Visible-light-promoted oxidative coupling of styrene with cyclic ethers

Article abstract of DOI:10.1007/s11426-019-9609-9

A new visible-light-promoted oxidative coupling of vinylarenes with cyclic ethers has been developed using rose bengal as photocatalyst and tert-butyl hydrogenperoxide (TBHP) as oxidant under ambient air at room temperature. A library of α-oxyalkylated ketones with broad functionalities has been synthesized in moderate to good yields. A radical mechanism is suggested for the present protocol.

Full text of DOI:10.1007/s11426-019-9609-9

SCIENCE CHINA
Chemistry
•ARTICLES•
https://doi.org/10.1007/s11426-019-9609-9
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Visible-light-promoted oxidative coupling of styrene with cyclic
ethers
Golam Kibriya, Debashis Ghosh & Alakananda Hajra*
Department of Chemistry, Visva-Bharati (A Central University), Santiniketan 731235, India
Received July 18, 2019; accepted September 9, 2019; published online October 22, 2019
A new visible-light-promoted oxidative coupling of vinylarenes with cyclic ethers has been developed using rose bengal as
photocatalyst and tert-butyl hydrogenperoxide (TBHP) as oxidant under ambient air at room temperature. A library of α-
oxyalkylated ketones with broad functionalities has been synthesized in moderate to good yields. A radical mechanism is
suggested for the present protocol.
visible-light, organophotocatalysis, oxidative coupling, oxyalkylation
Citation:
Kibriya G, Ghosh D, Hajra A. Visible-light-promoted oxidative coupling of styrene with cyclic ethers. Sci China Chem, 2019, 62, https://doi.org/
10.1007/s11426-019-9609-9
1 Introduction
form CX–CC bonds via difunctionalization have a great
synthetic impact [11]. On the other hand, cyclic ethers such as
tetrahydrofuran and 1,3-dioxolone are also important motifs.
Moreover, the infusion of cyclic ethers into vinylarenes serves
a biologically-potent molecular-scaffold. Although some
methodologies have been developed for the synthesis of α-
oxyalkyl ketones, the methods suffer from the use of metal
catalysts and high temperature (Scheme 1(a)) [11f–11j].
However, synthesis of α-oxyalkyl ketones via oxidative cou-
pling at room temperature under metal-free conditions is not
reported till now. Therefore, development of a straightforward
and efficient method for the synthesis of α-oxyalkyl ketones is
highly desirable in organic synthesis. In continuation of our
research interest in the field of visible-light photoredox cata-
lysis [12], herein, we report a visible-light-mediated oxidative
coupling of vinylarenes with cyclic ethers using rose bengal as
photosensitizer under aerobic conditions (Scheme 1(b)).
Recently, visible-light-mediated photoredox process has
emerged as a powerful tool in valuable synthetic organic
transformations [1]. Although the classic metal photo-
catalysts like ruthenium and iridium polypyridyl complexes
are commonly employed as efficient visible-light photo-
catalysts in various reactions, the high price and toxicity
limit their practical applicability [2]. Thus, organic dyes
being nontoxic, inexpensive and easy to handle are used as a
superior alternative to the transition-metal complexes in
photoredox catalyzed reactions [3].
Difunctionalization of vinylarenes is an important area in
organic synthesis [4]. Recently, a lot of effort has been made
for the transition-metal-catalyzed difunctionalization of vi-
nylarenes including dioxygenation [5], diamidation [6], di-
hydroxylation [7], hydroxyacetoxylation [8], diamination [9],
aminoacetoxylation [10] etc. Although difunctionalization of
vinylarenes offers huge range of structurally diverse products,
the reactions are mainly limited to CX–CX bond formations.
Therefore, the conversions of C–H bonds of vinylarenes to
2 Experimental
2.1 General information
All reagents were purchased from commercial sources and
*Corresponding author (email: alakananda.hajra@visva-bharati.ac.in)
© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
chem.scichina.com link.springer.com

