Base-Promoted Direct Synthesis of Sulfinates from N -Sulfonyl-hydrazones under Metal-Free Conditions

Article abstract of DOI:10.1055/s-0039-1690754

A base-promoted direct synthesis of sulfinates from N -sulfonylhydrazones is described. Various N -sulfonylhydrazones, derived from aldehydes and ketones, are converted into the corresponding sulfinates in moderate to good yields. This protocol possesses

Full text of DOI:10.1055/s-0039-1690754

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
en
Y.-Z. Ji et al.
Paper
Synthesis
Base-Promoted Direct Synthesis of Sulfinates from N-Sulfonyl-
hydrazones under Metal-Free Conditions
Yuan-Zhao Jia
Qin-Xi Wua
Hui-Jing Li*a,b
Dong-Hui Luoa
Yan-Chao Wu*a,b
O
NHSO2Ar2
DIPEA (1.0 equiv)
S
N
Ar2
+
N2
O
CH3NO2, 90 °C, 2 h
Ar1
R
Ar1
16 examples
moderate to good yields
R
one-pot synthesis
metal-free conditions
0
0
0
0-0
0
0
2-0
1
1
1-7
4
8
4
a School of Marine Science and Technology, Harbin Institute of
Technology, 2 Wenhuaxi Road, Weihai 264209, P. R. of China
b Weihai Institute of Marine Biomedical Industrial Technology,
Wendeng District, Weihai 264400, P. R. of China
lihuijing@iccas.ac.cn
ycwu@iccas.ac.cn
Received: 28.09.2019
Accepted after revision: 08.11.2019
Published online: 20.11.2019
lysts (e.g., copper, iron, and rhodium) and bases under heat-
ing conditions (Scheme 1).21 However, the synthesis of sul-
finates from N-tosylhydrazones is difficult, which has been
accomplished by special strategies such as using the Wittig
ylide in a polar aprotic solvent.22 Despite these advances,
general efficient methods to access sulfinates from N-tosyl-
hydrazones under simple conditions remain in demand.
Considering the importance of sulfinates in the area of
chemical and biological sciences,1–10 based on our recent
work on the sulfinates5b,13a,18c and N-tosylhydrazones,23 we
would like to report here a base-promoted direct synthesis
of sulfinates from N-tosylhydrazones under metal-free con-
ditions (Scheme 1).
DOI: 10.1055/s-0039-1690754; Art ID: ss-2019-f0556-op
Abstract A base-promoted direct synthesis of sulfinates from N-sulfo-
nylhydrazones is described. Various N-sulfonylhydrazones, derived from
aldehydes and ketones, are converted into the corresponding sulfinates
in moderate to good yields. This protocol possesses many advantages
such as readily available and stable starting materials, broad substrate
scope, and metal-free reaction conditions.
Key words sulfinates, hydrazones, DIPEA, carbonyl compounds, sulfo-
nylhydrazines
Sulfinates are one class of the most versatile intermedi-
ates in organic synthesis.1 They display a broad range of bi-
ological activities, such as stimulating the glucose uptake in
muscle cells,2 regulating the mitochondrial function of the
Parkinsonism protein DJ-1,3 employing as chemical probes
in living cells,4 etc.5 In addition, sulfinates behave as both
nucleophilic and electrophilic reagents, which provide con-
venient access to various sulfur compounds including sulf-
oxides,6,7 sulfinamides,8 sulfones,9 and thioethers.10
In general, sulfinates could be produced by sulfination
of sulfinyl cation [ArS=O]+ or sulfinyl radical [ArS=O]• with
alcohols. The sulfinyl cation [ArS=O]+ and radical [ArS=O]•
are in situ generated by activation of various different pre-
cursors, such as sulfinyl chloride,11 sulfinic acids12 (salts),13
sulfonyl chlorides,14 and sulfonylhydrazides,15 or by oxida-
tion of thiols16 and disulfides.17 In addition, other synthetic
methods for sulfinates, such as substitution of benzyl alco-
hols with arylsulfonylmethyl isocyanides,5b,18 are also de-
scribed.19
base
base
O
S
O
O
Tol
R
NHTs
R
S
Cu, Fe or Ru
N
metal-free
O
Tol
previous work21
this work
Ar
Ar
Ar
R
Scheme 1 Synthetic application of N-tosylhydrazones
4-Nitrobenzaldehyde N-tosylhydrazone (1a) was select-
ed as a model substrate for optimizing the reaction condi-
tions (Table 1). Reaction of 1a with K2CO3 (1.0 equiv) at 90
°C for 2 hours afforded the desired sulfinate 2a in 44% yield
(Table 1, entry 1). The choice of bases was important for this
reaction. The reaction was achieved in 12–50% yields with
the use of various inorganic and organic bases, including
Cs2CO3, KOH, DIPEA, Et3N, DMAP, and DBU (entries 2–7).
However, DIPEA was selected in our next investigations be-
cause it displayed the best efficiency (entries 1–7). Solvent
played an important role in this transformation. With the
use of various solvents including DCE, 1,4-dioxane, CH3CN,
DMSO, and DMF in comparison to CH3NO2, lower yields
were found (entries 4 and 8–12). The effect of different
temperatures was also investigated, and the reaction at 90
°C was found to give the sulfinate 2a in higher yield (entries
4 and 13–16). Further parameter optimizations identified
On the other hand, N-tosylhydrazones, as precursors of
diazo compounds, have been employed as building blocks
for the construction of C–C, C–O, C–N, C–B, and C–Si
bonds.20 Usually, decomposition of N-tosylhydrazones gen-
erates the sulfones in the presence of suitable metal cata-
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y.-Z. Ji et al.
Paper
Synthesis
the most effective loading of DIPEA was 1.0 equivalent (en-
tries 4 and 17–19). The reaction was also carried out under
argon atmosphere, and the same yield was found, which in-
dicated that oxygen atmosphere is not necessary for this re-
action (entry 20). Furthermore, scaling up N-tosylhydra-
zone 1a to 1.28 g, the reaction afforded the yield at a good
level (entry 21).
2 hours (Table 2, entries 1–8). Arylketone-derived N-tosyl-
hydrazones 1i–k reacted well under the standard condi-
tions to afford sulfinates 2i–k in moderate to good yields
(entries 9–11). Sulfonyl-derived hydrazones 1l–p could af-
ford the corresponding sulfinates 2l–p in good yields (en-
tries 12–16). No reaction took place on treatment of alkyl-
aldehyde-derived N-tosylhydrazones 1q under the standard
conditions, and the starting material could be recovered
(entry 17). N-Alkylated hydrazones 3b–e and 3j–k were ob-
served as by-products in some of the above reactions (en-
tries 2–5 and 10, 11). However, these compounds 3 contain-
ing nitro groups were not detected, which are consistent
with the literature.24
Table 1 Optimization of the Reaction Conditionsa
NNHTs
H
O
S
conditions
O
O2N
O2N
1a
2a
Sulfonylhydrazones can be readily prepared by mixing
sulfonyl hydrazides with the corresponding carbonyl com-
pounds. The one-pot synthesis of sulfinates 2 from carbonyl
compounds 4 and sulfonyl hydrazines 5 without the isola-
tion of arylsulfonylhydrazone intermediates was also inves-
tigated.
