Asymmetric synthesis of optically active 2-vinylpyrrolidines and 2-vinylpiperidines by palladium-catalysed cyclisation of amino allylic carbonates

Article abstract of DOI:10.1016/j.tetlet.2012.10.014

Optically active 2-vinylpyrrolidines and 2-vinylpiperidines were synthesised from the corresponding amino allylic carbonates via palladium-catalysed cyclisation. The use of chiral ligands gave the corresponding pyrrolidine and piperidine derivatives havin

Full text of DOI:10.1016/j.tetlet.2012.10.014

Tetrahedron Letters 53 (2012) 6826–6829
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Tetrahedron Letters
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Asymmetric synthesis of optically active 2-vinylpyrrolidines and
2-vinylpiperidines by palladium-catalysed cyclisation of amino allylic
carbonates
⇑
Beata Olszewska, Bogusław Kryczka, Anna Zawisza
´
´
Department of Organic and Applied Chemistry, University of Łódz, Tamka 12, 91-403 Łódz, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Optically active 2-vinylpyrrolidines and 2-vinylpiperidines were synthesised from the corresponding
amino allylic carbonates via palladium-catalysed cyclisation. The use of chiral ligands gave the corre-
sponding pyrrolidine and piperidine derivatives having er values from low to moderate.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 13 August 2012
Revised 11 September 2012
Accepted 4 October 2012
Available online 12 October 2012
Keywords:
Allylic carbonate
Cyclisation
Homogeneous catalysis
Nitrogen heterocycles
Palladium
Saturated nitrogen heterocycles, such as pyrrolidines, piperi-
dines and isoxazolidines, appear as subunits in a broad array of
biologically active and medicinally significant molecules.1 For
these reasons, the synthesis of these compounds has been of
long-standing interest. Many classical approaches to their con-
struction involve the use of C–N bond-forming reactions such as
reductive amination, nucleophilic substitution or dipolar cycload-
dition.2 Although these methods have proved to be quite useful,
their substrate scope and functional group tolerance are often lim-
ited. In recent years, several powerful new transformations have
been developed that involve the use of palladium-catalysed C–N
bond-forming reactions for construction of heterocyclic rings.3
These transformations frequently occur under mild conditions,
tolerate a broad array of functional groups and proceed with high
stereoselectivity.
electrophiles to Pd0. An important improvement in
p-allylpalla-
dium chemistry was achieved by the introduction of allylic carbon-
ates. Carbonates are highly reactive, and more importantly, their
reactions can be carried out under neutral conditions.10
Extending our previous work on the use of allyl carbonates in
the synthesis of O-heterocycles,11 herein we describe our prelimin-
ary results obtained on enantioselective Pd-catalysed allylic
aminations.
Experiments were performed with methyl and isobutyl carbon-
ates 5a–c (Scheme 1) using commercially available ligands (Fig. 1).
Substrates 5a–c were prepared by reduction of bromoesters
1a,b to the corresponding aldehydes12 followed by elongation of
the chain via Wittig reaction,13 reduction to the alcohol 3a,b,14
condensation with methyl or isobutyl chloroformate and, finally,
substitution of the bromine atom with a 4-methylbenzenesulfona-
mide group (tosyl group).
The synthesis of saturated nitrogen heterocycles via Pd-cata-
lysed and other C–N bond-forming reactions can be broadly classi-
fied into four categories: (i) amination reactions of alkenes, alkynes
and allenes;2a,2f,4 (ii) 1,3-dipolar cycloadditions;5 (iii) carbonyl-
ation processes;6 and (iv) intramolecular addition of nitrogen
The cyclisation was first studied with methyl carbonate 5a as
the substrate.15 Ring-closure of 5a occurred slowly (48 h) at room
temperature in the presence of a catalytic amount of Pd2(dba)3
associated with the (R,R)-Trost ligand, providing 2-vinylpyrrolidine
6a15,16 as a 45:55 mixture of enantiomers in 94% overall yield
(Table 1, entry 1).
nucleophiles to intermediate
ber of different strategies have been employed for the generation
p
-allylpalladium complexes.7 A num-
of reactive intermediate
p
-allylpalladium complexes, such as oxi-
Isobutyl carbonate 5b was more reactive under the same condi-
tions (Table 1, entry 2) and gave product 6a with the highest yield
(98%) and stereoselectivity (40:60 er) in 24 h. Longer chain isobutyl
carbonate 5c was also submitted to this cyclisation procedure in
the presence of the (R,R)-Trost ligand. Pyrrolidine 6b15,17 was
dative addition of alkenyl epoxides,8 allylic acetates9 and related
⇑
Corresponding author. Tel.: +48 42 6355764; fax: +48 42 6655162.
