Synthesis of 2-substituted pyrimidines and benzoxazoles via a visible-light-driven organocatalytic aerobic oxidation: Enhancement of the reaction rate and selectivity by a base

Article abstract of DOI:10.1039/c4gc00337c

An efficient visible-light-driven photocatalytic oxidation of various 2-substituted dihydropyrimidines and phenolic imines has been achieved using an organic photocatalyst eosin Y bis(tetrabutyl ammonium salt) (TBA-eosin Y) and inexpensive oxidant molecular oxygen. With the aid of a base, significantly enhanced photoinduced electron transfer from substrates dihydropyrimidines or phenolic imines to the excited state of TBA-eosin Y has enabled the aerobic oxidation to yield 2-(methylthio)pyrimidines or 2-arylbenzoxazoles selectively. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4gc00337c

View Article Online
View Journal
Green
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: L. Wang, Z. Ma, X.
Wei, Q. Meng, D. Yang, S. Du, Z. Chen, L. Wu and Q. Liu, Green Chem., 2014, DOI:
10.1039/C4GC00337C.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/greenchem

Page 1 of 7
Green Chemistry
View Article Online
DOI: 10.1039/C4GC00337C
Synthesis of 2-Subsituted Pyrimidines and Benzoxazoles via
a
Visible-Light-Driven Organocatalytic Aerobic Oxidation: Enhancement of
Reaction Rate and Selectivity by a Base
Lin Wang, Zhi-Gang Ma, Xiao-Jing Wei, Qing-Yuan Meng Deng-Tao Yang,
Shao-Fu Du, Zi-Fei Chen, Li-Zhu Wu and Qiang Liu
Table of Contents
With the aid of a base, a highly efficient visible-light-driven aerobic dehydrogenation of
2-subsituted dihydropyrimidines and phenolic imines has been achieved.

Green Chemistry
Page 2 of 7
Green Chemistry
RSCPublishing
View Article Online
DOI: 10.1039/C4GC00337C
COMMUNICATION
Synthesis of 2-Subsituted Pyrimidines and
Benzoxazoles via a Visible-Light-Driven
Organocatalytic Aerobic Oxidation:
Enhancement of Reaction Rate and Selectivity
by a Base
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2014,
Accepted 00th January 2014
Lin Wang,a Zhi-Gang Ma,a Xiao-Jing Wei,a Qing-Yuan Meng b Deng-Tao Yang,a
DOI: 10.1039/x0xx00000x
Shao-Fu Du,a Zi-Fei Chen,a Li-Zhu Wu* b and Qiang Liu*a
www.rsc.org/
An efficient visible-light-driven photocatalytic oxidation of studied extensively.7 Generally, there are two well-established
various 2- subsituted dihydropyrimidines and phenolic imines types of photocatalytic aerobic oxidations: energy-transfer and
has been achieved by using organic photocatalyst eosin Y electron-transfer oxygenations.8 Molecular oxygen can be either
bis(tetrabutyl ammonium salt) (TBA-eosinY) and inexpensive converted to singlet oxygen or reduced to superoxide radical
oxidant molecular oxygen. With the aid of
a base, anion. Unfortunately, in many cases, the two types occur
significantly enhanced photoinduced electron transfer from simultaneously, giving rise to a complex mixture of oxygenated
substrates dihydropyrimidines or phenolic imines to the products. In particular, the multiple parallel pathways of singlet
excited state of TBA-eosinY has enabled the aerobic oxidation oxygen such as “ene” reaction, cycloaddition, and heteroatom
to yield 2-(methylthio)pyrimidines or 2-arylbenzoxazoles oxidation always lead to poor chemoselectivity. 9 Therefore, an
selectively.
efficient improvement of the chemoselectivity of photocatalytic
aerobic oxidation by suppressing the side reaction of singlet
oxygen is highly desirable but still challenging.
Introduction
Molecular oxygen is a cheap, ecologically benign and most
abundant oxidant. Owing to the current demands to develop
sustainable chemical processes, this ideal reagent has attracted
widely attention and become the most promising alternative
approaches to traditional oxidation processes.1 The direct
oxidation of organic substrates by molecular oxygen at room
temperature is rare as the energy barrier for electron transfer
from the organic substrate to the oxidant is usually high. In order
to overcome the high energy barrier, often expensive reagents
and/or harsh conditions are required, thus diminishing the overall
sustainability of the process.2 Visible light is not only the main
wave band of solar energy on the earth's surface, but also the
most easily available light in daily life. In this context, driving
thermodynamically unfavourable aerobic oxidations by visible
light at room temperature is undoubtedly appealing because it
highly fulfills the increasing demand for “green chemistry”.3
Recently, some interesting results have demonstrated the great
potential and the bright prospect of this subject except that the
scope was limited to amines,4 arylboronic acids,5 and thiophenol6
etc.
