Amide Iridium Complexes As Catalysts for Transfer Hydrogenation Reduction of N-sulfonylimine

Article abstract of DOI:10.1021/acs.joc.0c02680

Sulfonamide moieties widely exist in natural products, biologically active substance, and pharmaceuticals. Here, an efficient water-soluble amide iridium complexes-catalyzed transfer hydrogenation reduction of N-sulfonylimine is developed, which can be carried out under environmentally friendly conditions, affording a series of sulfonamide compounds in excellent yields (96-98%). In comparison with organic solvents, water is shown to be critical for a high catalytic transfer hydrogenation reduction in which the catalyst loading can be as low as 0.001 mol %. These amide iridium complexes are easy to synthesize, one structure of which was determined by single-crystal X-ray diffraction. This protocol gives an operationally simple, practical, and environmentally friendly strategy for synthesis of sulfonamide compounds.

Full text of DOI:10.1021/acs.joc.0c02680

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Amide Iridium Complexes As Catalysts for Transfer Hydrogenation
Reduction of N‑sulfonylimine
Huiling Wen, Nianhua Luo, Qianheng Zhu, and Renshi Luo*
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ABSTRACT: Sulfonamide moieties widely exist in natural
products, biologically active substance, and pharmaceuticals.
Here, an efficient water-soluble amide iridium complexes-catalyzed
transfer hydrogenation reduction of N-sulfonylimine is developed,
which can be carried out under environmentally friendly
conditions, affording a series of sulfonamide compounds in
excellent yields (96−98%). In comparison with organic solvents,
water is shown to be critical for a high catalytic transfer
hydrogenation reduction in which the catalyst loading can be as
low as 0.001 mol %. These amide iridium complexes are easy to
synthesize, one structure of which was determined by single-crystal
X-ray diffraction. This protocol gives an operationally simple, practical, and environmentally friendly strategy for synthesis of
sulfonamide compounds.
catalysts have been explored to a lesser degree. In addition,
Cp*Ir catalysts containing dinitrogen ligands have shown
superior performance, which highlights the great potential of
Cp*Ir catalysts containing dinitrogen ligands in catalysis.7a
Recently, our group has been devoted to the application of
transfer hydrogenation reactions with Cp*Ir catalysts with
dinitrogen ligands (Scheme 1a) and developed some efficient
INTRODUCTION
■
Hydrogenation is the most effective transformation in chemical
synthesis.1 Direct hydrogenation and transfer hydrogenation
are two strategies to achieve hydrogenation. Compared with
direct hydrogenation, transfer hydrogenation showcases many
advantages and becomes a research center in hydrogenation
science.2 So far, great efforts and astonishing achievements
have been made in the development of transition-metal-
catalyzed symmetric, asymmetric transfer hydrogenation, and a
variety of transition metals, ligands, and hydrogen sources are
involved in the hydrogen transfer transformation, which has
become a central issue in organic synthesis.2 Since Mestroni’s
group first reported the iridium-catalyzed hydrogen transfer of
ketones,3 iridium has become one of the most active metals
employed in hydrogen transfer transformation.4 In 1999,
Noyori5a introduced the Cp*Ir catalysts for this trans-
formation, and a dramatic increase of this kind of catalysts
has occurred since then.5
Generally, there are two common mechanisms for metal-
catalyzed transfer hydrogenation reactions: The hydridic route
and direct hydrogen transfer.6 The commonly accepted
mechanism for Cp*Ir-catalyzed hydrogen transfer reactions is
the monohydride route (either inner- or outer-sphere),6a
Usually, Cp*Ir catalysts bearing diamine, triazolyl ligands,
NHC fragments, and half-sandwich cyclometalated Ir com-
plexes are employed as TH catalysts.2 As we all know, ancillary
ligands can significantly influence the coordination chemistry
and reactivity of transition-metal complexes. Although Cp*Ir
catalysts are so important in TH, research on the ligands’
effects at the Cp*Ir fragment is still not comprehensive.7
Compared with the Cp*Ru and Cp*Rh catalysts, the Cp*Ir
Scheme 1. Cp*Ir Catalysts
catalytic methodologies,8 but the development of more iridium
catalysts which possesses more efficient, broader substrates
scope or asymmetric catalysis remains an important goal.
Herein, we propose to design and employ half-sandwich
iridium complexes of perhydroindolinamide (Scheme 1b) to
investigate the catalytic performance.
Received: November 10, 2020
Published: February 17, 2021
https://dx.doi.org/10.1021/acs.joc.0c02680
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 3850−3859
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Sulfonamide moieties widely exist in natural products,
biologically active substances, and pharmaceuticals, such as
potential ETA antagonists,9 thromboxane receptor antago-
nists,10 antimycobacteria agents,11 matrix metalloproteinase
inhibitors,12 and human EP3 receptor antagonists13 (Scheme
2). Therefore, development of methods for the efficient
Scheme 4. X-ray ORTEP Drawing of Cat-3
Scheme 2. Selected Examples of Bioactive Benzylic N-
Alkylsulfonamide Pharmacores
complexes Cat-1−Cat-3 as precatalysts and HCO2H/Et3N as
the hydrogen source (Table 1). To our delight, the substrate
Table 1. Catalyst Screening and Optimization of the
Reaction Conditions for Transfer Hydrogenation
a
Reduction
synthesis of sulfonamide moiety is an important facet of
organic chemistry. One of the most common synthetic
strategies of the N-sulfonamide unit is achieved by the
reaction of sulfonyl chlorides with alkyl or aryl amine under
basic conditions.14 However, sulfonyl chlorides are often
difficult to handle and store due to their instability.15
Therefore, reduction of N-sulfonylimine is among the most
typical methods. Generally, there are two main types of
strategies, including transition-metal catalysts16 and metal-free
catalysts,17 to achieve the reduction of N-sulfonylimine. Until
now, progress in developing homogeneous catalytic systems,
including transition-metal catalysts such as Zr,16a Ir,16b and
Al16c employed in transformation of N-sulfonamide, has been
made. However, more improvements are needed in the
expansion of the substrate scope and catalytic efficiency.
