Acid-catalyzed regioselective sulfamination of γ-amino-alkenes and stereoselective rearrangement of pyrrolidines to piperidines

Article abstract of DOI:10.1016/j.tet.2012.08.043

This paper describes efficient acid-catalyzed regioselective sulfamination of γ-amino-alkenes to form pyrrolidines and stereoselective rearrangement of pyrrolidines to piperidines. A possible reaction mechanism has been proposed.

Full text of DOI:10.1016/j.tet.2012.08.043

Tetrahedron 68 (2012) 9853e9859
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Acid-catalyzed regioselective sulfamination of
g
-aminoealkenes and
stereoselective rearrangement of pyrrolidines to piperidines
,b,
Lijun Li a, Haining Wang a, Deshun Huang a, Yian Shi a
*
a Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190,
China
b Department of Chemistry, Colorado State University, Fort Collins, CO 80523, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2012
Received in revised form 13 August 2012
Accepted 15 August 2012
Available online 6 September 2012
This paper describes efficient acid-catalyzed regioselective sulfamination of g-aminoealkenes to form
pyrrolidines and stereoselective rearrangement of pyrrolidines to piperidines. A possible reaction
mechanism has been proposed.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Sulfamination
Thiiranium ions
Rearrangement
Acid-catalyzed
Regioselective
Stereoselective
1. Introduction
Pyrrolidines and piperidines are very important functional
moieties that are present in various biologically active compounds.1
Electrophilic cyclization of g-aminoealkenes provides a straight-
Scheme 1.
forward approach to pyrrolidines and piperidines.2e6 Our previous
studies have shown that either tetrahydrofurans or tetrahy-
dropyrans can be regioselectively formed from alkenols with sul-
fenamides depending upon acid catalysts used (Scheme 1).7e9
Mechanistic studies indicate that tetrahydrofurans are kinetically
favoured products and can stereoselectively rearrange to thermo-
dynamically favoured tetrahydropyrans under acid conditions.9
These observations prompted us to investigate whether similar
catalyst (Table 1, entries 1e5). In all the cases except for N-ethyl-
oxycarbonyl
yields (84e95%) and high regioselectivity. Considering the easy re-
moval of the Ns group, various N-2-nitrobenzenesulfonyl -ami-
g-aminoealkene 1a, pyrrolidines were formed in high
g
noealkenes (1fel) were subsequently investigated with CSA, TfOH,
and TsOH (Table 1, entries 6e12). In all the cases, 5-exo-products 3
were formed predominately in good yields (73e91%) (for X-ray
structure of 3j, see Supplementary data). For some trans-olefins,
small amounts of 6-endo products were formed (Table 1, entries 9
transformations can be achieved with
g-aminoealkenes to form
synthetically useful pyrrolidines and piperidines. Herein, we wish
to report our efforts on this subject.
and 11). In general, trans-
5-exo selectivity than trans-
g
-aminoealkenes give significantly higher
g
-hydroxyealkenes.9 The cyclization
also proceeded diastereoselectively. cis-Olefins gave threo-products
(Table 1, entries 1e8), and trans-olefins gave erythro-products (Table
1, entries 9e12). No other diastereoisomers were detected by 1H
NMR spectroscopic analysis of the crude products.
The rearrangement was examined with isolated pyrrolidine 3
and TfOH in CH2Cl2 at 25 ꢀC. As shown in Table 2, piperidine 4 was
formed as a major product except for entry 7. In some cases, pi-
peridine 4 could be separated from the corresponding pyrrolidine
2. Results and discussion
The cyclizations of
g-aminoealkenes (1aee) with different
substituents on the nitrogen atom were examined with methyl
benzenesulfenate (2) as the sulfur source10,11 and CSA or TfOH as
* Corresponding author. E-mail address: yian@lamar.colostate.edu (Y. Shi).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.043

9854
L. Li et al. / Tetrahedron 68 (2012) 9853e9859
Table 1
Sulfamination of
Table 2
g
-aminoealkenesa
Rearrangement of pyrrolidines to piperidinesa
Ratio 3:4d
Yield (%)e
Entry
Substrates
Ratio 3:4e
Yield (%) (3)f
Entry
Substrates (3)
Time (h)
1
2
3
1a, R1¼CO2Et
1b, R1¼Ts
Multiple products
>99:1
>99:1
>99:1
>99:1
1
3b, R1¼Ts
12
48
12
12
32:68
12:88
29:71
12:88h
99
2b
3
3c, R1¼Mts
3d, R1¼4-Ns
3e, R1¼Ns
80f
99
95
89
84
93
1c, R1¼Mts
1d, R1¼4-Ns
1e, R1¼Ns
4
86f
4
5b
5c
6
7
3f, R2¼H
24
12
48
11:89
10:90
95:5
98
96
-
6b
7c
8b
1f, R2¼H
>99:1
>99:1
>99:1
88
86
73
3g, R2¼CH3
3h, R2¼t-Bu
g
1g, R2¼CH3
1h, R2¼t-Bu
8
9
10
3i, R2¼n-C5H11
3j, R2¼Cy
12
24
24
12:88
15:85
16:84
82f
60f
81f
9c
1i, R2¼n-C5H11
1j, R2¼Cy
92:8
>99:1
93:7
91
87
77
10c
11c
3k, R2¼i-Bu
1k, R2¼i-Bu
a
Reactions were carried out with substrate 3 (0.50 mmol), TfOH (0.05 mmol) in
CH2Cl2 (2.5 mL) at 25 ꢀC unless otherwise stated.
b
With TfOH (0.10 mmol).
12d
c
With TfOH (0.50 mmol).
d
The ratio was determined by 1H NMR spectroscopic analysis of the crude
product.
e
a
Isolated yield of mixture 3 and 4 unless otherwise noted.
Reactions were carried out with substrate
1 (0.50 mmol), PhSOMe (2)
f
Isolated yield of 4.
(0.60 mmol), and CSA (0.05 mmol) in CH2Cl2 (2.5 mL) at 25 ꢀC for 1 h unless oth-
g
Trace amounts of 4 h were detected by 1H NMR spectroscopic analysis of the
erwise stated. Ts¼p-toluenesulfonyl; Mts¼2,4,6-trimethylbenzenesulfonyl; 4-
crude product.
