A convenient, transition metal-free synthesis of difluoromethyl selenoethers from organic selenocyanates and TMSCF2H

Article abstract of DOI:10.1016/j.tet.2018.08.001

An efficient and transition metal-free method for the synthesis of aryl or alkyl difluoromethyl selenides (RSeCF₂H) from the corresponding selenocyanates (RSeCN) and TMSCF₂H/t-BuOK is described. The reaction performed in THF at 0 °C for 24 h or at room temperature for 6 h supplied a series of RSeCF₂H in good to high yields. The successful preparation of difluoromethylselenolated sulfadimethoxine derivative and the scaled-up synthesis of 1-benzyl-5-((difluoromethyl)selanyl)indoline, as examples, suggested good practicability of this method. Advantages of the reaction include mild reaction conditions, good functional group tolerance, a wide range of substrates, and high efficiency. This protocol offered a number of novel difluoromethyl selenoethers, which would accelerate use of such compounds in the areas of life science.

Full text of DOI:10.1016/j.tet.2018.08.001

Accepted Manuscript
A convenient, transition metal-free synthesis of difluoromethyl selenoethers from
organic selenocyanates and TMSCF H
2
Tao Dong, Jing Nie, Cheng-Pan Zhang
PII:
S0040-4020(18)30938-4
10.1016/j.tet.2018.08.001
TET 29720
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 3 July 2018
Revised Date: 31 July 2018
Accepted Date: 2 August 2018
Please cite this article as: Dong T, Nie J, Zhang C-P, A convenient, transition metal-free synthesis of
difluoromethyl selenoethers from organic selenocyanates and TMSCF H, Tetrahedron (2018), doi:
2
10.1016/j.tet.2018.08.001.
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ACCEPTED MANUSCRIPT
Graphic Abstract

ACCEPTED MANUSCRIPT
A Convenient, Transition Metal-Free Synthesis of Difluoromethyl Selenoethers
from Organic Selenocyanates and TMSCF2H
Tao Dong, Jing Nie, Cheng-Pan Zhang*
School of Chemistry, Chemical Engineering and Life Science, Wuhan University of
Technology, 205 Luoshi Road, Wuhan, 430070, China
E-mail: cpzhang@whut.edu.cn, zhangchengpan1982@hotmail.com
Abstract
An efficient and transition metal-free method for the synthesis of aryl or alkyl
difluoromethyl selenides (RSeCF2H) from the corresponding selenocyanates (RSeCN)
o
and TMSCF2H/t-BuOK is described. The reaction performed in THF at 0 C for 24 h
or at room temperature for 6 h supplied a series of RSeCF2H in good to high yields.
The successful preparation of difluoromethylselenolated sulfadimethoxine derivative
and the scaled-up synthesis of 1-benzyl-5-((difluoromethyl)selanyl)indoline, as
examples, suggested good practicability of this method. Advantages of the reaction
include mild reaction conditions, good functional group tolerance, a wide range of
substrates, and high efficiency. This protocol offered a number of novel
difluoromethyl selenoethers, which would accelerate use of such compounds in the
areas of life science.
Keywords: Difluoromethyl Selenoether; Transition Metal-Free; Selenocyanate;
Difluoromethylselenol; Difluoromethylation.
1. Introduction
Fluorinated compounds have found wide applications in many fields ranging from
medicinal chemistry to materials science.1 The incorporation of fluoroalkyl groups
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into organic frameworks can dramatically change their physicochemical and
biological properties.2 In particular, the difluoromethyl group (HCF2) has been one of
the most privileged segments because of its unique stereoelectronic nature and great
potentials in the synthesis of bioactive molecules.3 The HCF2 group is a good
isopolar-isosteric substituent for hydroxy (OH) and thiol (SH) units, and it acts as a
more lipophilic hydrogen donor than the OH and SH groups in various hydrogen
bonding interactions.3 The combination of HCF2 group with chalcogens (X) gives
HCF2X functionalities with more specific and interesting properties. Among all
HCF2X moieties, the difluoromethylselenol group (HCF2Se) is the least studied,
despite the most relevant HCF2S functionality having been extensively explored.4
This may be attributed to the cognition that selenium-containing compounds are
usually highly toxic, easily oxidized, and with unpleasant odor.5 Nonetheless,
organoselenium compounds have possessed advantageous biological properties such
as antifungal, anticancer, and antiviral activities,5,6 some of which have been
investigated for the treatment of Alzheimer’s disease.6a The lack of
difluoromethylselenolation reagents and appropriate starting materials is considered to
be another bottleneck in the construction of HCF2Se molecules.
To date, there have been only several synthetic approaches reported for HCF2Se
compounds.7-11 In 1985, Suzuki et al. disclosed the first synthesis of aryl
difluoromethyl selenides from the reactions of HCF2Cl with arylselenolates in
alkaline aqueous media (5 examples).7 Later, Uneyama et al found that reaction of
CF2Br2 with benzeneselenolate, prepared in situ from diphenyl diselenide and sodium
borohydride in EtOH/DMF, gave difluoromethyl phenyl selenide as a major product
in 55% yield (1 example).8 Greaney et al described the difluoromethylation of
phenylselenol by using chlorodifluoroacetate as a difluorocarbene source, affording
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difluoromethyl phenyl selenide in 65% yield (1 example).9 Recently, Billard et al
reported a reaction of electron-rich indol or resorcinol with HCF2SeCl, which was in
situ generated from benzyl(difluoromethyl)selane and SO2Cl2, furnishing the
corresponding difluoromethylselenolated product in good yield (2 examples).10 With
HCF2SeCl reagent, the same research group again developed a transition metal-free
difluoromethylselenolation/cyclization of alkyne to form a isocoumarin derivative and
an oxidant-free difluoromethylselenolation of alkynyl copper(I) complex to yield a
difluoromethyl alkynyl selenide (single example for each).11 All these methods
suffered from a very limited substrate scope, relative inaccessibility of starting
materials, high cost, and/or low efficiency, supplying a small quantity of
HCF2Se-containing entities, which seriously restricted the application of this type of
molecules. Thus, the development of efficient and convenient methodologies for the
synthesis of various difluoromethylselenolated compounds is of great importance.
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Although trifluoromethylation of selenocyanates with TMSCF3 has been well
documented,12a,12d the interaction between RSeCN and TMSCF2H (a less reactive
reagent than TMSCF3)4f is rarely known.10 In this work, we successfully developed a
transition metal-free direct difluoromethylation of selenocyanates with TMSCF2H in
the presence of an appropriate initiator, building diverse difluoromethyl selenoethers
under mild conditions.