Scheme 1 Molecules containing the 2‐subsituted pyrimidine and benzoxazole
structural motif.
As viable alternatives of classical iridium- and ruthenium-
based transition metal photocatalysts, organic photocatalysts
have attracted an increasing interest in visible-light-driven
photoreactions in the recent years.10 We have shown that eosin
Y
bis(tetrabutyl ammonium salt) (TBA-eosinY) is an idea
photocatalyst for visible-light-induced aerobic cross-
dehydrogenative coupling (CDC) reaction, in which superoxide
radical anions rather than singlet oxygen was formed during
visible-light irradiation. 11 To further explore the advantages of the
metal-free visible-light-driven aerobic oxidations, we focused our
Regardless of the disadvantage of high-energy ultraviolet
radiation, molecular oxygen mediated photoreactions in the
presence of photosensitizers or photocatalysts have been
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1‐3 | 1

Page 3 of 7
COMMUNICATION
Green Chemistry
Journal Name
attention upon improving the chemoselectivity by regulating the Results and discussion
pathways of molecular oxygen in the reactions. In this paper, we
2-Substituted pyrimidines are extensively occurred in both
View Article Online
DOI: 10.1039/C4GC00337C
wish to report a highly efficient and selective visible-light-driven
aerobic oxidation of 1,4-dihydropyrimidines and phenolic imines
in the presence of TBA-eosinY and a base. With this system, 2-
subsituted pyrimidines and benzoxazoles, which are often found
in compounds that exhibit biological activities (Scheme 1),12,13
were produced in moderate to excellent yields respectively.
Mechanistic studies indicate that addition of a base significantly
contributes to the electron transfer from substrates to the excited
TBA-eosinY, thereby suppresses the side reaction of singlet
oxygen and results in the highly chemoselective oxidative
dehydrogenation.
natural products and synthetic compounds with interesting
biological properties.12 From a synthetic chemistry point of view,
dehyhrogenation of dihydropyrimidines (DHPMs) is one of the
most concise approaches to obtain pyrimidines because DHPMs
can be easily produced by Biginelli three-component coupling
reaction.14 However, due to its high oxidation potential, the
normal conditions for dehydrogenation of DHPMs require excess
corrosive or powerful oxidants, high temperatures, or both.15 The
utility of
a visible-light photocatalytic aerobic oxidation to
dehydrogenate DHPMs has not been reported.16 In this context,
our initial investigation focused on an efficient protocol for the
synthesis of 2-substituted pyrimidines through a visible-light
photocatalytic aerobic oxidation catalyzed by TBA-eosinY. As an
acetonitrile solution containing 2-(methylthio) DHPMs 1a and
Table 1 Optimization of the aromatization reaction conditions a
Br
Br
+X-O
Br
O
O
TBA-eosin Y, oxidant
hν = 450 nm
Sovlent, Base
O
O
TBA-eosinY (1 mol%) were irradiated by 3 W blue LEDs (λ = 450
Br
O
N
O
N
nm) in open vessels at ambient conditions for 8 hours, the
desired dehydrogenated product 1b was obtained in 38% yield
accompanying with the formation of complex mixture of
byproduct, which may mainly attributed to the decomposition of
primary oxygenated products from the reaction of DHPMs 1a and
singlet oxygen. Considering photocatalytic aerobic oxidation is
sensitive to the solvent polarity, we then performed the same
photosensitized oxidation in a variety of solvents (Table 1,
entries 1-7). As can be seen in Table 1, methanol was chosen as
the ideal organic solvent for the reaction. Replacement of air by
other oxidants including CBr4 and CCl3Br gave a similar yield but
a longer reaction time (Table 1, entries 8 and 9). Strikingly, when
2 equivalent of K2CO3 was added to the photocatalytic aerobic
oxidation system, the yield of pyrimidine 1b was significantly
improved (Table 1, entry 10). The best result was achieved in a
mixture of methanol and water (10:1 v/v) (Table 1, entry 11). In
this case we obtained the desired pyrimidine 1b in 90% isolated
yield. Interestingly, the employment of pure oxygen instead of air
decreased the yield of the dehydrogenated product (Table 1,
entry 12). Control experiments showed that the presence of TBA-
eosinY, air, and light source is necessary for the desired reaction
to proceed (Table 1, entries 13–15).
