FeBr3-catalyzed regioselective intramolecular sulfenoamination of unactivated terminal olefins

Article abstract of DOI:10.1016/j.tet.2019.130619

A method for regioselective intramolecular sulfenoamination of unactivated terminal olefins was reported. Using sulfonyl hydrazides as the sulfur sources, FeBr₃ as the catalyst and (NH₄)₂S₂O₈ as the oxidant, different sulfenylmethylpyrrolidines and sulfenylmethylpiperidines were obtained in moderate to high yields via intramolecular sulfenoamination of (sulfon)amidopentenes or (sulfon)amidohexenes.

Full text of DOI:10.1016/j.tet.2019.130619

Journal Pre-proof
FeBr -catalyzed regioselective intramolecular sulfenoamination of unactivated
3
terminal olefins
Lin-Chuang Zheng, Lin Li, Lili Duan, Yue-Ming Li
PII:
S0040-4020(19)30962-7
https://doi.org/10.1016/j.tet.2019.130619
TET 130619
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 July 2019
Revised Date: 12 September 2019
Accepted Date: 18 September 2019
Please cite this article as: Zheng L-C, Li L, Duan L, Li Y-M, FeBr -catalyzed regioselective
3
intramolecular sulfenoamination of unactivated terminal olefins, Tetrahedron (2019), doi: https://
doi.org/10.1016/j.tet.2019.130619.
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FeBr3-Catalyzed Regioselective
Intramolecular Sulfenoamination of
Unactivated Terminal Olefins
Lin-Chuang Zheng, Lin Li, Lili Duan, Yue-Ming Li*
Leave this area blank for abstract info.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of
Molecular Drug Research, Nankai University, Tianjin, People’s Republic of China

FeBr3-Catalyzed Regioselective Intramolecular Sulfenoamination of Unactivated
Terminal Olefins
Lin-Chuang Zheng a, Lin Li a, Lili Duan, a Yue-Ming Li a, b,
*
a State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of
Molecular Drug Research, Nankai University, Tianjin, People’s Republic of China
b CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai, People’s Republic of China
ABSTRACT:
A method for regioselective intramolecular sulfenoamination of
unactivated terminal olefins was reported. Using sulfonyl hydrazides as the sulfur
sources, FeBr3 as the catalyst and (NH4)2S2O8 as the oxidant, different
sulfenylmethylpyrrolidines and sulfenylmethylpiperidines were obtained in moderate to
high yields via intramolecular sulfenoamination of (sulfon)amidopentenes or
(sulfon)amidohexenes.
Keywords:
FeBr3
Sulfenoamination
Sulfenylmethylpyrrolidine
Sulfenylmethylpiperidine
Alkenyl sulfonamide
1. Introduction
*
Corresponding author. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key
Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China.
E-mail address: ymli@nankai.edu.cn (Y.-M. Li).
1

Heterocyclic compounds such as pyrrolidines or piperidines can be widely found in
natural products, agrochemicals and pharmaceuticals, and have played important roles
in organic synthesis and drug synthesis [1]. In particular, interesting bioactivities could
be obtained when additional heteroatoms such as sulfur atom was introduced to
piperidines or pyrrolidines [2]. For example, compounds A and B showed interesting
anti-inflammatory activity [3], compounds C were designed as monoamine transporter
inhibitors [4], compound D can be used as anti-mycobacterial agent [5] and compound E
can be used as TNF-α converting enzyme (TACE) inhibitor (Fig. 1) [3c].
N
S
R
SAr
N
S
X
N
R
R'
B
A
C
Ar
H
N
HOHNOC
N
HO
O
S(CH2)11CH3
S
O
N
HO
O
OH
D
E
Fig. 1. Examples of Vicinal Thioamine Skeletons in Medicinal Chemistry.
So far, a number of important pharmaceutical agents bearing sulfur-based fragments in
the adjacent position of the nitrogen heterocycles have been developed, and it is of high
interest to find straightforward methods for the construction of sulfenylated
N-heterocycles. While conventional functional group transformations have been
extensively developed as general methods for the construction of heterocyclic structures,
it is still highly desirable to develop new methods for the straightforward formation of
functionalized piperidines and pyrrolidines. As a consequence, direct functionalization
of unactivated olefins such as hydroxysulfenylation [6], alkoxysulfenylation [7], and
disulfidation [8] of olefins were developed as efficient routes to various
2

sulfur-containing heterocycles.
Vicinal addition of amino and sulfur fragments across a C=C double bond, namely inter-
or intramolecular sulfenoamination (or thioamination) allows the direct introduction of
sulfur atom and nitrogen atom to C=C double bond in one step, and can be regarded as a
straightforward method for the preparation of vicinal sulfenoamines. For example,
progresses have been achieved on sulfenoamination [9] which allow the assembly of
sulfenylated structures in a single step. Denmark et al. reported an efficient
sulfenoamination protocol in which thiiranium ions were generated from
arylthiophthalimides, and subsequent capture of the thiiranium ion intermediate with
certain nucleophiles (Scheme 1a) furnished a variety of sulfur-containing heterocycles
[10]. Zhu et al. reported a regioselective free radical 1,2- thioamidation of terminal
alkenes in the presence of NFSI and thiols (Scheme 1b) [9d].
Generally, these methods will use disulfides or thiols as the sulfenylating agents. Such
reagents are normally air and/or moisture sensitive, and are not always acceptable by
users due to the unpleasant odor of these compounds. Therefore, it is highly desirable to
develop sulfenoamination reactions using easily available sulfenylating agents as thiol
surrogates. We are interested in the preparation of different functionalized heterocyclic
compounds [11]. Herein, we report the sulfenoamination of unactivated terminal olefins
as a continuation of our program on the synthesis of substituted piperidines and
pyrrolidines (Scheme 1c).
3

Previous works:
NHTs
Ts
NHTs
N
R
PhthSAr or RSH
S
a)
b)
c)
SR
n
n
n
NR1
NR
NR1
NHR1
R2SH
R2N
SR2
This work:
NHR
NHR
Sulfonyl hydrazides
S
R
SR
Scheme 1. Strategies for Intramolecular Sulfenoamination of Alkenes.
2. Results and Discussion
Sulfonyl hydrazides can be easily prepared via reactions of sulfonyl chlorides with
hydrazine hydrate [12]. They are generally shelf-stable solids and have been found
widespread application in organic synthesis [13]. Recently, these compounds are also
utilized as sulfonyl sources [14] and sulfenyl sources [15] via the cleavage of N-S bond
and as aryl sources through the cleavage of C-S bond under certain conditions [16].
Enlightened by these results, intramolecular sulfenoamination of unactivated terminal
olefins were proposed using sulfonyl hydrazides as the electrophilic sulfenylating agents
in an attempt to generate various sulfenylated N-heterocycles. Thus,
N-(2,2-diphenylpent-4-en-1-yl)-4-methylbenzenesulfonamide
(1a)
and
p-toluenesulfonyl hydrazide (2a) were subjected to the sulfenoamination reaction using
FeBr3 as the catalyst and Na2S2O8 as the oxidant. The preliminary results are
summarized in Table 1. As these results showed, in the presence of 20 mol% of FeBr3
and 4 equiv of Na2S2O8 [6e], the reaction of 1a (0.25 mmol) and 2a (0.5 mmol) in
1,4-dioxane at 120 °C provided the desired product in 46% yield (Table 1, entry 1).
Encouraged by this preliminary result, promoters containing different halogens were
4