To our delight, after heating carbonyl compounds 4 and
arylsulfonyl hydrazides 5 at 25 °C for 2 hours, followed by
the addition of DIPEA, and stirring the mixture at 90 °C for
another 2 hours, the desired sulfinates 2 were gained in
similar yields, but without the need to isolate the arylsulfo-
nylhydrazone intermediates 1 (Table 3).
Entry
Base (equiv)b
Solvent
Temp (°C)
Yield (%)c
1
2
K2CO3 (1.0)
Cs2CO3 (1.0)
KOH (1.0)
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
DCE
90
90
90
90
90
90
90
90
90
90
90
90
30
50
70
110
90
90
90
90
90
44
42
40
50
42
12
15
18
20
23
26
45
30
40
45
48
26
48
45
50
48
3
4
DIPEA (1.0)
Et3N (1.0)
5
6
DMAP (1.0)
DBU (1.0)
7
8
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (1.0)
DIPEA (0.5)
DIPEA (2.0)
DIPEA (3.0)
DIPEA (1.0)
DIPEA (1.0)
To gain insight into the reaction mechanism, several
control experiments were carried out (Scheme 2). The reac-
tion of N-tosylhydrazone 1a still proceeded, when the radi-
cal scavenger TEMPO (2,2,6,6-tetramethyl-1-piperidiny-
loxy, Scheme 2a) or BHT (butylated hydroxytoluene,
Scheme 2b) was added. These results ruled out the possibil-
ity of a radical process. By treating N-alkylated hydrazone
3d in the presence of DIPEA (1.0 equiv) in CH3NO2 at 90 °C
for 2 hours, no reaction took place and the starting material
3d was recovered (Scheme 2c). These results indicated that
the reactions probably underwent a cleavage of the N–H
bond. The crossover experiment by employing two differ-
ent arylsulfonylhydrazones was next investigated. The reac-
tion of arylsulfonylhydrazones 1f (1.0 equiv) and 1l (1.0
equiv) under the standard conditions gave an equimolar
9
1,4-dioxane
CH3CN
10
11
12
13
14
15
16
17
18
19
20d
21e
DMSO
DMF
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
1
mixture of sulfinates 2a, 2f, 2l, and 2p as indicated by H
a General conditions: 1a (0.2 mmol) and base (0.1–0.6 mmol) in solvent
(1.0 mL) at 30–110 °C for 2 h.
NMR analysis (Scheme 2d). This result indicated that the re-
action might involve an intermolecular pathway.
b DIPEA: N,N-Diisopropylethylamine; DMAP: 4-dimethylaminopyridine;
DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene.
c Isolated yield.
Based on the above results and related reports in the lit-
erature,22 a possible reaction mechanism is illustrated in
Scheme 3. First, hydrazone anions 6 are formed in the pres-
ence of base from hydrazones 1. Tautomerization of hydra-
zone anions 6, followed by protonation with the Base-H
lead to intermediates 7. Subsequently, the nucleophilic O-
attack of the intermediates 7 onto another molecule of in-
termediates 7 generates the desired sulfinates 2 by releas-
ing N2. On the other hand, nucleophilic substitution reac-
tion of the intermediates 7 with hydrazone anions 6 can
form the N-alkylated hydrazones 3.
d Under argon.
e Reaction was carried out on a 1.28 g scale of 1a (4.0 mmol).
After the optimized reaction conditions in hand, the
scope of the reaction with various sulfonylhydrazones was
subsequently investigated (Table 2). Arylaldehyde-derived
N-tosylhydrazones 1a–h, with their aromatic rings bearing
hydrogen atoms, electron-donating, and electron-with-
drawing groups at the ortho-, meta-, and para-positions, re-
acted smoothly in the presence of DIPEA (1.0 equiv) at 90 °C
to afford sulfinates 2a–h in moderate to good yields within
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H

C
Y.-Z. Ji et al.
Paper
Synthesis
Table 2 Synthesis of Various Sulfinatesa
R3
R1 R2
R3
R2
O
S
H
N
DIPEA (1.0 equiv)
CH3NO2, 90 °C, 2 h
N
+
R1
O
N
S
N
S
O2
O2
R3
R1
R1
R2
R2
1
2
3
Entry
1
R1
R2
R3
Yield (%)b of 2/3
1
2
1a
1b
1c
1d
1e
1f
4-NO2C6H4
4-ClC6H4
4-CF3C6H4
Ph
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
50/N.D.
50/17
3
45/10
4
53/15
5
4-CH3C6H4
2-NO2C6H4
48/16
6
52/N.D.
54/N.D.
48/N.D.
46/N.D.
52/20
7
1g
1h
1i
2-NO2-5-FC6H3
2-NO2-5-ClC6H3
4-NO2C6H4
4-CF3C6H4
4-CF3C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
2-NO2C6H4
t-Bu
8
9
CH3
CH3
Et
H
10
11
12
13
14
15
16
17
1j
1k
1l
60/20
52/N.D.
54/N.D.
6/N.D.
51/N.D.
51/N.D.
N.R.
1m
1n
1o
1p
1q
H
OCH3
t-Bu
Br
H
H
H
H
H
CH3
a General conditions: 1 (0.5 mmol) and DIPEA (0.5 mmol) in CH3NO2 (2.0 mL) at 90 °C for 2 h.
b Isolated yield. N.R.: No reaction. N.D.: Not detected.
NNHTs
O
DIPEA (1.0 equiv)
S
O
(a)
H
CH3NO2, 90 °C, 2 h
O2N
O2N
TEMPO (2 equiv)
1a
2a, 50%
NNHTs
H
O
S
DIPEA (1.0 equiv)
O
(b)
(c)
CH3NO2, 90 °C, 2 h
O2N
Ph
O2N
BHT (2 equiv)
1a
2a, 50%
DIPEA (1.0 equiv)
CH3NO2, 90 °C, 2 h
Bn
N
no reaction
N
Ts
3d
H
O
S
O
N
Ph
N
S
S
O2
O
Ph
O
pTol
H
+
DIPEA (1.0 equiv)
CH3NO2, 90 °C, 2 h
O2N
O2N
O2N
(d)
1l
2l
2a
+
O
S
O
H
N
pTol
2a : 2f : 2l : 2p =
1 : 1 : 1 : 1
S
N
S
O
Ph
O
pTol
O2
+
H
NO2
NO2
1f
2p
2f
NO2
Scheme 2 Control experiments
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H

D
Y.-Z. Ji et al.