COO- X+
N
H
S
N
S
2a
1a
X = (nC4H9)4N
TBA-eosinY
Entry
Solvent
CH3CN
Additives
t (h)b Yield (%) c
1
2
3
Air
Air
Air
8
8
38
41
52
THF
CHCl3
CH2Cl2
PhCH3
PhCF3
MeOH
MeOH
MeOH
MeOH
5
4
Air
Air
Air
Air
7
9
7
1
2
2
1
56
60
69
66
67
64
83
5
6
7
8
CBr4 (2 eq.)
9
BrCCl3 (2 eq.)
10
Air，K2CO3 (2 eq.)
Air，K2CO3 (2 eq.)
With the optimal reaction conditions in hand, we next
investigated the substrate scope and limitation of 2-substituted
DHPMs (Table 2). A series of 2-S-alkylated DHPMs with various
substituents at C-4, C-5 and C-6 position of the DHPM ring were
found to undergo the desired oxidation dehydrogenation
smoothly under the standard reaction conditions, affording the
11d
MeOH
MeOH
MeOH
MeOH
MeOH
1
1
4
4
4
90
79
--
12d
O2(1 atm)，K2CO3 (2 eq.)
Air，K2CO3 (2 eq.)
Air，K2CO3 (2 eq.)
Ar，K2CO3 (2 eq.)
13d,e
14d,f
15d,g
--
corresponding target products in 70-98% yields (Table 2, 2a-2u).
In particular, 2-(methylthio) pyrimidine 2l as basic intermediate
for synthesis of rosuvastatin derivative S-4522, a HMG-GoA
reductase inhibitors,12b-12d was also efficiently produced in 97%
yield. It was reported that Isopropyl or cyclopropyl group located
at C-4 of DHPMs is sensitive to dehydrogenation conditions.15g,17
In our case, however, the desired products could be smoothly
--
a
Reaction conditions: 1a (0.1 mmol), TBA-eosinY (1 mol%), K2CO3 (0.2
mmol), Solvent 5 mL, air , 3 W 450 nm LED irradiation at RT. b The time
c
when 1a was no longer consumed. Isolated yield (average of two parallel
experiments). d With addition of 0.5 mL water. Reaction was carried out in
e
f
g
the dark. Reaction was performed without catalyst. Reaction was carried
out under argon.
obtained under the reaction conditions (Table 2, 2s
, 2t).
Furthermore, the dehydrogenation of 2-O-alkylated DHPMs
proceeded smoothly to give pyrimidines with satisfactory yields
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012

Green Chemistry
Page 4 of 7
COMMUNICATION
Journal Name
(Table 2, 2v
-2x). To demonstrate the practicability of this visible- molecular oxygen to generate either superoxide radical anion or
light driven photocatalytic process, we performed the aerobic singlet oxygen.18 In the present case, the sharp contrast of
dehydrogenation of 1a on a gram scale using the ambient selectivity between absence and presence of K2CO3
View AirnticdleicOantleinde
DOI: 10.1039/C4GC00337C
sunlight as the only source of irradiation. It was glad to see that that the undesired reaction between singlet oxygen and DHPMs
the reaction of 1a proceeded very well giving 2a in 86% yield was greatly suppressed by the addition of K2CO3. To assess the
within 4 hours (see ESI†).
generation ability of singlet oxygen in the photocatalytic TBA-
eosin Y system, 2,2,6,6-tetramethylpiperidine (TEMP) were
employed as a probe to react with singlet oxygen. The adduct
TEMPO can be easily detected by electron spin resonance (ESR)
Table 2: The substrate scope for 2-substituted pyrimidine.a ,b
spectroscopy.11 It is clearly shown in Figure
1 that when the
solution of TEMP, TBA-eosin Y, and 1a in air-saturated
methanol/water (10:1, v/v) was irradiated with the laser at 532
nm, a single radical was trapped (Figure 1, left, A), the spectrum
OEt
and hyperfine coupling constants of which are in agreement with
11
the reported values for the nitroxide radical TEMPO.
