Automated Electrochemical Selenenylations

Article abstract of DOI:10.1055/s-0039-1690868

Integrated electrochemical reactors in automated flow systems were utilised for selenenylation reactions. The automation allowed multiple electrochemical reactions of a programmed sequence to be performed in a fully autonomous way. Many functionalised selenenylated products were synthesised in short reaction times in good to high yields.

Full text of DOI:10.1055/s-0039-1690868

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–K
feature
A
en
N. Amri et al.
Feature
Synthesis
Automated Electrochemical Selenenylations
Nasser Amri
Substrates / Reagents
fully automated synthesis
Thomas Wirth*
0
0
0
0-0
0
0
2-
8
9
9
0-0
6
6
7
Products
R
School of Chemistry, Cardiff University,
Park Place, Cardiff, CF10 3AT, UK
wirth@cf.ac.uk
OR“
SeR’
R’SeSeR’ R“OH
R
Received: 28.01.2020
Accepted after revision: 09.03.2020
Published online:
Figure 1. Automation has the potential to reduce the neces-
sary manpower, to avoid human errors, and to make a posi-
tive contribution towards sustainable and green chemistry
by minimizing waste.6
DOI: 10.1055/s-0039-1690868; Art ID: ss-2020-z0059-fa
Abstract Integrated electrochemical reactors in automated flow sys-
tems were utilised for selenenylation reactions. The automation al-
lowed multiple electrochemical reactions of a programmed sequence
to be performed in a fully autonomous way. Many functionalised
selenenylated products were synthesised in short reaction times in
good to high yields.
R
OR’
SePh
R
8 mL
(PhSe)2, R’OH
0.6 mL
Key words alkenes, automated synthesis, electrolysis, flow micro-
reactors, selenium
8 mL
Figure 1 Automated selenenylations in flow electrochemistry
There have been large efforts in developing technologies
in organic synthesis to enhance product output in shorter
time.1 Continuous flow syntheses2 and electrochemical re-
actions3 have played a significant role in this development.
These areas of research are still actively pursued in aca-
demia and industry. We have designed and manufactured
an electrochemical flow microreactor device to improve the
efficiency of electrochemical flow reactions integrated with
inline mass spectrometric analysis.4 A much improved de-
vice is now commercially available.5 The advantage of being
able to remotely control flow electrochemical equipment is
demonstrated here with its inclusion in a fully automated
flow setup. In continuation of our efforts in the develop-
ment of tools and techniques we apply electrochemistry in
the selenenylation of alkenes as a modular reaction. In the
automated setup, the starting alkene, the diselenide as se-
lenenylating reagent and the nucleophile can be selected.
Different combinations will lead to different product solu-
tions, which can be collected separately. The automated se-
quence of different reactions with integrated cleaning cy-
cles allows an independent operation of many reactions,
which is only limited by the number of available collection
vials. A schematic representation of this system is shown in
Organoselenium compounds are interesting molecules
owing to their importance in medicinal and material chem-
istry and as reagents and catalysts.7 We have investigated
many different aspects of selenium chemistry in the past,
including some batch electrochemical transformations.8
Addition of selenium electrophiles to alkenes in the pres-
ence of nucleophiles is a general concept to access -substi-
tuted selenides; different reaction conditions and types of
oxidants are utilized to access the selenium electrophiles.
As an efficient and environmentally friendly protocol for
organic synthesis, electrochemical conversions have gained
more and more attention, as often an excess amount of con-
ventional chemical oxidants and reducing reagents can be
avoided.9 The electrochemical synthesis of -substituted
selenides is a very promising approach, as shown also in re-
cent publications.10 These methods are efficient, but to de-
velop robust reliable reaction conditions, much effort is still
required. We here describe the use of an automated electro-
chemical flow system for the synthesis of different -sub-
stituted selenides in a continuous process. To the best of our
knowledge, this is the first use of a flow electrochemical re-
actor integrated in an automated system.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
N. Amri et al.
Feature
Synthesis
We initiated our studies to identify optimal reaction
conditions for the three-component reaction using alkenes,
diphenyl diselenide, and different alcohols as nucleophiles
(Scheme 1). We used a Vapourtec automated flow system
with an integrated Ion electrochemical microflow reactor
to rapidly and automatically screen different reaction vari-
ables. The software allowed the setup of a number of reac-
tions, applying different reaction conditions and collecting
the individual reaction products in an automated way even
during overnight operation.
anode: graphite, cathode: Pt
192 mA, volume: 0.6 mL
alkene (0.15 M)
MeOH (30 equiv)
(PhSe)2 (0.05 M)
Bu4NI (7.5 mol%)
OMe
R2
flow rate: 0.6 mL⋅min–1, 25 °C
SePh
R1
OMe
MeO
R
OMe
SePh
SePh
SePh
R
26 (86%)
MeO
4 R = H (95%)
20 R = Me (75%)
21 R = iPr (16%)
22 R = Ph (25%)
5 R = 4-Me (91%)
6 R = 4-tBu (88%)
7 R = 4-OMe (63%)
8 R = 4-F (84%)
9 R = 4-Cl (74%)
10 R = 4-Br (87%)
11 R = 4-Ph (83%)
12 R = 3-Me (93%)
13 R = 3-F (61%)
14 R = 3-Cl (70%)
15 R = 3-Br (84%)
16 R = 2-Me (84%)
17 R = 2-F (64%)
18 R = 2-Cl (69%)
19 R = 2-Br (80%)
SePh
OMe
SePh
RSe
+
(RSe)2
+
Nu-H
R
27 (92%)
SePh
OMe
Nu
OMe
23 R = Me (84%)
24 R = Ph (0%)
25 R = CN (0%)
1
2
3
+
R
SePh
R
Scheme 1 Selenenylation of alkenes
28 R = cyclopentyl (75%, 2:3)
29 R = cyclohexyl (52%, 4:1)
30 R = n-hexyl (42%, 4:1)
As a model reaction, styrene (0.15 M), diphenyl disele-
nide (0.05 M), and MeOH (30 equiv) in MeCN were allowed
to react in the presence of graphite (Gr) as anode and plati-
num (Pt) as cathode, with a flow rate of 0.1 mL·min−1, and 5
mM tetrabutylammonium tetrafluoroborate (Bu4NBF4) as
the supporting electrolyte (Scheme 2). With a residence
time of 6 minutes and a current of 16 mA (2.0 F) at room
temperature, only 32% of the desired product 4 was ob-
tained. Theoretically, only 2.0 F electricity is required for
the two-electron oxidation. However, it was observed that
increasing the current from 16 mA to 32 mA (4 F) increases
the yield from 32% to 66% with recovery of starting materi-
als. A further increase of the current beyond 4.0 F led to a
decrease of the yield of the desired product 4.
SePh
OMe
OMe
O
OMe
SePh
Se
Ph
N
SePh
32 (14%)
Me
33 (72%)
34 (41%)a
31 (80%)
Scheme 2 Scope and limitations of the electrochemical methoxy-
selenenylations of alkenes. a Dibenzyl diselenide used instead of diphe-
nyl diselenide.
Different parameters for the flow electrochemical reac-
tions were studied such as solvents, electrolytes, flow rates,
and electrode materials. Different solvents and solvent mix-
tures such as acetonitrile, tetrahydrofuran, methanol, and
Biographical Sketches
Nasser Amri was born in
Jazan, Saudi Arabia in 1990. He
received his B.S. degree in
chemistry in 2012 at Jazan Uni-
versity. Subsequently, he start-
ed his work at the same
university. Later he moved to
the USA and obtained his M.S.
degree in 2016 at Emporia State
University. In 2017 he started
his PhD work under the supervi-
sion of Prof. T. Wirth at Cardiff
University in the area of flow
electrochemistry.
Thomas Wirth is professor of
organic chemistry at Cardiff
University. After receiving his
PhD from TU Berlin, he went to
Kyoto University as a JSPS fel-
low. Then he worked inde-
pendently at the University of
Basel before taking up his cur-
rent position at Cardiff Universi-
ty in 2000. He was awarded the
Werner Prize by the New Swiss
Chemical Society, the Wolfson
Research Merit Award by the
Royal Society, and the Bader
Award by the Royal Society of
Chemistry. In 2016 he was
elected as a fellow of The
Learned Society of Wales. His
main research interests concern
stereoselective electrophilic re-
actions, oxidative transforma-
tions with hypervalent iodine
reagents, and flow chemistry
performed in microreactors.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

C
N. Amri et al.
Feature
Synthesis
mixtures of acetonitrile/tetrahydrofuran were screened. It
was found that acetonitrile was the optimal solvent for this
reaction (see Supporting Information, SI). Lei and co-au-
thors reported an oxyselenenylation using styrene in a
batch electrochemical process using stoichiometric
amounts of tetrabutylammonium tetrafluoroborate
(Bu4NBF4) as a supporting electrolyte.10b We discovered that
under flow conditions only catalytic amounts of Bu4NBF4
were necessary to obtain identical results in a shorter reac-
tion time. Without any addition of electrolyte, the reaction
in the electrochemical flow reactor still led to a yield of 32%.
The presence of electrolyte has a significant influence on
the yield. Different electrolytes such as Bu4NBF4, Bu4NOTs,
Et4NCl, Bu4NBr, KI, and Bu4NI were screened in catalytic
amounts, and Bu4NI showed the highest yield of 87% (see
SI). From cyclic voltammetry studies (see SI) we presume
that, at the anode, iodide is oxidised sequentially from io-
dide to the iodine radical to the iodine cation: I– → I• → I+.10c
The iodine cation is known to activate the diselenide by
generating PhSeI and another reactive PhSe+ that reacts to
form the desired product.
