Straightforward and direct access to β-seleno- amines and sulfonylamides via the controlled addition of phenylselenomethyllithium (LiCH2SePh) to imines

Article abstract of DOI:10.1016/j.tet.2020.131220

The transfer of a α-methyl phenylseleno carbanion to variously functionalized N-aryl and N-sulfonyl imines is reported. The fast selenium-lithium exchange conducted on a diselenoacetal with n-BuLi enables the generation of the attacking homologative nucleophile under chemoselective conditions preserving concomitant potentially sensitive functionalities to the lithiating conditions. Uniformly high yields were observed, thus establishing a valuable and conceptually simple approach to the title compounds.

Full text of DOI:10.1016/j.tet.2020.131220

Journal Pre-proof
Straightforward and direct access to β-seleno- amines and sulfonylamides via the
controlled addition of phenylselenomethyllithium (LiCH SePh) to imines
2
Raffaele Senatore, Monika Malik, Saad Touqeer, Roberta Listro, Simona Collina,
Wolfgang Holzer, Vittorio Pace
PII:
S0040-4020(20)30355-0
https://doi.org/10.1016/j.tet.2020.131220
TET 131220
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 March 2020
Revised Date: 16 April 2020
Accepted Date: 17 April 2020
Please cite this article as: Senatore R, Malik M, Touqeer S, Listro R, Collina S, Holzer W, Pace V,
Straightforward and direct access to β-seleno- amines and sulfonylamides via the controlled addition
of phenylselenomethyllithium (LiCH SePh) to imines, Tetrahedron (2020), doi: https://doi.org/10.1016/
2
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Straightforward and Direct Access to β-Seleno- Amines and Sulfonylamides via the Controlled
Addition of Phenylselenomethyllithium (LiCH SePh) to Imines
2
a
a
a
b
b
a
Raffaele Senatore, Monika Malik, Saad Touqeer, Roberta Listro, Simona Collina, Wolfgang Holzer and
a,c
Vittorio Pace *
a
Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
b
Department of Drug Sciences, University of Pavia, Via Taramelli 6, 27100 Pavia, Italy.
c
Department of Chemistry, University of Turin, Via P. Giuria 7, 10125 Turin, Italy.
*
-
E-mail: vittorio.pace@univie.ac.at; vittorio.pace@unito.it – Web page: https://drugsynthesis.univie.ac.at/
Twitter: @LabPace
Dedicated to Prof. Dr. Nuno Maulide for his outstanding contributions to the art of Synthesis.
Abstract. The transfer of a α-methyl phenylseleno carbanion to variously functionalized N-aryl and N-
sulfonyl imines is reported. The fast selenium-lithium exchange conducted on a diselenoacetal with n-BuLi
enables the generation of the attacking homologative nucleophile under chemoselective conditions
preserving concomitant potentially sensitive functionalities to the lithiating conditions. Uniformly high
yields were observed, thus establishing a valuable and conceptually simple approach to the title
compounds.
Introduction.
Embodying selenium containing groups into an organic skeleton profoundly influences the physical-
chemical features of the resulting scaffold, thus complementing the reach and well-established portfolio of
1
(
stereoselective) transformations these organometallics offer. Indeed, there is a continuous and growing
interest towards the biological properties displayed by organoselenium analogues whose structures are
frequently encountered in enzymes governing important metabolic cascades (e.g. selenoprotein P,
2
glutathione peroxidase, inter alia). Additionally, recent uses of selenium-based pharmacologically active
substances emerged as valuable tools for treating important diseases, as exemplified by ebselen, thus
3
further increasing the potential of such a chalcogen-containing motifs. Evidently, the simultaneous
derivatization of organoselenium species with additional functionalities expands the chemical space and
the overall versatility of the so obtained materials. In this sense, including a nitrogen-centered group in a
relevant position may represent an effective strategy for tuning pivotal molecular properties (e.g. solubility,
cell permeability, metabolic parameters etc.) or, by focusing on pure synthetic aspects, it enables selective
4
chemistries en route to more complex architectures. In fact, the proper activation of these β-seleno amine-
5
type manifolds results in a versatile technique for assembling different aza-cycles such as aziridines or
6
diastereomerically enriched 2,4-disubstituted pyrrolidines. This applicative significance merged with the
7
potential exhibited in different areas including material science and drug design, motivated the
development of variously oriented tactics for the construction of the motif. In recent years, the amino- or
2
amido- selenation of olefins – i.e. the simultaneous installation into the sp -hydridized C-C bond of both the
1

selenium atom and the nitrogenated moiety - emerged as an attractive and practical solution.
Mechanistically, the electrophilic organoselenium agent generates a seleniranium ion susceptible of
nucleophilic attack by the N-containing partner. The protocol manifests strong dependence on the nature
and level of substitution of the competent olefin, as well as, on the nucleophilicity of the attacking amine or
8
9
10
amide groups. As a consequence, the adequate modulation – via ionic, electrochemical or radical
pathway - of these events becomes critical for the successful outcome of the targeted strategy. A logically
11
distinct approach involves the ring opening of an aziridine with an in situ generated selenium anion. It
appears conceivable that using these highly valuable synthons may pose severe limitations in terms of
costs. Alternatively, Outurquin proposed a two-steps methodology paved on forming highly unstable and
difficult to purify α-selenoimines (from the corresponding ketones) followed by the controlled reduction to
5a,12
the desired compounds.
Inspired by our work on homologation of carbon electrophiles with α-substituted methyllithiums
1
3
(
LiCHXY), in 2018 we reported a general approach for introducing substituted seleniummethyl fragments
13k,14
–
i.e. RSeCH – onto Weinreb amides.
The strategy paved on the generation of the carbanion from a
2
15
16
diselenoacetal by adapting seminal Reich’s studies, documented high versatility and chemoselectivity.
17
We reasoned that delivering this Se-centered carbanion to a given imine would produce the β-seleno
nitrogenated adduct through a conceptually intuitive and novel approach. To the best of our knowledge,
the employment of C-C bond forming operations for producing the title compounds is still unprecedented
and, herein we disclose our findings.
2

Scheme 1. General context of the presented work.
Results and Discussion.
We selected the naphthyl-substituted imine 1 as the model compound for accomplishing the formal
homologation with the lithiated α-methyl seleno carbanion (LiCH SePh). As anticipated, a convenient
2
1
5a
source of this species was individuated in the diselenoacetal (PhSeCH SePh) which undergoes an
2
extremely fast selenium-lithium exchange upon treatment with n-BuLi. Evidently, the genesis of the
requested carbanion is accompanied by the formation of the interconversion product – the selenoether n-
BuSePh (2b) – which guarantees a quantitative estimation of the process. The optimization study revealed
3

the adaptability of the conditions established for preparing α-selenoketones starting from Weinreb
1
4a
amides: PhSeCH SePh (1.3 equiv), n-BuLi (1.25 equiv) in Et O at -78 °C under non-Barbier type conditions
2
2
(
Table 1). Although the initial experiment showed the formation of the expected β-selenoamine 2 in a
reasonably good 70% yield, a noticeable amount of the aminic compound 2a generated by the direct attack
of n-BuLi to the azomethinic carbon was detected (entry 1). With the aim of improving the yield of 2, we
briefly screened the effect of additional parameters: i) the simple switching to THF as the reaction medium
did not alter significantly the 2:2a ratio (entry 2); ii) decreasing the lithiation time was detrimental in
agreement with our previous study on Weinreb amides (entries 3-4); iii) the use of alternative ethereal-
18
19
type solvents such as 2-MeTHF and CPME significantly decreased the efficiency (entries 5-6); iv)
pleasingly, the progressive increase of the loading of Se-carbanion enables to maximize the yield up to 93%,
being practically undetectable the formation of the side product 2a (entries 7-8); v) using a smaller excess
of diselenoacetal (2.0 equiv) compared to the lithiating agent (1.90 equiv) guarantees the full generation of
LiCH SePh and, thus to skip the concomitant, undesired attack of n-BuLi to 1.
2
Table 1. Model Reaction: Optimization
Entry Solvent LiCH SePh Lithiation time Ratio 2:2a Yield of 2
2
a
(%)
(
equiv)
(min)
b
1
Et O
THF
THF
1.25
1.25
1.25
1.25
1.25
1.25
1.60
1.90
1.90
60
60
45
30
60
60
60
60
60
76:24
78:22
75:25
77:23
65:45
71:29
93:7
70
73
68
64
50
58
84
93
90
2
2
3
4
5
6
7
8
THF
2-MeTHF
CPME
THF
THF
THF
>99:1
95:5
C
9
a
b
C
Isolated yield. 2a was isolated in 19% yield. PhSeCH SePh (1.90 equiv) and n-BuLi (1.90 equiv) were used.
2
With the optimal conditions in hand, we then explored the scope of the transformation. A series of
variously functionalized N-aryl imines easily undergoes the transformation giving the expected β-
phenylseleno adducts in high yields. The substitution on the aromatic ring of the starting N-phenyl-type
aldimines was perfectly tolerated: the presence of electron-donating functionalities such as methoxy at
different positions did not alter the efficiency of the methodology. Analogously, potentially sensitive
halogens – including the reactive bromo-derivatives (5 and 8) - could be introduced on the nucleus yielding
the corresponding seleno-amines. The chemoselectivity of the approach is further illustrated in the case of
the nitrile-bearing compound 10, in which this electrophilic group was preserved by the nucleophilic attack.
Switching to heteroaromatic aldimines was also possible, as documented by the 2-furyl (12) derivative. The
nature of the N-imine group can be conveniently shifted to a sulfonyl-analogue in order to prepare β-seleno
4

