Visible-Light-Induced Decarboxylative Acylation of Pyridine N-Oxides with α-Oxocarboxylic Acids Using Fluorescein Dimethylammonium as a Photocatalyst

Article abstract of DOI:10.1002/adsc.202100168

Herein, the development of a visible-light-induced catalytic system to achieve the decarboxylative acylation of pyridine N-oxides with α-oxocarboxylic acids, at room temperature and using the organic dye fluorescein dimethylammonium as a new type of photocatalyst, is reported. A series of 2-arylacylpyridine N-oxides were selectively synthesized in moderate to good yields by controlling the polarity of the reaction solvent. The developed strategy was successfully applied in the synthesis of an important intermediate of the drug, acrivastine, on a gram scale. Notably, this is the first time that fluorescein dimethylammonium has been used to catalyze the Minisci-type C?H decarboxylative acylation reaction. The mechanism of decarboxylative acylation was studied by capturing adducts of acyl radicals and 1,1-diphenylethylene to confirm a radical mechanism. The disclosed catalytic system provides a green synthetic strategy for decarboxylative acylation without the use of additional oxidants or metal catalysts. (Figure presented.).

Full text of DOI:10.1002/adsc.202100168

FULL PAPER
DOI: 10.1002/adsc.202100168
Visible-Light-Induced Decarboxylative Acylation of Pyridine N-
Oxides with α-Oxocarboxylic Acids Using Fluorescein
Dimethylammonium as a Photocatalyst
Chuanfu Hou,a Shouneng Sun,a Ziqi Liu,a Hui Zhang,a Yue Liu,a Qi An,a
Jian Zhao,a Junjie Ma,a Zhizhong Sun,a,* and Wenyi Chua,*
a
School of Chemistry and Materials Science,
Heilongjiang University,
Harbin 150080, People’s Republic of China
Tel.: +86-451-86609135
Fax: +86-451-86609135
E-mail: wenyichu@hlju.edu.cn; sunzz@hlju.edu.cn
Manuscript received: February 5, 2021; Revised manuscript received: March 25, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100168
Abstract: Herein, the development of a visible-light-induced catalytic system to achieve the decarboxylative
acylation of pyridine N-oxides with α-oxocarboxylic acids, at room temperature and using the organic dye
fluorescein dimethylammonium as a new type of photocatalyst, is reported. A series of 2-arylacylpyridine N-
oxides were selectively synthesized in moderate to good yields by controlling the polarity of the reaction
solvent. The developed strategy was successfully applied in the synthesis of an important intermediate of the
drug, acrivastine, on a gram scale. Notably, this is the first time that fluorescein dimethylammonium has been
used to catalyze the Minisci-type CÀ H decarboxylative acylation reaction. The mechanism of decarboxylative
acylation was studied by capturing adducts of acyl radicals and 1,1-diphenylethylene to confirm a radical
mechanism. The disclosed catalytic system provides a green synthetic strategy for decarboxylative acylation
without the use of additional oxidants or metal catalysts.
Keywords: Visible-light-induced; 2-Arylacylpyridine N-oxides; Fluorescein dimethylammonium; Decarboxyla-
tion acylation; Green synthetic strategy
Introduction
Pyridine and quinoline derivatives are widely used as
important scaffolds in bioactive molecules,[1] such as
antiparasitic drugs,[2] antituberculotic drugs,[3] antibac-
terial drugs[4] and anticancer drugs.[5] In addition,
pyridine and quinoline N-oxides are also used as
catalysts[6] and ligands[7] in many asymmetric reactions
or even as reactants. Because pyridine N-oxides are
easy to prepare and have good regioselectivity, direct
C2À H functionalization, including alkylation,[8]
amidation,[9] thiolation,[10] sulfonylation,[11] and similar
reactions[12] provide an effective and straightforward
route for the preparation of 2-substituted pyridine
derivatives. Particularly, 2-arylacylpyridine N-oxides
Figure 1. Representative drug molecules synthesized from 2-
serve as important intermediates for the synthesis of
arylacylpyridine N-oxides.
many drug molecules (Figure 1), such as drug
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acrivastine,[13]
drug
bepotastine,[14]
drug (Scheme 1b).[23] In 2019, Manna et al. used an ex-
carbinoxamine[15] and drug bepotastine besilate.[16] The pensive Iridium complex as a photocatalyst to obtain
NÀ O bonds of the N-oxides are instrumental in the acylation product under mild reaction conditions
improving the enantioselectivity of these drug (Scheme 1c).[24] Compared to the previously reported
molecules,[17] and the synthesis of derivatives of 2- strategy, Zhang and Manna’s methods could achieve
arylacylpyridine N-oxides has attracted increasing decarboxylative coupling at room temperature. How-
attention.
