Iodine-Mediated Coupling of Cyclic Amines with Sulfonyl Hydrazides: an Efficient Synthesis of Vinyl Sulfone Derivatives

Article abstract of DOI:10.1002/ejoc.202001510

An efficient iodine-mediated coupling of cyclic amines with sulfonyl hydrazides is reported. This transformation opens a new route to the synthesis of vinyl sulfones derivatives, which is a common structural motif in natural products and pharmaceuticals. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.

Full text of DOI:10.1002/ejoc.202001510

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Iodine-mediated coupling of cyclic amines with sulfonyl
hydrazides: an efficient synthesis of vinyl sulfone derivatives
Authors: Xiaona Rong, Jingwen Guo, Zheqi Hu, Lehao Huang, Yugui
Gu, Yuepiao Cai, Guang Liang, and Qinqin Xia
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001510
Link to VoR: https://doi.org/10.1002/ejoc.202001510
01/2020

10.1002/ejoc.202001510
European Journal of Organic Chemistry
FULL PAPER
Iodine-mediated coupling of cyclic amines with sulfonyl
hydrazides: an efficient synthesis of vinyl sulfone derivatives
Xiaona Rong,[a, b, c] Jingwen Guo,[a] Zheqi Hu,[a] Lehao Huang, [a] Yugui Gu,*[b] Yuepiao Cai, [a] Guang
Liang, [a] and Qinqin Xia*[a]
[a]
[b]
[c]
X. Rong, J. Guo, Z. Hu, L, Huang, Prof. Y. Cai, Prof. G. Liang, Prof. Q. Xia
School of Pharmaceutical Sciences
Wenzhou Medical University
Wenzhou 325035 (P. R. China)
E-mail: zdxiaqinqin@163.com
X. Rong, Prof. Y. Gu
College of Chemistry and Materials Engineering
Wenzhou University
Wenzhou 325035 (P. R. China)
E-mail: guyugui@163.com
X. Rong
Wenzhou Institute, University of CAS
Wenzhou, 325011, China
Supporting information for this article is given via a link at the end of the document.
Abstract: An efficient iodine-mediated coupling of cyclic amines with
sulfonyl hydrazides is herein reported. This transformation opens a
new route to the synthesis of vinyl sulfones derivatives, which is a
common structural motif in natural products and pharmaceuticals.
Tentative mechanistic studies suggest that this reaction is likely to
involve a radical process.
by several groups.[5f, 9] Compared with other sulfonation agents,
sulfonyl hydrazides are insensitive to air and moisture, are easy
to prepare, and yield eco-friendly by-products. Herein, we report
a method for the synthesis of vinyl sulfones via the iodine-
mediated coupling of cyclic amines with sulfonyl hydrazides
(Scheme 1).
Introduction
Vinyl sulfone derivatives are key functional units with significant
synthetic value as building blocks in organic transformations[1] as
Scheme 1. Coupling of cyclic amines with sulfonyl hydrazides
they show
a
broad range of useful biological and
pharmacological activities.[2] Therefore, considerable efforts
have been devoted to developing methodologies for the
synthesis of vinyl sulfones. Conventional methods for vinyl
sulfone synthesis include Knoevenagel condensation[3] and the
Horner–Emmons reaction.[4] In recent years, the direct coupling
of alkenes or alkynes with sodium sulphinates has been
developed for the synthesis of vinyl sulphones.[5] In addition,
cinnamic acids or phenylpropiolic acids have also been reacted
with sodium sulfinates to form vinyl sulfones.[6]
Amines and their derivatives are essential building blocks for
the preparation of pharmaceuticals and natural products.[7] In
particular, many C(3)-functionalized amines have remarkable
biological activities. Therefore, the development of synthetic
methods for the C(3)-H functionalization of amines has been a
hot topic in organic synthesis.[8] For example, Yuan and co-
workers developed the I2/TBHP-mediated β-C–H sulfonylation of
triethylamine.[8h] Recently, Talbot and co-workers proposed a
novel oxidative β-C–H sulfonylation of cyclic amines using N-
iodosuccinimide (NIS) as the oxidant.[8e] Lee and co-workers
reported the synthesis of β-amidovinyl sulfones by the
electrochemical coupling of arylsulfonyl hydrazides and tertiary
amines.[8i]
Results and Discussion
We started our investigations with 1-phenylpiperidine 1a and 4-
methylbenzene p-toluenesulfonyl hydrazide 2a as model
substrates. Several parameters, including the iodine source,
solvent, and additives, were analysed to investigate their impact
on the reaction outcome, and the results are listed in Table 1.
Initially, the reaction was carried out using NIS as the iodine
source at 80 °C. Gratifyingly, the desired product was obtained
in 35% yield after 12 h (Table 1, entry 1). Inspired by this result,
the reaction iodine sources were further examined, and a higher
yield was obtained when I2 was used (Table 1, entries 2 and 3).
Then, various bases were tested and NaHCO3 was found to be
optimal, giving the desired product in 71% yield (Table 1, entries
4–9). Solvent screening revealed that 1,4-dioxane was the most
suitable (entries 10–14). The yield of 3a decreased severely
when iodine sources, oxidants, and additives were absent
(entries 15–19). Obviously, these factors play a pivotal role in
the reaction system. Other temperatures (60 and 100 °C) were
further tested, and the yield of 3a increased to 83% at 100 °C
(entries 20 and 21). Finally, the effect of the reaction time was
also investigated, and 3.0 h was found to be optimal (entries 22
and 23).
Recently, readily accessible sulfonyl hydrazides have received
considerable attention as excellent synthons for many organic
transformations. Sulfonylation reactions via sulfonyl radicals
generated in situ from sulfonyl hydrazides have been developed
1
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
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Table 1. Optimization of Reaction Conditions. [a]
Iodine
Yield
(%)
Entry
Oxidant
Base
Solvent
source
1
2
NIS
NaI
TBHP
TBHP
Na2CO3
Na2CO3
THF
THF
35
trace
3
I2
TBHP
Na2CO3
THF
51
4
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
-
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
-
K2CO3
THF
57
49
71
65
33
28
47
65
81
0
5
Cs2CO3
NaHCO3
CH3COONa
NaOH
THF
6
THF
7
THF
8
THF
9
Et3N
THF
10
11
12
13
14
15[b]
16
17[c]
18
19
20[d]
21[e]
22[f]
23[g]
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
-
DCE
MeCN
1,4-dioxane
H2O
toluene
59
37
0
Scheme 2. Reaction of N-Benzyl piperidine 1a with various Sulfonyl
Hydrazide. Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmo1), TBHP (0.6
mmol), I2 (0.3 mmol), NaHCO3 (0.4 mmol), 1,4-dioxane (2 mL), 100 °C, 3
h.