sulfonyl imides (13-19). Interestingly, our approach constitutes an effective solution for accessing 14 whose
11
previous synthesis through the ring-opening of an aziridine was affected by limited regiocontrol.
A
comparable chemoselective profile was observed: halogen-containing groups – such as chlorine, fluoro,
trifluoromethyl and bromo – maintain unaltered the productivity of the homologative technique. Similarly,
poly- (naphtyl, 13) or heteroaromatic (2-furyl, 18 – 2-thienyl, 19) benzensulfonylimines acted as competent
starting materials without affecting the chemical integrity of these systems.
5

PhSeCH SePh (2.0 equiv)
2
R2
H
n-BuLi (1.9 equiv)
R2
N
HN
R1
SePh
R1
THF, -78 °C, 2.5 h
NH Cl (aq.)
4
N-Aryl Imines
Me
Me
Me
Br
HN
HN
HN
HN
Se
Se
Se
Se
MeO
MeO
MeO
OMe
2
(93 %)
3 (88 %)
4 (83 %)
5 (85 %)
Me
Me
Me
F
HN
HN
HN
HN
Se
Se
Se
Se
Cl
F
Br
Cl
6
(87 %)
7 (92 %)
8 (86 %)
9 (88 %)
Me
Me
HN
HN
HN
Se
Se
Se
O
NC
10 (92 %)
11 (89 %)
12 (86 %)
N-Sulfonyl Imines
O O
O O
O O
S
HN
S
S
Me
HN
HN
Se
Se
Se
Cl
CF3
15 (85 %)
13 (89 %)
14 (91 %)
O O
O O
O
O
S
O O
S
S
S
HN
HN
HN
HN
Se
Se
O
Se
S
Se
Br
F
16 (90 %)
17 (92 %)
18 (87 %)
19 (90 %)
Scheme 2. Scope of the protocol.
6

Conclusions.
In conclusion, we have developed a straightforward and versatile methodology for the transfer of a
selenium-centered methyllithium carbanion to variously functionalized imines. The selective lithiation of a
diselenoacetal (PhSeCH SePh) smoothly provides the homologating agent (LiCH SePh) which can be easily
2
2
released to the electrophilic azomethinic partners. The high degree of chemoselectivity, as well as the very
good to excellent yields observed, make this conceptually intuitive strategy of wide and general
applicability.
Experimental Part
Instrumentation and General Analytical Methods
Melting points were determined on a Reichert–Kofler hot-stage microscope and are uncorrected. Mass
spectra were obtained on a Shimadzu QP 1000 instrument (EI, 70 eV) and on a Bruker maXis 4G instrument
1
13
19
15
77
(
ESI-TOF, HRMS). H, C, F, N and Se NMR spectra were recorded with a Bruker Avance III 400
1
13
19
15
77
spectrometer (400 MHz for H, 100 MHz for C, 376 MHz for F, 40 MHz for N and 76 MHz for Se) at
2
97 K using a directly detecting broadband observe (BBFO) probe. The center of the (residual) solvent signal
1
13
was used as an internal standard which was related to TMS with δ 7.26 ppm ( H in CDCl ), δ 77.0 ppm ( C
3
1
9
15
in CDCl ). F NMR spectra were referenced via the Ξ ratio (absolute referencing). N NMR spectra (gs-
3
77
HMBC, gs-HSQC) were referenced against neat, external nitromethane. Se spectra were referenced
against diphenyldiselane (δ Ph Se 463 ppm). Spin-spin coupling constants (J) are given in Hz.
2
2
In nearly all cases, full and unambiguous assignment of all resonances was performed by combined
application of standard NMR techniques, such as APT, HSQC, HMBC, HSQCTOCSY, COSY and NOESY
experiments.
THF was distilled over Na / benzophenone. Chemicals were purchased from SigmaAldrich, Acros, Alfa Aesar
and TCI Europe. Solutions were evaporated under reduced pressure with a rotary evaporator. TLC was
carried out on aluminium sheets precoated with silica gel 60F254 (Merchery-Nagel, Merk); the spots were
visualised under UV light (λ = 254 nm) and/or KMnO (aq.) was used as revealing system.
4
General Procedure
To a solution of 1,1’-(methylenediselanyl)dibenzene (2.0 equiv) in dry THF (2 mL) a 2.5 M solution of n-BuLi
in hexanes (1.9 equiv) was added dropwise at -78 °C under argon and the reaction mixture was stirred at -
7
8 °C for 1 hour. Then, a solution of the starting imine (1.0 equiv) in dry THF (1 mL) was added and the
mixture was stirred at -78 °C for 2.5 hours before quenching with sat. aqueous NH Cl. The mixture was
4
exhaustively extracted with EtOAc. The combined organic extracts were washed with brine, dried over
Na SO and the solvent was removed under reduced pressure. The product was obtained after purification
2
4
by column chromatography on silica gel (n-hexane:EtOAc).
4
-methyl-N-[1-(2-naphthyl)-2-(phenylselanyl)ethyl]aniline (2)
7

By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and 4-methyl-N-(naphthalen-2-
2
ylmethylene)aniline (0.245 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 2 was obtained in 93 %
yield (0.387 g) as colourless oil after purification by column chromatography on silica gel (n-hexane:EtOAc
9
9:1).
1
H NMR (400 MHz, CDCl ): δ 7.81 (m, 1H, Naph H-1), 7.80 (m, 2H, Naph), 7.78 (m, 1H, Naph), 7.54 (m, 2H,
3
Ph 2 H-2,6), 7.47 (m, 1H, Naph H-3), 7.46 (m, 1H, Naph), 7.45 (m, 1H, Naph), 7.27 (m, 1H, Ph 2 H-4), 7.26 (m,
3
3
2
4
H, Ph 2 H-2,6), 6.87 (m, 2H, Ph 1 H-3,5), 6.43 (m, 2H, Ph 1 H-2,6), 4.59 (dd, J = 8.9 Hz, J = 4.6 Hz, 1H, CH),
2
3
2
3
.5 (brs, 1H, NH), 3.44 (dd, J = 12.6 Hz, J = 4.6 Hz, 1H, CH ), 3.28 (dd, J = 12.6 Hz, J = 8.9 Hz, 1H, CH ), 2.18
2
2
(
s, 3H, CH3).
13
C NMR (100 MHz, CDCl ): δ 144.7 (Ph 1 C-1), 140.3 (Naph C-2), 133.55 (Ph 2 C-2,6), 133.51 (Naph 8a),
3
1
33.0 (Naph 4a), 129.6 (Ph 1 C-3,5), 129.3 (Ph 2 C-1), 129.2 (Ph 2 C-3,5), 128.6 (Naph), 127.9 (Naph), 127.7
(
Naph), 127.5 (Ph 2 C-4), 127.1 (Ph 1 C-4), 126.1 (Naph), 125.7 (Naph), 125.2 (Naph C-1), 124.4 (Naph C-3),
1
14.0 (Ph 1 C-2,6), 58.4 (CH), 36.4 (CH ), 20.3 (CH ).
2
3
77
Se NMR (76 MHz, CDCl ): δ 267.3 (m).
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NSe: 418.1068; found: 418.1057.
25 24
4
-methyl-N-[1-(2-naphthyl)pentyl]aniline (2a)
1
H NMR (400 MHz, CDCl ): δ 7.82 (m, 3H, Naph H-4,5,8), 7.81 (s, 1H, Naph H-1), 7.50 (m, 1H, Naph H-3),
3
7
.47 (m, 1H, Naph H-6), 7.45 (m, 1H, Naph H-7), 6.89 (m, 2H, Ph H-3,5), 6.50 (m, 2H, Ph H-2,6), 4.44 (m, 1H,
CH), 3.9 – 4.4 (brs, 1H, NH), 2.18 (s, 3H, CH ), 1.88 (m, 2H, CH CH CH CH ), 1.37 (m, 2H, CH CH CH CH ),
3
2
2
2
3
2
2
2
3
3
1
.36 (m, 2H, CH CH CH CH ), 0.90 (t, J = 7.0 Hz, 3H, CH CH CH CH ).
2 2 2 3 2 2 2 3
13
C NMR (100 MHz, CDCl ): δ 145.2 (Ph C-1), 142.0 (Naph C-2), 133.5 (Naph C-8a), 132.8 (Naph C-4a), 129.6
3
(
Ph C-3,5), 128.3 (Naph), 127.8 (Naph), 127.6 (Naph), 126.4 (Ph C-4), 125.9 (Naph C-6), 125.4 (Naph C-7),
1
2
25.1 (Naph C-1), 124.8 (Naph C-3), 113.5 (Ph C-2,6), 58.8 (CH), 38.6 (CH CH CH CH ), 28.5 (CH CH CH CH ),
2 2 2 3 2 2 2 3
2.6 (CH CH CH CH ), 20.3 (CH ), 14.0 (CH CH CH CH ).
2
2
2
3
3
2
2
2
3
8

