2, 12.0 Hz, 1H), 2.51 (ddd, J=6.4, 7.9,
12.0 Hz, 1H), 3.22 (m, 1H), 3.53 (dd, J=1.6, 15.0 Hz, 1H),
4.15 (m, 1H), 4.60 (d, J=15.0 Hz, 1H), 5.05 (br, 1H), 5.09
(br, 1H), 5.18 (ddd, J=1.2, 1.5, 17.1 Hz, 1H), 5.21 (ddd, J=
1.3, 1.5, 10.4 Hz, 1H), 5.94 (ddd, J=6.6, 10.4, 17.1 Hz, 1H),
6.02 (br, 1H); 13C NMR (67.8 MHz, CDCl3): d=À0.7, 33.0,
43.7, 46.7, 53.8, 114.1, 117.5, 135.0, 137.2, 138.2, 138.8, 171.1;
EI-LR-MS: m/z=247 (M+), 232, 219, 174, 73; EI-HR-MS:
m/z=247.1366, calcd. for C14H21ONSi (M+): 247.1392.
9g’: IR (neat): n=1699 (s), 1674 (s) cmÀ1 1H NMR
;
(270 MHz, CDCl3): d=0.80–1.05 (m, 21H), 1.77 (ddd, J=
1.3, 2.3, 7.1 Hz, 3H), 2.46 (m, 1H), 3.03 (m, 1H), 3.96 (m,
1H), 4.59–4.73 (m, 2H), 5.58 (d, J=2.1 Hz, 1H), 5.78 (m,
1H), 5.89 (d, J=2.1 Hz, 1H), 6.52 (m, 1H); EI-LR-MS: m/
z=331 (M+), 288, 274, 244, 218, 202, 149, 109; EI-HR-MS:
m/z=331.2321, calcd. for C20H33ONSi (M+): 331.2332.
2-[3-(Triisopropylsilyl)-prop-2-ynyl]-2-azabicyclo-
[2.2.1]hept-5-en-3-one (8g)
3-Ethylidene-1-[3-(triisopropylsilyl)-prop-2-ynyl]-5-
vinyl-pyrrolidin-2-one (12g’)
A
To a solution of 8a (563.8 mg, 3.83 mmol) in THF (38 mL)
was added BuLi (2.8 mL, 4.41 mmol, 1.56M hexane solu-
tion) at À788C, and stirred for 1 h. To the resultant solution
was added TIPSOTf (2.1 mL, 7.66 mmol), and stirred for
0.5 h. Saturated NH4Cl solution was added, and the mixture
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 12g (8.6 mg, 0.03 mmol) and 1b
(4.4 mg, 5.18 mmol,) in toluene (2.0 mL) was stirred at 808C
for 4.5 h to afford the mixture of 9g and 9g’ (yield: 3.2 mg,
1242
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ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1231 – 1246

Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine Derivatives
FULL PAPERS
37%, 1:1) and the mixture of 12g and 12g’ (yield: 4.2 mg,
(dd, J=0.8, 17.0 Hz, 1H), 5.67 (ddd, J=8.9, 9.8, 17.0 Hz,
1H), 6.58 (m, 1H), 7.27–7.44 (m, 5H); 13C NMR (67.8 MHz,
CDCl3): d=14.6 (CH3), 29.3 (CH2), 30.9 (CH2), 57.7 (CH),
83.3 (C), 83.6 (C), 118.9 (CH2), 122.7 (C), 128.2 (CH), 128.3
(CH), 128.8 (CH), 131.0 (C), 131.7 (CH), 137.3 (CH), 167.7
(C); EI-LR-MS: m/z=251 (M+), 236, 146, 115, 105; EI-HR-
MS: m/z=251.1323, calcd. for C17H17ON (M+): 251.1310.
49%, 9:1).
12g’: IR (neat): n=2176 (w), 1701 (s), 1679 (s) cmÀ1
;
1H NMR (270 MHz, CDCl3): d=0.95–1.13 (m, 21H), 1.71
(ddd, J=1.8, 1.8, 7.1 Hz, 3H), 2.32 (m, 1H), 2.87 (m, 1H),
3.60 (d, J=17.5 Hz, 1H), 4.22 (ddd, J=4.3, 8.4, 8.7 Hz, 1H),
4.66 (d, J=17.5 Hz, 1H), 5.19 (dd, J=1.3, 9.7 Hz, 1H), 5.28
(dd, J=1.3, 17.0 Hz, 1H), 5.54 (ddd, J=8.7, 9.7, 17.0 Hz,
1H), 6.48 (m, 1H); EI-LR-MS: m/z=331 (M+), 288, 274,
250, 202, 149, 123, 109; EI-HR-MS: m/z=331.2320, calcd.
for C20H33ONSi (M+): 331.2332.
