Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of selenocyanates

Article abstract of DOI:10.1016/j.tet.2020.130978

A practical method for the umpolung selenocyanation of aryl ketones, alkyl ketones, β-ketoesters and electron-rich arenes has been developed, affording various selenocyanates in moderate to excellent yields. This transformation proceeds by an oxidative um

Full text of DOI:10.1016/j.tet.2020.130978

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Oxidative umpolung selenocyanation of ketones and arenes: An
efficient protocol to the synthesis of selenocyanates
,
,
Jianguo Cui a b, Meizhen Wei a, Liping Pang a, JunAn Xiao a *, Chunfang Gan a, Jiali Guo a,
Chuanfang Xie a, Qiming Zhu a, Yanmin Huang a
,
**
a Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Nanning Normal University, Nanning, 530001, PR China
b Guangxi Colleges and University Key Laboratory of Beibu Gulf Oil and Natural Gas Resource Effective Utilization, Beibuwan University, Qinzhou, 535000,
PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical method for the umpolung selenocyanation of aryl ketones, alkyl ketones, b-ketoesters and
Received 26 November 2019
Received in revised form
20 January 2020
Accepted 22 January 2020
Available online xxx
electron-rich arenes has been developed, affording various selenocyanates in moderate to excellent
yields. This transformation proceeds by an oxidative umpolung selenocyanation through nitrogen
oxides-mediated electrophilic selenocyanation process. This method is simpler, more efficient, and less
costly than precedent methods. Further transformations of the arylselenocyanate was performed to
prove the synthetic utility of this methodology.
© 2020 Elsevier Ltd. All rights reserved.
Keywords:
Selenocyanation
Aryl ketones
Electron-rich arenes
Electrophilic substitution
Umpolung
1. Introduction
synthetic intermediate to access seleno-containing compounds [7].
After introducing the selenocyano group into organic molecules, it
Selenium is a necessary trace element for the human body and
some animals to sustain life [1]. Compared with an inorganosele-
nium compound, organoselenium compounds have some excellent
characteristics, such as higher bioavailability, stronger bioactivity,
lower toxicity, smaller environmental pollution, anti-oxidation,
anti-inflammatory and anti-cancer, etc. [2] At present, some orga-
noselenium compounds have been used in clinical trials and pos-
sesses numerous biological activities such as anti-oxidation, anti-
inflammatory or anti-tumor activities, such as ebselen [3], ethase-
len [4] and selenazofurin [5], etc. Intrigued by the interested
properties of organoselenium in pharmaceuticals and bioactive
molecules, tremendous elegant methods have been developed to
synthesize organoselenium compounds in recently [6].
often endows the organic molecules with different biological ac-
tivities, such as antitumor activity [8] and antioxidant activity [9].
Traditionally, the introduction of selenocyano groups involves
KSeCN-mediated nucleophilic selenocyanation reaction. First, a
halogen atom was introduced into an organic substrate by the
halogenation. Then the selenocyanates were obtained by nucleo-
philic substitution of selenium cyanide anion to the halogen atom
[10]. On the other hand, electron-rich arylselenocyanates were
produced by electrophilic species such as diazonium salts [11],
diaryliodonium salts [12] with selenocyanate salts (KSeCN).
Some new direct selenocyanation methods have been proposed
[13]. For instance, natural deep eutectic solvent-catalyzed seleno-
cyanation of activated alkynes [14], iodine catalyzed selenocaya-
nation [15], bromine catalyzed selenocayanation [16], one-pot
synthesis of selenocyanates by triselenium dicyanide [17], seleno-
cyanation from olefin via hydroboration [18], selenocyanation via
organocopper reagents [19] and certain oxidant-mediated seleno-
cyanation [20]. In addition, some selenocyanations applied in
electron-rich aromatic substrates have also been developed [21].
Recently, we reported a new selenocyanation using selenocyano-
benziodoxolone as reagent by grinding under mild conditions [22].
Selenocyanates are a class of selenocompounds that generally
show interesting properties as chemopreventive, anti-
inflammatory agent or anticancer agents. They are also a valuable
* Corresponding author.
** Corresponding author.
E-mail addresses: jaxiao@csu.edu.cn (J. Xiao), huangyanmin828@163.com
(Y. Huang).
https://doi.org/10.1016/j.tet.2020.130978
0040-4020/© 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
selenocyanates, Tetrahedron, https://doi.org/10.1016/j.tet.2020.130978

2
J. Cui et al. / Tetrahedron xxx (xxxx) xxx
Table 1
However, the existing direct selenocyanation methods have the
Optimization of reaction conditions.a
disadvantages of expensive reagents or harsh reaction conditions,
and it is difficult to realize large-scale industrial application. In this
paper, a direct selenocyanation method which is simpler and more
effective and can be applied on an industrial scale has been pro-
posed for the synthesis of a-carbonyl selenocyanates and electron-
rich arylselenocyanates (Scheme 1).
Entry
Acid (C)b
Acid (equiv.)
Solvent
Yield (%)c
2. Results and discussion
1
2
3
4
p-TSA
TFA
3
3
3
3
3
3
3
3
1.5
4.5
3
3
3
3
3
3
3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
ethanol
methanol
CH2Cl2
THF
nr
57
49
93
50
80
71
28
89
60
66
45
nr
84
89
88
84
nr
The study began by examining electrophilic selenocyanation of
propiophenone 1a with KSeCN-NaNO2-acid system. First, a variety
of protic acids were evaluated. Delightedly, TFA, aq. HNO3(1 M) and
aq. HCl (3 M) delivered selenocyanate 2a with 57%, 49% and 93%
yields, respectively, by using sodium nitrite as an oxidant (Table 1,
entries 1e4). Subsequently, the yield of desired product 2a was
slightly decreased when decreasing the amount of KSeCN and
NaNO2 (Table 1 entries 5e6). Additionally, the yield of selenocya-
nate 2a was slightly improved when the title reaction was per-
formed at 60 ꢀC by using 1.0 equivalent of potassium selenocyanate
(Table 1, entry 7). Further increase of the concentration of aqueous
hydrochloric acid led to a relatively low yield of selenocyanate 2a
(28%, Table 1, entry 8). The amount of aq. HCl was also investigated
and 3 equiv. HCl showed the best result with a yield above 93%
(Table 1, entries 9e10 VS entry 4). Besides, other solvents, such as
ethanol, methanol, dichloromethane, tetrahydrofuran (THF),
dioxane and dimethyl sulfoxide (DMSO) were also examined and
MeCN was found to be the best (Table 1, entries 11e16 VS entry 4).
Notably, no desired product was detected when the title reaction
was performed in CH2Cl2. Presumably, the results could mainly
attribute to the poor solubility of potassium selenocyanate in
HNO3 (1 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (6 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
HCl (3 M)
5d
6e
7d,f
8
9
10
11
12
13
14
15
16
17g
18h
Dioxane
DMSO
MeCN
MeCN
3
a
Unless otherwise noted, reactions were performed with propiophenone (1a)
(0.5 mmol, 1.0 equiv.), KSeCN (1.5 mmol), NaNO2 (1.5 mmol), HCl (aq., 5 mL, 3 M) at
room temperature for 48 h.
b
Concentration of acid.
Isolated yield.
KSeCN (0.5 mmol), NaNO2 (0.5 mmol).