By
EtO2
C
MeO2C
contrast, when K2CO3 was added to the system, the nitroxide
radical TEMPO was not detected (Figure 1, left, B). If the
disappearance of singlet oxygen in the presence of K2CO3 was
attributed to the improvement electron transfer from 1a to the
excited TBA-eosin Y, the generation of TBA-eosin Y radical
anion should be detected in anaerobic methanol–water solutions
by flash-photolysis. Actually, when the solution of EY and 1a in
the presence of K2CO3 was excited with a 532 nm laser pulse, an
N
N
EtO2C
N
N
S
N
S
N
S
2b, 88%
2a, 90%
2c, 84%
2d, 81%
OCH3
O
O
OBn
EtO2
C
EtO2C
EtO2
C
N
N
N
N
S
N
S
N
S
absorption at 406 nm (τ0 = 469 μs) was clearly observed (Figure
2f, 82%
2g, 96%
2h, 87%
2e, 88%
1, right, B), which is in line with that of reported eosin Y radical
anion.19 On the contrary, no obvious absorption around 406 nm
was generated upon flash-photolysis of an anaerobic solution
containing TBA-eosin Y and 1a (Figure 1, right, A), indicating
that the electron transfer from 1a to the excited TBA-eosin Y is
ineffective in the absence of K2CO3.
Cl
Cl
F
CF3
Cl
S
EtO2C
MeO2C
EtO2C
MeO2C
N
N
N
N
N
S
N
S
N
N
S
2j, 93%
2l, 97%
2k, 74%
2i, 94%
Cl
OCH3
EtO2C
Ph
N
EtO2C
Ph
EtO2C
Ph
EtO2C
N
N
N
N
S
N
S
N
S
N
S
2m, 98%
2o, 89%
2n, 92%
2p, 90%
6
EtO2C
EtO2C
EtO2C
N
EtO2C
N
N
N
N
S
N
S
N
S
N
S
2s, 78%
2q, 89%
2t, 71%
2r, 84%
Cl
OCH3
O
N
EtO2C
EtO2C
EtO2C
N
N
EtO2
C
N
N
O
N
S
N
O
N
O
2x, 83%
2u, 70%
2v, 86%
2w, 80%
Figure 1 Left: ESR spectrum of a solution of TBA‐eosin Y (1.0
(1.0
10‐2 mol.L‐1), and TEMP (0.5 mol.L‐1) in air‐saturated methanol/ water(10:1
v/v) in the absence (A) and presence (B) of K2CO3 (2.0
10‐2 mol.L‐1)upon
×
10‐4mol.L‐1), 1a
×
a
Unless otherwise stated, the reaction conditions are: 1 (0.1 mmol), TBA-
×
eosinY (1 mol%), K2CO3 (0.2 mmol), Methanol 5 mL and H2O 0.5 mL, Air , irradiation for 20 s. Right: Transient absorption difference spectra of TBA‐eosin Y
×
3 W 450 nm LED visible-light irradiation at RT. b Isolated yield (average of (1.0
×
10‐5mol.L‐1) and 1a (1.0 10‐3 mol.L‐1) with 532 nm light in anaerobic
methanol/ water(10:1 v/v) in the absence (A) and presence (B) of K2CO3
two parallel experiments).
(2.0×
10‐3 mol.L‐1). Inset: kinetic traces at 406 nm obtained on laser photolysis of
(1.0×
mol.L‐1) with 532 nm light.
10‐5mol.L‐1) and 1a (1.0 10‐3 mol.L‐1) in presence of K2CO3 (2.0 10‐3
×
×
The high efficiency of the dehydrogenation intrigued our interest
in understanding the primary process of the visible-light-driven
aerobic oxidation. It is known that eosin Y can react with
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1‐3 | 3

Page 5 of 7
COMMUNICATION
Green Chemistry
Journal Name
Table 3: The substrate scope for 2-substituted benzoxazole.a, b
Further evidence for the base-enhanced electron transfer was
provided by electrochemical study (see ESI†). DHPMs 1a shows
View Article Online
an irreversible oxidation event at 1.10 V (vs. NHE) in a mixture of
DOI: 10.1039/C4GC00337C
methanol and water (10:1 v/v). While K2CO3 was introduced into
the solution, the first oxidation peak of DHPMs 1a was shifted to
0.58 V (vs. NHE), which may be ascribe to the oxidation of 1a
anion. Clearly, the driving force for the electron transfer from 1a
to the excited TBA-eosin Y is more powerful in the presence of
K2CO3. Combining the electrochemical data with EPR and flash-
photolysis studies, the high efficiency of the photocatalytic
aerobic dehydrogenation can be illustrated as shown in Scheme
2: With the aid of K2CO3, DHPMs 1a was partly dissociated to 1a
anion, a much stronger electron donor. The efficient electron
transfer from 1a to the excited TBA-eosin Y suppresses the
energy transfer between the excited TBA-eosin Y and molecular
oxygen, thereby the generation of singlet oxygen and its related
side reaction are minimized. Subsequent electron from eosin Y
radical anion to molecular oxygen produces superoxide radical
anions and regenerates the photocatalyst TBA-eosinY. The 1a
radical, generated by the electron transfer between the excited
Me
OMe
Cl
O
O
O
Me
OMe
Cl
N
N
N
4a, 90%
4b, 71%
4c, 80%
Me
O
O
O
N
N
N
4e, 96%
4d, 77%
4f, 87%
MeO
O
O
O
N
N
N
4h, 94%
4i, 93%
4g, 83%
Cl
O
O
O
F
Br
N
N
N
4l, 84%
4k, 75%
4j, 89%
O
O
O
TBA-eosin
Y and 1a anion, can further react with the
CF3
CN
N
N
N
photocatalyst or superoxide radical anions to afford the
4m, 82%
4o, 94%
4n, 79%
dehydrogenated product 2a selectively.