Paper
Synthesis
Table 3 Synthesis of Various Sulfinates from Carbonyl Compounds and
ate to good yields. The reactions were performed under
metal-free conditions, which offers attractive industrial
prospects. Sulfinates were also provided from carbonyl
compounds and sulfonylhydrazines without the isolation of
arylsulfonylhydrazone intermediates. One drawback of the
sulfinate synthesis is that some N-alkylated hydrazones
were formed as by-products. Further applications of this
method are ongoing in our laboratory.
Sulfonylhydrazinesa
R1
O
S
O
S
O
1) CH3NO2, 25 °C, 2 h
R2
+
H2NHN
Ar
O
R1
Ar
2) DIPEA (1.0 equiv)
90 °C, 2 h
O
R2
4
5
2
Entry
4
Ar
R1
5
R2
CH3
Yield (%)b of 2
1
2
3
4
5
4a
4d
4e
4i
4-NO2C6H4
Ph
H
5a
5a
5a
5a
5b
2a, 48
2d, 49
2e, 43
2i, 42
2l, 48
H
CH3
CH3
CH3
H
All commercially available chemicals used were from commercial
sources without any further purification. Melting points were gained
on a Gongyi X-5 microscopy digital melting point apparatus and are
uncorrected. High-resolution mass spectra (HRMS) were recorded on
an Electrothemal LTQ-Orbitrap mass spectrometer. IR spectra were
recorded on an Electrothemal Nicolet 380 spectrophotometer. 1H
NMR and 13C NMR spectra were recorded on a Bruker Avance III 400
MHz NMRn spectrometer. All signals for protons are recorded in ppm
using the residual NMR solvent signal as an internal reference (CDCl3,
7.26 ppm). All signals for carbon resonances are recorded in ppm us-
ing the residual NMR solvent signal as an internal reference (CDCl3,
77.0 ppm).
4-CH3C6H4
4-NO2C6H4
4-NO2C6H4
H
CH3
H
4l
a General conditions: (1) 4 (0.5 mmol) and 5 (0.5 mmol) in CH3NO2 (2.0
mL) at 25 °C for 2 h; (2) DIPEA (0.5 mmol) was added and stirred at 90 °C
for 2 h.
b Isolated yield.
Base
R
R
H
N
R
H
Base-H
– Base
Ar2
N
Ar2
Ar2
N
Ar1
N
S
Ar1
N
S
Ar1
N
S
– Base-H
R
O
O
O
O
O
O
1
6
7
Sulfinates from N-Sulfonylhydrazones; General Procedure
A mixture of a N-sulfonylhydrazone 1 (0.5 mmol, 1 equiv) and DIPEA
(65 mg, 0.5 mmol, 1 equiv) in CH3NO2 (2.0 mL) was stirred at 90 °C for
2 h. After completion of the reaction, H2O (5 mL) and EtOAc (10 mL)
were added. The two layers were separated, and the aqueous phase
was extracted with EtOAc (3 × 10 mL). The combined organic extracts
were washed by brine, dried (anhyd Na2SO4), filtered, and concentrat-
ed. The residue was purified by flash chromatography on silica gel
(100–200 mesh, elution with 15% EtOAc in PE) to afford the desired
sulfinates 2. In addition, N-alkylated hydrazone products 3 were also
formed in some examples.
R
R
O
N
Ar2
N
Ar2
Ar1
N
S
O
S
Ar1
N
S
+
Ar1
O
Ar2
– N2
O
O
O
7
7
2
Ar1
N
R
R
R
R
Ar2
N
Ar2
N
Ar1
N
S
+
N
Ar2
Ar1
N
S
Ar1
S
– N2
O
O
O
O
O
O
6
7
3
Scheme 3 Proposed mechanism
4-Nitrobenzyl 4-Methylbenzenesulfinate (2a)
As reported previously, the synthesis of sulfones from
sulfonylhydrazones is usually performed under the metal
reaction conditions.21 The reaction of metal catalyst and
sulfinate anions could generate an active ‘M–SO2Ar’ species,
which reacts with diazo cations to form the arylsulfonyl-
metal-carbene species. A subsequent ArSO2-migratory in-
sertion and protonation deliver the final product.20d,21b–d In
contrast with sulfone synthesis, our sulfinate synthesis
were performed under metal-free conditions, in which hy-
drazones might not be decomposed to sulfinate anions and
the nucleophile is still the sulfone function (Scheme 3). As
the sulfur atom of a sulfone exhibits a partial positive
charge, one of the oxygen atoms, exhibiting a partial nega-
tive charge, acts as the attacking atom and thus facilitates
the formation of a sulfinate.18c Moreover, the tetrahedral-
like sulfur atom is sterically crowded, which might prevent
it to act as the attacking atom and thus obviates the forma-
tion of a sulfone.
Yellow solid; yield: 72.7 mg (50%); mp 38–40 °C.
1H NMR (400 MHz, CDCl3):  = 8.15 (d, J = 7.8 Hz, 2 H), 7.62 (d, J = 7.1
Hz, 2 H), 7.42 (d, J = 7.7 Hz, 2 H), 7.35 (d, J = 7.3 Hz, 2 H), 5.07 (d, J =
12.6 Hz, 1 H), 4.59 (d, J = 12.6 Hz, 1 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 147.4, 143.2, 142.9, 140.8, 129.7,
128.4, 125.0, 123.4, 63.2, 21.3.
HRMS (ESI): m/z calcd for C14H14NO4S [M + H]+: 292.0638; found:
292.0645.
4-Chlorobenzyl 4-Methylbenzenesulfinate (2b)
Yellow liquid; yield: 70.0 mg (50%).
1H NMR (400 MHz, CDCl3):  = 7.63 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 7.9
Hz, 2 H), 7.27 (d, J = 8.2 Hz, 2 H), 7.19 (d, J = 8.3 Hz, 2 H), 4.97 (d, J =
11.6 Hz, 1 H), 4.50 (d, J = 11.6 Hz, 1 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 142.7, 141.2, 134.0, 133.9, 129.6,
129.5, 128.4, 125.0, 64.2, 21.2.
HRMS (ESI): m/z calcd for C14H13ClO2SNa [M + Na]+: 303.0217; found:
303.0223.
In summary, we have developed a facile synthesis of sul-
finates from N-sulfonylhydrazones by using base as a pro-
moter. A wide variety of sulfinates were obtained in moder-
N-(4-Chlorobenzyl)-N′-(4-chlorobenzylidene)-4-methylbenzene-
sulfonohydrazide (3b)
White solid; yield: 36.7 mg (17%); mp 146–148 °C.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H

E
Y.-Z. Ji et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 7.84 (d, J = 8.3 Hz, 2 H), 7.54 (s, 1 H),
7.45 (d, J = 8.5 Hz, 2 H), 7.33 (d, J = 8.2 Hz, 2 H), 7.29–7.27 (m, 2 H),
7.31–7.24 (m, 6 H), 4.82 (s, 2 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 142.3, 141.3, 137.8, 132.1, 129.3,
128.8, 128.3, 124.9, 65.2, 21.0, 20.8.