15
N NMR (40 MHz, CDCl ): δ -305.4.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H N: 304.2060; found: 304.2057.
22 26
14a
Butyl phenyl selenide (2b)
1
H NMR (400 MHz, CDCl ): δ 7.48 (m, 2H, Ph H-2,6), 7.25 (m, 2H, Ph H-3,5), 7.23 (m, 1H, Ph H-4), 2.92 (m,
3
3
2
H, CH CH CH CH ), 1.69 (m, 2H, CH CH CH CH ), 1.43 (m, 2H, CH CH CH CH ), 0.91 (t, J = 7.4 Hz, 3H,
2 2 2 3 2 2 2 3 2 2 2 3
CH CH CH CH ).
2
2
2
3
13
C NMR (100 MHz, CDCl ): δ 132.3 (Ph C-2,6), 130.7 (Ph C-1), 129.0 (Ph C-3,5), 126.6 (Ph C-4), 32.2
3
(
CH CH CH CH ), 27.6 (CH CH CH CH ), 22.9 (CH CH CH CH ), 13.5 (CH CH CH CH ).
2 2 2 3 2 2 2 3 2 2 2 3 2 2 2 3
77
Se NMR (76 MHz, CDCl ): δ 290.5.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H Se: 215.0333; found: 215.0336.
10 15
N-[1-(4-methoxyphenyl)-2-(phenylselanyl)ethyl]-4-methylaniline (3)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-methoxybenzylidene)-4-
methylaniline (0.225 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 3 was obtained in 88 % yield
2
(
0.348 g) as colourless oil after purification by column chromatography on silica gel (n-hexane:EtOAc 9:1).
1
H NMR (400 MHz, CDCl ): δ 7.50 (m, 2H, Ph 3 H-2,6), 7.26 (m, 3H, Ph 3 H-3,4,5), 7.25 (m, 2H, Ph 1 H-2,6),
3
3
3
6
.88 (m, 2H, Ph 2 H-3,5), 6.83 (m, 2H, Ph 1 H-3,5), 6.40 (m, 2H, Ph 2 H-2,6), 4.39 (dd, J = 8.4 Hz, J = 5.1 Hz,
2
3
1
H, CH), 4.0-4.8 (brs, 1H, NH), 3.78 (s, 3H, OCH ), 3.33 (dd, J = 12.5 Hz, J = 5.1 Hz, 1H, CH ), 3.22 (m, 1H,
3 2
CH ), 2.18 (s, 3H, CH ).
2
3
9

13
C NMR (100 MHz, CDCl ): δ 158.9 (Ph 1 C-4), 144.9 (Ph 2 C-1), 134.6 (Ph 1 C-1), 133.4 (Ph 3 C-2,6), 129.5
3
(
Ph 2 C-3,5), 129.4 (Ph 3 C-1), 129.2 (Ph 3 C -3,5), 127.5 (Ph 1 C-2,6), 127.4 (Ph 3 C-4), 127.2 (Ph 2 C-4),
14.1 (Ph 1 C-3,5, Ph 2 C-2,6), 57.7 (CH), 55.2 (OCH ), 36.4 (CH ), 20.4 (CH ).
1
3
2
3
77
Se NMR (76 MHz, CDCl ): δ 265.0 (m).
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NOSe: 398.1018; found: 398.1016.
22 24
N-[1-(2,4-dimethoxyphenyl)-2-(phenylselanyl)ethyl]-4-methylaniline (4)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(2,4-
dimethoxybenzylidene)-4-methylaniline (0.255 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 4 was
obtained in 83 % yield (0.354 g) as brown oil after purification by column chromatography on silica gel (n-
hexane:EtOAc 99:1).
1
3
H NMR (400 MHz, CDCl ): δ 7.51 (m, 2H, Ph 3 H-2,6), 7.24 (m, 3H, Ph 3 H-3,4,5), 7.21 (d, J = 8.4 Hz, 1H, Ph
3
4
1
H-6), 6.89 (m, 2H, Ph 2 H-3,5), 6.43 (d, J = 2.4 Hz, 1H, Ph 1 H-3), 6.39 (m, 3H, Ph 1 H-5, Ph 2 H-2,6), 4.78
3
3
2
(
dd, J = 8.3 Hz, J = 4.8 Hz, 1H, CH), 4.38 (brs, 1H, NH), 3.82 (s, 3H, 2-OCH ), 3.77 (s, 3H, 4-OCH ), 3.45 (dd, J
3 3
3
2
3
=
12.4 Hz, J = 4.8 Hz, 1H, CH ), 3.22 (dd, J = 12.4 Hz, J = 8.3 Hz, 1H, CH ), 2.19 (s, 3H, CH ).
2 2 3
13
C NMR (100 MHz, CDCl ): δ 160.0 (Ph 1 C-4), 157.6 (Ph 1 C-2), 144.8 (Ph 2 C-1), 132.9 (Ph 3 C-2,6), 130.2
3
(
(
(
Ph 3 C-1), 129.5 (Ph 2 C-3,5), 128.9 (Ph 3 C-3,5), 128.0 (Ph 1 C-6), 126.9 (Ph 3 C-4), 126.6 (Ph 2 C-4), 122.2
Ph 1 C-1), 113.8 (Ph 2 C-2,6), 104.1 (Ph 1 C-5), 98.7 (Ph 1 C-3), 55.3 (4-OCH ), 55.2 (2-OCH ), 53.0 (CH), 34.2
3
3
CH ), 20.3 (CH ).
2
3
77
Se NMR (76 MHz, CDCl ): δ 263.3 (m).
3
15
N NMR (40 MHz, CDCl ): δ -308.0.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NO Se: 428.1123; found: 428.1120.
23
26
2
4
-bromo-N-[1-(4-methoxyphenyl)-2-(phenylselanyl)ethyl]aniline (5)
1
0

By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and 4-bromo-N-(4-
methoxybenzylidene)aniline (0.290 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 5 was obtained in
2
8
9
5 % yield (0.392 g) as yellow oil after purification by column chromatography on silica gel (n-hexane:EtOAc
8:2).
1
H NMR (400 MHz, CDCl ): δ 7.51 (m, 2H, Ph 3 H-2,6), 7.28 (m, 1H, Ph 3 H-4), 7.27 (m, 2H, Ph 3 H-3,5), 7.22
3
3
(
m, 2H, Ph 1 H-2,6), 7.13 (m, 2H, Ph 2 H-3,5), 6.84 (m, 2H, Ph 1 H-3,5), 6.30 (m, 2H, Ph 2 H-2,6), 4.34 (dd, J
3
2
3
=
8.8 Hz, J = 4.6 Hz, 1H, CH), 3.8-5.0 (brs, 1H, NH), 3.78 (s, 3H, OCH ), 3.32 (dd, J = 12.6 Hz, J = 4.6 Hz, 1H,
3
2
3
CH ), 3.15 (dd, J = 12.6 Hz, J = 8.8 Hz, 1H, CH ).
2
2
13
C NMR (100 MHz, CDCl ): δ 159.1 (Ph 1 C-4), 146.0 (Ph 2 C-1), 134.0 (Ph 1 C-1), 133.6 (Ph3 C-2,6), 131.7
3
(
Ph 2 C-3,5), 129.3 (Ph 3 C-3,5), 129.0 (Ph 3 C-1), 127.6 (Ph 3 C-4), 127.3 (Ph 1 C-2,6), 115.3 (Ph 2 C-2,6),
14.2 (Ph 1 C-3,5), 109.5 (Ph 2 C-4), 57.2 (CH), 55.2 (OCH ), 36.4 (CH ).
1
3
2
77
Se NMR (76 MHz, CDCl ): δ 265.9 (m).
3
15
N NMR (40 MHz, CDCl ): δ -303.9.
3
+
HRMS (ESI), m/z [M + Na] calcd. for C H BrNNaOSe: 483.9786; found: 483.9785.
21 20
N-[1-(4-chlorophenyl)-2-(phenylselanyl)ethyl]-4-methylaniline (6)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-chlorobenzylidene)-4-
methylaniline (0.229 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 6 was obtained in 87 % yield
0.349 g) as brown oil after purification by column chromatography on silica gel (n-hexane:EtOAc 99:1).
(
1
1

