Cu-Catalyzed Radical Selenylation of Olefin: A Direct Access to Vinyl Selenides

Article abstract of DOI:10.1002/adsc.202000015

A method for the synthesis of vinyl selenides via Cu-catalyzed three-component reactions of arylboronic acids, Se powder and diarylethylenes has been developed. The reaction proceeds via addition of in situ generated selenium-centered radical to carbon-carbon double bond. This method highlights the use of easily accessible Se powder as selenium source in the construction of vinyl selenides for the first time. (Figure presented.).

Full text of DOI:10.1002/adsc.202000015

Title: Cu-Catalyzed Radical Selenylation of Olefin: A Direct Access to
Vinyl Selenides
Authors: Ye-Fei Yang, Chen-Yuan Li, Tao Leng, Xiaobo Huang,
Wenxia Gao, Yun-Bing Zhou, Miaochang Liu, and Huayue Wu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000015
Link to VoR: http://dx.doi.org/10.1002/adsc.202000015

10.1002/adsc.202000015
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Cu-Catalyzed Radical Selenylation of Olefin: A Direct Access to
Vinyl Selenides
Ye-Fei Yang, Chen-Yuan Li, Tao Leng, Xiao-Bo Huang, Wen-Xia Gao, Yun-Bing
Zhou,* Miao-Chang Liu,* and Hua-Yue Wu
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, People’s Republic of China
E-mail: zyb@wzu.edu.cn; mcl@wzu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A method for the synthesis of vinyl selenides via
Cu-catalyzed three-component reactions of arylboronic
acids, Se powder and diarylethylenes has been developed.
The reaction proceeds via addition of in situ generated
selenium-centered radical to carbon-carbon double bond.
This method highlights the use of easily accessible Se
powder as selenium source in the construction of vinyl
selenides for the first time.
Keywords: Selenylation; Olefin; Vinyl Selenides; Radical;
Se powder
Selenium-containing compounds are gaining
increasing attention due to their numerous
applications in candidate drugs and agrochemicals,
materials science as well as catalysis.[1] Among them,
vinyl selenides[2] serve as important synthetic
intermediates for the synthesis of vinyl synthons,[3]
versatile ethylene derivatives[4] and heteroclyclic
Scheme 1 Diverse synthetic routes to vinyl selenides.
compounds.[5] Considering their great importance, the
metals, the poor accessibility of the starting materials
and selenium sources, continue to fuel research into
the development of facile and efficient approaches for
the preparation of vinyl selenides.
development of efficient methods for the preparation
of vinyl selenides has aroused significant interest of
chemists. One of the synthetic methods relies on a
Wittig-type reaction with PhSeCl as the selenium
source (Scheme 1a).[6] Transition-metal-catalyzed or
light-promoted addition of selenium compounds
including RSeSeR,[7] RSeH[8] and RSeZnCl[9] to
alkynes have also emerged as effective methods for
the preparation of vinyl selenides (Scheme 1b).
Another classical method to access vinyl selenides
involves cross-coupling reactions between vinyl
halides (or boronic acids or borates) with RSeSeR[10]
(or KSeCN[11]) (Scheme 1c). Recently, ji’s group
developed a rhodium-catalyzed selenylation of N-
tosylacrylamides with RSeSeR as the selenium
source through N-tosylamide-assisted activation of
the alkenyl C(sp2)-H bond, providing a regioselective
access to (Z)-β-alkenyl selenides (Scheme 1d).[12]
Despite these achievements, certain issues associated
with existing methods including harsh reaction
conditions, the need for noble
Although Se powder as a selenium source is
inexpensive, available and bench-stable, it is indeed
beyond the scope of current state-of-the-art
methodologies for the construction of vinyl selenides
probably due to its chemical inertness. On the other
hand, Se powder as a selenium source has been
successfully applied in the preparation of diaryl
selenides via transition-metal-catalyzed reactions.[13]
In addition to transition-metal-catalyzed chemistry,
the in-situ generated aryl radical enables the efficient
activation of Se powder towards the generation of
aryl selenium radical, as demonstrated by our group
recently.[14] Inspired by this work, we envisaged the
possibility of extending the above-described strategy
to the preparation of vinyl selenides, using Se powder
as a selenium source. Specifically, we hoped to
exploit the radical addition of aryl selenium radical
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000015
Advanced Synthesis & Catalysis
intermediates derived from arylboronic acids and Se
powder to alkenes in combination with transition-
metal catalysis to access a series of vinyl selenides.