HRMS (ESI): m/z calcd for C15H16O2SNa [M + Na]+: 283.0763; found:
283.0772.
13C NMR (100 MHz, CDCl3):  = 145.2, 144.3, 136.0, 134.2, 133.7,
133.4, 132.2, 129.6, 129.0, 128.8, 128.4, 128.2, 128.0, 51.3, 21.5.
HRMS (ESI): m/z calcd for C21H19Cl2N2O2S [M + H]+: 433.0539; found:
4-Methyl-N-(4-methylbenzyl)-N′-(4-methylbenzylidene)benzene-
sulfonohydrazide (3e)
433.0546.
White solid; yield: 31.3 mg (16%); mp 150–152 °C.
1H NMR (400 MHz, CDCl3):  = 7.91 (dd, J = 8.2, 1.6 Hz, 2 H), 7.69 (s, 1
H), 7.46 (d, J = 7.8 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H), 7.29–7.27 (m, 2 H),
7.16–7.13 (m, 4 H), 4.82 (s, 2 H), 2.42 (s, 3 H), 2.34 (s, 3 H), 2.33 (s, 3
H).
4-(Trifluoromethyl)benzyl 4-Methylbenzenesulfinate (2c)
Yellow liquid; yield: 70.6 mg (45%).
1H NMR (400 MHz, CDCl3):  = 7.63 (d, J = 8.1 Hz, 2 H), 7.56 (d, J = 8.1
Hz, 2 H), 7.37 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H), 5.05 (d, J =
12.1 Hz, 1 H), 4.58 (d, J = 12.1 Hz, 1 H), 2.41 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 147.4, 143.8, 140.2, 137.0, 134.4,
132.3, 131.1, 129.3, 129.0, 128.0, 127.2, 126.7, 51.8, 21.3, 21.2, 20.8.
HRMS (ESI): m/z calcd for C23H25N2O2S [M + H]+: 393.1631; found:
393.1634.
13C NMR (100 MHz, CDCl3):  = 143.1, 141.2, 139.7, 130.3 (q, JC,F = 32.4
Hz), 129.7, 128.3, 125.3 (q, JC,F = 3.7 Hz), 125.2, 123.9 (q, JC,F = 272.1
Hz), 64.0, 21.3.
HRMS (ESI): m/z calcd for C15H13F3O2SNa [M + Na]+: 337.0481; found:
337.0487.
2-Nitrobenzyl 4-Methylbenzenesulfinate (2f)
Yellow solid; yield: 75.6 mg (52%); mp 30–32 °C.
1H NMR (400 MHz, CDCl3):  = 8.01 (d, J = 8.2 Hz, 1 H), 7.67–7.57 (m, 4
H), 7.42 (t, J = 7.7 Hz, 1 H), 7.32 (d, J = 7.9 Hz, 2 H), 5.41 (d, J = 14.5 Hz,
1 H), 5.01 (d, J = 14.5 Hz, 1 H), 2.40 (s, 3 H).
4-Methyl-N-[4-(trifluoromethyl)benzyl]-N′-[4-(trifluoromethyl)-
benzylidene]benzenesulfonohydrazide (3c)
White liquid; yield: 25 mg (10%).
1H NMR (400 MHz, CDCl3):  = 7.87 (d, J = 8.1 Hz, 2 H), 7.63–7.55 (m, 6
H), 7.51 (s, 1 H), 7.46 (d, J = 8.0 Hz, 2 H), 7.35 (d, J = 8.1 Hz, 2 H), 5.00
(s, 2 H), 2.44 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 147.0, 143.1, 141.0, 133.6, 132.2,
129.7, 129.3, 128.6, 124.9, 124.6, 62.3, 21.3.
HRMS (ESI): m/z calcd for C14H13NO4SNa [M + Na]+: 314.0457; found:
13C NMR (100 MHz, CDCl3):  = 144.6, 143.0, 139.1, 137.0, 134.3, 131.6
(q, JC,F = 32.6 Hz), 130.2 (q, JC,F = 32.4 Hz), 129.7, 128.1, 127.4, 126.9,
126.0 (q, JC,F = 3.5 Hz), 125.5 (q, JC,F = 3.7 Hz), 123.9 (q, JC,F = 272.2 Hz),
123.8 (q, JC,F = 272.2 Hz), 51.0, 21.5.
HRMS (ESI): m/z calcd for C23H19F6N2O2S [M + H]+: 501.1066; found:
501.1069.
314.0464.
5-Fluoro-2-nitrobenzyl 4-Methylbenzenesulfinate (2g)
Yellow solid; yield: 83.4 mg (54%); mp 36–38 °C.
1H NMR (400 MHz, CDCl3):  = 8.16 (dd, J = 9.0, 5.0 Hz, 1 H), 7.66 (d, J =
8.0 Hz, 2 H), 7.46 (dd, J = 9.3, 1.9 Hz, 1 H), 7.37 (d, J = 7.9 Hz, 2 H),
7.14–7.09 (m, 1 H), 5.45 (d, J = 15.6 Hz, 1 H), 5.03 (d, J = 15.6 Hz, 1 H),
2.44 (s, 3 H).
Benzyl 4-Methylbenzenesulfinate (2d)
Pale yellow liquid; yield: 65.1 mg (53%).
1H NMR (400 MHz, CDCl3):  = 7.66 (d, J = 7.6 Hz, 2 H), 7.34–7.29 (m, 7
H), 5.05 (d, J = 11.4 Hz, 1 H), 4.57 (d, J = 11.4 Hz, 1 H), 2.41 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 165.4 (d, JC,F = 257.8 Hz), 143.5, 142.8
(d, JC,F = 3.2 Hz), 140.9, 137.0 (d, JC,F = 9.2 Hz), 129.9, 127.9 (d, JC,F = 9.9
Hz), 125.1, 116.2 (d, JC,F = 25.8 Hz), 115.4 (d, JC,F = 23.5 Hz), 61.8, 21.5.
13C NMR (100 MHz, CDCl3):  = 142.4, 141.3, 135.2, 129.4, 128.1,
HRMS (ESI): m/z calcd for C14H13FNO4S [M + H]+: 310.0544; found:
128.0, 124.9, 65.1, 21.1.
310.0550.
HRMS (ESI): m/z calcd for C14H14O2SNa [M + Na]+: 269.0607; found:
269.0613.
5-Chloro-2-nitrobenzyl 4-Methylbenzenesulfinate (2h)
Pale yellow liquid; yield: 78.0 mg (48%).
