Direct C4-H phosphonation of 8-hydroxyquinoline derivatives employing photoredox catalysis and silver catalysis

Article abstract of DOI:10.1039/c8ob00370j

A simple and efficient protocol for the C4-H phosphonation of 8-hydroxyquinoline derivatives was developed under a photoredox/silver(i) cocatalysis system, providing a new approach to phosphonated 8-hydroxyquinoline derivatives. Note that the reaction did not occur at the C5 site, but regioselectively at an unusual C4 site. Moreover, the reaction proceeded smoothly under mild reaction conditions (a catalytic amount of silver salt and room temperature) with good functional group compatibility.

Full text of DOI:10.1039/c8ob00370j

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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DOI: 10.1039/C8OB00370J
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ARTICLE
Direct C4-H Phosphonation of 8-Hydroxyquinoline Derivatives
Employing Photoredox Catalysis and Silver Catalysis
Received 00th January 20xx,
Accepted 00th January 20xx
a
a,
b,
a,
Xiaoxue Su, Fan Yang, * Yusheng Wu, * and Yangjie Wu *
DOI: 10.1039/x0xx00000x
A simple and efficient protocol for the C4-H phosphonation of 8-hydroxyquinoline derivatives was developed under
photoredox/silver(I) cocatalysis system, providing a new approach to phosphonated 8-hydroxyquinoline derivatives. Note
that the reaction did not occur at the C5 site, but regioselectively at an unusual C4 site. Moreover, the reaction proceeded
smoothly under mild reaction conditions (a catalytic amount of silver salt and room temperature) with good functional
groups compatibility.
www.rsc.org/
4
c,4d,6
7
and 1-naphthylamine derivatives. For
derivatives
Introduction
example, our group has demonstrated silver-promoted C5-H or
C4-H phosphonation of 8-aminoquinoline amides (Scheme 1b
Organophosphorus compounds have received increasing
interest of many chemists owing to their wide existence in
various functional materials, pharmaceuticals and natural
4
c,4d
and c).
Although several versions of phosphonation of 8-
aminoquinoline amides has been demonstrated, to the best of
our knowledge, the reports for C4-H phosphonation of 8-
hydroxyquinoline esters remain rare.
1
products. Usually, construction of C-P bond can be realized
from the Pd-catalyzed classic cross-coupling of aryl halides
with H-phosphonates, which was first discovered by the group
2
of Hirao in 1981. However, these protocols typically require
On the other hand, photoredox catalysis has become a hot
topic and emerged as an environmentally friendly and
powerful tool in green chemistry, making the reaction under
prefunctionalized arenes such as aryl halides as starting
materials.
8
lower energy consumption and milder conditions. In
comparison, organic dyes as photocatalysts exhibited
superiority to transition metal counterparts due to their
commercial availability and lower cost. And herein, we
envisioned developing a mild and efficient catalyst version for
C4-H phosphonation of 8-hydroxyquinoline esters under a dual
catalysis of silver salt and organic dye-mediated photoredox
During the past decades, the direct functionalization of C-H
bonds has become a reliable and robust tool in organic
synthesis, and afterwards, a series of transformations from C-H
3
bond to C-C or C-heteroatom bond have been demonstrated.
Especially, various versions for C-H bond phosphonation of the
4
5
quinoline ring and other heterocycles were developed under
transition metal catalysis or even under transition metal-free
conditions.
(Scheme 1d).
In 2014, Huang described a direct C2-H phosphonation of
the quinoline ring with H-phosphonates without the help of
Previous work:
O
Cu/Ag
N
(
a
)
)
4
a
H
N
N
any directing group; Yu and co-workers also developed a
copper-catalyzed phosphonation of the 8-aminoquinoline
i
P(O Pr)
2
O
R1
O
OR2
R1
P
O
2
OR
4
b
O
Ag
(b
amides at the C2 site in the aromatic ring (Scheme 1a). In
recent years, the research interest in our group mainly focuses
on the C−H functionalization of arene derivatives at an unusual
site, especially the direct functionalization of 8-aminoquinoline
N
N
20 oC 24 h
H
1
H
N
R1
O
O
Ph
P
(c)
(d)
Ag/Acid red 94
N
Ph
H
8
h
N
This work:
eosin Y (3 mol%)
Ag
2
O (10 mol%)
(2.0 equiv
O
O
P
O
O
Ph
Ph
Ph
Ph
K
2
S
2
O
8
)
O
+
H
P
O
CH CN/H O (3:2)
3
2
N
N
rt, nitrogen,6 h
householdlight
Scheme 1. Direct phosphonation of quinoline derivatives.