KSeCN (1.0 mmol), NaNO2 (1.0 mmol).
The reaction was carried out at 60 ꢀC.
tert-Butyl nitrite was used as an oxidant.
tert-Butyl hydroperoxide was used as an oxidant.
c
d
e
f
g
t
h
dichloromethane. Furthermore, various oxidants such as BuONO
(tert-Butyl nitrite) and TBHP (tert-Butyl hydroperoxide) were also
considered. Not surprisingly, the reaction performed smoothly by
using BuONO as the oxidant and led to desired product 2a in 84%
t
selenocyanates in 32e99% yields for the aromatic ketones (Table 2,
2a-2p). It is worth noting that low yields (37% and 32%, respec-
tively) were observed for 2h and 2k. When 2-bromo substituted
aryl ketones was employed, due to steric reasons (Table 2, 2h).
However, when the methoxyl group was at the para-position of the
benzene ring, the benzene ring easily formed a quinone structure,
which affected the progress of the reaction (Table 2, 2k). The sub-
strate scope of this transformation was also successfully expanded
to other aromatic ketones and heterocyclic rings such as 2-
acetylthiophene, affording corresponding selenocyanates with
poor to excellent yields (Table 2, 2l-2n). Besides, acyclic aromatic
ketones bearing alkyl such as n-butyrophenone and valerophenone
was also tolerated and gave the desired products in 93% and 76%
yield, respectively (Table 2, 2o-2p).
yield (Table 1, entry 17), while the TBHP failed to give the desired
product (Table 1, entry 18). Thus, the optimized conditions were
confirmed by using KSeCN (1.5 mmol, 3 equiv.), NaNO2 (1.5 mmol, 3
equiv.), aq. HCl (3 M, 3 equiv.) in MeCN at room temperature.
With the optimized conditions established, we next investi-
gated the scope of this reaction by employing a variety of ketones.
As shown in Table 2, both electron-withdrawing and electron-
donating groups were well tolerated and gave
a-carbonyl
Subsequently, cyclic aryl ketones and alkyl ketones were
examined. Satisfyingly, both the cyclic aryl ketones and alkyl ke-
tones were well-tolerated, delivering corresponding selenocya-
nates in moderate yield (Table 2, 2q-2v). Furthermore, substitutions
with dual reactive site such as 1-cyclohexylethan-1-one, benzyla-
cetone and isobutylacetone were performed under the optimized
reaction conditions and afforded the corresponding selenocyanates
in good to excellent yields with excellent regioselectivities (Table 2,
2s-2u). It could be seen from 2t-2u that the selenocyanate substi-
tution mainly occurs in the a-carbon position which can form a
stable enol-form structure (thermodynamic regioisomer). Howev-
er, for the compound 2s, since the steric hindrance of the cyclohexyl
group is much larger than that of the methyl group, the seleno-
cyanation occurs on the methyl group having a small steric hin-
drance, and a kinetic regioisomer is obtained. The commonly used
solvent-acetone was also tested and led to the
a-selenocyanate
Scheme 1. Strategies of selenocyanation.
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
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J. Cui et al. / Tetrahedron xxx (xxxx) xxx
3
Table 2
Substrate scope of ketones and b
-ketoesters.a
acetone in relatively low yield (33%, Table 2, 2v). Notably, indanone
resulted in -diselenocyanate derivative 3 in 61% yield. We reason
that five-membered cyclic selenocyanate derived from indanone is
more active than six-membered cyclic selenocyanate 2q, leading to
yields (Table 3, 5l, 5n and 5o), except for 1-methoxynaphthalene
(Table 3, 5m). Finally, the structure of selenocyanate 5j was
unambiguously confirmed by single-crystal X-ray diffraction (CCDC
1918411).
b,b
the second electrophilic selenocyanation reaction. Besides,
b-
ketoesters were also screened and yielded the desired products in
good to excellent yields (Table 2, 2w-2y).
When p-trifluoromethylacetophenone and p-methylformate-
acetophenone were used as the reaction substrates, the product 2z
and 2aa were obtained in moderated yields (51% and 73%). How-
ever, when the p-nitroacetophenone was used as the reaction
substrate, the reaction yield is only 22%, and when the o-nitro-
acetophenone was used as the reaction substrate, the corre-
sponding selenocyanate was not obtained. The reason for this may
be similar to that in the case of 2k.
Encouragingly, the reaction was also applicable to the seleno-
cyanation of electron-rich arenes. Satisfyingly, both the N,N-
dimethylamino substituted arenes and methoxy substituted arenes
were well tolerated, affording corresponding selenocyanates in
moderate to excellent yields (Table 3, 5a-5j). It is worth mentioning
that N,N-dimethylamino-containing arenes afforded the seleno-
cyanated products 5a-5c in moderated yields (53%, 49% and 52%,
respectively). In particular, the yields of corresponding selenocya-
nates were dramatically dropped when bromo-containing methoxy
substituted arenes were employed (Table 3, 5k). It could be seen
that after a deactivating group halogen atom was introduced into
the benzene ring, the yield of the reaction was significantly
reduced. To further broaden the scope of the substrates, we also
investigated variety aromatic heterocyclic compounds such as
methoxynaphthalene and indole derivatives, and they were toler-
ated and afforded the corresponding selenocyanates in excellent
To demonstrate the practical utility of the above methodology, a
gram scale experiment was performed on a 7 mmol scale of 1a and
8 mmol scale of 4i under the standard conditions. Satisfyingly, the
desired product 2a and the electron-rich arylselenocyanate 5i were
obtained in 95% and 99% yields, respectively, proving the scalability
of the newly developed protocol. Moreover, the arylselenocyanate
5i could be converted to diselenide 6 in a good yield (99%)
(see Scheme 2).
The mechanism of the reaction was studied under different re-
action conditions in preparation of 2a. In the reaction, when only
KSeCN and HCl were used, without NaNO2, the product 2a was not
obtained. In addition, when HCl was not added, but only KSeCN and
NaNO2 were used, the reaction was unable to happen also. In the
study of the selenocyanation of the arenes, we found that when the
electron-withdrawing substituent is attached to the aromatic ring
alone, the reaction cannot occur, and when the weaker electron-
donating substituent such as alkyl is attached to the benzene
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
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Table 3
Substrate scope of arenes containing elelctro-donating group.a
Scheme 3. Putative mechanism.
to excellent yields. Experimental evidence reveals that the reaction
may be performed through an umpolung “þSeCN” mechanism.
Importantly, the synthetic utility of the newly developed protocol
was further demonstrated by gram-scale reaction and the trans-
formations of the selenocyanates. Moreover, this protocol might be
suitable for industrial production since it possesses the advantages
of low cost and easy operation. Further studies including in
asymmetric selenocyanation and bioactivity evaluation of seleno-
cyanates are currently ongoing in our laboratory.
Scheme 2. Gram-scale reaction and transformations of 2a and 5i.
ring, such as toluene and xylene, the reaction does not occur also.