1H NMR (400 MHz, CDCl3):  = 8.04 (d, J = 8.7 Hz, 1 H), 7.70 (d, J = 2.1
Hz, 1 H), 7.65 (d, J = 8.2 Hz, 2 H), 7.41 (dd, J = 8.8, 2.3 Hz, 1 H), 7.36 (d,
J = 8.0 Hz, 2 H), 5.41 (d, J = 15.2 Hz, 1 H), 4.98 (d, J = 15.2 Hz, 1 H), 2.44
(s, 3 H).
13C NMR (100 MHz, CDCl3):  = 159.8, 143.5, 140.8, 140.6, 134.8,
129.9, 129.3, 128.6, 126.3, 125.1, 61.3, 21.5.
N-Benzyl-N′-benzylidene-4-methylbenzenesulfonohydrazide (3d)
Yellow solid; yield: 27.3 mg (15%); mp 108–110 °C.
1H NMR (400 MHz, CDCl3):  = 7.92 (d, J = 8.2 Hz, 2 H), 7.64 (s, 1 H),
7.54–7.52 (m, 2 H), 7.40–7.26 (m, 10 H), 4.90 (s, 2 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 146.1, 143.9, 135.2, 134.4, 133.8,
129.9, 129.4, 128.7, 128.3, 128.0, 127.5, 127.1, 126.6, 51.7, 21.3.
HRMS (ESI): m/z calcd for C21H21N2O2S [M + H]+: 365.1318; found:
365.1324.
HRMS (ESI): m/z calcd for C14H13ClNO4S [M + H]+: 326.0248; found:
326.0253.
1-(4-Nitrophenyl)ethyl 4-Methylbenzenesulfinate (2i)
4-Methylbenzyl 4-Methylbenzenesulfinate (2e)
The product was obtained as a 1:1 mixture of diastereomers; yellow
solid; yield: 70.1 mg (46%); mp 41–43 °C.
1H NMR (400 MHz, CDCl3):  = 8.22 (d, J = 8.6 Hz, 1 H), 8.06 (d, J = 8.6 Hz, 1
H), 7.59 (d, J = 8.1 Hz, 1 H), 7.52 (d, J = 8.6 Hz, 1 H), 7.49 (d, J = 8.1 Hz, 1 H),
7.35 (d, J = 7.9 Hz, 1 H), 7.28 (d, J = 8.6 Hz, 1 H), 7.20 (d, J = 7.9 Hz, 1 H),
Yellow liquid; yield: 62.4 mg (48%).
1H NMR (400 MHz, CDCl3):  = 7.63 (d, J = 8.0 Hz, 2 H), 7.31 (d, J = 7.9
Hz, 2 H), 7.17 (d, J = 7.9 Hz, 2 H), 7.12 (d, J = 7.9 Hz, 2 H), 5.00 (d, J =
11.2 Hz, 1 H), 4.52 (d, J = 11.2 Hz, 1 H), 2.40 (s, 3 H), 2.32 (s, 3H).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H

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Y.-Z. Ji et al.
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Synthesis
5.48–5.42 (m, 1 H), 2.44 (s, 1.5 H), 2.36 (s, 1.5 H), 1.64 (d, J = 6.6 Hz, 1.5
H), 1.50 (d, J = 6.6 Hz, 1.5 H).
13C NMR (100 MHz, CDCl3):  = 149.1, 148.8, 147.5, 147.2, 143.2,
143.1, 141.9, 141.5, 129.7, 129.4, 127.0, 126.9, 125.1, 124.9, 123.8,
123.4, 74.4, 73.1, 24.4, 24.0, 21.5, 21.4.
HRMS (ESI): m/z calcd for C15H15NO4SNa [M + Na]+: 328.0614; found:
328.0619.
1H NMR (400 MHz, CDCl3):  = 7.63 (d, J = 8.2 Hz, 2 H), 7.56 (d, J = 8.2
Hz, 2 H), 7.45 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H), 5.21 (t, J = 6.7
Hz, 1 H), 2.40 (s, 3 H), 1.96–1.74 (m, 2 H), 0.85 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 144.7, 142.8, 142.3, 130.1 (q, JC,F = 32.4
Hz), 129.5, 126.9, 125.4 (q, JC,F = 3.7 Hz), 124.6, 123.9 (q, JC,F = 272.1
Hz), 80.8, 30.7, 21.2, 9.4.
HRMS (ESI): m/z calcd for C17H17F3O2SNa [M + Na]+: 365.0794; found:
365.0801.
1-[4-(Trifluoromethyl)phenyl]ethyl 4-Methylbenzenesulfinate
(2j)
4-Methyl-N-{1-[4-(trifluoromethyl)phenyl]propyl}-N′-{1-[4-(tri-
fluoromethyl)phenyl]propylidene}benzenesulfonohydrazide (3k)
First eluted fraction: Yellow solid; yield: 42.6 mg (26%); mp 37–39 °C.
Yellow liquid; yield: 55.6 mg (20%).
1H NMR (400 MHz, CDCl3):  = 7.46 (d, J = 8.1 Hz, 2 H), 7.43 (d, J = 8.0
Hz, 2 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.14 (d, J = 7.9 Hz, 2 H), 5.41 (q, J = 6.7
Hz, 1 H), 2.32 (s, 3 H), 1.62 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 145.5, 142.7, 141.5, 129.6 (q, JC,F = 32.4
Hz), 129.2, 126.3, 125.1, 125.0 (q, JC,F = 3.8 Hz), 123.9 (q, JC,F = 272.1
Hz), 73.4, 24.1, 21.1.
1H NMR (400 MHz, CDCl3):  = 7.87 (d, J = 8.2 Hz, 2 H), 7.74 (d, J = 8.3
Hz, 2 H), 7.37–7.31 (m, 6 H), 7.04 (d, J = 7.9 Hz, 2 H), 4.94 (dd, J = 10.0,
5.3 Hz, 1 H), 3.08–3.05 (m, 2 H), 2.33 (s, 3 H), 1.78–1.62 (m, 2 H), 0.94
(t, J = 7.6 Hz, 3 H), 0.70 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 183.8, 143.6, 141.9, 139.4, 134.6, 132.5
(q, JC,F = 32.6 Hz), 129.6 (q, JC,F = 32.2 Hz), 129.2, 128.8, 128.1, 128.0,
125.6 (q, JC,F = 3.6 Hz), 124.7 (q, JC,F = 3.6 Hz), 124.0 (q, JC,F = 272.0 Hz),
123.9 (q, JC,F = 272.4 Hz), 66.8, 23.6, 21.3, 11.3, 10.8.
HRMS (ESI): m/z calcd for C16H15F3O2SNa [M + Na]+: 351.0637; found:
351.0639.
Second eluted fraction; Yellow solid; yield: 42.6 mg (26%); mp 31–33
°C.