2-Ethylidene-6-(1-phenylvinyl)-1,2,5,7a-tetrahydro-
pyrrolizin-3-one (9c’) and 2-Ethylidene-6-methylene-
7-phenyl-1,5,6,8a-tetrahydro-2H-indolizin-3-one (10c’)
3-Ethylidene-1-prop-2-ynyl-5-vinylpyrrolidin-2-one
(12a’)
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 12c’ (13.9 mg, 0.06 mmol) and 1b
(4.7 mg, 5.53 mmol,) in toluene (2.8 mL) was stirred at 808C
for 0.5 h to afford 9c’ and 10c’.
To a solution of 12g (16.5 mg, 0.05 mmol) in THF (0.5 mL)
was added TBAF (0.15 mL, 0.15 mmol, 1m THF solution) at
08C, and stirred for 0.5 h. NH4Cl was added and the vola-
tiles were concentrated. The residue was purified bycolumn
chromatographyon silica gel (hexane/AcOEt, 2:1) to afford
12a’; yield: 8.7 mg (99%). IR (neat): n=2117 (w), 1696 (s),
9c’: yield: 8.5 mg (61%); IR (neat): n=1736 (m), 1698 (s),
1669 (s), 758 (m) cmÀ1 1H NMR (270 MHz, CDCl3): d=
;
1.76 (ddd, J=1.3, 2.3, 7.1 Hz, 3H), 2.48 (m, 1H), 3.00 (m,
1H), 4.05 (m, 1H), 4.69–4.80 (m, 2H), 5.23 (br, 2H), 5.71
(br, 1H), 6.55 (ddq, J=2.3, 3.3, 7.1 Hz, 1H), 7.25–7.40 (m,
5H); 13C NMR (67.8 MHz, CDCl3): d=14.9, 30.3, 51.3, 64.6,
116.5, 127.7, 128.2, 128.3, 129.1, 129.3, 133.9, 140.5, 142.8,
143.4, 172.1; EI-LR-MS: m/z=251 (M+), 148, 83; EI-HR-
MS: m/z= 251.1299, calcd. for C17H17ON (M+): 251.1310.
10c’: yield: 4.6 mg (33%); IR (neat): n=1694 (s), 1673 (s),
1676 (s) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.78 (ddd,
;
J=1.8, 1.8, 7.1 Hz, 3H), 2.18 (t, J=2.5 Hz, 1H), 2.40 (m,
1H), 2.95 (m, 1H), 3.61 (dd, J=2.5, 17.3 Hz, 1H), 4.25 (ddd,
J=4.5, 4.5, 8.6 Hz, 1H), 4.64 (dd, J=2.5, 17.3 Hz, 1H), 5.28
(dd, J=1.0, 9.9 Hz, 1H), 5.36 (dd, J=1.0, 17.0 Hz, 1H), 5.62
(ddd, J=8.6, 9.9, 17.0 Hz, 1H), 6.57 (m, 1H); 13C NMR
(67.8 MHz, CDCl3): d=14.6 (CH3), 29.2 (CH2), 30.0 (CH2),
57.6 (CH), 71.7 (CH), 77.8 (C), 119.1 (CH2), 128.9 (CH),
130.8 (C), 137.1 (CH), 167.7 (C); EI-LR-MS: m/z=175
(M+), 88, 73, 70; EI-HR-MS: m/z=175.0967, calcd. for
C11H13ON (M+): 175.0997.
1
755 (s) cmÀ1; H NMR (270 MHz, CDCl3): d=1.79 (ddd, J=
1.6, 1.9, 7.1 Hz, 3H), 2.42 (m, 1H), 3.04 (m, 1H), 3.82 (ddd,
J=1.8, 2.0, 15.2 Hz, 1H), 4.47 (m, 1H), 4.93 (d, J=15.2 Hz,
1H), 4.93 (m, 1H), 5.16 (br, 1H), 5.74 (br, 1H), 6.56 (m,
1H), 7.21–7.36 (m, 5H); EI-LR-MS: m/z=251 (M+), 236,
222, 174; EI-HR-MS: m/z=251.1336, calcd. for C17H17ON
(M+): 251.1310.
