N -Selenocyanato-Dibenzenesulfonimide: A New Electrophilic Selenocyanation Reagent

Article abstract of DOI:10.1055/a-1493-6885

A new electrophilic selenocyanation reagent N -seleno-cyanato-dibenzenesulfonimide was readily prepared in two steps from commercially available dibenzenesulfonimide for the first time. A variety of electrophilic selenocyanato reactions of nucleophiles have been achieved using it as selenocyanato source under mild and simple conditions. Numerous SeCN-containing compounds were obtained in moderate to excellent yields. Meanwhile, a Lewis acid mediated tandem selenocyanation/cyclization reaction of alkenes with phenols, which provided simple methods for the formation of various SeCN-containing chromanes and dihydrobenzofurans in moderate to good yields, has also been developed.

Full text of DOI:10.1055/a-1493-6885

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–G
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en
D. Zhu et al.
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Synthesis
N-Selenocyanato-Dibenzenesulfonimide: A New Electrophilic
Selenocyanation Reagent
Deng Zhu
Ai-Hui Ye
Zhi-Min Chen*
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School of Chemistry and Chemical Engineering,
Shanghai Key Laboratory for Molecular Engineering of
Chiral Drugs, Shanghai Jiao Tong University, Shanghai
200240, P. R. of China
chenzhimin221@sjtu.edu.cn
ZS2eMch0h0ia-o2MiCol4olic0norh,rfePCeCn.hsRhzpeh.eonCimnmhdiisinntra2gy2Aa1un@tdhsjoCturh.eemduic.canl Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai
Received: 31.03.2021
Accepted after revision: 28.04.2021
Published online: 28.04.2021
tion recently (Figure 1).7 In 2019, Xiao and co-workers de-
veloped the benziodoxolone-based electrophilic selenocya-
nated hypervalent iodine reagent BI-SeCN (1a), which was
the first electrophilic selenocyanation reagent.7b A variety
of racemic -selenocyanated ketones and -keto esters
were obtained under solvent-free condition in good to ex-
cellent yield with this reagent. In 2020, Chen’s group re-
ported N-selenocyanatosaccharin 1b, achieving the first
catalytic asymmetric selenocyanation reaction.7c Later, Xiao
and co-workers developed another new reagent N-seleno-
cyanatophthalimide (1c) and realized the synthesis of 3-
selenocyanato-substituted chromones and quinolinone
through grinding reaction without solvent.7d Our group has
been committed to the efficient and convenient prepara-
tion of sulfur- and selenium-containing compounds, partic-
ularly catalytic asymmetric manner, with the development
and application of new reagents.8 For example, in 2019, we
first reported the synthesis and application of N-thiocyana-
to-dibenzenesulfonimide, which showed high reactivity.9a
Afterwards, Chen’s group also reported this reagent and
demonstrated the anticipated enhanced reactivity.9b In-
spired by previous work and combined with our research
interest, we report herein a new electrophilic selenocyana-
tion reagent, N-selenocyanato-dibenzenesulfonimide (1d),
and its reactivity (Figure 1).
DOI: 10.1055/a-1493-6885; Art ID: ss-2021-z0187-fa
Abstract A new electrophilic selenocyanation reagent N-seleno-
cyanato-dibenzenesulfonimide was readily prepared in two steps from
commercially available dibenzenesulfonimide for the first time. A vari-
ety of electrophilic selenocyanato reactions of nucleophiles have been
achieved using it as selenocyanato source under mild and simple condi-
tions. Numerous SeCN-containing compounds were obtained in mod-
erate to excellent yields. Meanwhile, a Lewis acid mediated tandem
selenocyanation/cyclization reaction of alkenes with phenols, which
provided simple methods for the formation of various SeCN-containing
chromanes and dihydrobenzofurans in moderate to good yields, has
also been developed.
Key words N-selenocyanato-dibenzenesulfonimide, electrophilic seleno-
cyanation, chromane, dihydrobenzofuran, organoselenium compound
Due to the introduction of selenium, the physical and
chemical properties of the compounds will be greatly af-
fected,1 therefore organoselenium compounds2 are widely
found in biologically active natural products, functional
materials, and drug molecules. Among them, SeCN-contain-
ing compounds can act as excellent functional molecules3
not only like anticancer drugs towards colorectal cancer
(CRC) cells,4 but also important synthetic precursors for a
series of valuable organic selenides,5 such as selenides and
diselenides through specific transformations. Therefore, in
recent years, the introduction of selenocyanato group into
compounds has attracted more and more attention.6
SeCN
I
O
O
S
O
N SeCN
O
O
Electrophilic selenocyanation reaction is one of the di-
rect and efficient methods for the construction of SeCN-
containing compounds. Although the development of this
type reaction was once limited to the lack of electrophilic
selenocyanation reagent, some different electrophilic sele-
nocyanation reagents have successively been developed and
successfully applied to electrophilic selenocyanation reac-
1a (Xiao, 2019)
1b (Chen, 2020)
O
O O
N
O
O
S
S
N
SeCN
SeCN
O
1c (Xiao, 2021)
1d (this work)
Figure 1 Electrophilic selenocyanation reagents
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Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
D. Zhu et al.
Feature
Synthesis
We envisioned that the preparation of N-selenocyanato-
dibenzenesulfonimide may be achieved according to our
previous synthetic strategy of N-thiocyanato-dibenzenesul-
fonimide.9a To our delight, N-selenocyanato-dibenzenesul-
fonimide (1d) was easily synthesized in two steps in 74%
overall yield. N-Chloro-dibenzenesulfonimide, which was
prepared first, reacted with AgSeCN (1.2 equiv) in CH2Cl2 to
produce 1d as a faint yellow solid in 92% yield (Scheme 1).