further screened to find the most suitable reaction systems, and FeBr3 still showed the
best performance among the reactions (Table 1, entry 1 vs entries 2-10). A mixture of
3aa and 3aa’ was obtained in a radio of 3 to 1 when CuBr2 was used as the reaction
promoter (Table 1, entry 4). The latter compound was formed possibly via the
intramolecular bromoamination reaction [11a]. Various reaction media were also
screened (Table 1, entry 11-14), and 1,4-dioxane was found to be the most suitable
solvent for the reaction. Screening on the oxidants showed that (NH4)2S2O8 was the most
suitable oxidant for the reaction, and the desired product 3aa was obtained in 76%
yield (Table 1, entry 16). The good performance of (NH4)2S2O8 may be due to its good
solubility in 1,4-dioxane. Further screening on the amount of oxidant showed that no
significant decrease in the yield of 3aa was observed when the amount of (NH4)2S2O8
was reduced to 2 equiv (Table 1, entry 17). Lowering the reaction temperature caused
the reduce of reaction rate, and prolonged reaction time was needed to get meaningful
yield of the product. Reaction under argon atmosphere produced the product with
similar yield, and no significant difference was observed when further increasing the
amount of FeBr3 (Table 1, entries 18-20) [17]. The reaction proceeded rather sluggishly
in the absence of FeBr3 (Table 1, entry 21).
Table 1
Optimization of the Reaction Conditions.a
catalyst
oxidant
Ph
Ph
Ph
O
S
NHNH2
Br
S
CH3
Ph Ph
Ph
+
NHTs
O
solvent
120 °C, 24 h
N
Ts
3aa'
N
Ts
3aa
CH3
1a
2a
5

entry
1
catalyst
FeBr3
ZnBr2
MgBr2
CuBr2
MnI2
FeI2
solvent
oxidant
Na2S2O8
yield (%)b
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DCE
46
2
Na2S2O8
28
3
Na2S2O8
16
4
Na2S2O8
51 (3:1)c
5
Na2S2O8
trace
6
Na2S2O8
trace
7
ZnI2
Na2S2O8
not detected
8
FeCl3
MgCl2
I2
Na2S2O8
34
12
38
28
40
42
21
45
76
75
72
52
70
< 10
9
Na2S2O8
10
11
12
13
14
15
16
17d
18d,e
19d,f
20d,g
21
Na2S2O8
FeBr3
FeBr3
FeBr3
FeBr3
FeBr3
FeBr3
FeBr3
FeBr3
FeBr3
FeBr3
-
Na2S2O8
DMF
Na2S2O8
MeCN
Na2S2O8
toluene
Na2S2O8
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
K2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
6

Reaction conditions:
a The reactions were carried out with 1a (0.25 mmol), 2a (0.5 mmol, 2.0 equiv), catalyst
(0.2 equiv), oxidant (1.0 mmol, 4.0 equiv) in 2 mL of solvent at 120 °C under air
atmosphere for 24 h.
b Isolated yield based on 1a.
c Ratio of the desired product and the bromide in parentheses, determined by 1H NMR.
d (NH4)2S2O8 (0.5 mmol, 2.0 equiv).
e Under argon atmosphere.
f Reaction was carried out at 100 °C for 48 h.
g FeBr3 (0.3 equiv).
To further confirm the structure of the product, 3aa was carefully crystalized and the
single crystal was subjected to X-ray diffraction experiment. The ORTEP drawing of the
compound clearly showed the sulfenylmethylpyrrolidine structure (Fig. 2).
Fig. 2. ORTEP drawing of compound 3aa at 30% probability displacement ellipsoid (the
hydrogen atoms are omitted for clarity).
7

After the establishment of the optimal reaction conditions, the scope of the reaction was
explored with a variety of N-sulfonamide protected alkenes 1 as the substrates and
p-toluenesulfonyl hydrazide 2a as the sulfur source. The results are summarized in
Table 2. As shown in Table 2, the sulfenoamination reactions tolerated a wide range of
N-sulfonyl groups. The substituted phenylsulfonyl groups with different steric and
electronic substitution patterns showed no significant effect on the course of the
reactions. For example, substrates bearing whether electron-donating (3fa), or
electron-withdrawing groups (3ba, 3ca, 3da, 3ga) could all be employed in the
reactions and the desired products were obtained in satisfactory yields. Aliphatic
sulfonamides were tolerated as well, and pyrrolidines 3ha and 3ia bearing methyl or
n-butyl groups were obtained in good yields (74% and 79% yields, respectively). Other
substrates bearing gem-disubstituents such as cyclopentyl, cyclohexyl or dimethyl
groups also provided the desired products 3la-3oa in satisfactory isolated yields.
Monosubstituted substrate was also compatible with the reaction conditions, delivering
the desired product 3pa in good yield. Reactions of substrates without
gem-disubstituents were less successful, giving the corresponding products 3qa-3ta in
slightly lower yields of 57-73% possibly due to the lack of Thorpe-Ingold groups.
Generally, the reactions were less efficient for the formation of six-membered rings, the
desired sulfenomethylated piperidine derivatives 3ua-3va were obtained in only 49-68%
yields.
Table 2
Scope of the Substrates.a,b
8

R1
FeBr3
(NH4)2S2O8
O
S
R1 R1
NHNH2
S
CH3
n
R1
H
N
R2
+
S
O
1,4-dioxane
120 °C, 24 h
n
N
O2
1
CH3
SO2
R2
2a
3
substrat
e
entry
R1
R2
n
product
yield (%)
1
2
1a
1b
1c
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-MeC6H4
4-FC6H4
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
3aa
3ba
3ca
3da
3ea
3fa
75
71
70
78
73
78
78
74
79
80
79
57
73
74
40
71
3
4-BrC6H4
4-O2NC6H4
Ph
4
1d
1e
1f
5
6
3-MeC6H4
2-O2NC6H4
Me
7
1g
1h
1i
3ga
3ha
3ia
8
9
n-butyl
10
11
12
13
14
15
1j
2-naphthyl
1-naphthyl
4-O2NC6H4
4-MeC6H4
4-MeC6H4
4-O2NC6H4
3ja
1k
1l
3ka
3la
-(CH2)4-
-(CH2)4-
-(CH2)5-
Me
1m
1n
1o
3ma
3na
3oa
S
Ph
H
Ph
16
1p
N
Ts
N
3pa
(d.r.=1.5:1)
Ts
9

