Metal-free synthesis of unsymmetrical selenides from pyridinium salts and diselenides catalysed by visible light

Article abstract of DOI:10.1016/j.tetlet.2021.153071

We report the first metal-free selenolations of pyridinium salts with diselenides to prepare unsymmetrical organoselenides catalysed by visible light. This protocol is an efficient and green method for the preparation of unsymmetrical organoselenides because metal-free conditions and readily accessible diselenides are used.

Full text of DOI:10.1016/j.tetlet.2021.153071

Tetrahedron Letters 72 (2021) 153071
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Metal-free synthesis of unsymmetrical selenides from pyridinium salts
and diselenides catalysed by visible light
Liangshuo Ji a, Jiamin Qiao a, Ankun Li a, Zeyi Jiang a, Kui Lu b, Xia Zhao a,
⇑
a College of Chemistry, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Tianjin Normal University, Tianjin 300387, China
b China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science &
Technology, Tianjin 300457, China
a r t i c l e i n f o
a b s t r a c t
Article history:
We report the first metal-free selenolations of pyridinium salts with diselenides to prepare unsymmet-
rical organoselenides catalysed by visible light. This protocol is an efficient and green method for the
preparation of unsymmetrical organoselenides because metal-free conditions and readily accessible dis-
elenides are used.
Received 21 December 2020
Revised 29 March 2021
Accepted 6 April 2021
Available online 8 April 2021
Ó 2021 Elsevier Ltd. All rights reserved.
Keywords:
Selenolation
Pyridinium salts
Diselenides
Unsymmetrical organoselenide
Visible light catalysed
Introduction
research into developing efficient methods for carbon–chalcogen
bond formation [14], we demonstrate herein the metal-free syn-
Organoselenium compounds have been widely used as pharma-
ceuticals, agrochemicals, and functional materials [1]. Among these
compounds, organoselenides show antioxidant [2], antitumor [3],
cancer cell-growth inhibitory [4], glutathione reductase inhibitory
[4], 5-lipoxygenase inhibitory [5], and retinoic acid receptor (RAR)
agonist [6] activities (Fig. 1). Previous methods for the preparation
of unsymmetrical organoselenides often require the use of a tran-
sition-metal catalyst [7]. Although transitional-metal-free proto-
cols under oxidative [8] or basic condition [9] have been
reported, electron-rich aromatic substrates or strong bases are
usually required. Hence, the development of an efficient and green
method for preparing unsymmetrical organoselenides is highly
desirable.
thesis of unsymmetrical selenides from alkylpyridinium salts and
diselenides, catalysed by visible light (Scheme 1).
Results and discussion
We initially chose benzyl Katritzky salt 1a and diphenyldise-
lenide (2a) as model substrates for optimising the reaction param-
In the past decade, pyridinium salts have emerged as versatile
intermediates in organic synthesis because they can be used as
radical precursors through reductive single-electron transfer [10].
These salts have been used to form new CAC, CAN, CAO, and
CAB bonds through transition-metal catalysis [11], photocatalysis
[12], and Lewis base activation [13] (Scheme 1). However, car-
bon–chalcogen bond formation through the fragmentation of pyri-
dinium salts has not yet been reported. As a part of our ongoing
⇑
Corresponding author.
E-mail address: hxxyzhx@mail.tjnu.edu.cn (X. Zhao).
Fig. 1. Representative organoselenides with diverse functions.
https://doi.org/10.1016/j.tetlet.2021.153071
0040-4039/Ó 2021 Elsevier Ltd. All rights reserved.

L. Ji, J. Qiao, A. Li et al.
Tetrahedron Letters 72 (2021) 153071
83% was obtained when triethylamine was used as the reductant
(Entry 13).
Photocatalyst loading, as well as the light source were finally
examined. A lower Eosin Y loading of 10% resulted in a lower yield,
while a higher loading of 14% did not improve the yield. The
desired product was obtained in yields of 82% or 86% yield, respec-
tively, when a 21 W green LED lamp or a 26 W white LED lamp
were used as the light source. Notably, the reaction did not occur
in the absence of light or a photocatalyst. Moreover, only trace
products were observed without DIPEA. Hence, the optimised reac-
tion conditions for the selenolation of 1a were determined to be:
1a (0.4 mmol), 2a (0.48 mmol), DIPEA (0.8 mmol), Eosin Y
(0.048 mmol), and MeCN (2.0 mL) irradiated with blue LEDs
(24 W) at room temperature.