Although it is not very sensitive to air and temperature, we
suggest to store it under argon atmosphere and at low tem-
perature. The configuration of 1d was determined by X-ray
crystallography (Figure 2).10
Using 1d developed above, we first explored its reactivi-
ty with a variety of nucleophiles (Scheme 2). To our delight,
without adding any catalyst or additive, the corresponding
selenocyanated products of indole, aniline, phenol, thio-
phenol, and anisole derivatives were readily obtained in
moderate to excellent yields under mild conditions, which
showed the high reactivity of 1d. The reaction of indole
type compounds 3a–c occurs in excellent yields, while the
selenocyanation of aniline derivatives exclusively occurs at
the para-position to the amino group in excellent yields (→
3d, e). Similarly, selenocyanated phenol 3f was obtained in
moderate yield with the para-substitution of hydroxyl
group. It was worth noting that the S-substitution reaction
took place at the sulfhydryl group in the case of thiophe-
nols (→ 3g, h). Moreover, anisole derivatives were exclu-
sively mono-selenocyanated to 3i, j in good yields, and the
reaction of 1,3-dimethoxybenzene gave only 2,4-dime-
thoxy-1-selenocyanatobenzene (3i). In addition, we found
that some of the substrates could not react with 1d
smoothly without any catalyst, so TfOH was chosen as the
catalyst. Thus, benzothiophene (2k) and thiophene (2l)
could produce the corresponding products 3k and 3l in 69%
and 56% yield, respectively, in the presence of TfOH. Nota-
bly, the reaction of propiophenone produced the -seleno-
cyanated product 3m in 75% yield.
O O
O O
N
O
O
O
O
tBuOCl (1.1 equiv)
MeOH, rt, 81%
AgSeCN (1.2 equiv)
CH2Cl2, rt, 92%
PhO2S
PhO2S
S
S
S
S
NH
Ph
N
Ph
Ph
Ph
Cl
SeCN
1d
Scheme 1 Synthesis of N-selenocyanato-dibenzenesulfonimide
Figure 2 The configuration of 1d determined by X-ray crystallography
Biographical Sketches
Deng Zhu (right) was born in 1997 in Zhe-
jiang Province (P. R. of China). He received
his bachelor’s degree in Collaboration Inno-
vation Center of Yangtze Delta Green Phar-
maceuticals at Zhejiang University of
Technology in 2019. Currently, he is carry-
ing out his master’s studies under the direc-
tion of associate Prof. Zhi-Min Chen at
Shanghai Jiao Tong University.
B.Sc. degree in chemistry from Guangxi
Normal University in 2018. Now, she has
started her Ph.D. in organic chemistry at
the Shanghai Jiao Tong University under the
guidance of associate Prof. Zhi-Min Chen.
Her current interests focus on synthesis and
applications of new electrophilic sulfur and
selenium reagents.
in 2014 from Lanzhou University under the
supervision of Prof. Yong-Qiang Tu. After
spending three years (2014–2017) as a
postdoctoral fellow at Shanghai Jiao Tong
University (Mentor: Prof. Yong-Qiang Tu)
and University of Utah (USA; 2015–2017,
Mentor: Prof. Matthew S. Sigman), he was
appointed as associate professor at Shang-
hai Jiao Tong University in 2017. His re-
search focuses mainly on asymmetric
sulfur/selenium chemistry and synthesis of
natural products.
Zhi-Min Chen (left) received his B.S. from
Fuzhou University (P. R. of China) in 2009.
He obtained his Ph.D. in organic chemistry
Ai-Hui Ye (center) was born in Zhejiang
Province (P. R. of China). She obtained her
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

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D. Zhu et al.
Feature
Synthesis
SeCN
SeCN
H
O O
N
O
O
SeCN
R2
R2
S
S
1
Het
Het
O O
N
TMSCl (1.0 equiv)
MeCN, rt
R1
O
O
R
S
S
MeCN, rt
O
OH
SeCN
1d
H
SeCN
4
5
R
R
2
1d
3
SeCN
SeCN
MeO
SeCN
SeCN
SeCN
N
SeCN
O
O
O
SeCN
OMe
5b, 63%
N
N
H
5a, 78%
5c, 67%
H2N
H
3a, 96%
3b, 98%
3c, 97%
3d, 95%
SeCN
SeCN
S
S
SeCN
SeCN
MeO
SeCN
N
HO
F
O
3g, 58%
3e, 94%
3f, 54%
3h, 53%
Cl
5d, 65%
CCDC 2073817
OMe
SeCN
MeO
OMe
Scheme 3 Substrate scope of -substituted 2-allylphenols. Reagents
and conditions: -substituted 2-allylphenol 4 (0.1 mmol), 1d (0.13
mmol), and TMSCl (0.1 mmol) in MeCN (1 mL) were stirred at rt for
2–12 h under argon. Isolated yields are shown. 5b,d: AcCl was used
instead of TMSCl.