c
17
18
19
20
21
22
1q
1r
1s
1t
H
4-MeC6H4
4-MeOC6H4
2-MeC6H4
4-ClC6H4
1
1
1
1
2
2
3qa
3ra
3sa
3ta
3ua
3va
73
57
69
62
49
68
H
H
H
1u
1v
Ph
4-MeC6H4
4-MeC6H4
-(CH2)4-
Reaction conditions:
a
The reactions were carried out with 1 (0.25 mmol), 2a (0.5 mmol, 2.0 equiv), FeBr3
(0.2 equiv), (NH4)2S2O8 (0.5 mmol, 2.0 equiv) in 2 mL of 1,4-dioxane at 120 °C under air
atmosphere for 24 h.
b Isolated yield based on 1.
c Determined by 1H NMR.
When sulfonyl group was used as the nitrogen protecting groups, intramolecular
sulfenoamination reactions provided the N-sulfonylated piperidines or pyrrolidines as
the final products. To the best of our knowledge, removal of sulfonyl group from
sulfonamides generally required harsh conditions [18]. This limitation also called for
protective groups which could be readily removed under relatively mild conditions.
Given that removal of benzoyl group from benzamides is easier than that of sulfonyl
group from sulfonamides, preparation of N-benzoyl sulfenyl heterocycles would exhibit
more application potential.
In this regard, the sulfonamide substrates were replaced with carboxamide substrates to
10

further expand the scope of the reaction [9a]. The results are summarized in Table 3. To
our delight, a wide range of benzamides with different electronic substitution patterns
could be employed, and good to high yields (62-87%) were recorded for the respective
adducts (5aa-5fa, shown in Table 3).
It is worth mentioning that the corresponding free amine product 5ga was obtained in
51% yield when N-tert-butyloxycarbonylamino (N-Boc) alkene 4g was used as the
substrate (Table 3, entry 7). No desired product 5ga was obtained when free amine was
subjected to the reaction under the same condition, suggesting that 5ga was produced
via deprotection of the cyclization product. Replacing the N-Boc group with Fmoc or Cbz
was also possible, but the products were obtained as mixtures of both the piperidines
and pyrrolidines (Table 3, entries 8 and 9). Separation of these isomers was generally
difficult, and studies on these substrates were not further pursued at this stage.
Table 3
Reaction Scope of Alkenes 2.a
CH3
S
Ph
Ph
FeBr3
(NH4)2S2O8
R
O
S
NHNH2
Ph Ph
H
N
O
+
N
O
1,4-dioxane
120 °C, 24 h
R
CH3
O
5
4
2a
entry
substrate
R
product
5aa
yield (%)b
1
2
3
4
4a
4b
4c
4d
4-FC6H4
80
87
64
62
4-ClC6H4
4-BrC6H4
Ph
5ba
5ca
5da
11

5
6
4e
4f
4-MeC6H4
5ea
65
74
4-MeOC6H4
5fa
Ph
Ph
S
Ph Ph
H
7
4g
N
51
N
Boc
5ga
H
Reaction conditions:
a
The reactions were carried out with 4 (0.25 mmol), 2a (0.5 mmol, 2.0 equiv), FeBr3
(0.2 equiv), (NH4)2S2O8 (0.5 mmol, 2.0 equiv) in 2 mL of 1,4-dioxane at 120 °C under air
atmosphere for 24 h.
b Isolated yield based on 4.
c Determined by 1H NMR.
Next, different sulfonyl hydrazides were used as sulfur sources to test the feasibility of
the reaction. The results are summarized in Table 4. Studies showed that sulfonyl
hydrazides with different types of substituents at the para-positions of the benzene
rings, either electron-donating or electron-withdrawing, could be tolerated, giving the
desired products in good to high yields, except for 4-Br (3ae) and 4-t-Bu (3ah) which
gave products in slightly lower yields. Further, the position of the substituent on m- or p-
of benzene rings has a negligible effect on this reaction under standard conditions (3aa
and 3aj). However, when the o-substituted substrates were employed, dramatically
different results were observed. o-Fluoro substituted substrate 2k gave product 3ak in
high yield (89%), and o-nitro substituted substrate 2l gave product 3al in poor yield
(36%), possibly due to the larger steric hindrance of the nitro group than fluorine atom.
Alkyl sulfonyl hydrazide 2n could be employed as sulfur source, but the desired product
2an was obtained in low yield, possibly due to the low stability of the aliphatic sulfenyl
12

intermediate under the reaction conditions.
Table 4
Reaction Scope of Sulfonyl Hydrazides.a
FeBr3
O
Ph
Ph
S R
(NH4)2S2O8
Ph Ph
+
H2NHN S R
O
NHTs
1,4-dioxane
120 °C 24 h
N
Ts
1a
2
3
entry
2
2b
2c
2d
2e
2f
R
product
3ab
3ac
yield (%)b
84
1
2
Ph
4-FC6H4
4-ClC6H4
4-BrC6H4
84
3
3ad
3ae
3af
76
4
62
5
4-NO2C6H4
4-CF3C6H4
4-t-BuC6H4
4-MeOC6H4
3-MeC6H4
2-FC6H4
72
6
2g
2h
2i
3ag
3ah
3ai
72
7
53
8
80
9
2j
3aj
75
10
11
12
13
2k
2l
3ak
3al
89
2-O2NC6H4
2-naphthyl
n-butyl
36
2m
2n
3am
3an
82
36
Reaction conditions:
a
The reactions were carried out with 1a (0.25 mmol), 2 (0.5 mmol, 2.0 equiv), FeBr3
(0.2 equiv), (NH4)2S2O8 (0.5 mmol, 2.0 equiv) in 2 mL of 1,4-dioxane at 120 °C under air
13

atmosphere for 24 h.
b Isolated yield based on 1a.
To demonstrate the application potential of this reaction, several derivatization
reactions
were
carried
out
using
N-tosylpyrrolidine
3aa
and
N-(p-methylbenzoyl)pyrrolidine 5ea as the model compounds. As shown in Scheme 2,
treatment of 3aa with 2.0 equiv of m-chloroperbenzoic acid (m-CPBA) furnished sulfone
6 in 93% yield [6e]; treatment of 3aa with 1.0 equiv amount of PIDA furnished sulfoxide
7 in 88% yield [10f]. The removal of p-methylbenzoyl group was readily accomplished
by treating 5ea with 6 N HCl, and the corresponding deprotection product 5ga was
obtained in 72% yield [19]. The current methods thus provided entries to different
important sulfur-containing heterocycles.
Ph
Ph
Ts
a
N
Ts
6
Ph
Ph
S
b
O
Ph
Ph
N
Ts
3aa
S
S
CH3
N
7 (d.r.=1.3:1)d
Ts
CH3
CH3
S
Ph
Ph
Ph
Ph
c
N
NH
CH3
5ga
O
5ea
Reaction conditions: a 3aa, m-CPBA, DCM, r. t., overnight. b 3aa, AlCl3, PIDA, MeOH/DCM,
r. t., overnight. c 5ea, 6 N HCl, reflux, 24 h. d Isolated yield.
Scheme 2. Functional Group Transformation Using 3aa and 5ea as Precursors.
Wirth et al. reported an alkene thioamination protocol in which hypervalent iodine
reagents were used. In this method, the substrate first underwent intramolecular
14