O
O
O
CH2Cl
N
N
N
4q, 87%
4p, 93%
4r, 87%
Cl
O
Cl
O
Cl
O
F
Cl
Cl
N
N
N
4t, 71%
4s, 79%
4u, 92%
Me
O
Cl
Cl
O
O
N
Me
N
N
Me
4x, 61%
4v, 86%
4w, 67%
Me
Cl
MeO
Br
F
N
O
N
N
O
O
4z, 93%
N
4y, 90%
5a, 96%
Scheme 2 Proposed mechanism.
Me
N
O
N
O
Me
Cl
O
5d, 90%
5b, 93%
5c, 79%
With the understanding of reaction mechanism of the aerobic
oxidative dehydrogenation, we expanded the catalytic system to
oxidative cyclization of 2-subsituted phenolic imines, one of the
most popular methods for synthesizing 2-substituted
benzoxazoles.20 The phenol moiety can be easily dissociated to
the corresponding phenolate anion, a much stronger electron
donor in the presence of proper bases. This led us to assume
that the base-enhanced electron transfer from 2-subsituted
phenolic imines to the excited eosin Y could also suppress the
generation of singlet oxygen and its related side reaction,
resulting in the formation of 2-substituted benzoxazoles in high
selectivities. After several of attempts, we found that phenolic
imine 3a undergoes efficient oxidative cyclization upon visible
Me
Me
Me
N
O
Me
Me
MeO
Cl
N
O
N
O
5f, 84%
N
5g, 91%
5e, 85%
F
Me
Cl
N
O
N
O
F
Br
OMe
O
5h, 87%
5i, 91%
5j, 90%
Br
N
O
N
O
N
O
Cl
Br
Br
5m, 81%
5k, 89%
5l, 85%
a
Reaction conditions: 3 (0.1 mmol), TBA-eosinY (1 mol%), DBU (0.2
mmol), PhCF3 3 mL, Air (1 atm.) , 3 W 450 nm LED visible-light irradiation
at RT. b Isolated yield (average of two parallel experiments).
light irradiation using
1
mol% TBA-eosin
Y
with 1,8-
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012

Green Chemistry
Page 6 of 7
COMMUNICATION
Journal Name
diazabicyclo[5.4.0]undec-7-ene (DBU) as base in benzotrifluoride
(see ESI†).
Organometallics of Early Transition Metals, ed. F. Meyer, C.
Limberg, Springer, BerlinHeidelberg, 2007; Vol. 22, pp.17-37; (c) C.
View Article Online
The substrate scope of the visible-light driven aerobic oxidative
cyclization was exploited in Table 3. We found that phenolic
Parmeggiani and F. Cardona, Green Chem., 2012, 14, 547; (d) A. N.
DOI: 10.1039/C4GC00337C
Campbell and S. S. Stahl, Acc. Chem. Res., 2013, 45, 851.
imines
various aromatic aldehydes were readily converted to the desired
2-substituted benzoxazoles 4a–4w with moderate to excellent 4. (a) A. G. Condie, J. C. González-Gómez and C. R. J. Stephenson, J.
3
derived from the condensation of 2-aminophenols and 3. C. Gambarotti, L. Melone, T. Caronna and C. Punta, Current Organic
Chemistry, 2013, 17, 2406.
yields under our optimized reaction conditions. In general,
phenolic imines from electron-deficient and ortho-substitued
aldehydes were a little bit less efficient in the reaction. In addition,
the phenolic imine bearing cyclopropyl was also smoothly
transformed into 2-cyclopropylbenzoxazole 4x in 61% yield.
Moreover, we varied the substituents on the ortho-aminophenol
ring, and the corresponding products were formed in high to
Am. Chem. Soc., 2010, 132, 1464; (b) Y. Pan, S. Wang, C. W. Kee, E.
