Visible light-induced 4-phenylthioxanthone-catalyzed aerobic oxidation of triarylphosphines

Article abstract of DOI:10.1016/j.tetlet.2018.09.031

We report herein a visible light-induced oxidation of triarylphosphines under aerobic condition with excellent functional group tolerance. In this transformation, the photo catalyst 4-phenylthioxanthone acted as a photosensitizer for the in situ generation of singlet oxygen. This new approach provided a cheaper and greener method for the preparation of phosphine oxide, showing great advantages in environmental protocols.

Full text of DOI:10.1016/j.tetlet.2018.09.031

Accepted Manuscript
Visible Light-Induced 4-Phenylthioxanthone-Catalyzed Aerobic Oxidation of
Triarylphosphines
Aishun Ding, Shijie Li, Yang Chen, Ruiwen Jin, Cong Ye, Jianhua Hu, Hao Guo
PII:
S0040-4039(18)31112-2
https://doi.org/10.1016/j.tetlet.2018.09.031
TETL 50270
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
2 August 2018
7 September 2018
11 September 2018
Please cite this article as: Ding, A., Li, S., Chen, Y., Jin, R., Ye, C., Hu, J., Guo, H., Visible Light-Induced 4-
Phenylthioxanthone-Catalyzed Aerobic Oxidation of Triarylphosphines, Tetrahedron Letters (2018), doi: https://
doi.org/10.1016/j.tetlet.2018.09.031
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Visible Light-Induced 4-Phenylthioxanthone-Catalyzed Aerobic Oxidation of
Triarylphosphines
a
b
a
b
b
a
Aishun Ding , Shijie Li , Yang Chen , Ruiwen Jin , Cong Ye , Jianhua Hu , Hao
Guob,c,*,Hao_Guo@fudan.edu.cn
aState Key Laboratory of Molecular Engineering of Polymers and Department of
Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, PR
China
bDepartment of Chemistry, Fudan University, 2005 Songhu Road, Shanghai, 200438,
P. R. China. Tel: +86-21-31249190, Fax: +86-21-31249190, E-mail:.
cAcademy for Engineering and Technology, Fudan University, 220 Handan Road,
Shanghai, 200433, PR China
Abstract：We report herein a visible light-induced oxidation of triarylphosphines
under aerobic condition with excellent functional group tolerance. In this
transformation, the photo catalyst 4-phenylthioxanthone acted as a photosensitizer for
the in situ generation of singlet oxygen. This new approach provided a cheaper and
greener method for the preparation of phosphine oxide, showing great advantages in
environmental protocols.
Keywords: Photochemistry; Aerobic Oxidation; Phosphine; Phosphine Oxidation;
Visible Light
Visible light, as an abundant, inexhaustible and green energy source, has received
1
great attention, since MacMillan developed the direct asymmetric alkylation of
aldehydes by merging photoredox catalysis with organocatalysis under visible light
2
irradiation in 2008. Photoinduced aerobic oxidations are important reactions in
1

organic photochemistry, which are normally more environmentally friendly than
3
thermo-oxidations. A variety of photoinduced aerobic oxidations are processed via
electron transfer3a-3d or energy transfer3e-3g pathway in the presence of a suitable photo
catalyst. Phosphine oxide is an important fragment in organic compounds and
synthetically versatile intermediates in medication.4,5 Numerous methods have been
6
developed for the oxidation of phosphines into phosphine oxides. However,
stoichiometric external organic or inorganic oxidants are generally required in most of
these reactions,6a-6d which means that lots of toxic inorganic or organic wastes are
6
e
6f,6g
generated. In some cases, expensive additives or harsh conditions
are also
required. Thus, an efficient, environmentally friendly, and convenient method for the
oxidation of phosphine is always needed. Photoinduced aerobic oxidation provides a
nice method for the oxidation of phosphines, since oxygen is a green oxidant and the
reaction condition is normally quite mild. The photooxidation of phosphines by
singlet oxygen has been well studied.3f,7 Numerous photo sensitizers have been used
to generate singlet oxygen.3f, 7a In our previous study, we found that Eosin Y could be
used as the photo sensitizer to realize the photooxidation of triarylphosphines under
3
f
visible light irradiation and aerobic conditions. In this transformation, Eosin Y
played a key role in the energy transfer process, yielding singlet oxygen efficiently.
Recently, we have synthesized a series of thioxanthone derivatives to study their
photo catalytic activity. Interestingly, 4-phenylthioxanthone showed very nice
photocatalytic ability in the aerobic oxidation of thioethers into sulfoxides.8
Mechanism studies gained solid evidence to prove that singlet oxygen was the key
oxidant in this transformation. Based on our continuous research interest in this
field,3f,8,9 we did research in the visible light-induced 4-phenylthioxanthone-catalyzed
aerobic oxidation of triarylphosphines. Herein, we wish to report our recent
observations in this reaction (Scheme 1).
2