This indicates that the reaction is not carried out by a free radical
mechanism, but follows
a general electrophilic substitution
mechanism. Based on the experimental results, a plausible mech-
anism was proposed as shown in Scheme 3. Firstly, treating the
sodium nitrite with aqueous hydrochloric acid affords nitrogen
oxide active species. Subsequently, þSeCN ion was generated in situ
by the reaction of nitrogen oxide and potassium selenocyanate
4. Experimental
(Scheme 3a). Finally, the a-carbonyl selenocyanates and arylsele-
nocyanates were delivered, respectively, through the direct elec-
trophilic selenocyanation of ketones and electron-rich arenes with
“þSeCN” intermediate (Scheme 3b).
4.1. Reagents and instruments
All chemicals and solvents were analytical grade. Melting points
were measured on an X6 apparatus (Beijing Tech Instrument Co.
Ltd., Beijing, China), uncorrected. Infrared spectra were determined
with a Thermo Scientific Nicolet IS-10 Spectrophotometer (Thermo
Scientific, America); The 1H and 13C NMR spectra were recorded on
a Bruker AV-400 spectrometer at working frequencies 400 and
100 MHz and a Bruker AV-300 spectrometer at working frequencies
300 and 75 MHz. Chemical shifts are expressed in parts per million
3. Conclusions
In conclusion, we have developed a new method for the
umpolung selenocyanation of ketones and electron-rich arenes by
using KSeCN-NaNO2-HCl system. A variety of
a-carbonyl seleno-
cyanates, as well as arylselenocyanates were afforded in moderate
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
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J. Cui et al. / Tetrahedron xxx (xxxx) xxx
5
(
d
) values and coupling constants (J) in Hertz. HREIMS was
1H), 7.88 (d, J ¼ 8.1 Hz, 1H), 7.75 (d, J ¼ 8.1 Hz, 1H), 7.41 (t, J ¼ 7.8 Hz,
measured on an Agilent 6210 TOFMS instrument (Agilent Tech-
nologies, America).
1H), 4.88 (s, 2H); 13C NMR (75 MHz, CDCl3)
d: 192.2, 137.6, 135.4,
131.6,130.8,127.4,123.4,101.8, 37.8; HRMS (TOF-ESIþ) m/z: calcd for
C9H7BrNOSe [MþH]þ 303.8876, found 303.8865.
4.2. General procedure for the synthesis of selenocyanates
1-(2-Bromophenyl)-2-selenocyanatoethanone (2h): Yellowish
solid, yield: 37%, m.p. 56e57 ꢀC; IR (KBr)
n
: 3315, 2935, 2151, 1796,
1H NMR (300 MHz, CDCl3)
: 7.72e7.64 (m, 2H),
: 195.5,
To a solution of acetonitrile (15 mL), aqueous hydrochloric acid
(3 M, 5 mL) was added at 0 ꢀC, following by the addition of aqueous
sodium nitrite (0.104 g, 1.5 mmol, dissolved in 1.5 mL of distilled
water). After stirred at the same temperature for 10 min, KSeCN
(72.5 mg, 0.5 mmol) was added in one portion. The resulting so-
lution was stirred at the ice bath for 20 min. Afterwards, carbonyl
compound or electron-rich arene (0.5 mmol) was added and the
reaction mixture was continuously stirred in room temperature
until no starting material was observed (the progress was moni-
tored by TLC). The solvent was removed, the residue was extracted
with ethyl acetate and washed with brine. The combined organic
phases were dried, concentrated and purified by flash column
chromatography on silica gel to give pure target products.
1469, 989 cmꢁ1
;
d
7.49e7.41 (m, 2H), 4.85 (s, 2H); 13C NMR (75 MHz, CDCl3)
d
137.0, 134.5, 133.8, 130.7, 127.9, 120.2, 101.3, 39.2; HRMS (TOF-ESIþ)
m/z: calcd for C9H7BrNOSe [MþH]þ 303.8876, found 303.8863.
1-(3-Methylphenyl)-2-selenocyanatoethanone (2i): White
ꢀ
solid, yield: 68%, m.p. 84e85 C (lit. 43e44 ꢀC); IR (KBr)
n
: 3055,
2936, 2150, 1427, 1155, 785 cmꢁ1; 1H NMR (300 MHz, CDCl3)
: 7.75
(s, 1H), 7.74 (d, J ¼ 6.0 Hz, 1H), 7.50e7.38 (m, 2H), 4.91 (s, 2H), 2.43
(s, 3H); 13C NMR (75 MHz, CDCl3)
: 193.5, 139.1, 135.7, 133.8, 129.2,
d
d
129.0, 126.0, 102.1, 38.7, 21.3; HRMS (TOF-ESIþ) m/z: calcd for
C
10H9NOSeNa [MþNa]þ 261.9742, found 261.9742.
1-(4-Methylphenyl)-2-selenocyanatoethanone (2j): White
solid, yield: 87%, m.p. 135e136 ꢀC; IR (KBr)
n
: 2987, 2933, 2153,
1-Phenyl-2-selenocyanatopropan-1-one (2a): White solid,
1655, 1178, 806 cmꢁ1 1H NMR (300 MHz, CDCl3)
; d: 7.83 (d,
yield: 93%, m.p. 84e85 ꢀC; IR(KBr) v: 2929, 2155, 1679, 1446, 1238,
J ¼ 7.5 Hz, 2H), 7.31 (d, J ¼ 7.5 Hz, 2H), 4.89 (s, 2H), 2.44 (s, 3H); 13
C
999, 707 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d: 7.94 (d, J ¼ 7.2 Hz, 2H),
NMR (75 MHz, CDCl3) d: 192.9, 146.2, 131.3, 129.8, 128.9, 102.2, 38.6,
7.68 (t, J ¼ 7.2 Hz, 1H), 7.55 (t, J ¼ 7.5 Hz, 2H), 5.42 (q, J ¼ 7.2 Hz, 1H),
21.9; HRMS (TOF-ESIþ) m/z: calcd for C10H9NOSeNa [MþNa]þ
2.06 (d, J ¼ 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d: 197.1, 134.7,
261.9742, found 261.9744.
132.8, 129.2, 129.0, 102.7, 49.0, 21.4; HRMS (TOF-ESIþ) m/z: calcd for
C
10H9NOSeNa [MþNa]þ 261.9742, found 261.9747.
4.2.2. 1-(4-Methoxyphenyl)-2-selenocyanatoethanone (2k)
1-(4-Chlorophenyl)-2-selenocyanatopropan-1-one (2b): White
White solid, yield: 32%, m.p. 117e119 ꢀC; IR (KBr)
n
: 2934, 2848,
2151, 1686, 1298, 997, 822 cmꢁ1; 1H NMR (300 MHz, CDCl3)
: 7.94
(d, J ¼ 8.7 Hz, 2H), 6.99 (d, J ¼ 8.7 Hz, 2H), 4.91 (s, 2H), 3.91 (s, 3H);
solid, yield: 74%, m.p. 72e73 ꢀC (lit. 70e71 ꢀC); IR (KBr)
n
: 2921,
d
2514, 2160, 1791, 1440, 1230, 844 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.88 (d, J ¼ 8.4 Hz, 2H), 7.51 (d, J ¼ 8.4 Hz, 2H), 5.33 (q, J ¼ 7.2 Hz,
13C NMR (75 MHz, CDCl3)
d: 191.5, 164.9, 131.2, 126.8, 114.4, 102.2,
1H), 2.03 (d, J ¼ 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d: 195.8,
55.7, 38.6; HRMS (TOF-ESIþ) m/z: calcd for C10H10NO2Se [MþH]þ
141.3, 131.2, 130.4, 129.6, 102.3, 48.1, 21.0; HRMS (TOF-ESIþ) m/z:
calcd for C10H8NOSeClNa [MþNa]þ 295.9352, found 295.9332.