iodoamination, and subsequent nucleophilic substitution with the thiolate provided the
sulfenoamination product [10d]. As mentioned in the reaction condition optimization
step, bromoamination product was observed when CuBr2 was used as the bromide
source (Table 1, Entry 4). Control reactions were then carried out to see if the products
could be obtained from the bromoamination product under current reaction conditions
(Scheme 3). Study showed that no desired product 3aa was obtained when 1a was
replaced by 3aa’ under otherwise identical conditions, suggesting that sulfenoamination
pathway was more likely under current reaction conditions. In previous reports,
molecular oxygen was involved in an iodine-triggered aerobic sulfonylation of styrenes
[14f]. In the current study, reactions carried out under air atmosphere or under argon
atmosphere gave product in similar isolated yields, suggesting that molecular oxygen
made no contribution to the formation of the products.
standard
conditions
Br
Ph
Ph
O
S
Ph
Ph
NHNH2
S
CH3
+
O
N
N
Ts
CH3
Ts
not observed
3aa'
2a
Scheme 3. Control Reaction.
Combining the above observations with previous reports and our previous study
[6e,15a,20], a plausible reaction pathway is proposed in Scheme 4. Bromine is generated
in situ when bromide anion and suitable oxidant are present in the reaction mixture.
Sulfenyl bromide intermediate A is produced in situ from sulfonyl hydrazide 2 by the
action of bromine as reported previously.[13b] Electrophilic addition of intermediate A
to alkene 1 produces thiiranium ion intermediate B, and subsequent nucleophilic ring
opening gives the desired products 3 or 5. At the same time, the released bromide anion
15

is oxidized to bromine to complete the catalytic cycle.
ArSON=NH
ArSO2NHNH2
+
Br2
Br2 HOBr
HOBr
ArSN=NBr
ArSBr + N2
O
Ar S NHNH2
2
O
O
O
O
O
Br2
S
N2, H2O, HOBr
O
S
O
O
O
Ar SBr
A
Br
Ar
S
Br
product 3 or 5
NHTs
NHTs
1
B
Scheme 4. Possible Pathway of the Reactions.
3. Conclusion
In summary, we reported a highly regioselective intramolecular sulfenoamination of
unactivated terminal olefins with sulfonyl hydrazides. A range of sulfonyl hydrazides
were compatible with the current reaction system, and the desired products bearing the
sulfur units adjacent to the nitrogen-containing heterocycles were obtained in moderate
to high yields. Application of this transformation in organic synthesis is underway.
4. Experimental Section
4.1. General Experimental Information
Reactions were carried out with commercially available reagents in oven-dried
apparatus. 1H and 13C NMR spectra were recorded at 298 K using deuterated chloroform
as solvent and TMS as internal reference. Column chromatography was performed
16

employing 200-300 mesh silica gel unless otherwise noted. Thin layer chromatography
(TLC) was performed on silica gel GF254. Melting points were measured on a digital
melting-point apparatus without correction of the thermometer. HRMS analyses were
carried out with Varian FTICR-MS 7.0T. IR spectra were recorded on a BRUKER TENSOR
37. Unless otherwise indicated, starting materials and reagents used in the study were
purchased and were used as received without further purification.
4.2. Typical procedure for the intramolecular sulfenoamination of alkenes with 4-methyl
benzene sulfonyl hydrazide
A 35 mL Schlenk-type tube (with a Teflon high pressure valve) equipped with a
magnetic
stir
bar
was
charged
with
N-(2,2-diphenylpent-4-en-1-yl)-4-methylbenzenesulfonamide (1a, 0.25 mmol, 97.9 mg)
and p-toluenesulfonyl hydrazide (2a, 0.5 mmol, 93.2 mg). FeBr3 (0.05 mmol, 14.8 mg),
(NH4)2S2O8 (0.5 mmol, 0.114 g) and 1,4-dioxane (2 mL) were added to this system. The
tube was sealed and placed in an oil bath at 120 °C. The reaction mixture was allowed to
cool to ambient temperature after 24 hours of reaction at this temperature. The tube
was opened with care (Caution!). The reaction mixture was filtered and concentrated to
give the crude product. The residue was purified by column chromatography
(petroleum ether: ethyl acetate = 50: 1, v/v) to afford the desired product 3aa.
4.2.1. 4,4-Diphenyl-2-((4-tolylthio)methyl)-1-tosylpyrrolidine (3aa)
Compound 3aa was prepared according to the general procedure and was isolated as
white solid (96.3 mg, 75% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 118-121 °C. H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.0 Hz,
17

2H), 7.29 (q, J = 9.7, 8.5 Hz, 6H), 7.18 – 7.07 (m, 8H), 7.04 (d, J = 7.4 Hz, 2H), 4.50 (d, J =
10.0 Hz, 1H), 3.61 (d, J = 13.8 Hz, 2H), 3.43 (d, J = 10.1 Hz, 1H), 2.73 – 2.56 (m, 2H), 2.37
(s, 3H), 2.35 (s, 3H), 2.19 (t, J = 12.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 145.0, 144.9,
143.4, 136.5, 131.2, 130.4, 129.8, 129.6, 128.7, 128.6, 127.6, 126.8, 126.6, 126.4, 126.4,
58.6, 52.1, 41.7, 38.5, 21.5, 21.1. The NMR data were in agreement with reported results
[11a].
Crystal data for 3aa (CCDC 1920628): C31H31NO2S2, M = 513.69, a = 14.1662(8) Å, b =
16.2771(7) Å, c = 13.1633(7) Å, α = 90°, β = 112.579(6)°, γ = 90°, V = 2802.6(3) Å3, T =
294.15 K, space group P121/c1, Z = 4, μ(MoKα) = 0.218 mm-1, 37951 reflections
measured, 6940 independent reflections (Rint = 0.0458). The final R1 values were 0.0422
(I > 2σ(I)). The final wR(F2) values were 0.1007 (I > 2σ(I)). The final R1 values were
0.0767 (all data). The final wR(F2) values were 0.1136 (all data). The goodness of fit on
F2 was 1.017.
4.2.2. 1-((4-Fluorophenyl)sulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3ba)
Compound 3ba was prepared according to the general procedure and was isolated as
white solid (91.9 mg, 71% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 146-148 °C. H NMR (400 MHz, CDCl3) δ 7.37 – 7.32 (m, 2H),
7.28 – 7.24 (m, 2H), 7.19 (d, J = 2.2 Hz, 2H), 7.13 – 7.02 (m, 7H), 6.99 – 6.93 (m, 3H), 6.84
(t, J = 8.6 Hz, 2H), 4.41 (dd, J = 10.3, 1.2 Hz, 1H), 3.71 – 3.26 (m, 3H), 2.69 (dd, J = 13.1,
8.4 Hz, 1H), 2.64 – 2.47 (m, 1H), 2.30 (s, 3H), 2.28 – 2.17 (m, 1H). 13C NMR (101 MHz,
CDCl3) δ 144.8, 144.6, 136.7, 130.9, 130.1, 130.0, 129.9, 128.7, 128.7, 127.7, 126.71,
126.7, 126.7, 126.6, 126.4, 116.2, 116.0, 59.1, 58.8, 52.2, 42.0, 39.0, 21.1. 19F NMR (376
18