E-mail address: azawisza@chemia.uni.lodz.pl (A. Zawisza).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.10.014

B. Olszewska et al. / Tetrahedron Letters 53 (2012) 6826–6829
6827
b
c
a
d
Br
Br
CO2C2H5
Br
OCO2R
Br
CO2C2H5
OH
n
n
n
n
4a: n = 1, R = Me
1a: n = 1
1b
2a: n = 1
3a: n = 1
4b
2b
: n = 2
3b
: n = 1, R =
i
-Bu
: n = 2
: n = 2
4c
: n = 2, R =
i
-Bu
n
e
TsHN
N
Ts
OCO2R
n
5a: n = 1, R = Me
6a: n = 1
6b: n = 2
5b
: n = 1, R =
i
-Bu
5c
: n = 2, R =
i
-Bu
Scheme 1. Pd0-catalysed synthesis of heterocycles 6a,b; reagents and conditions: (a) 1. DIBAL-H, CH2Cl2, À78 °C, 2. Ph3P@CHO2C2H5, CH2Cl2, rt; (b) DIBAL-H, Et2O, 0 °C; (c)
ROCOCl, C5H5N, CH2Cl2, 0 °C?rt; (d) TsNHNa, TsNH2, DMSO, 60 °C; (e) [Pd], ligand.
H
Ph
O
O
cHex
O
O
Ph2P
PPh2
PPh2
Ph2P
NH
HN
PPh2
Fe
P
N
CH3
)-Josiphos
Figure 1. Ligands used in this work.
Ph
(S)-BINAP
(R,S
(R
,
R
)-Trost's ligand
L1 (S,S,aS)
Table 1
Pd0-catalysed allylic cyclisation of substrates 5a–c according to Scheme 1a
Entry
Substrate
Ligand
Product
Temp (°C)
Time (h)
Yield (%)b
er (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
5a
5b
5c
5a
5b
5c
5a
5a
5b
5b
5c
5c
5c
5a
5a
5b
5c
(R,R)-Trost
(R,R)-Trost
(R,R)-Trost
(S)-BINAP
(S)-BINAP
(S)-BINAP
(R,S)-Josiphos
(R,S)-Josiphos
(R,S)-Josiphos
(R,S)-Josiphos
(R,S)-Josiphos
(R,S)-Josiphos
(R,S)-Josiphos
L1
6a
6a
6b
6a
6a
6b
6a
6a
6a
6a
6b
6b
6b
6a
6a
6a
6b
20
20
20
20
20
20
20
60
20
60
20
20
60
20
60
20
20
48
24
24
48
48
48
96
96
48
48
48
168
72
24
24
24
24
94
98
99
97
97
45
73
78
87
96
10
82
92
0
45:55
40:60
61:39
41:59
36:64
65:35
47:53
46:54
41:59
50:50
66:34
65:35
53:47
—
L1
L1
L1
44
99
99
22:78
22:78
90:10
a
b
c
[5]:[Pd2(dba)3]:[ligand] = 40:1:2.2 (4.4), THF.
Yield refers to isolated pure products after column chromatography.
Enantioselectivity (er) was measured by chiral stationary phase HPLC on a chiral IA column (25 cm  4.6 mm); i-propanol/hexane (99:1), flow rate = 0.2 ml minÀ1
,
tR = 23.8 min and tR = 24.8 min for 6a; methanol, flow rate = 0.2 ml min-1, tR = 23.6 min and tR = 26.4 min for 6b; the first value corresponds to the enantiomer being eluted
first.
obtained in a very good yield (99%) and in a 61:39 ratio (Table 1,
entry 3). This Pd0-catalysed cyclisation was extended to other li-
gands. Reactions with (S)-BINAP required longer reaction times
and were characterised by moderate er values of 41:59, 36:64
and 65:35 (5a, 5b and 5c, respectively), affording quantitative
yields of pyrrolidine 6a (97%) and a moderate yield of piperidine
6b (45%) (Table 1, entries 4–6). The use of (R,S)-Josiphos as the chi-
ral ligand and carbonate 5a afforded 6a in a good yield of 73% after
96 h but with a very low er value of 47:53 (Table 1, entry 7).