SeCN
S
S
MeO
OMe
SeCN
SeCN
3k, 69%
3l, 56%
3i, 75%
3j, 80%
O
O
O O
N
O
O
S
S
MeCN, rt
SeCN
SeCN
3m, 75%
size diverse SeCN-containing dihydrobenzofurans and con-
struct oxa-quaternary stereocenters. After screening some
reaction conditions, we found that the desired product 7a
was delivered in 66% yield using acetyl chloride as the acid
promotor when -substituted 2-allylphenol 6a was used as
the model substrate. Similarly, some different -substituted
2-allylphenols were tested for the examination of the appli-
cability of this reaction. Generally, the desired products
were obtained in moderate to good yields (Scheme 4). It
was found that the ortho-substituted phenol 7b and the
alkene with the electron-deficient phenyl group 7c de-
creased the yield. Compared with 6a, substrate 6d with
electron-rich alkene gave a higher yield (79%) using
trimethylchlorosilane instead of acetyl chloride as the acid
2m
1d
Scheme 2 Substrate scope of different kinds of nucleophiles. Reagents
and conditions: Nucleophile 2 (0.1 mmol) and 1d (0.13 mmol) in MeCN
(1 mL) were stirred at rt for 20–30 min under argon. Isolated yields are
shown. 3k,l,m: TfOH (0.01 mmol) was added as the catalyst. 3l: From
thiophene (2l; 0.15 mmol) and 1d (0.1 mmol).
After preliminarily investigating the reactivity between
1d and various nucleophiles, we wondered whether difunc-
tionalization of olefins including selenocyanation could oc-
cur with reagent 1d. Considering that compounds with
chromane and dihydrobenzofuran frameworks are widely
present in biologically active molecules, and combined with
our previous research,8e we envisioned that the intramolec-
ular tandem selenocyanation/cyclization reaction between
2-allylphenols and 1d may be achieved.
To examine our hypothesis, -substituted 2-allylphenol
4a as the model substrate was reacted first with 1d in the
presence of trimethylchlorosilane as the acid activator in
acetonitrile at room temperature. To our delight, the de-
sired product 5a was readily obtained in 78% yield. Al-
though some other reaction conditions were investigated,
no better result was obtained. With the above conditions in
hand, three other -substituted 2-allylphenols were also in-
vestigated. In general, the desired selenocyanated chroman
skeleton compounds were obtained in moderate to good
yields (Scheme 3). In some cases 5b,d, acetyl chloride was
used as the acid activator. Meanwhile, we found that the
substrate with electron-rich substituent at phenyl group
could give a higher yield (5a vs 5b). The relative configura-
tion of 5d was determined by X-ray crystallography.11
Subsequently, in order to further broaden the applica-
tion range of 1d, several -substituted 2-allylphenols were
also chosen as the substrates, which could facilely synthe-
O O
N
O
O
O
OH
O
R2
AcCl (1.0 equiv)
MeCN, –20 °C
S
S
R1
R1
R2
SeCN
1d
SeCN
7
6
OMe
F
O
O
O
SeCN
SeCN
SeCN
O O
SeCN
7c, 59%
7d, 79%
7a, 66%
7b, 52%
O
O
OH
AcCl (1.0 equiv)
MeCN, rt
S
S
O
N
SeCN
1d
SeCN
6e
7e, 48%
Scheme 4 Substrate scope of -substituted 2-allylphenols and -sub-
stituted 2-homoallylphenol. Reagents and conditions: -substituted 2-al-
lylphenol (-substituted 2-homoallylphenol) 6 (0.1 mmol), 1d (0.13
mmol), and AcCl (0.1 mmol) in MeCN (1 mL) were stirred at –20 °C for
2–12 h under argon. Isolated yields are shown. 7d: TMSCl was used in-
stead of AcCl.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

D
D. Zhu et al.
Feature
Synthesis
promotor. Finally, -substituted 2-homoallylphenol 6e was
also subjected to this reaction and the corresponding chro-
man product 7e was obtained, albeit in only 48% yield.
Based on our previous work8e and the above results, a
possible mechanism for intramolecular selenocyanation of
2-allylphenol is proposed in Scheme 5. TMSCl may directly
activate 1d to form the more active ClSeCN, which then un-
dergoes the electrophilic addition to alkene, forming CN-
containing selenonium ion intermediate 8a. This is subse-
quently attacked by phenolic hydroxyl group and the prod-
uct 5a would be obtained after deprotonation, accompanied
by the formation of dibenzenesulfonimide. The excellent di-
astereoselectivity of this reaction could result from the col-
laborative process. For 1,1-disubstituted alkene substrates,
the regioselectivity may be attributed to distinct electronic
bias for selenonium ion opening.
N-Selenocyanato-Benzenesulfonamide (1d)
Under dark, water-free, and oxygen-free conditions, to a stirred solu-
tion of N-chloro-dibenzenesulfonimide (500 mg, 1.5 mmol) in CH2Cl2
(15 mL) was added silver selenocyanate (383 mg, 1.8 mmol, 1.2 equiv)
under an argon atmosphere. The flask was covered with thin foil and
stirred at rt for 3.5 h. After completion of the reaction, the undis-
solved solids were filtered off and the residue was concentrated un-
der vacuum to give 1d as a faint yellow solid; yield: 553 mg (1.38
mmol, 92%); mp 150–153 °C.
1H NMR (CD2Cl2, 400 MHz):  = 7.99 (d, J = 7.5 Hz, 4 H), 7.74 (t, J = 7.4
Hz, 2 H), 7.61 (t, J = 7.9 Hz, 4 H).
13C NMR (CD2Cl2, 101 MHz):  = 135.2, 129.8, 128.9, 102.4.
HRMS (APCI): m/z [M + H]+ calcd for C13H11N2O4S2Se: 402.9325;
found: 402.9319.
