Electrochemical Aminoselenation and Oxyselenation of Styrenes with Hydrogen Evolution

Article abstract of DOI:10.1021/acs.orglett.8b03274

The use of additive-free conditions is an ideal approach to prepare organoselenium reagents from readily available unsaturated substrates. Thus, we report the electro-induced aminoselenation and oxyselenation of styrenes without any acids or oxidants as additives. This transformation is compatible with various functional groups, which leads to vicinal difunctionalized organoselenium compounds. Our strategy improves the potential of this protocol for use in the pharmaceutical industry. Based upon the preliminary mechanism studies, we propose two possible pathways.

Full text of DOI:10.1021/acs.orglett.8b03274

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Electrochemical Aminoselenation and Oxyselenation of Styrenes
with Hydrogen Evolution
†
,‡,∥
§,∥
‡
‡
‡
‡
,§
Li Sun,
Yong Yuan,
Min Yao, Han Wang, Daoxin Wang, Meng Gao, Yi-Hung Chen,*
,
†,§
and Aiwen Lei*
†
College of Chemistry, Nanchang University, Nanchang 330031, Jiangxi, P.R. China
‡
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi, P.R. China
§
College of Chemistry and Molecular Sciences, the Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, Hubei,
P.R. China
*
S Supporting Information
ABSTRACT: The use of additive-free conditions is an ideal
approach to prepare organoselenium reagents from readily
available unsaturated substrates. Thus, we report the electro-
induced aminoselenation and oxyselenation of styrenes
without any acids or oxidants as additives. This transformation
is compatible with various functional groups, which leads to
vicinal difunctionalized organoselenium compounds. Our
strategy improves the potential of this protocol for use in
the pharmaceutical industry. Based upon the preliminary
mechanism studies, we propose two possible pathways.
rganoselenium reagents have demonstrated important
biological activities and versatile utilities in which
addition with nucleophiles generated vicinal difunctional
compounds 4.
O
phenylseleno compounds are widely used for organic syn-
In particular, the aminoselenation and oxyselenation of
olefins have attracted our attention. Despite major progress in
the field, the use of excess of acids, oxidants, or transition-metal
catalysts was required in previous reports in which the
generation of undesirable and toxic byproducts was unavoid-
able. The emerging electrosynthesis has been recognized as an
effective alternative for oxidants or reductants and minimized
1
thesis. The oxidative difunctionalization of easily available
unsaturated substrates (alkenes, alkynes or allenes) is a useful
method to build up this ubiquitous scaffold. Various Lewis
2
3
4
acids, Brønsted acids, or oxidants have been used for the
introduction of arylseleno functionality into an unsaturated
substrates 1 with a variety of arylseleno derivatives 2 (N-
arylselenophthalimide, diaryl diselenide, arylselenohalide, or
arylselenosuccinimide) as shown in Scheme 1a. Mechanistic
studies showed that additives activated seleno reagent 2 to
facilitate the formation of seleniranium ion 3 and subsequent
5
byproduct formation. Inspired by the recent development of
6
electrochemical alkene difunctionalization pioneered by the
Lin group, we launched electrochemical oxidative amino- and
oxyselenation projects (Scheme 1b) to avoid extra additives
which turned out to be a more environmentally benign and
economical approach.
Scheme 1. Preparation of Organoselenium Reagents via
Difunctionalization of Unsaturated Compounds
At the outset of our studies, we explored the amino-
selenation of styrene (1a) with benzotriazole (5a) and
diphenyl diselenide (2a) under different reaction parameters.