Herein, we describe our efforts on the design and synthesis of
amide iridium complexes, which present a highly efficient
transfer hydrogenation reduction of N-sulfonyl imine. In
comparison with organic solvents, water is shown to be critical
for a high catalytic transfer hydrogenation reduction.
b
entry
catalyst
solvent
time
yield (%)
1
2
3
4
5
6
Cat-1
Cat-2
Cat-3
TC-4
TC-5
TC-6
Cat-3
Cat-3
Cat-3
Cat-3
Cat-1
Cat-2
Cat-3
Cat-3
Cat-3
Cat-3
Cat-3
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
MeOH
toluene
hexane
1 min
1 min
1 min
15 min
15 min
15 min
5 min
10 min
20 min
8 h
60 h
50 h
30 h
96 h
1 min
30 min
30 min
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
<5
c
7
d
8
e
9
f
10
f
11
f
12
g
13
h
14
15
16
17
RESULTS AND DISCUSSION
■
<5
Synthesis of Amide Ir-Complexes Cat-1−Cat-3. First,
the ligands A−C were prepared according to the reported
methods (Scheme 3).18 With ligands A−C in hand, the amide
Ir-complexes Cat-1−Cat-3 were synthesized according to the
literature (Scheme 1b).19
a
The reactions of 1a (1 mmol, 1.0 equiv) and catalyst (1.0 mol %,
0.01 equiv) were carried out under in air and solvents (2.0 mL),
HCOOH/Et3N (5:2) (1.0 mL). Determined by GC−MS. The
catalyst loading was 0.75 mol %. The catalyst loading was 0.5 mol %.
The catalyst loading was 0.25 mol %. The catalyst loading was 0.1
mol %. The catalyst loading was 0.01 mol %. The catalyst loading
b
c
d
e
f
g
h
Scheme 3. Procedures for Synthesis of Ligands A−C
was 0.001 mol %.
was quantitativly converted to corresponding amine product
within 1 min by employing Ir-complexes Cat-1−Cat-3 as the
catalysts (Table 1, entries 1−3). Encouraged by this promising
result and intrigued by the curiosity about catalytic activity
between our catalysts and Tang’s catalysts, the compared
experiments were investigated between Cat-1−Cat-3 and TC
4−6 under the standard conditions, which demonstrated that
Cat-1−Cat-3 showed higher activity than TC 4−6 based on
the reaction time (Table 1, entries 1−6). Subsequently, Cat-3
was distinguished from cat-1 and cat-2 by decreasing the
catalyst loading to 0.1 mol % (Table 1, entries 7−9). As shown
in Table 1, Cat-3 showed the best catalytic activity. In this
catalytic system, we speculated the mechanism of this
transformation catalyzed by Cat-3 possibly via inner-sphere
monohydride route. The coordinative ability of Cat-3 with the
At the same time, the absolute configurations of amide Ir-
complexes Cat-3 was determined by single-crystal X-ray
diffraction (Scheme 4).
Catalytic Transfer Hydrogenation Reduction of N-
Sulfonylimine with Amide Ir-Complexes. Initially, we
started our investigation by choosing the (E)-N-benzylidene-
benzenesulfonamide (1a) as the model substrate, amide Ir-
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substrates is greatly enhanced due to the strong electron-
withdrawing CF3 group in the ligand, which plays an important
role in accelerating this transformation, compared with Tang’s
catalysts, cat-1 and cat-2.6 To explore the potential catalytic
efficiency, we next evaluated the catalytic performance of Cat-3
at higher S/C ratios. The results were shown in Table 1
(entries 7−10, entries 13 and 14). As can be seen in Table 1,
full conversion was achieved in 20 min even when the catalyst
loading was decreased to 0.25 mol % (Table 1, entry 9). But
when the catalyst loading was decreased to 0.01 and 0.001 mol
%, it took 30 and 96 h to achieve full conversion, respectively.
We speculated the actual TOF of the catalyst is very high when
active catalyst exists. But when 0.1 mol % or even lower
catalyst loading is employed, there is very little real active
catalyst, which consumes significantly higher reaction time.
Interestingly, we noticed that the reaction under the polar
solvents, such as H2O and MeOH, was faster than the
nonpolar solvents toluene and hexane (Table 1, entries 15−
17).
the imines with heteroaromatic (1am) and naphthalene ring
structures (1ak, 1al) all reacted well, affording excellent yields
in 96−98%. Meanwhile, the electron-donating, such as methyl
(1an) and methoxy (1ao, 1ap), or electron-withdrawing, such
as bromine (1aq) and chlorine (1ar), substituted imines were
also well tolerated.
Subsequently, methyl-substituted phenylsulfonamide imines
were also explored. As can be seen in Scheme 6, all substrates,
including electron-donating (1as−1av) or electron-withdraw-
ing substituents (1aw−1ba), were well tolerated in this
catalytic transfer hydrogenation reduction system, providing
various sulfonamide compounds in excellent yields (>96%
yield). Likewise, the N-(2-hydroxybenzyl)-4-methylbenzene-
sulfonamide possessing phenolic hydroxyl showed the same
activity (1bb). Similarly, N-benzyl-4-methoxyaniline is also a
good substrate (1bc).
To explore the potential substrates scope and the
asymmetric results of this chiral iridium complexes catalyzed
transfer hydrogenation reduction system, N-sulfonamideketi-
mine was chosen as the model reaction to investigate this
catalytic activity under the same conditions. To our
disappointment, the N-sulfonamide ketimine (Scheme 6,
1bd) was immediately decomposed into the corresponding
acetophenone under the standard reaction conditions. There-
fore, the chiral catalytic performance of this irdium complexed
is seriously limited in the N-sulfonamide ketimine substrates.
To explore the reactivities of different substrates and the
catalytic efficiency of this catalytic system, a lower catalyst
loading such as 0.1 mol % was also studied (Scheme 6). In
general, lower yields are obtained by using a lower catalyst
loading (0.1 mol %), and greatly prolonged reaction times are
needed, accompanied by a small amount of substrate
decomposition. Compared with 1.0 mol % catalyst, unequal
reactivities of different substrates are showcased by employing
0.1 mol % Cat-3 as catalyst. Generally, the electronegativities
of the R2 substituents have little effects on the activities of the
reaction, while they have more obvious effects on the R1
substituents. For example, when naphthalene (1al), hetero-
cyclic (1am), and benzene containing electron-donating
groups (1an−1ap) are employed as substrates, the reaction
activities are lower and longer reaction times are required. In
particular, when thiophene (1am) and 2-methoxyphenyl
imines (1ap) are employed as substrates, only moderate yields
are obtained.
With the best optimal conditions in hand, the substrate
scope of the aqueous HCO2H/Et3N conditions with 1.0 mol %
Cat-3 as the catalyst was initially screened in the reactions of
imines which were condensed by phenylsulfonamide with
different substituted aldehydes. As can be seen in Scheme 5,
Scheme 5. Transfer Hydrogenation Reduction of
Phenylsulfonamide Imines
Encouraged by the results, we next enforced a scale-up
experiment under the established conditions with 0.001 mol %
cat-3 catalyst loading at the scale of 1aa in 40 mmol, giving 2aa
in a yield of 90% (Scheme 7).
To better understand the reaction mechanism, we
conducted deuterated experiments (Scheme 8). Study showed
that the hydrogen inserted in the product of this hydrogen
transfer reduction came from formic acid. In addition, the
hydride iridium B (Scheme 9) which was detected by NMR by
mixing the iridium catalyst with formic acid and triethylamine,
and the distinctive high-field signal appeared at −12.3 ppm
(see the Supporting Information).