2-Ethylidene-6-methylene-1,5,6,8a-tetrahydro-2H-
indolizin-3-one (10a’)
2-[4-(Triisopropylsilyl)-but-3-ynyl]-2-azabicyclo-
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 12g’ (8.7 mg, 0.05 mmol) and 1b
(4.2 mg, 4.96 mmol,) in toluene (2.5 mL) was stirred at 808C
for 0.5 h to afford 7 (yield: 5.2 mg, 60%) and 10a’.
A
To a solution of 4 (3.07 g, 28.13 mmol) in CH3CN (150 mL)
was added K2CO3 (4.67 g, 33.76 mmol), KOH (4.74 g,
84.39 mmol) and BnNEt3Br (100 mg, 0.37 mmol) at room
temperature, and stirred for 5 min. To this solution was
added 2-(2-bromoethyl)-1,3-dioxolane (4.0 mL, 33.76 mmol),
and stirred at reflux for 1 h. The reaction mixture was fil-
tered, and undissolved material was washed with Et2O. The
filtrate was evapolated, and the residue was purified by
column chromatographyon silica gel (AcOEt) to afford 2-
10a’: 1.8 mg (21%); IR (neat): n=1694 (s), 1668 (s), 1599
(m) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.78 (ddd, J=
;
1.5, 1.8, 6.9 Hz, 3H), 2.31 (m, 1H), 2.98 (m, 1H), 3.68 (d,
J=15.4 Hz, 1H), 4.29 (m, 1H), 4.85 (d, J=15.4 Hz, 1H),
4.98 (s, 1H), 5.00 (s, 1H), 5.79 (d, J=9.9 Hz, 1H), 6.23 (dd,
J=1.9, 9.9 Hz, 1H), 6.52 (m, 1H); EI-LR-MS: m/z=175
(M+), 160, 146, 131, 117; EI-HR-MS: m/z=175.0995, calcd.
for C11H13ON (M+): 175.0997.
(2-[1,3]doxolan-2-yl-ethyl)-2-aza-bicyclo
one; yield: 5.44 g (92%). IR (neat): n=1699 (s), 1559 (w),
1140 (s) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.76–1.85
A
;
3-Ethylidene-1-(3-phenylprop-2-ynyl)-5-vinylpyrroli-
(m, 2H), 2.13 (ddd, J=1.5, 1.5, 7.6 Hz, 1H), 2.31 (ddd, J=
1.6, 1.6, 7.6 Hz, 1H), 3.01 (ddd, J=6.8, 7.9, 14.3 Hz, 1H),
3.31–3.43 (m, 2H), 3.82–4.00 (m, 4H), 4.21 (m, 1H), 4.86 (t,
J=4.7 Hz, 1H), 6.64 (ddd, J=1.5, 3.3, 5.3 Hz, 1H), 6.84
(ddd, J=0.7, 2.0, 5.3 Hz, 1H); 13C NMR (67.8 MHz, CDCl3):
d=31.6 (CH2), 38.6 (CH2), 53.3 (CH), 58.2 (CH2), 62.9
(CH), 64.3 (CH2), 64.4 (CH2), 102.0 (CH), 137.4 (CH), 139.2
(CH), 179.8 (C); EI-LR-MS: m/z=209 (M+), 142, 66; EI-
HR-MS: m/z=209.1078, calcd. for C11H15O3N (M+):
209.1052.
din-2-one (12c’)
To the solution of 12a’ (25.5 mg, 0.15 mmol), CuI (1.4 mg,
7.28 mmol), Pd(PPh3)4 (8.4 mg, 7.28 mmol) and Et3N (2 mL)
A
in benzene (1 mL) was added PhI (0.02 mL, 0.15 mmol) at
rt, and stirred for 16 h. The volatiles were removed under
reduced pressure, and the residue was purified bycolumn
chromatographyon silica gel (hexane/AcOEt, 3:2) to afford
12c’; yield: 34.3 mg (94%). IR (neat): n=2235 (w), 1697 (s),
1677 (s), 757 (s) cmÀ1; H NMR (270 MHz, CDCl3): d=1.78
1
(ddd, J=1.6, 1.7, 7.1 Hz, 3H), 2.41 (m, 1H), 2.96 (m, 1H),
3.85 (d, J=17.5 Hz, 1H), 4.32 (ddd, J=4.5, 8.2, 8.9 Hz, 1H),
4.86 (d, J=17.5 Hz, 1H), 5.30 (dd, J=0.8, 9.8 Hz, 1H), 5.39
To
bicyclo
tone (28 mL) was added H2O (4 mL) and TsOH·H2O
a
solution of 2-(2-[1,3]doxolan-2-yl-ethyl)-2-aza-
AHCTREUNG
Adv. Synth. Catal. 2007, 349, 1231 – 1246
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1243

Hideaki Wakamatsu et al.