The effect of flow rate/residence time on product yield
was studied to determine the optimal flow rate to avoid
mass-transfer limitations.11 Surprisingly, increasing the
flow rate to 0.2–0.4 mL·min–1 led to full conversion with
>99% yield. A further increase to flow rates above 0.4
mL·min–1 resulted in a drop in yield. This may be due to a
decreased conductivity at higher flow rates. An increase of
the electrolyte concentration from 5 mM to 7.5 mM also al-
lowed a quantitative yield to be obtained at flow rates up to
0.6 mL·min–1, corresponding to a calculated residence time
of 1.0 minutes (see SI). Due to the formation of hydrogen,
the actual residence time is lower. The increase in electro-
lyte concentration allowed a further reduction of the reac-
tion time.
out additional manual interference. The different product
solutions obtained were purified by using a Biotage Isolera
chromatography system. Due to the automated protocol, all
reactions shown were performed using identical amounts
and concentrations of reagents and 1.2 mmol alkene was
used in each experiment.
Pleasingly, the electrochemical reaction of many differ-
ent substituted styrene derivatives gave the desired prod-
ucts 4–27 in good to excellent yields, but for 21 and 22 the
yields were low. For disubstituted alkenes (24 and 25), no
product formation was observed (Scheme 2). Alkyl-substi-
tuted alkenes lead, as known, to regioisomeric mixtures
(28–30). While 3,4-dihydro-2H-pyran formed product 32 in
14% yield as the only regioisomer but, as reported, in a 1:1
(cis/trans) mixture,12 indole was selenenylated in the 3-po-
sition leading to 33.13 Other diselenides such as dibenzyl
diselenide can also be used, as demonstrated in the synthe-
sis of 34, where an MeCN/THF solvent mixture (1:1) was
used.
Variations of nucleophiles in the selenenylation are
shown in Scheme 3. Primary, secondary, and tertiary alco-
hols can be used in the selenenylation reactions as shown in
the formation of products 35–45. Even water, formic acid,
and acetic acid can be used, leading to products 46–48.
Benzotriazole also participated as an N-nucleophile in this
reaction to form the aminoselenenylated product 49 in 65%
yield.
anode: graphite, cathode: Pt
192 mA, volume: 0.6 mL
flow rate: 0.6 mL⋅min–1, 25 °C
Ph
OR
(0.15 M)
ROH (30 equiv)
(PhSe)2 (0.05 M)
Bu4NI (7.5 mol%)
SePh
Ph
H
35 R = Et (86%)
36 R = nPr (79%)
37 R = nBu (74%)
38 R = Bn (54%)
O
O
O
O
SePh
SePh
Ph
Ph
Different electrode materials were also screened4 (see
SI). Initially, platinum (Pt) was used as cathode and differ-
ent anode materials such as graphite (Gr), glassy carbon
(GC), boron-doped diamond (BDD), Panasonic carbon, PTFE
carbon, stainless steel (Fe), and nickel (Ni) were screened.
Among these, Gr as anode was found to be most efficient.
Furthermore, Gr as anode was then screened against vari-
ous cathodes such as Pt loaded on Nb, Pt loaded on Ti, Ni, Fe,
Gr, GC, and Zn. From this screening it was found that Gr as
anode and Pt as cathode constituted an optimal combina-
tion. A low-cost electrode (Pt loaded on Nb) still gave 95%
yield. The same trend was observed for Gr as a cathode and
anode.
With the optimised reaction conditions in hand, an in-
vestigation of the scope and general applicability of this
methodology using different alkenes, alcohols, and disele-
nides was performed in an automated way. Loading differ-
ent alkenes, alcohols and diselenides into the autosampler
allowed the reaction products shown in Schemes 2 and 3
and Figure 2 to be obtained in a fully automated way with-
39 R = CH2CH2C CH (56%)
40 R = cyclopropylmethyl (75%)
41 R = iPr (70%)
47 (41%)
48 (46%)
N
N
N
42 R = iBu (75%)
49 (65%)
43 R = cyclopentyl (71%)
44 R = cyclohexyl (63%)
45 R = tBu (47%)
SePh
Ph
46 R = H (81%)
Scheme 3 Different nucleophiles for the electrochemical selenenyla-
tion of styrene
Cyclic ethers and lactones are important cores in several
natural products and important bioactive molecules. This
methodology can also be expanded to intramolecular cy-
clizations and was found to be efficient to obtain a variety
of cyclised O-heterocycles as shown in Figure 2. The lac-
tones and ethers were obtained in moderate to good yields.
Furan 50 was obtained in 73% yield. Functionalised pyrans
51 and 52 were obtained in 67 and 58% yield, respectively.
Different functionalised and fused lactones 53–56 were ob-
tained in good yields. Similarly, dihydroindole 57 was ob-
tained in 33% yield. All the synthesised compounds were
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

D
N. Amri et al.
Feature
Synthesis
fully characterised by different spectroscopic techniques.
Among them, also a single crystal X-ray analysis was per-
formed for compound 21 (see SI) that further supports the
formation of the target molecules and the spectroscopic da-
ta.14 The selenium cation necessary for the addition and cy-
clisation reactions described here is believed to be formed
through sequential oxidation of diphenyl diselenide as al-
ready investigated by Breder, Siewert, and co-workers.10d
The oxidation potential required for a subsequent elimina-
tion of the selenide is not reached here.
tor5 powered by an Ion electrochemical power supply. The cyclic vol-
tammograms (see SI) were obtained by using an Orygalys OGF500 Po-
tentiostat/Galvanostat with OGFPWR power supply.
Electrochemical Oxyselenenylations of Alkenes; General Proce-
dure GP1
The electrolysis was performed in an undivided cell using a Vapourtec
Ion Electrochemical Flow Reactor (reactor volume 0.6 mL, spacer 0.5
mm) using a graphite (Gr) electrode as the anode and a platinum (Pt)
electrode as the cathode (active surface area 2 × 12 cm2). A solution of
alkene (0.15 M in MeCN) was placed in vial A and a mixture of diphe-
nyl diselenide (0.05 M), alcohol (30 equiv), and TBAI (0.0075 M) in
MeCN was placed in vial B. Each solution was injected into an 8 mL
sample loop. After that, the reactor temperature was set at 25 °C with
the flow rate 0.6 mL·min–1 and the current was set at 192 mA to turn
on automatically. Then, both solutions were pumped into a PTFE coil
(1 mm internal diameter) and mixed via a T-piece connected to a 30
cm PTFE coil before the inlet of the electrochemical reactor. After
reaching a steady state, the solution (12 mL) was collected automati-
cally into a collection glass vial. The solvent was removed under vacu-
um. The crude product was purified by column chromatography
(EtOAc/hexane).
O
O
O
O
SePh
SePh
SePh
O
SePh
50 (73%)
51 (67%)
52 (58%)
53 (65%)
O
O
O
O
Ts
N
SePh
SePh
SePh
SePh
O
O
54 (30%)
55 (68%)
56 (48%)
57 (33%)
Figure 2 Electrochemical selenocyclisations
Electrochemical Selenocyclisations; General Procedure GP2
The electrolysis was performed in an undivided cell using a Vapourtec
Ion Electrochemical Flow Reactor (reactor volume 0.6 mL, spacer 0.5
mm) using a graphite (Gr) electrode as the anode and a platinum (Pt)
electrode as the cathode (immersed surface area A 12 cm2). A solution
of alkene (0.15 M in MeCN) was placed in vial A and a mixture of di-
phenyl diselenide (0.05 M) and TBAI (0.0075 M) in MeCN was placed
in vial B. Each solution was injected into an 8 mL sample loop. After
that, the reactor temperature was set at 25 °C with the flow rate 0.6
mL·min–1 and the current set at 192 mA to turn on automatically.
Then both solutions were pumped into a PTFE coil (1 mm internal di-
ameter) and mixed via a T-piece connected to a 30 cm PTFE coil be-
fore the inlet of the electrochemical reactor. After reaching a steady
state, the solution (12 mL) was collected automatically into a collec-
tion glass vial. The solvent was removed under vacuum. The crude
product was purified by column chromatography (EtOAc/hexane).
To further demonstrate the synthetic potential of this
protocol, a gram-scale reaction was performed for the syn-
thesis of product 4, of which 1.52 g was obtained in 100
minutes, corresponding to 87% yield.
In summary, we have demonstrated that electrochemi-
cal reactions such as selenenylations of alkenes can be easi-
ly integrated in remote-controlled synthesis equipment, al-
lowing an automated synthesis of many derivatives in a
short time with minimal human interference. A library of
54 molecules resulting from alkoxy- and aza-selenenyla-
tions was obtained, including from intramolecular reac-
tions for the synthesis of heterocyclic compounds. A gram-
scale reaction was also performed to demonstrate the po-
tential of this electrochemically integrated automated flow
technology.
(2-Methoxy-2-phenylethyl)(phenyl)selane (4)
Compound 4 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 165 mg (95%); colourless oil.
The spectral data are in agreement with the literature.10a
1H NMR (500 MHz, CDCl3):  = 7.50–7.45 (m, 2 H), 7.38–7.29 (m, 5 H),
7.26–7.22 (m, 3 H), 4.35 (dd, J = 8.4, 5.0 Hz, 1 H), 3.33 (dd, J = 12.3, 8.4
Hz, 1 H), 3.25 (s, 3 H), 3.11 (dd, J = 12.3, 5.0 Hz, 1 H).