2. Results and discussions
The reaction of 1-methoxy-4-selenocyanatobenzene (1a) and TMSCF2H was chosen
as a model reaction to screen the optimal conditions. A mixture of 1a and CsF (2
equiv.) reacted with TMSCF2H (2 equiv.) in DMF at room temperature under a N2
atmosphere for 12 h to give (difluoromethyl)(4-methoxyphenyl)selane (2a) in 62%
yield (entry 1, Table 1). 1,2-Bis(4-methoxyphenyl)diselane (3a) was also formed in
this reaction (30% yield) (entry 1, Table 1). When the reaction of 1a, TMSCF2H, and
CsF was conducted in DMSO or CH3CN, the desired product (2a) was obtained in a
very low yield and the formation of byproduct 3a was enhanced (entries 2-3, Table 1).
If the same reaction was performed in THF, only trace amount of 2a and none of 3a
were observed (entry 4, Table 1), which might be accounted for by the much poor
solubility of CsF in the reaction solvent. While if t-BuOK was employed as a base in
THF, 65% of 2a and 36% of 3a were obtained (entry 5, Table 1). Reaction of 1a,
TMSCF2H, and t-BuOK in DMF gave 2a in 33% yield, accompanied by 32% of 3a
(entry 6, Table 1). To suppress the formation of 3a, the adding order of the reaction
materials was varied. Interestingly, when a solution of t-BuOK (2 equiv.) in THF was
added to a mixture of 1a and TMSCF2H (2 equiv.), the formation of byproduct (3a)
was almost completely prohibited and the desired product was obtained in 66% yield
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(entry 7, Table 1). These results suggested that the homocoupling of 1a competed with
the difluoromethylation of 1a under the reaction conditions. Furthermore, shortening
the reaction time of 1a, TMSCF2H and t-BuOK from 12 h to 6 h or 2 h at room
temperature resulted in 81% or 72% of 2a, respectively (Entries 8-9, Table 1). The
reaction temperature also had a considerable influence on the difluoromethylation.
Lowering the reaction temperature from room temperature to 0 °C or -20 °C furnished
the expected product in 71% or 65% yield (entries 10-11, Table 1). The production of
3a was completely inhibited. When the reaction of 1a, TMSCF2H and t-BuOK was
run at 0 oC for 24 h, 2a was formed in 95% yield (91% isolated yield) (entry 12, Table
1). Nevertheless, further extension of the reaction time to 36 h did not continuously
improve the yield of 2a (entry 13, Table 1). In addition, the molar ratios of the
reactants had a big effect on the reaction. By varying the molar ratio of
1a/TMSCF2H/t-BuOK from 1:2:2 to 1:1.5:1.5 or 1:1:1, the yield of 2a was
dramatically decreased (e.g., entry 14, Table 1). The use of 2 equivalents of t-BuOK
to work with 1a and TMSCF2H (1 equiv.) led to a lower yield of 2a as well (entry 15,
Table 1). Except formation of 2a in these cases, appreciable amounts of 3a were
detected along with an unknown byproduct which couldn’t be isolated by column
chromatography (entries 14-15, Table 1). It should be mentioned that, if the reaction
of 1a and TMSCF2H was conducted in the absence of CsF or t-BuOK, there was no
desired product or byproduct formed, suggesting the indispensability of a base (entry
16, Table 1). Interestingly, if 3a (instead of 1a) reacted with TMSCF2H and t-BuOK at
room temperature for 6 h, 2a was formed in 48% yield with recovery of 48% of 3a,
implying a much lower reactivity of 1,2-diaryldiselane in the present system (entry 17,
Table 1).4f
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Table 1 Screening the optimal reaction conditions for difluoromethylation of 1a
with TMSCF2H in the presence of CsF or t-BuOK
Entry
1 b
Base
CsF
Conditions
Yield (2a, %) a Yield (3a, %) a
DMF, N2, rt, 12 h
DMSO, N2, rt, 12 h
CH3CN, N2, rt, 12 h
THF, N2, rt, 12 h
THF, N2, rt, 12 h
DMF, N2, rt, 12 h
THF, N2, rt, 12 h
THF, N2, rt, 6 h
62
33
30
42
56
0
2 b
CsF
3 b
CsF
3
4 b
CsF
<1
65
5 b
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
-
36
32
<1
4
6 b
33
7 c
66
8 c
81
9 c
THF, N2, rt, 2 h
72
3
10 c
11 c
12 c
13 c
14 c,d
15 c,e
16 c,f
17 c,g
THF, N2, 0 oC, 12 h
THF, N2, -20 oC, 12 h
THF, N2, 0 oC, 24 h
THF, N2, 0 oC., 36 h
THF, N2, 0 oC, 24 h
THF, N2, 0 oC, 24 h
THF, N2, 0 oC, 24 h
THF, N2, rt, 6 h
71
0
65
0
95 (91)
91
0
0
20
38
18
0
40
0
t-BuOK
48
48
a Yields were determined by HPLC (λ = 232 nm, methanol/water = 90:10 (v/v)) using
2a and 3a as external standards, respectively (2a: tR = 4.47 min, 3a: tR = 9.97 min (tR
b
means the retention time)).
Reaction conditions: TMSCF2H (0.4 mmol) was
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c
added to a mixture of 1a (0.2 mmol) and base (0.4 mmol) in solvent (2 mL).
Reaction conditions: To a solution of 1a (0.2 mmol) and TMSCF2H (0.4 mmol) in
THF (1 mL) was added a solution of t-BuOK (0.4 mmol) in THF (1 mL).
d 1a (0.2
e
mmol), TMSCF2H (0.3 mmol), and t-BuOK (0.3 mmol).
1a (0.2 mmol),
f
TMSCF2H (0.2 mmol), and t-BuOK (0.4 mmol).
No CsF or t-BuOK was used.
g 3a (0.2 mmol) was used instead of 1a as starting material.
With the optimized (or standard) reaction conditions in hand (entry 12, Table 1), the
substrate scope of the transformation was tested. As summarized in Table 2, numerous
electron-rich arylselenocyanates (1b-i) reacted with TMSCF2H/t-BuOK under the
standard conditions to give the corresponding difluoromethylselenolated products
(2a-i)
in
54-94%
yields.
The
indol
derivatives
such
as
1-benzyl-5-selenocyanatoindoline (1j), 1-methyl-3-selenocyanato-1H-indole (1k), and
1-benzyl-3-selenocyanato-1H-indole (1l) treated similarly in the reaction provided
2j-l in 90-93% yield. It is noteworthy that reaction of 4-selenocyanatophenol (1m)
with 2 equivalents of TMSCF2H and 3.5 equivalents of t-BuOK furnished 70% of
4-((difluoromethyl)selanyl)phenol (2m). Since the acidic hydroxy group in 1m would
expend equal equivalent of t-BuOK, the use of a large excess of t-BuOK was helpful
for the high conversion of the starting material. The results also implied that the
hydroxy substituent on the aryl ring without protection hardly affected the
difluoromethylation reaction. Furthermore, arylselenocyanates (1n-p) bearing
electron-withdrawing groups such as nitro, cyano, and ester functionalities on the aryl
rings reacted under the standard conditions to give the expected products (2n-p) in
62-65% yields. It seemed that the electron-rich arylselenocyanates were more
efficiently transformed than the electron-deficient ones in these reactions.