2
Kibriya et al. Sci China Chem
hydrofuran (2a) as model substrates employing benzoyl
peroxide (BPO) as oxidant (3 equiv.), DABCO (2 equiv.) as
additive and rose bengal (RB) as a photocatalyst under 34 W
blue LED at room temperature. To our delight, 1-phenyl-2-
(tetrahydrofuran-2-yl)ethan-1-one (3aa) was obtained in
48% yield after 18 h under ambient air (Table 1, entry 1).
Further improvement of the yield was not observed even
after 36 h. Inspired by the initial result, we carried out the
reaction under different conditions to further improvement of
Table 1 Optimization of the reaction conditionsa)
Scheme 1 Synthesis of α-oxyalkyl ketones.
used without further purification. 1H nuclear magic re-
sonance (1H NMR) spectra were determined on 400 MHz
spectrometer as solutions in CDCl3. Chemical shifts are ex-
pressed in parts per million (δ) and the signals were reported
as s (singlet), d (doublet), t (triplet), m (multiplet), and
coupling constants (J) were given in Hz. 13C{1H} NMR
spectra were recorded at 100 MHz in CDCl3 solution. Che-
mical shifts as internal standard are referenced to CDCl3
1
(δ=7.26 for H and δ=77.16 for 13C{1H} NMR) as internal
standard. Thin layer chromatography (TLC) was done on
silica gel coated glass slide. All solvents were dried and
distilled before use. Commercially available solvents were
freshly distilled before the reaction. All reactions involving
moisture sensitive reactants were executed using oven dried
glassware.
Entry
1
Photocatalyst
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
eosin Y
Oxidant
BPO
Additive
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DBU
Yield (%)
48
2
H2O2
trace
31
3
DTBP
TBHP
K2S2O8
PhI(OAc)2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
–
4
88
2.1 General procedure for the synthesis of 3
5
42
6
26
A mixture of vinylarene (1, 0.25 mmol), ether (2, 2.0 mL),
rose bengal (2 mol%, 5 mg), 1,4-diazabicyclo[2.2.2]octane
(DABCO) (2.0 equiv., 56 mg) and tert-butyl hydrogenper-
oxide (TBHP) (3.0 equiv., 5.0–6.0 M in dacane, 0.105 mL)
was taken in an oven-dried reaction vessel equipped with a
magnetic stir bar. Then reaction mixture was irradiated using
Kessil 34 W blue LED at room temperature under open at-
mosphere for 18 h. The progress of the reaction was mon-
itored by TLC. After completion, the reaction mixture was
quenched with 10 mL water/ethyl acetate (1:3). Then the
reaction mixture was extracted with ethyl acetate and the
organic phase was dried over anhydrous Na2SO4. After
evaporating the solvent under reduced pressure, the crude
residue was obtained. Finally, it was purified by column
chromatography on silica gel (60–120 mesh) using petro-
leum ether/ethylacetate as an eluent to afford the pure pro-
ducts 3.
7
55
8
eosin B
65
9
rhodamine 6G
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
–
45
10
11
12
13
14
15
16
17
18
19
20
21
20
Et3N
trace
36
Na2CO3
K2CO3
25
Cs2CO3
DABCO
–
58
N.R.
N.R.
N.R.
52b), 82c)
45d), 72e)
N.R.f)
traceg)
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
DABCO
DABCO
DABCO
DABCO
DABCO
TBHP
TBHP
TBHP
TBHP
a) Reaction conditions: all reactions were carried out with 1a
(0.25 mmol), 2a (2.0 mL), photocatalyst (2 mol%), base (2.0 equiv.), oxi-
dant (3.0 equiv.), irradiated with 34 W blue LED for 18 h under air at room
temperature. N.R.=no reaction. b) 1.0 equiv. DABCO and c) 3.0 equiv.
DABCO. d) 2.0 equiv. TBHP and e) 4.0 equiv. TBHP. f) Under argon
atmosphere. g) 6.0 equiv. TBHP under argon atmosphere.
3 Results and discussion
We commenced our study using styrene (1a) and tetra-

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Kibriya et al. Sci China Chem
Table 2 Substrate scopea)
the yield and the results are summarized in Table 1. Initially,
we checked the effect of different oxidant such as H2O2, di-
tert-butyl peroxide (DTBP), TBHP, K2S2O8 and PhI(OAc)2
(Table 1, entries 2–6). Interestingly, highest product yield
was obtained (88%) in presence of TBHP (Table 1, entry 4).
The effect of other photocatalysts such as eosin Y, eosin B
and rhodamine 6G were also tested but these were not ef-
fective as rose bengal (Table 1, entries 7–9). We also
screened the effect of different bases like 1,8-diazabicyclo
[5.4.0]undec-7-ene (DBU), Et3N, Na2CO3, K2CO3 and Cs2
CO3 but these were not suitable like DABCO (Table 1, en-
tries 10–14). No product formation was observed in the ab-
sence of photocatalyst (Table 1, entry 15). The reaction did
not proceed without any base and oxidant (Table 1, entries 16
and 17). The yield of the product was decreased with de-
creasing the amount of DABCO but no significant im-
provement of the reaction yield was found with increasing
the loading of base (Table 1, entry 18). The yield of the
reaction decreases with decreasing as well as increasing the
amount of TBHP (Table 1, entry 19). Moreover, the forma-
tion of desired product was not observed under argon at-
mosphere (Table 1, entry 20). Also only trace amount of
desire product was observed even in the presence of excess
amount of TBHP under argon atmosphere (Table 1, entry
21). Thus, the optimized yield (88%) was obtained using
2 mol% rose bengal, 2.0 equiv. DABCO and 3.0 equiv.
TBHP under the irradiation with 34 W blue LED for 18 h
under ambient air at room temperature (Table 1, entry 4).
With the optimized reaction conditions in hand, next we
examined the substrate scope of this oxidative coupling re-
action. We first investigated the effect of different substituent
on styrene and the results are summarized in Table 2. Styrene
t
bearing electron-donating substituents like Me, Bu, OMe
and OtBu in different position of benzene ring afforded the
corresponding oxyalkylated ketones in excellent yields
(3ba–3ha). Halogen (F, Cl and Br)-containing styrenes also
worked well under the optimized reaction conditions (3ia-
3la). To our delight, 4-vinyl-1,1′-biphenyl and 2-vi-
nylnaphthalene also produced the desired coupling products
in 86% and 73% yield (3ma and 3na). In addition, α-methyl
styrene successfully furnished the corresponding oxyalky-
lated ketone in good yield (3oa). Next, we checked the
feasibility of other ethers in this oxidative coupling reaction.
2-Methyl tetrahydrofuran, 1,3-dioxolone, tetrahydropyran
and 1,4-dioxane effectively coupled with various styrenes
and afforded the corresponding oxyalkylated ketones with
good to excellent yields (3ab–3ke). However, 1-octene (1q),
diethyl ether (2f) and 2-propanol (2g) did not afford the
desired products.
a) Reaction conditions: 1 (0.25 mmol), 2 (2.0 mL), rose bengal (2 mol%
), DABCO (2.0 equiv.) and TBHP (5.0–6.0 M in dacane, 3.0 equiv.), ir-
radiated with 34 W blue LED for 18 h under ambient air at room tem-
perature.
To show the practical applicability of the current metho-
dology, gram-scale reaction was performed in the usual la-
boratory setup by taking styrene (1a) in 7 mmol scale. 1-
Phenyl-2-(tetrahydrofuran-2-yl)ethan-1-one (3aa) was ob-
Scheme 2 Gram-scale synthesis of 3aa.