All solvents and reagents were used as received without purification
or drying. TLC was performed on pre-coated aluminium sheets of
Merck silica gel 60 F254 (0.20 mm) and visualised by UV radiation
(254 nm). Automated column chromatography was performed on a
Biotage® Isolera Four using Biotage® cartridges SNAP Ultra 10 g. 1H,
13C, and 19F NMR spectra were obtained on Bruker DPX 400 or 500 ap-
paratus and were referenced to the residual proton solvent peak (1H:
CDCl3,  = 7.26; DMSO-d6,  = 2.50) and solvent 13C signal (13C: CDCl3,
 = 77.2; DMSO-d6,  = 39.5). IR spectra of neat samples (directly on
the crystal of the IR machine) were recorded on a Shimadzu FTIR Af-
finity-1S apparatus. EI and ES mass spectrometric measurements
were performed by R. Jenkins, R. Hick, T. Williams, and S. Waller at
Cardiff University on a Water LCR Premier XEtof. Melting points were
measured using a Gallenkamp variable heater with samples in open
capillary tubes. The electrochemical reactions were carried out in a
galvanostatic mode using a Vapourtec Ion Electrochemical flow reac-
13C NMR (126 MHz, CDCl3):  = 141.0, 132.7, 130.8, 129.2, 128.7,
128.2, 126.9, 126.8, 83.3, 57.2, 35.5.
(2-Methoxy-2-p-tolylethyl)(phenyl)selane (5)
Compound 5 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 167 mg (91%); colourless oil.
The spectral data are in agreement with the literature.15
1H NMR (400 MHz, CDCl3):  = 7.49–7.44 (m, 2 H), 7.26–7.14 (m, 7 H),
4.33 (dd, J = 8.4, 5.1 Hz, 1 H), 3.33 (dd, J = 12.2, 8.4 Hz, 1 H), 3.24 (s, 3
H), 3.10 (dd, J = 12.2, 5.1 Hz, 1 H), 2.36 (s, 3 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

E
N. Amri et al.
Feature
Synthesis
13C NMR (101 MHz, CDCl3):  = 137.7, 132.6, 130.9, 129.4, 129.1,
126.9, 126.8, 83.1, 57.0, 35.5, 21.3.
1H NMR (500 MHz, CDCl3):  = 7.49–7.43 (m, 4 H), 7.26–7.20 (m, 3 H),
7.18–7.14 (m, 2 H), 4.30 (dd, J = 7.9, 5.5 Hz, 1 H), 3.28 (dd, J = 12.4, 7.9
Hz, 1 H), 3.23 (s, 3 H), 3.06 (dd, J = 12.4, 5.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 140.0, 132.9, 131.8, 130.5, 129.2,
[2-(4-tert-Butylphenyl)-2-methoxyethyl](phenyl)selane (6)
128.9, 127.1, 122.1, 82.7, 57.2, 35.2.
Compound 6 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 20:1).
[2-(1,1′-Biphenyl-4-yl)-2-methoxyethyl](phenyl)selane (11)
Yield: 184 mg (88%); yellow oil.
Compound 11 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
The spectral data are in agreement with the literature.16
1H NMR (500 MHz, CDCl3):  = 7.51–7.43 (m, 2 H), 7.40–7.38 (m, 2 H),
7.26–7.18 (m, 5 H), 4.35 (dd, J = 8.5, 4.9 Hz, 1 H), 3.33 (dd, J = 12.3, 8.5
Hz, 1 H), 3.25 (s, 3 H), 3.11 (dd, J = 12.3, 4.9 Hz, 1 H), 1.32 (s, 9 H).
Yield: 184 mg (83%); pale yellow oil.
IR (neat): 3055, 2819, 1485, 1477, 1085, 732, 692 cm–1
.
13C NMR (126 MHz, CDCl3):  = 151.2, 138.0, 132.7, 130.9, 129.1,
126.9, 126.5, 125.5, 83.3, 57.2, 35.5, 34.7, 31.6.
1H NMR (500 MHz, CDCl3):  = 7.60–7.57 (m, 4 H), 7.50 –7.44 (m, 4 H),
7.39–7.34 (m, 3 H), 7.26–7.22 (m, 3 H), 4.41 (dd, J = 8.3, 5.2 Hz, 1 H),
3.37 (dd, J = 12.3, 8.3 Hz, 1 H), 3.30 (s, 3 H), 3.15 (dd, J = 12.3, 5.2 Hz, 1
H).
[2-Methoxy-2-(4-methoxyphenyl)ethyl](phenyl)selane (7)
13C NMR (126 MHz, CDCl3):  = 141.2, 140.9, 140.0, 132.8, 130.8,
Compound 7 was synthesised following GP1. It was purified by col-
129.1, 128.9, 127.4, 127.4, 127.2, 127.2, 126.9, 83.1, 57.2, 35.5.
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
HRMS (ESI): m/z [M – OMe]+ calcd for C20H17Se: 333.0522; found:
Yield: 122 mg (63%); colourless oil.
333.0525
The spectral data are in agreement with the literature.15
1H NMR (500 MHz, CDCl3):  = 7.49–7.43 (m, 2 H), 7.26–7.20 (m, 5 H),
6.89–6.82 (m, 2 H), 4.31 (dd, J = 8.2, 5.3 Hz, 1 H), 3.81 (s, 3 H), 3.33
(dd, J = 12.2, 8.3 Hz, 1 H), 3.22 (s, 3 H), 3.09 (dd, J = 12.2, 5.3 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 159.6, 133.0, 132.6, 130.9, 129.1,
128.0, 126.9, 114.0, 82.8, 56.9, 55.4, 35.5.
(2-Methoxy-2-m-tolylethyl)(phenyl)selane (12)
Compound 12 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 170 mg (93%); yellow oil.
IR (neat): 2981, 2820, 1477, 1437, 1084, 731 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.50–7.44 (m, 2 H), 7.26–7.20 (m, 4 H),
7.12–7.09 (m, 3 H), 4.32 (dd, J = 8.5, 5.0 Hz, 1 H), 3.32 (dd, J = 12.2, 8.5
Hz, 1 H), 3.25 (s, 3 H), 3.10 (dd, J = 12.2, 5.0 Hz, 1 H), 2.35 (s, 3 H).
[2-(4-Fluorophenyl)-2-methoxyethyl](phenyl)selane (8)
Compound 8 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
13C NMR (126 MHz, CDCl3):  = 141.0, 138.4, 132.7, 130.9, 129.1,
Yield: 156 mg (84%); colourless oil.
129.0, 128.6, 127.4, 126.9, 123.9, 83.4, 57.2, 35.5, 21.6.
HRMS (ESI): m/z [M – OMe]+ calcd for C15H15Se: 271.0366; found:
271.0374
The spectral data are in agreement with the literature.16
1H NMR (500 MHz, CDCl3):  = 7.50–7.42 (m, 2 H), 7.29–7.20 (m, 5 H),
7.07–6.97 (m, 2 H), 4.33 (dd, J = 8.0, 5.5 Hz, 1 H), 3.30 (dd, J = 12.3, 8.0
Hz, 1 H), 3.23 (s, 3 H), 3.07 (dd, J = 12.3, 5.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 162.6 (d, J = 243.7 Hz), 136.7 (d, J = 3.7
Hz), 132.8, 129.2, 128.4 (d, J = 8.7 Hz), 127.0, 115.5 (d, J = 22.5 Hz),
82.7, 56.1, 35.4.
[2-(3-Fluorophenyl)-2-methoxyethyl](phenyl)selane (13)
Compound 13 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 114 mg (61%); yellow oil.
IR (neat): 2932, 2822, 1477, 1436, 1089, 1072, 733 cm–1
.
[2-(4-Chlorophenyl)-2-methoxyethyl](phenyl)selane (9)
1H NMR (500 MHz, CDCl3):  = 7.50–7.44 (m, 2 H), 7.32–7.25 (m, 1 H),
7.24–7.21 (m, 3 H), 7.09–6.96 (m, 3 H), 4.33 (dd, J = 8.1, 5.2 Hz, 1 H),
3.29 (dd, J = 12.4, 8.2 Hz, 1 H), 3.26 (s, 3 H), 3.08 (dd, J = 12.4, 5.2 Hz, 1
H).
13C NMR (126 MHz, CDCl3):  = 163.2 (d, J = 245.0 Hz), 143.9 (d, J = 6.2
Hz), 132.9, 130.5, 130.2 (d, J = 7.5 Hz), 129.2, 127.1, 122.5 (d, J = 2.5
Hz), 115.1 (d, J = 21.2 Hz), 113.7 (d, J = 25.0 Hz), 113.52, 82.8 (d, J = 2.5
Hz), 57.3, 35.2.
Compound 9 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 144 mg (74%); colourless oil.
The spectral data are in agreement with the literature.15
1H NMR (400 MHz, CDCl3):  = 7.49–7.44 (m, 2 H), 7.32–7.28 (m, 2 H),
7.26–7.16 (m, 5 H), 4.31 (dd, J = 7.9, 5.5 Hz, 1 H), 3.29 (dd, J = 12.3, 8.0
Hz, 1 H), 3.23 (s, 3 H), 3.06 (dd, J = 12.3, 5.5 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 139.5, 133.9, 132.8, 130.5, 129.2,
128.9, 128.2, 127.1, 82.7, 57.2, 35.2.
19F NMR (471 MHz, CDCl3):  = –112.69 (s).
[2-(3-Chlorophenyl)-2-methoxyethyl](phenyl)selane (14)
[2-(4-Bromophenyl)-2-methoxyethyl](phenyl)selane (10)
Compound 14 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Compound 10 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 20:1).
Yield: 138 mg (70%); yellow oil.
IR (neat): 2986, 2821, 1475, 1437, 1099, 1074, 733 cm–1
Yield: 194 mg (87%); yellow oil.