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Additionally, if the above reactions were performed at room temperature for 6 h (entry
8, Table 1), comparable yields of the desired products were achieved in some cases
(e.g. 2a, 2e, 2g, 2i, 2l), while for others much lower yields of products were observed
(e.g. 2h, 2n). The nature of the substituents on the aryl moieties of arylselenocyanates
might be responsible for these changes.
Encouragingly, the reaction was also applicable to alkylselenocyanates. The primary
alkylselenocyanate,
such
as
(3-selenocyanatopropyl)benzene
(1q),
1-selenocyanatooctane (1r) and 1-selenocyanatohexadecane (1s), and the secondary
alkylselenocyanate like (3-selenocyanatobutyl)benzene (1t) reacted readily under the
standard conditions to furnish the difluoromethylselenolated products (2q-t) in
excellent yields, demonstrating good availability of this method. To our surprise,
treatment of (selenocyanatomethyl)benzene (1u) with TMSCF2H and t-BuOK at 0 oC
for 24 h or at room temperature for 6 h afforded benzyl(difluoromethyl)selane (2u)
19
19
only in 13% or 10% F NMR yield, respectively (33% F NMR yield was obtained
in the literature using TMSCF2H/CsF mixture).10,11 The reason for these low yields
remains unclear. Because compounds 2d and 2r were volatile and easily evaporated
during the workup and the drying processes, the NMR yields were reasonably higher
than the isolated ones. Moreover, it should be mentioned that all selenocyanates used
in this reaction could be simply synthesized from the relevant aromatic amines, arenes
and alkyl halides according to the literatures,12 which guaranteed easy accessibility of
diverse starting materials for the difluoromethylation.
Table 2 Synthesis of difluoromethyl selenoethers from different types of aryl- and
alkylselenocyanates.a
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t-BuOK (2 equiv)
THF, 0 oC, N2, 24 h
R SeCN
+
TMSCF2H
(2 equiv)
R SeCF2H
1
2
SeCF2H
SeCF2H
SeCF2H
SeCF2H
O
2a, 91%, 87%b
SeCF2H
2b, 75%, 63%b
2d, 54% (83%c)
2c, 76%
SeCF2H
SeCF2H
SeCF2H
O
O
PhO
Ph
2g, 94%, 92%b
SeCF2H
2h, 91%, 31%b, 79%d
2f, 86%, 64%b
2e, 78%, 78%b
SeCF2H
SeCF2H
SeCF2H
N
Bn
N
N
N
Bn
2l, 92%, 94%b
2i, 87% 87%b
2j, 93%
2k, 90%, 77%b
SeCF2H
SeCF2H
SeCF2H
SeCF2H
HO
O2N
NC
tBuO2C
2m, 70%e
2n, 62%, 26%b
2o, 64%, 55%b
2p, 65%
SeCF2H
SeCF2H
SeCF2H
2u, 13%c (10%b,c
n
SeCF2H
2q, 83%
2r, n = 5, 60% (84%c)
2s, n = 13, 88%
2t, 92%
)
a Reaction conditions: To a solution of selenocyanate 1 (0.2 mmol) and TMSCF2H
(0.4 mmol) in THF (1 mL) was added a solution of t-BuOK (0.4 mmol) in THF (1
o
mL), and the mixture was reacted at 0 C under a N2 atmosphere for 24 h. Isolated
b
19
yields.
Room temperature for 6 h. c The yields were determined by F NMR
d
o
using PhOCF3 as an internal standard.
used.
0 C for 6 h. e t-BuOK (0.7 mmol) was
To further illustrate the practicability of this method, a difluoromethylselenolated
analogue of sulfadimethoxine (a long-lasting sulfonamide antimicrobial) was
synthesized in a similar manner (Scheme 1). In the first step of the synthesis,
4-(N-(2,6-dimethoxypyrimidin-4-yl)sulfamoyl)benzenediazonium tetrafluoroborate (5)
was
derived
from
the
reaction
of
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4-amino-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide (4) with HBF4 and
tert-butyl nitrite. Then, a solution of 5 in CH3CN was treated with KSeCN in the
presence
of
CuCl,
CuCl2,
and
1,10-phenanthroline
to
give
N-(2,6-dimethoxypyrimidin-4-yl)-4-selenocyanatobenzenesulfonamide (1v) in 45%
yield.12a Finally, reaction of 1v with TMSCF2H (2 equiv) and t-BuOK (3 equiv) in
o
THF (1 mL) at 0 C for 24 h provided the difluoromethylselenolated product (2v) in
25% yield. In addition, the scaled-up synthesis of 2j from 1-benzylindoline was
investigated (Scheme 2). Treatment of 1-benzylindoline (10 mmol) with KSeCN (2
equiv.) in the presence of NIS, TBHP (70% aqueous solution), and acetic acid in
acetonitrile at room temperature for 36 h afforded 1-benzyl-5-selenocyanatoindoline
(1j) in 45% yield.12b Subsequently, 1j reacted with TMSCF2H (2 equiv.) and t-BuOK
(2 equiv.) in THF (10 mL) under the standard conditions to form 2j in 75% yield
(1.148 g). These selected examples hinted at usefulness of the present reactions for
the synthesis of various difluoromethyl selenoethers.
Scheme 1 Synthesis of 2v from sulfadimethoxine (4)
Scheme 2 Scaled-up synthesis of 2j from 1-benzylindoline
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Based on the above results and the previous reports,13 a plausible reaction
mechanism was suggested for this difluoromethylation (Scheme 3). First, t-BuOK
coordinates with the silicon center of Me3SiCF2H to form a pentacoordinate silicate
(6). Reaction of 6 with another equivalent of Me3SiCF2H generates a
K[Me3Si(CF2H)2] intermediate (7), which then undergoes a nucleophilic attack at the
selenium atom of RSeX (X = CN, SeR) to afford the desired product RSeCF2H (2).
However, construction of RSeCF2H by the direct difluoromethylation of RSeX with 6
cannot be excluded in the reactions at this stage. Additionally, minor RSeSeR species
observed in some reactions might be generated in situ from RSeCN, which could be
further converted to RSeCF2H under the reaction conditions. This hypothesis was
partially supported by the experimental data described in Table 1.
Scheme 3 A plausible reaction mechanism for the construction of RSeCF2H from
RSeX and Me3SiCF2H/t-BuOK
3. Conclusions
In summary, we have developed a convenient and transition metal-free method for
the construction of aryl and alkyl difluoromethyl selenides from the corresponding
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selenocyanates (RSeCN) and TMSCF2H in the presence of t-BuOK. The reaction
performed in THF at 0 oC for 24 h or at room temperature for 6 h supplied a series of
RSeCF2H in good to high yields. Various functionalities such as methoxy, hydroxyl,
ester, nitro, cyano, and amide groups, as well as heterocyclic moieties, were well
tolerated in the reaction. It was remarkable that the secondary alkyl selenocyanate
reacted under the standard conditions to give the desired product without formation of
β-H elimination byproduct even in the presence of strongly alkaline t-BuOK.