3a (entry 16). Either reducing or increasing reaction
temperature led to no observable improvements
(entries 17 and 18). The replacement of air with O2
atmosphere led to an increased yield (entries 19 and
20). In contrast, a negative effect was observed when
the reaction was conducted under N2 (entry 21).
Lowing the catalyst loading greatly reduced the
reaction efficiency (entry 22). Therefore, we chose
the conditions of entry 19 as the standard reaction
conditions where the reaction was performed in
DMSO at 120 ℃ under O2 in the presence of a
catalytic system containing CuBr2 and L1.
Table 1. Optimization of reaction conditions[a]
temp (oC)
entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16[b]
17[b]
18[b]
19[bc]
20[c]
21[bd]
22[bce]
catalyst
CuCl
CuI
Cu2O
CuCl2
CuBr2
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
yield (%)
41
50
46
66
70
42
53
59
0
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
80
Table 2. Scope of arylboronic acids[a]
Cu(OAc)2 DMSO
CuO
Cu(OTf)2
-
DMSO
DMSO
DMSO
DMF
DMA
NMP
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
63
59
0
0
0
0
82
0
73
87
74
59
15
THF
C2H5OH
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
150
120
120
120
120
aReaction conditions: 1a (0.8 mmol), Se powder (0.8
mmol), 2a (0.4 mmol), catalyst (0.04 mmol), solvent (2.0
mL), under air, 120 ℃, 12 h, isolated yields.
[b]tricyclohexylphonium tetrafluoroborate (0.04 mmol) was
e
used as ligand (L1). [c]Under O2. [d]Under N2. 5 mol% of
CuBr2 was used.
To test our idea, our initial effort focused on
screening reaction conditions by choosing 1,1-
diphenylethlene, Se powder and phenyl boric acid as
model substrates (Table 1). Gratifyingly, it was found
that the three-component reaction conducted in
[a]Reaction conditions: 1 (0.8 mmol), Se powder (0.8
mmol), 2a (0.4 mmol), CuBr2 (0.04 mmol), DMSO (2.0
mL), L1 (0.04 mmol), under O2, 12 h, 120 ℃, isolated
yields.
o
DMSO under air at 120 C using CuCl as a catalyst
afforded the desired product 3a with 41% yield (entry
1). Systematical screening for catalysts demonstrated
that the use of CuBr2 was the best choice and
afforded the desired product 3a in 70% yield (entry 5),
while other Cu salts led to moderate yields (entries 2-
4 and 6-8). In the absence of Cu catalysts, the
transformation was shut down (entry 9). Next, by
screening various solvents (entries 10-15), no better
results and even no formation of 3a were observed.
We then turned our attention to screening a series of
ligands (Table S1, see the supporting information).
To our delight, the use of tricyclohexylphonium
tetrafluoroborate (L1) as a ligand resulted in a
dramatic increase in the yield of the desired product
With the standard reaction conditions in hand, we
sought to investigate the substrate scope with respect
to boronic acids (Table 2). Arylboronic acids bearing
halogen (1b-1g) and strong electron-withdrawing
groups (1h and 1i) were well tolerated. It was also
observed that both bromine and iodine substituents
offer a good opportunity for further elaboration of the
products (3f and 3g). The substrates containing
electron-rich substituents such as isopropyl (1j),
methyl (1k-1m), methoxy (1n and 1o) and
trimethylsilyl (1p) groups were also amenable to the
reaction conditions, affording the corresponding
products in 40-76% yields. Moreover, it turned out
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000015
Advanced Synthesis & Catalysis
that the substituents at the meta (1d and 1m) and
para positions (1e and 1k) of the benzene ring gave
better yield than those at the ortho position (1c and
1l) probably due to steric hindrance. Remarkably, the
sterically hindered substrate 1q could be converted to
corresponding product 3q in an acceptable yield. The
with a ratio of 1:1 in most cases. Interestingly, good
stereoselectivity was observed for the synthesis of
product 4l. Unfortunately, the substrate with multiple
strong electron-rich substituents failed to give the
desired product 4q. Surprisingly, the reaction of N-
phenylmethacrylamide, Se and PhB(OH)2 afforded
the unexpected addition product 4p rather than vinyl
selenide under standard conditions (Scheme 2). After
substrate bearing
a
fused ring (1s) was
accommodated by the standard reaction conditions.
