Sequential addition reaction of lithium acetylides and Grignard reagents to thioiminium salts from thiolactams leading to 2,2-disubstituted cyclic amines

Article abstract of DOI:10.1016/j.tet.2006.04.065

The reaction of thioiminium salts derived from γ- and δ-thiolactams with lithium acetylides and Grignard reagents proceeded sequentially to give 2,2-disubstituted pyrrolidines and piperidines in moderate to high yields. In the initial step of the reaction

Full text of DOI:10.1016/j.tet.2006.04.065

Tetrahedron 62 (2006) 6312–6320
Sequential addition reaction of lithium acetylides and Grignard
reagents to thioiminium salts from thiolactams leading to
2,2-disubstituted cyclic amines
*
Toshiaki Murai, Rie Toshio and Yuichiro Mutoh
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
Received 20 March 2006; revised 13 April 2006; accepted 14 April 2006
Available online 12 May 2006
Abstract—The reaction of thioiminium salts derived from g- and d-thiolactams with lithium acetylides and Grignard reagents proceeded
sequentially to give 2,2-disubstituted pyrrolidines and piperidines in moderate to high yields. In the initial step of the reaction, 2-(methylthio)-
pyrrolidines and -piperidines may be formed. The use of lithium (trimethylsilyl)acetylide gave the products most effectively. Aryl-, alkyl-, and
allylmagnesium halides were used as Grignard reagents. Silylcarbocyclization of N-allyl 2-ethynyl cyclic amines with HSiMe2Ph in the
presence of a catalytic amount of Rh4(CO)12 was carried out to give trisubstituted hexahydro-1H-pyrrolizines and octahydroindolizines.
Ó 2006 Elsevier Ltd. All rights reserved.
–
I
MeI
THF
rt, 6 h
1. Introduction
+
S
N
SMe
N
R1
1
R
The development of new carbon–carbon bond-forming reac-
tions, in which multiple components are coupled in one op-
eration, is needed.1 In this context, we have recently reported
the sequential addition reactions of lithium acetylides and
Grignard reagents to thioiminium salts derived from acyclic
thioamides2 (Eq. 1) during the course of our studies on
thioamides.3
R2C CLi
H
LiAlH4
(2)
N
R2
R1
In this case, about 6 h was necessary for methylation of the
thiolactams. Due to the higher reactivity of MeOTf, the
methylation of thiolactams is expected to be complete within
a shorter reaction time. Furthermore, the introduction of two
different carbon nucleophiles to thioiminium salts derived
from thiolactams can lead to 2-alkynyl-2-substituted pyr-
rolidines and piperidines, which are not readily available
by ordinary synthetic methods. Several examples of the
alkynylation of cyclic imines and iminium salts leading to
2-alkynyl pyrrolidines5 and piperidines6 are known, but
reactions leading to 2-alkynyl-2-substituted pyrrolidines7
and piperidines7a,8 are rare. We report here sequential addi-
tion reactions of lithium acetylides and Grignard reagents
to thioiminium salts derived from g- and d-thiolactams.
Additionally, silylcarbocyclization was applied to the ob-
tained N-allyl 2-ethynyl-2-substituted cyclic amines.
MeS
1
S
–
MeOTf
OTf
+
1
2
2
R
NR
2
R
NR
2
2
NR
3
2
4
1)
2)
R C CLi
(1)
R
4
R MgX
1
R
3
R
In those studies, two different carbon nucleophiles were
selectively introduced to thioiminium salts, and no products,
to which the same carbon nucleophiles were doubly intro-
duced, were observed. Cyclic thioamides, i.e., g- and d-
thiolactams, can be used as a substrate in Eq. 1. In fact,
the methylation of g-thiolactams with methyl iodide has
been reported to take place.4 Alkynylation of the resulting
thioiminium salts followed by reduction gives 2-alkynyl
pyrrolidines (Eq. 2).4a
2. Results and discussion
Initially, methylation of N-methyl g-thiolactam 1a with
methyl triflate (MeOTf) was carried out (Eq. 3). This
reaction went to completion almost instantly to give thio-
iminium salt 2a. Lithium (trimethylsilyl)acetylide (3a)
(1.5 equiv) and phenylmagnesium bromide (4a) (2 equiv)
were then added to an Et2O solution of 2a to give
Keywords: Thiolactams; Thioiminium salts; Lithium acetylides; Grignard
reagents; 2,2-Disubstituted cyclic amines; Silylcarbocyclization.
* Corresponding author. Tel.: +81 58 293 2614; fax: +81 58 230 1893;
e-mail: mtoshi@cc.gifu-u.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.065

T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
6313
Table 1. Sequential reaction of thiolactam 1a with MeOTf, lithium silyl-
acetylide 3a, and Grignard reagents 4a
N-methyl-2-alkynyl-2-phenylpyrrolidine 5a in 87% yield.
2-(Methylthio)pyrrolidine 6a9 is probably formed in the
step of the addition of 3a. In the next step, the substitution
reaction occurs at the carbon atom bearing nitrogen and sul-
fur atoms with Grignard reagent 4a. As expected, products
derived from 2 equiv of the identical carbon nucleophiles
were not observed, and 2 equiv or one more equiv of
Grignard reagent 4a was enough to efficiently substitute
the MeS group in 6a. In the first step, thioiminium salt 2a
appears to react with more ionic organolithium reagents,
whereas in the second step, the coordination of the sulfur
atom to the Lewis acidic magnesium metal may facilitate
the reaction of Grignard reagents.
Grignard reagent 4
Product 5
Yield (%)b
Et
58
EtMgBr, 4b
N
SiMe3
Me
5b
MgCl
70
N
4c
SiMe3
SiMe3
Me 5c
–
OTf
MeOTf
+
96c
MgBr
N
Me
SMe
2a
N
S
1a
Et2O
N
Me
4d
5d
Me
rt, 30 sec
1)
Me3SiC CLi 3a
0 °C, then rt, 0.5 h
Ph
(3)
88c
N
Me
MgBr
N
Me
2)
PhMgBr 4a
rt, 3 h
SiMe3
4e
5a
SiMe3
5e
87%
SiMe3
SiMe3
Me3Si
51d
MgCl
N
Me
4f
5f
SMe
R = SiMe3
R = Ph
R = Bu-n
6a
6b
a
Reaction was carried out as follows, unless otherwise noted: to thiolactam
1a (1 mmol) in Et2O (5 mL) were added MeOTf (1 equiv), lithium silyl-
acetylide 3a (1.5 equiv), and Grignard reagents 4 (2 equiv).
Yields of crude product 5 with purity higher than 95%.
Thiolactam 1a (5 mmol) was used.
N
Me
6d
R
b
c
d
Next, a variety of Grignard reagents 4 were used for the
sequential reaction. The results are summarized in Table 1.
Ethyl-, cyclohexyl-, 2-propenyl-, 3-butenyl-, and silyl-
methylmagnesium halides 4b–4f were used as aliphatic
Grignard reagents. In all cases, the reaction proceeded
smoothly to give the corresponding 2-alkynyl-2-alkylpyrro-
lidines 5b–5f in good to high yields. The usual aqueous
workup of the reaction mixture followed by concentration
of the organic layers gave products 5 with high purity except
for the reaction with 4f.
Product 5f was purified by column chromatography on silica gel, and the
isolated yield is shown.
pyrrolidines 5k–5m and 5o, albeit in low to moderate yields
(entries 6–8 and 10). The sequential reaction of 2a with 3d
and LiAlH4 gave the product 5n in 59% yield, which sug-
gested the efficient formation of 6d and the lower efficiency
of the reaction of 6d with Grignard reagents 4.