ever, the use of the expensive hypervalent iodine
In recent years, significant advances have been reagent PhI(OCOCF3)2 and photocatalyst iridium was
made in Minisci-type reactions,[18] and many state-of- important for obtaining high yield of the products.
the-art methods for Minisci decarboxylative acylation Therefore, the development of a cheap and green
have been developed.[19] The decarboxylation cross- method for the sytnesis 2-arylacylpyridine N-oxides
coupling of a-keto acids with N-heteroaromatics is remains an important synthetic goal.
widely applied in Minisci decarboxylative acylation
Currently visible light catalysis is a popular
reactions. However, the Minisci decarboxylative acyla- research topic in synthetic chemistry and catalysis.[25]
tion of pyridine N-oxides have rarely been studied. However, because most organic molecules cannot
Classical acylation of electron-deficient N-heteroaro- absorb visible light, the photocatalytic transformations
matic compounds was accomplished via the Minisci geneall light, require the presence of a photosensitizer,
reaction[20] using α-keto acids as acylation reagents such as the expensive ruthenium and iridium com-
under harsh conditions (use of H2SO4 under reflux).[21] plexes or organic dyes. In recent years, fluorescein, an
To overcome this problem, several improved methods organic dye, has been found to possess excellent
have been reported. For example, in 2014, Suresh et al. photocatalytic activity in many reactions, such as
reported the decarboxylative coupling of electron- carbonylation,[26] arylation,[27] and condensation cycli-
deficient heteroaromatics using the Ag2CO3/K2S2O8 zation reactions.[28] Some studies have shown that
system (Scheme 1a).[22] Although this method is fluorescein is pH sensitive, and the visible light
effective and satisfactory, it has some drawbacks that absorption and fluorescence emission decreases with a
cannot be ignored, such as the need for high reaction decrease in pH.[29] The proton equilibria of fluorescein
temperatures and expensive transition metal catalysts. include cations, neutrons, monoanions, and dianions.
In 2018, Zhang et al. reported a simple and efficient Therefore, there are three types of acid-base equilibria
visible-light-induced method. The hypervalent iodine of fluorescein at pH 2, 4, and 6, respectively.[30] More
reagent PhI(OCOCF3)2 was used as an oxidant to importantly, the dianion state has the highest molar
realize the direct decarboxylative coupling of carbox- absorption coefficient, and its maximum absorption
ylic acids with N-heteroaromatic hydrocarbons wavelength (490 nm) showed a red shift compared to
the other three states.[31] In addition, fluorescein, at
pH 6, is mainly in the form of a dianion.[32] Inspired by
previous works, we designed and prepared fluorescein
dimethylammonium (FD) (pH=6.5) as a new type of
photocatalyst. The purpose of using FD was to
maintain the pH of the reaction system, such that
fluorescein mainly existed in the form of a dianion.
Herein, we report a new visible-light-induced
catalytic system for the decarboxylative acylation of
pyridine N-oxides with α-oxocarboxylic acids at room
temperature using organic dye, FD, as a photocatalyst
(Scheme 1d).
Results and Discussion
Pyridine N-oxide (1a) and phenylglyoxylic acid (2a)
were selected as model substrates to explore the
optimal reaction conditions, and the results are
summarized in Table 1. Initially, fluorescein was
selected as the photocatalyst in chloroform (CHCl3) to
obtain products 3a and 3a’ in 52% and 17% yields,
respectively (Table 1, entry 1). Next, based on this
result, other photocatalysts such as eosin Y, rhodamine
Scheme 1. Reported works and our work for decarboxylative
acylation.
B, methylene blue, malachite green, and fluorescein
dimethylammonium (FD) (Figure 2) were investigated
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Table 1. Optimization of the reaction conditions.[a]
fluorescein mainly exists in the form of dianion in the
reaction system as a result of using FD.
Furthermore, FD was used as the photocatalyst to
study the effect of the solvents on the reaction and
improve the selectivity of the reaction. Using methanol
(MeOH), a polar solvent, 3a and 3a’ were obtained in
15% and 48% yields, respectively (Table 1, entry 7).