Dubuisson, Y. Yang, K. P. Loh and C.-H. Tan, Green Chem., 2011,
13, 3341; (c) S. Zhu, A. Das, L. Bui, H. Zhou, D. P. Curran and M.
Rueping, J. Am. Chem. Soc., 2013, 135, 1823; (d) Y. Miyake, K.
Nakajima and Y. Nishibayashi, J. Am. Chem. Soc., 2012, 134, 3338;
(e) W.-J. Yoo, A. Tanoue and S. Kobayashi, Chem. Asian J., 2012, 7,
2764; (f) C. Vila and M. Rueping, Green Chem., 2013, 15, 2056; (g)
J. Xuan, Y. Cheng, J. An, L.-Q. Lu, X.-X. Zhang and W.-J. Xiao,
Chem. Commun., 2011, 47, 8337; (h) G. Zhao, C. Yang, L. Guo, H.
Sun, C. Chen and W. Xia, Chem. Commun., 2012, 48, 2337; (i) D. P.
Hari and B. König, Org. Lett., 2011, 13, 3852; (j) P. Kohls, D. Jadhav,
G. Pandey and O. Reiser, Org. Lett., 2012, 14, 672; (k) S. Cai, X.
Zhao, X. Wang, Q. Liu, Z. Li and D. Z. Wang, Angew. Chem., Int.
Ed., 2012, 51, 8050; (l) J. Liu, Q. Liu, H. Yi, C. Qin, R. Bai, X. Qi, Y.
Lan and A. Lei, Angew. Chem, Int, Ed., 2014, 53, 502.
excellent yields (4y-4z, 5a-5c), indicating the electronic property
had a minimal effect on the efficiency of the oxidative cyclization.
Finally, the scope of the reaction was expanded to phenolic
imines with substituents on both aromatic rings. In all these
cases (5d-5m), the desired 2-substituted benzoxazoles were
obtained in satisfying yields.
Conclusions
5. (a) Y.-Q, Zou, J.-R, Chen, X.-P, Liu, L.-Q, Lu, R. L. Davis, K. A.
Jørgensen and W.-J. Xiao, Angew. Chem, Int, Ed., 2012, 51, 784; (b)
Y. Yasu, T. Koike and M. Akita, Adv. Synth. Catal., 2012, 354, 18; (c)
In summary, we have developed a simple and highly efficient
method for aerobic catalytic oxidative dehydrogenation of 2-
subsituted dihydropyrimidines and phenolic imines by means of
visible-light irradiation. By combining cheap, readily available
organic dye TBA-eosin Y and the most economic oxidant
molecular oxygen, the desired 2-subsituted pyrimidines and
benzoxazoles were obtained selectively under ambient
conditions. ESR, Flash photolysis and electrochemical studies
reveal that addition of a base significantly contributes to the
electron transfer from substrates to the excited TBA-eosinY,
thereby suppresses the side reaction of singlet oxygen and
results in the highly chemoselective oxidation.
C. Yu, K. Lee, Y. You and E. J. Cho, Adv. Synth. Catal., 2013, 355
,
1471; (d) S. P. Pitre , C. D. McTiernan, H. Ismaili, and J. C. Scaiano,
J. Am. Chem. Soc., 2013, 135, 13286.
6. (a) Y. Cheng, J. Yang, Y. Qu and P. Li, Org. Lett., 2012, 14, 98; (b) E.
L. Tyson, M. S. Ament and T. P. Yoon, J. Org. Chem., 2013, 78,
2046; (c) T. M. Nguyen and D. A. Nicewicz, J. Am. Chem. Soc.
,
2013, 135, 9588; (d) X. Wang, G. D. Cuny and T. Noël, Angew.
Chem., 2013, 125, 8014; Angew. Chem. Int. Ed., 2013, 52, 7860; (e)
K. Qvortrup , D. A. Rankic and D. W. C. MacMillan, J. Am. Chem.
Soc., 2014, 136, 626.
7. (a) P. Klán and J. Wirz, Photochemistry of Organic Compounds: From
Concepts to Practice, John Wiley & Sons, 2009; (b) A. Albini and M.
Fagnoni, Handbook of Synthetic Photochemistry, WILEY-VCH
Verlag, GmbH & Co. KGaA, Weinheim, Germany, 2010.
Notes and references
State Key Laboratory of Applied Organic Chemistry, Lanzhou
a
University, Lanzhou 730000, P. R. China. E-mail: liuqiang@lzu.edu.cn
b
Key Laboratory of Photochemical Conversion and Optoelectronic
8. C. S. Foote, Photochem. Photobiol., 1991, 54, 659.
Materials, Technical Institute of Physics and Chemistry, the Chinese
Academy of Sciences, Beijing 100190, P. R. China. E-mail:
lzwu@mail.ipc.ac.cn.