Scheme 1. CAC, CAN, CAO, CAB, and CASe bond formation by the fragmentation of
pyridinium salts.
With the optimised reaction conditions in hand, the reaction
scope was next investigated by reacting1 various diselenides with
1a, the results of which are presented in Scheme 2. Diphenyldise-
lenides bearing electron-donating or electron-withdrawing sub-
stituents in the para-, meta-, or ortho-positions were converted
into the desired products (3ab–3aj) in good-to-excellent yields.
We next examined the reactions of a series of benzyl Katritzky
salts with 2a under the optimised conditions (Scheme 3). 4-
eters (Table 1). Hünig’s base (N,N-diisopropylethylamine, DIPEA), a
tertiary amine, was used as the reductant and Eosin Y was
employed as the photocatalyst, with the desired unsymmetrical
selenide 3aa obtained in 80% yield upon irradiation with blue LEDs
(24 W) in tetrahydrofuran (THF) at room temperature for 20 h
(Entry 1). To further improve the yield, various solvents, including
1,2-dichloroethane (DCE), acetonitrile (MeCN), toluene, N,N-
dimethylformamide (DMF), and 1,4-dioxane (Table 1, entries 2–
Table 1
Optimising the reaction conditions.a
Entry
Base (equiv.)
Cat. (mol%)
Solvent (mL)
Yield (%)a
1
2
3
4
5
6
7
8
DIPEA (2)
DIPEA (2)
DIPEA (2))
DIPEA (2)
DIPEA (2)
DIPEA (2)
DIPEA (2)
DIPEA (2))
DIPEA (2)
DIPEA (2)
DIPEA (2))
DIPEA (2)
Et3N (2)
DIPEA (2)
DIPEA (2)
DIPEA (2)
DIPEA (2)
DIPEA (2)
DIPEA (2)
Eosin Y (12)
Eosin Y (12)
Eosin Y (12)
Eosin Y (12)
Eosin Y (12)
Eosin Y (12)
Eosin B (12)
Rose Bengal (12)
Rhodamin B (12)
Na2-Eosin Y (12)
Methylene Blue (12)
fac-Ir(ppy)3 (1)
Eosin Y (12)
Eosin Y (10)
Eosin Y (14)
Eosin Y (12)
Eosin Y (12)
–
THF (2.0)
DCE (2.0)
MeCN (2.0)
Toluene (2.0)
DMF (2.0)
80
87
93
43
trace
trace
82
trace
62
trace
trace
67
83
88
92
82
86
–
–
trace
1,4-Dioxane (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
MeCN (2.0)
9
10
11
12
13
18
19
20b
21c
22
23d
24
–
Eosin Y (12)
a
b
c
Conditions: 1a (0.4 mmol), 2a (0.48 mmol), reductant (0.8 mmol), photocatalyst (12 mol%), solvent (2 mL), 24 W blue LED lamp, r.t., 20 h.
21 W green LED lamp.
26 W white LED lamp.
Without visible-light irradiation.
d
1
Aromatic heterocyclic diselenides, such as di(thiophen-2-yl)diselenide (2k), di(2-
chloropyridin-3-yl)diselenide (2l), di(pyridin-3-yl)diselenide (2m), and di(1-methyl-
1H-indol-5-yl)diselenide (2n) were well tolerated and afforded the desired products
(3ak–3an) in moderate-to-good yields. Moreover, alkyl diselenides such as diben-
zyldiselenide (2o), dicyclohexyldiselenide (2p) dibutyldiselenide (2q), and di(car-
boethoxymethyl)diselenide (2r) were compatible with this transformation to furnish
the desired products (3ao–3ar) in good-to-excellent yields.
6) were investigated, with MeCN affording the highest yield.