Using more strongly polar solvents, N, N-dimeth-
ylformamide (DMF) and water (H2O), the yield of 3a’
increased to 57% and 64%, respectively, whereas the
yield of 3a decreased to 11% and 9%, respectively
(Table 1, entries 8–9). The above results showed that
an increase in the polarity of the solvent improved the
yield of 3a’ but not that of 3a. Therefore, less polar
solvents, such as dichloromethane (DCM) and di-
chloroethane (DCE), were selected to improve the
yield of 3a (Table 1, entries 10–11). DCE gave the
target product 3a in 75% yield and only a small
amount of 3a’ (less than 5% yield) (Table 1, entry 11).
However, the use of nonpolar solvents, cyclohexane
and n-hexane, led only to the formation of 3a, in 17%
and 12% yields, respectively, which may be due to the
poor solubility of the reactants in the nonpolar solvents
(Table 1, entries 12–13). In addition, we screened other
light sources and the reaction time (Table S1). The
blue LEDs were determined as the optimal light source
of the reaction system. The 24 hours was determined
as the optimal reaction time of the reaction system.
Finally, the equivalent of photocatalyst was inves-
tigated. When the equivalent of FD was reduced to
4 mol%, the yield of 3a dropped to 54% (Table 1,
entry 14). Increasing the equivalent (6 mol%) had no
significant effect on the yield of 3a (Table 1, entry 15).
The products were obtained only in trace amounts in
the absence of a light source (Table 1, entry 11c),
whereas in the absence of FD, no product formation
was observed (Table 1, entry 16).
Entry Photocatalyst (mol%)
Solvent
Yield[b] (%)
of 3a/3a’
1
2
3
Fluorescein
(5 mol%)
Eosin Y
(5 mol%)
Rhodamine B
(5 mol%)
CHCl3
CHCl3
CHCl3
52/17
44/16
38/14
4
5
Methylene blue (5 mol%) CHCl3
Malachite green (5 mol%) CHCl3
25/11
9/<5
59/17
15/48
11/57
9/64
67/13
6
7
8
9
10
11
FD (5 mol%)
FD (5 mol%)
FD (5 mol%)
FD (5 mol%)
FD (5 mol%)
FD (5mol%)
CHCl3
MeOH
DMF
H2O
DCM
DCE
75/<5;
(trace/trace)[c]
12
13
14
15
16
FD (5 mol%)
FD (5 mol%)
FD (4 mol%)
FD (6 mol%)
–
cyclohexane 17/trace
n-hexane
DCE
DCE
DCE
12/trace
54/<5
75/<5
none/none
[a] 1a (0.250 mmol), 2a (0.375 mmol), photocatalyst, 10 W blue
LED, room temperature for 24 h.
[b] Isolated yields based on 1a.
[c] Without blue LED.
Based on the above experimental results, the
optimal reaction conditions for visible light-induced
decarboxylative acylation of pyridine N-oxide were the
use of FD (5 mol%) as the photocatalyst, DCE as the
reaction solvent and 10 W blue LED as the light source
at room temperature for 24 hours.
A variety of pyridine N-oxides and α-oxocarboxylic
acids were investigated under the optimal reaction
conditions to explore the substrate scope of the above-
disclosed reaction (Scheme 2). First, the effect of the
R1 substituent of the pyridine N-oxide (1) moiety on
the product yield was studied. The presence of the
electron-donating methyl group at the C-4 and C-3
Figure 2. Molecular structures of fluorescein dimeth-
ylammonium, fluorescein, eosin Y, rhodamine B, methylene
blue and malachite green.
(Table 1). Eosin Y gave products 3a and 3a’, with positions gave the corresponding products 3b and 3d
44% and 16% yields, respectively (Table 1, entry 2). in 82% and 71% yields, respectively, whereas electron-
Rhodamine B, methylene blue, and malachite green, withdrawing -Br substituent reduced the yields of
on the other hand, gave product 3a, albeit in low yields products 3c and 3e to 77% and 66%, respectively.
of 9–38% (Table 1, entries 3–5). Using FD as the Next, we studied the effect of the substituent R2 on the
photocatalyst yielded 59% and 17% of 3a and 3a’, α-oxocarboxylic acid (2) moiety. Compared to the
respectively (Table 1, entry 6). This may be because substrate containing the electron-withdrawing -Cl
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gave the corresponding products 3q and 3r in 83%
and 69% yields, respectively.