The spectral data are in agreement with the literature.16
.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

F
N. Amri et al.
Feature
Synthesis
1H NMR (500 MHz, CDCl3):  = 7.49–7.43 (m, 2 H), 7.29–7.27 (m, 1 H),
7.27–7.21 (m, 5 H), 7.19–7.14 (m, 1 H), 4.30 (dd, J = 8.1, 5.3 Hz, 1 H),
3.27 (dd, J = 12.4, 8.1 Hz, 1 H), 3.24 (s, 3 H), 3.06 (dd, J = 12.4, 5.3 Hz, 1
H).
13C NMR (101 MHz, CDCl3):  = 138.6, 133.2, 133.1, 130.6, 129.7,
129.1, 127.4, 127.4, 127.0, 79.3, 57.6, 34.1.
HRMS (ESI): m/z [M – OMe]+ calcd for C14H12ClSe: 290.9820; found:
290.9812
13C NMR (126 MHz, CDCl3):  = 143.2, 134.7, 133.0, 130.5, 130.0,
129.2, 128.4, 127.1, 127.0, 125.0, 82.8, 57.4, 35.2.
HRMS (ESI): m/z [M – OMe]+ calcd for C14H12ClSe: 290.9820; found:
[2-(2-Bromophenyl)-2-methoxyethyl](phenyl)selane (19)
Compound 19 was synthesised following GP1. It was purified by col-
290.9810
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 178 mg (80%); yellow oil.
IR (neat): 3055, 2824, 1475, 1435, 1072, 1022, 732, 690 cm–1
1H NMR (500 MHz, CDCl3):  = 7.56–7.53 (m, 2 H), 7.52–7.47 (m, 2 H),
7.36–7.32 (m, 1 H), 7.25–7.20(m, 3 H), 7.16–7.13 (m, 1 H), 4.79 (dd, J =
8.9, 3.7 Hz, 1 H), 3.29 (s, 3 H), 3.22 (dd, J = 12.6, 3.7 Hz, 1 H), 3.13 (dd,
J = 12.6, 8.9 Hz, 1 H).
[2-(3-Bromophenyl)-2-methoxyethyl](phenyl)selane (15)
.
Compound 15 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 187 mg (84%); yellow oil.
IR (neat): 2984, 2819, 1476, 1436, 1082, 1070, 732, 688 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.48–7.40 (m, 4 H), 7.26–7.18 (m, 5 H),
4.30 (dd, J = 8.1, 5.3 Hz, 1 H), 3.28 (dd, J = 12.4, 8.1 Hz, 1 H), 3.25 (s, 3
H), 3.06 (dd, J = 12.4, 5.3 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 143.5, 133.0, 131.3, 130.4, 130.3,
129.9, 129.2, 127.2, 125.5, 122.9, 82.8, 57.4, 35.2.
HRMS (ESI): m/z [M – OMe]+ calcd for C14H12BrSe: 334.9315; found:
334.9301
13C NMR (126 MHz, CDCl3):  = 143.5, 132.9, 131.3, 130.4, 130.3,
129.9, 129.2, 127.2, 125.5, 122.9, 82.8, 57.4, 35.2.
(2-Methoxy-2-phenylpropyl)(phenyl)selane (20)
(2-Methoxy-2-o-tolylethyl)(phenyl)selane (16)
Compound 20 was synthesised following GP1. It was purified by col-
Compound 16 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 138 mg (75%); yellow oil.
Yield: 154 mg (84%); yellow oil.
IR (neat): 2980, 2820, 1477, 1437, 1022, 729 cm–1
1H NMR (400 MHz, CDCl3):  = 7.53–7.50 (m, 2 H), 7.40–7.38 (m, 1 H),
7.25–7.11 (m, 6 H), 4.60 (dd, J = 9.0, 4.2 Hz, 1 H), 3.31–3.17 (m, 4 H),
3.07 (dd, J = 12.5, 4.2 Hz, 1 H), 2.22 (s, 3 H).
The spectral data are in agreement with the literature.17
.
1H NMR (500 MHz, CDCl3):  = 7.43–7.39 (m, 4 H), 7.36–7.32 (m, 2 H),
7.29–7.25 (m, 1 H), 7.20–7.16 (m, 3 H), 3.43 (d, J = 11.3 Hz, 1 H), 3.28
(d, J = 11.8 Hz, 1 H), 3.13 (s, 3 H), 1.72 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 143.8, 132.8, 131.5, 129.0, 128.4,
127.5, 126.8, 126.4, 79.1, 51.2, 42.6, 23.3.
13C NMR (101 MHz, CDCl3):  = 139.1, 135.7, 133.2, 130.7, 130.6,
129.1, 127.8, 127.1, 126.5, 126.0, 79.7, 57.1, 34.7, 19.1.
HRMS (ESI): m/z [M – OMe]+ calcd for C15H15Se: 271.0366; found:
(2-Methoxy-3-methyl-2-phenylbutyl)(phenyl)selane (21)
271.035
Compound 21 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
[2-(2-Fluorophenyl)-2-methoxyethyl](phenyl)selane (17)
Yield: 32 mg (16%); colourless solid; mp 87–88 °C.
Compound 17 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
IR (neat): 2966, 2818, 1471, 1170, 1070, 761, 744, 705, 690 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.60–7.55 (m, 2 H), 7.36–7.24 (m, 8 H),
3.79 (d, J = 12.0 Hz, 1 H), 3.62 (d, J = 12.0 Hz, 1 H), 3.26 (s, 3 H), 2.41
(dt, J = 13.6, 6.8 Hz, 1 H), 0.79 (d, J = 6.7 Hz, 3 H), 0.75 (d, J = 6.9 Hz,
3 H).
13C NMR (126 MHz, CDCl3):  = 139.3, 133.3, 131.0, 129.2, 128.0,
127.6, 127.1, 127.1, 83.7, 50.9, 35.4, 34.8, 18.2, 16.9.
Yield: 120 mg (64%); pale yellow oil.
IR (neat): 3086, 2824, 1477, 1436, 1105, 1088, 734 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.51–7.48 (m, 2 H), 7.44–7.40 (m, 1 H),
7.29–7.22 (m, 4 H), 7.18–7.14 (m, 1 H), 7.04–7.00 (m, 1 H), 4.75 (dd, J
= 8.2, 4.9 Hz, 1 H), 3.32–3.25 (m, 4 H), 3.20 (dd, J = 12.7, 4.6 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 160.5 (d, J = 245.0 Hz), 132.8, 130.6,
129.5 (d, J = 8.7 Hz), 129.1, 128.0 (d, J = 13.7 Hz), 127.7 (d, J = 3.7 Hz),
127.0, 124.5 (d, J = 3.7 Hz), 115.5 (d, J = 22.5 Hz), 76.6 (d, J = 1.3 Hz),
57.5, 34.1.
(2-Methoxy-2,2-diphenylethyl)(phenyl)selane (22)
Compound 22 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
19F NMR (471 MHz, CDCl3)  = –119.2.
Yield: 56 mg (25%); colourless solid; mp 76–78 °C.
The spectral data are in agreement with the literature.18
1H NMR (500 MHz, CDCl3):  = 7.44–7.34 (m, 6 H), 7.33–7.28 (m, 4 H),
7.26–7.17 (m, 5 H), 3.96 (s, 2 H), 3.16 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 144.3, 133.3, 130.9, 129.0, 128.1,
[2-(2-Chlorophenyl)-2-methoxyethyl](phenyl)selane (18)
Compound 18 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 134 mg (69%); yellow oil.
127.3, 127.1, 127.0, 82.2, 50.9, 37.9.
IR (neat): 2985, 2823, 1475, 1436, 1072, 1034, 733 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.55–7.49 (m, 3 H), 7.34–7.28 (m, 2 H),
7.26–7.19 (m, 4 H), 4.85 (dd, J = 8.7, 3.9 Hz, 1 H), 3.29 (s, 3 H), 3.23
(dd, J = 12.5, 3.9 Hz, 1 H), 3.16 (dd, J = 12.5, 8.7 Hz, 1 H).
(1-Methoxy-1-phenylpropan-2-yl)(phenyl)selane (23)
Compound 23 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

G
N. Amri et al.
Feature
Synthesis
Yield: 153 mg (84%); yellow oil.
The spectral data are in agreement with the literature.19
(2-Cyclohexyl-2-methoxyethyl)(phenyl)selane (29a) and (1-Cyclo-
hexyl-2-methoxyethyl)(phenyl)selane (29b)
Compound 29 was synthesised following the GP1. It was purified by
column chromatography (silica gel, hexane/ethyl acetate, 30:1).
1H NMR (400 MHz, CDCl3):  = 7.56–7.53 (m, 2 H), 7.38–7.22 (m, 8 H),
4.41 (d, J = 4.5 Hz, 1 H), 3.48 (qd, J = 7.0, 4.5 Hz, 1 H), 3.30 (s, 3 H), 1.35
(d, J = 7.1 Hz, 3 H).
Yield: 76 mg (43%); pale yellow oil.
13C NMR (101 MHz, CDCl3):  = 139.8, 134.7, 130.1, 129.1, 128.4,
127.9, 127.5, 127.2, 86.5, 57.7, 45.9, 16.5.
IR (neat): 2974, 2920, 2850, 1577, 1475, 1436, 1097, 1083, 1022, 734,
690 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.59–7.51 (a + b; m, 3.6 H), 7.29–7.20
(a + b; m, 6 H), 3.68 (a; dd, J = 10.1, 8.5 Hz, 1 H), 3.56 (a; dd, J = 10.1,
5.1 Hz, 1 H), 3.38 (b; s, 3 H), 3.30 (a; s, 3 H), 3.26–3.22 (a; m, 1 H),
3.21–3.03 (a + b; m, 2.5 H), 1.89–1.40 (a + b; m, 12 H), 1.35–1.05 (a +
b; m, 8 H).