1H NMR (400 MHz, CDCl3):  = 7.63 (d, J = 8.2 Hz, 2 H), 7.59 (d, J = 8.2
Hz, 2 H), 7.49 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 8.2 Hz, 2 H), 5.46 (q, J = 6.6
Hz, 1 H), 2.42 (s, 3 H), 1.52 (d, J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 145.8, 142.9, 142.2, 130.2 (q, JC,F = 32.4
Hz), 129.6, 126.5, 125.5 (q, JC,F = 3.7 Hz), 124.8, 123.9 (q, JC,F = 272.1
Hz), 75.2, 23.9, 21.3.
HRMS (ESI): m/z calcd for C27H27F6N2O2S [M + H]+: 557.1692; found:
557.1697.
4-Nitrobenzyl Benzenesulfinate (2l)
Yellow liquid; yield: 72.0 mg (52%).
1H NMR (400 MHz, CDCl3):  = 8.11 (d, J = 8.1 Hz, 2 H), 7.72 (d, J = 7.1
Hz, 2 H), 7.57–7.50 (m, 3 H), 7.40 (d, J = 8.4 Hz, 2 H), 5.07 (d, J = 12.7
Hz, 1 H), 4.61 (d, J = 12.7 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 147.5, 143.6, 142.7, 132.5, 129.1,
128.4, 125.0, 123.4, 63.7.
HRMS (ESI): m/z calcd for C16H15F3O2SNa [M + Na]+: 351.0637; found:
351.0641.
HRMS (ESI): m/z calcd for C13H12NO4S [M + H]+: 278.0482; found:
4-Methyl-N-{1-[4-(trifluoromethyl)phenyl]ethyl}-N′-{1-[4-(tri-
278.0487.
fluoromethyl)phenyl]ethylidene}benzenesulfonohydrazide (3j)
Pale yellow solid; yield: 52.8 mg (20%); mp 128–130 °C.
4-Nitrobenzyl 4-Methoxybenzenesulfinate (2m)
1H NMR (400 MHz, CDCl3):  = 7.98 (d, J = 8.2 Hz, 2 H), 7.72 (d, J = 8.2
Hz, 2 H), 7.51 (d, J = 8.0 Hz, 2 H), 7.43–7.38 (m, 4 H), 7.16 (d, J = 8.0 Hz,
2 H), 5.29 (q, J = 7.0 Hz, 1 H), 2.39 (s, 3 H), 2.39 (s, 3 H), 1.27 (d, J = 7.0
Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 178.7, 144.3, 143.9, 140.2, 134.4, 132.8
(q, JC,F = 32.6 Hz), 129.6 (q, JC,F = 32.4 Hz), 129.1, 128.3, 128.2, 127.5,
125.5 (q, JC,F = 3.7 Hz), 124.9 (q, JC,F = 3.6 Hz), 124.0 (q, JC,F = 272.1 Hz),
123.8 (q, JC,F = 272.3 Hz), 60.2, 21.3, 17.8.
Yellow liquid; yield: 82.9 mg (54%).
1H NMR (400 MHz, CDCl3):  = 8.14 (d, J = 8.0 Hz, 2 H), 7.66 (d, J = 8.6
Hz, 2 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.02 (d, J = 8.7 Hz, 2 H), 5.06 (d, J =
12.7 Hz, 1 H), 4.60 (d, J = 12.7 Hz, 1 H), 3.85 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 162.9, 147.6, 143.1, 135.4, 128.5,
127.0, 123.5, 114.5, 63.1, 55.5.
HRMS (ESI): m/z calcd for C14H14NO5S [M + H]+: 308.0587; found:
308.0591.
HRMS (ESI): m/z calcd for C25H23F6N2O2S [M + H]+: 529.1379; found:
529.1384.
4-Nitrobenzyl 4-Methoxybenzenesulfinate (2n)
1-[4-(Trifluoromethyl)phenyl]propyl 4-Methylbenzenesulfinate
(2k)
Yellow liquid; yield: 93.2 mg (56%).
1H NMR (400 MHz, CDCl3):  = 8.15 (d, J = 8.7 Hz, 2 H), 7.66 (d, J = 8.5
Hz, 2 H), 7.56 (d, J = 8.5 Hz, 2 H), 7.43 (d, J = 8.6 Hz, 2 H), 5.09 (d, J =
12.7 Hz, 1 H), 4.65 (d, J = 12.7 Hz, 1 H), 1.34 (s, 9 H).
13C NMR (100 MHz, CDCl3):  = 156.4, 147.7, 143.1, 140.9, 128.7,
126.2, 125.1, 123.6, 63.5, 35.1, 31.1.
First eluted fraction: Yellow solid; yield: 51.3 mg (30%); mp 28–30 °C.
1H NMR (400 MHz, CDCl3):  = 7.41 (t, J = 8.4 Hz, 4 H), 7.13 (d, J = 8.1
Hz, 2 H), 7.08 (d, J = 7.8 Hz, 2 H), 5.16 (t, J = 6.8 Hz, 1 H), 2.30 (s, 3 H),
1.98–1.77 (m, 2 H), 0.89 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 144.6, 142.6, 141.4, 129.4 (q, JC,F = 32.3
Hz), 129.1, 126.7, 125.0, 124.8 (q, JC,F = 3.7 Hz), 123.9 (q, JC,F = 272.1
Hz), 78.0, 30.9, 21.1, 9.6.
HRMS (ESI): m/z calcd for C17H20NO4S [M + H]+: 334.1108; found:
334.1112.
HRMS (ESI): m/z calcd for C17H17F3O2SNa [M + Na]+: 365.0794; found:
365.0798.
4-Nitrobenzyl 4-Bromobenzenesulfinate (2o)
Yellow liquid; yield: 90.4 mg (51%).
Second eluted fraction: Yellow solid; yield: 51.3 mg (30%); mp 59–61
°C.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H

G
Y.-Z. Ji et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 8.17 (d, J = 8.6 Hz, 2 H), 7.70 (d, J = 8.4
Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.43 (d, J = 8.5 Hz, 2 H), 5.10 (d, J =
12.6 Hz, 1 H), 4.61 (d, J = 12.6 Hz, 1 H).
(4) Hemmi, M.; Ikeda, Y.; Shindo, Y.; Nakajima, T.; Nishiyama, S.;
Oka, K.; Sato, M.; Hiruta, Y.; Citterio, D.; Suzuki, K. Chem. Asian J.
2018, 13, 648.
(5) (a) Liu, M.; Liu, Y.; Liu, A.; Zhang, D.; Chen, M.; Wu, C.; Hua, X.;
Zhou, S.; Li, Z. Chin. J. Org. Chem. 2016, 36, 1653. (b) Li, H. J.;
Wang, R.; Gao, J.; Wang, Y. Y.; Luo, D. H.; Wu, Y. C. Adv. Synth.