The photocatalyst and reductant were next investigated, with
Eosin B, Rose Bengal, Rhodamin B, Na2-Eosin Y, Methylene Blue,
and fac-Ir(ppy)3 examined; none of these photocatalysts gave
superior results to those obtained using Eosin Y. A lower yield of
2

L. Ji, J. Qiao, A. Li et al.
Tetrahedron Letters 72 (2021) 153071
Scheme 4. Plausible mechanism for the selenolation of a pyridinium salt.
Scheme 5. Scaling up the selenolation reaction.
Scheme 2. Selenolation of 1a: substrate scope.
ground-state Eosin Y, after which benzyl radical 6 reacts with dis-
elenide 2 to afford product 3.
We finally investigated the practical application of this transfor-
mation by selenolating 1a on a 5-mmol scale (Scheme 5), with the
desired product 3a notably obtained in 85% yield.
Conclusion
We selenolated pyridinium salts with diselenides under metal-
free conditions catalysed by visible light for the first time, with
Hünig’s base (DIPEA) as the reductant and Eosin Y as the photocat-
alyst. Readily accessible diselenides and metal-free conditions pro-
vide an alternative and green strategy for the synthesis of
unsymmetrical organoselenides. The formation of CAS bonds
employing pyridinium salts as radical precursors is currently being
investigated in our laboratory.
Declaration of Competing Interest
Scheme 3. Selenolations of benzyl Katritzky salts: substrate scope.
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Chlorobenzyl,
4-(tert-butyl)benzyl,
4-cyanobenzyl,
and
2-chlorobenzyl Katritzky salts (2b–2e) as well as 2,4,6-triphenyl-
1-(pyridin-3-ylmethyl)pyridin-1-ium, and 2,4,6-triphenyl-1-(pyri-
din-2-ylmethyl)pyridin-1-ium tetrafluoroborate (2f and 2g) were
smoothly converted to the desired products (3ba–3ga).
Acknowledgments
A plausible mechanism for the reaction of a Katritzky salt with a
diselenide is proposed on the basis of the aforementioned results
and related literature [15] (Scheme 4). Initially, photoexcited Eosin
Y (EY*) reduces Katritzky salt 1 by single-electron transfer to give
the dihydropyridinyl radical 4, which decomposes to the benzylic
radical 6 and the rearomatised pyridine derivative 5. Single elec-
tron reduction to EY+Á from DIPEA concurrently regenerates the
The authors sincerely thank the financial support from Natural
Science Foundation of Tianjin City (Grants 18JCQNJC76600) and
National Natural Science Foundation of China (Grants 21572158).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2021.153071.
3

L. Ji, J. Qiao, A. Li et al.
Tetrahedron Letters 72 (2021) 153071
(f) R.M. Montero, V.R. Yatham, H.-F. Yin, J. Davies, R. Martin, Org. Lett. 21
(2019) 2947–2951;
References
(g) H.-F. Yue, C. Zhu, L. Shen, Q.-Y. Geng, K.J. Hock, T.-T. Yuan, L.G. Cavallo, M.
Rueping, Chem. Sci. 10 (2019) 4430–4435;
(h) J. Yi, S.O. Badir, L.M. Kammer, M.R.G.A. Molander, Org. Lett. 21 (2019)
3346–3351;
(i) S. Plunkett, C.H. Basch, S.O. Santan, M.P. Watson, J. Am. Chem. Soc. 141
(2019) 2257–2262;
(j) J.-N. Liao, W.-Y. Guan, B.P. Boscoe, J.W. Tucker, J.W. Tomlin, M.R. Garnsey,
M.P. Watson, Org. Lett. 20 (2018) 3030–3033;
(k) J.-N. Liao, C.H. Basch, M.E. Hoerrner, M.R. Talley, B.P. Boscoe, J.W. Tucker,
M.R. Garnsey, M.P. Watson, Org. Lett. 21 (2018) 2941–2946;
(l) W.-Y. Guan, J.-N. Liao, M.P. Watson, Synthesis 50 (2018) 3231–3237;
(m) M.-M. Zhang, F. Liu, Org. Chem. Front. 5 (2018) 3443–3446;
(n) C.H. Basch, J.-N. Liao, J.-Y. Xu, J.J. Piane, M.P. Watson, J. Am. Chem. Soc. 139
(2017) 5313–5316.