13C NMR (126 MHz, CDCl3);  = 134.2, 132.7, 131.1, 130.5, 129.1,
129.1, 127.2, 126.8, 85.2, 74.0, 58.7, 58.3, 53.1, 41.4, 39.3, 31.7, 30.1,
30.0, 29.0, 28.3, 26.6, 26.5, 26.54, 26.4, 26.3.
(2-Methoxy-2-naphthalen-2-ylethyl)(phenyl)selane (26)
Compound 26 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 177 mg (86%); orange oil.
IR (neat): 3050, 2931, 1477, 1437, 1101, 1022, 735 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.87–7.81 (m, 3 H), 7.75 (s, 1 H), 7.52–
7.42 (m, 5 H), 7.25–7.14 (m, 3 H), 4.52 (dd, J = 8.3, 5.2 Hz, 1 H), 3.40
(dd, J = 12.3, 4.0 Hz, 1 H), 3.29 (s, 3 H), 3.19 (dd, J = 12.3, 5.2 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 138.5, 134.4, 133.5, 133.4, 132.9,
130.8, 129.2, 128.8, 128.2, 127.9, 127.1, 126.5, 126.4, 126.3, 124.3,
83.6, 77.3, 57.3, 35.4.
HRMS (ESI): m/z [M – OMe]+ calcd for C14H19Se: 263.0679; found:
263.0685.
(2-Methoxyoctyl)(phenyl)selane (30a) and (1-Methoxyoctan-2-
yl)(phenyl)selane (30b)
HRMS (ESI): m/z [M – OMe]+ calcd for C18H15Se: 307.0366; found:
307.0359
Compounds 30a and 30b were synthesised following GP1. It was pu-
rified by column chromatography (silica gel, hexane/ethyl acetate,
30:1).
(1-Methoxy-2,3-dihydro-1H-inden-2-yl)(phenyl)selane (27)
Yield: 75 mg (42%); colourless oil.
IR (neat): 2926, 2854, 1577, 1477, 1436, 1091, 1074, 734, 690 cm–1
Compound 27 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
.
1H NMR (500 MHz, CDCl3):  = 7.50–7.44 (a + b; m, 2 H), 7.20–7.14 (a
+ b; m, 4 H), 3.48 (b; dd, J = 9.9, 5.2 Hz, 1 H) , 3.42 (b; dd, J = 9.9, 7.5
Hz, 1 H), 3.33–3.27 (a; m, 1 H), 3.26 (a; s, 3 H), 3.25 (b; s, 3 H), 3.23–
3.18 (b; s,1 H), 3.03 (a; dd, J = 12.2, 5.5 Hz, 1 H), 2.94 (a; dd, J = 12.2,
6.1 Hz, 1 H), 1.58–1.13 (a + b; m, 12.5 H), 0.80 (a + b; m, 3.75 H).
13C NMR (126 MHz, CDCl3):  = 134.9, 133.0, 132.8, 130.9, 129.2,
129.1, 127.6, 126.9, 80.6, 76.0, 58.8, 57.1, 45.0, 32.3, 32.1, 31.9, 31.8,
29.4, 29.2, 27.8, 25.4, 22.7, 14.2.
Yield: 168 mg (92%); orange oil.
The spectral data are in agreement with the literature.16
1H NMR (400 MHz, CDCl3):  = 7.62–7.57 (m, 2 H), 7.39 (d, J = 7.1 Hz, 1
H), 7.32–7.19 (m, 6 H), 4.76 (d, J = 2.8 Hz, 1 H), 4.08–3.97 (m, 1 H),
3.60 (dd, J = 17.0, 7.4 Hz, 1 H), 3.36 (s, 3 H), 2.94 (dd, J = 17.0, 3.7 Hz, 1
H).
13C NMR (101 MHz, CDCl3):  = 142.3, 140.9, 134.4, 129.6, 129.3,
129.1, 127.8, 127.0, 125.7, 125.3, 90.3, 57.0, 44.8, 38.4.
(2-Methoxycyclohexyl)(phenyl)selane (31)
(2-Cyclopentyl-2-methoxyethyl)(phenyl)selane (28a) and (1-Cy-
clopentyl-2-methoxyethyl)(phenyl)selane (28b)
Compound 31 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Compounds 28a and 28b were synthesised following GP1. It was pu-
rified by column chromatography (silica gel, hexane/ethyl acetate,
30:1).
Yield: 130 mg (80%); yellow oil.
The spectral data are in agreement with the literature.20
1H NMR (500 MHz, CDCl3):  = 7.56–7.56 (m, 2 H), 7.28–7.23 (m, 3 H),
3.38 (s, 3 H), 3.27 (m, 1 H), 3.18 (m, 1 H), 2.15 (m, 1 H), 2.04–1.97 (m,
1 H), 1.76–1.45 (m, 3 H), 1.38–1.19 (m, 3 H).
Yield: 127 mg (75%); colourless oil.
The spectral data are in agreement with the literature.16
IR (neat): 2947, 2866, 1577, 1475, 1436, 1095, 906, 729, 690 cm–1
.
13C NMR (126 MHz, CDCl3):  = 135.5, 129.1, 128.9, 127.5, 82.4, 56.5,
1H NMR (500 MHz, CDCl3):  = 7.60–7.56 (a; m, 3 H), 7.54–7.51 (b; m,
2 H), 7.28–7.20 (a + b; m, 8 H), 3.59– 3.56 (a + b; m, 3 H), 3.38 (b; s, 3
H), 3.32 (a; s, 3 H), 3.32–3.22 (a + b; m, 3 H), 3.16 (a; dd, J = 12.3, 4.8
Hz, 1 H), 3.08 (a; dd, J = 12.3, 5.8 Hz, 1 H), 2.31–2.09 (a + b; m, 2.6 H),
1.94–1.15 (a + b; m, 20 H).
13C NMR (126 MHz, CDCl3):  = 134.6, 132.7, 131.1, 130.10, 129.2,
129.1, 127.4, 126.9, 84.4, 75.71, 58.9, 58.0, 51.85, 44.3, 42.1, 31.7,
31.5, 31.2, 29.35, 28.7, 25.7, 25.6, 25.64, 25.38.
47.5, 32.3, 30.4, 25.9, 23.6.
2-Methoxy-3-(phenylselanyl)tetrahydro-2H-pyran (32)
Compound 32 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 23 mg (14%); yellow oil.
The spectral data are in agreement with the literature.21
1H NMR (500 MHz, CDCl3):  = 7.59–7.54 (m, 2 H), 7.30–7.23 (m, 3 H),
4.51 (d, J = 4.9 Hz, 1 H), 3.90 (ddd, J = 11.2, 7.4, 3.6 Hz, 1 H), 3.58–3.49
(m, 1 H), 3.42 (s, 3 H), 3.27 (dt, J = 7.4, 4.6 Hz, 1 H), 2.20 (ddd, J = 16.9,
8.1, 3.9 Hz, 1 H), 1.86–1.68 (m, 2 H), 1.57–1.48 (m, 1 H).
HRMS (ESI): m/z [M – OMe]+ calcd for C13H17Se: 249.0522; found:
249.0524.
13C NMR (126 MHz, CDCl3):  = 134.9, 129.1, 129.0, 127.7, 103.2, 62.9,
55.7, 44.2, 27.5, 24.4.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

H
N. Amri et al.
Feature
Synthesis
1-Methyl-3-(phenylselanyl)-1H-indole (33)
[2-(Benzyloxy)-2-phenylethyl](phenyl)selane (38)
Compound 33 was synthesised following GP1. It was purified by col-
Compound 38 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 9:1).
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 125 mg (72%); colourless oil.
Yield: 119 mg (54%); yellow oil.
The spectral data are in agreement with the literature.22
The spectral data are in agreement with the literature.10a
1H NMR (500 MHz, CDCl3):  = 7.58–7.55 (m, 1 H), 7.31 (dt, J = 8.2, 0.9
Hz, 1 H), 7.26–6.95 (m, 8 H), 3.78 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 137.6, 135.8, 134.4, 130.8, 129.0,
128.8, 125.6, 122.6, 120.6, 120.6, 109.7, 96.1, 33.2.
1H NMR (400 MHz, CDCl3):  = 7.48–7.42 (m, 2 H), 7.40–7.27 (m, 10
H), 7.25–7.17 (m, 3 H), 4.58 (dd, J = 8.4, 5.0 Hz, 1 H), 4.50 (d, J = 11.8
Hz, 1 H), 4.32 (d, J = 11.8 Hz, 1 H), 3.45–3.83 (m, 1 H), 3.12–3.18 (m, 1
H).
13C NMR (126 MHz, CDCl3):  = 141.2, 138.2, 132.6, 130.9, 129.1,
128.8, 128.5, 128.3, 128.0, 127.7, 126.9, 126.9, 80.9, 71.0, 35.7.
Benzyl(2-methoxy-2-phenylethyl)selane (34)
Compound 34 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
[2-(But-3-yn-1-yloxy)-2-phenylethyl](phenyl)selane (39)
Compound 39 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 76 mg (41%); pale yellow oil.
The spectral data are in agreement with the literature.16
1H NMR (500 MHz, CDCl3):  = 7.38–7.33 (m, 2 H), 7.32–7.23 (m, 7 H),
7.23–7.17 (m, 1 H), 4.20 (dd, J = 8.0, 5.4 Hz, 1 H), 3.70 (d, J = 2.3 Hz, 2
H), 3.22 (s, 3 H), 2.90 (dd, J = 12.7, 8.0 Hz, 1 H), 2.67 (dd, J = 12.7, 5.4
Hz, 1 H).