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
I2
I2
I2
I2
I2
I2
I2
55
0
The scope of this reaction with a variety of piperidines was
also investigated, as illustrated in Scheme 3. A variety of N-aryl
piperidine derivatives, including methyl, tert-butyl, n-butyl, and
trimethyl groups on the aromatic ring, readily participated in the
reaction (4a–4d). N-Aryl piperidines with halogen substituents (-
F, -Cl, -Br) could also serve as practical substrates for the
reaction (4e–4h). N-Aryl piperidines bearing electron-donating
substituents also delivered vinyl sulfones in moderate yields (4i–
4k). The more bulky substrates 1-biphenyl-4-yl-piperidine and 1-
naphthalen-1-yl-piperidine also efficiently reacted with 2a,
affording products in 79% and 76% yields, respectively (4l and
4m). Heteroaryl piperidines gave the corresponding products in
low yields (4n). The piperidine ring bearing a substituent in the
4-position increases the steric hindrance for sulfonylation.
However, 4-methyl-1-phenyl-piperidine was also an effective
substrate in this transformation, furnishing the corresponding
product 4o in good yields up to 83%. When we increased the
ring size of the cyclic amine, a poor yield of 31% was obtained
(4p). To our delight, the reaction was also compatible with N-
benzyl piperidines and gave the corresponding products in
moderate yields (4q–4v). Moreover, the reaction was also
tolerant and selective towards N-alkyl substituents on the amine,
where the cyclohexyl example performed well with a yield of
47% (4w). Thus, the overall reaction offers excellent functional
group tolerance.
TBHP
TBHP
TBHP
TBHP
TBHP
0
NaHCO3
NaHCO3
NaHCO3
NaHCO3
61
83
74
91
[a] Reaction conditions: la (0.2 mmol), 2a (0.4 mmol), oxidant (0.6 mmol),
iodine source (0.3 mmol), addictive (0.4 mmol), solvent (2 mL), 80 °C, 12
h. [b] I2 0.5equiv. [c] TBHP 1.5 equiv. [d] at 60 °C. [e] at 100 °C. [f] at
100 °C, for 1 h. [g] at 100 °C, for 3 h.
With the optimized reaction conditions in hand, we next
explored the substrate scope of the reaction (Scheme 2).
Arylsulfonyl hydrazides bearing either electron-donating or
electron-withdrawing substituents readily reacted with 1a to
afford the desired products in moderate to good yields (3a–3j).
Generally, arylsulfonyl hydrazides with electron-withdrawing
groups (3e–3h) gave higher yields than those with electron-
donating groups (3i and 3j). To our delight, biphenyl sulfonyl
hydrazide, 1-naphthyl sulfonyl hydrazide, and 2-naphthyl
sulfonyl hydrazide with fused rings were also suitable reactants
and gave the corresponding products in moderate yields (3k–
3m). Moreover, an alkyl sulfonyl hydrazide afforded the
corresponding product in 29% yield (3n).
Furthermore,
a
scale-up reaction was performed to
demonstrate the practicability of the developed protocol (10
mmol scale). To our satisfaction, the reaction proceeded
smoothly under the optimized conditions to provide product 3a in
68% yield (Scheme 4).
2
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
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Scheme 5. Reaction in the presence of a free-radical scavenger.
Based on our experimental results and previous reports, a
proposed reaction pathway is proposed in Scheme 6. Initially,
TBHP decomposes to generate tert-butoxyl and tert-butylperoxy
radicals with the assistance of an iodide anion. Subsequently,
the hydrogen atom at the α-carbon of substrate 1a is abstracted
by the tert-butoxyl radical to form α-amino radical A. Then, the
single-electron oxidation of radical A by iodine provides iminium
ion B, which is deprotonated to afford enamine C.[10] In the
meantime, the tert-butoxyl radical abstracts a hydrogen atom
from sulfonyl hydrazide 2a, which initiates the generation of
sulfonyl radicals (D) and the release of molecular nitrogen.[5f, 9d,
11]
Afterwards, the radical addition reaction of D and enamine C
generates carbon radical E. Finally, radical E reacts with iodine
to generate iodosulfone F, which undergoes HI elimination
assisted by NaHCO3 to afford the final product 3a.
Scheme 3. Substrate scope with various piperidines. Reaction
conditions: l (0.2 mmol), 2a (0.4 mmol), TBHP (0.6 mmol), I2 (0.3 mmol),
NaHCO3 (0.4 mmol), 1,4-dioxane (2 mL), 100 °C, 3 h.
Scheme 6. Proposed Mechanism
Scheme 4. Gram scale application.
Conclusion
To gain more insight into the reaction mechanism, some
control experiments were explored (Scheme 5). When the
reaction was performed in the presence of the free radical
scavenger 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO, 1.0
equiv.), product 3a was obtained in 13% yield. When TEMPO
(2.5 equiv.) was added to the reaction, no conversion of product
3a was observed. These results indicate that the transformation
may proceed via a radical process.
In summary, an iodine-mediated coupling of cyclic amines with
sulfonyl hydrazides was developed. In this work, for the first time,
sulfonyl hydrazides were used for the sulfonylation of cyclic
amines. This system provides a both mild and easy-to-handle
method for the synthesis of biologically active vinyl sulfones and
shows potential as a new avenue for the further development of
sulfonylation transformations.