1-Phenyl-2-selenocyanatoethanone (2c): Yellowish solid, yield:
255.9877, found 255.9880.
4.2.3. 2-Selenocyanato-1-(thiophen-3-yl)ethanone (2l)
93%, m.p. 81e82 ꢀC (lit. 48e49 ꢀC); IR (KBr)
1796, 1462, 1268, 884 cmꢁ1
J ¼ 7.5 Hz, 2H), 7.70 (t, J ¼ 7.5 Hz, 1H), 7.55 (t, J ¼ 7.5 Hz, 2H), 4.95 (s,
n
: 2955, 2514, 2155,
White solid, yield: 99%, m.p. 107e109 ꢀC; IR (KBr)
n
: 3096, 2928,
;
1H NMR (300 MHz, CDCl3)
d: 7.97 (d,
2154, 1650, 1170, 798 cmꢁ1 1H NMR (300 MHz, CDCl3)
; d: 8.20 (s,
1H), 7.55 (d, J ¼ 4.8 Hz, 1H), 7.42 (d, J ¼ 4.8 Hz, 1H), 4.79 (s, 2H); 13
C
2H); 13C NMR (75 MHz, CDCl3)
d: 193.2, 134.9, 133.8, 129.2, 128.7,
NMR (75 MHz, CDCl3) d: 187.1, 138.6, 134.6, 127.6, 126.8, 101.9, 38.1;
101.8, 38.4; HRMS (TOF-ESIþ) m/z: calcd for C9H7NOSeNa [MþNa]þ
HRMS (TOF-ESIþ) m/z: calcd for C7H5NOSSeNa [MþNa]þ 253.9149,
247.9585, found 247.9571.
found 253.9143.
1-(4-Fluorophenyl)-2-selenocyanatoethanone (2d): Yellowish
solid, yield: 99%, m.p. 121e122 ꢀC (lit. 112e113 ꢀC); IR (KBr)
n
: 2990,
4.2.4. 1-(
White solid, yield: 33%, m.p. 147e148 ꢀC; IR (KBr)
1657, 1383, 1238, 996, 745 cmꢁ1; 1H NMR (300 MHz, CDCl3)
(s, 1H), 7.99e7.90 (m, 4H), 7.71e7.59 (m, 2H), 5.01 (s, 2H); 13C NMR
b-Naphthyl)-2-selenocyanatoethanone (2m)
2158, 1657, 1412, 1290, 1000, 824 cmꢁ1; 1H NMR (300 MHz, CDCl3)
n
: 2997, 2151,
: 8.43
d
: 7.98e8.03 (m, 2H), 7.21 (t, J ¼ 8.4 Hz, 2H), 4.91 (s, 2H); 13C NMR
d
(75 MHz, CDCl3)
d
: 191.6, 166.7 (d [1],JC-F ¼ 257.3 Hz), 131.6 (d [2],JC-
¼ 9.8 Hz), 130.3 (d [3],JC-F ¼ 3.0 Hz), 116.5 (d [2],JC-F ¼ 22.5 Hz),
(75 MHz, CDCl3) d: 193.1, 136.2, 132.3, 131.5, 130.9, 129.8, 129.6,
F
101.7, 38.1; 19F NMR (282 MHz, CDCl3)
d
: 101.2; HRMS (TOF-ESIþ) m/
129.1, 128.0, 127.5, 123.4, 102.1, 38.6; HRMS (TOF-ESIþ) m/z: calcd
for C13H10NOSe [MþH]þ 275.9928, found 275.9928.
z: calcd for C9H6NOSeFNa [MþNa]þ 265.9491, found 265.9499.
1-(4-Chlorophenyl)-2-selenocyanatoethanone (2e): Yellowish
solid, yield: 60%, m.p. 83e84 ꢀC; IR (KBr)
n
: 2985, 2155, 1796, 1657,
1399, 1178, 816 cmꢁ1; 1H NMR (300 MHz, CDCl3)
: 7.91 (s, 2H), 7.54
: 192.0, 141.6, 132.1,
4.2.5. 1-Selenocyanato-4-phenyl-2-butanone (2n)
d
White solid, yield: 39.0%, m.p. 126e128 ꢀC; IR (KBr)
n
: 2923,
(s, 2H), 4.90 (s, 2H); 13C NMR (75 MHz, CDCl3)
d
2504, 2153, 1794, 1654, 1389, 1150 cmꢁ1; 1H NMR (300 MHz, CDCl3)
130.1, 129.6, 101.6, 37.9; HRMS (TOF-ESIþ) m/z: calcd for C9H6NO-
d
: 7.68 (d, J ¼ 16.2 Hz, 1H), 7.61e7.58 (m, 2H), 7.47e7.45 (m, 3H),
SeClNa [MþNa]þ 281.9195, found 281.9204.
6.84 (d, J ¼ 16.2 Hz, 1H), 4.57 (s, 2H); 13C NMR (75 MHz, CDCl3)
d:
192.6,147.0, 133.5, 131.7, 129.2,128.8,122.8,101.8, 38.3; HRMS (TOF-
ESIþ) m/z: calcd for C11H9NOSeNa [MþNa]þ 273.9742, found
273.9745.
4.2.1. 1-(4-Bromophenyl)-2-selenocyanatoethanone (2f)
Yellowish solid, yield: 76%, m.p. 142e143 ꢀC (lit. 144e145 ꢀC); IR
(KBr)
n
: 2509, 1794, 1652, 1465, 1397, 1008, 871 cmꢁ1
;
1H NMR
1-Phenyl-2-selenocyanatobutanone (2o): White solid, yield:
(300 MHz, CDCl3)
d
: 7.84 (d, J ¼ 8.7 Hz, 2H), 7.70 (d, J ¼ 8.7 Hz, 2H),
93%, m.p. 89e90 ꢀC; IR (KBr)
n
2966, 2927, 2154, 1674, 1449, 1358,
4.90 (s, 2H); 13C NMR (75 MHz, CDCl3)
d
: 192.2, 132.6, 132.5, 130.5,
1267, 1142 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
: 7.92 (d, J ¼ 7.8 Hz,
130.1, 101.5, 37.9; HRMS (TOF-ESIþ) m/z: calcd for C9H6NOSeBrNa
[MþNa]þ 325.8690, found 325.8679.
2H), 7.64 (t, J ¼ 7.4 Hz, 1H), 7.50 (t, J ¼ 7.6 Hz, 2H), 5.38 (t, J ¼ 5.6 Hz,
1H), 2.26e2.35 (m, 2H), 1.01 (t, J ¼ 7.2 Hz, 1H); 13C NMR (100 MHz,
1-(3-Bromophenyl)-2-selenocyanatoethanone (2g): Yellowish
CDCl3)
d
: 196.8, 134.6, 133.5, 129.2, 128.9, 102.7, 56.0 (d, J ¼ 11.7 Hz),
solid, yield: 73%, m.p. 77e78 ꢀC; IR (KBr)
n
: 3063, 2931, 2154, 1664,
27.0, 10.7 (d, J ¼ 6.7 Hz); HRMS (TOF-ESIþ) m/z: calcd for
1421, 1176, 1012, 789 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
: 8.07 (s,
C
11H11NNaOSe [MþNa]þ 275.9904, found 275.9897.