Increasing the temperature to 60 °C did not improve the selectivity
of the reaction and resulted in only a slight increase in the yield
(Table 1, entry 8). Isobutyl carbonate 5b in the presence of the Josi-
phos ligand, similar to the results observed in the case of the Trost
ligand, gave pyrrolidine 6a in less time and with a better yield, but
with poor enantioselectivity 41:59 (Table 1, entry 9). The same
reaction at 60 °C afforded a 1:1 mixture of enantiomers (Table 1,
entry 10). Isobutyl carbonate 5c was less reactive and required a
much longer reaction times (Table 1, entries 11–13). Piperidine
6b was obtained in 10% yield after 48 h and 82% after 168 h as a
65:35 mixture, while at 60 °C, 6b was obtained in 92% yield after
72 h (53:47 er).
Finally, the asymmetric cyclisation of allylic carbonates 5a–c
was performed in the presence of the phosphorus amidite ligand,
L1. The cyclisation of compound 5a at room temperature did not
give the expected product 6a, but at 60 °C the same reaction affor-
ded a 22:78 mixture of enantiomers in 44% yield after 24 h (Table
1, entries 14–15). The more reactive carbonate 5b, at room temper-
ature gave quantitatively pyrrolidine 2a with good selectivity
(22:78 er) (Table 1, entry 16). Piperidine 6b was obtained in 99%
yield under the same conditions with an er value of 90:10 starting
from allylic carbonate 5c (Table 1, entry 17).
Table 2 illustrates the influence of the solvent on these intramo-
lecular aminations. The best results were obtained for the reaction
carried out in THF. Similar results were observed in toluene.

6828
B. Olszewska et al. / Tetrahedron Letters 53 (2012) 6826–6829
Table 2
Tetrahedron 2006, 62, 7213–7256; (f) Coldham, I.; Hufton, R. Chem. Rev. 2005,
105, 2765–2810.
Effect of solvent on the asymmetric allylic amination of substrate 5c using ligand L1a
3. (a) Li, J. J.; Gribble, G. Palladium in Heterocyclic Chemistry; Pergamon Press: New
York, 2000; (b) Zeni, G.; Larock, R. C. Chem. Rev. 2004, 104, 2285–2309; (c)
Wolfe, J. P.; Thomas, J. S. Curr. Org. Chem. 2005, 9, 625–656; (d) Balme, G.;
Bossharth, E.; Monteiro, N. Eur. J. Org. Chem. 2003, 4101–4111; (e) D’Souza, D.
M.; Müller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095–1108; (f) Zeni, G.; Larock, R. C.
Chem. Rev. 2006, 106, 4644–4680; (g) Minatti, A.; Muniz, K. Chem. Soc. Rev.
2007, 36, 1142–1152.
Entry
Solvent
Yield (%)
er (%)
1
2
3
4
THF
99
98
99
43
90:10
75:25
89:11
55:45
CH2Cl2
Toluene
CH3CN
4. (a) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400–3420; (b) Trend, R. M.;
Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem., Int. Ed. 2003, 42,
2892–2895; (c) Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. M. J. Am.
Chem. Soc. 2005, 127, 17778–17788; (d) Rogers, M. M.; Wendlandt, J. E.; Guzei,
I. A.; Stahl, S. S. Org. Lett. 2006, 8, 2257–2260; (e) Lu, X. Top. Catal. 2005, 35, 73–
86; (f) Lei, A.; Liu, G.; Lu, X. J. Org. Chem. 2002, 67, 974–980; (g) Kozawa, Y.;
Mori, M. Tetrahedron Lett. 2002, 43, 1499–1502; (h) Kimura, M.; Wakamiya, Y.;
Horino, Y.; Tamaru, Y. Tetrahedron Lett. 1997, 38, 3963–3966; (i) Meguro, M.;
Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421–5424; (j) Bajracharya, G. B.;
Huo, Z.; Yamamoto, Y. J. Org. Chem. 2005, 70, 4883–4886; (k) Bertrand, M. B.;
Leathen, M. L.; Wolfe, J. P. J. Org. Chem. 2007, 9, 457–460; (l) Scarborough, C. C.;
Stahl, S. S. Org. Lett. 2006, 8, 3251–3254; (m) Davies, I. W.; Scopes, D. I. C.;
Gallagher, T. Synlett 1993, 85–87.
a
[5c]:[Pd2(dba)3]:[ligand] = 40:1:4.4, 20 °C, 24 h.