Furthermore, the successful synthesis of difluoromethylselenolated sulfadimethoxine
derivative and the scaled-up preparation of 2j suggested good versatility of the
method. This protocol offered an efficient way to a family of novel difluoromethyl
selenoethers, which would encourage application of these molecules in life sciences.
4. Experimental Section
All reactions were carried out under a nitrogen atmosphere. Unless otherwise
specified, the NMR spectra were recorded in CDCl3 on a 500 MHz (for 1H), 471 MHz
19
13
(for F), and 126 MHz (for C) spectrometer. All chemical shifts were reported in
ppm relative to TMS for 1H NMR (0 ppm) and PhCF3 for 19F NMR (-63.0 ppm) as an
internal or external standard. The coupling constants were reported in Hertz (Hz). The
following abbreviations were used to explain the multiplicities: s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet, br = broad. Melting points were
measured and uncorrected. MS experiments were performed on a TOF-Q ESI or EI
instrument. Solvents (such as THF, CH3CN, DMF, DMSO) were dried before use
according to the literature.14 TMSCF2H was prepared according to the literature.15
Substrates such as 1a-i,12a 1j-m,12b 1n-p,12a 1q-u,12c and 1v12a were synthesized
according to the literatures. Other reagents used in the reactions were all purchased
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from the commercial sources and used without further purification.
4.1. Procedures for the synthesis of organic selenocyanates.
Procedure:12a Under a N2 atmosphere, an oven-dried round-bottom flask (100 mL)
was charged with CuCl (50 mg, 0.5 mmol), CuCl2 (68 mg, 0.5 mmol), 1,10-
phenanthroline (90 mg, 0.5 mmol), KSeCN (1.08 g, 7.5 mmol), and CH3CN (10 mL)
o
with stirring. The mixture was cooled to -25 C and a solution of aryldiazonium
tetrafluoroborate (5 mmol) in CH3CN (10 mL) was dropwise added (within 10 min).
The reaction mixture was maintained at -25 °C for 10 min, and then warmed to room
temperature for about 30 min. The resulting slurry was filtered through a short pad of
silica and washed with CH3CN (3 × 10 mL). The collected solutions were
concentrated under reduced pressure. The residue was purified by column
chromatography on silica gel using a mixture of petroleum ether and ethyl acetate as
eluents to give the desired product.
Note: all aryldiazonium tetrafluoroborates were prepared from the reactions of the
relevant aryl amines with an aqueous HBF4 solution and NaNO2 or tert-butyl nitrite
according to the literature.16
5-Selenocyanatobenzo[d][1,3]dioxole (1g). White solid (780 mg, 69% yield),
petroleum ether/ethyl acetate = 10:1 (v/v) as eluents for column chromatography. M.p.:
o
1
55-57 C. H NMR (500 MHz, CDCl3) δ 7.16 (dd, J = 8.0, 1.7 Hz, 1H), 7.15 (d, J =
13
1.7 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.04 (s, 2H). C NMR (126 MHz, CDCl3) δ
149.9, 149.0, 128.8, 114.5, 111.9, 109.9, 102.0, 101.8. IR (KBr): 3098, 3044, 3008,
2913, 2148, 1593, 1498, 1475, 1438, 1416, 1400, 1347, 1250, 1236, 1164, 1106, 1032,
74
928, 875, 850, 816, 722, 669 cm−1. HRMS-EI (m/z) calcd. for C8H5NO2 Se:
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220.9545, found: 220.9548.
1-Phenoxy-4-selenocyanatobenzene (1h). White solid (718 mg, 52% yield),
petroleum ether/ethyl acetate = 20:1 (v/v) as eluents for column chromatography. M.p.:
60-62 oC. 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 8.8 Hz, 2H), 7.40 (t, J = 7.9 Hz,
13
2H), 7.20 (t, J = 7.4 Hz, 1H), 7.05 (d, J = 8.6 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H). C
NMR (126 MHz, CDCl3) δ 159.8, 155.7, 135.8, 130.1, 124.6, 119.9, 119.8, 113.7,
101.8. IR (KBr): 3080, 3052, 2150, 1593, 1572, 1484, 1454, 1404, 1300, 1283, 1240,
1196, 1169, 1154, 1102, 1069, 1019, 1005, 918, 867, 836, 816, 800, 757, 700 cm−1.
HRMS-EI (m/z) calcd. for C13H9NO74Se: 268.9909, found: 268.9915.
N-(2,6-Dimethoxypyrimidin-4-yl)-4-selenocyanatobenzenesulfonamide (1v). White
solid (898 mg, 45% yield), petroleum ether/ethyl acetate = 2:1 (v/v) as eluents for
o
1
column chromatography. M.p.: 173-175 C. H NMR (500 MHz, DMSO-d6) δ 11.80
(brs, 1H), 7.98 (d, J = 7.9 Hz, 2H), 7.94 (d, J = 8.2 Hz, 2H), 5.97 (s, 1H), 3.81 (s, 3H),
13
3.75 (s, 3H). C NMR (126 MHz, DMSO-d6) δ 172.2, 164.5, 160.2, 141.1, 133.6,
131.5, 128.8, 105.3, 85.3, 55.1, 54.4. IR (KBr): 3242, 3096, 2987, 2952, 2156, 1583,
1493, 1473, 1446, 1376, 1352, 1328, 1279, 1261, 1209, 1198, 1159, 1102, 1070, 1008,
985, 884, 825, 816, 740, 716, 659, 631 cm-1. HRMS-ESI (m/z) calcd. for
[C13H13N4O4SSe]+ ([M + H]+): 400.9783, found: 400.9782.
Procedure:12c An oven-dried round-bottom flask (50 mL) was charged with
(3-iodobutyl)benzene (0.52 g, 2.0 mmol), KSeCN (346 mg, 2.4 mmol), and ethanol
(10 mL) with vigorous stirring. The mixture was reacted at 80 oC for 3 h, quenched by
aqueous saturated NaCl solution (20 mL), and extracted with ethyl acetate (3 × 20
14 / 27

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mL). The combined organic layers were dried over anhydrous Na2SO4 and
concentrated under reduced pressure. The residue was purified by flash column
chromatography on silica gel using petroleum ether/ethyl acetate = 20:1 (v/v) as
eluents to give (3-selenocyanatobutyl)benzene (1t) as a light yellow liquid (404 mg,
85%). 1H NMR (500 MHz, CDCl3) δ 7.32 (t, J = 7.5 Hz, 2H), 7.24 (d, J = 7.3 Hz, 1H),
7.20 (d, J = 7.6 Hz, 2H), 3.45 (m, 1H), 2.79 (m, 2H), 2.15 (m, 2H), 1.73 (d, J = 6.8 Hz,
13
3H). C NMR (126 MHz, CDCl3) δ 140.1, 128.7, 128.5, 126.5, 101.1, 43.4, 39.6,
34.0, 23.5. IR (KBr): 3085, 3062, 3027, 2960, 2925, 2861, 2148, 1603, 1584, 1496,
1454, 1381, 1357, 1285, 1255, 1231, 1211, 1163, 1113, 1091, 1060, 1031, 1003, 915,
816, 749, 700, 621 cm−1. HRMS-EI (m/z) calcd. for C11H13N74Se: 233.0273, found:
233.0278.