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
selenocyanates, Tetrahedron, https://doi.org/10.1016/j.tet.2020.130978

6
J. Cui et al. / Tetrahedron xxx (xxxx) xxx
1-Phenyl-2-selenocyanatopentanone (2p): White solid, yield:
76%, m.p. 66e67 ꢀC; IR (KBr)
2960, 2927, 2155,1374, 1447, 1270,
707 cmꢁ1; 1H NMR (300 MHz, CDCl3)
(t, J ¼ 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d: 196.1, 167.5, 151.2,
n
137.0, 132.9, 128.9, 126.3, 125.7, 100.8, 64.3, 61.8, 41.0, 13.9; HRMS
(TOF-ESIþ) m/z: calcd for C13H11NO3SeNa [MþNa]þ 331.9796, found
331.9813.
d:7.93 (d, J ¼ 7.2 Hz, 2H), 7.65
(t, J ¼ 7.4 Hz, 1H),7.51 (t, J ¼ 7.7 Hz, 2H), 5.33 (t, J ¼ 6.2 Hz, 1H),
2.19e2.29 (m, 2H), 1.52e1.64 (m, 1H, 1.32e1.45 (m, 1H), 0.93 (t,
Methyl 1-Oxo-2-selenocyanato-1,2,3,4-tetrahydronaphthalene-
J ¼ 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d:196.7, 134.6, 133.6,
2-carboxylate (2y): White solid, yield: 97%, m.p.133e135 ꢀC; IR
129.2, 128.8, 102.6, 53.7(J ¼ 12.4 Hz), 35.8, 20.0, 13.9 (d, J ¼ 7.0 Hz);
HRMS (TOF-ESIþ) m/z: calcd for C12H13NNaOSe [MþNa]þ 290.0060,
found 290.0055.
(KBr)
(300 MHz, CDCl3)
n
: 2959, 2158, 1799, 1671, 1477, 1323, 1071, 641 cmꢁ1; 1H NMR
d: 8.00 (d, J ¼ 7.9, 1H), 7.58 (t, J ¼ 7.8 Hz, 1H), 7.37
(t, J ¼ 7.5 Hz, 1H), 7.29 (d, J ¼ 7.8 Hz, 1H), 3.79 (s, 3H), 3.23e3.29 (m,
2-Selenocyanato-3,4-dihydronaphthalen-1(2H)-one
White solid, yield: 45%, m.p. 79e80 ꢀC (lit. 82e83 ꢀC); IR (KBr)
2906, 2512, 2148, 1797, 1594, 1457, 896 cmꢁ1 1H NMR (300 MHz,
CDCl3)
: 8.00 (d, J ¼ 8.1 Hz,1H), 7.59 (t, J ¼ 7.5 Hz,1H), 7.40e7.32 (m,
2H), 5.01 (dd, J ¼ 5.1, 13.5 Hz, 1H), 3.23e3.18 (m, 2H), 2.96e2.87 (m,
1H), 2.62e2.47 (m,1H); 13C NMR (75 MHz, CDCl3)
: 30.3, 32.5, 53.2,
(2q):
1H), 3.05e3.16 (m, 2H), 2.69e2.79 (m, 1H); 13C NMR (75 MHz,
n
CDCl3) d: 191.5, 167.8, 143.5, 135.4, 130.0, 129.2, 128.3, 127.5, 101.8
;
(SeCN), 64.3, 54.0, 35.0, 27.92; HRMS (TOF-ESIþ) m/z: C13H11NO3
SeNa [MþNa]þ 331.9796, found 331.9803.
-
d
1-(4-trifluoromethylphenyl)-2-selenocyanatoethanone
(2z):
: 2929, 2364,
2152,1797,1664,1581,1514,1414,1329,1284,1330,1182,1128, 1069,
d
White solid, yield: 51%, m.p. 106e107 ꢀC; IR (KBr)
n
102.5 (SeCN), 127.4, 127.8, 129.1, 130.5, 135.0, 144.1, 194.2; HREIMS
(m/z): 251.9920 [MþH]þ (calcd.for C11H10NOSe 251.9928).
2-Selenocyanatocycloheptanone (2r): Colorless oil, yield: 40%;
999, 827 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 8.10 (d, J ¼ 8.1 Hz, 2H),
7.82 (d, J ¼ 8.1 Hz, 2H), 4.93 (s, 2H); 13C NMR (100 MHz, CDCl3): 37.8,
100.3 (SeCN), 123.2 (d [1],JC-F ¼ 204 Hz), 126.3 (d [3],JC-F ¼ 2.8 Hz),
129.1, 135.8, 136.3 (d [2],JC-F ¼ 14 Hz), 192.4; 19F NMR (282 MHz,
IR (KBr)
n ;
2923, 2861, 2150, 1794, 1670, 1447, 1123, 1026, 879 cmꢁ1
1H NMR (300 MHz, DMSO-d6)
d: 5.22 (dd, J ¼ 3.6, 10.5 Hz, 1H),
2.63e2.72 (m, 1H), 2.36e2.47 (m, 2H), 2.02 (dd, J ¼ 12.0, 25.5 Hz,
CDCl3)
d
: 101.2; HREIMS (m/z): calcd. For C10H6F3NOSeNa [MþNa]þ
1H), 1.80e1.84 (m, 2H), 1.68e1.72 (m, 2H), 1.53e1.61 (m, 1H),
315.9459, found 315.9465.
1.34e1.45 (m, 1H); 13C NMR (75 MHz, CDCl3)
d: 211.5, 104.9, 59.6,
1-(4-methylbenzoate)-2-selenocyanatoethanone
(2aa)White
41.5, 32.8, 29.2, 28.9, 23.9; HRMS (TOF-ESIþ) m/z: calcd for
solid, yield: 73%, m.p. 97e99 ꢀC; IR (KBr)
n
: 2931, 2153, 1719, 1660,
1505, 1436, 1408, 1383, 1289, 1183, 1111, 999, 840, 762, 691 cmꢁ1; 1H
NMR (300 MHz, CDCl3)
: 8.20 (d, J ¼ 8.4 Hz, 2H), 8.04 (d, J ¼ 8.4 Hz,
C8H11NOSeK [MþK]þ 255.9637, found 255.9657.
1-Cyclohexyl-2-selenocyanatoethanone (2s): White solid, yield:
d
99%, m.p. 61e62 ꢀC; IR (KBr)
n
: 2940, 2855, 2513, 2151, 1796, 1682,
1H NMR (300 MHz, CDCl3)
: 4.37 (s, 2H),
2.57e2.50 (m, 1H), 1.93e1.67 (m, 5H), 1.45e1.19 (m, 5H); 13C NMR
2H), 4.95 (s, 2H), 3.99 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 192.8,
1388, 1229, 999 cmꢁ1
;
d
165.7, 136.8, 135.4, 130.3, 128.7, 101.5, 52.7, 38.2; HRMS (TOF-ESIþ)
m/z: calcd for C11H9NO3SeNa [MþNa]þ 305.9640, found 305.9633.