Catal. 2015, 357, 1393.
(6) (a) Nguyen, N. L. T.; Vo, H. T.; Duus, F.; Luu, T. X. T. Molecules
2017, 22, 1458. (b) Wei, L.; Xiao, M.; Xie, Z. Org. Lett. 2014, 16,
2784. (c) Rayner, P. J.; Gelardi, G.; O’Brien, P.; Horan, R. A. J.;
Blakemore, D. C. Org. Biomol. Chem. 2014, 12, 3499. (d) Nath, D.;
Fleming, F. F. Chem. Eur. J. 2013, 19, 2023. (e) Yuste, F.; Linares,
A. H.; Mastranzo, V. M.; Ortiz, B.; Sánchez-Obregón, R.; Fraile,
A.; Ruano, J. L. G. J. Org. Chem. 2011, 76, 4635. (f) Resek, J. E.;
Meyers, A. I. Tetrahedron Lett. 1995, 36, 7051.
13C NMR (100 MHz, CDCl3):  = 147.7, 143.0, 142.5, 132.5, 128.6,
127.5, 126.8, 123.7, 63.9.
HRMS (ESI): m/z calcd for C13H11BrNO4S [M + H]+: 355.9587, found:
355.9591.
2-Nitrobenzyl Benzenesulfinate (2p)
Yellow liquid; yield: 70.6 mg (51%).
1H NMR (400 MHz, CDCl3):  = 8.06 (d, J = 8.1 Hz, 1 H), 7.78–7.75 (m, 2
H), 7.70–7.55 (m, 5 H), 7.46 (t, J = 7.6 Hz, 1 H), 5.46 (d, J = 14.4 Hz, 1
H), 5.05 (d, J = 14.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 147.2, 144.0, 133.7, 132.5, 132.2,
(7) (a) Dherbassy, Q.; Djukic, J. P.; Wencel-Delord, J.; Colobert, F.
Angew. Chem. Int. Ed. 2018, 57, 4668. (b) Chelouan, A.; Recio, R.;
Alcudia, A.; Khiar, N.; Fernández, I. Eur. J. Org. Chem. 2014, 6935.
(c) Trost, B. M.; Rao, M.; Dieskau, A. P. J. Am. Chem. Soc. 2013,
135, 18697. (d) Rayner, P. J.; O’Brien, P.; Horan, R. A. J. J. Am.
Chem. Soc. 2013, 135, 8071. (e) Worch, C.; Atodiresei, I.; Raabe,
G.; Bolm, C. Chem. Eur. J. 2010, 16, 677. (f) Bürgi, J. J.; Mariz, R.;
Gatti, M.; Drinkel, E.; Luan, X.; Blumentritt, S.; Linden, A.; Dorta,
R. Angew. Chem. Int. Ed. 2009, 48, 2768. (g) Khiar, N.; Alcudia, F.;
Espartero, J. L.; Rodríguez, L.; Fernández, I. J. Am. Chem. Soc.
2000, 122, 7598.
(8) (a) Bujnicki, B.; Drabowicz, J.; Mikolajczyk, M. Molecules 2015,
20, 2949. (b) Maldonado, M. F.; Sehgelmeble, F.; Bjarnemark, F.;
Svensson, M.; Åhman, J.; Arvidsson, P. I. Tetrahedron 2012, 68,
7456. (c) Ruano, J. L. G.; Parra, A.; Marzo, L.; Yuste, F.;
Mastranzo, V. M. Tetrahedron 2011, 67, 2905. (d) Ruano, J. L. G.;
Parra, A.; Yuste, F.; Mastranzo, V. M. Synthesis 2008, 311.
(e) Han, Z.; Krishnamurthy, D.; Grover, P.; Fang, Q. K.; Su, X.;
Wilkinson, H. S.; Lu, Z. H.; Magierab, D.; Senanayake, C. H. Tetra-
hedron 2005, 61, 6386. (f) Han, Z.; Krishnamurthy, D.; Grover,
P.; Fang, Q. K.; Senanayake, C. H. J. Am. Chem. Soc. 2002, 124,
7880. (g) Davis, F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.;
Fanelli, D. L.; Zhang, H. J. Org. Chem. 1999, 64, 1403. (h) Evans, D.
A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy, J.; Cherry, D.
J. Am. Chem. Soc. 1992, 114, 5977.
129.5, 129.1, 128.8, 125.1, 124.8, 62.7.
HRMS (ESI): m/z calcd for C13H12NO4S [M + H]+: 278.0482; found:
278.0489.
One-Pot Synthesis of Sulfinates from Carbonyl Compounds and
Sulfonylhydrazides; General Procedure
A solution of the carbonyl compound 4 (0.5 mmol, 1 equiv) and sulfo-
nyl hydrazide 5 (65 mg, 0.5 mmol, 1 equiv) in MeNO2 (2.0 mL) was
stirred at 25 °C for 2 h. Then DIPEA (0.5 mmol, 1 equiv) was added to
the reaction mixture. The mixture was stirred at 90 °C for another 2 h.
After completion of the reaction, H2O (5 mL) and EtOAc (10 mL) were
added. The two layers were separated, and the aqueous phase was ex-
tracted with EtOAc (3 × 10 mL). The combined organic extracts were
washed by brine, dried (anhyd Na2SO4), filtered, and concentrated.
The residue was purified by flash chromatography on silica gel (100–
200 mesh, elution with 15% EtOAc in PE) to afford the desired sulfi-
nates 2.
Funding Information
This work was supported by the Key Technology Research and Devel-
opment Program of Shandong (2019GSF108089), the Natural Science
Foundation of Shandong Province (ZR2019MB009), the National Nat-
ural Science Foundation of China (21372054, 21672046), and the
(9) (a) Tata, R. R.; Hampton, C. S.; Harmata, M. Adv. Synth. Catal.
2017, 359, 1232. (b) Lujan-Montelongo, J. A.; Estevez, A. O.;
Fleming, F. F. Eur. J. Org. Chem. 2015, 1602.
fund from the Huancui District of Weihai City.
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3727.
Supporting Information
(11) Peltier, H. M.; Evans, J. W.; Ellman, J. A. Org. Lett. 2005, 7, 1733.
(12) (a) Gafur, S. H.; Waggoner, S. L.; Jacobsen, E.; Hamaker, C. G.;
Hitchcock, S. R. Synthesis 2018, 50, 4855. (b) Drabowicz, J.;
Kwiatkowska, M.; Kiełbasiński, P. Synthesis 2008, 3563.
(c) Hajipour, A. R.; Falahatib, A. R.; Ruoho, A. E. Tetrahedron Lett.
2006, 47, 2717. (d) Hajipour, A. R.; Mallakpour, S. E.; Afrousheh,
A. Tetrahedron 1999, 55, 2311. (e) Noguchi, Y.; Isoda, M.; Kuroki,
K.; Furukawa, M. Chem. Pharm. Bull. 1982, 30, 1646.