FULL PAPERS
(132.1 mg, 0.70 mmol) at room temperature, and stirred at
reflux for 26 h. After cooling to room temperature, saturat-
ed NaHCO3 solution was added, and the aqueous solution
was extracted with AcOEt. The organic phase was washed
with saturated NaCl solution, dried with MgSO4, and con-
centrated. The residue was used next reaction without fur-
ther purification.
To a solution of the crude product in CH2Cl2 (7 mL) was
added CBr4 (690.9 mg, 2.08 mmol) and PPh3 (1.09 g,
4.17 mmol) at 08C, and stirred for 1 h. The volatiles were re-
moved under reduced pressure, and the residue was purified
bycolumn chromatographyon silica gel (AcOEt) to afford
60.3 (CH), 81.9 (C), 105.5 (C), 117.1 (CH2), 119.1 (CH2),
135.5 (CH), 138.3 (CH), 174.5 (C); EI-LR-MS: m/z=345
(M+), 302, 150, 109; EI-HR-MS: m/z=345.2497, calcd. for
C21H35ONSi (M+): 345.2488.
1-But-3-ynyl-3-ethylidene-5-vinylpyrrolidin-2-one (16)
To a solution of 15 (11.5 mg, 0.03 mmol) in THF (0.5 mL)
was added TBAF (0.17 mL, 0.17 mmol, 1M THF solution)
at 08C, and stirred for 12 h. NH4Cl was added and the vola-
tiles were concentrated. The residue was purified bycolumn
chromatographyon silica gel (hexane/AcOEt, 3:2) to afford
16; yield: 6.0 mg (95%). IR (neat): n=2120 (w), 1694 (s),
2-(4,4-dbromo-but-3-enyl)-2-aza-bicyclo[2.2.1]hept-5-en-3-
G
1673 (s) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.76 (ddd,
;
one; yield: 135.7 mg (30%, 2 steps). IR (neat): n=1698 (s),
1560 (w) cmÀ1, 1H NMR (270 MHz, CDCl3): d=2.14–2.35
(m, 4H), 2.96 (dt, J=13.8, 6.8 Hz, 1H), 3.33 (dt, J=13.8,
6.6 Hz, 1H), 3.35 (m, 1H), 4.20 (m, 1H), 6.35 (t, J=7.1 Hz,
1H), 6.66 (ddd, J=1.5, 3.3, 5.3 Hz, 1H), 6.85 (ddd, J=0.7,
2.0, 5.3 Hz, 1H); 13C NMR (67.8 MHz, CDCl3): d=31.6
(CH2), 41.4 (CH2), 53.5 (CH), 58.7 (CH2), 63.1 (CH), 90.4
(C), 135.1 (CH), 138.0 (CH), 139.3 (CH), 180.3 (C); EI-LR-
MS: m/z=323 (M+), 321, 199, 122, 94, 88; EI-HR-MS: m/
z=322.9181, calcd. for C10H11ON81Br2 (M+): 322.9167.
J=1.8, 1.8, 7.1 Hz, 3H), 1.97 (t, J=2.6 Hz, 1H), 2.33–2.57
(m, 3H), 2.93 (m, 1H), 3.19 (ddd, J=6.7, 7.1, 13.7 Hz, 1H),
3.77 (ddd, J=6.1, 7.6, 13.7 Hz, 1H), 4.22 (ddd, J=4.1, 8.4,
8.4 Hz, 1H), 5.25 (dd, J=1.2, 9.8 Hz, 1H), 5.30 (dd, J=1.2,
17.0 Hz, 1H), 5.63 (ddd, J=8.9, 9.8, 17.0 Hz, 1H), 6.55 (m,
1H); 13C NMR (67.8 MHz, CDCl3): d=14.6 (CH3), 17.5
(CH2), 29.6 (CH2), 39.6 (CH2), 59.2 (CH), 69.7 (CH), 81.7
(C), 118.5 (CH2), 128.1 (CH), 131.1 (C), 138.1 (CH), 168.4
(C); EI-LR-MS: m/z=189 (M+), 150, 88; EI-HR-MS: m/z=
189.1138, calcd. for C12H15ON (M+): 189.1154.