Ns¼4-nitrobenzenesulfonyl;
Ns¼2-nitrobenzenesulfonyl;
CSA¼10-
h
The ratio did not change after 72 h.
camphorsulfonic
acid;
TsOH¼p-toluenesulfonic
acid;
TfOH¼tri-
fluoromethanesulfonic acid.
b
With TfOH (0.05 mmol) in CH2Cl2 (5.0 mL).
c
With PhSOMe (2) (1.0 mmol) and TsOH$H2O (0.10 mmol) in CH2Cl2 (5.0 mL) for
12 h.
d
In CH2Cl2 (5.0 mL) for 12 h.
e
The ratio was determined by 1H NMR spectroscopic analysis of the crude
product.
Fig. 1. The steric hindrance caused by the N-substituent in piperidine.
f
Isolated yield of 3.
by column chromatography (Table 2, entries 2, 4, 8e10) (for X-ray
structures of sulfone derivatives of 4e and 4j see Supplementary
data). The ratio of piperidine to pyrrolidine was found to be gen-
erally lower than that of tetrahydropyran to tetrahydrofuran,9
which is likely due to the steric hindrance caused by the N-sub-
stituent in piperidine as compared to the corresponding tetrahy-
dropyran (an example is shown in Fig. 1).12 When R2¼t-Bu, little
piperidine was formed (Table 2, entry 7).
As in the case of the rearrangement of tetrahydrofuran to tet-
rahydropyran,9,13 pyrrolidine 3 is the kinetically favoured product
and can be stereoselectively rearranged to the thermodynamically
favoured piperidine product 4 in the presence of acid catalyst TfOH,
likely via thiiranium ion intermediate 5 (Scheme 2).
To probe the reaction mechanism, optically active compounds
3m and 16 were prepared. The synthesis of pyrrolidine 3m is
outlined in Scheme 3. Asymmetric epoxidation14 of 1m followed by
cyclization gave alcohol 6 in 61% yield over two steps. Compound
3m was obtained from 6 by mesylation15 and nucleophilic sub-
stitution with NaSPh.16
Scheme 2.
The preparation of pyrrolidine 16 is shown in Scheme 4. Com-
pound 10, prepared by the addition of vinylmagnesium bromide to
aldehyde 9,17 was converted to ester 11 by JohnsoneClaisen rear-
rangement.18e20 Amino-alkene 13 was obtained from ester 11 by
reduction with LiAlH4, mesylation, and nucleophilic substitution.15
Compound 13 was converted to pyrrolidine 14 in a manner similar
to the reaction sequence from 1m to 3m. Compound 16 was syn-
thesized from 14 by desilylation, mesylation, and nucleophilic
substitution.
Treating enantiomerically enriched pyrrolidine 3m with TfOH
(1.0 equiv) in CH2Cl2 at 25 ꢀC led to the formation of optically active
piperidine product 4m in 78% yield without erosion of ee, sug-
gesting that the rearrangement proceeded via configurationally
stable thiiranium ion 5m (Scheme 5).9,21,22 The involvement of

L. Li et al. / Tetrahedron 68 (2012) 9853e9859
9855
Scheme 6.
4. Experimental section
4.1. General information and materials
Scheme 3.
All commercially available reagents were used without further
purification. All dry solvents were freshly distilled under nitrogen
from appropriate drying agents before use. Toluene, tetrahydrofu-
ran, and ethyl ether were distilled from sodiumebenzophenone.
CH2Cl2 was distilled from CaH2. CHCl3 was distilled from P2O5.
Column chromatography was performed on silica gel
(200e300 mesh). 1H NMR spectra were recorded on a 400 MHz
NMR spectrometer and 13C NMR spectra were recorded on
a 100 MHz NMR spectrometer. IR spectra were recorded on a FTIR
spectrometer. High resolution mass spectra (HRMS) were obtained
using EI-TOF or ESI-FTICR mass spectrometer. Melting points were
uncorrected.
Compounds 1aee, 1g, 1i, and 1m were prepared from com-
mercially available alcohols by tosylation, azidation, reduction with
LiAlH4, and subsequent protection.15,24 Compound 1f was prepared
by Mitsunobu reaction from the corresponding alcohol.25 Com-
pound 1h was prepared by Wittig reaction26 and Mitsunobu re-
action.25 Compounds 1jel were prepared by JohnsoneClaisen
rearrangement,18 reduction, and Mitsunobu reaction.25
Scheme 4.
4.2. Representative procedure for acid-catalyzed sulfamina-
tion (Table 1, entry 2)
To
a stirred solution of benzenesulfenate (2) (0.084 g,
0.60 mmol) and alkene 1b (0.155 g, 0.50 mmol) in CH2Cl2 (2.5 mL)
was added CSA (0.012 g, 0.05 mmol) at 25 ꢀC. Upon stirring at 25 ꢀC
for 1 h, the reaction mixture was filtered through a plug of silica gel
with CH2Cl2 as eluent, concentrated, and purified by column
chromatography (silica gel, eluent: petroleum ether/ethyl
acetate¼40:1) to give compound 3b as white solid (0.199 g, 95%).
Scheme 5.
4.2.1. threo-2-[1-(Phenylthio)hexyl]-1-tosylpyrrolidine (3b) (Table 1,
entry 2). White solid; mp 105e107 ꢀC; IR (film) 1345,1160 cmꢁ1; 1H
a thiiranium ion intermediate during the rearrangement was fur-
ther supported by the fact that racemic piperidine 19 was obtained
when optically active pyrrolidine 16 was subjected to the reaction
conditions. It is likely that the rearrangement proceeded via meso
thiiranium ion intermediate 17 rather than optically active azir-
idinium ion intermediate 18 (Scheme 6).9,23
NMR (400 MHz, CDCl3)
d
7.53 (d, J¼7.2 Hz, 2H), 7.41e7.33 (m, 4H),
7.33e7.26 (m, 1H), 7.15 (d, J¼8.0 Hz, 2H), 3.90 (dt, J¼11.6, 3.2 Hz, 1H)
3.62e3.53 (m, 1H), 3.51e3.38 (m, 1H), 3.27e3.16 (m, 1H), 2.37 (s,
3H), 1.98e1.85 (m, 2H), 1.80e1.62 (m, 3H), 1.58e1.42 (m, 1H),
1.42e1.20 (m, 6H), 0.92 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
143.5, 135.6, 133.6, 131.4, 129.7, 129.3, 127.8, 126.7, 62.2, 51.8, 51.2,
3. Conclusion
32.0, 27.8, 27.5, 26.8, 24.6, 22.8, 21.7, 14.3; Anal. Calcd for
C23H31NO2S2: C, 66.15; H, 7.48; N, 3.35; found: C, 65.99; H, 7.55;
N, 3.33.