4.2. General procedures for difluoromethylation of selenocyanates by TMSCF2H.
Procedure A: Under a N2 atmosphere, an oven-dried tube was charged with alkyl or
aryl selenocyanate 1 (0.2 mmol), TMSCF2H (0.4 mmol), and THF (1 mL) with
stirring. Then, a solution of t-BuOK (0.4 mmol) in THF (1 mL) was added dropwise
o
o
at 0 C. The mixture was reacted at 0 C for 24 hours, quenched by H2O (2 drops),
and concentrated to dryness. The residue was purified by column chromatography on
silica gel using petroleum ether or a mixture of petroleum ether and ethyl acetate as
eluents to give the difluoromethylated product.
Procedure B: Under a N2 atmosphere, an oven-dried tube was charged with aryl
selenocyanate 1 (0.2 mmol), TMSCF2H (0.4 mmol), and THF (1 mL) with stirring.
Then, a solution of t-BuOK (0.4 mmol) in THF (1 mL) was added at room
temperature. The mixture was reacted at room temperature for 6 hours, quenched by
H2O (2 drops), and concentrated to dryness. The residue was purified by column
15 / 27

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chromatography on silica gel using petroleum ether or a mixture of petroleum ether
and ethyl acetate as eluents to give the difluoromethylated product.
(Difluoromethyl)(4-methoxyphenyl)selane (2a). Light yellow oil (43.2 mg, 91% yield
from procedure A; 41.2 mg, 87% yield from procedure B), petroleum ether/ethyl
1
acetate = 40:1 (v/v) as eluents for column chromatography. H NMR (500 MHz,
CDCl3) δ 7.60 (d, J = 8.2 Hz, 2H), 7.10 (t, J = 55.6 Hz, 1H), 6.89 (d, J = 8.2 Hz, 2H),
3.83 (s, 3H). 19F NMR (471 MHz, CDCl3) δ -91.1 (d, J = 55.6 Hz, 2F). 13C NMR (126
MHz, CDCl3) δ 160.9, 138.4, 117.1 (t, J = 289.7 Hz), 115.2, 113.5 (t, J = 2.8 Hz),
55.3. IR (KBr): 3069, 3007, 2964, 2942, 2908, 2840, 1592, 1572, 1493, 1462, 1441,
1404, 1290, 1271, 1251, 1176, 1104, 1079, 1062, 1039, 1005, 827, 811, 793, 712, 691,
74
670, 631, 602 cm−1. HRMS-EI (m/z) calcd. for C8H8OF2 Se: 231.9768, found:
231.9769.
(Difluoromethyl)(4-tolyl)selane (2b). Light yellow oil (33.2 mg, 75% yield from
procedure A; 27.9 mg, 63% yield from procedure B), petroleum ether as eluent for
column chromatography. 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 8.1 Hz, 2H), 7.18
19
(d, J = 7.9 Hz, 2H), 7.13 (t, J = 55.5 Hz, 1H), 2.38 (s, 3H). F NMR (471 MHz,
13
CDCl3) δ -90.5 (d, J = 55.5 Hz, 2F). C NMR (126 MHz, CDCl3) δ 139.8, 136.5,
130.3, 119.8 (t, J = 2.7 Hz), 117.2 (t, J = 289.0 Hz), 21.3. IR (KBr): 3025, 2965, 2924,
2868, 1491, 1448, 1397, 1292, 1271, 1211, 1183, 1078, 1063, 1016, 805, 706, 690,
74
669 cm−1. HRMS-EI (m/z) calcd. for C8H8F2 Se: 215.9819, found: 215.9817.
(Difluoromethyl)(2,4-dimethylphenyl)selane (2c). Yellow oil (35.7 mg, 76% yield
1
from procedure A), petroleum ether as eluent for column chromatography. H NMR
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(500 MHz, CDCl3) δ 7.57 (d, J = 7.8 Hz, 1H), 7.15 (s, 1H), 7.09 (t, J = 55.4 Hz, 1H),
19
6.98 (d, J = 7.8 Hz, 1H), 2.49 (s, 3H), 2.34 (s, 3H). F NMR (471 MHz, CDCl3) δ
-90.0 (d, J = 55.4 Hz, 2F). 13C NMR (126 MHz, CDCl3) δ 142.7, 140.3, 138.0, 131.5,
127.7, 121.1 (t, J = 2.7 Hz), 117.4 (t, J = 289.1 Hz), 23.4, 21.1. IR (KBr): 3010, 2965,
2924, 2862, 1600, 1475, 1446, 1379, 1291, 1270, 1234, 1067, 1031, 877, 812, 722,
74
709, 689, 669 cm−1. HRMS-EI (m/z) calcd. for C9H10F2 Se: 229.9975, found:
229.9969.
(Difluoromethyl)(phenyl)selane (2d).9 Yellow oil (22.5 mg, 54% yield from
1
procedure A), petroleum ether as eluent for column chromatography. H NMR (500
MHz, CDCl3) δ 7.68 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.5 Hz, 1H), 7.37 (t, J = 7.5 Hz,
19
2H), 7.17 (t, J = 55.0 Hz, 1H). F NMR (471 MHz, CDCl3) δ -90.3 (d, J = 55.0 Hz,
2F). 13C NMR (126 MHz, CDCl3) δ 136.4, 129.5, 129.5, 123.5 (t, J = 2.6 Hz), 117.1 (t,
J = 289.4 Hz).
(Difluoromethyl)(naphthalen-1-yl)selane (2e). Light yellow oil (40.1 mg, 78% yield
from procedure A; 40.3 mg, 78% yield from procedure B), petroleum ether/ethyl
1
acetate = 40:1 (v/v) as eluents for column chromatography. H NMR (500 MHz,
CDCl3) δ 8.49 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 7.1, 0.7 Hz, 1H), 7.96 (d, J = 8.2 Hz,
1H), 7.89 (d, J = 8.1 Hz, 1H), 7.63 (tm, J = 7.5 Hz, 1H), 7.57 (tm, J = 7.4 Hz, 1H),
19
7.46 (t, J = 7.6 Hz, 1H), 7.15 (t, J = 55.3 Hz, 1H). F NMR (471 MHz, CDCl3) δ
-89.5 (d, J = 55.3 Hz, 2F). 13C NMR (126 MHz, CDCl3) δ 137.2, 135.4, 134.2, 131.0,
128.7, 128.1, 127.4, 126.6, 125.9, 123.2 (t, J = 2.7 Hz), 117.4 (t, J = 289.7 Hz). IR
(KBr): 3055, 2968, 2917, 2848, 1589, 1561, 1502, 1379, 1337, 1290, 1271, 1253,
1201, 1135, 1060, 958, 862, 797, 770, 736, 694, 676, 652, 620 cm−1. HRMS-EI (m/z)
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74
calcd. for C11H8F2 Se: 251.9819, found: 251.9825.