Scheme 1. Aerobic photooxidation of triarylphosphines
The initial investigation was carried out using tris(4-methoxyphenyl)phosphine 1a as
the model substrate, 5 mol% of 4-phenylthioxanthone as the photo catalyst, a 23 W
household lamp as the light source, and oxygen in air as the oxidant. A series of
common solvents were tested in the first step (entries 1-10, Table 1). To our great
delight, a stoichiometric yield of the desired product tris(4-methoxyphenyl)phosphine
oxide 2a was afforded in all the tested solvents. The only difference is that the
oxidation proceeded most quickly in CH
to the higher energy transfer efficiency and faster single electron transfer speed (vide
infra). Thus, CH OH was chosen as the best solvent. The oxidation of 1a in 3 mL of
CH OH gave almost the same result (entry 11, Table 1), however, the dissolution of
some other substrates was poor (vide infra). Thus, 30 mL of CH OH was applied in
3
OH (entry 10, Table 1), which might be due
3
3
3
the following studies. Finally, control experiments without catalyst (entry 12, Table 1)
or light (entry 13, Table 1) were carried out. The results indicated that both catalyst
and light played a key role in this transformation. Thus condition A (1 (0.2 mmol), 4-
phenylthioxanthone (5 mol%), CH
3
OH (30 mL), air (1 atm), 23 W household lamp,
and rt) was applied for the further studies.
3

Table 1. Optimization of the reaction conditionsa
Entry
Solvent
Acetone
THF
Time (min)
NMR Yield (%)b
>99
1
2
3
4
5
6
7
8
9
120
90
90
90
90
90
60
60
60
40
60
40
40
>99
DMSO
Ethyl acetate
DCM
>99
>99
>99
CH
Toluene
Et
EtOH
3
CN
>99
>99
2
O
>99
>99
1
0
CH
CH
CH
CH
3
3
3
3
OH
OH
OH
OH
>99 (100)c
>99
1
1d
1
1
2e
3g
0 (>99)f
0 (>99)f
a
A solution of 1a (0.2 mmol) in the tested solvent (30 mL) was irradiated by a 23 W
b
1
household lamp at rt under air atmosphere (1 atm). Yield determined by H NMR
analysis of the crude reaction mixture using dibromomethane (0.2 mmol) as internal
c
d
e
f
standard. Isolated yield. 3 mL of CH OH was applied. No catalyst was applied.
3
g
NMR recovery yield. The reaction was carried out without light.
With the optimal conditions in hands, we next investigated the substrate scope. As
shown in Table 2, the reaction showed nice tolerance to different substitutions. Firstly,
electron effect on the aryl ring was well studied. Reactants with a strong electron
donating group, like methoxy (2a) and ethoxy (2b), showed excellent reactivities.
Substrates bearing a weak electron donating group, like tert-butyl (2c), methyl (2d-f)
4