1
R C CLi3
1)
MeOTf
Conditions A
(4)
products 5
S
Lithium acetylides 3b–3e derived from phenylacetylene, 2-
methyl-1-butene-3-yne, 1-hexyne, and 1-ethynylcyclohex-
ene were also used for the sequential addition reaction to
2a (Eq. 4). The results are summarized in Table 2. As in
the reaction with lithium silylacetylide 3a, thioiminium
salt 2a was stirred with lithium phenylacetylide (3b) at
0 ꢀC–room temperature for 30 min. To the reaction mixture
was then added Grignard reagents 4a, 4b, and 4f, and the
mixture was stirred at room temperature for 3 h, but the
desired products 5g–5i were obtained in at most 40% yield
(entries 1, 3, and 4). To confirm the efficiency of the gener-
ation of 2-(methylthio)pyrrolidine 6b from 2a and 3b, the
reduction of in situ-generated 6b was carried out with
LiAlH4 to give 2-phenylethynylpyrrolidine (5j) in 59% yield
(entry 5). Thus, the addition of 3b to 2a occurs efficiently,
and lower yields in entries 1, 3, and 4 may be due to a less
efficient reaction of 6b with Grignard reagents 4. Attempts
to enhance the yields of 5g–5i by raising the reaction temper-
ature or by using a large excess of Grignard reagents 4 were
not successful, but the reaction with 4a under reflux in THF
gave the product 5g in slightly better yield (entry 2). The use
of lithium acetylides 3c–3e gave 2-alkynyl-2-alkyl or -aryl
N
Me
Et O 2) RMgX 4
2
Conditions B
rt, 30 sec
1a
Instead of g-thiolactam 1a, N-allyl g-thiolactam 1b was
chosen as a starting material (Eq. 5). As in the reaction of
1a, the corresponding pyrrolidines 7 were obtained in
good to high yields by reacting with lithium acetylide 3a
and Grignard reagents 4.
Me3SiC CLi3a
MeOTf
S
Et2O
N
0 °C then rt, 0.5 h
1b
rt, 30 sec
RMgBr 4
R
N
(5)
rt, 3 h
SiMe3
7
7c
7a
R = Ph 94%
R = Me 60%
R = Et
83%
55%
a
7d
7b
R = C H OMe-4
6
4
aafter the purification by column chromatography
on silica gel

6314
T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
a
Table 2. Sequential reaction of thiolactam 1a with MeOTf, lithium acetylides 3, and Grignard reagents 4 or LiAlH4
Entry
1
R1C^CLi 3
Conditions A
RMgBr 4 or LiAlH4
PhMgBr, 4a
Conditions B
rt, 3 h
Product 5
Yield (%)b
Ph
PhC^CLi, 3b
0 ꢀC, then rt, 0.5 h
30
N
Ph
Ph
Me
5g
2c
Reflux, 12 h
rt, 3 h
44
40
Et
3
3b
3b
3b
0 ꢀC, then rt, 0.75 h
0 ꢀC, then rt, 0.5 h
0 ꢀC, then rt, 0.5 h
EtMgBr, 4b
N
Me
5h
SiMe3
Ph
Me3Si
MgBr
4
rt, 3 h
36
59
N
Me
4f
5i
H
5d
LiAlH4
ꢁ10 ꢀC, 3 h
N
Me
Ph
5j
Ph
6
0 ꢀC, then rt, 0.5 h
4a
rt, 3 h
18
N
C
CLi
Me
3c
5k
Ph
7
BuC^CLi, 3d
ꢁ78 ꢀC, 1 h
4a
4b
ꢁ78 ꢀC, then rt, 3 h
40
40
N
Me
Bu
Bu
5l
Et
8
3d
3d
ꢁ30 ꢀC, 0.5 h
Reflux, 3 h
N
Me
5m
H
9d
0 ꢀC, 0.5 h
LiAlH4
ꢁ10 ꢀC, 3 h
59
41
N
Me
Bu
5n
Ph
ꢁ78 ꢀC, 1 h
4a
ꢁ78 ꢀC, then rt, 3 h
N
CLi
C
10
Me
3e
5o
a
Reaction was carried out as follows, unless otherwise noted: to thiolactam 1a (1 mmol) in Et2O (5 mL) were added MeOTf (1 equiv), lithium acetylide
(1.5 equiv), and Grignard reagent 4 (2 equiv). Products 5 were purified by column chromatography on silica gel.
Isolated yields.
Lithium phenylacetylide 3b (3 equiv) and phenylmagnesium bromide 4a (4 equiv) were used in THF.
LiAlH4 (2.6 equiv) was used.
b
c
d
The above results clearly show that the 2-(methylthio)pyrro-
lidine 6a derived from 2a and lithium silylacetylide 3a
undergoes a substitution reaction at the carbon atom adja-
cent to the nitrogen atom with Grignard reagents 4 with
better efficiency. This may be partly due to the electron-
withdrawing ability of the silicon atom enabling the carbon
atom bearing the sulfur and nitrogen atoms in 6a more elec-
tropositive.
d-Thiolactams 1c and 1d were also used as a starting mate-
rial. The results are summarized in Table 3. To confirm the
efficient generation of 2-(methylthio)piperidine 8,10 the re-
action mixture obtained from d-thiolactam 1c, MeOTf, and
lithium silylacetylide 3a was treated with LiAlH4 to give
2-silylethynylpiperidine 9a in good yield (entry 1). The
use of phenylmagnesium bromide (4a) produced the corre-
sponding product 9b in low yield (entry 2), whereas the

T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
6315
Table 3. Sequential reaction of thiolactam 1c and 1d with MeOTf, lithium
silylacetylide 3a, and LiAlH4 or Grignard reagents 4a
ethylpiperidine 12 proceeded in a similar manner to give
1,2,8a-trisubstituted octahydroindolizine12 13 as a mixture
of two diastereomers.16
Entry
LiAlH4 or R0MgBr
Product 9
Yield
(%)c
4 Conditionsb
Me2PhSiH
cat.
H
R
N
SiMe2Ph
H
R
Rh4(CO)12
(6)
1
LiAlH4, ꢁ10 ꢀC, 3 h
67d
S
N
N
N
N
N
Hexane
CO
SiMe3
H
9a
10
rt, 3 days
1c
11
10a R = C6H4-OMe-4
10b R = Ph
11a 85% (67 : 26 : 6 : 1)
11b 88% (70 : 26 : 3 : 1)
Ph
Et
10c
R = Me
21
2
3
1c
PhMgBr 4a, rt, 5 h
10d
R = Et
SiMe3
9b
H
SiMe2Ph
4-MeOC6H4
4-MeOC6H4
N
SiMe2Ph
H
N
1c
EtMgBr 4b, rt, 8 h
77
48
syn-E 11a
anti-Z 11a
SiMe3
SiMe3
9c
H
Me2PhSiH
cat.
MgBr
rt, 8 h
N
Bn
4
S
N
Bn
Et
4e
SiMe2Ph
93 : 7
Rh4(CO)12
9d
1d
Et
(7)
N
Hexane
CO
a
N
Reaction was carried out unless otherwise noted: to thiolactam 1 (1 mmol)
in Et2O (5 mL) were added MeOTf (1 equiv), lithium silylactylide 3a
(1.5 equiv), and Grignard reagents 4 (2 eqiuv). Products 9 were purified
by column chromatography on silica gel.
Reaction conditions of the reaction with LiAlH4 or Grignard reagents 4
are shown.
Isolated yields.