[1,1'-Biphenyl]-4-yl(difluoromethyl)selane (2f). Light yellow oil (48.9 mg, 86% yield
from procedure A; 36.1 mg, 64% yield from procedure B), petroleum ether as eluent
for column chromatography. 1H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz, 2H),
7.62-7.59 (m, 4H), 7.48 (t, J = 7.4 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 7.22 (t, J = 55.3
19
13
Hz, 1H). F NMR (471 MHz, CDCl3) δ -90.2 (d, J = 55.3 Hz, 2F). C NMR (126
MHz, CDCl3) δ 142.5, 140.0, 136.8, 129.0, 128.2, 128.0, 127.2, 122.3 (t, J = 2.8 Hz),
117.1 (t, J = 289.3 Hz). IR (KBr): 3061, 3024, 3009, 2967, 2922, 2852, 1589, 1553,
1476, 1446, 1392, 1318, 1289, 1107, 1080, 1060, 1045, 1031, 1007, 968, 950, 920,
74
831, 765, 718, 700, 670, 645 cm−1. HRMS-EI (m/z) calcd. for C13H10F2 Se: 277.9975,
found: 277.9984.
5-((Difluoromethyl)selanyl)benzo[d][1,3]dioxole (2g). Colorless oil (47.2 mg, 94%
yield from procedure A; 46.2 mg, 92% yield from procedure B), petroleum
ether/ethyl acetate = 40:1 (v/v) as eluents for column chromatography. 1H NMR (500
MHz, CDCl3) δ 7.18 (dd, J = 8.0, 1.6 Hz, 1H), 7.14 (d, J = 1.6 Hz, 1H), 7.11 (t, J =
19
55.5 Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.01 (s, 2H). F NMR (471 MHz, CDCl3) δ
-91.1 (d, J = 55.3 Hz, 2F). 13C NMR (126 MHz, CDCl3) δ 149.2, 148.3, 131.2, 117.0
(t, J = 289.6 Hz), 116.8, 114.3 (t, J = 2.9 Hz), 109.4, 101.6. IR (KBr): 3074, 3012,
2976, 2901, 2781, 1598, 1502, 1476, 1453, 1416, 1400, 1336, 1291, 1271, 1255, 1236,
1161, 1109, 1065, 1038, 935, 878, 861, 808, 721, 696, 673 cm−1. HRMS-EI (m/z)
74
calcd. for C8H6O2F2 Se: 245.9561, found: 245.9568.
(Difluoromethyl)(4-phenoxyphenyl)selane (2h). Colorless oil (54.6 mg, 91% yield
18 / 27

ACCEPTED MANUSCRIPT
from procedure A; 18.5 mg, 31% yield from procedure B; 47.2 mg, 79% yield from
o
1
reaction at 0 C for 6 h), petroleum ether as eluent for column chromatography. H
NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.7 Hz, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.18 (t, J
= 7.5 Hz, 1H), 7.14 (t, J = 55.4 Hz, 1H), 7.06 (dd, J = 8.5, 1.0 Hz, 2H), 6.97 (d, J =
8.7 Hz, 2H). 19F NMR (471 MHz, CDCl3) δ -90.8 (d, J = 55.4 Hz, 2F). 13C NMR (126
MHz, CDCl3) δ 159.2, 156.1, 138.5, 130.0, 124.2, 119.8, 119.1, 116.9 (t, J = 289.8
Hz), 116.1 (t, J = 2.9 Hz). IR (KBr): 3065, 3040, 2966, 1591, 1579, 1485, 1456, 1401,
1331, 1275, 1241, 1198, 1168, 1077, 1063, 1011, 962, 908, 869, 832, 795, 754, 711,
74
693, 669 cm−1. HRMS-EI (m/z) calcd. for C13H10OF2 Se: 293.9924, found:
293.9919.
4-((Difluoromethyl)selanyl)-N,N-dimethylaniline (2i). Light yellow oil (43.6 mg, 87%
yield from procedure A; 43.5 mg, 87% yield from procedure B), petroleum
ether/ethyl acetate = 40:1 (v/v) as eluents for column chromatography. 1H NMR (500
MHz, CDCl3) δ 7.53 (d, J = 5.9 Hz, 2H), 7.06 (t, J = 55.9 Hz, 1H), 6.67 (d, J = 6.7 Hz,
2H), 3.00 (s, 6H). 19F NMR (471 MHz, CDCl3) δ -91.4 (d, J = 55.9 Hz, 2F). 13C NMR
(126 MHz, CDCl3) δ 151.2, 138.2, 117.4 (t, J = 289.6 Hz). 112.9, 107.8 (t, J = 2.8 Hz),
40.2. IR (KBr): 3087, 3030, 2891, 2858, 2813, 1594, 1551, 1506, 1482, 1444, 1361,
1316, 1289, 1268, 1226, 1195, 1170, 1126, 1084, 1062, 997, 946, 811, 711, 691, 667
74
cm−1. HRMS-EI (m/z) calcd. for C9H11NF2 Se: 245.0084, found: 245.0088.
1-Benzyl-5-((difluoromethyl)selanyl)indoline (2j). Yellow oil (62.8 mg, 93% yield
from procedure A; 1.148 g, 75% yield on a large scale (1j, 4.53 mmol)), petroleum
ether/ethyl acetate = 40:1 (v/v) as eluents for column chromatography. 1H NMR (500
MHz, CDCl3) δ 7.39-7.35 (m, 6H), 7.31 (m, 1H), 7.08 (t, J = 55.8 Hz, 1H), 6.45 (d, J
19 / 27

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19
= 8.6 Hz, 1H), 4.32 (s, 2H), 3.44 (t, J = 8.5 Hz, 2H), 3.03 (t, J = 8.5 Hz, 2H). F
NMR (471 MHz, CDCl3) δ -91.3 (d, J = 55.8 Hz, 2F). 13C NMR (126 MHz, CDCl3) δ
153.7, 137.8, 137.1, 133.2, 131.4, 128.7, 127.8, 127.4, 117.6 (t, J = 289.3 Hz), 108.8
(t, J = 2.8 Hz), 107.1, 53.1, 52.7, 28.1. IR (KBr): 3167, 3085, 3062, 3029, 2958, 2923,
2844, 2705, 2582, 1596, 1495, 1471, 1454, 1439, 1384, 1356, 1315, 1269, 1202, 1178,
1155, 1107, 1065, 980, 943, 888, 804, 763, 734, 697, 670 cm−1. HRMS-ESI (m/z)
74
calcd. for [C16H16NF2 Se]+ ([M + H]+), 334.0470; found, 334.0472.
3-((Difluoromethyl)selanyl)-1-methyl-1H-indole (2k). Light yellow solid (46.9 mg,
90% yield from procedure A; 40.1 mg, 77% yield from procedure B), petroleum
ether/ethyl acetate = 40:1 (v/v) as eluents for column chromatography. M.p.: 53-55 oC.