To further explore the substrate scope and limita-
tions of this method, other aryl N-oxides and α-
oxocarboxylic acids were investigated. Quinoline N-
oxide was used as the reaction substrate to obtain
product 3s in 73% yield. For substituted quinoline N-
oxides, the electron-donating À CH3 group at the C-4
position gave the corresponding product 3t in 86%
yield, whereas the electron-withdrawing -Br group
gave the corresponding product 3u in 77% yield.
Different α-oxocarboxylic acids with quinoline N-
oxide also gave the desired products 3v–3x in 62–69%
yields. Isoquinoline N-oxide also afforded the corre-
sponding product 3y in 88% yield. In addition, we
explored the range of substrates for aliphatic α-
oxocarboxylic acids. Unfortunately, pyruvic acid and
trimethylpyruvic acid gave products 3z and 3aa in
relatively low yields of 38% and 45%, respectively.
Finally, since pyridine N-oxides are used as intermedi-
ates but deoxidation is often required to form the final
target, we also explored direct decarboxylative acyla-
tion of N-heterocycles to form 3ab–3ad directly from
the corresponding pyridine, quinoline and isoquinoline.
4-Methylpyridine, 4-methylquinoline and isoquinoline
gave productions 3ab, 3ac and 3ad in medium to
good yields of 57%, 61% and 64%, respectively.
Compared to the other aryl N-oxides, the yields of
3ab, 3ac and 3ad were slightly lower. Notably, the
Minisci decarboxylative acylation of isoquinoline only
selectively occurred at the C-1 position, and no
acylation reaction occurred at the C-4 position.
To further demonstrate the practicability of the
decarboxylation acylation, an important intermediate 5
of the prescription drug acrivastine, a short-acting
histamine 1 receptor antagonist, was synthesized in a
gram-scale reaction, as shown in Scheme 3. According
Scheme 2. Substrates scope of aryl N-oxides and α-oxocarbox-
ylic acids.a,b
group (3f and 3i), the electron-donating -CH3 (3g and
3j) and -OCH3 (3h) groups reduced the yield of the
expected products. When the -Cl substituent was
placed at different positions of α-oxocarboxylic acids,
products 3f, 3i, and 3k were obtained in 80%, 75%,
and 66% yields, respectively. α-Oxocarboxylic acids
with the À Cl substituent at the p-position gave the
highest yield due to less steric hindrance. Next, we
studied the expansion of the substituted pyridine N-
oxides (1) and the α-oxocarboxylic acids (2). Disub-
stituted 2-(3,4-dimethoxyphenyl)-2-oxoacetic acid also
showed good tolerance to give 3l in 71% yield. When
4-methylpyridine N-oxide and À Cl substituted α-
oxocarbonic acid were used as the reaction substrates,
the corresponding products (3m, 3n, and 3p) were
obtained in good yields (71–86%), with the highest
yield (86%) being obtained when -Cl was at the p-
position. In addition, 4-bromopyridine N-oxides also
Scheme 3. Gram-scale reaction for synthesis of the intermediate
of acrivastine.
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to a report in the literature,[33] acrivastine is synthesized a radical chain propogation exists in the reaction
from 2,6-dibromopyridine as the starting material by system (see the Supporting Information for further
introducing 2-benzoyl and acrylate through complex details).[38]
reaction steps. Herein, a new synthetic route was
Based on the above experimental results and
developed using pyridine N-oxide (1a) as the starting previous literature reports,[39] a plausible mechanism
material to obtain compound 3g via decarboxylative for the decarboxylation acylation reaction is described
acylation. Due to the NÀ O bond directing function of in Scheme 5. First, the photocatalyst FD is excited to
compound 3g and the activation of the CÀ H bond at the excited state FD* in the presence of visible-light
the C-2 position of the pyridine ring, compound 4 was irradiation. Then, the formed FD* interacts with O2 in
1
synthesized by a palladium-catalyzed C-2 selective air to generate singlet oxygen O2 and ground state FD
alkenylation reaction.[34] Finally, intermediate 5 was through energy transfer.[40] Subsequently, singlet oxy-
obtained via deoxidation with PBr3.[35] Compared with gen O2 reacts with phenylglyoxylic acid (2a) to form
1
*
the literature scheme, the new strategy has the the hydroperoxyl radical HO2 and intermediate A. The
advantages of mild reaction conditions, simple oper- intermediate A generates benzoyl radical B and
ation and high yield.