After considerable efforts, optimal yield of product 6a was
obtained in 80% yield under constant current (15 mA) for 4 h
n
in the presence of Bu NBF and CH CN/1,1,1,3,3,3-
4
4
3
hexafluoro-2-propanol (HFIP) = 8:2 as the cosolvent (Table
, entry 1). HFIP could be used to stabilized radicals. On the
1
contrary, the yield was slightly diminished by using CH CN
3
only (entry 2). Among a variety of supporting electrolytes,
n
n
Bu NClO and Bu NPF demonstrated lower efficiency
4
4
4
6
n
compared to Bu NBF (33−35% yield, entries 3 and 4). In
4
4
Received: December 20, 2018
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03274
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Optimization Study for the Electrochemical
Aminoselenation of Styrene
Scheme 2. Substrate Scope of Electrochemical
Aminoselenation
a
a
b
entry
variation from the standard reaction conditions
yield (%)
1
2
3
4
5
6
7
8
9
none
80
61
35
33
42
60
62
73
60
NR
CH CN (10 mL) instead of HFIP/CH CN
3
3
n
n
Bu NClO instead of Bu NBF
4
4
4
4
n
n
Bu NPF instead of Bu NBF
4
4
6
4
Pt(+)|Pt(−) instead of C(+)|Pt (−)
C(+)|C(−) instead of C(+)|Pt(−)
6 mA instead of 15 mA, 4 h
12 mA instead of 15 mA, 4 h
40 °C instead of rt
1
0
no electricity, N2
a
Standard reaction conditions: Pt plate (15 mm × 15 mm × 0.3 mm)
cathode, graphite rod anode (Φ 6 mm), constant current = 15 mA, 1a
n
(
0.5 mmol), 2a (0.25 mmol), 5a (0.5 mmol), Bu NBF (0.2 mmol),
a
4
4
Standard reaction conditions: Pt plate (15 mm × 15 mm × 0.3 mm)
HFIP (2 mL), CH CN (8 mL), room temperature, 4 h (4.6 F/mol),
undivided cell. Yield of isolated product.
3
cathode, graphite rod anode (Φ 6 mm), constant current = 15 mA, 1a
b
n
(
0.5 mmol), 2a (0.25 mmol), 5a (0.5 mmol), Bu NBF (0.2 mmol),
4
4
HFIP (2 mL), CH CN (8 mL), room temperature, 4 h (4.6 F/mol),
undivided cell. Yield of isolated product.
3
b
order to test the electrode effect, platinum plates or graphite
rods (Φ 6 mm) were applied for both electrodes and furnished
compound 6a in 42−60% yields (entries 5 and 6).
Furthermore, changing the operating current (6 mA or 12
mA) was proved to be less efficient as well (62−73%, entries 7
and 8). When the temperature was raised to 40 °C, 6a was
observed in 60% yield only. Control experiments showed that
no desired product was generated without electricity (entry
Scheme 3. Electrochemical Aminoselenation with Various
a
Amino Nucleophiles and Diselenide
1
0).
With the optimized reaction conditions in hand, we
examined electronic and steric effects for this reaction with
various styrene derivatives as shown in Scheme 2. Styrenes
bearing electron-rich and -deficient substitution at the para-,
meta-, and ortho-positions 1b−m reacted efficiently with
benzotriazole (5a) and diphenyl selenide (2a) to afford the
desired products 6b−m in 42−82% yield. It is noteworthy that
all valuable electrophilic functional groups, such as fluoro,
chloro, bromo, or ester substitutions, are well tolerated.
Furthermore, vinylnaphthalene (1n), 1,1-diphenylethylene
(1o), and α-methylstyrene (1p) were used as substrates to
render the desired products 6n−p in moderate to good yield
(
53−73%).
Electrochemical alkene difunctionalization was further
probed with various amino sources, such as benzotriazole 5b,
saccharin (5c), pyrazole 5d−e, and sulfamide (5f), affording
the corresponding β-amido selenides 6q−u (Scheme 3) in
reasonable yields (35−64%). We were pleased to discover that
anilines 5g,h were applicable under the reaction conditions,
and the desired amidoselenides 6v,w could be obtained in 73
and 64% yield, respectively. In addition, aliphatic diselenides
also led to the desired products 6x,y in moderate to good
yields. This reaction therefore represents a breakthrough to the
limited intermolecular selenide difunctionalization and im-
proves the potential of this protocol for use in the
pharmaceutical industry.
a
Standard reaction conditions: Pt plate (15 mm × 15 mm × 0.3 mm)
cathode, graphite rod anode (Φ 6 mm), constant current = 15 mA, 1a
n
(
0.5 mmol), 2 (0.25 mmol), 5 (0.5 mmol), Bu NBF (0.2 mmol),
4
4
HFIP (2 mL), CH CN (8 mL), room temperature, 4 h (4.6 F/mol),
3
b
undivided cell. Yield of isolated product.