On the basis of our experimental results and previous
reports,20,6 a plausible mechanism is proposed in Scheme 9. As
we know, the formate anion exchanged with the chloride
ligand on bis-nitrogen iridium complexes to yield active A
first.21 Subsequently, active catalyst A gave rise to iridium
hydride B along with extruding carbon dioxide. Then the
imines were trapped by iridium hydride B and formed a four-
the electron-donating substituents Me (1ab), and OMe (1ac,
1ad) were well tolerated, affording the desire products in yields
of 97−98%. Likewise, different halide substituents (Cl, Br, and
F) (1ae−1ai) were also tolerated in different positions of the
phenyl ring in nearly quantitative yields. Notably, the nitro
substituent that is sensitive to hydrogenation was again
tolerated in this catalytic system, providing the corresponding
product 2aj in high yields of 97%. Interestingly, the electron-
withdrawing substituted imines (1ae−2ag) were distinguished
from electron-donating substituted imines (1ab−2ad) by
decreasing the catalyst loading to 0.1 mol % in general.
Next, the transfer hydrogenation reduction of various
substituted phenylsulfonamide imines was investigated with
1.0 mol % Cat-3, which is summarized in Scheme 6. First,
chlorine-substituted phenylsulfonamide imines were inves-
tigated under standard conditions. Encouragingly, the elec-
tronic effects of the substituents are not obvious. For example,
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Scheme 6. Transfer Hydrogenation Reduction of Substituted Phenylsulfonamide Imines
a
b
1.0 mol % catalyst was added. 0.1 mol % catalyst was added.
membered transition intermediate C. Finally, the desired
products were achieved via protonation.
Scheme 7. Large-Scale Experiment
CONCLUSIONS
■
In summary, we have designed and synthesized a type of amide
iridium complex as an efficient catalyst for transfer hydro-
genation reduction of N-sulfonylaldimines by using formic acid
as the hydrogen source and water as the solvent in air. This
protocol allows for a low catalyst loading as 0.001 mol %,
offering an efficient method for synthesis of sulfonamide
compounds. The broad substrate scope, simple operation,
good functional group tolerance, and excellent yield are the
attractive features of this transformation. The application of
ketimine substrate and its asymmetric catalysis research is
underway.
Scheme 8. Deuterated Experiments
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(2S,3aS,7aS)-N-(4-methoxyphenyl) octahydro-1H-indole-2-car-
Scheme 9. Proposed Reaction Mechanism
1
boxamide (B). White solid; mp 130.0−131.0 °C (38.9 g, 96%); H
NMR (400 MHz, CDCl3) 9.82 (s, 1H), 7.50 (d, J = 8.9 Hz, 2H), 6.86
(d, J = 8.9 Hz, 2H), 3.84 (dd, J = 10.6, 4.8 Hz, 1H), 3.78 (s, 3H),
3.38−3.32 (m, 1H), 2.39−2.28 (m, 1H), 2.08−1.96 (m, 2H), 1.93−
1.84 (m, 1H), 1.65−1.43 (m, 5H), 1.42−1.16 (m, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 174.1, 156.2, 131.4, 120.8, 114.3, 59.4,
57.6, 55.6, 38.2, 35.7, 29.5, 27.7, 23.7, 22.0; HRMS (ESI) m/z [M +
H]+ Calcd for C16H23N2O2 275.1760; Found 275.1756.
(2S,3aS,7aS)-N-(4-(Trifluoromethyl)phenyl) octahydro-1H-in-
dole-2-carboxamide (C). White solid; mp 83.0−84.0 °C (44.2 g,
1
96%); H NMR (400 MHz, CDCl3) 10.22 (s, 1H), 7.74 (d, J = 8.5
Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 3.90 (dd, J = 10.7, 4.8 Hz, 1H),
3.41 (q, J = 5.1 Hz, 1H), 2.48−2.30 (m, 1H), 2.18−1.84 (m, 3H),
1.75−1.39 (m, 6H), 1.37−1.19 (m, 2H); 13C{1H} NMR (101 MHz,
4
3
CDCl3) δ 174.8, 141.0, 126.4 (q, JC−F = 3.8 Hz), 125.7 (q, JC−F
=
1
33.3 Hz), 124.3 (q, JC−F = 272.7 Hz), 118.8, 59.5, 57.7, 38.2, 35.7,
29.4, 27.7, 23.6, 22.1; 19F{1H} NMR (367 MHz, CDCl3) δ −62.00.
HRMS (ESI) m/z [M + H]+ Calcd for C16H20F3N2O 313.1528;
Found 313.1525.
General Procedure for Preparation of Catalysts Cat-1−Cat-3.
Catalysts Cat-1−Cat-3 were synthesized according to the literature19
by mixing [IrCp*Cl2]2 (1.0 equiv) and the corresponding ligands A−
C (2.0 equiv) in dry dichloromethane at room temperature. After
being stirred overnight, the yellow solutions were evaporated to
obtain yellow solids, which were used directly in the reduction of
imine. A single crystal of Cat-3 suitable for X-ray diffraction analysis
was obtained in MeOH after many attempts.
EXPERIMENTAL SECTION
■
General Information. Reagents were purchased from commercial
sources. 1H and 13C nuclear magnetic resonance (NMR) spectra were
recorded on Bruker AVANCE NEO 400 MHz NMR spectrometers.
Chemical shifts (δ) are reported in ppm from internal tetramethylsi-
lane or the central CDCl3 resonance (δ = 7.26 ppm) for 1H NMR and
relative to the central CDCl3 resonance (δ = 77.16 ppm) for 13C
NMR spectroscopy. The melting points were determined on WRR
melting point apparatus and are uncorrected. Conversion was
monitored by thin-layer chromatography (TLC). Flash column
chromatography was performed over silica gel (200−300 mesh).
HRMS ESI data were acquired on a Bruker microTOF II
spectrometer.
1
Cat-1. Yellow solid; mp 181−182.0 °C (608 mg, 98%); H NMR
(400 MHz, D2O) δ 7.32 (d, J = 7.9 Hz, 2H), 6.96 (d, J = 7.9 Hz, 2H),
3.86−3.72 (m, 2H), 2.54−2.41 (m, 1H), 2.39 (s, 3H), 2.19−2.06 (m,
1H), 1.99−1.85 (m, 1H), 1.84−1.62 (m, 4H), 1.61−1.53 (m, 2H),
1.52−1.44 (m, 1H), 1.43 (s, 15H), 1.32−1.17 (m, 2H); 13C{1H}
NMR (101 MHz, D2O) δ 192.4, 145.3, 137.0, 129.7, 125.3, 90.5, 63.5,
61.2, 38.8, 30.0, 29.4, 24.3, 20.0, 18.7, 8.6; HRMS (ESI) m/z [M +
H]+ Calcd for C26H37N2OClIr 621.2224; Found 621.2221.