releases CO2 by decarboxylation. Next, the benzoyl
To determine the mechanism of the decarboxylative radical B interacts with pyridine N-oxide (1a) to
acylation reaction, control experiments were con- generate intermediate C which undergoes single elec-
ducted, as shown in Scheme 4. When a radical tron transfer (SET) by the action of hydroperoxy
*
inhibition experiment was conducted using 1,1- radical HO2 to give intermediate D. Finally, the
diphenylethylene[36] as a blocker under standard con- product, 2-arylacylpyridine N-oxide (3a) and hydrogen
ditions, the desired product 3a was not detected, and peroxide H2O2 are generated by the deprotonation of
1,1-diphenylethylene free radical adduct 6 was isolated the intermediate D. Alternatively, intermediate C
in 52% yield (Scheme 4a). This proved that the undergoes single electron transfer (SET) by O2 in air to
reaction proceeds through a radical pathway. Because give intermediate D and the superoxide radical anion
*
*
À
of the open reaction system, the effect of O2 in air on O2 À . The superoxide radical anion O2 reacts with
the reaction system was verified. When the model phenylglyoxylic acid (2a) to form the benzoyl radical
reaction was conducted under N2, only a trace amount B which interacts with pyridine N-oxide (1a) to
of 3a was detected. However, under an O2 atmosphere, generate intermediate C again, thereby sustaining the
the yield of 3a did not increased significantly radical chain propogation.
(Scheme 4b). The above experiments show that O2 in
air was necessary, and sufficient, for this conversion.
Conclusion
Subsequently, when 1,4-Diazabicyclo[2.2.2] octane, a
1
strong O2 physical quencher)[37] was added to the In summary, we have developed an efficient strategy
reaction system, the desired product 3a was not for the photoinduced selective decarboxylative acyla-
1
detected. This result showed that the O2-mediated tion of N-heteroaryl N-oxides with α-oxocarboxylic
procedure might be involved in this conversion acids under mild conditions. A series of 2-arylacylpyr-
(Scheme 4c). According to the optimization of the idine N-oxide derivatives were synthesized in moderate
reaction conditions (Table 1), light and photocatalyst to good yields using fluorescein dimethylammonium
are essential for this reaction, which also showed that as a new type of photocatalyst under blue light. In
the reaction is a free radical reaction mechanism addition, an important intermediate of the drug
photoinduced. In addition, the measurement of quan- acrivastine was synthesized on a gram scale using the
tum yield (Φ=20.12) is greater than 1, which suggests above strategy. A free radical reaction mechanism was
Scheme 4. Control experiments.
Scheme 5. Plausible reaction mechanism.
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[5] R. D. Kruschel, A. Buzid, U. B. R. Khandavilli, S. E.
Lawrence, J. D. Glennon, F. O. McCarthy, Org. Biomol.
Chem. 2020, 18, 557–568.
[6] a) J. Chen, B. Captain, N. Takenaka, Org. Lett. 2011,
1654–1657; b) E. Gnanamani, N. Someshwar, C. R.
Ramanathan, Adv. Synth. Catal. 2012, 354, 2101–2106;
c) T. Ikai, T. Yoshida, Org. Biomol. Chem. 2019, 17,
8537–8540.
[7] a) X. H. Ren, P. Wang, J. Y. Cheng, Y. B. Dong, J. Mol.
Struct. 2018, 1161, 145–151; b) R. M. R. Dumpala, N.
Rawat, A. Boda, S. M. Ali, B. S. Tomar, Spectrochim.
Acta Part A 2018, 190, 150–163; c) R. Puttreddy, J. M.
Rautiainen, T. Mäkelä, K. Rissanen, Angew. Chem. Int.
Ed. 2019, 58, 18610–18618.
[8] a) S. Han, P. Chakrasali, J. Park, H. Oh, S. Kim, K. Kim,
A. K. Pandey, S. H. Han, S. B. Han, I. S. Kim, Angew.
Chem. Int. Ed. 2018, 57, 12737–12740; b) W. Zhou, T.
Miura, M. Murakami, Angew. Chem. Int. Ed. 2018, 57,
5139–5142; Angew. Chem. 2018, 130, 5233–5236;
c) J. H. Xu, W. B. Wu, J. Wu, Org. Lett. 2019, 21, 5321–
5325.
[9] a) L. Y. Xie, S. Peng, L. H. Lu, J. Hu, W. H. Bao, F.