Table 3
Effect of the palladium precursor on the asymmetric allylic amination of substrate 5ca
Entry
[Pd] precursor
Ligand
Time (h)
Yield (%)
er (%)
1
2
3
4
5
6
7
8
9
Pd2dba3
[PdCl(C3H5)]2
Pd(OAc)2
Pd2dba3
[PdCl(C3H5)]2
Pd(OAc)2
Pd2dba3
[PdCl(C3H5)]2
Pd(OAc)2
(S)-BINAP
(S)-BINAP
(S)-BINAP
(R,S)-Josiphos
(R,S)-Josiphos
(R,S)-Josiphos
L1
48
24
24
48
24
24
24
24
24
45
89
83
10
50
95
99
0
65:35
56:44
40:60
66:34
61:39
54:46
90:10
—
5. (a) Kimura, M.; Tamaki, T.; Nakata, M.; Tohyama, K.; Tamaru, Y. Angew. Chem.,
Int. Ed. 2008, 47, 5803–5805; (b) Baeg, J.-O.; Alper, H. J. Am. Chem. Soc. 1994,
116, 1220–1224; (c) Baeg, J.-O.; Bensimon, C.; Alper, H. J. Am. Chem. Soc. 1995,
117, 4700–4701.
L1
L1
6. (a) Grigg, R.; Srdharan, V.; Suganthan, S.; Bridge, A. W. Tetrahedron 1995, 51,
295–306; (b) Chao, C. S.; Chu, D. Y.; Lee, D. Y.; Shim, S. C.; Kim, T. J.; Lim, W. T.;
Heo, N. H. Synth. Commun. 1997, 27, 4141–4158; (c) Gabriele, B.; Salerno, G.;
Costa, M.; Chiusoli, G. P. J. Organomet. Chem. 2003, 687, 219–228; (d) Gabriele,
B.; Mancuso, R.; Salerno, G.; Costa, M. J. Org. Chem. 2003, 68, 601–604; (e) Li, F.;
Xia, C. J. Catal. 2004, 227, 542–546; (f) Gabriele, B.; Plastina, P.; Salerno, G.;
Mancuso, R.; Costa, M. Org. Lett. 2007, 9, 3319–3322; (g) Mizutani, T.; Ukaji, Y.;
Inomata, K. Bull. Chem. Soc. Jpn. 2003, 76, 1251–1256; (h) Danishefsky, S.;
Taniyama, E. Tetrahedron Lett. 1983, 24, 15–18; (i) Bates, R. W.; Sa-Ei, K. Org.
Lett. 2002, 4, 4225–4227.
7. (a) Hyland, C. Tetrahedron 2005, 61, 3457–3471; (b) Patil, N. T.; Yamamoto, Y.
Top. Organomet. 2006, 19, 91–113.
8. (a) Trost, B. M.; Sudhakar, A. R. J. Am. Chem. Soc. 1987, 109, 3792–3794; (b)
Trost, B. M.; Sudhakar, A. R. J. Am. Chem. Soc. 1988, 110, 7933–7935; (c) Trost, B.
M.; Hurnaus, R. Tetrahedron Lett. 1989, 30, 3893–3896.
9. (a) Trost, B. M.; Machacek, M. R.; Aponick, A. Acc. Chem. Res. 2006, 39, 747–760;
(b) Trost, B. M.; Crawley, M. I. Chem. Rev. 2003, 103, 2921–2943; (c) Trost, B. M.
Acc. Chem. Res. 1996, 29, 355–364; (d) Trost, B. M.; Van Vranken, D. L. Chem. Rev.
1996, 96, 395–422; (e) Trost, B. M.; Krische, M. J.; Radinov, R.; Zanoni, G. J. Am.
Chem. Soc. 1996, 118, 6297–6298.
10. (a) Tsuji, J.; Minami, I. Acc. Chem. Res. 1987, 20, 140; (b) Tsuji, J.; Shimizu, I.;
Minami, I.; Ohashi, Y. Tetrahedron Lett. 1982, 46, 4809–4812; (c) Seki, M.; Mori,
Y.; Hatsuda, M.; Yamada, S.-I. J. Org. Chem. 2002, 67, 5527–5536.
11. (a) Zawisza, A.; Sinou, D. Tetrahedron Lett. 2006, 47, 3271–3274; (b) Zawisza,
A.; Fenêt, B.; Sinou, D. Eur. J. Org. Chem. 2007, 2296–2309; (c) Olszewska, B.;
Kryczka, B.; Zawisza, A. Lett. Org. Chem. 2012, 9, 563–567.