To a solution of 2-(4,4-dibromo-but-3-enyl)-2-aza-bicyclo-
A
was added BuLi (0.56 mL, 0.88 mmol, 1.58M in hexane solu-
tion) at À788C, and stirred for 1 h. To this solution was
added TIPSOTf (0.17 mL, 0.64 mmol), and stirred at 08C
for 1 h and at room tempertaure for 0.5 h. Saturated NH4Cl
solution was added, and the mixture was extracted with
AcOEt. The organic phase was washed with saturated NaCl
solution, dried with MgSO4, and concentrated. The residue
was purified bycolumn chromatographyon silica gel
(hexane/AcOEt, 2:1) to afford 14; yield: 21.2 mg (17%). IR
2-Ethylidene-7-vinyl-1,5,6,8a-tetrahydro-2H-indolizin-
3-one (17)
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 16 (9.2 mg, 0.05 mmol) and 1b
(4.1 mg, 4.86 mmol,) in toluene (2.4 mL) was stirred at 808C
for 0.5 h to afford 17; yield: 6.8 mg (74%). IR (KBr): n=
1687 (s), 1664 (s), 1638 (m) cmÀ1 1H NMR (270 MHz,
;
CDCl3): d=1.76 (ddd, J=1.6, 2.0, 7.1 Hz, 3H), 2.24–2.35
(m, 3H), 2.89–3.03 (m, 2H), 4.28 (m, 1H), 4.41 (dd, J=2.6,
5.2, 13.1 Hz, 1H), 5.06 (d, J=10.7 Hz, 1H), 5.18 (d, J=
17.6 Hz, 1H), 5.71 (br, 1H), 6.34 (dd, J=10.7, 17.6 Hz, 1H),
6.51 (m, 1H); 13C NMR (67.8 MHz, CDCl3): d=14.6, 23.4,
29.3, 36.5, 52.4, 113.0, 127.6, 128.8, 132.2, 134.7, 138.1, 166.9;
EI-LR-MS: m/z=189 (M+), 174, 162, 146, 132, 117, 106, 91;
EI-HR-MS: m/z=189.1169, calcd. for C12H15ON (M+):
189.1154.
(neat): n=2173 (m), 1714 (s), 1560 (w) cmÀ1 1H NMR
;
(270 MHz, CDCl3): d=0.98–1.16 (m, 21H), 2.14 (d, J=
7.6 Hz, 1H), 2.28–2.49 (m, 3H), 3.08 (dt, J=13.7, 6.9 Hz,
1H), 3.33 (m, 1H), 3.39 (dt, J=13.7, 6.8 Hz, 1H), 4.40 (m,
1H), 6.64 (ddd, J=1.5, 3.3, 5.1 Hz, 1H), 6.87 (dd, J=2.1,
5.1 Hz, 1H); 13C NMR (67.8 MHz, CDCl3): d=11.2 (CH),
18.5 (CH3), 19.8 (CH2), 43.0 (CH2), 53.7 (CH), 58.9 (CH2),
63.9 (CH), 82.2 (C), 105.8 (C), 138.2 (CH), 139.8 (CH),
180.5 (C); EI-LR-MS: m/z=317 (M+), 274, 208, 180, 166,
138, 100, 86, 66; EI-HR-MS: m/z=317.2171, calcd. for
C19H31ONSi (M+): 317.2175.