and phenyl (2g), also gave excellent yields. Meanwhile, no obvious effect on the
position of the methyl group was observed (2d-f). For weak electron withdrawing
group, like fluorine atom (2i) and chlorine atom (2j), substituted triarylphosphines,
the oxidation proceeded smoothly to yield the corresponding triarylphosphie oxides in
excellent yields. Finally, strong electron withdrawing groups, like methoxy carbonyl
(
2k), nitrile (2l), and trifluoromethyl (2m), were introduced to the aryl ring. The
corresponding products were formed in excellent yields. Notablely, 1-naphthyl (2n),
-thienyl (2o), 2-furyl (2p), and 2-pyridyl (2q) could also be well toleranted under the
2
standard photooxidation condition, affording the desired products in excellent yields.
We were delight to see that this method was also suitable for oxidation of
alkylphosphines, such as monoalkyl phophine (2r), dialkyl phosphine (2s), and
trialkyl phosphine (2t), to their corresponding phosphine oxides.
Table 2. Photooxidation of 1 under Condition Aa
Condition A
Ar P
3
Ar P O
3
2
1
b
2
a, 40 min, 100%
2b, 1 h, 93%
2c, 4 h, 90%
2
d, 1 h, 100%
2e, 1 h, 97%
2f, 1 h, 98%
Ph
Ph
P
O
Ph
b
2
g , 4 h, 91%
2h, 40 min, 97%
2i, 1 h, 92%
5

2
j, 1.5 h, 95%
2k, 5 h, 95%
2l, 6 h, 89%
b
2
2
2
m, 5 h, 94%
p, 4.5 h, 98%
s, 1 h, 98%
2n, 5 h, 93%
2o, 1 h, 90%
2q, 2 h, 91%
2r, 80 min, 99%
2t, 1 h, 98%
a
A solution of 1 (0.2 mmol) and 4-phenylthioxanthone (5 mol%) in MeOH (30 mL)
was irradiated by a 23 W household lamp at rt under air atmosphere (1 atm). Isolated
b
yield was reported. In this case, the reactant could not be dissolved in 30 mL of
CH
3
3
OH. Thus, the reaction was carried out in a mixed solvent of CH
2
Cl (5 mL) and
2
CH
OH (25 mL).
Next, gram scale reaction was carried out. As shown in Scheme 2, the reaction of
.049 g of 1h gave a 95% isolated yield of 2h. This result clearly demonstrated that
1
this oxidation could be easily realized in an excellent yield on gram scale, which
meant that this aerobic photooxidation might have high potential applications in
organic synthesis.
6

Scheme 2. Gram scale oxidation of 1h under Condition A
In order to get a better understanding of the mechanism, singlet oxygen ( O
quenching experiment was carried out using 1,4-diazabicyclo[2.2.2]octane as the
1
2
)
1
0
-·) quenching experiment was
singlet oxygen quencher and superoxide anion (O
2
carried out using (Z)-N-tert-butyl-1-phenylmethanimine oxide as the superoxide anion
11
quencher (Scheme 3). When 3 equiv. of 1,4-diazabicyclo[2.2.2]octane was applied,
the oxidation of 1h was totally inhibited, which indicated that singlet oxygen should
1
0
be involved as a key intermediate in this reaction. The oxidation did not occur with
the addition of 3 equiv. of (Z)-N-tert-butyl-1-phenylmethanimine oxide, which
demonstrated that superoxide anion should be generated and played a key role in this
11
oxidation. These results strongly suggested that both singlet oxygen and superoxide
anion were the key intermediates in this aerobic photooxidation.
O
N
N
N
(3 equiv.)
(3 equiv.)
O quenching
P
4
5
P
P
1
O quenching
2
2
Condition A, 40 min
Condition A, 40 min
1
h
1h
1h
9
4% recovered
8
5% recovered
Scheme 3. Quenching experiments
According to the above experiment results and literature precedents,3f,8,9,12,13
a
possible mechanism was proposed as shown in Scheme 4. Firstly, 4-
*
phenylthioxanthone (PC) reaches its excited state (PC ) under the irradiation of
14
*
3
visible light. Then the energy transferred from PC to oxygen ( O ), affording singlet
2
1
).3f,8 Next, the reductive triarylphosphine 1 and the oxidative singlet
oxygen ( O
2
oxygen underwent single electron oxidation to afford species 3 and superoxide anion
7