MHz, CDCl3) δ -105.3. IR (KBr): 2929, 1591, 1492, 1338, 1232, 1166, 1083, 833, 810,
+
705, 545 cm-1. HRMS (m/z): [M + H]+ calcd for C30H29FNO2S2 : 518.1618; found:
518.1622.
4.2.3. 1-((4-Bromophenyl)sulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3ca)
Compound 3ca was prepared according to the general procedure and was isolated as
white solid (101.3 mg, 70% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 134-136 °C. H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.2 Hz,
4H), 7.17 (tq, J = 6.8, 4.1, 2.9 Hz, 6H), 7.12 – 7.08 (m, 4H), 7.04 (dt, J = 5.1, 2.8 Hz, 2H),
6.95 – 6.91 (m, 2H), 4.38 (d, J = 10.4 Hz, 1H), 3.63 – 3.50 (m, 3H), 2.76 (dd, J = 13.2, 7.9
Hz, 1H), 2.51 (dd, J = 13.1, 5.1 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 1H). 13C NMR (101 MHz,
CDCl3) δ 144.9, 144.3, 136.8, 135.3, 132.1, 131.1, 130.9, 129.9, 128.8, 128.7, 128.7, 127.7,
126.7, 126.6, 126.6, 126.3, 59.3, 58.9, 52.3, 42.1, 39.2, 21.1. IR (KBr): 2922, 1571, 1490,
1344, 1164, 1072, 1043, 813, 700, 607 cm-1. HRMS (m/z): [M + H]+ calcd for
+
C30H29BrNO2S2 : 579.0851; found: 579.0854.
4.2.4. 1-((4-Nitrophenyl)sulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3da)
Compound 3da was prepared according to the general procedure and was isolated as
yellow solid (106.2 mg, 78% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 159-162 °C. H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.7 Hz,
2H), 7.39 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 7.9 Hz, 2H), 7.20 – 7.16 (m, 2H), 7.15 – 7.07 (m,
5H), 6.97 – 6.93 (m, 3H), 6.92 – 6.88 (m, 2H), 4.37 (d, J = 10.8 Hz, 1H), 3.79 (d, J = 10.7
Hz, 1H), 3.66 (dd, J = 13.4, 2.9 Hz, 1H), 3.62 – 3.57 (m, 1H), 2.94 (dd, J = 13.4, 7.4 Hz, 1H),
2.53 – 2.39 (m, 2H), 2.35 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 149.7, 144.8, 143.9, 142.3,
19

137.2, 131.3, 131.0, 123.0, 128.8, 128.6, 128.2, 126.8, 126.6, 126.4, 126.4, 123.9, 60.1,
59.1, 52.4, 42.4, 39.7, 21.1. IR (KBr): 2925, 1529, 1350, 1166, 1031, 705, 611, 561 cm-1.
+
HRMS (m/z): [M + H]+ calcd for C30H29N2O4S2 :545.1563; found; 545.1566.
4.2.5. 4,4-Diphenyl-1-(phenylsulfonyl)-2-((4-tolylthio)methyl)pyrrolidine (3ea)
Compound 3ea was prepared according to the general procedure and was isolated as
white solid (91.2 mg, 73% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 157-159 °C. H NMR (400 MHz, CDCl3) δ 7.53 – 7.45 (m, 3H),
7.34 – 7.28 (m, 8H), 7.18 – 7.09 (m, 6H), 7.07 – 7.04 (m, 2H), 4.50 (dd, J = 10.1, 1.4 Hz,
1H), 3.69 – 3.57 (m, 2H), 3.46 (d, J = 10.1 Hz, 1H), 2.74 – 2.58 (m, 2H), 2.37 (s, 3H), 2.25
– 2.15 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 144.9, 144.8, 136.5, 136.1, 132.7, 131.1,
130.6, 129.8, 129.0, 128.7, 128.6, 127.5, 126.8, 126.7, 126.6, 126.3, 58.6, 58.6, 52.1, 41.8,
38.6, 21.1. IR (KBr): 2974, 2923, 1490, 1446, 1340, 1164, 1089, 1031, 813, 748, 694,
+
597, 570, 507 cm-1. HRMS (m/z): [M + H]+ calcd for C30H30NO2S2 : 500.1712; found:
500.1708.
4.2.6. 4,4-Diphenyl-1-(3-tolylsulfonyl)-2-((4-tolylthio)methyl)pyrrolidine (3fa)
Compound 3fa was prepared according to the general procedure and was isolated as
pale yellow viscous oil (100.2 mg, 78% yield) after flash chromatography (petroleum
1
ether: ethyl acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 8.6, 2.2 Hz,
5H), 7.22 – 7.12 (m, 6H), 7.09 – 7.02 (m, 5H), 6.99 – 6.94 (m, 3H), 4.42 (dd, J = 10.1, 1.4
Hz, 1H), 3.62 – 3.55 (m, 2H), 3.37 (d, J = 10.1 Hz, 1H), 2.67 – 2.51 (m, 2H), 2.26 (s, 3H),
2.17 (s, 3H), 2.11 (dd, J = 14.2, 11.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 144.9, 144.9,
139.2, 133.6, 130.3, 129.9, 128.9, 128.7, 128.6, 128.4, 127.9, 127.8, 126.8, 126.7, 126.6,
20

126.4, 124.8, 58.6, 52.2, 41.8, 38.4, 21.4, 21.1. IR (KBr): 2922, 2360, 1494, 1340, 1157,
+
1016, 750, 698, 611, 578, 491 cm-1. HRMS (m/z): [M + H]+ calcd for C31H32NO2S2 :
514.1869; found: 514.1871.
4.2.7. 1-((2-Nitrophenyl)sulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3ga)
Compound 3ga was prepared according to the general procedure and was isolated as
pale yellow solid (106.2 mg, 78% yield) after flash chromatography (petroleum ether:
1
ethyl acetate = 50: 1, v/v). m.p. 75-77 °C. H NMR (400 MHz, CDCl3) δ 7.49 (s, 1H), 7.41
(t, J = 7.5 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H), 7.18 – 7.13 (m, 4H),
7.13 – 7.06 (m, 5H), 7.04 – 6.96 (m, 4H), 6.93 (d, J = 7.2 Hz, 1H), 4.24 (d, J = 10.9 Hz, 1H),
4.19 – 4.06 (m, 2H), 3.42 (dd, J = 13.3, 3.2 Hz, 1H), 2.96 (dd, J = 13.1, 7.3 Hz, 1H), 2.62 –
2.48 (m, 2H), 2.22 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 143.7, 142.6, 135.4, 132.4, 130.5,
130.4, 129.2, 129.1, 128.8, 127.6, 127.5, 125.7, 125.6, 125.5, 125.4, 122.8, 58.6, 57.8,
51.7, 41.6, 38.1, 20.0. IR (KBr): 2920, 2360, 1541, 1492, 1352, 1166, 1029, 775, 702, 603,
574 cm-1. HRMS (m/z): [M + H]+ calcd for C30H29N2O4S2 : 545.1563; found: 545.1565.
+
4.2.8. 1-(Methylsulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3ha)
Compound 3ha was prepared according to the general procedure and was isolated as
pale yellow solid (90 mg, 74% yield) after flash chromatography (petroleum ether: ethyl
acetate = 50: 1, v/v). m.p. 60-62 °C. 1H NMR (400 MHz, CDCl3) δ 7.26 – 7.17 (m, 8H), 7.15
– 7.08 (m, 4H), 7.02 (d, J = 8.0 Hz, 2H), 4.16 (d, J = 11.0 Hz, 1H), 4.06 (d, J = 1.6 Hz, 1H),
3.90 – 3.79 (m, 1H), 3.53 (dd, J = 13.3, 3.2 Hz, 1H), 3.14 (ddd, J = 13.4, 7.2, 1.6 Hz, 1H),
2.66 (dd, J = 13.3, 9.9 Hz, 1H), 2.45 (dd, J = 13.4, 7.5 Hz, 1H), 2.23 (s, 3H), 2.18 (s, 3H). 13
C
NMR (101 MHz, CDCl3) δ 144.9, 144.4, 136.3, 131.6, 129.9, 129.6, 128.9, 128.8, 127.1,
21