2-Diselenocyano-2,3-dihydro-1H-indanone (3): White solid,
(75 MHz, CDCl3) d: 207.0, 101.7, 49.6, 38.8, 28.5, 25.5, 25.3; HRMS
(TOF-ESIþ) m/z: calcd for C9H14NOSe [MþH]þ 232.0241, found
yield: 61%, m.p. 69e71 ꢀC; IR (KBr)
n: 3135, 2153, 1712, 1654, 1603,
232.0240.
1588, 1560, 1465,1431, 1401, 1327, 1299, 1274, 1210, 1153, 1184, 1023,
3-Selenocyanato-4-phenyl-2-butanone (2t): White solid, yield:
1007, 750 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.90 (d, J ¼ 7.5 Hz, 1H),
56%, m.p. 95e96 ꢀC (Lit. 57e58 ꢀC); IR (KBr)
n
: 2924, 2855, 2150,
7.80 (t, J ¼ 7.5 Hz, 1H), 7.52e7.58 (m, 2H), 4.08 (s, 2H); 13C NMR
(75 MHz, CDCl3): 44.5, 55.9,100.12 (SeCN), 126.3,126.5,129.7, 130.3,
137.9, 148.4, 195.4; HREIMS (m/z): calcd. For C11H6N2OSe2Na
[MþNa]þ 364.8708, found 364.8706.
1704, 1361, 1152, 954, 744 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d:
7.31e7.38 (m, 3H), 7.18e7.25 (m, 2H), 4.36 (t, J ¼ 7.4 Hz, 1H), 3.48
(dd, J ¼ 7.8, 14.4 Hz,1H), 3.36 (dd, J ¼ 6.9, 14.4 Hz,1H), 2.29 (s, 3H).;
13C NMR (100 MHz, CDCl3)
d: 202.6, 136.4, 129.1, 129.0, 127.7, 100.6,
N,N-dimethyl-4-selenocyanatoaniline (5a): White solid, yield:
53%, m.p.129e131 ꢀC; IR (KBr) v: 2917, 2141, 1510, 1374, 1076.18,
55.4(d, J ¼ 7.7 Hz), 38.0, 28.5 (d, J ¼ 7.1 Hz); HRMS (TOF-ESIþ) m/z:
calcd for C11H11NNaOSe [MþNa]þ 275.9898, found 275.9903.
3-Selenocyanato-5-methyl-2-hexanone (2u): Brown oil, yield:
805 cmꢁ1 1H NMR (300 MHz, CDCl3)
; d: 3.01 (s, 6H), 6.66 (d,
J ¼ 6.9 Hz, 2H), 7.53 (d, J ¼ 6.9 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d:
73%; IR (KBr)
n
: 2960, 2153, 1708, 1362, 1179, 877 cmꢁ1
;
1H NMR
151.65, 136.38, 113.32, 104.40, 102.85, 40.13; HRMS (TOF-ESIþ) m/z:
calcd for C9H11N2Se [MþH]þ 227.0087, found 227.0090.
(300 MHz, CDCl3)
d
: (300 MHz, CDCl3) 4.14 (t, J ¼ 7.2 Hz,1H), 2.40 (s,
3H), 1.99e2.08 (m, 1H), 1.78e1.93 (m, 2H), 1.01 (d, J ¼ 1.8 Hz, 3H),
3-Bromo-4-selenocyano-N,N-dimethylaniline (5b): White solid,
yield: 49%, m.p.78e80 ꢀC; IR (KBr) v: 3091, 2154, 1656, 1454, 1092,
0.98 (d, J ¼ 1.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d: 202.9, 100.5,
52.5, 40.1, 27.4, 26.7, 22.3, 22.1; HRMS (TOF-ESIþ) m/z: calcd for
959 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.52 (d, J ¼ 8.7 Hz, 1H), 6.87
C8H13NNaOSe [MþNa]þ242.0055, found 242.0057.
(d, J ¼ 2.7 Hz,1H), 6.58 (dd, J ¼ 2.7, 8.7 Hz,1H), 2.96 (s, 6H); 13C NMR
1-Selenocyanatoacetone (2v): Brown oil, yield: 33%; IR (KBr)
n
:
(100 MHz, CDCl3)
d
: 152.1, 134.9, 127.2, 116.2 (d, J ¼ 5), 112.7, 107.9,
2921, 2509, 2150, 1699, 1356, 670 cmꢁ1; 1H NMR (300 MHz, CDCl3)
102.3, 40.2 (d, J ¼ 4); HRMS (TOF-ESIþ) m/z: calcd for C9H10BrN2Se
d
: 4.25 (s, 2H), 2.38 (s, 3H); 13C NMR (75 MHz, CDCl3)
d: 201.2, 101.2,
[MþH]þ 304.9187, found 304.9179.
39.7, 28.4; HRMS (TOF-ESIþ) m/z: calcd for C4H6NOSe [MþH]þ
3-Methyl-4-selenocyano-N,N-dimethylaniline (5c): yellowish
solid, yield: 52%, m.p. 94e96 ꢀC; IR(KBr) v: 2922, 2806, 2140, 1591,
163.9609, found 163.9615.
Ethyl 3-oxo-3-phenyl-2-selenocyanatopropanoate (2w): Color-
1501, 1368, 1074, 804 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d: 7.54 (d,
less oil, yield: 89%; IR (KBr)
n
: 2978, 2155, 1796, 1734, 1450, 1235,
: 8.01 (d, J ¼ 7.5 Hz, 2H),
J ¼ 8.7 Hz, 1H), 6.63 (s, 1H), 6.51 (d, J ¼ 8.7 Hz, 1H), 3.00 (s, 6H), 2.55
876 cmꢁ1; 1H NMR (300 MHz, DMSO-d6)
d
(s, 3H); 13C NMR (75 MHz, CDCl3)
d: 152.3, 142.9, 137.6, 114.2, 111.0,
7.75 (t, J ¼ 7.2 Hz, 1H), 7.60 (t, J ¼ 7.5 Hz, 2H), 6.37 (s, 1H), 4.17e4.23
106.3, 102.4, 40.1, 23.7; HRMS (TOF-ESIþ) m/z: calcd for C10H13N2Se
[MþH]þ 241.0328, found 241.0242.
(m, 2H), 1.15 (t, J ¼ 7.2 Hz, 3H); 13C NMR (75 MHz, DMSO-d6)
d:
191.5, 167.2, 135.3, 133.9, 129.6, 129.4, 103.3, 63.0, 51.8, 14.2; HRMS
(TOF-ESIþ) m/z: calcd for C12H11NO3SeNa [MþNa]þ 319.9796, found
319.9800.