Experimental Section
General information. All of the reagents and solvents were
purchased from commercial suppliers and used without further
purification. All experiments were carried out under air, and
3
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
FULL PAPER
oven-dried glassware was used in all cases. 1H and 13C NMR
spectra were recorded at 500 and 125 MHz, respectively. 1H
NMR and 13C NMR chemical shifts are reported in ppm using
tetramethylsilane (TMS) as an internal standard or residual
nondeuterated solvent peak as an internal standard. High-
resolution mass spectra were recorded on an ESI-Q-TOF mass
spectrometer.
7.36 (t, J = 8.0 Hz, 2H), 7.20-7.13 (m, 2H), 7.09 (d, J = 13.4, 7.5
Hz, 3H), 3.60-3.53 (m, 2H), 2.27 (t, J = 6.2 Hz, 2H), 2.02-1.95 (m,
2H); 13C NMR (126 MHz, CDCl3) δ 164.88 (d, JC-F = 254.0 Hz),
145.30, 139.60, 138.11 (d, JC-F = 2.8 Hz), 129.78 (d, JC-F = 9.5
Hz), 129.53, 123.63, 117.90, 116.10 (d, JC-F = 22.4 Hz), 107.42,
45.94, 21.13, 20.00; HRMS (ESI) calcd for C17H16FNO2S [M+H]+:
318.0959. Found: 318.0959.
General procedures D the preparation of 3a-4w. An oven-
dried Schlenk tube equipped with a magnetic stir bar was
charged with piperidines 1 (0.2 mmol), sulfonyl hydrazides 2
(0.4mmol), I2 (0.3 mmol), NaHCO3 (0.4 mmol), TBHP (0.6 mmol)
and 1,4-dioxane (2 mL). The mixture was stirred at 100 °C for 3
h under air. After completion of the reaction, the mixture was
then cooled to room temperature, diluted with 30 mL of H2O, and
extracted with EtOAc (3×20 mL). The combined organic extracts
were dried over Na2SO4, filtered, and concentrated under
vacuum. The residue was purified by column chromatography
on silica gel to give the products.
5-((4-chlorophenyl)sulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3f). Light yellow solid, 87% yield, M.p. 122-
124 °C; 1H NMR (500 MHz, CDCl3) δ 7.85 (s, 1H), 7.82-7.77 (m,
2H), 7.48-7.43 (m, 2H), 7.36 (m, J = 8.4, 7.6 Hz, 2H), 7.12-7.07
(m, 7.6 Hz, 3H), 3.60-3.53 (m, 2H), 2.27 (t, J = 6.2 Hz, 2H), 2.02-
1.95 (m, 2H); 13C NMR (126 MHz,CDCl3) δ 145.26, 140.59,
139.87, 138.58, 129.55, 129.22, 128.61, 123.72, 117.95, 107.10,
45.98, 21.11, 19.99; HRMS (ESI) calcd for C17H19ClNO2S
[M+H]+: 334.0663. Found: 334.0668.
5-((4-nitrophenyl)sulfonyl)-1-phenyl-1,2,3,4-
1-phenyl-5-tosyl-1,2,3,4-tetrahydropyridine (3a). Light yellow
solid, 91% yield, M.p. 133-135 °C; 1H NMR (500 MHz, CDCl3) δ
7.85 (s, 1H), 7.75 (d, J = 8.2 Hz, 2H), 7.37-7.32 (m, 2H), 7.29 (d,
J = 8.1 Hz, 2H), 7.10-7.07 (m, 3H), 3.58-3.53 (m, 2H), 2.41 (s,
3H), 2.27 (t, J = 6.2 Hz, 2H), 2.00-1.93 (m, 2H); 13C NMR (126
MHz, CDCl3) δ 145.39, 142.84, 139.07, 139.04, 129.56, 129.49,
127.17, 123.37, 117.74 , 108.13, 45.85, 21.51, 21.18, 20.04;
HRMS (ESI) calcd for C18H19NO2S [M+Na]+: 336.1029. Found:
336.1046.
tetrahydropyridine (3g). Orange-red solid, 83% yield, M.p. 148-
150 °C; H NMR (500 MHz, CDCl3) δ 8.34 (d, J = 8.8 Hz, 2H),
1
8.05 (d, J = 8.8 Hz, 2H), 7.90 (s, 1H), 7.39 (t, J = 8.0 Hz, 2H),
7.15 (t, J = 7.4 Hz, 1H), 7.13 – 7.08 (m, 2H), 3.64 – 3.58 (m, 2H),
2.31 (t, J = 6.2 Hz, 2H), 2.04 – 1.99 (m, 2H); 13C NMR (126
MHz, CDCl3) δ 149.77, 148.01, 145.08, 141.25, 129.64, 128.29,
124.29, 124.25, 118.26, 105.64, 46.18, 21.02, 19.96; HRMS
(ESI) calcd for C17H16N2O4S [M+H]+: 345.0904. Found: 345.0909.
1-phenyl-5-((4-(trifluoromethyl)phenyl)sulfonyl)-1,2,3,4-
1-phenyl-5-(phenylsulfonyl)-1,2,3,4-tetrahydropyridine (3b).
White solid, 80% yield, M.p. 146-148 °C; 1H NMR (500 MHz,
CDCl3) δ 7.88-.7.86 (m, 3H), 7.56-7.46 (m, 3H), 7.35 (t, J = 7.9
Hz, 2H), 7.09 (t, J = 7.9 Hz, 3H), 3.58-3.53 (m, 2H), 2.28 (t, J =
6.2 Hz, 2H), 2.01-1.94 (m, 2H); 13C NMR (126 MHz, CDCl3) δ
145.33, 141.93, 139.46, 132.18, 129.51, 128.96, 127.09, 123.50,
117.80, 107.62, 45.89, 21.14, 20.02; HRMS (ESI) for
C17H17NO2S [M+H]+: 300.1053. Found: 300.1049.
tetrahydropyridine (3h). White solid, 85% yield, M.p. 148-
150 °C; H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.2 Hz, 2H),
1
7.89 (s, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.37 (t, J = 8.0 Hz, 2H),
7.15 – 7.05 (m, 3H), 3.63 – 3.56 (m, 2H), 2.30 (t, J = 6.1 Hz, 2H),
2.06 – 1.94 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 145.69,
145.19, 140.59, 133.82 (q, JC-F = 32.8 Hz), 129.58, 127.59,
126.11 (q, JC-F = 3.6 Hz), 123.95, 123.41 (q, JC-F = 273.2 Hz),
118.10, 106.35, 46.07, 21.07, 19.98; HRMS (ESI) calcd for
C18H16F3NO2S [M+H]+: 368.0927. Found: 368.0933.