9. (a) M. V. George and V. Bhat, Chemical Rev., 1979, 79, 447; (b) E. L.
Clennana, and A. Pace, Tetrahedron, 2005, 61, 6665; (c) M. N.
Alberti, G. C. Vougioukalakis and M. Orfanopoulos, J. Org. Chem.,
2009, 74, 7274.
Electronic Supplementary Information (ESI) available: Detailed
experimental procedures, gram scale experiment, electrochemistry data,
detailed condition optimization for synthesis of 2-Subsituted
Benzoxazoles, and spectral data (1H NMR, 13C NMR, MS/HRMS) for all
compounds. See DOI: 10.1039/c000000x/
10. For recent reviews on visible-light photoredox catalysis, see: (a) J. M.
R. Narayanam and C. R. J. Stephenson, Chem. Soc. Rev., 2011, 40,
102; (b) C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem.
Rev., 2013, 113, 5322; (c) T. P. Yoon, M. A. Ischay and J. Du, Nat.
Chem., 2010, 2, 527; (d) J. Xuan and W.-J. Xiao, Angew. Chem.,
2012, 124, 6934; J. Xuan and W. J. Xiao, Angew. Chem, Int, Ed.,
2012, 51, 6828; (e) D. Ravelli and M. Fagnoni, ChemCatChem, 2012,
4, 169; (f) L. Shi and W. Xia, Chem. Soc. Rev., 2012, 41, 7687.
11. Q. Liu, Y.-N. Li, H.-H. Zhang, B. Chen, C.-H. Tung and L.-Z. Wu,
Chem.–Eur. J., 2012, 18, 620.
1. (a) I. Hermans, J. Peeters and P. A. Jacobs, Topics in Catalysis, 2008,
48, 41; (b) I. Hermans, J. Peeters and P. A. Jacobs, Topics in
Catalysis, 2008, 50, 124; (c) I. Hermans, E. S. Spier, U.
Neuenschwander, N. Turrà and A. Baiker, Topics in Catalysis, 2009,
52, 1162.
2. (a) T. Punniyamurthy, S. Velusamy and J. Iqbal, Chem. Rev., 2005,
105, 2329; (b) K. H. Theopold, Dioxygen Activation by
12. (a) K. Singh, K. Singh, B. Wan, S. Franzblau, K. Chibale and J.
Balzarini, Eur. J. Med. Chem., 2011, 46, 2290; (b) M. Watanabe, H.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1‐3 | 5

Page 7 of 7
COMMUNICATION
Green Chemistry
Journal Name
Koike, T. Ishiba, T. Okada, S. Seo and K. Hirai, Bioorg. Med.
Chem., 1997, 5, 437; (c) S. Ahmad, C. S. Madsen, P. D. Stein, E.
Janovitz, C. Huang, K. Ngu, S. Bisaha, L. J. Kennedy, B.-C. Chen, R.
Zhao, D. Sitkoff, H. Monshizadegan, X. Yin, C. S. Ryan, R. Zhang,
M. Giancarli, E. Bird, M. Chang, X. Chen, R. Setters, D. Search, S.
Zhuang, V. Nguyen-Tran, C. A. Cuff, T. Harrity, C. J. Darienzo, T.
Li, R. A. Reeves, M. A. Blanar, J. C. Barrish, R. Zahler and J. A.
Robl, J. Med. Chem., 2008, 51, 2722; (d) L. A. Hobson, O. Akiti, S.
S. Deshmukh, S. Harper , K. Katipally, C. J. Lai , R. C.
Livingston , E. Lo, M. M. Miller, S. Ramakrishnan, L. Shen, J. Spink,
S. Tummala, C. Wei, K. Yamamoto, J. Young and R. L. Parsons, Org.
Process Res. Dev., 2010, 14, 441; (e) C. O. Kappe, Eur. J. Med.
Chem., 2010, 35, 1043.
H. Cheon, Adv. Synth. Catal., 2012, 354, 2992; (c) Y. Shih, C. Ke, C.
Pan and Y. Huang, RSC Adv., 2013, 3, 7330; (d) R. S. Varma and D.
View Article Online
Kumar, J. Heterocycl. Chem., 1998, 35, 1539; (e) J.-Z. Zhang, Q.