126.8, 126.5, 59.7, 59.0, 53.2, 42.7, 39.3, 35.7, 21.0. IR (KBr): 2925, 2360, 1596, 1494,
1448, 1336, 1153, 1029, 968, 806, 752, 700, 516 cm-1. HRMS (m/z): [M + H]+ calcd for
+
C25H28NO2S2 : 438.1556; found: 438.1560.
4.2.9. 1-(Butylsulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3ia)
Compound 3ia was prepared according to the general procedure and was isolated as
pale yellow viscous oil (94.8 mg, 79% yield) after flash chromatography (petroleum
1
ether: ethyl acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 1.2 Hz, 2H),
7.24 – 7.17 (m, 6H), 7.16 – 7.09 (m, 4H), 7.03 (d, J = 8.0 Hz, 2H), 4.15 (dd, J = 10.8, 1.6 Hz,
1H), 4.05 (d, J = 10.8 Hz, 1H), 3.98 – 3.91 (m, 1H), 3.49 (dd, J = 13.2, 3.1 Hz, 1H), 3.07
(ddd, J = 13.2, 7.1, 1.6 Hz, 1H), 2.71 (dd, J = 13.3, 9.5 Hz, 1H), 2.50 (dd, J = 13.2, 7.8 Hz,
1H), 2.46 – 2.39 (m, 1H), 2.32 – 2.26 (m, 1H), 2.24 (s, 3H), 1.62 – 1.43 (m, 2H), 1.21 –
1.09 (m, 2H), 0.75 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 145.1, 144.4, 136.3,
131.7, 129.8, 129.6, 128.8, 128.7, 126.9, 126.8, 126.7, 126.6, 59.3, 58.7, 53.2, 50.2, 42.7,
39.2, 25.0, 21.6, 21.0, 13.5. IR (KBr): 2958, 2929, 2871, 1596, 1494, 1330, 1147, 1029,
+
806, 700, 611, 530 cm-1. HRMS (m/z): [M + H]+ calcd for C28H34NO2S2 : 480.2025; found:
480.2029.
4.2.10. 1-(Naphthalen-2-ylsulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine (3ja)
Compound 3ja was prepared according to the general procedure and was isolated as
white solid (110 mg, 80% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 67-69 °C. H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 1.7 Hz, 1H),
7.72 (d, J = 8.1 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.53 – 7.43 (m,
2H), 7.37 (dd, J = 8.7, 1.8 Hz, 1H), 7.27 (d, J = 7.9 Hz, 2H), 7.16 (d, J = 6.5 Hz, 4H), 7.08 (dd,
22

J = 11.7, 7.3 Hz, 3H), 6.86 (d, J = 6.7 Hz, 4H), 6.81 – 6.76 (m, 1H), 4.45 (d, J = 10.2 Hz, 1H),
3.70 – 3.65 (m, 2H), 3.51 (d, J = 10.2 Hz, 1H), 2.58 (t, J = 7.3 Hz, 2H), 2.31 (s, 3H), 2.21
(dd, J = 14.0, 11.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 145.0, 144.5, 136.5, 134.8, 133.3,
132.1, 131.2, 130.5, 130.0, 129.3, 129.2, 128.9, 128.8, 128.7, 128.4, 127.8, 127.3, 126.8,
126.7, 126.4, 126.3, 122.8, 58.9, 58.8, 52.2, 41.9, 38.7, 21.2. IR (KBr): 3055, 2922, 2868,
1492, 1340, 1163, 1076, 1029, 810, 748, 700, 661, 545 cm-1. HRMS (m/z): [M + H]+ calcd
+
for C34H32NO2S2 : 550.1869; found: 550.1872.
4.2.11.
1-(Naphthalen-1-ylsulfonyl)-4,4-diphenyl-2-((4-tolylthio)methyl)pyrrolidine
(3ka)
Compound 3ka was prepared according to the general procedure and was isolated as
white solid (108.6 mg, 79% yield) after flash chromatography (petroleum ether: ethyl
acetate = 50: 1, v/v). m.p. 66-68 °C. 1H NMR (400 MHz, CDCl3) δ 8.64 (dd, J = 8.6, 1.1 Hz,
1H), 7.98 (dd, J = 7.4, 1.3 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.77 (dd, J = 8.1, 1.4 Hz, 1H),
7.45 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.38 (ddd, J = 8.5, 6.9, 1.5 Hz, 1H), 7.31 (dd, J = 8.1, 7.4
Hz, 1H), 7.20 – 7.14 (m, 2H), 7.13 – 7.02 (m, 7H), 6.94 – 6.86 (m, 5H), 4.18 (dd, J = 10.2,
1.0 Hz, 1H), 4.06 – 4.01 (m, 1H), 3.79 (d, J = 10.1 Hz, 1H), 3.49 (dd, J = 13.5, 3.2 Hz, 1H),
2.75 (dd, J = 13.0, 8.0 Hz, 1H), 2.64 – 2.53 (m, 1H), 2.28 (s, 3H), 2.26 (d, J = 4.3 Hz, 1H).
13C NMR (101 MHz, CDCl3) δ 143.8, 143.1, 135.4, 133.4, 133.3, 132.9, 129.1, 128.9, 128.8,
127.9, 127.8, 127.5, 127.2, 127.0, 125.7, 125.6, 125.6, 125.4, 125.1, 124.0, 123.0, 57.8,
57.1, 51.5, 41.3, 37.6, 20.0. IR (KBr): 3057, 2922, 2360, 1492, 1330, 1161, 1130, 1029,
+
804, 771, 700, 601, 518 cm-1. HRMS (m/z): [M + H]+ calcd for C34H32NO2S2 : 550.1869;
found: 550.1873.
23