Synthesis of the Ligands A−C.18 To solution of (2S,3aS,7aS)-
octahydro-1H-indole-2-carboxylic acid (25.0 g, 147.9 mmol, 1.0
equiv), dichloromethane (250.0 mL), and di-tert-butyl dicarbonate
(35.5 g, 1.1 equiv) was added TEA (23.0 mL, 1.1 equiv) at room
temperature and the mixture stirred overnight until full conversion.
The pH of the reaction mixture was adjusted to about 7−8 with citric
acid solution. The organic layer was separated, and the inorganic
layers were re-extracted with dichloromethane. The combined organic
layers were washed with brine, dried over Na2SO4, and concentrated
to afford 2-1, which was used in the next step directly.
To a solution of compound 2-1 and Et3N in dichloromethane was
added ethyl carbonochloridate (1.2 equiv) dropwise at 0 °C and the
mixture stirred for 1 h. Amines (1.2 equiv) were added, and the
reaction was stirred overnight. The reaction was wash sequentially
with citric acid solution, saturated Na2CO3, and brine. The organic
layer was dried over Na2SO4 and concentrated to afford compounds
3−1.
Cat-2. Yellow solid; mp 181−182.0 °C (624.5 mg, 98%); 1H NMR
(400 MHz, D2O) δ 7.08 (d, J = 9.1 Hz, 2H), 7.02 (d, J = 9.1 Hz, 2H),
3.85 (s, 3H), 3.77−3.66 (m, 1H), 2.55−2.38 (m, 1H), 2.17−2.06 (m,
1H), 1.96−1.87 (m, 1H), 1.85−1.61 (m, 6H), 1.42 (s, 15H), 1.31−
1.19 (m, 3H); 13C{1H} NMR (101 MHz, D2O) δ 191.4, 157.3, 141.6,
126.6, 114.5, 90.1, 63.3, 61.4, 55.5, 38.7, 29.5, 29.4, 24.4, 24.3, 18.8,
8.6; HRMS (ESI) m/z [M + H]+ Calcd for C26H37N2O2ClIr
637.2173; Found 637.2148.
Cat-3: Yellow solid; mp 191−192.0 °C (660.5 mg, 98%); 1H NMR
(400 MHz, D2O) δ 7.32 (d, J = 7.8 Hz, 2H), 6.96 (d, J = 7.8 Hz, 2H),
3.82 (dd, J = 7.6, 10.0 Hz, 1H), 3.78−3.70 (m, 1H), 2.55−2.42 (m,
1H), 2.23−2.08 (m, 1H), 2.01−1.89 (m, 1H), 1.87−1.60 (m, 5H),
1.54−1.44 (m, 1H), 1.42 (s, 15H), 1.33−1.23 (m, 3H); 13C{1H}
NMR (101 MHz, D2O) δ 190.6, 151.4, 126.7, 126.6, 126.4, 89.9, 63.3,
61.4, 38.8, 29.3, 24.4, 24.3, 23.0, 18.8, 8.51; HRMS (ESI) m/z [M +
H]+ Calcd for C26H34N2OClF3Ir 675.1941; Found 675.1918.
General Procedure for the Synthesis of Imine. A solution of
aldehyde (1.0 equiv) and amide derivatives (1.0 equiv) was added
To a solution of compounds 3-1 (1.0 equiv) in CH2Cl2 was added
TFA (20.0 equiv). The solution was stirred until completion. The
reaction was neutralized with saturated Na2CO3 until pH ∼9. The
aqueous layer was extracted with CH2Cl2 (3 × 50.0 mL). The
combined organic layers were washed with brine and dried over
Na2SO4. Finally, the crude product was purified by flash column
chromatography with petroleum ether/EtOAc (1:1) and concentrated
to afford amides A−C.
(2S,3aS,7aS)-N-(p-Tolyl)octahydro-1H-indole-2-carboxamide
(A). White solid; mp 129.0−130.0 °C (36.6 g, 96%); H NMR (400
Si(OEt)4 (1.2 equiv) and the mixture stirred in a flask equipped at
160 °C until the reaction were completed. The reaction mixture was
suspended in Et2O or n-pentane, filtered, and washed by Et2O or n-
pentane. The target product was directly used in the reaction without
further purification. Imines 1aa,22 1ab,23 1ad,23a 1ae,24 1af,25 1ai,26
1aj,27 1an,28 1ao,29 1ap,30 1aq,30 1ar,28 1as,31 1at,32 1au,31,33 1av,32
1aw,31 1ax,31,32 1ay,25 1az,34 1ba,35 1bb,36 and 1bc37 were prepared
according to the literature.
1
MHz, CDCl3) δ 9.90 (s, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.13 (d, J =
8.2 Hz, 2H), 3.84 (dd, J = 10.7, 4.7 Hz, 1H), 3.36 (q, J = 4.7 Hz, 1H),
2.39−2.32 (m, 1H), 2.31 (s, 3H), 2.22−2.08 (m, 1H), 2.04−1.94 (m,
1H), 1.93−1.85 (m, 1H), 1.65−1.54 (m, 3H), 1.53−1.46 (m, 2H),
1.43−1.35 (m, 1H), 1.34−1.28 (m, 1H), 1.27−1.17 (m, 1H);
13C{1H} NMR (101 MHz, CDCl3) δ 174.2, 135.5, 133.5, 129.6,
119.2, 59.4, 57.6, 38.1, 35.7, 29.5, 27.7, 23.8, 22.0, 21.0; HRMS (ESI)
m/z [M + H]+ Calcd for C16H23N2O 259.1810; Found 259.1807.
(E)-N-(2-Methoxybenzylidene)benzenesulfonamide (1ac). Light
1
yellow solid; yield 10.2 g, 92%; H NMR (400 MHz, CDCl3) δ 9.57
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(s, 1H), 8.12−7.98 (m, 3H), 7.65−7.48 (m, 4H), 7.02−6.94 (m, 2H),
3.93 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 167.0, 161.9,
138.8, 137.2, 133.4, 129.5, 129.2 (2C), 128.0 (2C), 126.5, 121.0,
111.6, 55.9; HRMS (ESI) m/z [M + H]+ Calcd for C14H14NO3S
276.0694; Found 276.0691.
δ 157.2, 140.3, 132.3, 129.8, 129.4, 128.8, 127.0, 124.2, 120.5, 110.1,
55.2, 44.0.
N-(4-Methoxybenzyl)benzenesulfonamide (2ad).38 Purified with
petroleum ether/EtOAc (10:1). Colorless oil; yield 269.5 mg, 98%;
1H NMR (400 MHz, CDCl3) δ 7.87−7.80 (m, 2H), 7.56 (t, J = 7.4
Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.07 (d, J = 8.6 Hz, 2H), 6.75 (d, J
= 8.6 Hz, 2H), 5.17 (t, J = 5.9 Hz, 1H), 4.04 (d, J = 6.1 Hz, 2H), 3.74
(s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 159.2, 140.0, 132.7,
129.3, 129.2, 128.3, 127.1, 114.0, 55.3, 46.8.