1-phenyl-5-(o-tolylsulfonyl)-1,2,3,4-tetrahydropyridine (3c).
White solid, 69% yield, M.p. 124-126 °C; 1H NMR (500 MHz,
CDCl3) δ 8.03 (d, J = 7.9 Hz, 1H), 7.87 (s, 1H), 7.44 (t, J = 7.5
Hz, 1H), 7.38-7.33 (m, 3H), 7.27 (d, J = 7.1 Hz, 1H), 7.12-7.06
(m, 3H), 3.61-3.57 (m, 2H), 2.61 (s, 3H), 2.19 (t, J = 6.3 Hz, 2H),
5-((4-methoxyphenyl)sulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3i). Light yellow oil, 60% yield; 1H NMR
(500 MHz, CDCl3) δ 7.84 (s, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.34 (t,
J = 7.8 Hz, 2H), 7.08 (t, J = 7.1 Hz, 3H), 6.96 (d, J = 8.5 Hz, 2H),
1.99-1.92 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 145.41, 139.78, 3.85 (s, 3H), 3.57 – 3.52 (m, 2H), 2.27 (t, J = 6.1 Hz, 2H), 1.98 –
138.60, 137.31, 132.56, 132.54, 129.80, 129.55, 126.20, 123.46,
117.81, 106.99, 46.02, 21.22, 20.17 , 19.99; HRMS (ESI) calcd
for C18H19NO2S [M+Na]+: 336.1029. Found: 336.1035.
1.95 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 162.62, 145.43,
138.72, 133.69, 129.47, 129.22, 123.30, 117.71, 114.13, 108.55,
55.57, 45.84, 21.21, 20.03; HRMS (ESI) calcd for C18H19NO3S
[M+H]+: 330.1158. Found: 330.1167.
5-((4-(tert-butyl)phenyl)sulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3d). Dark yellow oil, 70% yield; 1H NMR
(500 MHz, CDCl3) δ 7.78 (s, 1H), 7.70 (d, J = 8.5 Hz, 2H), 7.42
(d, J = 8.5 Hz, 2H), 7.30-7.24 (m, 2H), 7.00 (d, J = 8.1 Hz, 3H),
3.52-3.45 (m, 2H), 2.23 (t, J = 6.2 Hz, 2H), 1.95-1.85 (m, 2H),
1.26 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 155.82, 145.41,
139.12, 138.95, 129.49, 126.94, 125.92, 123.36, 117.74, 108.12,
45.85, 35.09, 31.15, 21.19, 20.05; HRMS (ESI) calcd for
C21H25NO2S [M+H]+: 356.1679. Found: 356.1680.
5-((3,4-dimethoxyphenyl)sulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3j). Yellow oil, 67% yield; H NMR (500
1
MHz, CDCl3) δ 7.85 (s, 1H), 7.48 – 7.46 (m, 1H), 7.37 – 7.33 (m,
3H), 7.09 (t, J = 7.4 Hz, 3H), 6.93 (d, J = 8.4 Hz, 1H), 3.93 (d, J
= 2.0 Hz, 6H), 3.59 – 3.55 (m, 2H), 2.29 (t, J = 6.2 Hz, 2H), 2.02
– 1.96 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 152.26, 149.06,
145.41, 138.75, 133.79, 129.49, 123.35, 121.05, 117.71, 110.66,
109.79, 108.36, 56.27, 56.16, 45.84, 21.20, 20.07; HRMS (ESI)
calcd for C19H21NO4S [M+H]+: 360.1264. Found: 360.1268.
5-((4-fluorophenyl)sulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3e). Light yellow solid, 60% yield, M.p.
153-155 °C; 1H NMR (500 MHz, CDCl3) δ 7.89-7.84 (m, 3H),
5-([1,1'-biphenyl]-4-ylsulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3k). Light yellow oil, 70% yield; 1H NMR
4
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
FULL PAPER
(500 MHz, CDCl3) δ 7.95 – 7.89 (m, 3H), 7.70 (d, J = 8.2 Hz, 2H), CDCl3) δ 7.74 (s, 1H), 7.66 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 8.0
7.60 (d, J = 7.4 Hz, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.42 – 7.33 (m,
3H), 7.09 (d, J = 8.1 Hz, 3H), 3.60 – 3.55 (m, 2H), 2.34 (t, J =
6.0 Hz, 2H), 2.03 – 1.97 (m, 2H); 13C NMR (126 MHz, CDCl3) δ
145.38, 145.09, 140.63, 139.58, 139.49, 129.52, 129.00, 128.32,
127.64, 127.61, 127.32, 123.52, 117.86, 107.84, 45.94, 21.20,
Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 6.91 (d, J = 7.9 Hz, 2H), 3.47 –
3.42 (m, 2H), 2.50 (t, J = 7.7 Hz, 2H), 2.32 (s, 3H), 2.18 (t, J =
6.1 Hz, 2H), 1.91 – 1.83 (m, 2H), 1.53 – 1.44 (m, 2H), 1.31 –
1.22 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H); 13C NMR (126 MHz,
CDCl3) δ 143.27, 142.79, 139.51, 139.11, 138.26, 129.55,
20.08; HRMS (ESI): m/z calcd for C23H21NO2S [M+H]+: 376.1366. 129.36, 127.10, 117.89, 106.99, 46.05, 34.82, 33.66, 22.27,
Found: 376.1396.
21.49, 21.17, 20.01, 13.93; HRMS (ESI) calcd for C22H27NO2S
[M+H]+: 370.1835. Found: 370.1846.