Yield: 112 mg (57%); yellow oil.
IR (neat): 3057, 2868, 1477, 1437, 1095, 733, 700 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.50–7.47 (m, 2 H), 7.37–7.28 (m, 5 H),
7.25–7.20 (m, 3 H), 4.51 (dd, J = 8.5, 5.0 Hz, 1 H), 3.52–3.42(m, 2 H),
3.35 (dd, J = 12.4, 8.5 Hz, 1 H), 3.09 (dd, J = 12.4, 5.0 Hz, 1 H), 2.50–
2.40 (m, 2 H), 1.95 (t, J = 2.7 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 141.3, 139.5, 129.1, 128.6, 128.5,
128.1, 126.8, 126.8, 84.3, 57.0, 31.0, 28.0.
13C NMR (126 MHz, CDCl3):  = 141.2, 132.7, 130.9, 129.1, 128.7,
128.3, 126.9, 126.8, 82.1, 81.3, 69.5, 67.4, 35.5, 20.0.
HRMS (ESI): m/z [M + Na]+ calcd for C18H18OSeNa: 349.0447; found:
(2-Ethoxy-2-phenylethyl)(phenyl)selane (35)
Compound 35 was synthesised following GP1. It was purified by col-
349.0448
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 157 mg (86%); yellow oil.
The spectral data are in agreement with the literature.10a
1H NMR (400 MHz, CDCl3):  = 7.56–7.43 (m, 2 H), 7.38–7.19 (m, 8 H),
4.47 (dd, J = 8.5, 5.1 Hz, 1 H), 3.38 (m, 3 H), 3.10 (dd, J = 12.2, 5.1 Hz, 1
H), 1.19 (t, J = 7.0 Hz, 3 H).
[2-(Cyclopropylmethoxy)-2-phenylethyl](phenyl)selane (40)
Compound 40 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 150 mg (75%); yellow oil.
The spectral data are in agreement with the literature.17
IR (neat): 3003, 2858, 1477, 1437, 1089, 1022, 733, 700 cm–1
.
13C NMR (101 MHz, CDCl3):  = 141.8, 132.7, 131.0, 129.1, 128.6,
128.1, 126.9, 126.7, 81.5, 64.8, 35.7, 15.4.
1H NMR (500 MHz, CDCl3):  = 7.44–7.41 (m, 2 H), 7.29–7.13 (m, 8 H),
4.44 (dd, J = 8.4, 5.2 Hz, 1 H), 3.31 (dd, J = 12.2, 8.5 Hz, 1 H), 3.15–3.07
(m, 2 H), 3.04 (dd, J = 12.2, 5.1 Hz, 1 H), 1.03–0.93 (m, 1 H), 0.47–0.38
(m, 2 H), 0.12–0.01 (m, 2 H).
Phenyl(2-phenyl-2-propoxyethyl)selane (36)
Compound 36 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
13C NMR (126 MHz, CDCl3):  = 141.7, 132.6, 131.0, 129.1, 128.6,
Yield: 152 mg (79%); yellow oil.
128.1, 126.8, 126.7, 81.22, 74.0, 35.8, 10.8, 3.4, 3.1.
HRMS (ESI): m/z [M + Na]+ calcd for C18H20OSeNa: 351.0604; found:
351.0615
IR (neat): 2958, 2874, 1477, 1091, 734, 700 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.51–7.30 (m, 2 H), 7.28–7.06 (m, 8 H),
4.36 (dd, J = 8.6, 4.9 Hz, 1 H), 3.19 (m, 3 H), 2.99 (dd, J = 12.2, 4.9 Hz, 1
H), 1.58–1.39 (m, 2 H), 0.81 (t, J = 7.4 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 141.9, 132.6, 131.2, 129.1, 128.6,
128.1, 126.8, 126.7, 81.7, 71.2, 35.9, 23.1, 10.8.
(2-Isopropoxy-2-phenylethyl)(phenyl)selane (41)
Compound 41 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 134 mg (70%); yellow oil.
(2-Butoxy-2-phenylethyl)(phenyl)selane (37)
The spectral data are in agreement with the literature.17
Compound 37 was synthesised following GP1. It was purified by col-
1H NMR (400 MHz, CDCl3):  = 7.54–7.40 (m, 2 H), 7.35–7.11 (m, 8 H),
4.59 (dd, J = 9.9, 3.6 Hz, 1 H), 3.60–3.44 (m, 1 H), 3.31 (dd, J = 12.1, 8.8
Hz, 1 H), 3.08 (dd, J = 12.1, 4.8 Hz, 1 H), 1.17 (d, J = 6.0 Hz, 3 H), 1.08 (d,
J = 6.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 142.6, 132.5, 131.2, 129.1, 128.6,
128.0, 126.7, 78.9, 69.9, 36.2, 23.4, 21.5.
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
Yield: 148 mg (74%); yellow oil.
The spectral data are in agreement with the literature.10a
1H NMR (400 MHz, CDCl3):  = 7.53–7.41 (m, 2 H), 7.38–7.16 (m, 8 H),
4.46 (dd, J = 8.7, 4.9 Hz, 1 H), 3.40–3.23 (m, 3 H), 3.09 (dd, J = 12.2, 4.9
Hz, 1 H), 1.54 (m, 2 H), 1.43–1.31 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 141.9, 132.6, 131.2, 129.1, 128.6,
128.1, 126.8, 126.7, 81.7, 69.3, 35.9, 32.0, 19.5, 14.0.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

I
N. Amri et al.
Feature
Synthesis
(2-Isobutoxy-2-phenylethyl)(phenyl)selane (42)
1-Phenyl-2-(phenylselanyl)ethyl Formate (47)
Compound 42 was synthesised following GP1. It was purified by col-
Compound 47 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 150 mg (75%); yellow oil.
Yield: 76 mg (41%); colourless oil.
The spectral data are in agreement with the literature.10a
The spectral data are in agreement with the literature.10a
1H NMR (400 MHz, CDCl3):  = 7.56–7.43 (m, 2 H), 7.38–7.18 (m, 8 H),
4.46 (dd, J = 8.8, 4.8 Hz, 1 H), 3.36 (dd, J = 12.1, 8.8 Hz, 1 H), 3.16–3.01
(m, 3 H), 1.86 (m, 1 H), 0.98–0.81 (m, 6 H).
1H NMR (500 MHz, CDCl3):  = 8.00 (s, 1 H), 7.44–7.40 (m, 2 H), 7.30–
7.13 (m, 8 H), 5.94 (dd, J = 8.9, 5.8 Hz, 1 H), 3.32 (dd, J = 12.9, 8.0 Hz, 1
H), 3.18 (dd, J = 13.2, 6.1 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 142.6, 132.4, 131.2, 129.1, 128.5,
13C NMR (126 MHz, CDCl3):  = 160.0, 138.8, 135.5, 133.4, 129.3,
127.9, 126.7, 78.9, 69.9, 36.2, 23.4, 21.5.
128.8, 128.7, 127.5, 126.8, 75.1, 33.2.
[2-(Cyclopentyloxy)-2-phenylethyl](phenyl)selane (43)
1-Phenyl-2-(phenylselanyl)ethyl Acetate (48)
Compound 43 was synthesised following GP1. It was purified by col-
Compound 48 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 148 mg (71%); yellow oil.
Yield: 92 mg (46%); colourless oil.
IR (neat): 3057, 2868, 1476, 1437, 1072, 1022, 732, 700 cm–1
.
The spectral data are in agreement with the literature.10a
1H NMR (500 MHz, CDCl3):  = 7.45–7.37 (m, 2 H), 7.29–7.10 (m, 8 H),
4.47 (dd, J = 9.2, 4.4 Hz, 1 H), 3.92–3.52 (m, 1 H), 3.22 (dd, J = 12.2, 9.2
Hz, 1 H), 2.99 (dd, J = 12.2, 4.5 Hz, 1 H), 1.74–1.34 (m, 8 H).
1H NMR (500 MHz, CDCl3):  = 7.46–7.40 (m, 2 H), 7.28–7.16 (m, 8 H),
5.87 (dd, J = 8.0, 5.7 Hz, 1 H), 3.31 (dd, J = 12.8, 8.0 Hz, 1 H), 3.16 (dd, J
= 12.8, 5.7 Hz, 1 H), 1.95 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 142.5, 132.4, 131.4, 129.1, 128.6,
13C NMR (126 MHz, CDCl3):  = 170.1, 139.5, 133.2, 129.9, 129.2,
127.9, 126.8, 126.7, 79.6, 79.4, 36.2, 33.2, 31.7, 23.5.
128.6, 128.5, 127.3, 126.7, 75.3, 33.5, 21.2.
[2-(Cyclohexyloxy)-2-phenylethyl](phenyl)selane (44)
1-[1-Phenyl-2-(phenylselanyl)ethyl]-1H-benzo[d][1,2,3]triazole (49)
Compound 44 was synthesised following GP1. It was purified by col-
Compound 49 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
umn chromatography (silica gel, hexane/ethyl acetate, 9:1).
Yield: 135 mg (62%); yellow oil.
Yield: 147 mg (65%); colourless oil.
IR (neat): 2927, 2854, 1477, 1436, 1070, 733, 700 cm–1
.
The spectral data are in agreement with the literature.10a
1H NMR (500 MHz, CDCl3):  = 7.40 (m, 2 H), 7.29–7.09 (m, 8 H), 4.57
(dd, J = 9.0, 4.6 Hz, 1 H), 3.24 (dd, J = 12.1, 9.0 Hz, 1 H), 3.16–3.07 (m, 1
H), 2.99 (dd, J = 12.1, 4.6 Hz, 1 H), 1.68 (m, 4 H), 1.42–0.92 (m, 6 H).