H
rt, 3 days
13
65%
12
b
In summary, we have demonstrated the sequential reaction
of g- and d-thiolactams with MeOTf, lithium acetylides,
and Grignard reagents to give 2-alkynyl-2-substituted pyrro-
lidines and piperidines in low to high yields. The synthesis of
trisubstituted pyrrolizines and indolizines was achieved by
Rh4(CO)12-catalyzed silylcarbocyclization.
c
d
LiAlH4 (2.6 equiv) was used.
reaction with ethylmagnesium bromide (4b) led to the
product 9c in better yield (entry 3).
3. Experimental
3.1. General methods
SMe
N
R
SiMe3
8
The IR spectra were obtained on a JASCO FTIR 410 spectro-
1
photometer. H (399.7 MHz) and 13C (100.4 MHz) NMR
spectra were measured on a JEOL a-400 spectrometer.
The 1H and the 13C chemical shifts are reported in d values
referred to Me4Si and CHCl3 as an internal standard, respec-
tively. All spectra were acquired in the proton-decoupled
mode. Phase-sensitive NOESY spectra were measured
with a Varian Inova 500 NMR spectrometer. The mass spec-
tra (MS) were taken on SHIMADZU GCMS QP1000 and
JEOL MStation 700 spectrometers. The high-resolution
mass spectra (HRMS) were measured on JEOL GC-mate
II and JEOL MStation 700 mass spectrometers.
Finally, 2-alkynyl-2-substituted pyrrolidines and piperidines
obtained above were subjected to silylcarbocyclization de-
veloped by Ojima and his co-workers.11 N-Allyl-2-ethynyl-
pyrrolidines 10, obtained by the desilylation of cyclic
amines 7 and 9, were reacted with HSiPhMe2 in the presence
of Rh4(CO)12 under a CO atmosphere (Eq. 6). The silylcar-
bocyclization of acyclic amines has been reported to be com-
plete within 1 min, but in the reaction of 10a, only a starting
cyclic amine 10a was observed after 1 min. To efficiently
complete the cyclization, the reaction was carried out under
various reaction conditions. Consequently, the reaction at
room temperature for 3 days gave 1,2,7a-trisubstituted hexa-
hydro-1H-pyrrolizine12 11a as a mixture of four diastereo-
mers (67:26:6:1) in 85% yield. The stereochemistry of the
two major diastereomers was estimated to be anti-Z-11a15
and syn-E-11a by phase-sensitive NOESY spectroscopy. A
similar reaction of 10b took place to give the corresponding
pyrrolizine 11b, whereas 2-ethynyl-2-alkylpyrrolidines 10c
and 10d did not react at all under identical reaction condi-
tions. In contrast, the silylcarbocyclization of 2-ethynyl-2-
3.2. General procedure for the sequential addition
reaction of lithium acetylides and Grignard reagents
to thioiminium salts derived from g-thiolactams
In a typical example, to an Et2O (5 mL) solution of 1-methyl-
2-pyrrolidinethione (0.115 g, 1.0 mmol) was added methyl
triflate (0.115 mL, 1.0 mmol) at room temperature, and the
mixture was stirred at this temperature for 30 s. To this
was added an Et2O solution (5 mL) of the alkynyllithium

6316
T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
prepared
from
(trimethylsilyl)acetylene
(0.21 mL,
(s, 9H), 1.35 (dt, J¼12.7, 4.9 Hz, 1H), 1.66–1.82 (m, 4H),
1.5 mmol) and BuLi (1.6 M solution in hexane, 0.94 mL,
1.5 mmol) at 0 ꢀC, and this was stirred for 0.5 h at room tem-
perature. To this was added phenylmagnesium bromide
(1.0 M solution in THF, 2.0 mL, 2.0 mmol) at room temper-
ature, and the mixture was stirred at this temperature for 3 h.
The resulting mixture was poured into a saturated aqueous
solution of NH4Cl, and extracted with Et2O. The organic
layer was dried over MgSO4 and concentrated in vacuo to
give the amine 5a (0.206 g, 87%) as an orange oil.
1.99–2.08 (m, 2H), 2.21–2.26 (m, 4H), 2.39–2.43 (m, 1H),
2.89–2.94 (m, 1H), 4.91 (d, J¼10.3 Hz, 1H), 4.99 (d,
J¼17.1 Hz, 1H), 5.82 (dddd, J¼17.0, 12.7, 10.2, 6.3 Hz,
1H); 13C NMR (CDCl3) d 0.35, 20.4, 29.8, 35.5, 37.8,
38.0, 53.9, 64.1, 89.9, 105.6, 114.3, 138.7; MS (EI) m/z
235 (M+); HRMS Calcd for C14H25NSi: 235.1756 (M+).
Found: 235.1750.
3.2.6. 1-Methyl-2-(1-trimethylsilyl)methyl-2-(2-trimeth-
ylsilyl)ethynylpyrrolidine (5f). Yellow oil: IR (neat)
2958, 2903, 2843, 2813, 2785, 2153, 1450, 1415, 1345,
1250, 1207, 1138, 1101, 1018, 986, 925, 842, 760,
3.2.1. 1-Methyl-2-phenyl-2-(2-trimethylsilyl)ethynylpyr-
rolidine (5a). IR (neat) 3060, 3026, 2959, 2902, 2878,
2843, 2817, 2787, 2156, 1621, 1601, 1447, 1250, 880,
1
697 cmꢁ1; H NMR (CDCl3) d 0.09 (s, 9H), 0.15 (s, 9H),
843, 759 cmꢁ1; H NMR (CDCl3) d 0.22 (s, 9H), 1.89–
0.67 (d, J¼14.2 Hz, 1H), 1.29 (d, J¼14.2 Hz, 1H), 1.66–
1.76 (m, 3H), 2.06–2.10 (m, 1H), 2.24 (s, 3H), 2.37–2.43
(m, 1H), 2.91–2.95 (m, 1H); 13C NMR (CDCl3) d 0.21,
0.23, 20.2, 27.4, 34.9, 39.8, 52.8, 62.3, 89.0, 106.5; MS
(EI) m/z 267 (M+); HRMS Calcd for C14H29NSi: 267.1839
(M+). Found: 267.1841.
1
2.02 (m, 3H), 2.09 (s, 3H), 2.23–2.29 (m, 1H), 2.61 (q,
J¼8.4 Hz, 1H), 3.13–3.18 (m, 1H), 7.02 (t, J¼6.3 Hz, 1H),
7.10 (t, J¼6.8 Hz, 2H), 7.45 (d, J¼7.8 Hz, 2H); 13C NMR
(CDCl3) d 0.41, 21.4, 35.8, 44.5, 53.6, 68.9, 92.1, 104.0,
127.0, 127.4, 128.3, 142.5; MS (EI) m/z 257 (M+); HRMS
Calcd for C16H23NSi: 257.1600 (M+). Found: 257.1582.
3.2.7. 1-Methyl-2-phenyl-2-(2-phenyl)ethynylpyrrolidine
(5g). Yellow oil: IR (neat) 3060, 3031, 2963, 2906, 2816,
2787, 1947, 1599, 1489, 1445, 1414, 1260, 1027, 865,
3.2.2. 1-Methyl-2-ethyl-2-(2-trimethylsilyl)ethynylpyrro-
lidine (5b). Orange oil: IR (neat) 2966, 2880, 2844, 2811,
2787, 2153, 1460, 1378, 1306, 1251, 1082, 1031, 971,
920, 879, 842, 760, 689 cmꢁ1; 1H NMR (CDCl3) d 0.10 (s,
9H), 0.93 (t, J¼7.6 Hz, 3H), 1.22–1.31 (m, 1H), 1.59–1.75
(m, 4H), 1.93–1.99 (m, 1H), 2.18 (s, 3H), 2.38–2.44 (m,
1H), 2.89–2.94 (m, 1H); 13C (NMR) d 0.39, 9.8, 20.3,
31.4, 35.5, 37.4, 54.1, 65.1, 89.6, 105.7; MS (EI) m/z 180
(M+ꢁCH2CH3); HRMS Calcd for C12H23NSi: 209.1600
(M+). Found: 209.1585.