Nevertheless, in the case of heterocyclic boronic
acids (1t and 1u) or alkylboronic acids (1v), no
reactions took place, which could be attributed to the
coordination of Cu catalyst with heteroatom.
Table 4. The Reaction of ArB(OH)2, Se powder and
maleimide [a]
Table 3. Scope of 1,1-diarylethylenes[a]
[a]Reaction conditions: 1 (0.8 mmol), Se powder (0.8
mmol), 5 (0.4 mmol), CuBr2 (0.04 mmol), DMSO (2.0
mL), L1 (0.04 mmol), under O2, 12 h, 120 ℃, isolated
yields.
preliminary screening of ligands (Table S2), the yield
of 4r could be increased to 40% by using tri-m-
tolylphosphane as a ligand.
[a]Reaction conditions: 1a (0.8 mmol), Se powder (0.8
mmol), 2 (0.4 mmol), CuBr2 (0.04 mmol), DMSO (2.0
mL), L1 (0.04 mmol), under O2, 12 h, 120 ℃, isolated
yields. [b]The ratio of E-isomer and Z-isomer, determined
by GC-MS. [c]The ratio of E-isomer and Z-isomer,
determined by 1HNMP.
Schheme
2.
Unexpected
selenylation
of
N-
phenylmethacrylamide.
We then tested the substrate scope with respect to
1,1-diarylethylenes (Table 3). The reaction was
highly tolerant of most functional groups such as
halogen (2a-2f, 2j and 2k), methyl (2g-2j) and
methylthio (2l) under the standard reaction conditions.
In the case of asymmetric 1,1-diarylethylenes, a
mixture of E-isomers and Z-isomers was obtained
Scheme 3. Control experiments. Standard conditions:
CuBr2 (0.04 mmol), DMSO (2.0 mL), L1 (0.04 mmol),
under O2, 12 h, 120 ℃, isolated yields.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000015
Advanced Synthesis & Catalysis
In addition to 1,1-diarylethylenes, the feasibility of
transfer (SET) with Cu(II) to afford intermediate D
which is deprotonated to give the desired product
(Path I). According to this mechanism, the relatively
poor stability of intermediates C and D may be
responsible for the reaction failing when using other
alkenes such as styrene and cyclohexene.
Alternatively, aryl selenium radical B reacts with
CuBr2 to generate ArSeBr which adds to 2a to give
intermediate F. The resulting intermediate F then
undergoes HBr elimination to provide the desired
product (Path II).
maleimides as the substrates in this protocol was
assessed (Table 4). N-phenyl-substituted maleimide
reacted well with various arylboronic acids to deliver
the desired products in 28-72% yields (6a-6j).
Furthermore, N-methyl-substituted maleimide proved
to be a viable substrate (5k). Unfortunately, further
examination on substrate scope led to no better
results.[15]
In conclusion, we developed
a facile and
convenient method for the synthesis of vinyl
selenides through Cu-catalyzed three-component
radical reactions of arylboronic acids, Se powder and
diarylethylenes. In particular, this method highlights
the use of Se powder as selenium source in the
construction of vinyl selenides for the first time. Key
to the success of this method was the generation of an
aryl selenium radical intermediate. In addition, the
method offers a strategy for activating of Se powder
by in-situ generated radicals, further expanding the
use of Se powder in the preparation of organic
selenium compounds.
Experimental Section
Scheme 4 A plausible mechanism.