DOI: 10.1039/C4GC00337C
Zhu and X. Huang, Synth. Commun., 2002, 32, 2175; (f) Y.-X. Chen,
L.-F. Qian, W. Zhang and B. Han, Angew. Chem., 2008, 120, 9470;
Angew. Chem. Int. Ed., 2008, 47, 9330.
13. (a) M. S. Malamas, E. S. Manas, R. E. McDevitt, I. Gunawan, Z. B.
Xu, M. D. Collini, C. P. Miller, T. Dinh, R. A. Henderson, J. C. Keith
and H. A. Harris, J. Med. Chem., 2004, 47, 5021; (b) Y. Tagawa, H.
Koba, K. Tomoike and K. Sunmoto, Heterocycles, 2011, 83, 867; (c)
D. R. Chancellor, K. E. Davies, O. D. Moor, C. R. Dorgan, P. D.
Johnson, A. G. Lambert, D. Lawrence, C. Lecci, C. Maillol, P. J.
Middleton, G. Nugent, S. D. Poignant, A. C. Potter, P. D. Price, R. J.
Pye, R. Storer, J. M. Tinsley, R. v. Well, R. Vickers, J. Vile, F. J.
Wilkes, F. X. Wilson, S. P. Wren and G. M. Wynne, J. Med. Chem.,
2011, 54, 3241; (d) C. J. Smith, A. Ali, L. Chen, M. L. Hammond, M.
S. Anderson, Y. Chen, S. S. Eveland, Q. Guo, S. A. Hyland, D. P.
Milot, C. P. Sparrow, S. D. Wright and P. J. Sinclair, Bioorg. Med.
Chem. Lett., 2010, 20, 346; (e) E. d. O. Vizioli, C. M. Chin, R. F.
Menegon, L. Blau, J. L. D. Santos and M. d. C. Longo, PCT Int. Appl
WO 2009/124371 A2.
,
14. (a) C. O. Kappe, Tetrahedron, 1993, 49, 6937; (b) C. O. Kappe, Acc.
Chem. Res., 2000, 33, 879; (c) S. Bose, L. Fatima and H. B. Mereyala,
J. Org. Chem., 2003, 68, 587.
15. (a) K. Yamamoto, Y. G. Chen and F. G. Buono, Org. Lett., 2005, 7
,
4673; (b) P. Shanmugam and P. T. Perumal, Tetrahedron, 2006, 62
,
9726; (c) J. M. Kremsner, A. Stadler and C. O. Kappe, J. Comb.
Chem., 2007, 9, 285; (d) M. Matloobi and C. O. Kappe, J. Comb.
Chem., 2007, 9, 275; (e) N. N. Karade, S. V. Gampawar, J. M.
Kondre and G. B. Tiwari, Tetrahedron Lett., 2008, 49, 6698; (f) K.
Singh and K. Singh, Aust. J. Chem., 2008, 61, 910; (g) B. Han, R.-F.
Han, Y.-W. Ren, X.-Y. Duan, Y.-C. Xu and W. Zhang, Tetrahedron,
2011, 67, 5615.
16. (a) H. R. Memarian, A. Farhadi, H. Sabzyan and M. Soleymani, J.
Photochem. Photobiol. A: Chem. 2010, 209, 95; (b) Q. Liu, Y.-N.
Li, H.-H. Zhang, B. Chen, C.-H. Tung and L.-Z. Wu, J. Org. Chem.,
2011, 76, 1444.
17. N. N. Karade, S. V. Gampawar, N. P. Tale and S. B. Kedar, J.
Heterocycl. Chem., 2010, 47, 740.
18. C.-H. Tung, L.-Z. Wu, L.-P. Zhang and B. Chen, Acc. Chem. Res.
2003, 36, 39, and references therein.
19. (a) E. Joselevich and I. Willner, J. Phys. Chem., 1995, 99, 6903; (b) S.
D. M. Islam, T. Konishi, M. Fujitsuka, O. Ito, Y. Nakamura and Y.
Usui, Photochem. Photobiol., 2000, 71, 675; (c) X. -J. Yang, B. Chen,
L.-Q. Zheng, L.-Z. Wu and C.-H. Tung, Green Chem., 2014, 16,
1082; (d) H.-H. Zhang, K. Feng, B. Chen, Q.-Y. Meng, Z.-J. Li, C.-H.
Tung and L.-Z. Wu, Catal. Sci. Technol., 2013, 3, 1815.
20. (a) W.-J. Yoo, H. Yuan, H. Miyamura and S. Kobayash, Adv. Synth.
Catal., 2011, 353, 3085; (b) Y.-H. Cho, C.-Y. Lee, D.-C. Ha and C.-
6 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012