5-(naphthalen-1-ylsulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3l). Light yellow solid, 65% yield, M.p. 144-
146 °C; H NMR (500 MHz, CDCl3) δ 8.76 (d, J = 8.6 Hz, 1H),
1-mesityl-5-tosyl-1,2,3,4-tetrahydropyridine (4d). Yellow solid,
75% yield, M.p. 166-168 °C; H NMR (500 MHz, CDCl3) δ 7.72
1
1
8.32 (d, J = 7.3 Hz, 1H), 8.05 (d, J = 9.5 Hz, 2H), 7.93 (d, J = 8.1
Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.56 (t, J = 7.8 Hz, 2H), 7.38 (t,
J = 7.9 Hz, 2H), 7.11 (t, J = 9.0 Hz, 3H), 3.55 – 3.48 (m, 2H),
(d, J = 8.2 Hz, 2H), 7.28 (d, J = 7.6 Hz, 3H), 6.89 (s, 2H), 3.27 –
3.23 (m, 2H), 2.41 (s, 3H), 2.31 – 2.25 (m, 5H), 2.17 (s, 6H),
1.99-1.94 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 143.76,
2.18 (t, J = 6.2 Hz, 2H), 1.92 – 1.84 (m, 2H); 13C NMR (126 MHz, 142.31 , 141.22, 139.91, 137.52, 135.67, 129.45,129.41, 126.90,
CDCl3) δ 145.48, 139.61, 135.89, 134.33, 134.04, 129.90,
129.56, 129.00, 128.47, 127.89, 126.61, 124.62, 124.35, 123.53,
117.97, 108.13, 46.01, 21.11, 20.12; HRMS (ESI) calcd for
C21H19NO2S [M+H]+: 350.1209. Found: 350.1223.
101.71, 47.27, 21.47, 21.23, 20.90, 19.83, 17.86; HRMS (ESI)
calcd for C21H25NO2S [M+H]+: 356.1679. Found: 356.1680.
1-(4-fluorophenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4e).
Yellow solid, 70% yield, M.p. 174-176 °C; 1H NMR (500 MHz,
CDCl3) δ 7.74 (s, 3H), 7.29 (d, J = 7.6 Hz, 2H), 7.06 – 7.03 (m,
4H), 3.53 – 3.51 (m, 2H), 2.43 – 2.42 (m, 3H), 2.28 – 2.26 (m,
2H), 1.99 – 1.95 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 159.15
(d, JC-F = 243.8 Hz), 142.87, 141.92 (d, JC-F = 2.3 Hz), 139.27,
138.98, 129.55, 127.17, 119.66 (d, JC-F = 7.9 Hz), 116.16 (d, JC-F
= 22.8 Hz), 108.11, 46.40, 21.48, 21.16, 19.92; HRMS (ESI)
calcd for C18H18FNO2S [M+H]+: 332.1115. Found: 332.1122.
5-(naphthalen-2-ylsulfonyl)-1-phenyl-1,2,3,4-
tetrahydropyridine (3m). Light yellow solid, 67% yield, M.p.
1
140-142 °C; H NMR (500 MHz, CDCl3) δ 8.46 (s, 1H), 7.97 –
7.92 (m, 3H), 7.89 (d, J = 7.8 Hz, 1H), 7.83 – 7.81 (m, 1H), 7.63
– 7.57 (m, 2H), 7.38 – 7.34 (m, 2H), 7.11 – 7.08 (m, 3H), 3.57 –
3.51 (m, 2H), 2.30 (t, J = 6.2 Hz, 2H), 1.98 – 1.91 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 145.36, 139.58, 138.76, 134.70,
132.33, 129.53, 129.26, 128.52, 128.24, 127.89, 127.34, 123.54,
122.73, 117.85, 107.75, 45.93, 21.17, 20.07; HRMS (ESI) calcd
for C21H19NO2S [M+H]+: 350.1209. Found: 350.1220.
1-(4-chlorophenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4f).
Yellow solid, 66% yield, M.p. 200-202 °C; 1H NMR (500 MHz,
CDCl3) δ 7.78 (s, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.31 – 7.28 (m,
4H), 6.99 (d, J = 8.7 Hz, 2H), 3.53 – 3.49 (m, 2H), 2.42 (s, 3H),
2.27 (t, J = 6.2 Hz, 2H), 1.99 – 1.94 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ 143.96, 143.02, 138.77, 138.42, 129.60, 129.46,
128.54, 127.21, 118.83, 109.24, 45.91, 21.50, 21.11, 19.95;
HRMS (ESI) calcd for C18H18ClNO2S [M+H]+: 348.0820. Found:
348.0825.
5-(methylsulfonyl)-1-phenyl-1,2,3,4-tetrahydropyridine (3n).
Dark yellow oil, 29% yield; 1H NMR (500 MHz, CDCl3) δ 7.69 (s,
1H), 7.34 (t, J = 7.7 Hz, 2H), 7.10 – 7.06 (m, 3H), 3.66-3.59 (m,
2H), 2.93 (s, 3H), 2.49 (t, J = 6.2 Hz, 2H), 2.13 – 2.06 (m, 2H);
13C NMR (126 MHz, CDCl3) δ 145.35, 139.72, 129.49, 123.52,
117.84, 107.32, 45.90, 42.21, 21.20, 20.44; HRMS (ESI) calcd
for C12H15NO2S [M+H]+: 238.0896. Found: 238.0911.
1-(4-bromophenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4g).
1-(p-tolyl)-5-tosyl-1,2,3,4-tetrahydropyridine (4a).[8e] Yellow
solid, 92% yield, M.p. 91-93 °C; 1H NMR (500 MHz, CDCl3) δ
7.81 (s, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H),
7.14 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.1 Hz, 2H), 3.52 (d, J = 4.9
Hz, 2H), 2.40 (s, 3H), 2.31 (s, 3H), 2.26 (t, J = 6.0 Hz, 2H), 1.98
– 1.91 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 143.18, 142.72,
139.43, 139.23, 133.13, 129.98, 129.51, 127.12, 117.94, 107.20,
46.07, 21.47, 21.18, 20.60, 20.03.
Yellow solid, 68% yield, M.p. 200-202 °C; 1H NMR (500 MHz,
CDCl3) δ 7.78 (s, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.6
Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 3.53 –
3.49 (m, 2H), 2.42 (s, 3H), 2.27 (t, J = 6.2 Hz, 2H), 2.00 – 1.93
(m, 2H); 13C NMR (126 MHz, CDCl3) δ 144.41, 143.03, 138.73,
138.27, 132.40, 129.60, 127.23, 119.14, 116.00, 109.46, 45.83,
21.51, 21.11, 19.96; HRMS (ESI) calcd for C18H18BrNO2S
[M+H]+: 392.0314. Found: 392.0325.