In summary, we have developed an efficient acid-catalyzed
regioselective and diastereoselective sulfamination of
g-amino-
alkenes to form pyrrolidines in high yields. The resulting pyrroli-
dines can be stereoselectively rearranged to piperidines via
a thiiranium ion intermediate in the presence of strong acid TfOH.
The current work provides a viable method to synthesize useful
pyrrolidines and piperidines as well as better understanding of the
thiiranium ion-based rearrangement.
4.2.2. threo-1-(Mesitylsulfonyl)-2-[1-(phenylthio)hexyl]pyrrolidine
(3c) (Table 1, entry 3). Pale yellow oil; IR (film) 1604, 1467,
1314 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.32e7.13 (m, 5H), 6.88 (s,
2H), 4.15e4.07 (m, 1H), 3.69e3.58 (m, 1H), 3.23e3.14 (m, 1H),
2.91e2.82 (m, 1H), 2.49 (s, 6H), 2.29 (s, 3H), 2.19e2.08 (m, 1H),
2.07e1.94 (m, 1H), 1.85e1.75 (m, 2H), 1.67e1.52 (m, 2H), 1.33e1.11

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L. Li et al. / Tetrahedron 68 (2012) 9853e9859
(m, 5H), 1.07e0.92 (m, 1H), 0.88 (t, J¼6.8 Hz, 3H); 13C NMR
1.37e1.19 (m, 4H), 0.87 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
(100 MHz, CDCl3)
d
142.7, 140.3, 135.3, 133.4, 132.2, 131.6, 129.1,
d 148.7, 135.9, 133.6, 132.5, 131.6, 131.4, 130.9, 129.1, 126.8, 124.1,
126.9, 62.1, 52.5, 49.9, 32.0, 28.5, 27.8, 27.6, 25.4, 22.9, 22.8, 21.1,
14.2; Anal. Calcd for C25H35NO2S2: C, 67.37; H, 7.92; N, 3.14; found:
C, 67.25; H, 7.85; N, 3.13.
63.7, 55.4, 50.3, 34.4, 31.8, 28.1, 27.2, 25.5, 22.7, 14.2; Anal. Calcd for
C22H28N2O4S2: C, 58.90; H, 6.29; N, 6.24; found: C, 58.62; H, 6.35;
N, 6.04.
4.2.3. threo-1-(4-Nitrophenylsulfonyl)-2-[1-(phenylthio)hexyl]-pyr-
4.2.9. erythro-2-[(Cyclohexyl)(phenylthio)methyl]-1-(2-nitro-phe-
rolidine (3d) (Table 1, entry 4). White solid; mp 139e141 ꢀC; IR
nylsulfonyl)pyrrolidine (3j) (Table 1ꢁ, 1entry 10). White solid; mp
(film) 1522, 1159 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
8.18 (d,
144e145 ꢀC; IR (film) 1545, 1163 cm 1H NMR (400 MHz, CDCl3)
;
J¼8.8 Hz, 2H), 7.60e7.49 (m, 4H), 7.46e7.33 (m, 3H), 3.89 (dt, J¼11.6,
3.2 Hz, 1H) 3.58e3.44 (m, 2H), 3.25e3.16 (m, 1H), 2.05e1.92 (m,
1H),1.90e1.65 (m, 4H),1.58e1.45 (m,1H),1.45e1.20 (m, 6H), 0.93 (t,
d
7.90 (d, J¼8.0 Hz, 1H), 7.66e7.59 (m, 1H), 7.58e7.51 (m, 2H), 7.41 (d,
J¼7.6 Hz, 2H), 7.25e7.18 (m, 2H), 7.14 (t, J¼7.2 Hz, 1H), 4.50e4.43 (m,
1H), 3.66e3.58 (m, 1H), 3.58e3.52 (m, 1H), 3.50e3.41 (m, 1H),
2.14e2.05 (m, 1H), 2.04e1.91 (m, 3H), 1.89e1.69 (m, 3H), 1.68e1.49
J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 150.2,142.1,135.2,132.2,
129.4, 128.9, 127.3, 124.3, 62.5, 52.1, 51.4, 31.9, 27.7, 27.4, 26.8, 24.6,
22.8, 14.3; Anal. Calcd for C22H28N2O4S2: C, 58.90; H, 6.29; N, 6.24;
found: C, 58.74; H, 6.35; N, 6.15.
(m, 3H), 1.39e1.07 (m, 5H); 13C NMR (100 MHz, CDCl3)
d 148.7, 137.5,
133.5,132.6,131.5,130.9,130.7,129.1,126.4,124.2,62.4, 62.3, 50.0, 42.5,
31.4, 31.1, 28.9, 26.6, 26.53, 26.49, 25.7; Anal. Calcd for C23H28N2O4S2:
C, 59.97; H, 6.13; N, 6.08; found: C, 59.99; H, 6.18; N, 6.14.
4.2.4. threo-1-(2-Nitrophenylsulfonyl)-2-[1-(phenylthio)hexyl]-pyr-
rolidine (3e) (Table 1, entry 5). White solid; mp 78e81 ꢀC; IR (film)
4.2.10. erythro-2-[3-Methyl-1-(phenylthio)butyl]-1-(2-nitro-phenyl-
1546, 1372, 1163 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.66e7.59 (m,
sulfonyl)pyrrolidine (3k) (Table 1,ꢁ1entry 11). White solid; mp
1H), 7.56e7.41 (m, 5H), 7.39e7.32 (m, 2H), 7.32e7.25 (m, 1H),
4.02e3.94 (m, 1H), 3.78e3.69 (m, 1H), 3.69e3.60 (m, 1H),
3.49e3.38 (m, 1H), 2.07e1.97 (m, 2H), 1.90e1.57 (m, 4H), 1.40e1.19
79e80 ꢀC; IR (film) 1545, 1164 cm
;
1H NMR (400 MHz, CDCl3)
d
7.94 (d, J¼8.0 Hz, 1H), 7.66e7.59 (m, 1H), 7.59e7.52 (m, 2H), 7.40
(d, J¼7.6 Hz, 2H), 7.29e7.21 (m, 2H), 7.20e7.15 (m, 1H), 4.30e4.20
(m, 1H), 3.81e3.72 (m, 1H), 3.67e3.58 (m, 1H), 3.48e3.38 (m, 1H),
2.10e1.86 (m, 4H), 1.69e1.56 (m, 1H), 1.51e1.39 (m, 2H), 0.93 (d,
J¼6.8 Hz, 3H), 0.87 (d, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
(m, 6H), 0.88 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 148.6,
135.5, 133.6, 131.6, 131.3, 131.2, 129.3, 127.0, 124.1, 63.0, 52.2, 51.2,
31.9, 27.8, 27.6, 27.3, 25.0, 22.8, 14.3; Anal. Calcd for C22H28N2O4S2:
C, 58.90; H, 6.29; N, 6.24; found: C, 59.04; H, 6.46; N, 6.15.