(E)-N-(2-Bromobenzylidene)benzenesulfonamide (1ag). Light
1
yellow solid; yield 8.8 g, 93%; H NMR (400 MHz, CDCl3) δ 9.45
(s, 1H), 8.15 (dd, J = 7.7, 1.5 Hz, 1H), 8.03 (d, J = 7.7 Hz, 2H), 7.66
(t, J = 7.5 Hz, 2H), 7.57 (t, J = 7.7 Hz, 2H), 7.49−7.34 (m, 2H).
13C{1H} NMR (101 MHz, CDCl3) δ 169.8, 137.8, 136.0, 134.0,
133.9, 131.3, 130.8, 129.4, 129.2, 128.4, 128.1; HRMS (ESI) m/z: [M
+ H]+ Calcd for C13H11BrNO2S 323.9694; Found: 323.9691.
(E)-N-(3-Bromobenzylidene)benzenesulfonamide (1ah). Light
N-(4-Chlorobenzyl)benzenesulfonamide (2ae).38,40 Purified with
1
petroleum ether/EtOAc (5:1). White solid; yield 273.4 mg, 98%; H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.7 Hz, 2H), 7.59 (t, J = 7.4
Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.12 (d, J
= 8.4 Hz, 2H), 5.44 (t, J = 6.2 Hz, 1H), 4.10 (d, J = 6.3 Hz, 2H);
13C{1H} NMR (101 MHz, CDCl3) δ 139.8, 135.0, 133.7, 132.9,
129.3, 129.2, 128.8, 127.1, 46.5.
1
yellow solid; yield 7.2 g, 91%; H NMR (400 MHz, CDCl3) δ 8.99
(s, 1H), 8.10 (s, 1H), 8.01 (d, J = 7.9 Hz, 2H), 7.83 (d, J = 7.7 Hz,
1H), 7.73 (d, J = 8.1 Hz, 1H), 7.69−7.62 (m, 1H), 7.60−7.54 (m,
2H), 7.38 (t, J = 7.9 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ
169.1, 137.9, 134.3, 134.0, 133.4, 130.8, 130.4, 129.4, 128.3, 126.5,
123.5; HRMS (ESI) m/z [M + H]+ Calcd for C13H11BrNO2S
323.9694; Found 323.9691.
N-(2-Chlorobenzyl)benzenesulfonamide (2af).39 Purified with
petroleum ether/EtOAc (5:1). White solid; yield 270.6 mg, 97%;
1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.1 Hz, 2H), 7.52 (t, J =
7.3 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.33−7.26 (m, 1H), 7.25−7.20
(m, 1H), 7.19−7.08 (m, 2H), 5.60 (t, J = 6.2 Hz, 1H), 4.25 (d, J = 6.5
Hz, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 139.9, 133.8, 133.2,
132.6, 130.1, 129.4, 129.2, 129.0, 127.0, 126.9, 45.0.
(E)-4-Chloro-N-(naphthalen-2-ylmethylene)benzenesulfonamide
1
(1ak). White solid; yield 5.3 g, 92%; H NMR (400 MHz, CDCl3) δ
9.20 (s, 1H), 8.34 (s, 1H), 8.05−7.93 (m, 4H), 7.92−7.86 (m, 2H),
7.65 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.53 (d, J = 8.6 Hz,
2H); 13C{1H} NMR (101 MHz, CDCl3) δ 171.0, 140.1, 137.0, 136.8,
136.7, 132.7, 130.0, 129.8, 129.7, 129.6, 129.6, 129.4, 128.2, 127.5,
124.1; HRMS (ESI) m/z [M + H]+ Calcd for C17H13ClNO2S
330.0356; Found 330.0353
N-(2-Bromobenzyl)benzenesulfonamide (2ag).39 Purified with
petroleum ether/EtOAc (5:1). Colorless oil; Yield: 316.5 mg, 98%;
1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.8 Hz, 2H), 7.57−7.49
(m, 1H), 7.45 (t, J = 8.2 Hz, 3H), 7.30 (d, J = 7.6 Hz, 1H), 7.20 (t, J
= 7.5 Hz, 1H), 7.09 (td, J = 7.8, 1.3 Hz, 1H), 5.40 (t, J = 6.4 Hz, 1H),
4.25 (d, J = 6.5 Hz, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 140.0,
135.4, 132.8, 132.7, 130.5, 129.6, 129.1, 127.7, 127.1, 123.5, 47.5.
N-(3-Bromobenzyl)benzenesulfonamide (2ah). Purified with
petroleum ether/EtOAc (5:1). White solid; yield 313.3 mg, 97%;
(E)-4-Chloro-N-(naphthalen-1-ylmethylene)benzenesulfonamide
1
(1al). White solid; yield 6.2 g, 93%; H NMR (400 MHz, CDCl3) δ
9.63 (s, 1H), 8.97 (d, J = 8.6 Hz, 1H), 8.15 (dd, J = 7.7, 15.9 Hz, 2H),
8.01 (d, J = 8.6 Hz, 2H), 7.93 (d, J = 8.1 Hz, 1H), 7.73−7.66 (m,
1H), 7.63−7.56 (m, 2H), 7.53 (d, J = 8.5 Hz, 2H); 13C{1H} NMR
(101 MHz, CDCl3) δ 171.0, 140.4, 137.0, 136.8, 136.7, 132.7, 130.0,
129.8, 129.7, 129.6, 129.6, 129.5, 129.4, 128.2, 128.1, 127.5, 124.1;
HRMS (ESI) m/z [M + H]+ Calcd for C17H13ClNO2S 330.0356;
Found 330.0353.
(E)-4-Chloro-N-(thiophene-2-ylmethylene)benzenesulfonamide
(1am). White solid; yield 4.5 g, 91%; 1H NMR (400 MHz, CDCl3) δ
9.12 (s, 1H), 9.90 (d, J = 8.6 Hz, 2H), 7.80 (d, J = 4.3 Hz, 2H), 7.49
(d, J = 8.6 Hz, 2H), 7.21 (t, J = 4.4 Hz, 1H); 13C{1H} NMR (101
MHz, CDCl3) δ 163.1, 140.2, 139.8, 138.0, 137.5, 137.1, 129.5, 129.4,
129.2; HRMS (ESI) m/z [M + H]+ Calcd for C11H9ClNO2S2
285.9763; Found 285.9760.
1
mp 73.9−74.2; H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.8 Hz,
2H), 7.61−7.54 (m, 1H), 7.52−7.44 (m, 2H), 7.35−7.29 m, 2H),
7.16−7.07 (m, 2H), 5.57 (t, J = 6.3 Hz, 1H), 4.10 (d, J = 6.4 Hz, 2H);
13C{1H} NMR (101 MHz, CDCl3) δ 139.7, 138.7, 132.9, 130.9,
130.8, 130.2, 129.2, 127.0, 126.5, 122.6, 46.5; HRMS (ESI) m/z [M +
Na]+ Calcd for C13H12BrNNaO2S 347.9670; Found 347.9663.