1
796, 756, 699 cmꢁ1; H NMR (CDCl3) d 1.88–2.08 (m,
3H), 2.13 (s, 3H), 2.28–2.34 (m, 1H), 2.67 (q, J¼8.8 Hz,
1H), 3.13–3.18 (m, 1H), 7.16–7.69 (m, 10H); 13C NMR
(CDCl3) d 21.5, 36.0, 44.6, 53.8, 68.9, 87.9, 88.3, 123.5,
126.8, 127.2, 127.3, 128.2, 128.3, 131.8, 142.8; MS (EI)
m/z 261 (M+), 184 (M+ꢁC6H5); HRMS Calcd for
C19H19N: 261.1517 (M+). Found: 261.1488.
3.2.8. 1-Methyl-2-ethyl-2-(2-phenyl)ethynylpyrrolidine
(5h). Yellow oil: IR (neat) 3055, 2968, 2877, 2786, 1600,
1573, 1489, 1443, 1345, 1231, 1147, 1031, 914, 755,
3.2.3. 1-Methyl-2-cyclohexyl-2-(2-trimethylsilyl)ethynyl-
pyrrolidine (5c). Orange oil: IR (neat) 2927, 2852, 2788,
2671, 2153, 1649, 1578, 1449, 1408, 1345, 1299, 1250,
1
596 cmꢁ1; H NMR (CDCl3) d 1.08 (t, J¼7.6 Hz, 3H,),
1213, 1164, 1105, 1045, 1000, 877, 842, 760, 689 cmꢁ1
;
1.40–1.49 (m, 1H), 1.78–1.95 (m, 4H), 2.12–2.17 (m, 1H),
2.36 (s, 3H), 2.57–2.64 (m, 1H), 3.03–3.08 (m, 1H), 7.26–
7.32 (m, 3H), 7.40–7.44 (m, 2H); 13C NMR d 9.9, 20.4,
31.7, 35.7, 37.6, 54.4, 65.2, 86.2, 89.2, 123.6, 127.7,
128.2, 131.7; MS (EI) m/z 184 (M+ꢁCH2CH3); HRMS
Calcd for C13H14N: 184.1126 (M+ꢁCH2CH3). Found:
184.1114.
1H NMR (CDCl3) d 0.08 (s, 9H), 0.84–0.92 (m, 2H), 1.05–
1.21 (m, 4H), 1.44–1.45 (m, 1H), 1.57–1.74 (m, 7H),
1.93–1.96 (m, 1H), 2.10 (s, 3H), 2.33–2.38 (m, 1H), 2.87
(dt, J¼8.5, 2.0 Hz, 1H); 13C NMR (CDCl3) d 0.45, 20.4,
25.5, 26.4, 26.9, 27.2, 29.8, 32.8, 35.2, 42.8, 53.9, 67.6,
88.8, 107.1; MS (EI) m/z 263 (M+), 180 (M+ꢁC6H11);
HRMS Calcd for C16H29NSi: 263.2069 (M+). Found:
263.2082.
3.2.9. 1-Methyl-2-(1-trimethylsilyl)methyl-2-(2-phenyl)-
ethynylpyrrolidine (5i). Yellow oil: IR (neat) 3080, 3056,
3033, 2952, 2904, 2841, 2810, 2784, 1945, 1742, 1598,
3.2.4. 1-Methyl-2-(2-propenyl)-2-(2-trimethylsilyl)ethy-
nylpyrrolidine (5d). Orange oil: IR (neat) 3077, 2960,
2907, 2845, 2813, 2788, 2677, 2154, 1641, 1449, 1416,
1347, 1251, 1201, 1167, 1110, 1045, 994, 949, 913, 843,
1
1573, 1545, 1490, 1248, 846, 755, 691 cmꢁ1; H NMR
(CDCl3) d 0.10 (s, 9H), 0.73 (d, J¼13.9 Hz, 1H), 1.37 (d,
J¼13.9 Hz, 1H), 1.73–1.80 (m, 3H), 2.13–2.18 (m, 1H),
2.30 (s, 3H), 2.45–2.53 (m, 1H), 2.95–3.00 (m, 1H), 7.22–
7.27 (m, 3H), 7.34–7.37 (m, 2H); 13C NMR (CDCl3) d 0.2,
20.3, 27.6, 35.1, 40.0, 53.1, 62.4, 85.8, 90.1, 123.6, 127.7,
128.2, 131.5; MS (EI): m/z 271 (M+); HRMS Calcd for
C17H25NSi: 271.1756 (M+). Found: 271.1779.
1
760, 698 cmꢁ1; H NMR (CDCl3) d 0.16 (s, 9H), 1.71–
1.84 (m, 3H), 1.92–1.98 (m, 1H), 2.16 (dd, J¼13.5,
7.6 Hz, 1H), 2.27 (s, 3H), 2.44–2.52 (m, 2H), 2.97 (dt,
J¼8.5, 3.2 Hz, 1H,), 5.01–5.13 (m, 2H), 5.90 (dddd,
J¼17.1, 10.3, 7.8, 6.8 Hz, 1H); 13C NMR (CDCl3) d 0.36,
20.3, 35.5, 37.5, 42.9, 54.0, 63.6, 89.8, 105.7, 117.4,
134.3; MS (EI) m/z 221 (M+); HRMS Calcd for
C13H23NSi: 221.1600 (M+). Found: 221.1620.
3.2.10. 1-Methyl-2-(2-phenyl)ethynylpyrrolidine (5j).
Yellow oil: IR (neat) 2975, 2877, 2838, 2777, 1739, 1599,
1
1490, 1444, 1355, 1241, 1046, 757, 691 cmꢁ1; H NMR
3.2.5. 1-Methyl-2-(3-butenyl)-2-(2-trimethylsilyl)ethy-
nylpyrrolidine (5e). Orange oil: IR (neat) 3078, 2959,
2847, 2788, 2153, 1641, 1451, 1346, 1250, 1165, 1109,
(CDCl3) d 1.77–1.83 (m, 1H), 1.90–2.06 (m, 2H), 2.15–
2.24 (m, 1H), 2.39 (q, J¼8.8 Hz, 1H), 2.48 (s, 3H), 2.94
(dt, J¼8.8, 3.9 Hz, 1H), 3.30 (t, J¼7.1 Hz, 1H), 7.26–7.29
(m, 3H), 7.41–7.45 (m, 2H); 13C NMR (CDCl3) d 22.4,
1
1031, 910, 843, 760, 698 cmꢁ1; H NMR (CDCl3) d 0.11

T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
6317
32.2, 39.9, 54.8, 57.0, 84.1, 88.8, 123.3, 127.8, 128.1, 131.6;
MS (EI) m/z 185 (M+); HRMS Calcd for C13H15N: 185.1204
(M+). Found: 185.1179.