4.2.12. 2-((4-Nitrophenyl)sulfonyl)-3-((4-tolylthio)methyl)-2-azaspiro[4.4]nonane (3la)
Compound 3la was prepared according to the general procedure and was isolated as
yellow solid (63.4 mg, 57% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 90-93 °C. H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.8 Hz, 2H),
7.69 (d, J = 8.8 Hz, 2H), 7.34 – 7.23 (m, 2H), 7.11 (d, J = 7.9 Hz, 2H), 3.72 (dd, J = 13.4, 3.0
Hz, 1H), 3.54 – 3.46 (m, 1H), 3.28 (d, J = 10.2 Hz, 1H), 2.97 (d, J = 10.2 Hz, 1H), 2.81 (dd, J
= 13.4, 10.4 Hz, 1H), 2.33 (s, 3H), 1.88 (dd, J = 12.9, 7.7 Hz, 1H), 1.73 (dd, J = 13.0, 6.7 Hz,
1H), 1.61 – 1.33 (m, 6H), 1.01 – 0.90 (m, 1H), 0.87 – 0.80 (m, 1H). 13C NMR (101 MHz,
CDCl3) δ 150.0, 142.9, 136.9, 131.2, 130.7, 129.9, 128.6, 124.1, 60.5, 59.6, 48.6, 43.5, 39.9,
36.7, 36.4, 24.6, 24.3, 21.1. IR (KBr): 2962, 2923, 2869, 2368, 1533, 1346, 1161, 1085,
+
813, 611, 572 cm-1. HRMS (m/z): [M + H]+ calcd for C22H27N2O4S2 : 447.1407; found:
447.1403.
4.2.13. 3-((4-Tolylthio)methyl)-2-tosyl-2-azaspiro[4.4]nonane (3ma)
Compound 3ma was prepared according to the general procedure and was isolated as
pale yellow viscous oil (75.9 mg, 73% yield) after flash chromatography (petroleum
1
ether: ethyl acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.8 Hz, 2H),
7.32 – 7.27 (m, 2H), 7.14 (d, J = 8.3 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.80 (d, J = 13.5 Hz,
1H), 3.47 (d, J = 8.5 Hz, 1H), 3.23 (dd, J = 10.5, 3.2 Hz, 1H), 2.94 – 2.87 (m, 1H), 2.83 –
2.72 (m, 1H), 2.33 (s, 3H), 2.30 (s, 3H), 1.80 (d, J = 9.7 Hz, 1H), 1.68 (q, J = 7.0, 5.7 Hz,
1H), 1.57 – 1.33 (m, 6H), 0.94 – 0.85 (m, 1H), 0.81 – 0.75 (m, 1H). 13C NMR (101 MHz,
CDCl3) δ 143.4, 136.3, 133.8, 131.6, 130.1, 129.8, 129.5, 127.6, 60.3, 59.2, 48.4, 43.5, 39.8,
36.7, 36.5, 24.6, 24.2, 21.6, 21.1. IR (KBr): 2954, 2866, 1596, 1492, 1344, 1159, 804, 663,
24

+
590, 551, 491 cm-1. HRMS (m/z): [M + H]+ calcd for C23H30NO2S2 : 416.1712; found:
416.1716.
4.2.14. 3-((4-Tolylthio)methyl)-2-tosyl-2-azaspiro[4.5]decane (3na)
Compound 3na was prepared according to the general procedure and was isolated as
pale yellow viscous oil (79.5 mg, 74% yield) after flash chromatography (petroleum
1
ether: ethyl acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.0 Hz, 2H),
7.29 (d, J = 7.9 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 3.82 (dd, J = 13.3,
3.0 Hz, 1H), 3.51 – 3.44 (m, 1H), 3.12 (s, 2H), 2.77 (dd, J = 13.3, 10.4 Hz, 1H), 2.33 (s, 3H),
2.30 (s, 3H), 1.84 (dd, J = 13.1, 7.5 Hz, 1H), 1.54 – 1.45 (m, 1H), 1.38 – 1.26 (m, 4H), 1.19
– 1.00 (m, 4H), 0.70 – 0.62 (m, 1H), 0.54 – 0.45 (m, 1H). 13C NMR (101 MHz, CDCl3) δ
143.3, 136.3, 134.1, 131.8, 130.2, 129.8, 129.5, 127.5, 59.1, 58.4, 44.3, 41.2, 40.6, 36.3,
34.3, 25.8, 23.6, 22.9, 21.5, 21.1. The NMR data were in agreement with reported results
[9d].
4.2.15.
4,4-Dimethyl-1-((4-nitrophenyl)sulfonyl)-2-((4-tolylthio)methyl)pyrrolidine
(3oa)
Compound 3oa was prepared according to the general procedure and was isolated as
yellow solid (42.1 mg, 40% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 109-111 °C. H NMR (400 MHz, CDCl3) δ 8.21 – 8.13 (m, 2H),
7.76 – 7.68 (m, 2H), 7.26 (d, J = 7.7 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 3.72 (dd, J = 13.4, 2.9
Hz, 1H), 3.59 (d, J = 7.3 Hz, 1H), 3.17 (d, J = 10.4 Hz, 1H), 3.02 (d, J = 10.4 Hz, 1H), 2.83
(dd, J = 13.3, 9.9 Hz, 1H), 2.32 (s, 3H), 1.83 (dd, J = 13.1, 7.5 Hz, 1H), 1.61 (dd, J = 13.0,
7.9 Hz, 1H), 1.00 (s, 3H), 0.47 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 149.9, 143.3, 136.9,
25

131.3, 130.7, 129.9, 128.5, 124.1, 62.1, 59.6, 45.8, 40.3, 37.6, 26.1, 25.9, 21.1. IR (KBr):
2962, 2923, 2368, 1533, 1346, 1163, 1085, 813, 730, 611, 572 cm-1. HRMS (m/z): [M +
+
H]+ calcd for C20H25N2O4S2 : 421.1250; found: 421.1250.
4.2.16. 4-Phenyl-2-((4-tolylthio)methyl)-1-tosylpyrrolidine (3pa)
Compound 3pa was prepared according to the general procedure and was isolated as
pale yellow oil (77.7 mg, 71% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.47 (dd, J = 30.8, 8.2 Hz, 2H), 7.33 –
7.26 (m, 2H), 7.22 – 7.06 (m, 7H), 6.99 – 6.93 (m, 2H), 3.86 – 3.58 (m, 3H), 3.45 – 3.28
(m, 1H), 2.91 – 2.72 (m, 1H), 2.50 – 2.36 (m, 1H), 2.33 (d, J = 6.7 Hz, 3H), 2.32 – 2.26 (m,
3H), 2.25 (d, J = 5.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 142.6, 142.6, 138.1, 135.3,
133.4, 132.1, 130.5, 130.2, 129.0, 128.9, 128.9, 128.8, 128.8, 128.8, 128.7, 128.6, 127.6,
127.5, 126.6, 126.5, 126.4, 126.0, 125.9, 125.9, 58.9, 57.8, 54.5, 54.4, 41.8, 40.2, 39.2,
38.4, 37.9, 35.0, 20.5, 20.5, 20.0. The NMR data were in agreement with reported results
[9d].
4.2.17. 2-((4-Tolylthio)methyl)-1-tosylpyrrolidine (3qa)
Compound 3qa was prepared according to the general procedure and was isolated as
pale yellow oil (66 mg, 73% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.48-7.43 (m, 2H), 7.31-7.26 (m, 2H),
7.15 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 3.62-3.48 (m, 2H), 3.46-3.36 (m, 1H),
3.05-2.99 (m, 1H), 2.72-2.61 (m, 1H), 2.33 (s, 3H), 2.29 (s, 3H), 1.84-1.76 (m, 1H),
1.76-1.68 (m, 1H), 1.60-1.50 (m, 1H), 1.48-1.40 (m, 1H). 13C NMR (101 MHz, CDCl3) δ
143.4, 136.2, 133.9, 131.6, 129.8, 129.7, 129.6, 127.5, 59.0, 49.7, 39.0, 30.3, 23.8, 21.5,
26