1
H NMR (400 MHz, CDCl ): δ 7.51 (m, 2H, Ph 3 H-2,6), 7.27 (m, 7H, Ph 1 H-2,3,5,6, Ph 3 H-3,4,5), 6.90 (m,
3
3
3
2
H, Ph 2 H-3,5), 6.35 (m, 2H, Ph 2 H-2,6), 4.40 (dd, J = 8.8 Hz, J = 4.6 Hz, 1H, CH), 4.36 (brs, 1H, NH), 3.32
2
3
2
3
(
dd, J = 12.6 Hz, J = 4.5 Hz, 1H, CH ), 3.16 (dd, J = 12.6 Hz, J = 8.8 Hz, 1H, CH ), 2.20 (s, 3H, CH ).
2 2 3
13
C NMR (100 MHz, CDCl ): δ 144.4 (Ph 2 C-1), 141.3 (Ph 1 C-1), 133.6 (Ph 3 C-2,6), 133.0 (Ph 1 C-4), 129.6
3
(
Ph 2 C-3,5), 129.3 (Ph 3 C-3,5), 129.0 (Ph 3 C-1), 128.9 (Ph 1 C-3,5), 127.7 (Ph1 C-2,6), 127.6 (Ph 3 C-4),
27.3 (Ph 2 C-4), 113.9 (Ph 2 C-2,6), 57.4 (CH), 36.4 (CH ), 20.3 (CH ).
1
2
3
77
Se NMR (76 MHz, CDCl ): δ 266.0 (m).
3
15
N NMR (40 MHz, CDCl ): δ -307.1.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H ClNSe: 402.0522; found: 402.0523.
21 21
N-[1-(4-fluorophenyl)-2-(phenylselanyl)ethyl]-4-methylaniline (7)
Me
Ph 2
HN
Se
Ph 1
Ph 3
F
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-fluorobenzylidene)-4-
methylaniline (0.213 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 7 was obtained in 92 % yield
2
(
0.353 g) as yellow oil after purification by column chromatography on silica gel (n-hexane:EtOAc 99:1).
1
H NMR (400 MHz, CDCl ): δ 7.50 (m, 2H, Ph 3 H-2,6), 7.30 (m, 2H, Ph 1 H-2,6), 7.27 (m, 1H, Ph 3 H-4), 7.26
3
3
(
m, 2H, Ph 3 H-3,5), 6.98 (m, 2H, Ph 1 H-3,5), 6.89 (m, 2H, Ph 2 H-3,5), 6.36 (m, 2H, Ph 2 H-2,6), 4.41 (dd, J
3
2
3
2
=
1
8.7 Hz, J = 4.8 Hz, 1H, CH), 4.35 (brs, 1H, NH), 3.32 (dd, J = 12.6 Hz, J = 4.8 Hz, 1H, CH ), 3.18 (dd, J =
2
3
2.6 Hz, J = 8.7 Hz, 1H, CH ), 2.19 (s, 3H, CH ).
2
3
1
3
1
4
C NMR (100 MHz, CDCl ): δ 162.1 (d, J = 245.5 Hz, Ph 1 C-4), 144.4 (Ph 2 C-1), 138.3 (d, J = 3.1 Hz, Ph
3
C,F
C,F
3
1
1
3
C-1), 133.5 (Ph 3 C-2,6), 129.6 (Ph 2 C-3,5), 129.3 (Ph 3 C-3,5), 129.1 (Ph 3 C-1), 127.9 (d, J = 8.0 Hz, Ph
C,F
2
C-2,6), 127.5 (Ph 3 C-4), 127.4 (Ph 2 C-4), 115.6 (d, J = 21.4 Hz, Ph 1 C-3,5), 114.0 (Ph 2 C-2,6), 57.5 (CH),
C,F
6.5 (CH ), 20.3 (CH ).
2
3
7
1
1
7
Se NMR (76 MHz, CDCl ): δ 265.6 (m).
3
9
F NMR (376 MHz, CDCl ): δ -115.2 (m).
3
5
N NMR (40 MHz, CDCl ): δ -312.9.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H FNSe: 386.0818; found: 386.0812.
21 21
1
2

N-[1-[4-bromophenyl)-2-(phenylselanyl)ethyl]-4-methylaniline (8)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-bromobenzylidene)-4-
methylaniline (0.274 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 8 was obtained in 86 % yield
(
0.383 g) as yellowish oil after purification by column chromatography on silica gel (n-hexane:EtOAc 98:2).
1
H NMR (400 MHz, CDCl ): δ 7.49 (m, 2H, Ph 3 H-2,6), 7.40 (m, 2H, Ph 1 H-3,5), 7.27 (m, 1H, Ph 3 H-4), 7.26
3
3
(
m, 2H, Ph 3 H-3,5), 7.21 (m, 2H, Ph 1 H-2,6), 6.89 (m, 2H, Ph 2 H-3,5), 6.36 (m, 2H, Ph 2 H-2,6), 4.37 (dd, J
3
2
3
2
=
1
8.6 Hz, J = 4.8 Hz, 1H, CH), 4.0-5.0 (brs, 1H, NH), 3.32 (dd, J = 12.6 Hz, J = 4.8 Hz, 1H, CH ), 3.18 (dd, J =
2
3
2.6 Hz, J = 8.6 Hz, 1H, CH ), 2.19 (s, 3H, CH ).
2
3
13
C NMR (100 MHz, CDCl ): 144.0 (Ph 2 C-1), 141.6 (Ph 1 C-1), 133.6 (Ph 3 C-2,6), 131.8 (Ph 1 C-3,5), 129.6
3
(
Ph 2 C-3,5), 129.3 (Ph 3 C-3,5), 129.0 (Ph 3 C-1), 128.2 (Ph 1 C-2,6), 127.6 (Ph 2 C-4, Ph 3 C-4), 121.2 (Ph 1
C-4), 114.2 (Ph 2 C-2,6), 57.8 (CH), 36.1 (CH ), 20.4 (CH ).
2
3
77
Se NMR (76 MHz, CDCl ): δ 266.5 (m).
3
+
HRMS (ESI), m/z [M + H] calcd. for C H BrNSe: 446.0017; found: 446.0021.
21 21
N-[1-(4-chlorophenyl)-2-(phenylselanyl)ethyl]-4-fluoroaniline (9)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-chlorobenzylidene)-4-
fluoroaniline (0.233 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 9 was obtained in 88 % yield
0.356 g) as yellowish oil after purification by column chromatography on silica gel (n-hexane:EtOAc 98:2).
(
1
3