A 25 mL Schlenk tube equipped with a stir bar and O2
atmosphere was charged with phenylboronic acid (0.8
mmol), selenium (0.8 mmol), 1, 1-phenylethylene (0.4
mmol), tricyclohexylphonium tetrafluoroborate (L1) (0.04
mmol), CuBr2 (0.04 mmol) and 2 mL DMSO. The tube
was fitted with a rubber septum, then the septum was
replaced by a Teflon screwcap. The reaction mixture was
stirred at 120 ℃ for 12 h. After cooling down, the reaction
mixture was diluted with 10 mL of ethyl ether, filtered
through a pad of silica gel, followed by washing the pad of
the silica gel with the same solvent (20 mL), concentrated
under reduced pressure. The residue was then purified by
flash chromatography on silica gel to provide the
corresponding product.
To elucidate the reaction mechanism, a series of
control experiments were performed (Scheme 3). A
mixture of PhB(OH)2 and Se powder was subjected
to the standard conditions, leading to the formation of
diphenyl diselenide in 87% yield (Scheme 3a). The
absence of CuBr2 resulted in no formation of
diphenyl diselenide, demonstrating the importance of
CuBr2 for this transformation (Scheme 3b). The same
result was observed by the addition of TEMPO into
the reaction between PhB(OH)2 and Se powder,
supporting a radical process (Scheme 3c). The
reaction between diphenyl diselenide and 1,1-
phenylethylene proceeded well to afford the desired Acknowledgements
product 3a under the standard conditions (Scheme
We are grateful for financial support from the National Natural
3d), even or in the absence of CuBr2 or L1 (Scheme
3e). The addition of tempo completely suppressed the
formation of 3a, implying that the transformation
involved a radical process (Scheme 3f). Interestingly,
PhSeBr also successfully reacted with 1,1-
phenylethylene to afford 3a under the standard
conditions (Scheme 3g).
Science Foundation of China (21901187 and 21672164).
References
[1] a) G. Mugesh, W.-W. Mont, H. Sies, Chem. Rev. 2001,
101, 2125; b) G. Mugesh, H. B. Singh, Acc. Chem. Res.
2002, 35, 226; c) C. W. Nogueira, G. Zeni, J. B. T.
Rocha, Chem. Rev. 2004, 104, 6255; d) S. T. Manjare,
Y. Kim, D. G. Churchill, Acc. Chem. Res. 2014, 47,
2985; e) L. Shao, Y. Li, J.-M. Lu, X. Jiang, Org. Chem.
Front. 2019, 6, 2999;
In line with the above experimental results, a
plausible mechanism for selenylation of 1,1-
diarylethylenes was postulated (Scheme 4). The
reaction starts with the formation of aryl radical
species A from the arylboronic acid in the presence of
Cu(II) catalyst. Next, the in-situ generated aryl
radical A enables the efficient activation of Se
powder towards the generation of aryl selenium
radical B, followed by dimerization to form diphenyl
diselenide in a reversible manner. The addition of
aryl selenium radical B to diarylethylene produces
carbon-centred radical intermediate C. The resulting
intermediate C then undergoes single electron
[2] a) G. Perin, E. J. Lenardão, R. G. Jacob, R. B. Panatieri,
Chem. Rev. 2009, 109, 1277; b) F. Alonso, I. P.
Beletskaya, M. Yus, Chem. Rev. 2004, 104, 3079; c) I.
P. Beletskaya, V. P. Ananikov, Chem. Rev. 2011, 111,
1596.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000015
Advanced Synthesis & Catalysis
[3] N. K. Gusarova, N. A. Chernysheva, S. V. Yas’ko, T. I.
Kazantseva, I. A. Ushakov, B. A. Trofimov, Synthesis
2008, 2743.
[11] A. A. Herediaa, A. B. Peñéñory, RSC Adv. 2015, 5,
105699.
[12] C. Liu, Y. Fang, S.-Y. Wang, S.-J. Ji, Org. Lett. 2018,
20, 6112.
[4] a) M. Hamaguchi, T. Nagai, J. Org. Chem. 1989, 54,
3957; b) B. A. Trofimov, N. K. Gusarova, S. F.
Malysheva, N. I. Ivanova, B. G. Sukhov, N. A.
Belogorlova, V. A. Kuimov, Synthesis 2002, 2207.