Zeng, Z. Tang, X. Xu, W. M. He, ACS Sustainable
Chem. Eng. 2018, 6, 7989–7994; b) L. Y. Xie, S. Peng,
F. Liu, J. Y. Yi, M. Wang, Z. Tang, X. Xu, W. M. He,
Adv. Synth. Catal. 2018, 360, 4259–4264.
[10] a) M. Lai, K. Zhai, C. Cheng, Z. Wu, M. Zhao, Org.
Chem. Front. 2018, 5, 2986–2991; b) R. Muta, T.
Torigoe, Y. Kuninobu, Org. Lett. 2019, 21, 4289–4292.
[11] M. Jiang, Y. Yuan, T. Wang, Y. Xiong, J. Li, H. Guo, A.
Lei, Chem. Commun. 2019, 55, 13852–13855.
proposed for the reaction, which was verified through
a free radical capture experiment. The disclosed
catalytic system avoids the use of oxidants or metals
and conforms to the concepts of green chemistry. Other
photocatalytic methods continue to be studied in our
laboratory.
Experimental Section
Preparation of 2-Arylacylpyridine N-Oxides
To an ovendried 10 mL quartz vial containing a magnetic
stirring bar and a condenser, aryl N-oxide (0.2500 mmol,
1 equiv), α-oxocarboxylic acid (0.3750 mmol, 1.5 equiv.) and
fluorescein dimethylammonium (0.0125 mmol, 5 mol%) were
added followed by dichloroethane (2 mL). The reaction mixture
was kept stirring at room temperature for 24 h (monitored by
TLC) under the irradiation of 10 W blue LED. Next saturated
aqueous NaHCO3 solution (20 mL) was added to the reaction
mixture and extracted with CH2Cl2 (10 mL×3). The organic
extracts were dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The solvent was then removed under
reduced pressure, and the product was purified by flash column
chromatography.
Acknowledgements
We are grateful for the Foundation for Engineering Technology
Talent Training from Ministry of Education of China (Grant No.
19JDGC005), the Research Project of the Natural Science
Foundation of Heilongjiang Province of China (No. B2018012)
and financial support from Project Supported by the College
Students’ Innovative Entrepreneurial Training Plan Program of
China (No. 202010212013).
[12] a) F. Roudesly, L. F. Veiros, J. Oble, G. Poli, Org. Lett.
2018, 20, 2346–2350; b) Y. Yuan, M. Jiang, T. Wang, Y.
Xiong, J. Li, H. Guo, A. Lei, Chem. Commun. 2019, 55,
11091–11094.
References
[13] a) V. K. Manna, P. Marks, J. R. Gibson, J. Int. Med. Res.
1992, 20, 106–111; b) R. J. Dockhorn, B. O. Williams,
R. L. Sanders, Ann. Allergy. As. Im. 1996, 76, 204–208.
[14] a) M. Kobayashi, K. Kabashima, M. Nakamura, Y.
Tokura, Skin Pharmacol. Physiol. 2009, 22, 45–48;
b) J. B. Wingard, F. S. Mah, Clinical. Ophthalmology.
(Auckland, NZ). 2011, 5, 201.
[15] a) G. Hite, V. Barouh, H. Dall, D. Patel, J. Med. Chem.
1971, 14, 834–836; b) A. F. Casy, A. F. Drake, C. R.
Ganellin, A. D. Mercer, C. Upton, Chirality. 1992, 4,
356–366.
[16] a) L. Bielory, S. Duttachoudhury, A. McMunn, Expert
Opin. Pharmacother. 2013, 14, 2553–2569; b) I. Carril-
lo-Martin, A. Gonzalez-Estrada, V. Dimov, Expert Opin.
Pharmacother. 2018, 19, 1727–1730.
[17] a) M. Holmquist, G. Blay, M. C. Muñoz, J. R. Pedro,
Org. Lett. 2014, 16, 1204–1207; b) B. Wang, H. Zhou,
G. Lu, Q. Liu, X. Jiang, Org. Lett. 2017, 19, 2094–2097;
c) Q. Liu, C. Wang, H. Zhou, B. Wang, J. Lv, L. Cao, Y.
Fu, Org. Lett. 2018, 20, 971–974.
[1] a) L. Bonilla-Ramirez, A. Rios, M. Quiliano, G. Ramir-
ez-Calderon, I. Beltrán-Hortelano, J. F. Franetich, L.