1H NMR (500 MHz, CDCl3) δ 7.77 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.34
(td, J = 6.9, 1.1 Hz, 1H), 7.32 (s, 1H), 7.28 (td, J = 7.8, 1.0 Hz, 1H), 6.98 (t, J = 55.8
19
13
Hz, 1H), 3.84 (s, 3H). F NMR (471 MHz, CDCl3) δ -90.8 (d, J = 55.8 Hz, 2F). C
NMR (126 MHz, CDCl3) δ 137.3, 136.4, 131.0, 122.7, 120.8, 120.2, 117.2 (t, J =
290.3 Hz), 109.7, 91.1 (t, J = 3.5 Hz), 33.1. IR (KBr): 3116, 3070, 3053, 2943, 2912,
2872, 2823, 1636, 1612, 1588, 1570, 1510, 1481, 1459, 1424, 1372, 1355, 1334, 1296,
1240, 1169, 1151, 1129, 1111, 1063, 1038, 1027, 1008, 952, 929, 821, 763, 739, 668
74
cm−1. HRMS-ESI (m/z) calcd. for [C10H10NF2 Se]+ ([M + H]+), 256.0001; found,
256.0001.
1-Benzyl-3-((difluoromethyl)selanyl)-1H-indole (2l). White solid (61.8 mg, 92%
yield from procedure A; 63.1 mg, 94% yield from procedure B), petroleum
ether/ethyl acetate = 40:1 (v/v) as eluents for column chromatography. M.p.: 51-53 oC.
1H NMR (500 MHz, CDCl3) δ 7.81 (m, 1H), 7.40 (s, 1H), 7.37-7.33 (m, 4H),
20 / 27

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7.31-7.27 (m, 2H), 7.18 (d, J = 6.7 Hz, 2H), 7.01 (t, J = 55.7 Hz, 1H), 5.35 (s, 2H).
13
19F NMR (471 MHz, CDCl3) δ -90.6 (d, J = 55.7 Hz, 2F). C NMR (126 MHz,
CDCl3) δ 136.9, 136.5, 135.8, 131.3, 129.0, 128.1, 127.1, 122.9, 121.1, 120.4, 117.2 (t,
J = 290.3 Hz), 110.2, 92.1 (t, J = 3.6 Hz), 50.5. IR (KBr): 3106, 3060, 3028, 2963,
1651, 1603, 1508, 1495, 1479, 1458, 1442 1387, 1357 1339, 1314, 1285, 1255, 1199,
1165, 1054, 1039, 759, 741, 731, 698, 667, 632 cm−1. HRMS-ESI (m/z) calcd. for
74
[C16H14NF2 Se]+ ([M + H]+), 332.0314; found, 332.0317.
4-((Difluoromethyl)selanyl)phenol (2m). Light yellow oil (31.1 mg, 70% yield from
procedure A (note: t-BuOK (0.7 mmol) was used); petroleum ether/ethyl acetate =
1
5:1 (v/v) as eluents for column chromatography. H NMR (500 MHz, CDCl3) δ 7.56
(d, J = 8.6 Hz, 2H), 7.09 (t, J = 55.6 Hz, 1H), 6.83 (d, J = 8.6 Hz, 2H), 5.16 (s, 1H).
13
19F NMR (471 MHz, CDCl3) δ -91.1 (d, J = 55.4 Hz, 2F). C NMR (126 MHz,
CDCl3) δ 157.0, 138.7, 117.0 (t, J = 289.0 Hz), 116.6, 113.7 (t, J = 3.0 Hz). IR (KBr):
3398, 2931, 2855, 1622, 1596, 1584, 1510, 1493, 1450, 1433, 1336, 1268, 1190, 1172,
1150, 1077, 1062, 828, 758, 711, 686, 671, 606 cm−1. HRMS-EI (m/z) calcd. for
74
C7H6OF2 Se: 217.9611, found: 217.9607.
(Difluoromethyl)(4-nitrophenyl)selane (2n). Yellow oil (31.9 mg, 62% yield from
procedure A; 13.2 mg, 26% yield from procedure B), petroleum ether/ethyl acetate
1
= 20:1 (v/v) as eluents for column chromatography. H NMR (500 MHz, CDCl3) δ
8.20 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H), 7.27 (t, J = 54.6 Hz, 1H). 19F NMR
(471 MHz, CDCl3) δ -89.8 (d, J = 54.6 Hz, 2F). 13C NMR (126 MHz, CDCl3) δ 148.4,
136.0, 132.3 (t, J = 2.7 Hz), 124.2, 116.1 (t, J = 290.7 Hz). IR (KBr): 3055, 2974,
1589, 1561, 1502, 1379, 1337, 1290, 1271, 1253, 1201, 1064, 958, 797, 770, 736, 694,
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74
676, 652, 620 cm−1. HRMS-EI (m/z) calcd. for C7H5NO2F2 Se: 246.9513, found:
246.9506.
4-((Difluoromethyl)selanyl)benzonitrile (2o). Light yellow oil (29.6 mg, 64% yield
from procedure A; 25.5 mg, 55% yield from procedure B), petroleum ether/ethyl
1
acetate = 10:1 (v/v) as eluents for column chromatography. H NMR (500 MHz,
CDCl3) δ 7.77 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 7.24 (t, J = 54.7 Hz, 1H).
13
19F NMR (471 MHz, CDCl3) δ -89.9 (d, J = 54.6 Hz, 2F). C NMR (126 MHz,
CDCl3) δ 136.0, 132.7, 130.0 (t, J = 2.7 Hz), 118.1, 116.2 (t, J = 290.8 Hz), 113.2. IR
(KBr): 3088, 3035, 2922, 2849, 2232, 1586, 1481, 1398, 1390, 1322, 1303, 1283,
1051, 1030, 1016, 961, 830, 717, 678, 664 cm−1. HRMS-ESI (m/z) calcd. for
[C8H6NF2 Se]+ ([M + H]+), 227.9688; found, 227.9688.
74
Tert-butyl 4-((difluoromethyl)selanyl)benzoate (2p). White solid (40.2 mg, 65% yield
from procedure A), petroleum ether/ethyl acetate = 20:1 (v/v) as eluents for column
o
1
chromatography. M.p.: 30-32 C. H NMR (500 MHz, CDCl3) δ 7.95 (d, J = 8.0 Hz,
19
2H), 7.69 (d, J = 8.0 Hz, 2H), 7.20 (t, J = 55.0 Hz, 1H), 1.60 (s, 9H). F NMR (471
13
MHz, CDCl3) δ -90.0 (d, J = 55.0 Hz, 2F). C NMR (126 MHz, CDCl3) δ 165.0,
135.4, 132.8, 130.3, 128.8 (t, J = 2.7 Hz), 116.7 (t, J = 289.3 Hz). 81.6, 28.2. IR (KBr):
2978, 2933, 1714, 1591, 1565, 1478, 1456, 1394, 1369, 1296, 1274, 1258, 1165, 1121,
1077, 1062, 1015, 881, 849, 761, 694, 685, 667, 630 cm−1. HRMS-EI (m/z) calcd. for
74
C12H14O2F2 Se: 302.0187, found: 302.0178.