3.2.16. 1-(2-Propenyl)-2-phenyl-2-(2-trimethylsilyl)ethy-
nylpyrrolidine (7a). Orange oil: IR (neat) 3389, 3063,
2959, 2815, 2155, 1737, 1598, 1447, 1249, 1167, 1098,
916, 841, 759, 699 cmꢁ1 1H NMR (CDCl3) d 0.15 (s,
;
3.2.11. 1-Methyl-2-phenyl-2-(3-methyl-3-buten-1-ynyl)-
pyrrolidine (5k). Yellow oil: IR (neat) 3423, 3060, 3030,
2969, 2843, 2816, 2787, 2514, 2346, 1946, 1794, 1600, 1483,
9H), 1.78–1.92 (m, 3H), 2.13–2.19 (m, 1H), 2.38–2.44 (m,
1H), 2.65 (dd, J¼13.7, 7.8 Hz, 1H), 2.94–2.98 (m, 1H),
3.20 (dt, J¼8.8, 3.1 Hz, 1H), 4.94 (d, J¼10.3 Hz, 1H),
5.09 (d, J¼17.1 Hz, 1H), 5.76 (dddd, J¼17.6, 10.3, 7.8,
4.9 Hz, 1H), 7.16 (t, J¼7.3 Hz, 1H), 7.24 (t, J¼7.6 Hz,
2H), 7.63 (d, J¼8.3 Hz, 2H); 13C NMR (CDCl3) d 0.39,
21.4, 44.4, 50.7, 53.5, 68.6, 91.6, 104.6, 115.8, 126.7,
127.2, 128.1, 136.9, 143.0; MS (EI) m/z 206 (M+ꢁC6H5);
HRMS Calcd for C18H25NSi: 283.1756 (M+). Found:
283.1741.
1
1446, 1299, 1173, 895, 738, 699 cmꢁ1; H NMR (CDCl3)
d 1.82–2.01 (m, 6H), 2.05 (s, 3H), 2.18–2.24 (m, 1H), 2.58
(q, J¼8.6 Hz, 1H), 3.08–3.13 (m, 1H), 5.15 (quint,
J¼1.23 Hz, 1H), 5.26 (quint, J¼1.23 Hz, 1H), 7.15–7.19 (m,
1H), 7.24–7.28 (m, 2H), 7.59–7.61 (m, 2H); 13C NMR
(CDCl3) d 21.5, 24.1, 35.9, 44.5, 53.7, 68.7, 86.8, 89.5, 121.1,
126.8, 127.2, 128.1, 128.8, 142.9; MS (EI) m/z 225 (M+);
HRMS Calcd for C16H19N: 225.1518 (M+). Found: 225.1530.
3.2.17. 1-(2-Propenyl)-2-methyl-2-(2-trimethylsilyl)ethy-
nylpyrrolidine (7b). Orange oil: IR (neat) 3080, 2961,
2812, 2155, 1718, 1644, 1418, 1350, 1251, 1098, 1020,
3.2.12. 1-Methyl-2-phenyl-2-hexynylpyrrolidine (5l).
Yellow oil: IR (neat) 2934, 2861, 2785, 1601, 1487, 1447,
1
1
1299, 1244, 1172, 1055, 913, 756, 699 cmꢁ1; H NMR
843, 760 cmꢁ1; H NMR (CDCl3) d 0.13 (s, 9H), 1.33 (s,
(CDCl3) d 0.87 (t, J¼7.3 Hz, 3H), 1.36–1.53 (m, 4H),
1.80–1.98 (m, 3H), 2.02 (s, 3H), 2.12–2.18 (m, 1H), 2.26
(t, J¼6.8 Hz, 2H), 2.55 (q, J¼8.7 Hz, 1H), 3.06–3.11 (m,
1H), 7.16 (t, J¼7.3 Hz, 1H), 7.25 (t, J¼7.3 Hz, 2H), 7.62
(d, J¼7.3 Hz, 2H); 13C NMR (CDCl3) d 13.7, 18.5, 21.5,
22.0, 31.4, 35.8, 44.7, 53.6, 68.4, 77.7, 88.3, 126.9, 127.0,
128.0, 143.4; MS (EI) m/z 241 (M+); HRMS Calcd for
C17H23N: 241.1830 (M+). Found: 241.1831.
3H), 1.68–1.79 (m, 3H), 2.02–2.07 (m, 1H), 2.30–2.36 (m,
1H), 2.79 (dd, J¼13.2, 7.8 Hz, 1H), 2.98–3.04 (m, 1H),
3.30 (dd, J¼13.2, 5.9 Hz, 1H), 5.05 (d, J¼9.8 Hz, 1H),
5.18 (d, J¼17.1 Hz, 1H), 5.89 (dddd, J¼17.6, 9.8, 7.8,
5.4 Hz, 1H); 13C NMR (CDCl3) d 0.37, 20.2, 25.6, 40.4,
51.5, 53.5, 60.1, 88.2, 107.2, 116.6, 136.9; MS (EI) m/z
221 (M+), 206 (M+ꢁCH3); HRMS Calcd for C13H23NSi:
221.1600 (M+). Found: 221.1569.
3.2.13. 1-Methyl-2-ethyl-2-hexynylpyrrolidine (5m).
Yellow oil: IR (neat) 2964, 2934, 2875, 2786, 1460, 1378,
3.2.18. 1-(2-Propenyl)-2-ethyl-2-(2-trimethylsilyl)ethy-
nylpyrrolidine (7c). Orange oil: IR (neat) 3079, 2967,
2879, 2811, 2153, 1643, 1460, 1417, 1378, 1350, 1250,
1
1260, 1231, 1083, 1031, 909, 806, 404 cmꢁ1; H NMR
1
(CDCl3) d 0.87 (t, J¼7.3 Hz, 3H), 0.95 (t, J¼7.6 Hz, 3H),
1.21–1.31 (m, 1H), 1.35–1.46 (m, 4H), 1.62–1.75 (m, 4H),
1.91–1.96 (m, 1H), 2.16 (t, J¼6.8 Hz, 2H), 2.20 (s, 3H),
2.43 (q, J¼8.6 Hz, 1H), 2.90–2.95 (m, 1H); 13C NMR
(CDCl3) d 9.9, 13.7, 18.3, 20.2, 21.9, 31.4, 31.8, 35.5,
37.7, 54.2, 64.6, 78.9, 85.8; MS (EI) m/z 164
(M+ꢁCH2CH3); HRMS Calcd for C11H18N: 164.1439
(M+ꢁCH2CH3). Found: 164.1406.
1144, 995, 842, 760 cmꢁ1; H NMR (CDCl3) d 0.14 (s,
9H), 0.96 (t, J¼7.6 Hz, 3H), 1.32–1.41 (m, 1H), 1.66–1.81
(m, 4H), 1.97–2.01 (m, 1H), 2.31–2.37 (m, 1H), 2.77 (dd,
J¼13.2, 7.8 Hz, 1H), 3.02–3.07 (m, 1H), 3.31 (dd, J¼13.7,
5.4 Hz, 1H), 5.04 (d, J¼10.2 Hz, 1H), 5.18 (d, J¼17.1 Hz,
1H), 5.88 (dddd, J¼17.6, 10.3, 8.3, 5.4 Hz, 1H); 13C NMR
(CDCl3) d 0.41, 9.6, 20.3, 31.7, 37.4, 51.8, 53.5, 64.8,
89.1, 106.6, 116.3, 137.1; MS (EI) m/z 206
(M+ꢁCH2CH3); HRMS Calcd for C12H20NSi: 206.1365
(M+ꢁCH2CH3). Found: 206.1354.
3.2.14. 1-Methyl-2-hexynylpyrrolidine (5n). Yellow oil:
IR (neat) 2958, 2873, 2775, 2235, 1641, 1458, 1353, 1321,
1
1219, 1159, 1115, 1039, 904, 733, 407 cmꢁ1; H NMR
3.2.19. 1-(2-Propenyl)-2-(4-methoxyphenyl)-2-(2-tri-
methylsilyl)ethynylpyrrolidine (7d). Yellow oil: IR (neat)
3076, 2957, 2813, 2155, 1643, 1611, 1582, 1509, 1464,
(CDCl3) d 0.84 (t, J¼7.3 Hz, 3H), 1.30–1.46 (m, 4H),
1.62–1.71 (m, 1H), 1.75–1.84 (m, 2H), 1.98–2.05 (m, 1H),
2.14 (td, J¼7.3, 1.8 Hz, 2H), 2.19–2.25 (m, 1H), 2.33 (s,
3H), 2.79–2.85 (m, 1H), 2.94 (t, J¼6.8 Hz, 1H); 13C NMR
(CDCl3) d 13.6, 18.4, 21.9, 22.2, 31.0, 32.4, 39.8, 54.8,
56.8, 79.2, 84.2; MS (EI) m/z 165 (M+); HRMS Calcd for
C11H19N: 165.1517 (M+). Found: 165.1493.