d
148.7, 135.8, 133.5, 132.6, 131.6, 131.4, 130.9, 129.1, 126.8, 124.2,
63.8, 53.2, 50.3, 43.7, 28.0, 25.7, 25.5, 22.8, 22.6; Anal. Calcd for
C21H26N2O4S2: C, 58.04; H, 6.03; N, 6.45; found: C, 58.07; H, 6.08; N,
6.47.
4.2.5. 1-(2-Nitrophenylsulfonyl)-2-(phenylthiomethyl)pyrrolidine
(3f) (Table 1, entry 6). White solid; mp 78e80 ꢀC; IR (film) 1539,
1163 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.83 (d, J¼8.4 Hz, 1H),
7.70e7.63 (m, 1H), 7.63e7.54 (m, 2H), 7.44e7.37 (m, 2H), 7.36e7.28
(m, 2H), 7.22 (t, J¼7.2 Hz, 1H), 4.09e4.00 (m, 1H), 3.59e3.40 (m,
3H), 2.83 (dd, J¼13.6, 10.4 Hz, 1H), 2.09e1.88 (m, 3H), 1.88e1.73 (m,
4.2.11. erythro-2-Methyl-1-(2-nitrophenylsulfonyl)-2-[1-(phenyl-
thio)hexyl]pyrrolidine (3l) (Table 1, entry 12). Yellow oil; IR (film)
1545, 1373, 1161 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 8.11 (d,
1H); 13C NMR (100 MHz, CDCl3)
d
148.6, 135.4, 133.8, 131.8, 131.6,
J¼8.0 Hz, 1H), 7.58e7.38 (m, 5H), 7.28e7.21 (m, 2H), 7.15 (t,
J¼7.2 Hz, 1H), 4.12 (dd, J¼8.8, 3.2 Hz, 1H), 3.72e3.63 (m, 1H),
3.42e3.32 (m, 1H), 2.36e2.26 (m, 1H), 1.97e1.73 (m, 4H), 1.65 (s,
3H), 1.65e1.42 (m, 2H), 1.41e1.28 (m, 1H), 1.28e1.10 (m, 4H), 0.80 (t,
130.9, 129.4, 129.2, 126.4, 124.1, 59.8, 49.4, 38.3, 30.6, 24.1; Anal.
Calcd for C17H18N2O4S2: C, 53.95; H, 4.79; N, 7.40; found: C, 53.99;
H, 4.79; N, 7.32.
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 148.8, 136.6, 134.2,
4.2.6. threo-1-(2-Nitrophenylsulfonyl)-2-[1-(phenylthio)ethyl]-pyr-
133.3, 131.5, 130.8, 130.1, 129.0, 126.4, 123.8, 73.5, 58.8, 50.9, 37.6,
34.2, 31.9, 27.6, 25.8, 23.3, 22.5, 14.1; HRMS (EI) Calcd for
C23H30N2O4S2 (Mþ): 462.1647; found: 462.1652.
rolidine (3g) (Table 1, entry 7). Light yellow solid; mp 121e122 ꢀC;
IR (film) 1545, 1164 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 7.68e7.46
(m, 6H), 7.40e7.33 (m, 2H), 7.33e7.26 (m, 1H), 4.03e3.93 (m, 2H),
3.65e3.55 (m, 1H), 3.52e3.40 (m, 1H), 2.10e1.80 (m, 3H), 1.73e1.61
4.3. Representative procedure for rearrangement of pyrroli-
dine to piperidine (Table 2, entry 2)
(m, 1H), 1.28 (d, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 148.8,
134.8, 133.7, 131.9, 131.4, 131.2, 129.3, 127.2, 124.1, 62.6, 50.7, 45.9,
26.6, 25.1, 13.9; Anal. Calcd for C18H20N2O4S2: C, 55.08; H, 5.14; N,
7.14; found: C, 54.96; H, 5.14; N, 7.11.
To a stirred solution of 3c (0.223 g, 0.50 mmol) in CH2Cl2
(2.5 mL) was added TfOH (0.015 g, 0.10 mmol) at 25 ꢀC. Upon
stirring at 25 ꢀC for 48 h, the reaction mixture was filtered through
a plug of silica gel with CH2Cl2 (50 mL) as eluent, concentrated, and
purified by column chromatography (silica gel, eluent: petroleum
ether/ethyl acetate¼100:1) to give compound 4c as pale yellow oil
(0.178 g, 80%).
4.2.7. threo-2-[2,2-Dimethyl-1-(phenylthio)propyl]-1-(2-nitro-phe-
nylsulfonyl)pyrrolidine (3h) (Table 1, entry 8). White solid; mp
177e178 ꢀC; IR (film) 1544, 1162 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
7.77 (d, J¼7.6 Hz,1H), 7.64 (t, J¼7.6 Hz,1H), 7.60e7.50 (m, 4H), 7.30
(t, J¼7.6 Hz, 2H), 7.22 (t, J¼7.2 Hz, 1H), 4.42e4.35 (m, 1H), 3.27e3.17
(m, 1H), 3.15e3.01 (m, 2H), 2.04e1.91 (m, 1H), 1.85e1.75 (m, 1H),
4.3.1. syn-2-Pentyl-3-phenylthio-1-tosylpiperidine (4b) (Table 2, en-
1.61e1.42 (m, 2H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3)
d
148.7,
try 1). Yellow oil; IR (film) 1466, 1334, 1160 cmꢁ1 1H NMR
;
137.9, 133.4, 132.2, 132.0, 131.7, 131.2, 129.0, 126.8, 124.1, 68.1, 62.9,
49.1, 36.1, 33.4, 29.2, 24.1; HRMS (EI) Calcd for C21H26N2O4S2 (Mþ):
434.1334; found: 434.1339.