1H NMR (500 MHz, CDCl3):  = 8.10–7.94 (m, 1 H), 7.46–7.39 (m, 2 H),
7.38–7.19 (m, 11 H), 5.85 (dd, J = 9.4, 5.8 Hz, 1 H), 4.25 (dd, J = 13.1,
9.4 Hz, 1 H), 3.82 (dd, J = 13.1, 5.8 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  = 142.8, 132.3, 131.4, 129.1, 128.5,
13C NMR (126 MHz, CDCl3):  = 146.1, 138.4, 133.7, 133.1, 129.3,
127.9, 126.7, 126.6, 78.5, 75.7, 36.4, 33.5, 31.4, 25.9, 24.2, 24.0.
129.0, 129.0, 128.8, 127.8, 127.3, 126.9, 124.0, 120.1, 109.6, 63.6, 32.6.
(2-tert-Butoxy-2-phenylethyl)(phenyl)selane (45)
2-[(Phenylselanyl)methyl]tetrahydrofuran (50)
Compound 45 was synthesised following GP1. It was purified by col-
Compound 50 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 30:1).
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 93 mg (47%); yellow oil.
Yield: 105 mg (73%); pale yellow oil.
IR (neat): 2972, 2931, 1477, 1436, 1072, 1190, 731, 700 cm–1
.
The spectral data are in agreement with the literature.25
1H NMR (400 MHz, CDCl3):  = 7.41–7.31 (m, 2 H), 7.27–7.06 (m, 8 H),
4.60 (dd, J = 8.6, 4.8 Hz, 1 H), 3.14 (dd, J = 12.1, 8.6 Hz, 1 H), 2.95 (dd, J
= 12.1, 4.8 Hz, 1 H), 1.02 (s, 9 H).
13C NMR (101 MHz, CDCl3):  = 145.3, 132.2, 131.5, 129.1, 128.4,
127.4, 126.6, 126.3, 75.0, 74.2, 37.4, 28.9.
1H NMR (500 MHz, CDCl3):  = 7.59–7.50 (m, 2 H), 7.30–7.22 (m, 3 H),
4.30–4.03 (m, 1 H), 4.01–3.88 (m, 1 H), 3.84–3.66 (m, 1 H), 3.15 (dd, J
= 12.2, 5.8 Hz, 1 H), 3.01 (dd, J = 12.2, 6.9 Hz, 1 H), 2.14–2.05 (m, 1 H),
2.03–1.80 (m, 2 H), 1.65 (m, 1 H).
13C NMR (126 MHz, CDCl3):  = 137.4, 132.7, 129.2, 127.0, 78.4, 78.4,
33.2, 31.7, 26.1.
1-Phenyl-2-(phenylselanyl)ethan-1-ol (46)
2-[(Phenylselanyl)methyl]tetrahydro-2H-pyran (51)
Compound 46 was synthesised following GP1. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 9:1).
Compound 51 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 134 mg (81%); colourless oil.
Yield: 103 mg (67%); pale yellow oil.
The spectral data are in agreement with the literature.25
1H NMR (500 MHz, CDCl3):  = 7.55–7.46 (m, 2 H), 7.29–7.18 (m, 3 H),
4.04–3.95 (m, 1 H), 3.92–3.26 (m, 2 H), 3.07 (dd, J = 12.2, 6.9 Hz, 1 H),
2.93 (dd, J = 12.2, 5.7 Hz, 1 H), 1.99–1.68 (m, 2 H), 1.61–1.43 (m, 3 H),
1.37–1.26 (m, 1 H).
The spectral data are in agreement with the literature.10a
1H NMR (500 MHz, CDCl3):  = 7.60–7.51 (m, 2 H), 7.38–7.32 (m, 4 H),
7.32–7.26 (m, 4 H), 4.76 (dd, J = 9.4, 3.5 Hz, 1 H), 3.31 (dd, J = 12.8, 3.7
Hz, 1 H), 3.15 (dd, J = 12.8, 9.4 Hz, 1 H), 2.79 (s, 1 H).
13C NMR (126 MHz, CDCl3):  = 142.6, 133.3, 129.4, 129.3, 128.7,
128.1, 127.6, 125.9, 72.4, 38.6.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

J
N. Amri et al.
Feature
Synthesis
13C NMR (126 MHz, CDCl3):  = 132.5, 130.9, 129.1, 126.8, 77.2, 68.9,
The spectral data are in agreement with the literature.25
33.8, 31.9, 25.9, 23.5.
1H NMR (500 MHz, CDCl3):  = 7.97–7.87 (m, 1 H), 7.60–7.45 (m, 5 H),
7.30–7.19 (m, 3 H), 5.72–5.55 (m, 1 H), 3.46 (dd, J = 13.2, 5.0 Hz, 1 H),
3.32 (dd, J = 13.2, 6.4 Hz, 1 H).
2-Methyl-3-(phenylselanyl)tetrahydro-2H-pyran (52)
13C NMR (126 MHz, CDCl3):  = 169.9, 148.5, 133.8, 133.6, 129.5,
129.2, 129.0, 127.7, 126.6, 125.7, 122.4, 79.1, 31.8.
Compound 52 was synthesised as a 1:1 mixture (cis : trans) following
GP2. It was purified by column chromatography (silica gel, hex-
ane/ethyl acetate, 9:1).
Yield: 89 mg (58%); colourless oil.
2-[(Phenylselanyl)methyl]-1-tosylindoline (57)
The spectral data are in agreement with the literature.21
Compound 57 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
1H NMR (500 MHz, CDCl3):  = 7.61–7.55 (m, 4 H), 7.31–7.23 (m, 6 H),
3.96–3.86 (m, 3 H), 3.78 (dt, J = 9.4, 6.6 Hz, 1 H), 3.46–3.29 (m, 3 H),
2.99–2.89 (m, 1 H), 2.22–2.10 (m, 1 H), 2.09–1.99 (m, 1 H), 1.95–1.83
(m, 2 H), 1.75–1.53 (m, 4 H), 1.44 (d, J = 7.0 Hz, 3 H), 1.35 (d, J = 6.1 Hz,
3 H).
13C NMR (126 MHz, CDCl3):  = 135.6, 135.3, 134.9, 129.1, 129.0,
128.2, 127.9, 127.6, 83.0, 78.4, 68.6, 68.2, 47.2, 44.4, 32.5, 30.4, 28.2,
26.3, 21.3, 18.9.
Yield: 87 mg (33%); yellow solid; mp 70–72 °C.
The spectral data are in agreement with the literature.26
1H NMR (500 MHz, CDCl3):  = 7.65 (d, J = 8.1 Hz, 1 H), 7.61–7.54 (m, 2
H), 7.39–7.29 (m, 5 H), 7.23–7.18 (m, 1 H), 7.11–7.08 (m, 2 H), 7.04–
7.01 (m, 2 H), 4.36–4.11 (m, 1 H), 3.65 (dd, J = 12.5, 3.5 Hz, 1 H), 2.96–
2.81 (m, 3 H), 2.32 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 144.0, 141.4, 134.7, 132.6, 131.1,
129.7, 129.4, 128.9, 127.9, 127.2, 127.1, 125.3, 124.8, 117.1, 61.7, 34.2,
33.2, 21.6.
5-[(Phenylselanyl)methyl]dihydrofuran-2(3H)-one (53)
Compound 53 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 101 mg (65%); pale yellow oil.
The spectral data are in agreement with the literature.20
1H NMR (500 MHz, CDCl3):  = 7.62–7.46 (m, 2 H), 7.33–7.26 (m, 3 H),
4.69–4.61 (m, 1 H), 3.29 (dd, J = 12.9, 4.8 Hz, 1 H), 3.01 (dd, J = 12.9,
8.0 Hz, 1 H), 2.62–2.36 (m, 3 H), 2.00–1.90 (m, 1 H).
Funding Information
The support from Cardiff University and from the Chemistry Depart-
ment, Jazan University, Saudi Arabia, is appreciated.
C
ard
i
f
U
n
i
v
ersity(J)
a
z
a
n
U
n
i
v
ersity()
13C NMR (126 MHz, CDCl3):  = 176.7, 133.4, 129.5, 128.9, 127.8, 79.5,
32.0, 28.9, 27.8.
Acknowledgment
We thank D. Guthrie and M. Nuno, Vapourtec Inc., for many discus-
sions and for providing the equipment and support for this research.
Fruitful discussions with Dr. M. N. Khan, Cardiff University, are grate-
fully acknowledged.
5-Phenyl-4-(phenylselanyl)dihydrofuran-2(3H)-one (54)
Compound 54 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 58 mg (30%); colourless oil.
Supporting Information
The spectral data are in agreement with the literature.23
1H NMR (400 MHz, CDCl3):  = 7.55–7.52 (m, 2 H), 7.40–7.28 (m, 8 H),
5.38 (d, J = 6.9 Hz, 1 H), 3.79– 3.71 (m, 1 H), 3.04 (dd, J = 18.0, 8.3 Hz, 1
H), 2.67 (dd, J = 18.0, 8.4 Hz, 1 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690868.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
13C NMR (101 MHz, CDCl3):  = 174.7, 137.4, 136.3, 129.7, 129.2,
129.1, 128.9, 126.1, 125.9, 86.3, 42.38, 36.1.
References
(1) (a) Alcácer, V.; Cruz-Machado, V. Eng. Sci. Technol. Int. J. 2019,
22, 899. (b) Fitzpatrick, D. E.; Battilocchio, C.; Ley, S. V. ACS Cent.
Sci. 2016, 2, 131. (c) Kreimeyer, A.; Eckes, P.; Fischer, C.; Lauke,
H.; Schuhmacher, P. Angew. Chem. Int. Ed. 2015, 54, 3178.