(f) Furukawa, M.; Ohkawara, T.; Noguchi, Y.; Nishikawa, M.;
Tommatsu, M. Chem. Pharm. Bull. 1980, 28, 134.
(13) (a) Ji, Y. Z.; Li, H. J.; Zhang, J. Y.; Wu, Y. C. Eur. J. Org. Chem. 2019,
1846. (b) Tranquilino, A.; Andrade, S. R. C. P.; da Silva, A. P. M.;
Menezes, P. H.; Oliveira, R. A. Tetrahedron Lett. 2017, 58, 1265.
(c) Jacobsen, E.; Chavda, M. K.; Zikpi, K. M.; Waggoner, S. L.;
Passini, D. J.; Wolfe, J. A.; Larson, R.; Beckley, C.; Hamaker, C. G.;
Hitchcock, S. R. Tetrahedron Lett. 2017, 58, 3073. (d) Huang, M.;
Hu, L.; Shen, H.; Liu, Q.; Hussain, M. I.; Pana, J.; Xiong, Y. Green
Chem. 2016, 18, 1874.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690754.
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References
(1) (a) Tapia-Pineda, A.; Perez-Arrieta, C.; Silva-Cuevas, C.; Paleo, E.;
Lujan-Montelongo, J. A. J. Chem. Educ. 2016, 93, 1470. (b) Robak,
M. T.; Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600.
(c) Fernández, I.; Khiar, N. Chem. Rev. 2003, 103, 3651.
(2) Kim, J. H.; Lee, J. O.; Lee, S. K.; Moon, J. W.; You, G. Y.; Kim, S. J.;
Park, S. H.; Park, J. M.; Lim, S. Y.; Suh, P. G.; Uhm, K. O.; Song, M.
S.; Kim, H. S. J. Biol. Chem. 2011, 286, 7567.
(3) Blackinton, J.; Lakshminarasimhan, M.; Thomas, K. J.; Ahmad,
R.; Greggio, E.; Raza, A. S.; Cookson, M. R.; Wilson, M. A. J. Biol.
Chem. 2011, 284, 6476.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H

H
Y.-Z. Ji et al.
Paper
Synthesis
(14) Watanabe, Y.; Mase, N.; Tateyama, M.; Toru, T. Tetrahedron:
Asymmetry 1999, 10, 737.
(15) Du, B.; Li, Z.; Qian, P.; Han, J.; Pan, Y. Chem. Asian J. 2016, 11,
478.
(16) (a) Zhou, C.; Tan, Z.; Jiang, H.; Zhang, M. Green Chem. 2018, 20,
1992. (b) Shyam, P. K.; Kim, Y. K.; Lee, C.; Jang, H. Y. Adv. Synth.
Catal. 2016, 358, 56.
(17) (a) Xia, M.; Chen, Z. C. Synth. Commun. 1997, 27, 1321.
(b) Brownbridge, P.; Jowett, I. C. Synthesis 1988, 252.
(18) (a) Pogaku, N.; Krishna, P. R.; Prapurna, Y. L. Synth. Commun.
2017, 47, 1239. (b) Kadari, L.; Krishna, P. R.; Prapurna, Y. L. Adv.
Synth. Catal. 2016, 358, 3863. (c) Ji, Y. Z.; Wang, M.; Li, H. J.; Liu,
Y.; Wu, Y. C. Eur. J. Org. Chem. 2016, 4077.
(19) (a) Du, B.; Wang, W.; Wang, Y.; Qi, Z.; Tian, J.; Zhou, J.; Wang, X.;
Han, J.; Ma, J.; Pan, Y. Chem. Asian J. 2018, 13, 404. (b) Wei, J.;
Sun, Z. Org. Lett. 2015, 17, 5396.
(20) (a) Arunprasath, D.; Bala, B. D.; Sekar, G. Adv. Synth. Catal. 2019,
361, 1172. (b) Wang, H.; Deng, Y. H.; Shao, Z. Synthesis 2018, 50,
2281. (c) Hossain, M. L.; Wang, J. Chem. Rec. 2018, 18, 1548.
(d) Xia, Y.; Qiu, D.; Wang, J. Chem. Rev. 2017, 117, 13810. (e) Qiu,
D.; Mo, F.; Zhang, Y.; Wang, J. Adv. Organomet. Chem. 2017, 67,
151. (f) Jadhav, A. P.; Ray, D.; Rao, V. U. B.; Singh, R. P. Eur. J. Org.
Chem. 2016, 2369. (g) Xu, K.; Shen, C.; Shan, S. Chin. J. Org. Chem.
2015, 35, 294. (h) Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res.
2013, 46, 236. (i) Zhang, Y.; Wang, J. Top. Curr. Chem. 2012, 327,
239. (j) Shao, Z.; Zhang, H. Chem. Soc. Rev. 2012, 41, 560.
(k) Barluenga, J.; Valdés, C. Angew. Chem. Int. Ed. 2011, 50, 7486.
(21) (a) Zhao, J. L.; Guo, S. H.; Qiu, J.; Gou, X. F.; Hua, C. W.; Chen, B.
Tetrahedron Lett. 2016, 57, 2375. (b) Barluenga, J.; Tomás-
Gamasa, M.; Aznar, F.; Valdés, C. Eur. J. Org. Chem. 2011, 1520.
(c) Feng, X. W.; Wang, J.; Zhang, J.; Yang, J.; Wang, N.; Yu, X. Q.
Org. Lett. 2010, 12, 4408. (d) Zhang, J. L.; Chan, P. W. H.; Che, C.
M. Tetrahedron Lett. 2003, 44, 8733.
(22) Choudhary, D.; Khatri, V.; Basak, A. K. Org. Lett. 2018, 20, 1703.
(23) (a) Ji, Y. Z.; Li, H. J.; Liu, Y.; Wu, Y. C. Synthesis 2019, 51, in press;
DOI: 10.1055/s-0039-1690712. (b) Wang, J. L.; Li, H. J.; Wu, Y. C.
J. Org. Chem. 2018, 83, 8716. (c) Wang, H. S.; Li, H. J.; Zhang, Z.
G.; Wu, Y. C. Eur. J. Org. Chem. 2018, 915. (d) Wang, H. S.; Li, H. J.;
Nan, X.; Luo, Y. Y.; Wu, Y. C. J. Org. Chem. 2017, 82, 12914.
(e) Wu, Q. X.; Li, H. J.; Wang, H. S.; Zhang, Z. G.; Wang, C. C.; Wu,
Y. C. Synlett 2015, 26, 243.
(24) (a) Sha, Q.; Wei, Y. Tetrahedron 2013, 69, 3829. (b) Liu, J. B.; Yan,
H.; Lu, G. Tetrahedron Lett. 2013, 54, 891.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–H