1-(4-(tert-butyl)phenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4b). Yellow oil, 85% yield; 1H NMR (500 MHz, CDCl3) δ 7.84 (s,
1H), 7.74 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.6 Hz, 2H), 7.28 (d, J
= 7.9 Hz, 2H), 7.02 (d, J = 8.6 Hz, 2H), 3.60 – 3.49 (m, 2H), 2.41
(s, 3H), 2.27 (t, J = 6.0 Hz, 2H), 1.99 – 1.92 (m, 2H), 1.31 (s,
9H); 13C NMR (126 MHz, CDCl3) δ 153.04, 149.48, 149.30,
145.95, 145.64, 136.06, 133.64, 132.83, 124.05, 113.69, 52.45,
40.81, 37.89, 28.01, 27.70, 26.54; HRMS (ESI) calcd for
C21H20N2O2S [M+H]+: 370.1835. Found: 370.1838.
1-(2,6-dichlorophenyl)-5-tosyl-1,2,3,4-tetrahydropyridine(4h).
White solid, 68% yield, M.p. 156-158 °C; 1H NMR (500 MHz,
CDCl3) δ 7.76 (d, J = 7.9 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 7.30
– 7.27 (m, 3H), 7.21 (t, J = 8.1 Hz, 1H), 3.38 – 3.33 (m, 2H),
2.42 (s, 3H), 2.28 (t, J = 6.2 Hz, 2H), 2.05 – 1.96 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 142.67, 142.64, 140.66, 139.28,
134.98, 129.48, 129.13, 129.00, 127.16, 105.41, 47.06, 21.48,
20.93, 19.76; HRMS (ESI) calcd for C18H17Cl2NO2S [M+Na]+:
404.0249. Found: 404.0248.
1-(4-butylphenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4c).
1-(4-methoxyphenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
1
Yellow oil, 90% yield; Yellow oil, 90% yiled; 1H NMR (500 MHz,
(4i).[8e] Yellow solid, 53% yield, M.p. 176-178 °C; H NMR (500
5
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
FULL PAPER
MHz, CDCl3) δ 7.74 (d, J = 7.5 Hz, 3H), 7.28 (d, J = 10.1 Hz, 2H), 7.7 Hz, 2H), 7.27 (d, J = 8.3 Hz, 2H), 7.14 – 7.09 (m, 3H), 3.67-
7.01 (d, J = 7.4 Hz, 2H), 6.88 (d, J = 7.4 Hz, 2H), 3.80 (s, 3H),
3.51 (s, 2H), 2.41 (s, 3H), 2.26 (t, J = 5.4 Hz, 2H), 1.95 (s, 2H);
13C NMR (126 MHz, CDCl3) δ 156.25, 142.63, 139.97, 139.39,
129.49, 127.09, 119.93, 114.72, 106.43, 55.61, 46.62, 21.45,
21.20, 19.97.
3.60 (m, 1H), 3.56 (m, 1H), 2.67 – 2.60 (m, 1H), 2.41 (s, 3H),
1.82-1.70 (m, 2H), 1.06 (d, J = 6.9 Hz, 3H); 13C NMR (126 MHz,
CDCl3) δ 145.22, 142.66, 140.27, 139.19, 129.51,129.49, 127.13,
123.52, 117.78, 112.47, 41.92, 28.63, 25.13, 21.48, 21.39;
HRMS (ESI) calcd for C19H21NO2S [M+H]+: 328.1366. Found:
328.1373.
1-(3,5-dimethoxyphenyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4j). Yellow oil, 60% yield; 1H NMR (500 MHz, CDCl3) δ 7.74 (s,
1H), 7.66 (d, J = 7.4 Hz, 2H), 7.21 (d, J = 7.5 Hz, 2H), 6.13 (s,
3H), 3.73 (s, 6H), 3.46 – 3.41 (m, 2H), 2.34 (s, 3H), 2.18 (t, J =
6.3 Hz, 2H), 1.88 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 161.61,
147.29, 142.89, 138.92, 129.55, 127.18, 108.44, 96.72, 95.14,
55.49, 46.01, 21.47, 21.17, 20.14; HRMS (ESI) calcd for
C20H23NO4S [M+H]+: 374.1421. Found: 374.1429.
1-phenyl-6-tosyl-2,3,4,5-tetrahydro-1H-azepine (4p). Light
yellow oil, 31% yield; 1H NMR (500 MHz, CDCl3) δ 7.78 (s, 1H),
7.75 (d, J = 8.1 Hz, 2H), 7.35 (t, J = 7.9 Hz, 2H), 7.29 (d, J = 7.9
Hz, 2H), 7.11 (s, 2H), 7.09 (s, 1H), 3.85-3.80 (m, 2H), 2.47 –
2.43 (m, 2H), 2.42 (s, 3H), 1.86 (m, 2H), 1.77 (m, 2H); 13C NMR
(126 MHz, CDCl3) δ 147.38, 144.63, 142.81, 139.08, 129.52,
129.42, 127.30, 123.84, 119.68, 113.75, 51.70, 27.98, 25.95,
25.56, 21.49; HRMS (ESI) calcd for C19H21NO2S [M+H]+:
328.1366. Found: 328.1374.
5-tosyl-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyridine
(4k). Yellow solid, 73% yield, M.p. 152-154 °C; 1H NMR (500
MHz, CDCl3) δ 7.78 – 7.72 (m, 3H), 7.29 (d, J = 8.0 Hz, 2H),
6.26 (s, 2H), 3.88 (s, 6H), 3.82 (s, 3H), 3.56 – 3.50 (m, 2H), 2.42
(s, 3H), 2.27 (t, J = 6.1 Hz, 2H), 2.00 – 1.95 (m, 2H); 13C NMR
(126 MHz,CDCl3) δ 153.81, 142.90, 142.11, 139.41, 138.94,
134.75, 129.56, 127.15, 107.70, 96.41, 61.02, 56.34, 46.61,
21.50, 21.18, 20.07; HRMS (ESI) calcd for C21H25NO5S [M+Na]+:
426.1346. Found: 426.1360.
1-benzyl-5-tosyl-1,2,3,4-tetrahydropyridine (4q).[8e] White
1
solid, 68% yield, M.p. 155-157 °C; H NMR (500 MHz, CDCl3) δ
7.64 (d, J = 8.0 Hz, 2H), 7.41 (s, 1H), 7.26 (d, J = 7.3 Hz, 2H),
7.22 (d, J = 7.0 Hz, 1H), 7.20 – 7.17 (m, 2H), 7.11 (d, J= 7.3 Hz,
2H), 4.21 (s, 2H), 2.91 – 2.80 (m, 2H), 2.32 (s, 3H), 2.07 (t, J =
6.1 Hz, 2H), 1.71 – 1.63 (m, 2H); 13C NMR (126 MHz, CDCl3) δ
144.15, 142.29, 139.89, 136.53, 129.41, 128.83, 127.94, 127.48,
126.88, 101.24, 59.68, 45.02, 21.43, 21.01, 19.67; HRMS (ESI)
calcd for C19H21NO2S [M+H]+: 328.1366. Found: 328.1365.
1-([1,1'-biphenyl]-4-yl)-5-tosyl-1,2,3,4-tetrahydropyridine (4l).
Light yellow solid, 71% yield, M.p. 168-170 °C; 1H NMR (500
MHz, CDCl3) δ 7.90 (s, 1H), 7.76 (d, J = 7.9 Hz, 2H), 7.57 (t, J =
7.7 Hz, 4H), 7.43 (t, J = 7.5 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H),
7.29 (d, J = 7.9 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 3.61-3.55 (m,
2H), 2.41 (s, 3H), 2.29 (t, J = 6.1 Hz, 2H), 2.02 – 1.96 (m, 2H);
13C NMR (126 MHz, CDCl3) δ 144.55, 142.88, 140.17, 139.03,
138.73, 136.22, 129.57, 128.85, 128.06, 127.21, 127.18, 126.75,
117.87, 108.62, 45.86, 21.50, 21.20, 20.07; HRMS (ESI) calcd
for C24H23NO2S [M+Na]+: 412.1342. Found: 412.1360.
1-(4-fluorobenzyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4r).
1
Yellow oil, 65% yield; H NMR (500 MHz, CDCl3) δ 7.72 (d, J =
7.5 Hz, 2H), 7.47 (s, 1H), 7.27 (s, 2H), 7.20 – 7.15 (m, 2H), 7.04
(t, J = 8.1 Hz, 2H), 4.27 (s, 2H), 2.92 (s, 2H), 2.41 (s, 3H), 2.16 (t,
J = 5.6 Hz, 2H), 1.79 – 1.73 (m, 2H); 13C NMR (126 MHz, CDCl3)
δ 162.48 (d, JC-F = 247.0 Hz), 143.89, 142.38, 139.75, 132.25 (d,
JC-F = 2.9 Hz), 129.42, 129.19 (d, JC-F = 8.2 Hz), 126.90, 115.75
(d, JC-F = 21.7 Hz), 101.77, 58.94, 44.95, 21.41, 21.00, 19.65;
HRMS (ESI) calcd for C19H20FNO2S [M+H]+: 346.1272. Found:
346.1286.
1-(naphthalen-1-yl)-5-tosyl-1,2,3,4-tetrahydropyridine (4m).
Light yellow oil, 80% yield; 1H NMR (500 MHz, CDCl3) δ 7.89 (d,
J = 8.8 Hz, 1H), 7.84 (d, J = 8.7 Hz, 1H), 7.77 (d, J = 8.0 Hz, 3H), 1-(4-chlorobenzyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4s).
7.63 (s, 1H), 7.55 – 7.51 (m, 2H), 7.44 (t, J = 7.8 Hz, 1H), 7.30
(d, J = 7.9 Hz, 2H), 7.26 (s, 1H), 3.57 (s, 2H), 2.42 (s, 3H), 2.39
(t, J = 6.2 Hz, 2H), 2.09 – 2.02 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ 143.47, 143.22, 142.68, 139.43, 134.81, 129.55,
129.20, 128.70, 127.29, 127.13, 126.79, 126.52, 125.64, 122.70,
122.52, 105.90, 49.49, 21.57, 21.51, 20.22; HRMS (ESI) calcd
for C22H21NO2S [M+H]+: 364.1366. Found: 364.1366.
Light yellow soild, 57% yield; M.p. 104-106 °C; 1H NMR (500
MHz, CDCl3) δ 7.63 (d, J = 8.1 Hz, 2H), 7.38 (s, 1H), 7.24 (d, J =
8.1 Hz, 2H), 7.21 – 7.18 (m, 2H), 7.06 (d, J = 8.3 Hz, 2H), 4.18
(s, 2H), 2.90 – 2.80 (m, 2H), 2.33 (s, 3H), 2.08 (t, J = 6.1 Hz, 2H),
1.71 – 1.64 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 143.87,
142.42, 139.68, 135.07, 133.82, 129.44, 129.01, 128.86, 126.89,
101.91, 58.95, 45.01, 21.44, 20.98, 19.62; HRMS (ESI) calcd for
C19H20ClNO2S [M+Na]+: 384.0801. Found: 384.0809.
5-tosyl-3,4-dihydro-2H-1,2'-bipyridine (4n). Yellow solid, 20%
yield, M.p. 170-172 °C; 1H NMR (500 MHz, CDCl3) δ 8.50 (s,
1H), 8.32 (d, J = 4.3 Hz, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.65 (t, J
= 7.8 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 6.93 (t, J = 7.4 Hz, 2H),
3.74 – 3.67 (m, 2H), 2.41 (s, 3H), 2.30 (t, J = 6.2 Hz, 2H), 2.01 –
1.92 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 153.27, 147.17,
142.10, 137.60, 137.32, 135.06, 128.60, 126.37, 116.58, 110.35,
107.68, 42.01, 20.50, 20.13, 19.49; HRMS (ESI) calcd for
C17H18N2O2S [M+H]+: 315.1162. Found: 315.1160.