Formic acid (7a), acetic acid (7b), butyric acid 7c,d, benzoic
acid (7e), and cycloproylcarboxylic acid 7f proved to be very
good nucleophiles for this transformation, affording the
corresponding products 8a−f in 41−90% yield. Notably,
when benzoic acid was used as the nucleophile, the desired
product 8e was obtained in 90% yield. However, when water
was used as the nucleophile, only 35% of the corresponding
product 8g was isolated. Encouraging by these results, we have
In consideration of the remarkably broad substrate scope
displayed by the electrochemical conditions, we performed this
transformation with several other nucleophiles including
carboxylic acids, water, and alcohols (Scheme 4, 7a−l).
B
DOI: 10.1021/acs.orglett.8b03274
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 4. Electrochemical Oxyselenation with Various
Oxy-nucleophiles
Thereafter, radical addition of A to alkene provides radical B
in good regioselectivity. Subsequently, further anodic oxida-
tion, nucleophilic attack as well as deprotonation leads to the
formation of product 4. Alternatively, we cannot rule out the
pathway that diphenyl diselenide (2a) undergoes anodic
oxidation followed by the formation of the cyclic selenium
a
8
intermediate E, which reacts with NuH to form the final
product.
We have developed highly efficient electrochemical amino-
selenation and oxyselenation reactions which can run at room
temperature without any hazardous additives (acids, oxidants,
or transition metals). This provides a green way for the
synthesis of phenylselenenylated molecules. In the amino-
selenation, secondary phenylalkyl amines can act as a reaction
component to generate aminated products which are difficult
to make via known methods. Further applications of
electrochemical difunctionalization of olefins are currently
underway in our laboratory.
a
Standard reaction conditions: Pt plate (15 mm × 15 mm × 0.3 mm)
cathode, graphite rod anode (Φ 6 mm), constant current = 15 mA, 1a
(
0.5 mmol), 7 (1 mL) (7d−f 10 equiv), diphenyl selenide 2a (0.25
n
mmol), Bu NBF (0.2 mmol), HFIP (2 mL), CH CN (8 mL), room
4
4
3
b
temperature, 4 h (4.6 F/mol), undivided cell. Yield of isolated
ASSOCIATED CONTENT
■
product. c Using CH CN (10 mL) as solvent only.
3
*
S
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03274.
extended the scope of this oxyselenation to various alcohols
7
h−l and obtained the desired products 8h−l in moderate
yields (40−67%). Low conversion of starting materials was the
main reason for reactions in lower yields.
Experimental procedure, characterization data, and
1
13
To gain some insight into the reaction mechanism, three
substrates were conducted in cyclic voltammetry experiments
copies of H and C NMR spectra (PDF)
(
Figure S1). An obvious oxidation peak of substrate 1a could
AUTHOR INFORMATION
Corresponding Authors
■
*
*
be observed at 2.25 V (Figure S1, red line), while there was no
obvious oxidation peak for benzotriazole (5a). Moreover, the
diphenyl diselenide (2a) demonstrated an oxidation peak at
E-mail: aiwenlei@whu.edu.cn.
E-mail: yihungchen@whu.edu.cn.
ORCID
1
.88 V (Figure S1, blue line). A reduction peak of diphenyl
diselenide (2a) was observed at −1.74 V under the reaction
solvent system (Figure S2, blue line). Therefore, the diphenyl
diselenide (2a) may involve in both oxidation and reduction
processes in the catalytic cycle.
Yong Yuan: 0000-0003-3196-1747
Yi-Hung Chen: 0000-0001-6731-1119
Aiwen Lei: 0000-0001-8417-3061
Author Contributions
On the basis of our mechanistic studies and literature
7
reports, the proposed mechanism of electrochemical oxidative
∥
L.S. and Y.Y. contributed equally to this work.
Notes
amino- and oxyselenation of styrenes is depicted in Scheme 5.
The reaction might be initiated by the formation of seleno
radical A and selenium anion via cathodic reduction.
The authors declare no competing financial interest.
Scheme 5. Proposed Reaction Mechanism
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (21702081, 21702150), China Post-
doctoral Science Foundation (BX201600114, 2016M602340),
and Jiangxi Provincial Education Department Foundation
(
GJJ160325).
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DOI: 10.1021/acs.orglett.8b03274
Org. Lett. XXXX, XXX, XXX−XXX