N-(3-Fluorobenzyl)benzenesulfonamide (2ai). Purified with
petroleum ether/EtOAc (5:1). Colorless oil; yield 255.1 mg, 97%;
1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.8 Hz, 2H), 7.55 (t, J =
7.3 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.23−7.14 (m, 1H), 6.95 (d, J =
7.7 Hz, 1H), 6.92−6.83 (m, 2H), 5.62 (t, J = 6.3 Hz, 1H), 4.10 (d, J =
1
6.4 Hz, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 162.8 (d, JC−F
=
=
General Procedure for Transfer Hydrogenation of N-
Sulfonylimine. The reaction flask was charged with a mixture of 1
(1.0 mmol), cat-3 (1 mol %), H2O (2.0 mL), and hydrogen donor (1
mL, HCO2H/Et3N = 5:2) at room temperature. Upon full conversion
of imine, as monitored by TLC, the mixture was isolated via a short
silica column with petroleum ether/EtOAc (20:1−2:1) to afford the
desired product.
3
2
246.4 Hz), 139.8, 139.0 (d, JC−F = 7.2 Hz), 132.8, 130.1 (d, JC−F
8.1 Hz), 129.2, 127.0, 123.4 (d, 4JC−F = 2.9 Hz), 114.8 (d, 2JC−F = 8.1
Hz), 114.5 (d, JC−F = 7.2 Hz), 46.5; 19F{1H} NMR (367 MHz,
3
CDCl3) δ −122.66; HRMS (ESI) m/z [M + Na]+ Calcd for
C13H12FNNaO2S 288.0470; Found 288.0464.
N-(4-Nitrobenzyl)benzenesulfonamide (2aj):38 Purified with
petroleum ether/EtOAc (4:1). White solid; yield 281.3 mg, 97%;
1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.6 Hz, 2H), 7.84 (d, J =
7.5 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.39
(d, J = 8.5 Hz, 2H), 5.43 (t, J = 6.2 Hz, 1H), 4.25 (d, J = 6.5 Hz, 2H);
13C{1H} NMR (101 MHz, CDCl3) δ 147.6, 144.0, 139.7, 133.2,
129.4, 128.5, 127.1, 123.9, 46.5.
N-Benzylbenzenesulfonamide (2aa).22 Purified with petroleum
1
ether/EtOAc (5:1). Colorless oil; yield 240.1 mg, 98%; H NMR
(400 MHz, CDCl3) δ 7.89−7.82 (m, 2H), 7.60−7.54 (m, 1H), 7.52−
7.44 (m, 2H), 7.31−7.22 (m, 3H), 7.21−7.14 (m, 2H), 5.46 (t, J =
6.3 Hz, 1H), 4.13 (d, J = 6.3 Hz, 2H); 13C{1H} NMR (101 MHz,
CDCl3) δ 139.9, 136.3, 132.6, 129.1, 128.6, 127.9, 127.8, 127.1, 47.1.
N-(4-Methylbenzyl)benzenesulfonamide (2ab).23 Purified with
petroleum ether/EtOAc (10:1). White solid; yield 253.9 mg, 98%; 1H
NMR (400 MHz, CDCl3) δ 7.86 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.5
Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.06 (m, 4H), 5.22 (t, J = 6.0 Hz,
1H), 4.07 (d, J = 6.2 Hz, 2H), 2.29 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 139.9, 137.6, 133.3, 132.6, 129.3, 129.1, 127.9, 127.1,
47.0, 21.1.
4-Chloro-N-(naphthalen-2-ylmethyl)benzenesulfonamide (2ak).
Purified with petroleum ether/EtOAc (5:1). White solid; yield 319.1
mg, 97%; mp 149.8−150.0 °C; 1H NMR (400 MHz, CDCl3) δ 7.82−
7.77 (m, 1H), 7.76−7.69 (m, 4H), 7.58 (s, 1H), 7.50−7.44 (m, 2H),
7.39−7.34 (m, 2H), 7.29−7.23 (m, 1H), 5.17 (t, J = 5.7 Hz, 1H),
4.28 (d, J = 6.2 Hz, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 139.3,
138.6, 133.4, 133.2, 133.0, 129.4, 128.8, 128.7, 127.9, 127.8, 126.9,
126.6, 126.4, 125.7, 47.6; HRMS (ESI) m/z [M + Na]+ Calcd for
C17H14ClNNaO2S 354.0331; Found 354.0325.
N-(2-Methoxybenzyl)benzenesulfonamide (2ac).22 Purified with
1
petroleum ether/EtOAc (5:1). White solid; yield 266.8 mg, 97%; H
NMR (400 MHz, CDCl3) δ 7.91−7.71 (m, 2H), 7.52−7.46 (m, 1H),
7.44−7.36 (m, 2H), 7.23−7.15 (m, 1H), 7.09−7.05 (m, 1H), 6.80 (t,
J = 7.4 Hz, 1H), 6.72(d, J = 8.2 Hz, 1H), 5.41 (t, J = 6.2 Hz, 1H), 4.18
(d, J = 6.4 Hz, 2H), 3.72 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3)
4-Chloro-N-(naphthalen-1-ylmethyl)benzenesulfonamide (2al).
Purified with petroleum ether/EtOAc (5:1). White solid; yield 322.4
1
mg, 98%; M.p.128.6−128.8; H NMR (400 MHz, CDCl3) δ 7.89−
7.83 (m, 1H), 7.82−7.76 (m, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.69−
3855
https://dx.doi.org/10.1021/acs.joc.0c02680
J. Org. Chem. 2021, 86, 3850−3859

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
7.63 (m, 2H), 7.50−7.43 (m, 2H), 7.36−7.22 (m, 4H), 5.23 (t, J =
5.7 Hz, 1H), 4.50 (d, J = 5.9 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 139.1, 138.2, 133.8, 131.1, 131.1, 129.3, 129.2, 128.9, 128.6,
127.2, 126.8, 126.2, 125.2, 123.2, 45.5; HRMS (ESI) m/z [M + Na]+
Calcd for C17H14ClNNaO2S 354.0331; Found 354.0325.
7.20−7.13 (m, 3H), 7.06 (dd, J = 7.4, 1.2 Hz, 1H), 6.77 (t, J = 7.4 Hz,
1H), 6.70(d, J = 8.2 Hz, 1H), 5.42 (t, J = 6.3 Hz, 1H), 4.12 (d, J = 6.4
Hz, 2H), 3.69 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 157.2, 143.0, 137.2, 129.7, 129.4, 129.1, 127.0, 124.3, 120.4,
110.1, 55.1, 43.8, 21.4.