1
1415, 1349, 1250, 1172, 1038, 843, 760, 699 cmꢁ1; H
NMR (CDCl3) d 0.21 (s, 9H), 1.84–1.96 (m, 3H), 2.16–
2.22 (m, 1H), 2.41–2.47 (m, 1H), 2.67 (dd, J¼13.7,
7.8 Hz, 1H), 2.98–3.03 (m, 1H), 3.24 (dt, J¼8.3, 2.9 Hz,
1H), 3.79 (s, 3H), 5.00 (d, J¼10.2 Hz, 1H), 5.15 (dd,
J¼17.1, 0.98 Hz, 1H), 5.80 (dddd, J¼17.6, 10.2, 7.8,
4.9 Hz, 1H), 6.85 (d, J¼8.8 Hz, 2H), 7.59 (d, J¼8.8 Hz,
2H); 13C NMR (CDCl3) d 0.41, 21.3, 44.2, 50.6, 53.4,
55.3, 68.1, 91.5, 104.7, 113.4, 115.8, 127.9, 134.9, 136.9,
158.8; MS (EI) m/z 313 (M+); HRMS Calcd for
C19H27NOSi: 313.1862 (M+). Found: 313.1836.
3.2.15. 1-Methyl-2-phenyl-2-(1-cyclohexenyl)ethynylpyr-
rolidine (5o). Yellow oil: IR (neat) 3060, 2935, 2840, 2785,
2204, 1948, 1810, 1741, 1600, 1488, 1446, 1346, 1297,
1
1241, 1173, 1055, 918, 756, 699 cmꢁ1; H NMR (CDCl3)
d 1.51–1.63 (m, 4H), 1.82–1.89 (m, 2H), 1.94–2.07 (m,
6H), 2.12–2.23 (m, 3H), 2.58 (dd, J¼17.1, 8.8 Hz, 1H),
3.08–3.13 (m, 1H), 6.08 (quint, J¼2.0 Hz, 1H), 7.16 (t,
J¼7.3 Hz, 1H), 7.25 (t, J¼7.8 Hz, 2H), 7.62 (d, J¼7.3 Hz,
2H); 13C NMR (CDCl3) d 21.5, 21.6, 22.4, 25.6, 29.9,
35.9, 44.6, 53.7, 68.8, 84.7, 90.2, 120.7, 126.8, 127.1,
128.1, 134.0, 143.1; MS (EI) m/z 265 (M+); HRMS Calcd
for C19H23N: 265.1830 (M+). Found: 265.1810.
3.2.20. 1-(2-Propenyl)-2-(2-trimethylsilyl)ethynylpiperi-
dine (9a). Yellow oil: IR (neat) 3080, 2937, 2861, 2814,
2157, 1745, 1643, 1442, 1420, 1319, 1250, 1124, 955,
920, 843, 760 cmꢁ1 1H NMR (CDCl3) d 0.11 (s, 9H),
;
1.36–1.61 (m, 4H), 1.66–1.70 (m, 2H), 2.39–2.44 (m, 2H),
2.96 (dd, J¼7.3, 5.9 Hz, 1H), 3.06–3.11 (m, 1H), 3.50 (s,

6318
T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
1H), 5.07 (d, J¼10.2 Hz, 1H), 5.15 (d, J¼17.1 Hz, 1H), 5.78
(dddd, J¼17.1, 13.2, 10.3, 6.4 Hz, 1H); 13C NMR (CDCl3)
d 0.25, 20.6, 25.6, 31.2, 48.9, 52.1, 59.3, 90.6, 103.5,
118.0, 135.2; MS (EI) m/z 221 (M+); HRMS Calcd for
C13H23NSi: 221.1600 (M+). Found: 221.1569.
1172, 1037, 919, 831, 794 cmꢁ1 1H NMR (CDCl3)
;
d 1.87–2.00 (m, 3H), 2.20–2.26 (m, 1H), 2.44–2.51 (m,
1H), 2.56 (s, 1H), 2.72 (dd, J¼13.7, 8.3 Hz, 1H), 3.01–
3.06 (m, 1H), 3.27 (dt, J¼8.5, 3.2 Hz, 1H), 3.79 (s, 3H),
5.01 (dt, J¼11.2, 1.5 Hz, 1H), 5.17 (dq, J¼17.1, 1.5 Hz,
1H), 5.81 (dddd, J¼17.1, 10.2, 8.3, 4.9 Hz, 1H), 6.85 (d,
J¼8.8 Hz, 2H), 7.62 (d, J¼8.8 Hz, 2H); 13C NMR
(CDCl3) d 21.2, 44.3, 50.5, 53.2, 55.2, 67.5, 75.1, 82.5,
113.4, 115.9, 127.8, 134.6, 136.7, 158.8; MS (EI) m/z 241
(M+); HRMS Calcd for C16H19NO: 241.1467 (M+). Found:
241.1458.
3.2.21. 1-(2-Propenyl)-2-phenyl-2-(2-trimethylsilyl)ethy-
nylpiperidine (9b). Yellow oil: IR (neat) 3062, 2935,
2860, 2817, 2724, 2156, 1642, 1601, 1488, 1446, 1347,
1
1250, 1222, 1131, 1012, 915, 843, 700 cmꢁ1; H NMR
(CDCl3) d 0.19 (s, 9H), 1.47–1.71 (m, 6H), 2.28–2.38 (m,
2H), 2.84–2.90 (m, 2H), 4.94 (d, J¼10.3 Hz, 1H), 5.04 (d,
J¼17.1 Hz, 1H), 5.65 (dddd, J¼17.6, 10.2, 7.8, 4.4 Hz,
1H), 7.16 (t, J¼7.3 Hz, 1H), 7.24 (t, J¼7.6 Hz, 2H), 7.67
(d, J¼7.3 Hz, 2H); 13C NMR (CDCl3) d 0.48, 22.3, 25.9,
43.3, 48.2, 55.8, 65.5, 93.4, 103.6, 116.0, 126.6, 127.1,
128.1, 136.8, 145.6; MS (EI) m/z 297 (M+); HRMS Calcd
for C19H27NSi: 297.1913 (M+). Found: 297.1888.
3.3.2. 1-(2-Propenyl)-2-phenyl-2-ethynylpyrrolidine
(10b). Yellow oil: IR (neat) 3300, 3062, 3025, 2977, 2878,
2816, 1642, 1600, 1488, 1446, 1418, 1350, 1262, 1098,
1
918, 758, 699 cmꢁ1; H NMR (CDCl3) d 1.88–2.03 (m,
3H), 2.24–2.30 (m, 1H), 2.48–2.55 (m, 1H), 2.57 (s, 1H),
2.76 (dd, J¼13.7, 8.3 Hz, 1H), 3.04–3.09 (m, 1H), 3.31
(dt, J¼8.6, 3.1 Hz, 1H), 5.03 (d, J¼10.3 Hz, 1H), 5.19 (dq,
J¼17.1, 1.5 Hz, 1H), 5.84 (dddd, J¼17.1, 10.2, 7.8,
4.4 Hz, 1H), 7.25 (t, J¼7.3 Hz, 1H), 7.33 (t, J¼7.6 Hz,
2H), 7.72 (d, J¼7.3 Hz, 2H); 13C NMR (CDCl3) d 21.3,
44.5, 50.6, 53.4, 68.0, 75.1, 82.4, 116.0, 126.6, 127.3,
128.2, 136.7, 142.7; MS (EI) m/z 211 (M+), 170
(M+ꢁCH2CH]CH2); HRMS Calcd for C15H17N:
211.1361 (M+). Found: 211.1375.