Selenocyanation; General Procedure
At rt, 2 (0.10 mmol) and 1d (52.1 mg, 0.13 mmol) were added to an
over-dried 10 mL flask equipped with a stir bar. The flask was then
sealed with a septum. Anhyd MeCN (1 mL) was added via a syringe,
and the solution was stirred for about 20 min. After the completion of
the reaction (monitored by TLC), the solvent was removed under re-
duced pressure, and the crude product was purified by silica gel flash
column chromatography.
O O
N
Cl–
MeO
O
O
S
S
4a
Se CN
Ph
Ph
Ph
+ TMSCl
5a
ClSeCN
O
H
SeCN
8a
Scheme 5 Proposed mechanism
3-Selenocyanato-1H-indole (3a)
In summary, we have developed a convenient and effi-
cient method for the synthesis of a new electrophilic sele-
nocyanation reagent, N-selenocyanato-dibenzenesulfonim-
ide (1d), which showed good reactivity with various nucleo-
Orange solid; Rf = 0.20 (silica gel, PE:EtOAc 5:1, v/v); yield: 21.2 mg
(0.096 mmol, 96%); mp 80–82 °C.
1H NMR (CDCl3, 400 MHz):  = 8.74 (s, 1 H), 7.76–7.74 (m, 1 H), 7.48–
7.40 (m, 2 H), 7.33–7.29 (m, 2 H).
philes. Furthermore,
a Lewis acid mediated tandem
13C NMR (CDCl3, 101 MHz):  = 136.1, 132.0, 128.8, 123.9, 121.9,
selenocyanation/cyclization reaction of alkenes with phe-
nols was explored for the first time. Various SeCN-contain-
ing chromanes and dihydrobenzofurans were readily syn-
thesized in moderate to good yields. Further exploration of
the applications of reagent 1d are underway in our lab.
119.6, 112.0, 102.2, 89.5.
HRMS (ESI): m/z [M + Na]+ calcd for C9H6N2SeNa: 244.9588; found:
244.9589.
3-Methyl-2-selenocyanato-1H-indole (3b)
Orange solid; Rf = 0.35 (silica gel, PE:EtOAc 8:1, v/v); yield: 23.0 mg
(0.098 mmol, 98%); mp 87–88 °C.
1H NMR (CDCl3, 400 MHz):  = 8.31 (s, 1 H), 7.59 (d, J = 8.0 Hz, 1 H),
7.35 (d, J = 8.2 Hz, 1 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.18 (t, J = 7.5 Hz, 1 H),
2.46 (s, 3 H).
13C NMR (CDCl3, 101 MHz):  = 138.2, 127.7, 124.9, 122.5, 120.4,
119.9, 111.3, 107.8, 100.1, 10.5.
Unless otherwise noted, all reactions were carried out under an at-
mosphere of argon. All chemicals were purchased from commercial
suppliers and used without further purification. In addition to com-
mercially available extra anhydrous solvents, all solvents were puri-
fied by standard operating method. TLC was performed with EMD sil-
ica gel 60 F254 plates eluting with solvents indicated; visualized by a
HRMS (ESI): m/z [M + Na]+ calcd for C10H8N2SeNa: 258.9745; found:
258.9744.
1
254 nm UV lamp and stained with phosphomolybdic acid (PMA). H
NMR, 13C NMR, and 19F NMR spectra were obtained on a Bruker AM-
400 spectrometer. Chemical shifts () were quoted in ppm relative to
deuterated solvent as internal standard (CDCl3: 7.26 ppm for 1H NMR;
CDCl3: 77.16 ppm for 13C NMR), multiplicities are indicated by stan-
dard abbreviations. High-resolution mass spectral analysis (HRMS)
data were measured on a Bruker impact II(Q-TOF) mass spectrometer
by means of the ESI technique and a Fourier Transform Ion Cyclotron
(SolariX 7.0T). Crystallographic data was obtained from a Bruker D8
VENTURE diffractometer. Melting points were measured on a melting
point apparatus and are uncorrected. Substrates 2 were purchased
from commercial suppliers while substrates 4 and 6 were prepared
according to previously reported procedures.8e
1-Methyl-3-selenocyanato-1H-indole (3c)
Yellow solid; Rf = 0.40 (silica gel, PE:EtOAc 5:1, v/v); yield: 22.7 mg
(0.097 mmol, 97%); mp 80–82 °C.
1H NMR (CDCl3, 400 MHz):  = 7.75 (d, J = 7.3 Hz, 1 H), 7.39–7.29 (m, 4
H), 3.81 (s, 3 H).
13C NMR (CDCl3, 101 MHz):  = 137.3, 136.0, 129.6, 123.4, 121.6,
119.9, 110.1, 101.9, 87.3, 33.4.
HRMS (ESI): m/z [M + Na]+ calcd for C10H8N2SeNa: 258.9745; found:
258.9745.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

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D. Zhu et al.
Feature
Synthesis
4-Selenocyanatoaniline (3d)
1,3,5-Trimethoxy-2-selenocyanatobenzene (3j)
Yellow solid; Rf = 0.30 (silica gel, PE:EtOAc 2:1, v/v); yield: 18.8 mg
White solid; Rf = 0.30 (silica gel, PE:EtOAc 5:1, v/v); yield: 21.3 mg
(0.095 mmol, 95%); mp 73–74 °C.
(0.080 mmol, 80%); mp 97–99 °C.
1H NMR (CDCl3, 400 MHz):  = 7.44 (d, J = 8.4 Hz, 2 H), 6.64 (d, J = 8.4
1H NMR (CDCl3, 400 MHz):  = 6.17 (s, 2 H), 3.90 (s, 6 H), 3.84 (s, 3 H).