(400 MHz, CDCl3)
d
7.62 (d, J¼8.0 Hz, 2H), 7.34e7.26 (m, 5H), 7.23 (d,
J¼8.0 Hz, 2H), 4.00e3.93 (m, 1H), 3.90e3.82 (m, 1H), 3.12 (dt,
J¼12.8, 4.0 Hz, 1H), 3.04e2.92 (m, 1H), 2.41 (s, 3H), 1.85e1.00 (m,
12H), 0.83 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 143.1,
4.2.8. erythro-1-(2-Nitrophenylsulfonyl)-2-[1-(phenylthio)-hexyl]
138.9, 134.3, 131.8, 129.8, 129.2, 127.3, 127.1, 56.1, 47.9, 39.5, 31.6,
25.9, 25.8, 25.7, 24.0, 22.6, 21.6, 14.1; HRMS (EI) Calcd for
C23H31NO2S2 (Mþ): 417.1796; found: 417.1801.
pyrrolidine (3i) (Table 1, entry 9). Yellow oil; IR (film) 1545,
1163 cmꢁ1; 1H NMR (400 MHz, CDCl3)
(t, J¼7.6 Hz, 1H), 7.55 (t, J¼8.4 Hz, 2H), 7.40 (d, J¼7.6 Hz, 2H), 7.24 (t,
J¼7.6 Hz, 2H), 7.18 (t, J¼7.6 Hz, 1H), 4.34e4.21 (m, 1H), 3.70e3.57
(m, 2H), 3.49e3.38 (m, 1H), 2.10e1.90 (m, 3H), 1.72e1.37 (m, 5H),
d
7.93 (d, J¼7.6 Hz, 1H), 7.63
4.3.2. syn-1-(Mesitylsulfonyl)-2-pentyl-3-(phenylthio)piperidine
(4c) (Table 2, entry 2). White solid; mp 73e75 ꢀC; IR (film) 1604,

L. Li et al. / Tetrahedron 68 (2012) 9853e9859
9857
1439, 1322, 1150 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.47e7.41 (m,
3.90e3.82 (m,1H), 3.65e3.57 (m,1H), 3.05e2.94 (m, 1H), 2.05e1.89
(m, 2H), 1.84e1.69 (m, 6H), 1.69e1.60 (m, 1H), 1.51e1.41 (m, 1H),
2H), 7.33e7.19 (m, 3H), 6.85 (s, 2H), 4.07e3.98 (m, 1H), 3.94e3.87
(m, 1H), 3.48e3.39 (m, 1H), 3.02e2.92 (m, 1H), 2.45 (s, 6H), 2.25 (s,
3H), 2.01e1.92 (m, 1H), 1.85e1.49 (m, 5H), 1.09e0.76 (m, 5H), 0.68
(t, J¼7.2 Hz, 3H), 0.45e0.29 (m, 1H); 13C NMR (100 MHz, CDCl3)
1.31e0.96 (m, 5H); 13C NMR (100 MHz, CDCl3)
d 148.5, 135.6, 135.1,
133.1,132.0, 131.2,131.1,129.3,127.1,123.7, 63.9, 45.2, 42.0, 37.7, 31.5,
29.8, 26.6, 26.5, 26.2, 24.2, 20.2; Anal. Calcd for C23H28N2O4S2: C,
59.97; H, 6.13; N, 6.08; found: C, 60.38; H, 6.28; N, 6.03.
d
142.3, 140.0, 134.4, 133.9, 132.0, 131.5, 129.3, 127.1, 55.9, 47.8, 39.4,
31.5, 27.4, 26.3, 25.5, 24.5, 23.0, 22.7, 21.0, 13.9; Anal. Calcd for
C25H35NO2S2: C, 67.37; H, 7.92; N, 3.14; found: C, 67.60; H, 7.99;
N, 3.09.
4.3.9. anti-2-(2-Methylpropyl)-1-(2-nitrophenylsulfonyl)-3-(phenyl-
thio)piperidine (4k) (Table 2, entry 10). Yellow oil; IR (film) 1537,
1469, 1169 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.14 (d, J¼7.2 Hz, 1H),
4.3.3. syn-1-(4-Nitrophenylsulfonyl)-2-pentyl-3-(phenylthio)-piperi-
7.68e7.58 (m, 3H), 7.30e7.18 (m, 5H), 4.11e4.04 (m, 1H), 3.94e3.86
(m, 1H), 3.40e3.34 (m, 1H), 3.18e3.09 (m, 1H), 2.15e1.91 (m, 2H),
1.85e1.71 (m, 2H), 1.60e1.42 (m, 3H), 0.88 (d, J¼6.4 Hz, 3H), 0.79 (d,
dine (4d) (Table 2, entry 3). White solid; IR (film) 1530, 1349,
1164 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.25 (d, J¼8.8 Hz, 2H), 7.86
(d, J¼8.8 Hz, 2H), 7.38e7.30 (m, 5H), 4.02e3.93 (m, 1H), 3.93e3.82
(m, 1H), 3.11e2.94 (m, 2H), 1.90e1.57 (m, 5H), 1.47e1.10 (m, 6H),
1.09e0.97 (m,1H), 0.83 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
J¼6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 148.2, 135.2, 134.5,
133.3, 132.1, 131.7, 131.4, 129.2, 127.4, 124.3, 56.3, 47.0, 41.3, 40.0,
25.5, 23.6, 21.6, 20.3; HRMS (EI) Calcd for C21H26N2O4S2 (Mþ):
434.1334; found: 434.1340.
d
149.8, 147.5, 134.0, 132.3, 129.3, 128.1, 127.9, 124.5, 56.8, 48.9, 39.8,
31.5, 25.9, 25.8, 25.7, 23.9, 22.6, 14.1; HRMS (EI) Calcd for
C22H28N2O4S2 (Mþ): 448.1491; found: 448.1496.