3.2.22. 1-(2-Propenyl)-2-ethyl-2-(2-trimethylsilyl)ethy-
nylpiperidine (9c). Orange oil: IR (neat) 2935, 2810,
2154, 1641, 1444, 1250, 1161, 1085, 992, 905, 859, 842,
1
760, 698 cmꢁ1; H NMR (CDCl3) d 0.11 (s, 9H), 0.87 (t,
J¼7.8 Hz, 3H), 1.19–1.73 (m, 8H), 2.18 (dt, J¼11.7,
2.4 Hz, 1H), 2.50 (dd, J¼13.7, 7.8 Hz, 1H), 2.70 (d,
J¼12.2 Hz, 1H), 3.34 (dt, J¼14.2, 2.4 Hz, 1H), 5.00
(d, J¼10.2 Hz, 1H), 5.09 (d, J¼17.1 Hz, 1H), 5.78 (dddd,
J¼17.5, 10.3, 8.3, 4.9 Hz, 1H); 13C NMR (CDCl3) d 0.46,
8.0, 21.6, 25.8, 32.4, 35.4, 48.6, 54.1, 59.3, 89.8, 106.7,
116.4, 137.1; MS (EI) m/z 220 (M+ꢁCH2CH3); HRMS
Calcd for C13H22NSi: 220.1522 (M+ꢁCH2CH3). Found:
220.1528.
3.3.3. 1-(2-Propenyl)-2-methyl-2-ethynylpyrrolidine
(10c). Yellow oil: IR (neat) 3303, 2975, 2814, 1643, 1443,
1
1370, 1351, 1260, 1143, 995, 919, 636 cmꢁ1; H NMR
(CDCl3) d 1.31 (s, 3H), 1.67–1.77 (m, 3H), 2.02–2.06 (m,
1H), 2.23 (s, 1H), 2.26–2.33 (m, 1H), 2.77 (dd, J¼13.2,
7.8 Hz, 1H), 2.97–3.02 (m, 1H), 3.28 (dd, J¼13.2, 4.9 Hz,
1H), 5.00 (d, J¼9.8 Hz, 1H), 5.15 (d, J¼17.1 Hz, 1H),
5.83 (dddd, J¼17.6, 9.8, 7.8, 5.4 Hz, 1H); 13C NMR
(CDCl3) d 20.1, 25.6, 40.4, 51.4, 53.3, 59.5, 72.1, 84.7,
116.6, 136.7; MS (EI) m/z 149 (M+); HRMS Calcd for
C9H12N: 134.0970 (M+ꢁCH3). Found: 134.0937.
3.2.23. 1-Phenylmethyl-2-(3-butenyl)-2-(2-trimethylsilyl)
ethynylpiperidine (9d). Yellow oil: IR (neat) 3063, 3028,
2935, 2861, 2804, 2153, 1640, 1603, 1495, 1452, 1360,
1250, 1162, 1067, 991, 842, 728, 640 cmꢁ1 1H NMR
;
(CDCl3) d 0.14 (s, 9H), 1.25–1.41 (m, 2H), 1.50–1.64 (m,
4H), 1.73–1.85 (m, 2H), 2.13–2.23 (m, 3H), 2.47 (d,
J¼11.7 Hz, 1H), 2.94 (d, J¼14.2 Hz, 1H), 3.93
(d, J¼14.2 Hz, 1H), 4.85 (d, J¼10.3 Hz, 1H), 4.93 (d,
J¼17.1 Hz, 1H), 5.74 (dddd, J¼17.0, 12.7, 10.2, 6.3 Hz,
1H), 7.11–7.28 (m, 5H); 13C NMR (CDCl3) d 0.53, 21.8,
25.9, 27.7, 36.1, 39.2, 48.6, 55.0, 58.8, 89.9, 106.6, 114.3,
126.5, 128.2, 128.6, 138.9, 140.5; MS (EI) m/z 325 (M+);
HRMS Calcd for C21H31NSi: 325.2226 (M+). Found:
325.2215.
3.3.4. 1-(2-Propenyl)-2-ethyl-2-ethynylpyrrolidine (10d).
Yellow oil: IR (neat) 3303, 3079, 2971, 2936, 2880, 2813,
2362, 2095, 1643, 1460, 1351, 1260, 1143, 997, 918,
635 cmꢁ1
;
1H NMR (CDCl3) d 0.97 (t, J¼7.3 Hz, 3H),
1.34–1.43 (m, 1H), 1.68–1.81 (m, 4H), 1.97–2.02 (m, 1H),
2.26 (s, 1H), 2.31–2.37 (m, 1H), 2.77 (dd, J¼13.2, 7.8 Hz,
1H), 3.03–3.08 (m, 1H), 3.31 (dd, J¼13.2, 5.4 Hz, 1H),
5.02 (d, J¼9.8 Hz, 1H), 5.17 (dd, J¼17.1, 0.98 Hz, 1H),
5.85 (dddd, J¼17.1, 10.2, 8.3, 5.4 Hz, 1H); 13C NMR
(CDCl3) d 9.4, 20.2, 31.7, 37.3, 51.7, 53.3, 64.1, 72.8,
84.1, 116.4, 136.8; MS (EI) m/z 134 (M+ꢁCH2CH3);
HRMS Calcd for C9H12N: 134.0970 (M+ꢁCH2CH3).
Found: 134.0956.
3.3. General procedure for the desilylation of cyclic
amines 7 and 9 with K2CO3 in MeOH
In a typical experiment, a mixture of 1-(2-propenyl)-2-
phenyl-2-(2-trimethylsilyl)ethynylpyrrolidine 7a (0.603 g,
2.1 mmol) and K2CO3 (0.290 g, 2.1 mmol) in MeOH
(10 mL) was stirred at room temperature for 5 h, and then
treated with an aqueous solution of NH4Cl, extracted with
ether, washed with brine, dried over MgSO4 and con-
centrated in vacuo to give the amine 10b (0.415 g, 93%) as
a yellow oil.
3.3.5. 1-(2-Propenyl)-2-ethyl-2-ethynylpiperidine (12).
Yellow oil: IR (neat) 3305, 2935, 2812, 2095, 1643, 1443,
1
1347, 1261, 1166, 1019, 918, 805, 637 cmꢁ1; H NMR
(CDCl3) d 0.92 (t, J¼7.8 Hz, 3H), 1.37–1.78 (m, 8H), 2.23
(td, J¼11.7, 2.9 Hz, 1H), 2.30 (s, 1H), 2.56 (dd, J¼14.2,
8.3 Hz, 1H), 2.77 (dt, J¼12.2, 2.9 Hz, 1H), 3.41 (d,
J¼14.2 Hz, 1H), 5.04 (d, J¼10.2 Hz, 1H), 5.14 (d,
J¼17.1 Hz, 1H), 5.81 (dddd, J¼17.5, 10.3, 8.3, 4.9 Hz,
1H); 13C NMR (CDCl3) d 7.9, 21.5, 25.7, 32.6, 35.4, 48.6,
54.0, 58.8, 73.4, 84.1, 116.5, 136.9; MS (EI) m/z 148
3.3.1. 1-(2-Propenyl)-2-(4-methoxyphenyl)-2-ethynyl-
pyrrolidine (10a). Yellow oil: IR (neat) 3296, 3075, 2955,
2815, 1643, 1609, 1581, 1509, 1463, 1416, 1349, 1249,

T. Murai et al. / Tetrahedron 62 (2006) 6312–6320
6319
(M+ꢁCH2CH3); HRMS Calcd for C12H19N: 177.1517 (M+).
m/z 347 (M+); HRMS Calcd for C23H29NSi: 347.2069
Found: 177.1507.