[13] a) D. Luo, G. Wu, H. Yang, M. Liu, W. Gao, X.
Huang, J. Chen, H. Wu, J. Org. Chem. 2016, 81, 4485;
b) C. Gao, G. Wu, L. Min, M. Liu, W. Gao, J. Ding, J.
Chen, X. Huang, H. Wu, J. Org. Chem. 2017, 82, 250;
c) D. Hu, M. Liu, H. Wu, W. Gao, G. Wu, Org. Chem.
Front. 2018, 5, 1352; d) S. J. Balkrishna, S. Kumar, G.
K. Azad, B. S. Bhakuni, P. Panini,a N. Ahalawat, R. S.
Tomar, M. R. Dettyc, S. Kumar. Org. Biomol. Chem.
2014, 12, 1215; e) A. Kumar, S. Kumar, Tetrahedron
2014, 70, 1763.
[5] L. Bagnoli, C. Scarponi, M. G. Rossi, L. Testaferri, M.
Tiecco, Chem. Eur. J. 2011, 17, 993.
[6] O. Boutureira, M. I. Matheu, Y. Díaz, S. Castillón,
Carbohydr. Res. 2007, 342, 736.
[7] a) G. Sartori, J. S. S. Neto, A. P. Pesarico, D. F. Back,
C. W. Nogueira, G. Zeni, Org. Biomol. Chem. 2013, 11,
1199; b) H. Kuniyasu, A. Ogawa, S.-I. Miyazaki, I.
Ryu, N. Kambe, N. Sonoda, J. Am. Chem. Soc. 1991,
113, 9796.
[14] a) T. Leng, G. Wu, Y.-B. Zhou, W. Gao, J. Ding, X.
Huang, M. Liu, H. Wu, Adv. Synth. Catal. 2018, 360,
4336; b) C. An, C.-Y. Li, X.-B. Huang, W.-X. Gao, Y.-
B. Zhou, M.-C. Liu, H.-Y. Wu, Org. Lett. 2019, 21,
6710.
[8] a) S. Kawaguchi, M. Kotani, S. Atobe, A. Nomoto, M.
Sonoda, A. Ogawa, Organometallics 2011, 30, 6766; b)
T. Ozaki, M. Kotani, H. Kusano, A. Nomoto, A.
Ogawa, J. Organomet. Chem. 2011, 696, 450.
[15] An attempted synthesis of sulfur and tellurium
derivatives failed when using sulfur or tellurium
instead of selenium. Likewise, the transformation of
iodobenzene, styrenes and cyclohexanone failed.
[9] B. Battistelli, T. Lorenzo, M. Tiecco, C. Santi, Eur.
J .Org. Chem. 2011, 1848.
[10] a) D. Kundu, N. Mukherjee, B. C. Ranu, RSC Adv.
2013, 3, 117; b) A. L. Braga, T. Barcellos, M. W.
Paixao, A. M. Deobald, M. Godoi, H. A. Stefani, R.
Cella, A. Sharma, Organometallics 2008, 27, 4009; c)
C. C. Silveira, P. C. S. Santos, S. R. Mendes, A. L.
Braga, J. Organomet. Chem. 2008, 693, 3787; d) V. P.
Reddy, K. Swapna, A. V. Kumar, K. R. Rao,
Tetrahedron Lett. 2010, 51, 293; e) L. C. Gonalves, G.
F. Fiss, G. Perin, D. Alves, R. G. Jacob, E. J. Lenardão,
Tetrahedron Lett. 2010, 51, 6772; f) A. Saha, D. Saha,
B. C. Ranu, Org. Biomol. Chem. 2009, 7, 1652.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000015
Advanced Synthesis & Catalysis
COMMUNICATION
Cu-Catalyzed Radical Selenylation of Olefin: A
Direct Access to Vinyl Selenides
Adv. Synth. Catal. Year, Volume, Page – Page
Ye-Fei Yang, Chen-Yuan Li, Tao Leng, Xiao-Bo
Huang, Wen-Xia Gao, Yun-Bing Zhou,* Miao-
Chang Liu,* and Hua-Yue Wu
6
This article is protected by copyright. All rights reserved.