4
Kibriya et al. Sci China Chem
tained without significant decrease in the yield (83%)
(Scheme 2).
To find out the mechanistic insights of the reaction path-
way, few control experiments were carried out (Scheme 3).
Styrene (1a) failed to give the corresponding α-oxyalkylated
ketone product (3aa) in the presence of radical scavengers
butoxy radical t-BuO• and hydroxyl radical HO• [13a–13c].
Abstraction of hydrogen from THF (2a) by tert-butyloxy
radical generates a α-oxy radical intermediate A which adds
on to styrene (1a) to give the benzylic radical intermediate B.
Then intermediate B combinations with aerobic oxygen (O2)
to form the peroxy radical intermediate C, which on further
combination with another molecule of intermediate B fol-
lowed by homolysis of O–O bond gives rise to intermediate
E [13b,13c]. Finally, intermediate E is oxidized by hydroxyl
radical HO• to afford the final product 3aa.
like
2,2,6,6-tetramethylpiperidine-1-oxyl
(TEMPO)
(Scheme 3, eq A, (i)) and 2,6-di-tert-butyl-4-methyl phenol
(BHT) (Scheme 3, eq A, (ii)). Moreover, with the addition of
stoichiometric amount 1,1-diphenylethylene, the present re-
action completely suppressed along with the formation of 2-
(2,2-diphenylvinyl)tetrahydrofuran (4aa) in 76% yield
(Scheme 3, eq B). These observations clearly suggest the
radical pathway of the reaction.
4 Conclusions
On the basis of control experiments and literature reports
[13], a plausible mechanistic pathway has been outlined in
Scheme 4. Initially, the ground state of RB is converted to its
excited state RB* under blue LED irradiation. Then, RB*
transfers its energy to t-BuOOH and returns to its ground-
state. Although there is an another possibility that RB* can
transfer its energy to 3O2 to convert it into 1O2 and returns to
its ground-state, the possibility of the reaction pathway via
In summary, we have developed a straightforward and effi-
cient method for the synthesis of α-oxyalkyl ketones via
oxidative coupling of vinylarenes and cyclic ethers under
irradiation of blue LED at room temperature. A variety of
oxyalkylated ketones with broad functionalities was syn-
thesized under the optimized reaction conditions with good
yields. Metal-free, mild reaction conditions, ambient air and
gram-scale synthesis are the attractive features of this pro-
tocol. To the best of our knowledge, this is the first report of a
visible-light-promoted oxyalkylation of vinylarenes. We
believe that the present methodology opens a new door in
organic synthesis to synthesize α-oxyalkyl ketones.
1O2 might be excluded as the reaction occurs in the presence
1
of DABCO which is known as O2 quencher [13h–13i].
Subsequently, t-BuOOH produces two radical species: tert-
Acknowledgements This work was supported by Council of Scientific and
Industrial Research (CSIR), and New Delhi (02(0307)/17/EMR-II). D.G
thanks University Grants Commission (UGC) (DSK) for his fellowship.
Conflict of interest The authors declare that they have no conflict of
interest.
Supporting information The supporting information is available online at
http://chem.scichina.com and http://link.springer.com/journal/11426. The
supporting materials are published as submitted, without typesetting or
editing. The responsibility for scientific accuracy and content remains en-
tirely with the authors.
Scheme 3 Control experiments.
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