Corcuera, M. Bordessoulles, A. Vettorazzi, A. L. de Cer-
ain, I. Aldana, D. Mazier, A. Pabon, S. Galiano, Eur. J.
Med. Chem. 2018, 158, 68–81; b) A. Horton, K. Nash, E.
Tackie-Yarboi, A. Kostrevski, A. Novak, A. Raghavan, J.
Tulsulkar, Q. Alhadidi, N. Wamer, B. Langenderfer, K.
Royster, M. Ducharme, K. Hagood, M. Post, Z. A. Shah,
I. T. Schiefer, J. Med. Chem. 2018, 61, 4593–4607;
c) K. L. Dobo, S. Coffing, W. C. Gunther, M. Homiski,
Environ. Mol. Mutagen. 2019, 60, 588–593.
[2] V. V. Kouznetsov, L. Y. V. Méndez, C. E. P. Galvis,
M. C. O. Villamizar, New J. Chem. 2020, 44, 12–19.
[3] S. Srinivasarao, A. Nandikolla, A. Suresh, A. K. Ewa, A.
Głogowska, B. Ghosh, B. K. Kumar, S. Murugesan, S.
Pulya, H. Aggarwal, K. V. G. C. Sekhar, Bioorg. Chem.
2020, 100, 103955.
[4] R. S. Keri, S. S. Pandule, S. Budagumpi, B. M. Nagaraja,
Arch. Pharm. 2018, 351, 1700325.
[18] R. S. Proctor, R. J. Phipps, Angew. Chem. Int. Ed. 2019,
58, 13666–13699.
Adv. Synth. Catal. 2021, 363, 1–8
6
© 2021 Wiley-VCH GmbH
��
These are not the final page numbers!

FULL PAPER
asc.wiley-vch.de
[19] a) Q. Q. Wang, K. Xu, Y. Y. Jiang, Y. G. Liu, B. G. Sun, [31] a) G. De Cremer, M. B. Roeffaers, M. Baruah, M. Sliwa,
C. C. Zeng, Org. Lett. 2017, 19, 5517–5520; b) X. Z.
Wang, C. C. Zeng, Tetrahedron. 2019, 75, 1425–1430;
c) M. T. Westwood, C. J. Lamb, D. R. Sutherland, A. L.
Lee, Org. Lett. 2019, 21, 7119–7123.
B. F. Sels, J. Hofkens, D. E. De Vos, J. Am. Chem. Soc.
2007, 129, 15458–15459; b) V. R. Batistela, J. Costa Ce-
dran, H. P. M. De Oliveira, I. S. Scarminio, L. T. Ueno,
A. E. Hora Machado, N. Hioka, Dyes Pigm. 2010, 86,
15–24.
[20] a) F. Minisci, F. Fontana, E. Vismara, J. Heterocycl.
Chem. 1990, 27, 79–96; b) F. Fontana, F. Minisci, M. C. [32] L. S. De Clerck, C. H. Bridts, A. M. Mertens, M. M.
Nogueira Barbosa, E. Vismara, J. Org. Chem. 1991, 56,
2866–2869; c) F. Coppa, F. Fontana, E. Lazzarini, F.
Minisci, Heterocycles 1993, 36, 2687–2696.
Moens, W. J. Stevens, J. Immunol. Methods. 1994, 172,
115–124.
[33] J. W. Findlay, R. F. Butz, G. G. Coker, R. L. Deangelis,
R. M. Welch, J. Pharm. Sci-Us. 1984, 73, 1339–1344.
[21] a) G. A. Kraus, A. Melekhov, Tetrahedron Lett. 1998,
39, 3957–3960; b) H. Wang, S. L. Zhou, L. N. Guo, [34] a) S. H. Cho, S. J. Hwang, S. Chang, J. Am. Chem. Soc.
X. H. Duan, Tetrahedron. 2015, 71, 630–636; c) G.
Fang, X. Cong, G. Zanoni, Q. Liu, X. Bi, Adv. Synth.
Catal. 2017, 359, 1422–1502.
2008, 130, 9254–9256; b) K. Zhai, M. Lai, Z. Wu, M.
Zhao, Y. Jing, P. Liu, Catal. Commun. 2018, 116, 20–26.
[35] a) D. Wenkert, A. R. Woodward, J. Org. Chem. 1983,
48, 283–289; b) K. S. Kanyiva, Y. Nakao, T. Hiyama,
Angew. Chem. Int. Ed. 2007, 119, 9028–9030; c) S. H.