4-selenocyanoanisole (5d): White solid, yield: 44%,
m.p.67e68 ꢀC; IR (KBr) v: 3071, 2846, 2150, 1586, 1490, 1181,
826 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.61 (d, J ¼ 8.7 Hz, 2H), 6.93
Ethyl
carboxylate (2x): White solid, yield: 77%, m.p. 83e85 ꢀC; IR (KBr)
: 3062, 2986, 2151, 1726, 1603, 1269, 1025, 750 cmꢁ1 1H NMR
(300 MHz, CDCl3)
: 7.91 (d, J ¼ 7.8 Hz, 1H), 7.76 (t, J ¼ 7.5 Hz, 1H),
7.49e7.56 (m, 2H), 4.19e4.34 (m, 3H), 3.84 (d, J ¼ 18.6 Hz, 1H), 1.29
1-Oxo-2-selenocyanato-2,3-dihydro-1H-indene-2-
(d, J ¼ 8.7 Hz, 2H), 3.84 (s, 3H); 13C NMR (75 MHz, CDCl3)
d: 161.4,
136.0, 116.0, 111.1, 102.1, 55.5; HRMS (TOF-ESIþ) m/z: calcd for
C8H7NNaOSe [MþNa]þ 235.9591, found 235.9593.
n
;
d
2-hydroxyl-4-methoxy-5-selenocyanobenzaldehyde
(5e):
White solid, yield: 54%, m.p.136e137 ꢀC; IR(KBr) v: 3232, 2951,
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
selenocyanates, Tetrahedron, https://doi.org/10.1016/j.tet.2020.130978

J. Cui et al. / Tetrahedron xxx (xxxx) xxx
7
2838, 2154, 1662, 1483, 1041, 878 cmꢁ1; 1H NMR (300 MHz, CDCl3)
: 11.66 (s, 1H), 9.79 (s, 1H), 7.81 (s, 1H), 6.53 (s, 1H), 3.99 (s, 3H); 13
84e85 ꢀC; IR (KBr) v: 3350, 2934,2149, 1797, 1494, 1405, 1065,
745 cmꢁ1; 1H NMR (300 MHz, CDCl3)
: 8.86 (s, 1H), 7.45e7.78 (m,
1H), 7.41e7.46 (m, 2H), 7.28e7.34 (m, 2H);13C NMR (100 MHz,
d
C
d
NMR (75 MHz, CDCl3) d: 194.0,165.6,163.0,137.0,116.5,102.7,100.9,
100.2, 57.0; HRMS (TOF-ESIþ) m/z: calcd for C9H8NO3Se [MþH]þ
CDCl3) d:136.1, 131.9, 128.8, 123.8, 121.9, 121.9, 119.6; HRMS (TOF-
257.9664, found 257.9671.
ESIþ) m/z: calcd for C9H6N2SeNa [MþNa]þ 244.9594, found
2-methoxy-4-selenocyanoanisole (5f): White solid, yield: 51%,
m.p. 65e66 ꢀC; IR (KBr) v: 3109, 2841, 2146, 1578, 1330, 1018,
244.9590.
1-methyl-5-methoxy-3-selenocyanato-1H-indole (5o): Brown
solid, yield: 94%, m.p. 98e99 ꢀC; IR (KBr) v: 3108, 2926, 2362, 2148,
803 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.22 (d, J ¼ 8.4 Hz, 1H), 7.13
(s, 1H), 6.86 (d, J ¼ 8.4 Hz, 1H), 3.88 (s, 3H), 3.87 (s, 3H); 13C NMR
1619, 1219, 1029, 803 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
: 7.33 (s,
1H), 7.26 (d, J ¼ 9.0 Hz,1H), 7.14e7.15 (m, 1H), 6.98e7.01 (m, 1H),
3.93 (s, 1H), 3.77 (s, 1H);13C NMR (100 MHz, CDCl3)
: 155.7, 136.2,
(75 MHz, CDCl3) d: 151.0, 150.0, 127.5, 116.9, 112.4, 111.0, 102.1, 56.2,
56.0; HRMS (TOF-ESIþ) m/z: calcd for C9H9NNaO2Se [MþNa]þ
d
265.9696, found 265.9694.
136.2, 132.3, 130.3, 114.0, 111.0, 101.9, 100.9, 86.5, 55.9(J ¼ 7.9 Hz),
33.54 (J ¼ 7.3 Hz); HRMS (TOF-ESIþ) m/z: calcd for C11H10N2OSeNa
[MþNa]þ 288.9856, found 288.9856.
3-methoxy-4-selenocyanoanisole (5g): Colorless oil, yield: 99%;
IR (KBr) v: 2942,2153,1588,1309,1163,834 cmꢁ1; 1H NMR (300 MHz,
CDCl3)
d
: 7.45 (d, J ¼ 8.4 Hz,1H), 6.50 (dd, J ¼ 2.1, 8.4 Hz,1H), 6.45 (d,
J ¼ 2.1 Hz,1H), 3.83 (s, 3H), 3.78 (s, 3H); 13C NMR (75 MHz, CDCl3)
d:
4.3. Gram scale experiments
162.5, 157.9, 132.9, 107.0, 101.9, 101.5, 99.3, 56.2, 55.7; HRMS (TOF-
ESIþ) m/z: calcd for C9H9NNaO2Se [MþNa]þ 265.9696, found
265.9698.
4.3.1. Synthesis of 1-phenyl-2-selenocyanatopropan-1-one (2a) on
7 mmol scale
1, 2-ethoxy-4-selenocyanobenzene (5h): White solid, yield:
To a solution of acetonitrile (210 mL), aqueous hydrochloric acid
(3 M, 70 mL) was added at 0 ꢀC, following by the addition of
aqueous sodium nitrite (1.45 g, 21 mmol, dissolved in 21 mL of
distilled water). After stirred at the same temperature for 10 min,
KSeCN (3.042 g, 21 mmol) was added in one portion. The resulting
solution was stirred at the ice bath for 20 min. Afterwards, pro-
piophenone 1a (0.94 g, 7.8 mmol) was added and the reaction
mixture was continuously stirred in room temperature until no
starting material was observed (the progress was monitored by
TLC). The solvent was removed, the residue was extracted with
ethyl acetate (60 mL ꢂ 3) and washed with brine. The combined
organic phases were dried, concentrated and purified by flash
column chromatography on silica gel (hexane/EtOAc ¼ 4:1) to give
1.58 g of 2a in 95% yield.
90%, m.p. 146e148 ꢀC; IR (KBr) v: 3103, 2978, 2147, 1578, 1228, 1041,
800 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.20 (d, J ¼ 8.4 Hz, 1H), 7.15
(s, 1H), 6.85 (d, J ¼ 8.4 Hz, 1H), 4.10 (q, J ¼ 6.6 Hz, 4H), 1.47 (t,
J ¼ 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d: 150.7, 149.7, 127.4, 118.7,
114.0, 110.8, 102.2, 64.9, 64.6, 14.6; HRMS (TOF-ESIþ) m/z: calcd for
C
11H13NNaO2Se [MþNa]þ 294.0009, found 294.0005.
2-methyl-4-selenocyanoanisole (5i): White solid, yield: 99%,
m.p. 52e53 ꢀC; IR (KBr) v: 3016, 2841, 2146, 1571, 1021, 814 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
: 7.46 (d, J ¼ 8.7 Hz, 1H), 7.44 (s, 1H),
6.81 (d, J ¼ 8.7 Hz, 1H), 3.84 (s, 3H), 2.22 (s, 3H); 13C NMR (75 MHz,
CDCl3) d: 159.5, 136.4, 133.5, 129.4, 111.5, 110.5, 102.4, 55.5, 16.2;
HRMS (TOF-ESIþ) m/z: calcd for C9H9NNaOSe [MþNa]þ 249.9742,
found 249.9750.