1
H NMR (400 MHz, CDCl ): δ 7.50 (m, 2H, Ph 3 H-2,6), 7.27 (m, 7H, Ph 1 H-2,3,5,6, Ph 3 H-3,4,5), 6.78 (m,
3
3
3
2
H, Ph 2 H-3,5), 6.35 (m, 2H, Ph 2 H-2,6), 4.31 (dd, J = 8.9 Hz, J = 4.5 Hz, 1H, CH), 4.0-4.9 (brs, 1H, NH), 3.32
2
3
2
3
(
dd, J = 12.7 Hz, J = 4.5 Hz, 1H, CH ), 3.14 (dd, J = 12.7 Hz, J = 8.9 Hz, 1H, CH ).
2 2
13
1
C NMR (100 MHz, CDCl ): δ 156.2 (d, J = 235.9 Hz, Ph 2 C-4), 142.9 (Ph 2 C-1), 140.8 (Ph 1 C-1), 133.7
3
C,F
(
Ph 3 C-2,6), 133.3 (Ph 1 C-4), 129.3 (Ph 3 C-3,5), 129.0 (Ph 1 C-3,5), 128.7 (Ph 3 C-1), 127.7 (Ph 1 C-2,6, Ph 3
2
C-4), 115.6 (d, J = 22.4 Hz, Ph 2 C-3,5), 114.8 (m, Ph 2 C-2,6), 58.0 (CH), 36.2 (CH ).
C,F
2
77
19
15
Se NMR (76 MHz, CDCl ): δ 266.6 (m).
3
F NMR (376 MHz, CDCl ): δ -127.0 (m).
3
N NMR (40 MHz, CDCl ): δ -307.9.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H ClFNSe: 406.0272; found: 406.0270.
20 18
4
-{1-[(4-methylphenyl)amino]-2-(phenylselanyl)ethyl}benzonitrile (10)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and 4-((p-
2
tolylimino)methyl)benzonitrile (0.220 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 10 was obtained
in 92 % yield (0.360 g) as yellowish oil after purification by column chromatography on silica gel (n-
hexane:EtOAc 99:1).
1
H NMR (400 MHz, CDCl ): δ 7.57 (m, 2H, Ph 1 H-2,6), 7.49 (m, 2H, Ph 3 H-2,6), 7.45 (m, 2H, Ph 1 H-3,5),
3
7
.28 (m, 1H, Ph 3 H-4), 7.26 (m, 2H, Ph 3 H-3,5), 6.89 (m, 2H, Ph 2 H-3,5), 6.32 (m, 2H, Ph 2 H-2,6), 4.44 (dd,
3
3
2
3
2
J = 8.7 Hz, J = 4.5 Hz, 1H, CH), 4.1-4.9 (brs, 1H, NH), 3.32 (dd, J = 12.8 Hz, J = 4.5 Hz, 1H, CH ), 3.16 (dd, J
2
3
=
12.8 Hz, J = 8.7 Hz, 1H, CH ), 2.19 (s, 3H, CH ).
2 3
13
C NMR (100 MHz, CDCl ): δ 148.3 (Ph 1 C-4), 143.9 (Ph 2 C-1), 133.7 (Ph 3 C-2,6), 132.6 (Ph 1 C-2,6), 129.7
3
(
Ph 2 C-3,5), 129.3 (Ph 3 C-3,5), 128.6 (Ph 3 C-1), 127.8 (Ph 2 C-4, Ph 3 C-4), 127.3 (Ph 1 C-3,5), 118.7 (C≡N),
14.0 (Ph 2 C-2,6), 111.3 (Ph 1 C-1), 57.9 (CH), 35.9 (CH ), 20.3 (CH ).
1
2
3
77
Se NMR (76 MHz, CDCl ): δ 267.8
3
15
N NMR (40 MHz, CDCl ): δ -308.3
3
1
4

+
HRMS (ESI), m/z [M + H] calcd. for C H N Se: 393.0864; found: 393.0866.
22
21
2
N-[1-phenyl-2-(phenylselanyl)ethyl]aniline (11)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-benzylideneaniline (0.181
g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 11 was obtained in 89 % yield (0.313 g) as yellow solid
after purification by column chromatography on silica gel (n-hexane:EtOAc 99:1).
mp: 125-127 °C
1
H NMR (400 MHz, CDCl ): δ 7.52 (m, 2H, Ph 3 H-2,6), 7.35 (m, 2H, Ph 1 H-2,6), 7.31 (m, 2H, Ph 1 H-3,5),
3
7
2
.27 (m, 3H, Ph 3 H-3,4,5), 7.25 (m, 1H, Ph 1 H-4), 7.07 (m, 2H, Ph 2 H-3,5), 6.67 (m, 1H, Ph 2 H-4), 6.45 (m,
3
3
2
3
H, Ph 2 H-2,6), 4.46 (dd, J = 8.8 Hz, J = 4.7 Hz, 1H, CH), 4.3-4.7 (brs, 1H, NH), 3.37 (dd, J = 12.6 Hz, J = 4.7
2
3
Hz, 1H, CH ), 3.22 (dd, J = 12.6 Hz, J = 8.8 Hz, 1H, CH ).
2
2
13
C NMR (100 MHz, CDCl ): δ 147.0 (Ph 2 C-1), 142.6 (Ph 1 C-1), 133.5 (Ph 3 C-2,6), 129.3 (Ph 3 C-1), 129.2
3
(
Ph 3 C-3,5), 129.0 (Ph 2 C-3,5), 128.8 (Ph 1 C-3,5), 127.53 (Ph 3 C-4), 127.49 (Ph 1 C-4), 126.3 (Ph 1 C-2,6),
1
17.8 (Ph 2 C-4), 113.8 (Ph 2 C-2,6), 57.9 (CH), 36.4 (CH2).
77
Se NMR (76 MHz, CDCl ): δ 266.7 (m)
3
15
N NMR (40 MHz, CDCl ): δ -305.1.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NSe: 354.0755; found: 354.0751.
20 20
N-[1-(2-furyl)-2-(phenylselanyl)ethyl]-4-methylaniline (12)
1
5

By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(furan-2-ylmethylene)-4-
methylaniline (0.185 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 12 was obtained in 86 % yield
2
(
0.306 g) as yellow oil after purification by column chromatography on silica gel (n-hexane:EtOAc 99:1).
1
3
4
H NMR (400 MHz, CDCl ): δ 7.49 (m, 2H, Ph 2 H-2,6), 7.30 (dd, J = 1.8 Hz, J = 0.9 Hz, 1H, Furyl H-5), 7.25
3
3
3
(
m, 3H, Ph 2 H-3,4,5), 6.93 (m, 2H, Ph 1 H-3,5), 6.45 (m, 2H, Ph 1 H-2,6), 6.27 (dd, J = 3.2 Hz, J = 1.8 Hz, 1H,
2
3
Furyl H-4), 6.19 (m, 1H, Furyl H-3), 4.68 (m, 1H, CH), 4.03-4.30 (brs, 1H, NH), 3.40 (dd, J = 12.5 Hz, J = 6.5
2
3
Hz, 1H, CH ), 3.36 (dd, J = 12.5 Hz, J = 6.3 Hz, 1H, CH ), 2.21 (s, 3H, CH ).
2
2
3
13
C NMR (100 MHz, CDCl ): δ 154.6 (Furyl C-2), 144.1 (Ph 1 C-1), 141.8 (Furyl C-5), 133.4 (Ph 2 C-2,6), 129.7
3
(
(
Ph 1 C-3,5), 129.5 (Ph 2 C-1), 129.1 (Ph 2 C-3,5), 127.6 (Ph 1 C-4), 127.3 (Ph 2 C-4), 114.0 (Ph 1 C-2,6), 110.3
Furyl C-4), 106.8 (Furyl C-3), 52.4 (CH), 32.9 (CH ), 20.4 (CH ).
2
3
77
Se NMR (76 MHz, CDCl ): δ 262.2 (m).
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NOSe: 358.0705; found: 358.0707.
19 20
N-(1-(naphthalen-2-yl)-2-(phenylselanyl)ethyl)benzenesulfonamide (13)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(naphthalen-2-
ylmethylene)benzenesulfonamide (0.295 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 13 was
obtained in 89 % yield (0.414 g) as colourless oil after purification by column chromatography on silica gel
(
n-hexane:EtOAc 9:1).
1
H NMR (400 MHz, CDCl ): δ 7.74 (m, 1H, Naph H-5), 7.67 (m, 1H, Naph H-8), 7.63 (m, 1H, Naph H-4), 7.61
3
(
m, 2H, Ph 1 H-2,6), 7.46 (m, 1H, Naph H-1), 7.45 (m, 2H, Naph H-6, Naph H-7), 7.38 (m, 1H, Ph 1 H-4), 7.37
m, 2H, Ph 2 H-2,6), 7.24 (m, 3H, Ph 1 H-3,5, Ph 2 H-4), 7.22 (m, 2H, Ph 2 H-3,5), 7.14 (m, 1H, Naph H-3),
(
3
2
3
2
5
.43 (d, J = 5.5 Hz, 1H, NH), 4.58 (m, 1H, CH), 3.32 (dd, J = 12.8 Hz, J = 7.3 Hz, 1H, CH ), 3.25 (dd, J = 12.8
2
3
Hz, J = 6.4 Hz, 1H, CH ).
2
13
C NMR (100 MHz, CDCl ): δ 139.9 (Ph1 C-1), 136.4 (Naph C-2), 133.3 (Ph 2 C-2,6), 132.96 (Naph C-8a),
3
1
32.94 (Naph C-4a), 132.4 (Ph 1 C-4), 129.3 (Ph 2 C-3,5), 128.7 (Ph 1 C-3,5), 128.52 (Naph C-4), 128.51 (Ph 2
C-1), 127.9 (Naph C-8), 127.59 (Ph 2 C-4), 127.77 (Naph C-5), 127.1 (Ph 1 C-2,6), 126.3 (Naph C-7), 126.2
(
Naph C-6), 126.1 (Naph C-1), 124.0 (Naph C-3), 57.3 (CH), 35.0 (CH2).
77
Se NMR (76 MHz, CDCl ): δ 257.8 (m).
3
1
6