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With these optimized reaction conditions in hand, the
scope of different phosphonation reagents in the reaction was
investigated (Table 2). The reaction of different
diarylphosphine oxides lead to desired products in mostly
moderate to good yields and diphenylphosphine oxide showed
Results and discussion
Initially, the phosphonation of 8-hydroxyquinoline esters 1a
with diphenylphosphine oxide 2a was explored as a model
reaction, and the results are displayed in Table 1. The reaction
was first performed using Ag
system in the presence of K
desired product 3aa in 50% isolated yield (Table 1, entry 1).
2
O and acid red 94 as a catalyst
the best reactivity (3aa-3ad). However, the products could not
2 2 8
S O as an oxidant, affording the
be observed in the case of dialkyl H-phosphonates.
a,b
When other silver salts were also checked in this reaction, only Table 2. Substrate scope of phosphonation reagents
3 2 3
AgNO and Ag CO afforded the products in lower yields of
44% and 48%, respectively (Table 1, entries 2-6, and
Supporting Information (SI)); among various photocatalysts,
eosin Y exhibited a higher activity, leading to the product in
78% yield (Table 1, entries 7-11). Some oxidants were then
2
2
O
8
4 2 2 8
evaluated such as Na S and (NH ) S O , the products were
obtained in relatively lower yields of 57% and 45%,
respectively (Table 1, entries 7 vs 12-14, and SI). Finally, some
control experiments were explored. For example, reducing the
reaction time to 4 h, performing the reaction in air or oxygen
did not afford the better results (Table 1, entries 15-17vs entry
7
). The molecular structure of 3aa was unambiguously
9
confirmed by single crystal X-ray diffraction study.
a
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), Ag
mol%), 26 W household light, K (0.2 mmol, 2 equiv) in CH
under nitrogen for 6 h. Isolated yield.
2
O (10 mol%), eosin Y (3
a
Table 1. Screening of reaction conditions
2
S
2
O
8
3
CN/H O (1.0 mL)
2
b
Subsequently, the substrate scope of 8-hydroxyquinoline
esters was examined, and the results are summarized as Table
3
. The results demonstrated that both electron-donating (Me
and OMe) and electron-withdrawing (e.g., F, Cl, Br, I, CN and
CF ) groups on the benzene ring were all well tolerated (3aa
-
3
3va). Moreover, the substrates bearing the electron-donating
group on the quinoline ring could also smoothly afford the
desired products in moderate yields (3ta-3va). Nevertheless,
aliphatic 8-hydroxyquinoline esters can also be tolerated in
this phosphonation, albeit resulting in the target products in
lower yields of 34% and 37%, respectively (3wa and 3xa).
Furthermore, the product 3aa could be easily transformed into
C4 phosphonated 8-hydroxyquinoline 4a in 77% yield via
hydrolysis process (Scheme 2)
b
Entry Photocatalyst
AgX
Oxidant Yield (%)
1
2
3
4
5
6
7
8
9
acid red 94
acid red 94
acid red 94
acid red 94
acid red 94
acid red 94
eosin Y
Ag O
K S O
50
<5
37
<5
44
48
78
43
42
20
43
38
57
45
57
34
<5
2
2
2
2
2
2
2
2
2
8
8
8
8
8
8
AgOAc
K
K
K
S
S
S
O
O
O
AgNO
Ag PO
2
3
4
AgNO3
K S O
2
2
2
2
2
2
2
2
O
O
O
Ph
Ph
NaOH
EtOH
Ph
Ph
P
Ag
Ag
Ag
Ag O
2
CO
3
K
K
K
S
S
S
O
O
P
O
HO
2
O
8
N
80 oC, air, 12h
hydrolysis
N
eosin B
2
O
O
8
8
8
8
3
aa
4a, 77%
[Ru(bpy) ]Cl
K S O
3
2
2
2
2
2
2
2
2
1
0
1
2
3
4
Alizarin red S
Ir(bpy)
Ag
Ag
Ag
2
2
2
O
O
O
K
K
S
S
O
O
Scheme 2. The hydrolysis of 3aa
1
1
1
1
3
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
TBHP
Ag O
Na S O
2
2
2
8
To further demonstrate the synthetic utility of this
reaction, a gram-scale reaction was conducted to afford the
desired product 3aa in 56% yield (Scheme 3).