12. Fernandez-Garcia, C.; McKervey, M. A Tetrahedron: Asymmetry 1995, 6, 2905–2906.
13. (a) Enders, D.; Nolte, B.; Raabe, G.; Runsink, J. Tetrahedron: Asymmetry 2002, 13,
285–292; (b) Fischer, C.; Smith, S. W.; Powell, D. A.; Fu, G. C. J. Am. Chem. Soc.
2006, 128, 1472–1473.
14. (a) Oppolzer, W.; Gorrichon, L.; Bird, T. G. C. Helv. Chim. Acta 1981, 64, 186–187;
(b) Fraunhoffer, K. J.; Bachovchin, D. A.; White, M. C. Org. Lett. 2005, 7, 223–
226; (c) Jung, M. E.; Zhang, T.-H.; Lui, R. M.; Gutierrez, O.; Houk, K. N. J. Org.
Chem. 2010, 75, 6933–6940.
80
83:17
a
[5c]:[Pd2(dba)3]:[ligand] = 40:1:2.2 (4.4); [5c]:[PdCl(C3H5)]2:[ligand] = 50:1:2.2
(4.4); [5c]:[Pd(OAc)2]:[ligand] = 40:1:2.2 (4.4); THF, 20 °C.
In CH2Cl2, product 6b was obtained in an excellent yield but
somewhat lower enantioselectivity. The use of CH3CN resulted in
a significant decrease in both the yield and selectivity.
We also investigated the effect of the palladium precursor on
this cyclisation reaction (Table 3).15
The reaction using [PdCl(C3H5)]2 or Pd(OAc)2 as the palladium
precursor provided good yields of 6b (Table 3, entries 2, 3, 5 and
6), but the enantioselectivity decreased. Cyclisation of 5c in the
presence of Pd(OAc)2 and ligand L1 gave a product with a lower
yield and selectivity than for the reaction catalysed by Pd2(dba)3
and L1 (Table 3, entries 7 and 9). It should also be noted that no
cyclisation product was observed with the use of [PdCl(C3H5)]2
and ligand L1 (Table 3, entry 8).
2-Vinylpyrrolidine and 2-vinylpiperidines were obtained in rel-
atively good yields and with enantiomeric ratios of up to 90:10 via
the Pd0-catalysed cyclisation of the corresponding amino allylic
carbonates. The highest enantioselectivities were obtained using
the phosphorus amidite ligand L1; some of the yields were very
good with Josiphos, but the enantioselectivities were lower.
15. General procedure for the Pd0-Catalysed Reaction: The catalytic system was
prepared by stirring Pd2(dba)3 (22.9 mg, 0.025 mmol) and the ligand
(0.055 mmol or 0.11 mmol) in an appropriate anhydrous solvent (3 mL) for
0.5 h in a Schlenk tube under argon. This solution was added, under argon, to a
Schlenk tube containing the unsaturated tosylamino carbonate 5a–c (1 mmol)
in an appropriate anhydrous solvent (3 mL). The solution was stirred at 25 °C
(or 60 °C). After 24 h, removal of the solvent followed by column
chromatography using a mixture of hexanes/EtOAc (2:1) as the eluent gave
the corresponding product.
Acknowledgements
This work was part-financed by the European Union within the
European Regional Development Fund (POIG.01.01.02-14-102/09).
Supplementary data
General procedure for the PdII-Catalysed Reaction: A solution of [PdCl(C3H5)]2
(5.5 mg, 0.015 mmol) and ligand (0.033 mmol or 0.066 mmol) or Pd(OAc)2
(3.4 mg, 0.015 mmol) and ligand (0.033 mmol or 0.066 mmol) in anhydrous
THF (3 mL) was added to unsaturated tosylamino carbonate 5a–c {0.75 mmol
for [PdCl(C3H5)]2 or 0.6 mmol for Pd(OAc)2} in THF (3 mL) under an argon
atmosphere. The mixture was stirred at room temperature for 24 h. The solvent
was evaporated and the residue was purified by column chromatography
(hexanes/EtOAc 2:1).
Supplementary data associated with this article can be found, in
the
online
version,
at
http://dx.doi.org/10.1016/
j.tetlet.2012.10.014.