15
N NMR (40 MHz, CDCl ): δ -271.7.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NO SSe: 468.0531; found: 468.0532.
24
22
2
11
4
-methyl-N-[1-phenyl-2-(phenylselanyl)ethyl]benzenesulfonamide (14)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-benzylidene-4-
methylbenzenesulfonamide (0.261 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 14 was obtained in
1 % yield (0.391 g) as white solid after purification by column chromatography on silica gel (n-
2
9
hexane:EtOAc 99:1).
mp: 92-93 °C (lit. 92-93 °C).
1
H NMR (400 MHz, CDCl ): δ 7.51 (m, 2H, Ph 2 H-2,6), 7.34 (m, 2H, Ph 3 H-2,6), 7.26 (m, 1H, Ph 3 H-4), 7.22
3
(
m, 2H, Ph 3 H-3,5), 7.20 (m, 2H, Ph 1 H-3,5), 7.19 (m, 1H, Ph 1 H-4), 7.12 (m, 2H, Ph 2 H-3,5), 7.06 (m, 2H,
2
3
2
Ph 1 H-2,6), 5.27 (m, 1H, NH), 4.37 (m, 1H, CH) 3.24 (dd, J = 12.8Hz, J = 7.2Hz, 1H, CH ), 3.16 (dd, J = 12.8
2
3
Hz, J = 6.4 Hz, 1H, CH ), 2.37 (s, 3H, CH ).
2
3
13
C NMR (100 MHz, CDCl ): δ 143.2 (Ph 2 C-4), 139.5 (Ph 1 C-1), 136.9 (Ph 2 C-1), 133.2 (Ph 3 C-2,6), 129.4
3
(
(
Ph 2 C-3,5), 129.2 (Ph 3 C-3,5), 128.7 (Ph 3 C-1), 128.5 (Ph 1 C-3,5), 128.0 (Ph 1 C-4), 127.5 (Ph 3 C-4), 127.2
Ph 2 C-2,6), 126.6 (Ph 1 C-2,6), 57.1 (CH), 35.1 (CH ), 21.5 (CH ).
2
3
77
Se NMR (76 MHz, CDCl ): δ 256.8 (m)
3
15
N NMR (40 MHz, CDCl ): δ -271.4.
3
+
HRMS (ESI), m/z [M + Na] calcd. for C H NNaO SSe: 454.0350; found: 454.0342.
21
21
2
N-{1-[4-chloro-3-(trifluoromethyl)phenyl]-2-(phenylselanyl)ethyl} benzensulfonamide (15)
1
7

By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-chloro-3-
trifluoromethyl)benzylidene)benzenesulfonamide (0.347 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL),
2
(
compound 15 was obtained in 85 % yield (0.440 g) as yellow solid after purification by column
chromatography on silica gel (n-hexane:EtOAc 99:1).
mp: 125-126 °C
1
H NMR (400 MHz, CDCl ): δ 7.59 (m, 2H, Ph 2 H-2,6), 7.50 (m, 1H, Ph 2 H-4) 7.35 (m, 2H, Ph 2 H-3,5), 7.32
3
(
m, 2H, Ph 3 H-2,6), 7.28 (m, 1H, Ph 3 H-4), 7.25 (m, 1H, Ph 1 H-5), 7.23 (m, 1H, Ph 1 H-2), 7.22 (m, 2H, Ph 3
3
3
H-3,5), 7.18 (m, 1H, Ph 1 H-6), 5.43 (d, J = 5.0 Hz, 1H, NH), 4.45 (m, 1H, CH) 3.11 (d, J = 6.6 Hz, 2H, CH ).
2
1
3
C NMR (100 MHz, CDCl ): δ 139.7 (Ph 2 C-1), 138.5 (Ph 1 C-1), 133.7 (Ph 3 C-2,6), 132.9 (Ph 2 C-4), 131.8
3
3
(
2
q, J = 1.9 Hz, Ph 1 C-4), 131.4 (Ph 1 C-5), 131.3 (Ph 1 C-6), 129.4 (Ph 3 C-3,5), 128.9 (Ph 2 C-3,5), 128.3 (q,
C,F
3
J = 31.5 Hz, Ph 1 C-3), 128.1 (Ph 3 C-4), 127.6 (Ph 3 C-1), 127.1 (Ph 2 C-2,6), 125.9 (q, J = 5.4 Hz, Ph 1 C-
C,F
C,F
1
2
), 122.4 (q, J = 273.7 Hz, CF ), 56.2 (CH), 34.9 (CH ).
C,F 3 2
19
F NMR (376 MHz, CDCl ): δ -62.7 (s, CF ).
3
3
15
N NMR (40 MHz, CDCl ): δ -272.8.
3
+
HRMS (ESI), m/z [M + Na] calcd. for C H ClF NNaO SSe: 541.9678; found: 541.9691.
21
17
3
2
N-[1-(4-bromophenyl)-2-(phenylselanyl)ethyl]benzenesulfonamide (16)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-
2
bromobenzylidene)benzenesulfonamide (0.324 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 16 was
obtained in 90 % yield (0.445 g) as white solid after purification by column chromatography on silica gel (n-
hexane:EtOAc 99:1).
1
8

mp: 124-125 °C
1
H NMR (400 MHz, CDCl ): δ 7.61 (m, 2H, Ph 2 H-2,6), 7.50 (m, 1H, Ph 2 H-4), 7.35 (m, 2H, Ph 2 H-3,5), 7.33
3
(
m, 2H, Ph 3 H-2,6), 7.27 (m, 1H, Ph 3 H-4), 7.27 (m, 2H, Ph 1 H-3,5), 7.22 (m, 2H, Ph 3 H-3,5), 6.91 (m, 2H,
3
2
3
Ph 1 H-2,6), 5.37 (d, J = 5.5 Hz, 1H, NH), 4.35 (m, 1H, CH), 3.16 (dd, J = 12.9 Hz, J = 7.4 Hz, 1H, CH ), 3.11
2
2
3
(
dd, J = 12.9 Hz, J = 6.2 Hz, 1H, CH ).
2
13
C NMR (100 MHz, CDCl ): δ 139.8 (Ph 2 C-1), 138.4 (Ph 1 C-1), 133.4 (Ph 3 C-2,6), 132.6 (Ph 2 C-4), 131.6
3
(
Ph 1 C-3,5), 129.4 (Ph 3 C-3,5), 128.9 (Ph 2 C-3,5), 128.4 (Ph 1 C-2,6), 128.2 (Ph 3 C-1), 127.8 (Ph 3 C-4),
1
27.1 (Ph 2 C-2,6), 122.0 (Ph 1 C-4), 56.6 (CH), 34.9 (CH2).
77
Se NMR (76 MHz, CDCl ): δ 257.9 (m).
3
15
N NMR (40 MHz, CDCl ): δ -272.2.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H BrNO SSe: 495.9480; found: 495.9476.
20
19
2
N-[1-(4-fluorophenyl)-2-(phenylselanyl)ethyl]benzenesulfonamide (17)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(4-
fluorobenzylidene)benzenesulfonamide (0.263 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 17 was
obtained in 92 % yield (0.399 g) as yellowish solid after purification by column chromatography on silica gel
(
n-hexane:EtOAc 98:2).
mp: 99-102 °C
1
H NMR (400 MHz, CDCl ): δ 7.61 (m, 2H, Ph 2 H-2,6), 7.48 (m, 1H, Ph 2 H-4), 7.35 (m, 2H, Ph 3 H-2,6), 7.34
3
(
m, 2H, Ph 2 H-3,5), 7.27 (m, 1H, Ph 3 H-4), 7.23 (m, 2H, Ph 3 H-3,5), 7.00 (m, 2H, Ph 1 H-2,6), 6.83 (m, 2H,
3
2
3
Ph 1 H-3,5), 5.38 (d, 1H, J = 5.4 Hz, 1H, NH), 4.38 (m, 1H, CH), 3.18 (dd, J = 12.9 Hz, J = 7.4 Hz, 1H, CH ),
2
2
3
3
.12 (dd, J = 12.9 Hz, J = 6.3 Hz, 1H, CH ).
2
1
3
1
4
C NMR (100 MHz, CDCl ): δ 162.3 (d, J = 247.0 Hz, Ph 1 C-4), 139.9 (Ph 2 C-1), 135.1 (d, J = 3.2 Hz, Ph
3
C,F
C,F
3
1
C-1), 133.4 (Ph 3 C-2,6), 132.6 (Ph 2 C-4), 129.3 (Ph 3 C-3,5), 128.8 (Ph 2 C-3,5), 128.4 (d, J = 8.3 Hz, Ph 1
C,F
2
C-2,6), 128.3 (Ph 3 C-1), 127.7 (Ph 3 C-4), 127.1 (Ph 2 C-2,6), 115.4 (d, J = 21.6 Hz, Ph 1 C-3,5), 56.5 (CH),
C,F
3
5.1 (CH2).
77
Se NMR (76 MHz, CDCl ): δ 258.0 (m).
3
1
9