Ag
Ag
Ag
2
2
2
O
O
O
(NH
4
)
2
S
2
O
8
c)
1
1
1
5
6
7
K
K
K S O
2
S
2
O
O
8
d)
e)
2
S
2
8
8
eosin Y (3 mol%)
Ag2O (10 mol%)
Ag O
2
2 2
O
O
O
O
K2S2O8 (2.0 equiv)
Ph
Ph
a
P
Ph
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), AgX (10 mol%), photocatalyst
3 mol%, 26 W household light), oxidant (0.2 mmol, 2 equiv) in CH CN/H O(3:2)
+
O
H
P
O
Ph CH3CN/H2O (3:2)
rt, nitrogen, 6 h
(
(
3
2
N
N
b
c
d
e
1.0 mL) under nitrogen for 6 h. Isolated yield. For 4 h. Under air. Under
household light
1a, 5.0 mmol
2a, 1.8 equiv
3aa, 56%
oxygen
.
Scheme 3. A gram scale experiment.
2
| J. Name., 2012, 00, 1-3
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a,b
Table 3. Substrate scope of 8-hydroxyquinoline esters
Scheme 4. Control experiment
standard conditions, indicating that the oxidative
phosphonation might proceed via a radical process (Scheme
5b).
Based on above experimental results and previous
4
b,4c,4d
reports
In the first case, the coordination of 8-hydroxyquinoline ester
with Ag(I) affords a chelated intermediate . Meanwhile, a
phosphonyl radical and an sulfate radical can be generated
, a plausible mechanism is illustrated in Scheme 5.
1
a
B
A
from the oxidation of diphenylphosphine oxide 2a in the
presence of K S O via a photoredox catalytic cycle. The radical
2
2
8
addition of the phosphonyl radical
then occurs at the C4 position to form an intermediate radical
. Subsequently, the intermediate is generated through
oxidation of the intermediate by the sulfate radical via a
single electron transfer (SET) process. Finally, decomposition
of intermediate occurs, releasing a proton and successfully
A to the intermediate B
C
D
C
D
affording the desired product 3aa, along with the regeneration
of the active Ag(I) species to fulfil the catalytic cycle.
a
Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), Ag
2
O (10 mol%), eosin Y (3
CN/H O (1.0 mL)
mol%), 26 W household light, K
2
S
O
2 8
(0.2 mmol, 2 equiv), CH
3
2
b
under nitrogen for 6 h. Isolated yield.
To gain insight into the reaction mechanism, some control
experiments were performed (Scheme 4). Taking structurally
similar substrates (5a) instead of the 8-hydroxyquinoline esters
in the phosphonation with diphenylphosphine oxide 2a did not
lead to any product. The reaction of 1-naphthol ester also did
not afford any product, indicating that the N,O dichelated 8-
hydroxyquinoline skeleton is essential for the successful
conversion. The reactive site might be determined by the
stronger coordination bond of X→Ag. For example,
phosphonation product is not detected for 1-naphthol ester
due to no coordination effect of naphthalene ring to Ag atom;
N
pyr→M is stronger than the O→Ag in 8-hydroxyquinoline, so Scheme 5. Proposed mechanism of the phosphonation
the reaction of 8-hydroxyquinoline esters would reactions
regioselectively occur at the C4 position. The phosphonation
was then performed in the presence of the radical scavenger
2
,2,6,6-tetramethylpiperidine N-oxide (TEMPO) or 2,6-di-tert-
Conclusions
butyl-4-methylphenol (BHT), and the reaction was successfully
inhibited (Scheme 5a). Furthermore, an adduct 6a of
phosphine oxide and BHT was detected by HR-MS under
In conclusion, we have successfully developed a convenient
and environmentally friendly method for C4-H phosphonation
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of 8-hydroxyquinoline esters with diarylphosphine oxides
under dual catalysis of eosin Y and silver salt under external
base- or acid-free conditions, thereby providing a simple
approach to the C4 phosphonated quinoline scaffolds. The
reaction features high regioselectivity at the unusual C4 site,
good functional group tolerance and mild conditions.