Hz, 2 H), 3.95 (s, 2 H).
13C NMR (CDCl3, 101 MHz):  = 148.9, 136.6, 116.4, 107.3, 102.8.
13C NMR (CDCl3, 101 MHz):  = 164.3, 160.9, 102.1, 91.5, 89.9, 56.5,
55.7.
HRMS (ESI): m/z [M + Na]+ calcd for C7H6N2SNae: 220.9588; found:
HRMS (ESI): m/z [M + Na]+ calcd for C10H11NO3SeNa: 295.9796; found:
220.9589.
295.9796.
N,N-Dimethyl-4-selenocyanatoaniline (3e)
3-Selenocyanatobenzo[b]thiophene (3k)
Yellow solid; Rf = 0.30 (silica gel, PE:EtOAc 8:1, v/v); yield: 21.3 mg
White solid; Rf = 0.45 (silica gel, PE:EtOAc 10:1, v/v); yield: 16.4 mg
(0.094 mmol, 94%); mp 97–98 °C.
(0.069 mmol, 69%); mp 120–122 °C.
1H NMR (CDCl3, 400 MHz):  = 7.51 (d, J = 8.9 Hz, 2 H), 6.65 (d, J = 9.0
Hz, 2 H), 2.99 (s, 6 H).
1H NMR (CDCl3, 400 MHz):  = 7.98 (d, J = 8.0 Hz, 1 H), 7.92 (d, J = 6.5
Hz, 2 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H).
13C NMR (CDCl3, 101 MHz):  = 151.8, 136.5, 113.4, 104.5, 102.9, 40.2.
13C NMR (CDCl3, 101 MHz):  = 139.6, 138.6, 135.3, 125.8, 125.8,
123.4, 123.1, 109.2, 100.1.
HRMS (APCI): m/z [M]+ calcd for C9H5NSSe: 238.9308; found:
HRMS (ESI): m/z [M + H]+ calcd for C9H11N2Se: 227.0082; found:
227.0079.
238.9302.
4-Selenocyanatophenol (3f)
2-Selenocyanatothiophene (3l)
Yellow solid; Rf = 0.35 (silica gel, PE:EtOAc 2:1, v/v); yield: 10.7 mg
(0.054 mmol, 54%); mp 75–77 °C.
Colorless oil; Rf = 0.50 (silica gel, PE:EtOAc 5:1, v/v); yield: 10.3 mg
(0.056 mmol, 56%).
1H NMR (CDCl3, 400 MHz):  = 7.55 (d, J = 8.7 Hz, 2 H), 6.86 (d, J = 8.7
Hz, 2 H), 5.67 (s, 1 H).
13C NMR (CDCl3, 101 MHz):  = 158.0, 136.5, 117.7, 111.0, 102.6.
HRMS (ESI): m/z [M + H]+ calcd for C7H6NOSe: 199.9609; found:
199.9611.
1H NMR (CDCl3, 400 MHz):  = 7.60 (dd, J = 5.4, 1.2 Hz, 1 H), 7.47 (dd, J
= 3.7, 1.2 Hz, 1 H), 7.09 (dd, J = 5.4, 3.7 Hz, 1 H).
13C NMR (CDCl3, 101 MHz):  = 139.1, 134.6, 128.8, 112.6, 101.0.
HRMS (ESI): m/z [M + H]+ calcd for C5H4NSSe: 189.9224; found:
189.9225.
SeS-(4-Fluorophenyl) (Selenothioperoxocyanate) (3g)
1-Phenyl-2-selenocyanatopropan-1-one (3m)
Yellow oil; Rf = 0.50 (silica gel, pure PE); yield: 13.3 mg (0.058 mmol,
58%).
White solid; Rf = 0.50 (silica gel, PE:EtOAc 6:1, v/v); yield: 17.6 mg
(0.075 mmol, 75%); mp 74–76 °C.
1H NMR (CDCl3, 400 MHz):  = 7.57–7.47 (m, 2 H), 7.05–6.91 (m, 2 H).
1H NMR (CDCl3, 400 MHz):  = 7.92 (d, J = 7.4 Hz, 2 H), 7.67 (t, J = 7.5
Hz, 1 H), 7.53 (t, J = 7.7 Hz, 2 H), 5.40 (q, J = 7.3 Hz, 1 H), 2.05 (d, J = 7.3
Hz, 3 H).
13C NMR (CDCl3, 101 MHz):  = 197.2, 134.8, 132.9, 129.3, 129.1,
102.8, 49.2, 21.5.
13C NMR (CDCl3, 101 MHz):  = 163.3 (d, JC,F = 249.6 Hz), 134.5, 134.4
(d, JC,F = 8.4 Hz), 132.1 (d, JC,F = 3.4 Hz), 116.4 (d, JC,F = 22.0 Hz).
19F NMR (CDCl3, 376 MHz):  = –112.26 (s, 1 F).
HRMS (MALDI): m/z [M]+ calcd for C7H4FNSSe: 232.9214; found:
232.9208.
HRMS (ESI): m/z [M + Na]+ calcd for C10H9NOSeNa: 261.9742; found:
261.9743.
SeS-(4-Methoxyphenyl) (Selenothioperoxocyanate) (3h)
Yellow solid; Rf = 0.50 (silica gel, PE:EtOAc 10:1, v/v); yield: 12.8 mg
(0.053 mmol, 53%); mp 64–65 °C.