[1] (a) G. Mugesh, W.-W. du Mont, H. Sies, Chem. Rev. 101 (2001) 2125–2180;
(b) A.C. Lockhart, E. Calvo, A.W. Tolcher, E.K. Rowinsky, G. Shackleton, J.G.
Morrison, R. Rafi, W. Vermeulen, M.L. Rothenberg, Am. J. Clin. Oncol. 32 (2009)
9–14;
(c) L. Zhao, J. Li, Y. Li, J. Liu, T. Wirth, Z. Li, Bioorg. Med. Chem. 20 (2012) 2558–
2563;
(d) K. Banerjee, G. Padmavathi, D. Bhattacherjee, S. Saha, A.B. Kunnumakkara,
K.P. Bhabak, Org. Biomol. Chem. 16 (2018) 8769–8782.
[2] L. Savegnago, A.I. Vieira, N. Seusb, B.S. Goldani, M.R. Castro, E.J. Lenardão, D.
Alves, Tetrahedron Lett. 54 (2013) 40–44.
[3] J.A. Woods, J.A. Hadfield, A.T. McGown, B.W. Fox, Bioorg. Med. Chem. 1 (1993)
333–340.
[4] L. Engman, I. Cotgreave, M. Angulo, C.W. Taylor, G.D. Paine-Murrieta, G. Powis,
Anticancer Res. 17 (1997) 4599–4605.
[5] L. Engman, D. Stern, H. Frisell, K. Vessman, M. Berglund, B. Ek, C.M. Andersson,
Bioorg. Med. Chem. 3 (1995) 1255–1262.
[6] (a) C. Millois, P. Diaz, Org. Lett. 2 (2000) 1705–1708;
(b) Y. Koide, M. Kawaguchi, Y. Urano, K. Hanaoka, T. Komatsu, M. Abo, T. Terai,
T. Nagano, Chem. Commun. 48 (2012) 3091–3093.
[12] (a) Y. Yang, C.-H. Xu, F. Teng, J.-H. Li, Adv. Synth. Catal. 362 (2020) 3369–3373;
(b) F.J.R. Klauck, H. Yoon, M.J. James, M. Lautens, F. Glorius, ACS Catal. 9 (2019)
236–241;
(c) X. Jiang, M.-M. Zhang, W. Xiong, L.-Q. Lu, W.-J. Xiao, Angew. Chem., Int. Ed.
58 (2019) 2402–2406;
(d) A.C. Sun, E.J. McClain, J.W. Beatty, C.R.J. Stephenson, Org. Lett. 20 (2018)
3487–3490;
(e) J.-J. Wu, L. He, A. Noble, V.K. Aggarwal, J. Am. Chem. Soc. 140 (2018)
10700–10704;
(f) W.-L. Yu, J.-Q. Chen, Y.-L. Wei, Z.-Y. Wang, P.-F. Xu, Chem. Commun. 54
(2018) 1948–1951;
(g) J.-N. Mo, W.-L. Yu, J.-Q. Chen, X.-Q. Hu, P.-F. Xu, Org. Lett. 20 (2018) 4471–
4474;
(h) F.J.R. Klauck, M.J. Jame, F. Glorius, Angew. Chem. Int. Ed. 56 (2017) 12336–
12339.
[7] (a) For selected examples: M. Matsumura, H. Kumagai, Y. Murata, N.
Kakusawa, S. Yasuike J. Organomet. Chem. 807 (2016) 11–16;
(b) B. Goldani, V.G. Ricordi, N. Seus, E.J. Lenardão, R.F. Schumacher, D. Alves, J.
Org. Chem. 81 (2016) 11472–11476;
(c) C. Gao, G. Wu, L. Min, M. Liu, W. Gao, J. Ding, J. Chen, X. Huang, H. Wu, J.
Org. Chem. 82 (2017) 250;
(d) Q. Chen, P. Wang, T. Yan, M. Cai, J. Organomet. Chem. 840 (2017) 38–46;
(e) D. Hu, M. Liu, H. Wu, W. Gao, G. Wu, Org. Chem. Front. 5 (2018) 1352–
1355;
(f) A.A. Chaugule, A.A. Pawar, A.H. Tamboli, H.A. Bandal, W.-J. Chung, H. Kim,
Chem. Eng. J. 351 (2018) 490–497;
(g) A.J. Sahani, A.S. Burange, S. Narasimhan, R.V. Jayaram, ChemistrySelect. 3
(2018) 12291–12296;
[13] (a) L.-L. Wang, H.-B. Han, Z.-H. Cui, J.-W. Zhao, Z.-W. Bu, Q.-L. Wang, Org. Lett.