References and notes
1-Tosyl-2-vinylpyrrolidine (6a). 1H NMR (600 MHz, CDCl3): d = 1.50–1.95 (m,
4H, 2H-3, 2H-4), 2.43 (s, 3H, CH3), 3.24 (ddd, 1H, J = 9.8, 7.1, 4.5 Hz, H-5), 3.44
(ddd, 1H, J = 9.8, 6.8, 4.5 Hz, H-5), 4.08–4.20 (m, 1H, H-2), 5.12 (dd, 1H, J = 10.2,
1.1 Hz, CH@CH2), 5.27 (dd, 1H, J = 17.0, 1.1 Hz, CH@CH2), 5.82 (ddd, 1H, J = 17.0,
10.2, 6.1 Hz, CH@CH2), 7.30 (d, 2H, J = 8.0 Hz, C6H4), 7.30 (d, 2H, J = 8.0, C6H4).
13C NMR (150 MHz, CDCl3): d = 21.4 (CH3), 23.6 (C-4), 32.2 (C-3), 48.7 (C-5),
61.8 (C-2), 115.2 (CH@CH2), 127.5, 129.3 (C6H4), 138.7 (CH@CH2), 135.0, 143.2
(C6H4); EI-MS m/z 251.1 (14%, M+), 91.1 (100), 224.1 (65), 155.0 (63), 96.1 (59);
HRMS (EI) Calcd for C13H17NO2S (M+) 251.0980. Found 251.0975.
1. (a) Lewis, J. R. Nat. Prod. Rep. 2001, 18, 95–128; (b) Kang, E. J.; Lee, E. Chem. Rev.
2005, 105, 4348–4378; (c) Bermejo, A.; Figadere, B.; Zafra-Polo, M.-C.;
Barrachina, I.; Estornell, E.; Cortes, D. Nat. Prod. Rep. 2005, 22, 269–309; (d)
Saleem, M.; Kim, H. J.; Ali, M. S.; Lee, Y. S. Nat. Prod. Rep. 2005, 22, 696–716; (e)
Daly, J. W.; Spande, T. F.; Garraffo, H. M. J. Nat. Prod. 2005, 68, 1556–1575.
2. (a) Kanemasa, S. Synlett 2002, 1371–1387; (b) Gothelf, K. V.; Jorgensen, K. A.
Chem. Commun. 2000, 1449–1458; (c) Felpin, F.-X.; Lebreton, J. Eur. J. Org. Chem.
2003, 3693–3712; (d) Pyne, S. G.; Davis, A. S.; Gates, N. J.; Hartley, J. P.; Lindsay,
K. B.; Machan, T.; Tang, M. Synlett 2004, 2670–2680; (e) Bellina, F.; Rossi, R.

B. Olszewska et al. / Tetrahedron Letters 53 (2012) 6826–6829
6829
1-Tosyl-2-vinylpiperidine (6b). 1H NMR (600 MHz, CDCl3):d = 1.30–1.75 (m, 6H,
2H-3, 2H-4, 2H-5), 2.43 (s, 3H, CH3), 2.94 (ddd, 1H, J = 13.5, 12.8, 2.4 Hz, H-6),
3.68 (d, 1H, J = 13.5 Hz, H-6), 4.59 (br s, 1H, H-2), 5.10 (d, 1H, J = 10.6 Hz,
CH@CH2), 5.17 (d, 1H, J = 17.4 Hz, CH@CH2), 5.70 (ddd, 1H, J = 17.4, 10.6, 5.2 Hz,
CH@CH2), 7.28 (d, 2H, J = 8.3 Hz, C6H4), 7.69 (d, 2H, J = 8.3 Hz, C6H4). 13C NMR
(150 MHz, CDCl3): d = 19.0 (C-4), 21.4 (CH3), 24.9 (C-5), 29.6 (C-3), 41.6 (C-2),
55.0 (C-6), 117.0 (CH@CH2), 127.2, 129.4 (C6H4), 135.4 (CH@CH2), 137.8, 143.3
(C6H4); EI-MS m/z 265.1 (11%, M+), 91.1 (100), 155.0 (95), 110.1 (67), 238.1
(50); HRMS (EI) Calcd for C14H19NO2S (M+) 265.1137. Found 265.1140.
16. (a) Tamaru, Y.; Hojo, M.; Yoshida, Z. J. Org. Chem. 1988, 53, 5731–5741.
17. (a) Macsári, I.; Szabó, K. J. Chem. Eur. J. 2001, 7, 4097–4106; (b) Guerinot, A.;
Serra-Muns, A.; Gnamm, C.; Bensoussan, C.; Reymond, S.; Cossy, J. Org. Lett.
2010, 12, 1808–1811; (c) Seki, T.; Tanaka, S.; Kitamura, M. Org. Lett. 2012, 14,
608–611.