2-Prop-2-ynyl-2-azabicyclo[2.2.2]oct-5-en-3-one (19a)
R
To a suspension of NaH (75 mg, 1.87 mmol) in DMF (5 mL)
was added 2-azabicyclo[2.2.2]oct-5-en-3-one (192.4 mg,
1.56 mmol), which was prepared bya literature procedure,
AHCTREUNG
[12]
1-[4-(Triisopropylsilyl)-but-3-ynyl]-3,5-divinyl-
pyrrolidin-2-one (15)
in DMF (5 mL) at 08C, and stirred at room temperature for
1 h. To this suspension was added propargyl bromide
(0.18 mL, 2.34 mmol) at 08C, and stirred at room tempera-
ture for 2 h. Saturated NH4Cl solution was added, and the
mixture was extracted with AcOEt. The organic phase was
washed with saturated NaCl solution, dried with MgSO4,
and concentrated. The residue was purified bycolumn chro-
matographyon silica gel (hexane/AcOEt, 2:3) to afford 19a;
yield: 250 mg (99%). IR (neat): n=2117 (w), 1670 (s), 1614
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 14 (30.5 mg, 0.10 mmol) and 1b
(16.3 mg, 19.21 mmol,) in toluene (4.8 mL) was stirred at
808C for 1 h to afford 15; yield: 13.5 mg (41%). IR (neat):
n=2173 (m), 1695 (s) cmÀ1 1H NMR (270 MHz, CDCl3):
;
d=0.98–1.10 (m, 21H), 1.67 (ddd, J=7.9, 9.7, 13.0 Hz, 1H),
2.36–2.65 (m, 3H), 3.05–3.19 (m, 2H), 3.68 (ddd, J=6.4, 6.6,
7.1 Hz, 1H), 4.17 (dt, J=8.1, 7.7 Hz, 1H), 5.19 (ddd, J=1.3,
1.5, 17.1 Hz, 1H), 5.20 (ddd, J=1.3, 1.5, 10.7 Hz, 1H), 5.27
(dd, J=1.3, 9.9 Hz, 1H), 5.34 (dd, J=1.3, 17.0 Hz, 1H), 5.65
(ddd, J=8.7, 9.9, 17.0 Hz, 1H), 5.94 (ddd, J=6.6, 10.7,
17.1 Hz, 1H); 13C NMR (67.8 MHz, CDCl3): d=11.2 (CH),
18.6 (CH2), 18.6 (CH3), 32.4 (CH2), 39.8 (CH2), 45.6 (CH),
(m) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.41–1.55 (m,
;
2H), 1.84 (m, 1H), 2.02 (m, 1H), 2.22 (t, J=2.6 Hz, 1H),
3.48 (m, 1H), 4.03 (dd, J=2.6, 7.6 Hz, 1H), 4.17 (dd, J=2.6,
7.6 Hz, 1H), 4.43 (m, 1H), 6.36 (ddd, J=1.8, 6.1, 7.6 Hz,
1H), 6.46 (ddd, J=1.5, 5.4, 7.6 Hz, 1H); 13C NMR
(67.8 MHz, CDCl3): d=21.0, 25.9, 32.6, 43.8, 53.2, 71.7, 77.8,
1244
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ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1231 – 1246

Synthesis of Pyrrolizidine, Indolizidine, and Quinolizidine Derivatives
FULL PAPERS
131.3, 132.3, 172.5; EI-LR-MS: m/z=161 (M+), 133, 104, 88,
80; EI-HR-MS: m/z=161.0825, calcd. for C10H11ON (M+):
161.0841.
1H); 13C NMR (67.8 MHz, CDCl3): d=À0.6, 21.0, 25.9,
33.6, 43.9, 53.0, 88.3, 99.8, 131.5, 132.4, 172.6; EI-LR-MS:
m/z=233 (M+), 205, 190, 106; EI-HR-MS: m/z=233.1249,
calcd. for C13H19ONSi (M+): 233.1236.
7-Methylene-3-vinyl-1,2,3,6,7,9a-hexahydroquinolizin-
4-one (20a) and 5-(3-Oxo-2-azabicyclo[2.2.2]oct-5-en-
2-ylmethyl)-2-phenyl-3a,4,7,7a-tetrahydroisoindole-
1,3-dione (23a)
2-[2-Methylene-3-(trimethylsilyl)-but-3-enyl]-2-azabi-
cyclo[2.2.2]oct-5-en-3-one (21b)
G
U
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 19b (38.4 mg, 0.16 mmol) and 1b
(14.0 mg, 16.45 mmol,) in toluene (8.2 mL) was stirred at
808C for 0.5 h to afford 21b; yield: 33.4 mg (78%). IR
According to the typical procedure for the metathesis reac-
tion of 8, a solution of 19a (37.2 mg, 0.23 mmol) and 1b
(19.6 mg, 23.08 mmol,) in toluene (12 mL) was stirred at
808C for 0.5 h to afford 20a and 21a as an inseparable mix-
ture bycolumn chromatographyon silica gel. The yields of
20a (11.7 mg, 27%) and 21a (18.4 mg, 42%) were deter-
mined by 1H NMR using (E)-stilbene as an internal stan-
dard.