(d) Ley, S. V.; Fitzpatrick, D. E.; Myers, R. M.; Battilocchio, C.;
Ingham, R. J. Angew. Chem. Int. Ed. 2015, 54, 10122. (e) Prieto,
G.; Schüth, F. Angew. Chem. Int. Ed. 2015, 54, 3222. (f) Ley, S. V.;
Fitzpatrick, D. E.; Ingham, R. J.; Myers, R. M. Angew. Chem. Int.
Ed. 2015, 54, 3449.
(2) (a) Science of Synthesis: Flow Chemistry; Jamison, T. F.; Koch, G.,
Ed.; Thieme: Stuttgart, 2018. (b) Microreactors in Organic Syn-
thesis and Catalysis; Wirth, T., Ed.; Wiley-VCH: Weinheim, 2013.
(c) Yoshida, J. Flash Chemistry: Fast Organic Synthesis in Micro-
systems; Wiley-VCH: Weinheim, 2008.
6-(Phenylselanyl)hexahydro-2H-cyclopenta[b]furan-2-one (55)
Compound 55 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 115 mg (68%); colourless oil.
The spectral data are in agreement with the literature.24
1H NMR (500 MHz, CDCl3):  = 7.64–7.42 (m, 2 H), 7.34–7.25 (m, 3 H),
4.90 (d, J = 6.3 Hz, 1 H), 3.97–3.78 (m, 1 H), 3.15–3.04 (m, 1 H), 2.87–
2.73 (m, 1 H), 2.34 (dd, J = 18.4, 2.5 Hz, 1 H), 2.28–2.18 (m, 2 H), 1.91–
1.71 (m, 1 H), 1.61–1.51 (m, 1 H).
13C NMR (126 MHz, CDCl3):  = 177.0, 133.8, 129.5, 128.8, 127.9, 90.7,
46.4, 37.2, 36.1, 32.6, 30.2.
(3) (a) Jing, Q.; Moeller, K. D. Acc. Chem. Res. 2020, 53, 135.
(b) Folgueiras Amador, A. A.; Wirth, T. In Science of Synthesis:
Flow Chemistry; Jamison, T. F.; Koch, G., Ed.; Thieme: Stuttgart,
2018, 147. (c) Pletcher, D.; Green, R. A.; Brown, R. C. D. Chem.
3-[(Phenylselanyl)methyl]isobenzofuran-1(3H)-one (56)
Compound 56 was synthesised following GP2. It was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate, 4:1).
Yield: 87 mg (48%); colourless oil.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K

K
N. Amri et al.
Feature
Synthesis
Rev. 2018, 118, 4573. (d) Atobe, M.; Tateno, H.; Matsumura, Y.
Chem. Rev. 2018, 118, 4541. (e) Wiebe, A.; Gieshoff, T.; Möhle,
S.; Rodrigo, E.; Zirbes, M.; Waldvogel, S. R. Angew. Chem. Int. Ed.
2018, 57, 5594.
(10) (a) Yuan, Y.; Lei, A. Acc. Chem. Res. 2019, 52, 3309. (b) Sun, L.;
Yuan, Y.; Yao, M.; Wang, H.; Wang, D.; Gao, M.; Chen, Y. H.; Lei,
A. Org. Lett. 2019, 21, 1297. (c) Chen, J.; Mei, L.; Wang, H.; Hu, L.;
Sun, X.; Shi, J.; Li, Q. ChemistryOpen 2019, 7, 1230. (d) Wilken,
M.; Ortgies, S.; Breder, A.; Siewert, I. ACS Catal. 2018, 8, 10901.
(11) (a) Folgueiras-Amador, A. A.; Qian, X.-Y.; Xu, H.-C.; Wirth, T.
Chem. Eur. J. 2018, 24, 487. (b) Laudadio, G.; Straathof, N. J. W.;
Lanting, M. D.; Knoops, B.; Hessel, V.; Noël, T. Green Chem. 2017,
19, 4061.
(4) (a) Elsherbini, M.; Wirth, T. Acc. Chem. Res. 2019, 52, 3287.
(b) Folgueiras-Amador, A. A.; Philipps, K.; Guilbaud, S.;
Poelakker, J.; Wirth, T. Angew. Chem. Int. Ed. 2017, 56, 15446.
(c) Amri, N.; Skilton, R. A.; Guthrie, D.; Wirth, T. Synlett 2019,
30, 1183.
(5) https://www.vapourtec.com/products/flow-reactors/ion-
electrochemical-reactor-features/ (accessed January 2020).
(6) (a) Shaabani, S.; Xu, R.; Ahmadianmoghaddam, M.; Gao, L.;
Stahorsky, M.; Olechno, J.; Ellson, R.; Kossenjans, M.; Helan, V.;
Dömling, A. Green Chem. 2019, 21, 225. (b) Trobe, M.; Burke, M.
D. Angew. Chem. Int. Ed. 2018, 57, 4192. (c) Panza, M.; Pistorio, S.
G.; Stine, K. J.; Demchenko, A. V. Chem. Rev. 2018, 118, 8105.
(d) Mijalis, A. J.; Thomas, D. A.; Simon, M. D.; Adamo, A.;
Beaumont, R.; Jensen, K. F.; Pentelute, B. L. Nat. Chem. Biol. 2017,
13, 464. (e) Reizman, B. J.; Jensen, K. F. Acc. Chem. Res. 2016, 49,
1786. (f) Yoshida, J.; Kim, H.; Nagaki, A. ChemSusChem 2011, 4,
331. (g) Merrifield, R. B.; Stewart, J. M.; Jernberg, N. Anal. Chem.
1966, 38, 1905.
(7) (a) Singh, F. V.; Wirth, T. Catal. Sci. Technol. 2019, 9, 1073.
(b) Singh, F. V.; Wirth, T. In Organoselenium Compounds in
Biology and Medicine: Synthesis, Biological and Therapeutic
Treatments; Jain, V. K.; Priyadarsini, K. I., Ed.; The Royal Society
of Chemistry: London, 2018, 77. (c) Mukherjee, A. J.; Zade, S. S.;
Singh, H. B.; Sunoj, R. B. Chem. Rev. 2010, 110, 4357.
(d) Organoselenium Chemistry; Wirth, T., Ed.; Springer: Berlin,
2000. (e) Back, T. G. Organoselenium Chemistry: A Practical
Approach; Oxford University Press: Oxford, 1999.
(12) Kaye, A.; Neidle, S.; Reese, C. B. Tetrahedron Lett. 1988, 29, 2711.
(13) Meirinho, A. G.; Pereira, V. F.; Martins, G. M.; Saba, S.; Rafique,
J.; Braga, A. L.; Mendes, S. R. Eur. J. Org. Chem. 2019, 6465.
(14) CCDC-1980248 (21) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
(15) Perin, G.; Santoni, P.; Barcellos, A. M.; Nobre, P. C.; Jacob, R. G.;
Lenardão, E. J.; Santi, C. Eur. J. Org. Chem. 2018, 1224.
(16) Yu, C.; Shi, H.; Yan, J. ARKIVOC 2015, 266.
(17) Vieira, A. A.; Azeredo, J. B.; Godoi, M.; Santi, C.; Da Silva Júnior,
E. N.; Braga, A. L. J. Org. Chem. 2015, 80, 2120.
(18) Bosman, C.; D’Annibale, A.; Resta, S.; Trogolo, C. Tetrahedron
Lett. 1994, 35, 6525.
(19) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Bartoli, D. Tet-
rahedron 1988, 44, 2261.
(20) Conner, E. S.; Crocker, K. E.; Fernando, R. G.; Fronczek, F. R.;
Stanley, G. G.; Ragains, J. R. Org. Lett. 2013, 15, 5558.
(21) Kostić, M.; Verdía, P.; Fernández-Stefanuto, V.; Puchta, R.; Tojo,
E. J. Phys. Org. Chem. 2019, 32, 1.
(22) Vásquez-Céspedes, S.; Ferry, A.; Candish, L.; Glorius, F. Angew.
Chem. Int. Ed. 2015, 54, 5772.
(8) Niyomura, O.; Cox, M.; Wirth, T. Synlett 2006, 251.
(9) (a) Jiang, Y.; Xu, K.; Zeng, C. Chem. Rev. 2018, 118, 4485.
(b) Moeller, K. D. Chem. Rev. 2018, 118, 4817. (c) Francke, R.;
Schille, B.; Roemelt, M. Chem. Rev. 2018, 118, 4631. (d) Yoshida,
J.; Shimizu, A.; Hayashi, R. Chem. Rev. 2018, 118, 4702.
(e) Ibanez, J. G.; Rincón, M. E.; Gutierrez-Granados, S.; Chahma,
M.; Jaramillo-Quintero, O. A.; Frontana-Uribe, B. A. Chem. Rev.
2018, 118, 4731. (f) Nutting, J. E.; Rafiee, M.; Stahl, S. S. Chem.
Rev. 2018, 118, 4834.
(23) Denmark, S. E.; Collins, W. R. Org. Lett. 2007, 9, 3801.
(24) Nicolaou, K. C.; Seitz, S. P.; Sipio, W. J.; Blount, J. F. J. Am. Chem.
Soc. 1979, 101, 3884.
(25) Zhang, Q. B.; Yuan, P. F.; Kai, L. L.; Liu, K.; Ban, Y. L.; Wang, X. Y.;
Wu, L. Z.; Liu, Q. Org. Lett. 2019, 21, 885.
(26) Ni, Y.; Zuo, H.; Li, Y.; Wu, Y.; Zhong, F. Org. Lett. 2018, 20, 4350.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–K