4.4. Procedure for Scheme 3
4.3.4. syn-1-(2-Nitrophenylsulfonyl)-2-pentyl-3-(phenylthio)-piperi-
4.4.1. erythro-1-(Mesitylsulfonyl)-2-[1-(hydroxy)hexyl]pyrrolidine
(6). g-Aminoealkene 1m (3.20 g, 9.49 mmol) was subjected to the
dine (4e) (Table 2, entry 4). Yellow oil; IR (film) 1544, 1163 cmꢁ1; 1H
NMR (400 MHz, CDCl3)
d
7.92e7.86 (m, 1H), 7.68e7.54 (m, 3H),
asymmetric epoxidation conditions14 to give the crude epoxide,
which was dissolved in CH2Cl2 (50 mL), followed by the addition of
CSA (0.221 g, 0.95 mmol). Upon stirring at 25 ꢀC for 1.5 h, the re-
action mixture was filtered through a plug of silica gel with CH2Cl2
as eluent, concentrated, and purified by column chromatography
(silica gel, eluent: petroleum ether/ethyl acetate¼30:1 to 20:1 to
7.47e7.41 (m, 2H), 7.38e7.31 (m, 2H), 7.30e7.23 (m, 1H), 4.00e3.86
(m, 2H), 3.59e3.50 (m, 1H), 3.12e3.01 (m, 1H), 1.95e1.86 (m, 1H),
1.81e1.58 (m, 5H), 1.14e0.99 (m, 5H), 0.78e0.63 (m, 4H); 13C NMR
(100 MHz, CDCl3)
d 147.7, 134.5, 134.3, 133.5, 131.8, 131.5, 131.1,
129.3, 127.3, 124.4, 57.2, 48.5, 40.1, 31.6, 26.9, 25.9, 25.6, 24.3, 22.6,
14.0; Anal. Calcd for C22H28N2O4S2: C, 58.90; H, 6.29; N, 6.24; found:
C, 58.66; H, 6.25; N, 5.93.
5:1) to afford compound 6 as yellow oil (2.04 g, 61% over two steps).
20
[a
]
¼ꢁ108.5 (c 0.97, CHCl3); IR (film) 3257, 1457, 1309, 1150 cmꢁ1
;
D
1H NMR (400 MHz, CDCl3)
d 6.95 (s, 2H), 3.85e3.78 (m, 1H),
4.3.5. 1-(2-Nitrophenylsulfonyl)-3-(phenylthio)piperidine (4f) (Table
3.77e3.68 (m, 1H), 3.46e3.37 (m, 1H), 3.14e2.96 (m, 1H), 2.64 (s,
6H), 2.29 (s, 3H), 2.06e1.72 (m, 5H), 1.46e1.13 (m, 8H), 0.87 (t,
2, entry 5). Yellow oil; IR (film) 1545, 1166 cmꢁ1
;
1H NMR
(400 MHz, CDCl3)
d
7.91e7.85 (m, 1H), 7.71e7.53 (m, 3H), 7.43e7.37
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 143.0, 140.2, 133.1, 132.3,
(m, 2H), 7.34e7.19 (m, 3H), 3.95e3.84 (m, 1H), 3.77e3.68 (m, 1H),
3.26e3.15 (m, 1H), 2.88e2.74 (m, 2H), 2.15e2.06 (m, 1H), 1.90e1.78
(m, 1H), 1.76e1.62 (m, 1H), 1.46e1.33 (m, 1H); 13C NMR (100 MHz,
72.3, 64.0, 49.3, 33.3, 31.9, 25.9, 25.7, 25.4, 23.0, 22.7, 21.1, 14.2;
HRMS (EI) Calcd for C19H31NO3S (Mþ): 353.2025; found: 353.2030.
CDCl3)
d
148.2, 133.8, 133.2, 132.1, 132.0, 131.8, 130.9, 129.3, 127.6,
4.4.2. threo-1-(Mesitylsulfonyl)-2-[1-(phenylthio)hexyl]pyrrolidine
(3m). To a solution of alcohol 6 (1.73 g, 4.90 mmol) and Et3N
(1.49 g, 14.70 mmol) in dry THF (30 mL) was added MsCl (0.842 g,
7.35 mmol) dropwise at 0 ꢀC.15 Upon stirring at 25 ꢀC for 3 h, the
reaction mixture was filtered through a plug of silica gel with ethyl
acetate as eluent and concentrated to give mesylate 7, which was
dissolved in dry THF (50 mL), followed by the addition of PhSNa16
(1.29 g, 9.80 mmol). The reaction mixture was refluxed for 24 h,
cooled to rt, diluted with H2O and ethyl acetate, extracted with
ethyl acetate (3ꢂ70 mL), washed with brine, dried over MgSO4,
filtered, concentrated, and purified by column chromatography
(silica gel, eluent: petroleum ether/ethyl acetate¼50:1) to give
a mixture of 3m and 8 (1:0.6) as yellow oil (0.834 g, 27% for 3m
from 6) (88% ee for 3m).
124.3, 51.4, 46.1, 43.7, 30.4, 25.4; HRMS (ESI) Calcd for C17H19N2O4S2
(MþH): 379.0781; found: 379.0779.
4.3.6. syn-2-Methyl-1-(2-nitrophenylsulfonyl)-3-(phenylthio)-piper-
idine (4g) (Table 2, entry 6). Yellow oil; IR (film) 1544, 1169 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.92 (d, J¼8.0 Hz, 1H), 7.70e7.57 (m,
3H), 7.41e7.35 (m, 2H), 7.34e7.21 (m, 3H), 4.23e4.13 (m, 1H),
3.75e3.66 (m, 1H), 3.48e3.37 (m, 1H), 3.16e3.05 (m, 1H), 1.92e1.85
(m, 1H), 1.79e1.61 (m, 3H), 1.25 (d, J¼6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3)
d 147.8, 134.0, 133.8, 133.6, 131.9, 131.3, 131.0,
129.3, 127.3, 124.5, 52.0, 48.1, 39.9, 26.3, 24.9, 11.03; HRMS (ESI)
Calcd for C18H21N2O4S2 (MþH): 393.0937; found: 393.0939.