3-Selenocyanatochromanes 5; General Procedure
At rt, 4 (0.10 mmol), 1d (52.1 mg, 0.13 mmol), and Me3SiCl (13.0 L,
0.10 mmol) were added to an over-dried 10 mL flask equipped with a
stir bar. The flask was then sealed with a septum. Anhyd MeCN (1 mL)
was added via a syringe, and the solution was stirred for 2 h to 12 h.
After completion of the reaction (monitored by TLC), the solvent was
removed under reduced pressure, and the crude product was purified
by silica gel flash column chromatography.
1H NMR (CDCl3, 400 MHz):  = 7.40 (d, J = 8.7 Hz, 2 H), 6.83 (d, J = 8.7
Hz, 2 H), 3.80 (s, 3 H).
13C NMR (CDCl3, 101 MHz):  = 160.1, 134.6, 132.8, 128.6, 114.8, 55.5.
HRMS (APCI): m/z [M + H]+ calcd for C8H8NOSSe: 245.9492; found:
245.9486.
2,4-Dimethoxy-1-selenocyanatobenzene (3i)
6-Methoxy-2-phenyl-3-selenocyanatochromane (5a)
Colorless oil; Rf = 0.35 (silica gel, PE:EtOAc 10:1, v/v); yield: 17.9 mg
(0.075 mmol, 75%).
1H NMR (CDCl3, 400 MHz):  = 7.52 (d, J = 8.6 Hz, 1 H), 6.55 (dd, J = 8.7,
2.5 Hz, 1 H), 6.49 (d, J = 2.5 Hz, 1 H), 3.88 (s, 3 H), 3.82 (s, 3 H).
13C NMR (CDCl3, 101 MHz):  = 162.6, 158.0, 133.1, 106.9, 101.9,
101.9, 99.5, 56.3, 55.8.
HRMS (ESI): m/z [M + Na]+ calcd for C9H9NO2SeNa: 265.9691; found:
Colorless oil; Rf = 0.50 (silica gel, PE:EtOAc 5:1, v/v); yield: 26.6 mg
(0.078 mmol, 78%).
1H NMR (CDCl3, 400 MHz):  = 7.46–7.36 (m, 5 H), 6.87 (d, J = 8.9 Hz, 1
H), 6.78 (dd, J = 8.9, 3.0 Hz, 1 H), 6.62 (d, J = 2.9 Hz, 1 H), 5.13 (d, J = 8.2
Hz, 1 H), 4.13 (td, J = 8.3, 6.5 Hz, 1 H), 3.77 (s, 3 H), 3.37 (d, J = 7.0 Hz, 2
H).
265.9694.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

F
D. Zhu et al.
Feature
Synthesis
13C NMR (CDCl3, 101 MHz):  = 154.4, 147.7, 138.0, 129.5, 129.2,
HRMS (ESI): m/z [M + Na]+ calcd for C16H13NOSeNa: 338.0055; found:
126.8, 120.2, 117.9, 114.9, 113.4, 100.5, 80.3, 55.8, 44.7, 33.5.
338.0050.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NO2SeNa: 368.0160; found:
368.0157.
7-Methyl-2-phenyl-2-(selenocyanatomethyl)-2,3-dihydrobenzo-
furan (7b)
Colorless oil; Rf =0.50 (silica gel, PE:EtOAc 5:1, v/v); yield: 16.8 mg
6-Methyl-2-phenyl-3-selenocyanatochromane (5b)
(0.052 mmol, 52%).
Yellow oil; Rf = 0.60 (silica gel, PE:EtOAc 10:1, v/v); yield: 20.6 mg
(0.063 mmol, 63%).
1H NMR (CDCl3, 400 MHz):  = 7.47 (d, J = 7.7 Hz, 2 H), 7.41 (t, J = 7.5
Hz, 2 H), 7.34 (t, J = 7.2 Hz, 1 H), 7.04–6.96 (m, 2 H), 6.82 (t, J = 7.4 Hz,
1 H), 3.78–3.66 (m, 3 H), 3.58 (d, J = 15.7 Hz, 1 H), 2.35 (s, 3 H).
1H NMR (CDCl3, 400 MHz):  = 7.43–7.38 (m, 5 H), 7.08 (d, J = 7.2 Hz, 1
H), 6.94 (d, J = 7.5 Hz, 1 H), 6.87 (t, J = 7.4 Hz, 1 H), 5.24 (d, J = 7.9 Hz, 1
H), 4.12 (td, J = 8.0, 5.9 Hz, 1 H), 3.47–3.19 (m, 2 H), 2.22 (s, 3 H).
13C NMR (CDCl3, 101 MHz):  = 156.4, 142.9, 130.0, 128.9, 128.4,
125.0, 124.6, 122.4, 121.6, 120.4, 102.1, 88.7, 43.4, 41.5, 15.4.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NOSeNa: 352.0211; found:
13C NMR (CDCl3, 101 MHz):  = 151.8, 138.4, 129.8, 129.4, 129.1,
126.9, 126.6, 126.4, 121.2, 119.0, 100.6, 80.3, 45.0, 33.1, 16.1.
352.0209.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NOSeNa: 352.0211; found:
352.0206.
2-(4-Fluorophenyl)-2-(selenocyanatomethyl)-2,3-dihydrobenzo-
furan (7c)
2-(4-Methoxyphenyl)-3-selenocyanatochromane (5c)
Colorless oil; Rf = 0.45 (silica gel, PE:EtOAc 5:1, v/v); yield: 19.2 mg
(0.059 mmol, 59%).
Colorless oil; Rf = 0.65 (silica gel, PE:EtOAc 5:1, v/v); yield: 22.6 mg
(0.067 mmol, 67%).