22 (2020) 873–878;
(b) T. Kawajiri, M. Kato, H. Nakata, R. Goto, S. Aibara, R. Ohta, H. Fujioka, H.
Sajiki, Y. Sawama, J. Org. Chem. 84 (2019) 3853–3870;
(c) J.-P. Hu, G.-Q. Wang, S.-H. Li, Z.-Z. Shi, Angew. Chem. Int. Ed. 57 (2018)
15227–15232.
(h) S. Wu, J. Shi, C.-P. Zhang, Org. Biomol. Chem. 17 (2019) 7468–7473.
[8] (a) A. Dey, A. Hajra, J. Org. Chem. 84 (2019) 14904–14910;
(b) D. Lemir, W.D. Castro-Godoy, A.A. Heredia, L.C. Schmidt, J.E. Argüello, RSC
Adv. 9 (2019) 22685–22694.
[9] (a) Y. Yu, Y. Zhou, Z. Song, G. Liang, Org. Biomol. Chem. 16 (2018) 4958–4962;
(b) A. Kumar, B.S. Bhakuni, C.D. Prasad, S. Kumar, S. Kumar, Tetrahedron 69
(2013) 5383–5392.
[10] F.-S. He, S.-Q. Ye, J. Wu, ACS Catal. 9 (2019) 8943–8960.
[11] (a) D. Zhang, S.-X. Dong, Q.-W. He, Y. Luo, Y. Liu, X.-H. Liu, X.-M. Feng, Chem.
Commun. 56 (2020) 12757–12760;
[14] (a) X. Zhao, L. Zhang, T. Li, G. Liu, H. Wang, K. Lu, Chem. Commun. 50 (2014)
13121–13123;
(b) X. Zhao, L. Zhang, X. Lu, T. Li, K. Lu, J. Org. Chem. 80 (2015) 2918–2924;
(c) X. Zhao, T. Li, L. Zhang, K. Lu, Org. Biomol. Chem. 14 (2016) 1131–1137;
(d) X. Zhao, Z. Deng, A. Wei, B. Li, K. Lu, Org. Biomol. Chem. 14 (2016) 7304–
7312;
(e) X. Zhao, X. Lu, A. Wei, X. Jia, J. Chen, K. Lu, Tetrahedron Lett. 57 (2016)
5330–5333;
(f) X. Zhao, X.-F. Wei, M.-M. Tian, X.-C. Zheng, L.-S. Ji, Q. Li, Y.-H. Lin, K. Lu,
Tetrahedron Lett. 60 (2019) 1796–1799;
(g) K. Lu, Q. Li, X.-L. Xi, T. Zhou, X. Zhao, J. Org. Chem. 85 (2020) 1224–1231;
(h) J.-J. Liu, M.-M. Tian, Y.-X. Li, X.-W. Shan, A.-K. Li, K. Lu, M. Fagnoni, S. Protti,
X. Zhao, Eur. J. Org. Chem. 47 (2020) 7358–7367.
(b) W.-J. Li, J. Tang, S. Li, X.-L. Zheng, M.-L. Yuan, B. Xu, W.-D. Jiang, H.-Y. Fu, R.-
X. Li, H. Chen, Org. Lett. 22 (2020) 7814–7819;
(c) J. Wang, M.E. Hoerrner, M.P. Watson, D.J. Weix, Angew. Chem. Int. Ed. 59
(2020) 13484–13489;
(d) F.T. Pulikottil, R. Pilli, R.V. Suku, R. Rasappan, Org. Lett. 22 (2020) 2902–
2907;
(e) M.E. Hoerrner, K.M. Baker, C.H. Basch, E.M. Bampo, M.P. Watson, Org. Lett.
21 (2019) 7356–7360;
[15] M. Ociepa, J. Turkowska, D. Gryko, ACS Catal. 8 (2018) 11362–11367.
4