21.1. The NMR data were in agreement with reported results [9d].
4.2.18. 1-((4-Methoxyphenyl)sulfonyl)-2-((4-tolylthio)methyl)pyrrolidine (3ra)
Compound 3ra was prepared according to the general procedure and was isolated as
pale yellow solid (53.8 mg, 57% yield) after flash chromatography (petroleum ether:
ethyl acetate = 50: 1, v/v). m.p. 77-79 °C. 1H NMR (400 MHz, CDCl3) δ 7.55-7.48 (m, 2H),
7.29 (d, J = 7.9 Hz, 2H), 7.09 (d, J = 7.8 Hz, 2H), 6.87-6.78 (m, 2H), 3.78 (s, 3H), 3.60-3.47
(m, 2H), 3.43-3.37 (m, 1H), 3.05-2.96 (m, 1H), 2.67 (dd, J = 13.2, 10.4 Hz, 1H), 2.29 (s,
3H), 1.85-1.75 (m, 1H), 1.73 (dd, J = 12.2, 6.8 Hz, 1H), 1.62-1.51 (m, 1H), 1.46 (td, J = 6.9,
3.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 162.9, 136.1, 131.6, 129.8, 129.7, 129.6, 128.6,
114.1, 59.0, 55.6, 49.8, 39.1, 30.3, 23.8, 21.1. IR (KBr): 2873, 2360, 1593, 1496, 1332,
+
1155, 1024, 811, 667, 557 cm-1. HRMS (m/z): [M + H]+ calcd for C19H24NO3S2 : 378.1192;
found: 378.1197.
4.2.19. 1-(2-Tolylsulfonyl)-2-((4-tolylthio)methyl)pyrrolidine (3sa)
Compound 3sa was prepared according to the general procedure and was isolated as
pale yellow oil (62.4 mg, 69% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.35 (d, J = 6.7 Hz, 1H),
7.24-7.11 (m, 4H), 7.02 (d, J = 5.6 Hz, 2H), 3.87 (d, J = 3.5 Hz, 1H), 3.25 (q, J = 6.1, 5.6 Hz,
3H), 2.68-2.56 (m, 1H), 2.53 (s, 3H), 2.24 (s, 3H), 1.97-1.66 (m, 4H). 13C NMR (101 MHz,
CDCl3) δ 138.0, 137.1, 136.3, 132.8, 131.5, 129.8, 129.8, 129.4, 126.1, 58.8, 48.9, 38.5,
30.4, 24.1, 21.0, 20.7. IR (KBr): 2972, 2873, 1683, 1492, 1315, 1068, 806, 709, 611, 491
+
cm-1. HRMS (m/z): [M + H]+ calcd for C19H24NO2S2 : 362.1243; found: 362.1246.
4.2.20. 1-((4-Chlorophenyl)sulfonyl)-2-((4-tolylthio)methyl)pyrrolidine (3ta)
27

Compound 3ta was prepared according to the general procedure and was isolated as
pale yellow oil (53.7 mg, 62% yield) after flash chromatography (petroleum ether: ethyl
acetate = 50: 1, v/v). 1H NMR (400 MHz, CDCl3) δ 7.49 (dd, J = 7.4, 3.8 Hz, 2H), 7.36-7.25
(m, 4H), 7.13-7.06 (m, 2H), 3.59-3.37 (m, 3H), 3.00 (d, J = 9.0 Hz, 1H), 2.75-2.59 (m, 1H),
2.30 (s, 3H), 1.89-1.69 (m, 2H), 1.64-1.43 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 139.2,
136.4, 135.4, 131.3, 130.1, 129.8, 129.3, 128.9, 59.2, 49.8, 39.1, 30.3, 23.8, 21.1. IR (KBr):
2923, 2871, 1585, 1475, 1350, 1163, 1091, 827, 756, 628, 580, 482 cm-1. HRMS (m/z):
+
[M + H]+ calcd for C18H21ClNO2S2 : 382.0697; found: 382.0695.
4.2.21. 5,5-Diphenyl-2-((4-tolylthio)methyl)-1-tosylpiperidine (3ua)
Compound 3ua was prepared according to the general procedure and was isolated as
white solid (64.7 mg, 49% yield) after flash chromatography (petroleum ether: ethyl
1
acetate = 50: 1, v/v). m.p. 129-132 °C. H NMR (400 MHz, CDCl3) δ 7.38-7.26 (m, 4H),
7.16 (d, J = 7.9 Hz, 6H), 7.10 (dd, J = 7.7, 2.6 Hz, 4H), 7.03 (dd, J = 7.8, 2.7 Hz, 4H), 4.63 (d,
J = 13.2 Hz, 1H), 3.75 (dd, J = 10.7, 4.7 Hz, 1H), 3.13 (dd, J = 13.2, 3.1 Hz, 1H), 2.95 (t, J =
12.5 Hz, 1H), 2.86 (d, J = 13.0 Hz, 1H), 2.41-2.32 (m, 1H), 2.29 (s, 3H), 2.26 (s, 3H),
2.18-2.06 (m, 1H), 2.04 (d, J = 14.3 Hz, 1H), 1.49 (q, J = 10.3 Hz, 1H). 13C NMR (101 MHz,
CDCl3) δ 147.2, 143.5, 143.3, 137.0, 136.9, 131.1, 130.9, 129.8, 129.6, 128.5, 128.4, 128.0,
127.5, 126.6, 126.4, 126.1, 51.6, 48.5, 45.7, 31.7, 28.8, 21.8, 21.5, 21.1. IR (KBr): 2954,
2864, 2360, 1494, 1340, 1159, 947, 811, 700, 663, 549 cm-1. HRMS (m/z): [M + H]+ calcd
+
for C32H34NO2S2 : 528.2025; found: 528.2030.
4.2.22. 8-((4-Tolylthio)methyl)-7-tosyl-7-azaspiro[4.5]decane (3va)
Compound 3va was prepared according to the general procedure and was isolated as
28