1H NMR (CDCl3, 400 MHz):  = 7.34 (d, J = 8.4 Hz, 2 H), 7.19 (t, J = 7.8
Hz, 1 H), 7.11 (d, J = 7.6 Hz, 1 H), 6.99–6.90 (m, 4 H), 5.09 (d, J = 8.8 Hz,
1 H), 4.11 (td, J = 8.8, 6.4 Hz, 1 H), 3.83 (s, 3 H), 3.47–3.40 (m, 2 H).
13C NMR (CDCl3, 101 MHz):  = 160.6, 154.0, 129.8, 129.3, 128.5,
128.3, 121.7, 119.85, 117.1, 114.5, 100.4, 80.2, 55.5, 44.7, 33.8.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NO2SeNa: 368.0160; found:
368.0161.
1H NMR (CDCl3, 400 MHz):  = 7.45 (dd, J = 8.7, 5.2 Hz, 2 H), 7.23–7.14
(m, 2 H), 7.09 (t, J = 8.6 Hz, 2 H), 6.97–6.88 (m, 2 H), 3.76–3.63 (m, 3
H), 3.55 (d, J = 15.8 Hz, 1 H).
13C NMR (CDCl3, 101 MHz):  = 162.6 (d, JC,F = 247.8 Hz), 157.9, 138.4
(d, JC,F = 3.2 Hz), 128.9, 127.0 (d, JC,F = 8.3 Hz), 125.2, 125.1, 121.9,
115.9 (d, JC,F = 21.8 Hz), 110.1, 101.8, 88.9, 43.1, 41.3.
19F NMR (CDCl3, 376 MHz):  = –113.55 (s, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C16H12FNOSeNa: 355.9960;
found: 355.9955.
2-(4-Chlorophenyl)-3-selenocyanatochromane (5d)
White solid; Rf = 0.55 (silica gel, PE:EtOAc 5:1, v/v); yield: 22.4 mg
(0.065 mmol, 65%); mp 143–145 °C.
1H NMR (CDCl3, 400 MHz):  = 7.40 (d, J = 8.5 Hz, 2 H), 7.35 (d, J = 8.4
Hz, 2 H), 7.25–7.16 (m, 1 H), 7.10 (d, J = 7.6 Hz, 1 H), 6.98 (t, J = 7.5 Hz,
1 H), 6.92 (d, J = 8.3 Hz, 1 H), 5.17 (d, J = 8.3 Hz, 1 H), 4.02 (td, J = 8.2,
6.5 Hz, 1 H), 3.39 (d, J = 7.3 Hz, 2 H).
13C NMR (CDCl3, 101 MHz):  = 153.6, 136.5, 135.4, 129.4, 129.3,
128.7, 128.3, 122.0, 119.6, 117.1, 100.0, 79.9, 44.4, 33.1.
HRMS (ESI): m/z [M + Na]+ calcd for C16H12ClNOSeNa: 371.9665;
found: 371.9662.
2-(4-Methoxyphenyl)-2-(selenocyanatomethyl)-2,3-dihydro-
benzofuran (7d)
Colorless oil; Rf = 0.45 (silica gel, PE:EtOAc 5:1, v/v); yield: 26.8 mg
(0.079 mmol, 79%).
1H NMR (CDCl3, 400 MHz):  = 7.41–7.34 (m, 2 H), 7.21–7.11 (m, 2 H),
6.94–6.89 (m, 4 H), 3.81 (s, 3 H), 3.75–3.65 (m, 3 H), 3.55 (d, J = 15.7
Hz, 1 H).
13C NMR (CDCl3, 101 MHz):  = 159.6, 158.0, 134.5, 128.8, 126.3,
125.5, 125.2, 121.6, 114.3, 110.0, 102.2, 89.1, 55.4, 42.9, 41.5.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NO2SeNa: 368.0160; found:
368.0162.
2,3-Dihydrobenzofurans 7; General Procedure
At –20 °C, 6 (0.10 mmol), 1d (52.1 mg, 0.13 mmol), and AcCl (4.0 L,
0.10 mmol) were added to an over-dried 10 mL flask equipped with a
stir bar. The flask was the sealed with a septum. Anhyd MeCN (1 mL)
was added via a syringe, and the solution was stirred for 2 h to 12 h.
After completion of the reaction (monitored by TLC), the solvent was
removed under reduced pressure, and the crude product was purified
by silica gel flash column chromatography.
2-Phenyl-2-(selenocyanatomethyl)chromane (7e)
Colorless oil; Rf = 0.50 (silica gel, PE:EtOAc 5:1, v/v); yield: 15.8 mg
(0.048 mmol, 48%).
1H NMR (CDCl3, 400 MHz):  = 7.35–7.26 (m, 5 H), 7.16 (ddd, J = 8.8,
7.2, 1.8 Hz, 1 H), 7.01 (dd, J = 8.3, 1.2 Hz, 1 H), 6.95 (dd, J = 7.6, 1.7 Hz,
1 H), 6.85 (td, J = 7.4, 1.2 Hz, 1 H), 3.63 (d, J = 1.7 Hz, 2 H), 2.73–2.65
(m, 1 H), 2.51–2.39 (m, 3 H).
2-Phenyl-2-(selenocyanatomethyl)-2,3-dihydrobenzofuran (7a)
13C NMR (CDCl3, 101 MHz):  = 153.0, 140.9, 129.5, 129.1, 128.3,
127.9, 125.5, 121.3, 121.2, 117.0, 102.6, 79.2, 42.4, 30.4, 22.3.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NOSeNa: 352.0211; found:
352.0213.