Gao, X. Li, J. Xu, Y. Wu, W. Chen, G. Tang and Y. Zhao, Chem.
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Lett. 2016, 18, 452-455.
6
7
8
(a) H. Qiao, S. Sun, F. Yang, Y. Zhu, W. Zhu, Y. Dong, Y. Wu, X.
Kong, L. Jiang and Y. Wu, Org. Lett. 2015, 17, 6086-6089; (b)
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Wu, Org. Lett. 2016, 18, 4594-4597; (b) P. Bai, S. Sun, Z. Li, H.
Experimental
Typical Procedure
A 20 mL Schlenk tube was equipped with a magnetic stir bar
Qiao, X. Su, F. Yang, Y. Wu and Y. Wu, J. Org. Chem. 2017, 82
,
and charged with 8-hydroxyquinoline derivative
diarylphosphine oxide (0.2 mmol), eosin Y (2.1 mg, 0.003
mmol, 3 mol%), K (0.2 mmol, 2 equiv), Ag O (2.3 mg, 0.01
mmol, 10 mol%) in CH CN/H O(3:2) (1.0 mL). The resulting
1 (0.1 mmol),
1
For selected reports for C−H funcꢀonalizaꢀon under
2119-12127.
2
2
S
2
O
8
2
photoredox catalysis: (a) X. Li, X. Gu and P. Li, ACS Catal.
2014, 4, 1897-1900; (b) W. Yang, S. Yang, P. Li and L. Wang,
3
2
Chem. Commun. 2015, 51, 7520-7523; (c) K. Luo, Y. Z. Chen,
W. C. Yang, J. Zhu and L. Wu, Org. Lett. 2016, 18, 452-455;
mixture was stirred under the irradiation of 26 W household
light under nitrogen at room temperature for 6 h. Upon
(
d) E. Meggers, Chem. Commun. 2015, 51, 3290-3301; (e) G.
completion, the mixture was added into H
extracted with CH Cl (20 mL) three times. The combined
organic layer was dried over anhydrous Na SO and filtered.
2
O (20 mL) and
Zhang, C. Bian and A. Lei, Chinese J. Catal. 2015, 36, 1428-
1439; (f) J. W. Beatty and C. R. J. Stephenson, Acc. Chem. Res.
2015, 48, 1474-1484; (g) H. Huang, K. Jia and Y. Chen, ACS
2
2
2
4
Catal. 2016,
CCDC1580532
6
, 4983-4988.
3aa
After evaporation of the solvent under vacuum, the residue
was purified by column chromatography on silica gel (100‒200
9
(
)
contains
the
supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
mesh) using CH
2 2
Cl /ethyl acetate as an eluent (2:1, V/V) to
afford the pure product
3.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (nos. 21102134, 21172200) for financial support.
Notes and references
1
(a) Q. A. Khan, J. Lu and S. M. Hecht, J. Nat. Prod. 2009, 72,
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T. Hirao, T. Masunaga, Y. Ohshiro and T. Agawa, Synthesis
2
3
1
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4
5
For reports of the phosphonation of the quinoline ring, see:
(
a) C.-B. Xiang, Y.-J. Bian, X.-R. Mao and Z.-Z. Huang, J. Org.
Chem. 2012, 77, 7706-7710; (b) S. Wang, R. Guo, G. Wang,
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3
Qiao, S. Sun, Y. Zhang, H. Zhu, X. Yu, F. Yang, Y. Wu, Z. Li and
Y. Wu, Org. Chem. Front. 2017, 4, 1981-1986.
For selected reports of the phosphonation of heterocycles
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and M. Murakami, Angew. Chem. Int. Ed. 2013, 52, 9801-
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4
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00370J
Direct C4-H Phosphonation of 8-Hydroxyquinoline Derivatives
Employing Photoredox Catalysis and Silver Catalysis
A simple and efficient protocol for the C4-H phosphonation of 8-hydroxyquinoline derivatives was developed under
photoredox/silver(I) cocatalysis system