3-methyl-4-selenocyanoanisole (5j): White solid, yield: 90%,
m.p. 53e55 ꢀC; IR (KBr) v: 3081, 3007, 2938, 2155, 1567, 1242, 1053,
4.3.2. Synthesis of 2-methyl-4-selenocyanoanisole (5i) on 8 mmol
scale
878 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 7.60 (d, J ¼ 8.7 Hz, 1H), 6.86
(d, J ¼ 2.1 Hz, 1H), 6.72 (dd, J ¼ 2.1, 8.7 Hz, 1H), 3.79 (s, 3H), 2.51 (s,
To a solution of acetonitrile (240 mL), aqueous hydrochloric acid
(3 M, 80 mL) was added at 0 ꢀC, following by the addition of
aqueous sodium nitrite (1.66 g, 24 mmol, dissolved in 24 mL of
distilled water). After stirred at the same temperature for 10 min,
KSeCN (3.48 mg, 24 mmol) was added in one portion. The resulting
solution was stirred at the ice bath for 20 min. Afterwards, 2-
methylanisole (0.98 g, 8 mmol) was added and the reaction
mixture was continuously stirred in room temperature until no
starting material was observed (the progress was monitored by
TLC). The solvent was removed, the residue was extracted with
ethyl acetate (80 mL ꢂ 3) and washed with brine. The combined
organic phases were dried, concentrated and purified by flash
column chromatography on silica gel (hexane/EtOAc ¼ 4:1) to give
1.83 g of 5i in 99% yield.
3H); 13C NMR (75 MHz, CDCl3)
d: 161.8, 143.2, 137.3, 117.0, 113.2,
112.6, 101.8, 55.4, 23.2; HRMS (TOF-ESIþ) m/z: calcd for
C9H9NNaOSe [MþNa]þ 249.9747, found 249.9750.
2-Bromo-4-selenocyanoanisole (5k): White solid, yield: 27%,
m.p. 56e57 ꢀC; IR (KBr) v: 3087, 2923, 2147, 1573, 1293, 1050,
814 cmꢁ1 1H NMR (300 MHz, CDCl3)
; d: 7.88 (s, 1H), 7.62 (d,
J ¼ 8.7 Hz, 1H), 6.93 (d, J ¼ 8.7 Hz, 1H), 3.94 (s, 3H); 13C NMR
(75 MHz, CDCl3) d: 157.8, 138.6, 134.9, 113.2,111.8, 101.5, 56.5; HRMS
(TOF-ESIþ) m/z: calcd for C8H6BrNNaOSe [MþNa]þ 313.8696, found
313.8693.
1-selenocyano-2-methoxynaphthalene (5l): White solid, yield:
97%, m.p. 146e148 ꢀC; IR (KBr) v: 2947, 2143, 1591, 1270, 1058,
810 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
: 8.25 (d, J ¼ 8.4 Hz, 1H), 7.93
(d, J ¼ 9.0 Hz, 1H), 7.79 (d, J ¼ 7.8 Hz, 1H), 7.63 (t, J ¼ 7.8 Hz, 1H), 7.43
(t, J ¼ 7.5 Hz, 1H), 7.26 (d, J ¼ 9.0 Hz, 1H), 4.04 (s, 3H); 13C NMR
4.4. Experimental procedure for the synthesis of 3-methyl-4-
methoxyphenyldiselenide 6
(75 MHz, CDCl3) d: 158.1, 134.8, 133.8, 129.7, 128.7, 128.6, 126.2,
124.5, 112.9, 104.8, 101.6, 57.0; HRMS (TOF-ESIþ) m/z: calcd for
C
12H9NNaOSe [MþNa]þ 285.9747, found 285.9745.
To a solution of 2-methyl-4-selenocyanoanisole 5i (0.1 mmol,
22.7 mg) in methanol (1 mL), KOH (0.2 mmol, 11.2 mg, 2 equiv.) was
added. The reaction mixture was stirred at room temperature for
12 h. Then, solvent was removed in vacuo and the residue was
extracted with EtOAc (3 mL ꢂ 2) and washed with brine. The
combined organic phases were dried, concentrated and purified by
flash column chromatography on silica gel (hexane/EtOAc ¼ 19:1)
to give 20.0 mg of diselenide 6 as orange solid.
4-selenocyano-1-methoxynaphthalene (5m): White solid,
yield: 63%, m.p. 116e118 ꢀC; IR (KBr) v: 3727, 2926, 2514, 2120, 1797,
1588, 1527, 1365, 1091 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d: 8.34 (d,
J ¼ 8.4 Hz, 1H), 8.24 (d, J ¼ 8.4 Hz, 1H), 7.93 (d, J ¼ 7.8 Hz,1H), 7.71 (t,
J ¼ 7.5 Hz, 1H), 7.59 (t, J ¼ 7.8 Hz, 1H), 6.77 (d, J ¼ 8.1 Hz, 1H), 4.02 (s,
3H);13C NMR (100 MHz, CDCl3)
d: 158.6, 136.9, 134.4, 128.7, 127.0,
126.8, 126.4, 123.0, 110.3, 104.3, 101.7, 55.9 (d, J ¼ 8.0 Hz); HRMS
(TOF-ESIþ) m/z: calcd for C12H9NNaOSe [MþNa]þ 285.9742, found
285.9745.
2 Bis(3-methyl-4-methoxyphenyl)diselenide (6): Orange solid,
yield: 99%, m.p. 62e64 ꢀC; IR (KBr) v 2922, 1796, 1586, 1486, 1246,
3-selenocyanato-1H-indole (5n): Brown solid, yield: 96%, m.p.
1140,1026, 815; 1H NMR (300 MHz, CDCl3)
d: 7.52 (d, J ¼ 8.1 Hz, 2H),
Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
selenocyanates, Tetrahedron, https://doi.org/10.1016/j.tet.2020.130978

8
J. Cui et al. / Tetrahedron xxx (xxxx) xxx
7.49 (s, 2H), 6.79 (d, J ¼ 8.1 Hz, 2H), 3.87 (s, 6H), 2.30 (s, 6H); 13C
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NMR (75 MHz, CDCl3) d: 158.4, 136.4, 133.0, 127.7, 121.7, 110.6, 55.4,
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~
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424.9529, found 424.9521.
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and sub-
mitted along with the manuscript and graphic files to the appro-
priate editorial office.
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Declaration of competing interest
There are no conflicts to declare.
Acknowledgements
(c) F. Victor, C.S.N. Ana, M.A. Marcela, R.B.G. Claudia, V.N. de Souza Marcus,
R.A.V. Thatyana, Curr. Org. Synth. 12 (2015) 140e149.
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The authors acknowledge the financial support from the Na-
tional Natural Science Foundation of China (No. 21762008), the
(d) D. Plano, D.N. Karelia, M.K. Pandey, J.E. Spallholz, S. Amin, A.K. Sharma,
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Guangxi
Natural
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Foundation
of
China
(No.
2018GXNSFAA281245; No. 2019AC20202) and “Bagui Scholar”
Program of Guangxi Province of China, PR China.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.130978.
(b) K. Sun, X. Wang, F. Fu, C. Zhang, Y. Chen, L. Liu, Green Chem. 19 (2017)
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Please cite this article as: J. Cui et al., Oxidative umpolung selenocyanation of ketones and arenes: An efficient protocol to the synthesis of
selenocyanates, Tetrahedron, https://doi.org/10.1016/j.tet.2020.130978