4.3.7. anti-1-(2-Nitrophenylsulfonyl)-2-pentyl-3-(phenylthio)-piper-
idine (4i) (Table 2, entry 8). Pale yellow oil; IR (film) 1541,
4.5. Procedure for Scheme 4
1164 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
8.10 (d, J¼8.0 Hz, 1H),
7.69e7.55 (m, 3H), 7.30e7.18 (m, 5H), 4.06e3.97 (m, 1H), 3.97e3.89
(m, 1H), 3.46e3.38 (m, 1H), 3.19e3.08 (m, 1H), 2.19e1.91 (m, 2H),
1.87e1.60 (m, 3H), 1.58e1.48 (m, 1H), 1.33e1.12 (m, 6H), 0.85 (t,
4.5.1. 6-(tert-Butyldiphenylsilyloxy)hex-1-en-3-ol (10). To a solution
of aldehyde 917 (6.57 g, 20.14 mmol) in dry THF (25 mL) was added
dropwise a solution of vinylmagnesium bromide in THF (1.0 M)
(30.2 mL, 30.2 mmol) at ꢁ40 ꢀC under N2.18 Upon warming to rt and
stirring for 2 h, the reaction mixture was quenched with saturated
aqueous NH4Cl, extracted with ethyl ether (3ꢂ80 mL), washed with
brine and dried over MgSO4, filtered, concentrated, and purified by
column chromatography (silica gel, eluent: petroleum ether/ethyl
acetate¼10:1 to 5:1) to afford allylic alcohol 10 as colourless oil
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 148.1, 135.3, 134.6, 133.3,
131.7, 131.4, 131.3, 129.2, 127.1, 124.2, 58.1, 46.3, 41.3, 31.5, 31.1, 26.3,
23.5, 22.5, 20.3, 14.1; HRMS (EI) Calcd for C22H28N2O4S2 (Mþ):
448.1490; found: 448.1496.
4.3.8. anti-2-Cyclohexyl-1-(2-nitrophenylsulfonyl)-3-(phenylthio)pi-
peridine (4j) (Table 2, entry 9). White solid; mp 137e138 ꢀC; IR
(6.37 g, 89%). IR (film) 3384, 1428, 1111 cmꢁ1
CDCl3)
5.23 (dt, J¼17.2, 1.6 Hz, 1H), 5.11 (dt, J¼10.4, 1.2 Hz, 1H), 4.19e4.10
;
1H NMR (400 MHz,
(film) 1544, 1163 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.20e8.16 (m,
d 7.71e7.64 (m, 4H), 7.47e7.36 (m, 6H), 5.93e5.82 (m, 1H),
1H), 7.66e7.53 (m, 3H), 7.31e7.18 (m, 5H), 4.03e3.94 (m, 1H),

9858
L. Li et al. / Tetrahedron 68 (2012) 9853e9859
(m, 1H), 3.74e3.66 (m, 2H), 2.09 (d, J¼4.4 Hz, 1H), 1.73e1.60 (m,
4H), 1.06 (s, 9H); 13C NMR (100 MHz, CDCl3)
141.4, 135.8, 134.0,
129.8, 127.9, 114.7, 73.0, 64.2, 34.1, 28.6, 27.1, 19.4; HRMS (ESI) Calcd
for C22H30NaO2Si (MþNa): 377.1907; found: 377.1909.
three steps) in a manner similar to the reaction sequence from 12 to
20
d
13. Compound 16: white solid; mp 45e47 ꢀC; [
CHCl3) (88% ee); IR (film) 3315, 1603, 1314, 1150 cmꢁ1
(400 MHz, CDCl3) 7.29e7.14 (m, 5H), 6.95 (s, 2H), 6.88 (s, 2H),
a]
¼ꢁ3.8 (c 0.89,
D
;
1H NMR
d
4.75e4.65 (m, 1H), 4.16e4.08 (m, 1H), 3.48e3.39 (m, 1H), 3.23e3.12
(m, 1H), 3.09e3.00 (m, 1H), 2.96e2.79 (m, 2H), 2.65 (s, 6H), 2.47 (s,
6H), 2.30 (s, 3H), 2.29 (s, 3H), 2.17e2.03 (m, 1H), 1.99e1.89 (m, 1H),
1.86e1.65 (m, 4H), 1.34e1.12 (m, 2H); 13C NMR (100 MHz, CDCl3)
4.5.2. (E)-Ethyl 8-(tert-butyldiphenylsilyloxy)oct-4-enoate (11). A
stirred mixture of propionic acid (0.133 g, 1.8 mmol), triethyl
orthoacetate (17.52 g, 108.0 mmol), and allylic alcohol 10 (6.37 g,
18.0 mmol) was heated in an oil bath (138 ꢀC).18e20 Ethanol, formed
during the reaction, was simultaneously removed by distillation.
Upon heating for 4 h, the reaction mixture was cooled to room
temperature, quenched with saturated aqueous NaHCO3, and di-
luted with CH2Cl2. Upon addition of an aqueous HCl-solution (1 M)
(100 mL), the reaction mixture was stirred for 30 min, extracted
with CH2Cl2 (3ꢂ100 mL), washed with saturated aqueous NaHCO3
and brine, dried over MgSO4, filtered, concentrated, and purified by
column chromatography (silica gel, eluent: petroleum ether/ethyl
acetate¼50:1) to afford ester 11 as colourless oil (6.29 g, 82%). IR
d
143.0, 142.3, 140.3, 139.2, 135.0, 134.1, 133.1, 132.3, 132.2, 131.2,
129.3, 127.1, 62.3, 51.7, 49.7, 42.2, 28.1, 27.7, 25.6, 25.2, 23.2, 23.0,
22.9, 21.2, 21.1; HRMS (EI) Calcd for C32H42N2O4S3 (Mþ): 614.2307;
found: 614.2314.
4.6. Procedure for Scheme 5
To a stirred solution of 3m (mixture of 3m and 8: 0.192 g,
3m:8¼1:0.6, 0.30 mmol for 3m) in CH2Cl2 (3 mL) was added TfOH
(0.045 g, 0.30 mmol) at 25 ꢀC. Upon stirring at 25 ꢀC for 24 h, the
reaction mixture was filtered through a plug of silica gel with
CH2Cl2 (50 mL) as eluent, concentrated, and purified by column
chromatography (silica gel, eluent: petroleum ether/ethyl
(film) 1737, 1428, 1111 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 7.72e7.66
(m, 4H), 7.46e7.36 (m, 6H), 5.53e5.37 (m, 2H), 4.14 (q, J¼7.2 Hz,
2H), 3.68 (t, J¼6.4 Hz, 2H), 2.39e2.26 (m, 4H), 2.10 (q, J¼6.4 Hz, 2H),
1.64 (quintet, J¼6.8 Hz, 2H), 1.27 (t, J¼6.8 Hz, 3H), 1.07 (s, 9H); 13C
acetate¼100:1) to give compound 4m as pale yellow oil (0.105 g,
20
NMR (100 MHz, CDCl3)
d 173.4, 135.8, 134.3, 131.3, 129.7, 128.6,
78%). [
a]
¼þ148 (c 0.80, CHCl3) (88% ee).