(neat): n=1673 (s), 1616 (m) cmÀ1 1H NMR (270 MHz,
;
CDCl3): d=0.16 (s, 9H), 1.39–1.45 (m, 2H), 1.75–1.83 (m,
2H), 3.45 (m, 1H), 3.86 (d, J=15.7 Hz, 1H), 4.11 (m, 1H),
4.17 (d, J=15.7 Hz, 1H), 4.96 (s, 1H), 5.05 (s, 1H), 5.44 (d,
J=2.1 Hz, 1H), 5.77 (d, J=2.1 Hz, 1H), 6.30–6.40 (m, 2H);
13C NMR (67.8 MHz, CDCl3): d=À0.7, 21.5, 26.0, 44.3, 47.6,
53.1, 115.1, 126.9, 132.1, 132.8, 145.6, 149.3, 173.3; EI-LR-
MS: m/z=261 (M+), 246, 233, 218, 188, 160, 80; EI-HR-MS:
m/z=261.1523, calcd for C15H23ONSi (M+): 261.1549.
The mixture of 20a (27.5 mg) and 21a (47.3 mg,
0.25 mmol) with N-phenylmaleimide (43.3 mg, 0.25 mmol,
1.0 equiv. for 21a) in toluene (1.2 mL) was stirred at 608C
for 18 h. The volatiles were removed in reduced pressure,
and the residue was purified bycolumn chromatographyon
silica gel (hexane/AcOEt, 1:2) to afford 23a as a diastereo-
meric mixture (ratio of diastereomers was 2:3), and recov-
ered 20a.
20a: IR (neat): n=1716 (m), 1643 (s) cmÀ1 1H NMR
;
References
(270 MHz, CDCl3): d=1.60–2.00 (m, 4H), 3.22 (m, 1H),
3.34 (d, J=14.9 Hz, 1H), 4.09 (m, 1H), 4.93 (s, 1H), 5.00 (s,
1H), 5.12 (d, J=16.8 Hz, 1H), 5.15 (d, J=10.6 Hz, 1H),
5.30 (d, J=14.9 Hz, 1H), 5.62 (d, J=9.9 Hz, 1H), 5.90 (ddd,
J=6.1, 10.6, 16.8 Hz, 1H), 6.25 (dd, J=2.5, 9.9 Hz, 1H);
13C NMR (67.8 MHz, CDCl3): d=24.5, 25.9, 44.1, 45.1, 55.0,
112.5, 116.4, 127.7, 130.4, 136.8, 138.0, 169.6; EI-LR-MS:
m/z=189 (M+), 160, 136, 121, 107, 81; EI-HR-MS: m/z=
189.1124, calcd. for C12H15ON (M+): 189.1154.
[1] a) P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs,
Angew. Chem. Int. Ed. 1995, 34, 2039; b) M. Scholl, S.
Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953.
[2] a) Handbook of Metathesis, (Ed.: R. H. Grubbs),
Wiley-VCH, Weinheim, 2003; b) Topics in Organome-
tallic Chemistry, Vol. 1, (Ed.: A. Fꢂrstner), Springer-
Verlag, Berlin Heidelberg, 1998.
[3] a) M. Mori, Top. Organomet. Chem. 1998, 1, 133;
b) C. S. Poulsen, R. Madsen, Synthesis 2003, 1; c) S. T.
Diver, A. J. Giessert, Chem. Rev. 2004, 104, 1317.
[4] Selected reports from our laboratory; a) A. Kinoshita,
M. Mori, Synlett 1994, 1020; b) A. Kinoshita, N. Sakaki-
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c) M. Mori, N. Sakakibara, A. Kinoshita, J. Org. Chem.
1998, 63, 6082; d) M. Mori, K. Tonogaki, N. Nishiguchi,
J. Org. Chem. 2002, 67, 224; e) K. Tonogaki, M. Mori,
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Mori, Org. Lett. 2001, 3, 1161; g) M. Mori, Y. Kuzuba,
T. Kitamura, Y. Sato, Org. Lett. 2002, 4, 3855; h) T. Ki-
tamura, Y. Kuzuba, Y. Sato, H. Wakamatsu, R. Fujita,
M. Mori, Tetrahedron 2004, 60, 7375; i) M. Mori, H.
Wakamatsu, K. Tonogaki, R. Fujita, T. Kitamura, Y.
Sato, J. Org. Chem. 2005, 70, 1066.
[5] a) W. J. Zuercher, M. Hashimoto, R. H. Grubbs, J. Am.