N-(4-Methoxybenzyl)-4-methylbenzenesulfonamide (2av).41 Pu-
rified with petroleum ether/EtOAc (10:1). White solid; yield 283.3
4-Chloro-N-(thiophene-2-ylmethyl) benzenesulfonamide (2am).
Purified with petroleum ether/EtOAc (5:1). White solid; yield 273.6
mg, 96%; mp 114.5−114.6; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J
= 8.6 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 7.16 (dd, J = 4.7, 1.5 Hz,
1H), 6.87−6.79 (m, 2H), 5.45 (t, J = 5.9 Hz, 1H), 4.33 (d, J = 6.1 Hz,
2H); 13C{1H} NMR (101 MHz, CDCl3) δ 139.2, 138.8, 138.5, 129.4,
128.6, 126.9, 126.8, 126.0, 42.0; HRMS (ESI) m/z [M − H]− Calcd
for C11H9ClNO2S2 285.9763; Found 285.9769.
1
mg, 98%; H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.1 Hz, 2H),
7.29 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.4 Hz,
2H), 5.06 (t, J = 5.9 Hz, 1H), 4.04 (d, J = 6.1 Hz, 2H), 3.77 (s, 3H),
2.44 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 159.2, 143.5,
136.9, 129.8, 129.3, 128.4, 127.2, 114.0, 55.3, 46.8, 21.6.
4-Methyl-N-(4-nitrobenzyl)benzenesulfonamide (2aw).41 Puri-
fied with petroleum ether/EtOAc (4:1). White solid; yield 294.9
4-Chloro-N-(4-methylbenzyl)benzenesulfonamide (2an).41 Puri-
fied with petroleum ether/EtOAc (5:1). White solid; yield 287.2 mg,
1
mg, 97%; H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.7 Hz, 2H),
1
7.73 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.1 Hz,
2H), 5.49 (t, J = 6.5 Hz, 1H), 4.23 (d, J = 6.5 Hz, 2H), 2.44 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 147.5, 144.2, 144.1, 136.6,
130.0, 128.6, 127.2, 123.8, 46.4, 21.6.
98%; H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.7 Hz, 2H), 7.44
(d, J = 8.7 Hz, 2H), 7.07 (s, 4H), 5.32 (t, J = 5.9 Hz, 1H), 4.09 (d, J =
6.1 Hz, 2H), 2.32 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
139.1, 138.6, 137.8, 133.0, 129.4, 129.4, 128.6, 127.9, 47.1, 21.2.
4-Chloro-N-(4-methoxybenzyl)benzenesulfonamide (2ao). Puri-
fied with petroleum ether/EtOAc (5:1). White solid; yield 302.8 mg,
98%; mp 98.8−99.0; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.6
Hz, 2H), 7.46 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H), 6.80 (d, J
= 8.7 Hz, 2H), 5.03 (t, J = 5.9 Hz, 1H), 4.09 (d, J = 6.1 Hz, 2H), 3.79
(s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 159.5, 139.2, 138.7,
129.5, 129.4, 128.7, 128.0, 114.2, 55.4, 46.9; HRMS (ESI) m/z [M +
Na]+ Calcd for C14H14ClNNaO3S 334.0281; Found 334.0274.
4-Chloro-N-(2-methoxybenzyl)benzenesulfonamide (2ap). Puri-
fied with petroleum ether/EtOAc (5:1). Colorless oil; yield 296.7 mg,
N-(4-Chlorobenzyl)-4-methylbenzenesulfonamide (2ax).40,41 Pu-
rified with petroleum ether/EtOAc (5:1). White solid; yield 284.2 mg,
1
97%; H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.31
(d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H),
4.97 (t, J = 6.2 Hz, 1H), 4.10 (d, J = 6.3 Hz, 2H), 2.46 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 143.8, 136.9, 135.0, 133.8,
129.9, 129.3, 128.9, 127.3, 46.7, 21.7.
N-(2-Chlorobenzyl)-4-methylbenzenesulfonamide (2ay).40 Puri-
fied with petroleum ether/EtOAc (5:1). White solid; yield 287.2 mg,
98%; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.35−
7.29 (m, 1H), 7.28−7.20 (m, 3H), 7.19−7.11 (m, 2H), 5.44 (t, J =
6.4 Hz, 1H), 4.23 (d, J = 6.5 Hz, 2H), 2.40 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 143.4, 136.9, 134.0, 133.3, 130.1, 129.6, 129.4,
129.2, 127.1, 127.0, 45.0, 21.5.
1
98%; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.7 Hz, 2H), 7.29
(dd, J = 8.7 Hz, 2H), 7.16 (td, J = 8.0, 1.7 Hz, 1H), 7.03 (dd, J = 7.4,
1.6 Hz, 1H), 6.77 (td, J = 7.4, 0.9 Hz, 1H), 6.66 (d, J = 8.1 Hz, 1H),
5.67 (t, J = 6.4 Hz, 1H), 4.15 (d, J = 6.4 Hz, 2H), 3.68 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 157.1, 138.9, 138.5, 129.8,
129.3, 128.9, 128.4, 123.9, 120.4, 110.0, 55.1, 44.0; HRMS (ESI) m/z
[M + Na]+ Calcd for C14H14ClNNaO3S 334.0281; Found 334.0274.
N-(2-Bromobenzyl)-4-chlorobenzenesulfonamide (2aq). Purified
with petroleum ether/EtOAc (5:1). White solid; yield 346.2 mg, 97%;
N-(2-Bromobenzyl)-4-methylbenzenesulfonamide (2az).41 Puri-
fied with petroleum ether/EtOAc (5:1). Colorless oil; yield 323.5 mg,
1
96%; H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.1 Hz, 2H), 7.45
(d, J = 7.9 Hz, 1H), 7.32 (d, J = 7.5 Hz, 1H), 7.25 (d, J = 8.1 Hz, 2H),
7.21 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 7.4 Hz, 1H), 5.35 (t, J = 6.5 Hz,
1H), 4.22 (d, J = 6.5 Hz, 2H), 2.41 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 143.5, 136.9, 135.6, 132.8, 130.4, 129.7, 129.5, 127.7,
127.1, 123.4, 47.4, 21.6.
1
mp 88.2−88.4; H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.7 Hz,
2H), 7.44 (dd, J = 7.9, 1.1 Hz, 1H), 7.39 (d, J = 8.7 Hz, 2H), 7.29
(dd, J = 7.6, 1.7 Hz, 1H), 7.21 (td, J = 7.5, 1.2 Hz, 1H), 7.12 (td, J =
7.7, 1.8 Hz, 1H), 5.44 (t, J = 6.4 Hz, 1H), 4.26 (d, J = 6.5 Hz, 2H);
13C{1H} NMR (101 MHz, CDCl3) δ 139.1, 138.6, 135.2, 132.9,
130.7, 129.8, 129.3, 128.6, 127.8, 123.6, 47.5; HRMS (ESI) m/z [M +
Na]+ Calcd for C13H11BrClNO2SNa 381.9280; Found 381.9282.