D
127.8, 63.4, 60.4, 34.6, 32.5, 28.9, 28.1, 27.1, 19.4, 14.5; HRMS (ESI)
Calcd for C26H36NaO3Si (MþNa): 447.2326; found: 447.2331.
4.7. Procedure for Scheme 6
4.5.3. (E)-N-[8-(tert-Butyldiphenylsilyloxy)oct-4-enyl]mesityl-sul-
fonamide (13). To a suspension of LiAlH4 (1.08 g, 28.27 mmol) in dry
Et2O (50 mL) was added dropwise a solution of ester 11 (12.08 g,
28.47 mmol) in Et2O (50 mL) at 0 ꢀC. Upon stirring at rt for 2 h, the
reaction mixture was cooled to 0 ꢀC, quenched by slow addition of
H2O until no bubble was seen, filtered through a plug of silica gel
with Et2O as eluent, and concentrated to afford crude alcohol 12 as
colourless oil (10.0 g, 92%).
Alcohol 12 (13.12 g, 34.30 mmol) was dissolved in THF (100 mL),
followed by the successive addition of MsCl (4.72 g, 41.20 mmol)
and Et3N (17.30 g, 171.0 mmol) at 0 ꢀC. Upon stirring at rt for 1.5 h,
the reaction mixture was filtered through a plug of silica gel with
ethyl acetate as eluent and concentrated to give the mesylate as
yellow oil.
A solution of 16 (0.123 g, 0.20 mmol) and TfOH (0.030 g,
0.20 mmol) in CH2Cl2 (2 mL) was stirred at 27 ꢀC for 24 h. The re-
action mixture was filtered through a plug of silica gel with ethyl
acetate as eluent, concentrated, and purified by column chroma-
tography (silica gel, eluent: petroleum ether/dichloromethane/
ethyl acetate¼20:2:1) to give a mixture of 16 and 19 (ratio
16:19¼16:84) as white solid (0.109 g, 74% for 19 from 16).
syn-1-(Mesitylsulfonyl)-2-[(3-mesitylsulfonylamino)propyl]-3-
(phenylthio)piperidine (19) White solid; IR (film) 3311, 1320,
1151 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 7.40e7.35 (m, 2H),
7.31e7.20 (m, 3H), 6.94 (s, 2H), 6.86 (s, 2H), 4.15e4.07 (m, 1H),
3.90e3.82 (m, 1H), 3.80e3.72 (m, 1H), 3.50e3.41 (m, 1H),
2.92e2.79 (m, 1H), 2.59 (s, 6H), 2.58e2.50 (m, 2H), 2.42 (s, 6H),
2.30 (s, 3H), 2.26 (s, 3H), 1.99e1.88 (m, 1H), 1.84e1.49 (m, 5H),
1.21e1.16 (m, 1H), 0.74e0.59 (m, 1H); 13C NMR (100 MHz, CDCl3)
A
mixture of KOH (2.88 g, 51.45 mmol) and 2,4,6-
trimethylbenzenesulfonylamide (10.24 g, 51.45 mmol) in DMF
(200 mL) was stirred at 120 ꢀC for 30 min. To this hot solution was
dropwise added, a solution of the above mesylate in DMF (20 mL).
The resulting reaction mixture was stirred at 120 ꢀC for 5 h and
cooled to rt, diluted with H2O, extracted with Et2O for three times,
washed with brine, dried over MgSO4, filtered, concentrated, and
purified by column chromatography (silica gel, eluent: petroleum
ether/ethyl acetate/dichloromethane¼100:1:1 to 50:1:1 to 30:1:1)
to afford compound 13 as pale yellow oil (12.88 g, 67% over two
d
142.6, 142.3, 139.9, 139.2, 134.1, 134.0, 133.7, 132.2, 131.3, 129.4,
127.3, 55.3, 47.7, 42.1, 39.4, 27.0, 26.1, 26.0, 23.1, 23.0, 21.6, 21.13,
21.10; HRMS (ESI) Calcd for C32H43N2O4S3 (MþH): 615.2380;
found: 615.2390.
Acknowledgements
We gratefully acknowledge the National Basic Research Program
of China (973 program, 2011CB808600), the National Natural Sci-
ence Foundation of China (21172221), and the Chinese Academy of
Sciences for the financial support.
;
steps). IR (film) 3300, 1323, 1154, 1111 cmꢁ1 1H NMR (400 MHz,
CDCl3) 7.74e7.61 (m, 4H), 7.46e7.32 (m, 6H), 6.95 (s, 2H),
d
5.36e5.18 (m, 2H), 4.39 (t, J¼6.0 Hz, 1H), 3.63 (t, J¼6.4 Hz, 2H), 2.87
(q, J¼6.8 Hz, 2H), 2.63 (s, 6H), 2.29 (s, 3H), 2.06e1.98 (m, 2H),
1.97e1.88 (m, 2H), 1.62e1.52 (m, 2H), 1.52e1.42 (m, 2H), 1.05 (s,
Supplementary data
9H); 13C NMR (100 MHz, CDCl3)
d 142.3, 139.3, 135.8, 134.3, 133.9,
132.1, 131.5, 129.7, 129.0, 127.8, 63.4, 42.2, 32.5, 29.7, 29.5, 28.9, 27.1,
23.2, 21.1, 19.4; HRMS (ESI) Calcd for C33H45NNaO3SSi (MþNa):
586.2782; found: 586.2796.
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2012.08.043.
References and notes
4.5.4. threo-1-(Mesitylsulfonyl)-2-[(4-mesitylsulfonylamino-1-
phenylthio)butyl]pyrrolidine (16). Compound 13 was converted to
compound 14 in a manner similar to the reaction sequence from
1m to 3m. A mixture of 14 and 15 was obtained (2.58 g, 14:15¼2:1,
35% yield for 14 from 13). Compound 14 was deprotected with TBAF
and subsequently converted to compound 16 (1.07 g, 64% over
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