(M+). Found: 347.2041.
3.4.4. syn-1-[E-(Dimethylsilyl)methylidene]-7a-phenyl-
2-methylhexahydro-1H-pyrrolizine. 1H NMR (CDCl3)
d 0.33 (s, 3H), 0.35 (s, 3H), 0.81 (d, J¼6.8 Hz, 3H), 1.62–
1.71 (m, 1H), 1.74–1.84 (m, 1H), 1.97–2.04 (m, 1H),
2.10–2.17 (m, 1H), 2.61–2.67 (m, 1H), 2.72–2.76 (m, 3H,
CH2), 3.01–3.07 (m, 1H), 5.60 (s, 1H), 7.10–7.13 (m, 1H),
7.19–7.24 (m, 2H), 7.27–7.29 (m, 3H), 7.45–7.48 (m, 2H),
7.54–7.56 (m, 2H); 13C NMR (CDCl3) d ꢁ0.81, ꢁ0.65,
21.3, 25.0, 39.0, 40.6, 54.1, 59.2, 80.9, 117.4, 126.0,
127.8, 127.9, 128.9, 133.8, 139.8, 147.4, 171.5.
3.4. General procedure for the silylcarbocyclization of
cyclic amines 10 and 12
In a typical example, a two-necked flask equipped with a
stirring bar and a CO inlet was charged with Rh4(CO)12
(1.9 mg, 0.0025 mmol). After the flask was purged with
CO, hexane (1 mL) was added to dissolve the catalyst.
Me2PhSiH (0.038 mL, 0.25 mmol) was added via a syringe.
After the reaction mixture was stirred for 5 min at room tem-
perature, it was then cannulated into a flask containing a
solution of 1-(2-propenyl)-2-phenyl-2-ethynylpyrrolidine
10b (0.106 g, 0.5 mmol), Me2PhSiH (0.077 mL, 0.5 mmol)
in hexane (1 mL) via CO pressure without stirring. The
resulting mixture was stirred for 72 h. The reaction mixture
was concentrated under reduced pressure, and the residue
was purified by column chromatography (SiO2, hexane/
EtOAc/Et3N¼3:1:1 vol %) to give a mixture of four dia-
stereomers of the bicyclic compound 11b (0.153 g, 88%,
70:26:3:1) as a yellow oil.
3.4.5. Major isomer of 1-[E-(dimethylsilyl)methylidene]-
8a-ethyl-2-methyloctahydroindolizine (13). Yellow oil: IR
(neat) 3067, 2927, 2797, 1619, 1483, 1427, 1372, 1329,
1
1248, 1113, 974, 832, 700 cmꢁ1; H NMR (CDCl3) d 0.29
(s, 3H), 0.31 (s, 3H), 0.71 (t, J¼7.3 Hz, 3H), 0.96 (t,
J¼6.8 Hz, 3H), 1.08–1.11 (m, 2H), 1.30 (sext, J¼7.3 Hz,
1H), 1.42–1.65 (m, 4H), 1.95 (sext, J¼7.3 Hz, 1H), 2.49
(sext, J¼7.3 Hz, 1H), 2.65–2.73 (m, 2H), 2.78–2.84 (m,
1H), 2.91 (t, J¼8.3 Hz, 1H), 5.15 (d, J¼2.4 Hz, 1H), 7.24–
7.26 (m, 3H), 7.45–7.48 (m, 2H); 13C NMR (CDCl3)
d ꢁ0.63, ꢁ0.45, 7.8, 18.9, 21.2, 21.5, 24.0, 30.8, 36.6,
43.9, 56.2, 67.0, 113.2, 127.7, 128.7, 133.8, 140.1; MS
(EI) m/z 313 (M+); HRMS Calcd for C20H31NSi: 313.2226
(M+). Found: 313.2249.
3.4.1. anti-1-[Z-(Dimethylsilyl)methylidene]-7a-(4-meth-
oxyphenyl)-2-methylhexahydro-1H-pyrrolizine (11a).
Yellow oil: IR (neat) 3067, 2955, 2833, 1609, 1508, 1462,
1427, 1375, 1302, 1247, 1176, 1114, 1038, 836, 774,
1
639 cmꢁ1; H NMR (CDCl3) d 0.27 (s, 3H), 0.29 (s, 3H),
1.03 (d, J¼6.8 Hz, 3H), 1.62–1.71 (m, 1H), 1.87–1.96 (m,
1H), 2.00–2.06 (m, 1H), 2.24–2.30 (m, 1H), 2.38 (dd,
J¼10.3, 6.8 Hz, 1H), 2.68–2.73 (m, 1H), 2.76–2.82 (m,
1H), 2.90–2.96 (m, 1H), 3.24 (dd, J¼10.3, 8.3 Hz, 1H),
3.73 (s, 3H), 5.36 (d, J¼2.4 Hz, 1H), 6.79 (d, J¼8.8 Hz,
2H), 7.22–7.29 (m, 3H), 7.37–7.40 (m, 4H); 13C NMR
(CDCl3) d ꢁ0.52, 22.0, 24.8, 37.3, 38.6, 53.5, 55.2, 60.2,
82.2, 113.2, 117.9, 127.7, 127.8, 128.7, 133.7, 138.8,
139.9, 158.0, 173.4; MS (EI) m/z 377 (M+); HRMS Calcd
for C24H31NOSi: 377.2175 (M+). Found: 377.2165.
Acknowledgements
This work was supported in part by a Grant-in-Aid
for Scientific Research on Priority Area (No. 18037024,
‘Advanced Molecular Transformations of Carbon Re-
sources’) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
References and notes
3.4.2. syn-1-[E-(Dimethylsilyl)methylidene]-7a-(4-meth-
oxyphenyl)-2-methylhexahydro-1H-pyrrolizine. H NMR
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(CDCl3) d 0.35 (t, J¼4.6 Hz, 6H), 0.84 (d, J¼6.8 Hz, 3H),
1.63–1.72 (m, 1H), 1.74–1.84 (m, 1H), 1.97–2.03 (m, 1H),
2.08–2.15 (m, 1H), 2.58–2.65 (m, 1H), 2.68–2.78 (m, 3H),
3.00–3.06 (m, 1H), 3.73 (s, 3H), 5.56 (s, 1H), 6.77 (d,
J¼9.3 Hz, 2H), 7.28–7.30 (m, 2H), 7.43–7.50 (m, 4H),
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2-methylhexahydro-1H-pyrrolizine (11b). Yellow oil: IR
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1
1028, 836, 762, 730, 700, 641 cmꢁ1; H NMR (CDCl3)
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1.71 (m, 1H), 1.87–1.96 (m, 1H), 2.03–2.10 (m, 1H),
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7.16 (m, 1H), 7.20–7.29 (m, 5H), 7.36–7.39 (m, 2H),
7.46–7.49 (m, 2H); 13C NMR (CDCl3) d ꢁ0.49, 22.0,
25.0, 37.8, 38.8, 53.9, 60.4, 82.6, 118.1, 126.2, 126.7,
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16. The stereochemistry of 13 was not determined, but the geome-
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the basis of phase-sensitive NOESY spectroscopy.