4-Chloro-N-(4-chlorobenzyl)benzenesulfonamide (2ar). Purified
with petroleum ether/EtOAc (5:1). White solid; yield 306.7 mg, 98%;
Mp 114.2−114.4; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.7 Hz,
2H), 7.42 (d, J = 8.7 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 7.10 (d, J =
8.5 Hz, 2H), 5.48 (t, J = 6.2 Hz, 1H), 4.06 (d, J = 6.3 Hz, 2H);
13C{1H} NMR (101 MHz, CDCl3) δ 139.4, 138.3, 134.6, 133.9,
129.5, 129.3, 128.9, 128.6, 46.6; HRMS (ESI) m/z [M − H]− Calcd
for C13H10Cl2NO2S 313.9809; Found 313.9815.
N-(3-Fluorobenzyl)-4-methylbenzenesulfonamide (2ba).42 Puri-
fied with petroleum ether/EtOAc (5:1). White solid; yield 265.9 mg,
1
96%; H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.26
(d, J = 8.1 Hz, 2H), 7.19 (dd, J = 14.4, 7.8 Hz, 1H), 6.98 (d, J = 7.7
Hz, 1H), 6.93−6.84 (m, 2H), 5.68 (t, J = 6.4 Hz, 1H), 4.08 (d, J = 6.5
Hz, 2H), 2.41 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 162.7 (d,
J = 246.2 Hz), 143.6, 139.2 (d, J = 7.2 Hz), 136.7, 130.1 (d, J = 8.1
Hz), 129.7, 127.1, 123.4 (d, J = 2.9 Hz), 114.7 (d, J = 18.5 Hz), 114.5
(d, J = 17.6 Hz), 46.5 (d, J = 1.7 Hz), 21.5.
N-(2-Hydroxybenzyl)-4-methylbenzenesulfonamide (2bb).43 Pu-
rified with petroleum ether/EtOAc (2:1). White solid; yield 269.5 mg,
98%; 1H NMR (400 MHz, acetone-d6) δ 8.54 (s, 1H), 7.79 (d, J = 8.3
Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 7.25−7.19 (m, 1H), 7.08 (td, J =
7.9, 1.5 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.77 (t, J = 7.5 Hz, 1H),
6.63 (t, J = 6.3 Hz, 1H), 4.14 (d, J = 6.4 Hz, 2H), 2.37 (s, 3H);
13C{1H} NMR (101 MHz, acetone-d6) δ 155.4, 143.6, 138.6, 130.2,
129.9, 129.2, 127.6, 124.2, 120.2, 115.6, 42.9, 21.3.
N-Benzyl-4-methylbenzenesulfonamide (2as).38 Purified with
petroleum ether/EtOAc (5:1). White solid; yield 253.8 mg, 98%;
1H NMR (400 MHz, CDCl3) δ 7.81−7.69 (m, 2H), 7.36−7.14 (m,
7H), 5.30 (t, J = 6.2 Hz, 1H), 4.10 (d, J = 6.3 Hz, 2H), 2.44 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 143.4, 136.8, 136.4, 129.7,
128.6, 127.9, 127.7, 127.2, 47.2, 21.5.
N-Benzyl-4-methoxyaniline (2bc):44 Purified with petroleum
1
ether/EtOAc (20:1). White solid; yield 206.8 mg, 98%; H NMR
4-Methyl-N-(4-methylbenzyl)benzenesulfonamide (2at).42 Puri-
fied with petroleum ether/EtOAc (10:1). White solid; yield 260.4 mg,
(400 MHz, CDCl3) δ 7.49−7.38 (m, 4H), 7.37−7.31 (m, 1H), 6.89−
6.82 (m, 2H), 6.70−6.63 (m, 2H), 4.35 (s, 2H), 3.81 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 152.2, 142.5, 139.8, 128.6,
127.6, 127.2, 115.0, 114.2, 55.8, 49.2.
1
98%; H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz, 2H), 7.28
(d, J = 8.1 Hz, 2H), 7.08 (q, J = 8.2 Hz, 4H), 5.35 (t, J = 6.1 Hz, 1H),
4.06 (d, J = 6.2 Hz, 2H), 2.44 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 143.3, 137.3, 136.8, 133.4, 129.6, 129.2, 127.8,
127.1, 46.9, 21.5, 21.0.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02680.
■
N-(2-Methoxybenzyl)-4-methylbenzenesulfonamide (2au).41 Pu-
rified with petroleum ether/EtOAc (10:1). Colorless oil; yield 280.4
sı
1
mg, 97%; H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 2H),
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Article
1H and 13C NMR spectra for all compounds prepared
(PDF)
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Accession Codes
CCDC 2040520 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Author
Renshi Luo − School of Pharmaceutical Sciences, Gannan
Medical University, Ganzhou 341000, China; orcid.org/
0000-0001-8966-0387; Email: luorenshi2010@163.com
■
Authors
Huiling Wen − School of Pharmaceutical Sciences, Gannan
Medical University, Ganzhou 341000, China
Nianhua Luo − School of Pharmaceutical Sciences, Gannan
Medical University, Ganzhou 341000, China
Qianheng Zhu − School of Pharmaceutical Sciences, Gannan
Medical University, Ganzhou 341000, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02680
(7) (a) Liu, J.; Wu, X.; Iggo, J. A.; Xiao, J. Half-sandwich iridium
complexes-synthesis and applications in catalysis. Coord. Chem. Rev.
2008, 252, 782−809. (b) Iglesias, M.; Oro, L. A. A leap forward in
iridium-NHC catalysis: new horizons and mechanistic insights. Chem.
Soc. Rev. 2018, 47, 2772−2808.
Notes
The authors declare no competing financial interest.
(8) (a) Luo, N. H.; Liao, J. H.; Ouyang, L.; Wen, H. L.; Liu, J. T.;
Tang, W. P.; Luo, R. S. Highly pH-Dependent Chemoselective
Transfer Hydrogenation of α, β-Unsaturated Aldehydes in Water.
Organometallics 2019, 38, 3025−3031. (b) Luo, N. H.; Liao, J. H.;
Ouyang, L.; Wen, H. L.; Zhong, Y. H.; Liu, J. T.; Tang, W. P.; Luo, R.
S. Highly Selective Hydroxylation and Alkoxylation of Silanes: One-
Pot Silane Oxidation and Reduction of Aldehydes/Ketones. Organo-
metallics 2020, 39, 165−171.
ACKNOWLEDGMENTS
■
The authors thank the National Natural Science Foundation of
China (21962004, 21562004), Jiangxi provincial department of
science and technology (20192BAB203004). This work was
financially supported by Gannan Medical University
(QD201832, QD201816, YJ202027) and the Jiangxi Educa-
tion Hall Science and Technology Foundation (GJJ190829).
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