Cho, S. J. Hwang, S. Chang, J. Am. Chem. Soc. 2008,
130, 9254–9256.
[22] R. Suresh, R. S. Kumaran, V. Senthilkumar, S. Muthusu-
bramanian, RSC Adv. 2014, 4, 31685–31688.
[23] X. Y. Zhang, W. Z. Weng, H. Liang, H. Yang, B. Zhang,
Org. Lett. 2018, 20, 4686–4690.
[24] S. Manna, K. R. Prabhu, J. Org. Chem. 2019, 84, 5067– [36] a) M. Litt, J. A. Seiner, Macromolecules. 1971, 4, 314–
5077.
316; b) S. Viala, K. Tauer, M. Antonietti, R. P. Krüger,
W. Bremser, Polymer. 2002, 43, 7231–7241; c) S. Viala,
K. Tauer, M. Antonietti, I. Lacik, W. Bremser, Polymer.
2005, 46, 7843–7854.
[25] a) S. He, X. Chen, F. Zeng, P. Lu, Y. Peng, L. Qu, B. Yu,
Chinese. Chem. Lett. 2020, 31, 1863–1867; b) Z. Gan,
G. Li, X. Yang, Q. Yan, G. Xu, G. Li, Y. Jiang, D. Yang,
Sci. China Chem. 2020, 63, 1652–1658; c) K. J. Liu, Z. [37] a) S. K. Silverman, C. S. Foote, J. Am. Chem. Soc. 1991,
Wang, L. H. Lu, J. Y. Chen, F. Zeng, Y. W. Lin, Z. Cao,
X. Yu, W. M. He, Green Chem. 2021, 23, 496–500;
113, 7672–7675; b) M. Klaper, T. Linker, J. Am. Chem.
Soc. 2015, 137, 13744–13747.
d) W. H. Bao, Z. Wang, Z. Cao, X. C. Wang, X. R. Ma, [38] M. A. Cismesia, T. P. Yoon, Chem. Sci. 2015, 6, 5426–
X. Y. Yu, W. M. He, Adv. Synth. Catal. 2021, 363, 757–
761.
5434.
[39] a) J. Liu, Q. Liu, H. Yi, C. Qin, R. Bai, X. Qi, Y. Lan, A.
Lei, Angew. Chem. Int. Ed. 2014, 53, 502–506; Angew.
Chem. 2014, 126, 512–516; b) Q. Shi, P. Li, X. Zhu, L.
Wang, Green Chem. 2016, 18, 4916–4923; c) R. A.
Garza-Sanchez, A. Tlahuext-Aca, G. Tavakoli, F. Glo-
rius, ACS Catal. 2017, 7, 4057–4061; d) S. Manna, K. R.
Prabhu, J. Org. Chem. 2019, 84, 5067–5077; e) L. Y.
Xie, Y. S. Bai, X. Q. Xu, X. Peng, H. S. Tang, Y. Huang,
W. M. He, Green Chem. 2020, 22, 1720–1725; f) P. Bao,
F. Liu, Y. Lv, H. Yue, J. S. Li, W. Wei, Org. Chem. Front.
2020, 7, 492–498.
[26] Q. Q. Zhou, W. Guo, W. Ding, X. Wu, X. Chen, L. Q.
Lu, W. J. Xiao, Angew. Chem. Int. Ed. 2015, 54, 11196–
11199; Angew. Chem. 2015, 127, 11348–11351.
[27] M. N. Hopkinson, B. Sahoo, F. Glorius, Adv. Synth.
Catal. 2014, 356, 2794–2800.
[28] Z. Li, H. Song, R. Guo, M. Zuo, C. Hou, S. Sun, X. He,
Z. Sun, W. Chu, Green Chem. 2019, 21, 3602–3605.
[29] R. Sjöback, J. Nygren, M. Kubista, Spectrochim. Acta
Part A 1995, 51, L7-L21.
[30] a) B. Rotman, J. A. Zderic, M. Edelstein, Proc. Natl.
Acad. Sci. USA 1963, 50, 1; b) N. Klonis, W. H. Sawyer, [40] D. Ravelli, M. Fagnoni, A. Albini, Chem. Soc. Rev. 2013,
J. Fluoresc. 1996, 6, 147–157.
42, 97–113.
Adv. Synth. Catal. 2021, 363, 1–8
7
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Visible-Light-Induced Decarboxylative Acylation of Pyridine
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Adv. Synth. Catal. 2021, 363, 1–8
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