1
9
5
F NMR (376 MHz, CDCl ): δ -113.9 (m).
3
1
N NMR (40 MHz, CDCl ): δ -271.6.
3
+
HRMS (ESI), m/z [M + Na] calcd. for C H FNNaO SSe: 458.0100; found: 458.0108.
20
18
2
N-[1-(2-furyl)-2-(phenylselanyl)ethyl]benzenesulfonamide (18)
By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
2
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(furan-2-
ylmethylene)benzenesulfonamide (0.235 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 18 was
obtained in 87 % yield (0.353 g) as yellowish oil after purification by column chromatography on silica gel
(
n-hexane:EtOAc 9:1).
1
H NMR (400 MHz, CDCl ): δ 7.70 (m, 2H, Ph 1 H-2,6), 7.50 (m, 1H, Ph 1 H-4), 7.39 (m, 2H, Ph 1 H-3,5), 7.39
3
3
4
(
m, 2H, Ph2 H-2,6), 7.25 (m, 1H, Ph 2 H-4), 7.24 (m, 2H, Ph 2 H-3,5), 7.11 (dd, J = 1.8 Hz, J = 0.8 Hz, 1H,
3
3
3
Furyl H-5), 6.12 (dd, J = 3.3 Hz, J = 1.8 Hz, 1H, Furyl H-4), 5.99 (m, 1H, Furyl H-3), 5.30 (d, J = 8.0 Hz, 1H,
2
3
2
3
NH), 4.63 (m, 1H, CH), 3.36 (dd, J = 12.7 Hz, J = 5.7 Hz, 1H, CH ), 3.17 (dd, J = 12.7 Hz, J = 7.3 Hz, 1H, CH ).
2
2
13
C NMR (100 MHz, CDCl ): δ 151.2 (Furyl C-2), 142.2 (Furyl C-5), 140.2 (Ph 1 C-1), 133.2 (Ph 2 C-2,6), 132.5
3
(
(
Ph 1 C-4), 129.2 (Ph 2 C-3,5), 128.9 (Ph 1 C-3,5), 128.8 (Ph 2 C-1), 127.4 (Ph 2 C-4), 127.0 (Ph 1 C-2,6), 110.2
Furyl C-4), 108.0 (Furyl C-3), 51.4 (CH), 32.5 (CH2).
77
Se NMR (76 MHz, CDCl ): δ 260.3 (m).
3
15
N NMR (40 MHz, CDCl ): δ -274.5.
3
+
HRMS (ESI), m/z [M + Na] calcd. for C H NNaO SSe: 429.9987; found: 429.9987.
18
17
3
N-[2-(phenylselanyl)-1-(2-thienyl)ethyl]benzenesulfonamide (19)
2
0

By Following the general procedure, starting from 1,1’-(methylenediselanyl)dibenzene (0.652 g, 2.0 mmol,
.0 equiv) in dry THF (2 mL), n-BuLi (2.5 M, 0.76 mL, 1.9 mmol, 1.9 equiv) and N-(thiophen-2-
2
ylmethylene)benzenesulfonamide (0.251 g, 1.0 mmol, 1.0 equiv) in dry THF (1 mL), compound 19 was
obtained in 90 % yield (0.379 g) as yellowish oil after purification by column chromatography on silica gel
(
n-hexane:EtOAc 9:1).
1
H NMR (400 MHz, CDCl ): δ 7.68 (m, 2H, Ph 1 H-2,6), 7.50 (m, 1H, Ph 1 H-4), 7.42 (m, 2H, Ph 2 H-2,6), 7.37
3
3
4
(
m, 2H, Ph 1 H-3,5), 7.27 (m, 1H, Ph 2 H-4), 7.26 (m, 2H, Ph 2 H-3,5), 7.12 (dd, J = 5.1 Hz, J = 1.2 Hz, 1H, Th
3
3
3
H-5), 6.81 (dd, J = 5.1 Hz, J = 3.5 Hz, 1H, Th H-4), 6.74 (m, 1H, Th H-3), 5.31 (d, J = 6.8 Hz, 1H, NH), 4.79 (m,
2
3
2
3
1
H, CH), 3.40 (dd, J = 12.8 Hz, J = 6.0 Hz, 1H, CH ), 3.20 (dd, J = 12.8 Hz, J = 6.7 Hz, 1H, CH ).
2 2
13
C NMR (100 MHz, CDCl ): δ 143.1 (Th C-2), 140.0 (Ph 1 C-1), 133.3 (Ph 2 C-2,6), 132.6 (Ph 1 C-4), 129.3 (Ph
3
2
C-3,5), 128.9 (Ph 1 C-3,5), 128.8 (Ph 2 C-1), 127.6 (Ph 2 C-4), 127.1 (Ph 1 C-2,6), 126.7 (Th C-4), 125.5 (Th
C-3), 125.4 (Th C-5), 53.1 (CH), 35.7 (CH2).
77
Se NMR (76 MHz, CDCl ): δ 259.0 (m).
3
15
N NMR (40 MHz, CDCl ): δ -268.8.
3
+
HRMS (ESI), m/z [M + H] calcd. for C H NO S Se: 423.9939; found: 423.9936.
18
18
2 2
Acknowledgments. The Authors are grateful to the University of Vienna for generous support. S. T. thanks
the OEAD for a Pakistan-Austria doctoral grant. R. L. thanks the University of Pavia for a visiting PhD
fellowship.
References
(1) For authoritative references, see: (a) Organoselenium Chemistry: Modern Developments in Organic Synthesis in
Top. Curr. Chem.; Wirth, T., Ed.; Springer: Berlin, Heidelberg, 2000; Vol. 208. (b) Freudendahl, D. M.; Santoro, S.;
Shahzad, S. A.; Santi, C.; Wirth, T. Angew. Chem. Int. Ed. 2009, 48, 8409-8411. (c) Freudendahl, D. M.; Shahzad, S. A.;
Wirth, T. Eur. J. Org. Chem. 2009, 2009, 1649-1664. (d) Wirth, T. Organoselenium Chemistry: Synthesis and Reactions;
Wiley-VCH: Weinheim, 2011. (e) Mukherjee, A. J.; Zade, S. S.; Singh, H. B.; Sunoj, R. B. Chem. Rev. 2010, 110, 4357-
4
(
416. (f) Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Pergamon: Oxford, 1986.
2) For excellent reviews, see: (a) Weekley, C. M.; Harris, H. H. Chem. Soc. Rev. 2013, 42, 8870-8894. (b) Nogueira, C.
W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004, 104, 6255-6286.
3) (a) Sarma, B. K.; Mugesh, G. J. Am. Chem. Soc. 2005, 127, 11477-11485. (b) Mugesh, G.; du Mont, W.-W.; Sies, H.
(
Chem. Rev. 2001, 101, 2125-2180. (c) Bhuyan, B. J.; Mugesh, G. Biological and Biochemical Aspects of Selenium
Compounds. In Organoselenium Chemistry; Wiley-VCH Verlag GmbH & Co. KGaA: 2011; pp. 361-396. (d) Sands, K. N.;
Back, T. G. Tetrahedron 2018, 74, 4959-4967.
(
4) (a) Mailyan, A. K.; Eickhoff, J. A.; Minakova, A. S.; Gu, Z.; Lu, P.; Zakarian, A. Chem. Rev. 2016, 116, 4441-4557. (b)
Bariwal, J.; Van der Eycken, E. Chem. Soc. Rev. 2013, 42, 9283-9303.
5) (a) Miniejew, C.; Outurquin, F.; Pannecoucke, X. Org. Biomol. Chem. 2004, 2, 1575-1576. (b) Ward, V. R.; Cooper,
(
M. A.; Ward, A. D. J. Chem. Soc., Perkin Trans. 1 2001, 944-945. (c) Demarcus, M.; Filigheddu, S. N.; Mann, A.; Taddei,
M. Tetrahedron Lett. 1999, 40, 4417-4420.
(6) (a) Besev, M.; Engman, L. Org. Lett. 2000, 2, 1589-1592. (b) Shanks, D.; Berlin, S.; Beşev, M.; Ottosson, H.; Engman,
L. J. Org. Chem. 2004, 69, 1487-1491.
2
1