(Difluoromethyl)(3-phenylpropyl)selane (2q). Yellow oil (41.2 mg, 83% yield from
1
procedure A), petroleum ether as eluent for column chromatography. H NMR (500
MHz, CDCl3) δ 7.32 (t, J = 7.4 Hz, 2H), 7.24-7.20 (m, 3H), 7.17 (t, J = 55.1 Hz, 1H),
22 / 27

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19
2.88 (t, J = 7.3 Hz, 2H), 2.76 (t, J = 7.4 Hz, 2H), 2.12 (m, 2H). F NMR (471 MHz,
13
CDCl3) δ -91.2 (d, J = 55.1 Hz, 2F). C NMR (126 MHz, CDCl3) δ 140.9, 128.5,
128.5, 126.2, 115.5 (t, J = 285.8 Hz), 35.7, 32.4, 22.2 (t, J = 2.6 Hz). IR (KBr): 3085,
3063, 3027, 2937, 2855, 1603, 1496, 1454, 1422, 1299, 1279, 1239, 1195, 1179, 1060,
74
1033, 909, 795, 745, 699 cm−1. HRMS-EI (m/z) calcd. for C10H12F2 Se: 244.0132,
found: 244.0135.
(Difluoromethyl)(octyl)selane (2r). Colorless oil (29.1 mg, 60% yield from
1
procedure A), petroleum ether as eluent for column chromatography. H NMR (500
MHz, CDCl3) δ 7.17 (t, J = 55.2 Hz, 1H), 2.86 (t, J = 7.5 Hz, 2H), 1.76 (m, 2H), 1.40
19
(m, 2H), 1.34-1.27 (m, 8H), 0.89 (t, J = 6.8 Hz, 3H). F NMR (471 MHz, CDCl3) δ
13
-91.5 (d, J = 55.2 Hz, 2F). C NMR (126 MHz, CDCl3) δ 115.5 (t, J = 286.2 Hz),
31.8, 30.8, 29.8, 29.1, 29.0, 22.9 (t, J = 2.5 Hz), 22.6, 14.1; IR (KBr): 2957, 2927,
2855, 1465, 1378, 1297, 1279, 1235, 1060, 1041, 721, 692 cm−1. HRMS-EI (m/z)
74
calcd. for C9H18F2 Se: 238.0601, found: 238.0593.
(Difluoromethyl)(hexadecyl)selane (2s). Colorless oil (62.8 mg, 88% yield from
1
procedure A), petroleum ether as eluent for column chromatography. H NMR (500
MHz, CDCl3) δ 7.17 (t, J = 55.1 Hz, 1H), 2.86 (t, J = 7.5 Hz, 2H), 1.76 (m, 2H), 1.39
(m, 2H), 1.32-1.26 (m, 24H), 0.89 (t, J = 6.8 Hz, 3H). 19F NMR (471 MHz, CDCl3) δ
13
-91.5 (d, J = 55.0 Hz, 2F). C NMR (126 MHz, CDCl3) δ 115.5 (t, J = 286.3 Hz),
32.0, 30.8, 29.8, 29.7, 29.7 (overlap), 29.7, 29.7, 29.6, 29.5, 29.4, 29.0, 22.9 (t, J = 2.4
Hz), 22.7, 14.1. IR (KBr): 2924, 2853, 1465, 1376, 1297, 1278, 1058, 1042, 721, 691
74
cm−1. HRMS-EI (m/z) calcd. for C17H34F2 Se: 350.1853, found: 350.1857.
(Difluoromethyl)(4-phenylbutan-2-yl)selane (2t). Yellow oil (48.3 mg, 92% yield
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1
from procedure A), petroleum ether as eluent for column chromatography. H NMR
(500 MHz, CDCl3) δ 7.31 (t, J = 8.2 Hz, 2H), 7.24-7.21 (m, 3H), 7.22 (t, J = 55.1 Hz,
19
1H), 3.43 (m, 1H), 2.79 (m, 2H), 2.04 (m, 2H), 1.62 (d, J = 7.0 Hz, 3H). F NMR
(471 MHz, CDCl3) δ -90.5 (dd, J = 55.1, 13.5 Hz, 2F). 13C NMR (126 MHz, CDCl3) δ
141.2, 128.5, 128.4, 126.1, 116.0 (t, J = 286.2 Hz), 39.8, 36.5 (t, J = 1.7 Hz), 33.8,
23.5. IR (KBr): 3085, 3063, 3027, 2958, 2925, 2859, 1603, 1496, 1454, 1380, 1296,
1280, 1230, 1211, 1166, 1059, 1034, 747, 698, 680 cm−1. HRMS-EI (m/z) calcd. for
74
C11H14F2 Se: 258.0288, found: 258.0293.
4-((Difluoromethyl)selanyl)-N-(2,6-dimethoxypyrimidin-4-yl)benzenesulfonamide
(2v). White solid (21.2 mg, 25% yield from procedure A (note: t-BuOK (0.6 mmol)
was used)), petroleum ether/ethyl acetate = 2:1 (v/v) as eluents for column
o
1
chromatography. M.p.: 140-142 C. H NMR (500 MHz, CDCl3) δ 8.14 (brs, 1H),
7.92 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 7.7 Hz, 2H), 7.23 (t, J = 54.7 Hz, 1H), 6.24 (s,
1H), 3.93 (s, 3H), 3.89 (s, 3H). 19F NMR (471 MHz, CDCl3) δ -89.7 (d, J = 54.9 Hz,
13
2F). C NMR (126 MHz, CDCl3) δ 172.8, 164.5, 158.4, 140.2, 135.9, 130.9 (t, J =
3.0 Hz), 128.1, 116.3 (t, J = 290.3 Hz), 85.9, 54.9, 54.3. IR (KBr): 3216, 3082, 2996,
2954, 2897, 2864, 1600, 1585, 1476, 1458, 1440, 1384, 1361, 1326, 1287, 1208, 1181,
1153, 1108, 1088, 1075 1062, 1042, 1011, 998, 983, 884, 825, 786, 743, 667, 624
cm−1. HRMS-ESI (m/z) calcd. for [C13H14F2N3O4S74Se]+ ([M + H]+): 419.9892, found:
419.9898.
Acknowledgements
We thank the Wuhan University of Technology, the National Natural Science
Foundation of China (21602165), the “Chutian Scholar” Program from Department of
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Education of Hubei Province (China), the “Hundred Talent” Program of Hubei
Province, the Wuhan Youth Chen-Guang Project (2016070204010113), and the
Excellent Dissertation Cultivation Funds of Wuhan University of Technology
(2017-YS-082) for financial support.
Supplementary data
19
13
The Supplementary data (1H, F, and C NMR spectra for all products) associated
with this article can be found free of charge online.
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