Colorless oil; Rf = 0.45 (silica gel, PE:EtOAc 5:1, v/v); yield: 20.6 mg
(0.066 mmol, 66%).
1H NMR (CDCl3, 400 MHz):  = 7.48–7.46 (m, 2 H), 7.41 (t, J = 7.5 Hz, 2
H), 7.36–7.32 (m, 1 H), 7.23–7.14 (m, 2 H), 6.97–6.89 (m, 2 H), 3.76–
3.68 (m, 3 H), 3.58 (d, J = 15.8 Hz, 1 H).
13C NMR (CDCl3, 101 MHz):  = 158.0, 142.6, 129.0, 128.8, 128.4,
Conflict of Interest
125.4, 125.2, 125.0, 121.7, 110.1, 102.0, 89.2, 43.0, 41.3.
The authors declare no conflict of interest.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

G
D. Zhu et al.
Feature
Synthesis
Funding Information
(4) Plano, D.; Karelia, D. N.; Pandey, M. K.; Spallholz, J. E.; Amin, S.;
Sharma, A. K. J. Med. Chem. 2016, 59, 1946.
We thank the NSFC (Nos. 21871178, 22071149, 21702135), and the
STCSM (19JC1430100) for the financial support. This research was
also supported by The Program for Professor of Special Appointment
(5) (a) Mukherjee, N.; Kundu, D.; Ranu, B. C. Adv. Synth. Catal. 2017,
359, 329. (b) Guan, Y.; Townsend, S. D. Org. Lett. 2017, 19, 5252.
(c) Krief, A.; Dumont, W.; Delmotte, C. Angew. Chem. Int. Ed.
2000, 39, 1669. (d) Krief, A.; Delmotte, C.; Dumont, W. Tetrahe-
dron 1997, 53, 12147.
(Eastern Scholar) at Shanghai Institutions of Higher Learning.
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(6) For selected examples, see: (a) Guo, W.; Tan, W.; Zhao, M.;
Zheng, L.; Tao, K.; Chen, D.; Fan, X. J. Org. Chem. 2018, 83, 6580.
(b) Frei, R.; Courant, T.; Wodrich, M. D.; Waser, J. Chem. Eur. J.
2015, 21, 2662. (c) Feng, C.; Peng, Y.; Ding, G.; Li, X.; Cui, C.; Yan,
Y. Chem. Commun. 2018, 54, 13367. (d) Redon, S.; Kosso, A. R. O.;
Broggi, J.; Vanelle, P. Tetrahedron Lett. 2017, 58, 2771. (e) Redon,
S.; Kosso, A. R. O.; Broggi, J.; Vanelle, P. Synthesis 2019, 51, 3758.
(7) (a) Gao, M.; Vuagnat, M.; Chen, M.-Y.; Pannecoucke, X.; Jubault,
P.; Besset, T. Chem. Eur. J. 2021, 27, 6145. (b) Xiao, J.-A.; Li, Y.-C.;
Cheng, X.-L.; Chen, W.-Q.; Cui, J.; Huang, Y.; Huang, J.; Xiao, Q.;
Su, W.; Yang, H. Org. Chem. Front. 2019, 6, 1967. (c) Wu, D.; Qiu,
J.; Li, C.; Yuan, L.; Yin, H.; Chen, F.-X. J. Org. Chem. 2020, 85, 934.
(d) Xiao, J.-A.; Cheng, X.-L.; Meng, R.-F.; Qin, X.-S.; Peng, H.; Ren,
J.-W.; Xie, Z.-Z.; Cui, J.-G.; Huang, Y.-M. Synthesis 2021, 53, 954.
(8) (a) Xie, Y.-Y.; Chen, Z.-M.; Luo, H.-Y.; Shao, H.; Tu, Y.-Q.; Bao, X.-
G.; Cao, R.-F.; Zhang, S.-Y.; Tian, J.-M. Angew. Chem. Int. Ed. 2019,
58, 12491. (b) Luo, H.-Y.; Xie, Y.-Y.; Song, X.-F.; Dong, J.-W.; Zhu,
D.; Chen, Z.-M. Chem. Commun. 2019, 55, 9367. (c) Luo, H.-Y.;
Dong, J.-W.; Xie, Y.-Y.; Song, X.-F.; Zhu, D.; Ding, T.-M.; Liu, Y.-Y.;
Chen, Z.-M. Chem. Eur. J. 2019, 25, 15411. (d) Song, X.-F.; Ye, A.-
H.; Xie, Y.-Y.; Dong, J.-W.; Chen, C.; Zhang, Y.; Chen, Z.-M. Org.
Lett. 2019, 21, 9550. (e) Song, X.-F.; Ding, T.-M.; Zhu, D.; Huang,
J.; Chen, Z.-M. Org. Lett. 2020, 22, 7052.
(9) (a) Ye, A.-H.; Zhang, Y.; Xie, Y.-Y.; Luo, H.-Y.; Dong, J.-W.; Liu, X.-
D.; Song, X.-F.; Ding, T.-M.; Chen, Z.-M. Org. Lett. 2019, 21, 5106.
(b) Li, C.; Long, P.; Wu, H.; Yin, H.; Chen, F.-X. Org. Biomol. Chem.
2019, 17, 7131.
(10) CCDC 2061576 (1d) contains the supplementary crystallo-
graphic data for this paper. The data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/structures
(11) CCDC 2073817 (5d) contains the supplementary crystallo-
graphic data for this paper. The data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/structures
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1493-6885. Su
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G