1-(4-bromobenzyl)-5-tosyl-1,2,3,4-tetrahydropyridine
(4t).
Light yellow soild, 58% yield, M.p. 117-119 °C; 1H NMR (500
MHz, CDCl3) δ 7.71 (d, J = 8.2 Hz, 2H), 7.48 (s, 1H), 7.46 (s,
2H), 7.28 – 7.27 (m, 2H), 7.08 (d, J = 8.3 Hz, 2H), 4.25 (s, 2H),
2.96 – 2.88 (m, 2H), 2.41 (s, 3H), 2.16 (t, J = 6.1 Hz, 2H), 1.79 –
1.72 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 143.88, 142.43,
139.65, 135.59, 131.99, 129.45, 129.19, 126.90, 121.90, 101.97,
59.02, 45.03, 21.45, 20.99, 19.62. HRMS (ESI) calcd for
C19H20BrNO2S [M+H]+: 406.0471. Found: 406.0469.
4-methyl-1-phenyl-5-tosyl-1,2,3,4-tetrahydropyridine
(4o).
Light yellow solid, 83% yield, M.p. 170-172 °C; 1H NMR (500
1-(4-methoxybenzyl)-5-tosyl-1,2,3,4-tetrahydropyridine (4u).
[8e]
MHz, CDCl3) δ 7.93 (s, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.37 (t, J =
Light yellow solid, 59% yield, M.p. 88-90 °C; 1H NMR (500
6
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
FULL PAPER
MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.49 (s, 1H), 7.26 (d, J =
3.7 Hz, 2H), 7.12 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H),
4.23 (s, 2H), 3.81 (s, 3H), 2.98 – 2.85 (m, 2H), 2.41 (s, 3H), 2.15
(t, J = 6.1 Hz, 2H), 1.79 – 1.69 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ 159.43, 144.08, 142.28, 139.86, 129.40, 128.88,
128.38, 126.88, 114.24, 59.22, 55.32, 44.81, 21.44, 21.00, 19.68.
996; g) B. A. Frankel, M. Bentley, R. G. Kruger, D. G. McCafferty,
J. Am. Chem. Soc. 2004, 126, 3404-3405; h) G. Wang, U.
Mahesh, G. Y. J. Chen, S. Q. Yao, Org. Lett. 2003, 5, 737-740.
[3] S. Chodroff, W. F. Whitmore, J. Am. Chem. Soc. 1950, 72, 1073-
1076.
[4] I. C. Popoff, J. L. Dever, G. R. Leader, J. Org. Chem. 1969, 34,
(4v).[8e]
1128-1130.
1-(4-nitrobenzyl)-5-tosyl-1,2,3,4-tetrahydropyridine
Light yellow solid, 62% yield, M.p. 103-105 °C; 1H NMR (500
MHz, CDCl3) δ 8.21 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 7.8 Hz, 2H),
7.48 (s, 1H), 7.39 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 8.6 Hz, 2H),
4.42 (s, 2H), 2.97 (s, 2H), 2.42 (s, 3H), 2.19 (t, J = 6.0 Hz, 2H),
1.85 – 1.75 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 147.76,
144.15, 143.66, 142.68, 139.35, 129.53, 128.17, 126.96, 124.10,
103.23, 58.82, 45.45, 21.44, 20.99, 19.54.
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Kuhakarn, Eur. J. Org. Chem. 2010, 5633-5641; b) Y. Gao, W. Q.
Wu, Y. B. Huang, K. F. Huang, H. F. Jiang, Org. Chem. Front.
2014, 1, 361-364; c) A. U. Meyer, S. Jager, D. P. Hari, B. Konig,
Adv. Synth. Catal. 2015, 357, 2050-2054; d) Y. D. Sun, A.
Abdukader, D. Lu, H. Y. Zhang, C. J. Liu, Green. Chem. 2017,
19, 1255-1258; e) G. Zhang, J.-G. Fu, Q. Zhao, G.-S. Zhang, M.-
Y. Li, C.-G. Feng, G.-Q. Lin, Chem. Commun. 2020, 56, 4688-
4691; f) S. Tang, Y. Wu, W. Q. Liao, R. P. Bai, C. Liu, A. W. Lei,
Chem. Commun. 2014, 50, 4496-4499; g) L. L. Wang, H. L. Yue,
D. S. Yang, H. H. Cui, M. H. Zhu, J. M. Wang, W. Wei, H. Wang,
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1-(cyclohexylmethyl)-5-tosyl-1,2,3,4-tetrahydropyridine (4w).
Light yellow solid, 47% yield, M.p. 136 -138 °C; 1H NMR (500
MHz, CDCl3) δ 7.69 (d, J = 7.8 Hz, 2H), 7.27 (s, 1H), 7.26 (s,
2H), 3.05 (d, J = 4.5 Hz, 2H), 2.95 (d, J = 7.0 Hz, 2H), 2.39 (s,
3H), 2.14 (t, J = 6.0 Hz, 2H), 1.78 (dd, J = 11.9, 5.9 Hz, 3H),
1.66 (d, J = 12.1 Hz, 2H), 1.31 – 1.14 (m, 5H), 0.87 (dd, J = 21.3,
11.0 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 144.72, 142.08,
140.13, 129.33, 126.79, 100.00, 62.62, 46.10, 36.83, 30.64,
26.33, 25.75, 21.40, 21.10, 19.69; HRMS (ESI) calcd for
C19H27NO2S [M+H]+: 334.1835. Found: 334.1824.
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We are grateful for the financial support from the National
Natural Science Foundation of China (21602159, 21877085),
Zhejiang Provincial Natural Science Foundation of China
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Keywords: sulfonyl hydrazide • cyclic amine • peroxide • radical
• sulfone
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
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10.1002/ejoc.202001510
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
A highly efficient and generally applicable methodology for the construction of vinyl sulfone derivatives from cyclic amines and
sulfonyl hydrazides in one step was developed. This protocol could be applied for the C−S bond formation of N-Aryl piperidines, N-
alkyl piperidines and heteroaryl piperidines with sulfonyl hydrazides.
9
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