(
(
7) For comprehensive overviews, see: (a) Manjare, S. T.; Kim, Y.; Churchill, D. G. Acc. Chem. Res. 2014, 47, 2985-2998.
b) Selenium and Tellurium Chemistry. From Small Molecules to Biomolecules and Materials; Woollins, J. D.; Laitinen,
R., Eds.; Springer-Verlag: Berlin, 2011.
(
(
(
8) Tang, E.; Wang, W.; Zhao, Y.; Zhang, M.; Dai, X. Org. Lett. 2016, 18, 176-179.
9) Sun, L.; Yuan, Y.; Yao, M.; Wang, H.; Wang, D.; Gao, M.; Chen, Y.-H.; Lei, A. Org. Lett. 2019, 21, 1297-1300.
10) (a) Sun, K.; Wang, X.; Lv, Y.; Li, G.; Jiao, H.; Dai, C.; Li, Y.; Zhang, C.; Liu, L. Chem. Commun. 2016, 52, 8471-8474. (b)
Liu, Y.; Li, C.; Mu, S.; Li, Y.; Feng, R.; Sun, K. Asian J. Org. Chem. 2018, 7, 720-723.
(
(
(
11) Ganesh, V.; Chandrasekaran, S. Synthesis 2009, 3267-3278.
12) Miniejew, C.; Outurquin, F.; Pannecoucke, X. Tetrahedron 2005, 61, 447-456.
13) For precedents from our group, see: (a) Castoldi, L.; Monticelli, S.; Senatore, R.; Ielo, L.; Pace, V. Chem. Commun.
2
2
018, 54, 6692-6704. (b) Pace, V. Aust. J. Chem. 2014, 67, 311-313. (c) Pace, V.; Holzer, W.; De Kimpe, N. Chem. Rec.
016, 16, 2061-2076. (d) Pace, V.; Castoldi, L.; Monticelli, S.; Rui, M.; Collina, S. Synlett 2017, 28, 879-888. (e)
Monticelli, S.; Urban, E.; Langer, T.; Holzer, W.; Pace, V. Adv. Synth. Catal. 2019, 361, 1001-1006.. (f) Pace, V.; Castoldi,
L.; Mamuye, A. D.; Langer, T.; Holzer, W. Adv. Synth. Catal. 2016, 358, 172-177. (g) Ielo, L.; Touqeer, S.; Roller, A.;
Langer, T.; Holzer, W.; Pace, V. Angew. Chem. Int. Ed. 2019, 58, 2479-2484. (h) Pace, V.; Castoldi, L.; Mazzeo, E.; Rui,
M.; Langer, T.; Holzer, W. Angew. Chem. Int. Ed. 2017, 56, 12677-12682. (i) Pace, V.; Castoldi, L.; Monticelli, S.;
Safranek, S.; Roller, A.; Langer, T.; Holzer, W. Chem. Eur. J. 2015, 21, 18966-18970. (j) Castoldi, L.; Ielo, L.; Holzer, W.;
Giester, G.; Roller, A.; Pace, V. J. Org. Chem. 2018, 83, 4336-4347. (k) Parisi, G.; Colella, M.; Monticelli, S.; Romanazzi,
G.; Holzer, W.; Langer, T.; Degennaro, L.; Pace, V.; Luisi, R. J. Am. Chem. Soc. 2017, 139, 13648-13651. (l) Pace, V.;
Castoldi, L.; Mamuye, A. D.; Holzer, W. Synthesis 2014, 46, 2897-2909.
(14) (a) Senatore, R.; Castoldi, L.; Ielo, L.; Holzer, W.; Pace, V. Org. Lett. 2018, 20, 2685-2688. (b) Castoldi, L.; Holzer,
W.; Langer, T.; Pace, V. Chem. Commun. 2017, 53, 9498-9501. (c) Pace, V.; Murgia, I.; Westermayer, S.; Langer, T.;
Holzer, W. Chem. Commun. 2016, 52, 7584-7587. (d) Monticelli, S.; Holzer, W.; Langer, T.; Roller, A.; Olofsson, B.; Pace,
V. ChemSusChem 2019, doi:10.1002/cssc.201802815. (e) Senatore, R.; Ielo, L.; Urban, E.; Holzer, W.; Pace, V. Eur. J.
Org. Chem. 2018, 2466-2470. (f) Mamuye, A. D.; Castoldi, L.; Azzena, U.; Holzer, W.; Pace, V. Org. Biomol. Chem. 2015,
1
3, 1969-1973. (g) Miele, M.; Citarella, A.; Micale, N.; Holzer, W.; Pace, V. Org. Lett. 2019, 21, 8261-8265. (h) Senatore,
R.; Ielo, L.; Monticelli, S.; Castoldi, L.; Pace, V. Synthesis 2019, 51, 2792-2808. (i) Castoldi, L.; Ielo, L.; Hoyos, P.; Hernáiz,
M. J.; De Luca, L.; Alcántara, A. R.; Holzer, W.; Pace, V. Tetrahedron 2018, 74, 2211-2217.
(
15) (a) Pace, V.; Pelosi, A.; Antermite, D.; Rosati, O.; Curini, M.; Holzer, W. Chem. Commun. 2016, 52, 2639-2642. (b)
Touqeer, S.; Castoldi, L.; Langer, T.; Holzer, W.; Pace, V. Chem. Commun. 2018, 54, 10112-10115.
16) For seminal studies, see: (a) Reich, H. J.; Reich, I. L.; Renga, J. M. J. Am. Chem. Soc. 1973, 95, 5813-5815. (b) Reich,
(
H. J.; Renga, J. M.; Reich, I. L. J. Am. Chem. Soc. 1975, 97, 5434-5447. (c) Reich, H. J.; Chow, F.; Shah, S. K. J. Am. Chem.
Soc. 1979, 101, 6638-6648. (d) Reich, H. J. Acc. Chem. Res. 1979, 12, 22-30. (d) Reich, H. J.; Jasperse, C. P.; Renga, J. M.
J. Org. Chem. 1986, 51, 2981-2988.
(17) For an excellent overview of seleno-stabilized carbanions, see: (a) Krief, A.; Kremer, A. 3.02 Organolithium
Compounds Bearing a Phenyl-, a Vinyl-, and/or a Seleno Group on their Carbanionic Centers: Synthesis by Se/Li
Exchange and Unusual Synthetic Applications A2 - Knochel, P. In Comprehensive Organic Synthesis (Second Edition);
Elsevier: Amsterdam, 2014; pp. 56-156. (b) Krief, A. Selenium Stabilization. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 1; pp. 629-728. (c) Krief, A. Tetrahedron 1980, 36, 2531-2640. (d)
Comasseto, J. V.; Dos Santos, A. A.; Wendler, E. P. Selenium-Stabilized Carbanions. In Organoselenium Chemistry:
Synthesis and Reactions; Wirth, T., Ed.; Wiley: Weinheim, 2011; pp. 147-189. (d) The addition of a selenium-
containing titanium enolate to imines has been reported, see: Silveira, C. C.; Vieira, A. S.; Braga, A. L.; Russowsky, D.
Tetrahedron 2005, 61, 9312-9318.
(18) For recent reviews, see: (a) Monticelli, S.; Castoldi, L.; Murgia, I.; Senatore, R.; Mazzeo, E.; Wackerlig, J.; Urban, E.;
Langer, T.; Pace, V. Monat. Chem. 2017, 148, 37-48. (b) Pace, V.; Hoyos, P.; Castoldi, L.; Domínguez de María, P.;
Alcántara, A. R. ChemSusChem 2012, 5, 1369-1379.
(19) For a recent review, see: Azzena, U.; Carraro, M.; Pisano, L.; Monticelli, S.; Bartolotta, R.; Pace, V. ChemSusChem
2
019, 12, 40-70.
2
2