Chem. Soc. 1996, 118, 6634; b) R. Stragies, S. Blechert,
Synlett 1998, 169; c) S. D. Burke, K. J. Quinn, V. J.
Chen, J. Org. Chem. 1998, 63, 8626; d) A. Fꢂrstner, H.
Szillat, B. Gabor, R. Mynott, J. Am. Chem. Soc. 1998,
120, 8305; e) J. A. Adams, J. G. Ford, P. J. Stamatos,
A. H. Hoveyda, J. Org. Chem. 1999, 64, 9690.
23a: yield: 90.3 mg (99%); IR (neat): n=1710 (s), 1667
(s) cmÀ1 1H NMR (270 MHz, CDCl3): d=1.38–1.49 (m,
;
2H), 1.77–1.88 (m, 2H), 2.21–2.42 (m, 2H), 2.47 (m, 0.6H),
2.53 (m, 0.4H), 2.64 (m, 0.6H), 2.70 (m, 0.4H), 3.18–3.30
(m, 2H), 3.43–3.52 (m, 1.6H), 3.66 (d, J=15.8 Hz, 0.6H),
3.93–4.28 (m, 1.8H), 5.65 (m, 0.4H), 5.73 (m, 0.6H), 6.24–
6.40 (m, 2H), 7.20–7.50 (m, 5H); EI-LR-MS: m/z=362
(M+), 334, 283, 255, 240, 200, 160, 142, 80; EI-HR-MS:
m/z=362.1619, calcd. for C22H22O3N2 (M+): 362.1630.
2-[3-(Trimethylsilyl)-prop-2-ynyl]-2-azabicyclo-
[2.2.2]oct-5-en-3-one (19b)
To a solution of 19a (307.1 mg, 1.91 mmol) in THF (19 mL)
was added BuLi (1.46 mL, 2.29 mmol, 1.57M hexane solu-
tion) at À788C, and stirred for 1 h. To the resultant solution
was added TMSCl (0.48 mL, 3.81 mmol), and stirred for 1 h.
Saturated NH4Cl solution was added, and the mixture was
extracted with AcOEt. The organic phase was washed with
saturated NaCl solution, dried with MgSO4, and concentrat-
ed. The residue was purified bycolumn chromatographyon
silica gel (hexane/AcOEt, 1:1) to afford 19b; yield: 258.9 mg
(58%). IR (neat): n=2178 (w), 1682 (s), 1614 (m) cmÀ1
;
[6] M. E. B. Smith, N. Derrien, M. C. Lloyd, S. J. C. Taylor,
D. A. Chaplin, R. McCague, Tetrahedron Lett. 2001, 42,
1347.
[7] a) O. Mitsunobu, Synthesis 1981, 1; b) D. L. Hughes,
Org. React. 1992, 42, 335.
1H NMR (270 MHz, CDCl3): d=0.16 (s, 9H), 1.40–1.53 (m,
2H), 1.85 (m, 1H), 2.00 (m, 1H), 3.47 (m, 1H), 3.98 (d, J=
17.6 Hz, 1H), 4.21 (d, J=17.6 Hz, 1H), 4.44 (m, 1H), 6.35
(ddd, J=1.9, 6.1, 7.4 Hz, 1H), 6.44 (ddd, J=1.8, 5.5, 7.4 Hz,
Adv. Synth. Catal. 2007, 349, 1231 – 1246
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1245

Hideaki Wakamatsu et al.
FULL PAPERS
[8] a) T. Fukuyama, C.-K. Jow, M. Cheung, Tetrahedron
Lett. 1995, 36, 6373; b) T. Kan, T. Fukuyama, Chem.
Commun. 2004, 353.
[9] The stereochemistryof 7 was determined byNOE ex-
periment. In this reaction, the double bond of the sub-
stituent was isomerized to conjugate with the carbonyl
group. Presumablythis is a thermodnyamic product
and the isomerization would occur in the presence of
DBU. It is not clear whether the isomerization of the
double bond and then ring construction occur or the
ring construction and then the isomerization of the
double bond occur.
[10] O. Arjona, A. G. Csꢃkꢄ, V. Leꢅn, R. Medel, J. Plumet,
Tetrahedron Lett. 2004, 45, 565.
[11] ROMP (ring-opening metathesis polymerization) of
the cycloalkene would proceed under an argon atmos-
phere.
[12] J. R. Malpass, N. J. Tweddle, J. Chem. Soc., Perkin
Trans. 1 1977, 874.
1246
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ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 1231 – 1246