O - ).8,12 Then 3 reacted with superoxide radical anion to give intermediate 4. 4 and
·
9
(
2
another molecule of 1 finally furnished 2 as the product.9
Scheme 4. Proposed mechanism
In conclusion, a visible light-induced oxidation of triarylphosphine was developed
under aerobic condition. This reaction provided a cheaper and greener method for the
preparation of phosphine oxide derivatives. Considering that this method is
environmental friendly and the substrate scope is broad, this protocol may be widely
used in the oxidation of phosphine derivatives.
Acknowledgments
We greatly acknowledge the financial support from Fundamental Research Funds for
the Central Universities, Pioneering Project of Academy for Engineering and
Technology, Fudan University (gyy2017-002).
8

References:
(
1) (a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113,
5
1
4
322. (b) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem. Rev. 2016, 116,
0035. (c) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011,
0, 102. (d) Deng, X.; Li, Z.; García, H. Chem. Eur. J. 2017, 23, 11189. (e)
Chaudhary, R.; Natarajan, P. ChemistrySelect. 2017, 2, 6458. (f) Xie, J.; Jin,
H.; Hashmi, A. S. K. Chem. Soc. Rev. 2017, 46, 5193. (g) Mohapatra, L.;
Parida, K. Catal. Sci. Technol. 2017, 7, 2153.
(
(
2) Nicewicz, D. A.; MacMillan, D. W. C. Science 2008, 322, 77.
3) (a) Ren, L.; Yang, M.; Tung, C.; Wu, L.; Cong, H. ACS Catal. 2017, 7,
8
134. (b) Talla, A.; Driessen, B.; Straathof, N. J. W.; Milroy, L.; Brunsveld,
L.; Hessel, V.; NoÜla, T. Adv. Synth. Catal. 2015, 357, 2180. (c) Wang, L.;
Ma, Z.; Wei, X.; Meng, Q.; Yang, D.; Du, S.; Chen, Z.; Wu, L.; Liu, Q.
Green Chem. 2014, 16, 3752. (d) Pagire, S. K.; Kreitmeier, P.; Reiser, O.
Angew. Chem., Int. Ed. 2017, 56, 10928. (e) Chen, Y.; Wang, Z. U.; Wang,
H.; Lu, J.; Yu, S.; Jiang, H. J. Am. Chem. Soc. 2017, 139, 2035. (f) Zhang,
Y.; Ye, C.; Li, S.; Ding, A.; Gu, G.; Guo, H. RSC Adv. 2017, 7, 13240. (g)
Yang, S.; Li, P.; Wang, Z.; Wang, L. Org. Lett. 2017, 19, 3386. (h)
Omymen, W. M.; Rogan, J. R.; Jugović, B. Z.; Gvozdenović, M. M.; Grgur,
B. N. J. Saudi Chem. Soc. 2017, 21, 990. (i) Ma, J.; Zhu, C.; Xu, Y.; Lu, J.;
Huang, L.; Yang, Z. J. Saudi Chem. Soc. 2017, 21, 132.
(
(
4) (a) Zhao, D.; Wang, R. Chem. Soc. Rev. 2012, 41, 2095. (b) Hibner-Kulicka, P.;
Joule, J. A.; Skalika, J.; Bałczewski, P. RSC Adv. 2017, 7, 9194.
5) (a) Clarion, L.; Jacquard, C.; Sainte-Catherine, O.; Loiseau, S.; Filippini, D.;
Hirlemann, M.; Volle, J.; Virieux, D.; Lecouvey, M.; Pirat, J.; Bakalara, N. J. Med.
Chem. 2012, 55, 2196. (b) O’Brien, C. J.; Tellez, J. L.; Nixon, Z. S.; Kang, L. J.;
Carter, A. L.; Kunkel, S. R.; Przeworski, K. C.; Chass, G. A. Angew. Chem., Int.
Ed. 2009, 48, 6836. (c) Gilard, V.; Martino, R.; Malet-Martino, M.; Niemeyer, U.;
Pohl, J. J. Med. Chem. 1999, 42, 2542. (d) Du, G.; Zou, X.; Dai,B.; He, L. J.
9

Saudi Chem. Soc. 2017, 21, 450.
(
6) (a) Karsch, H. H. Phosphorus, Sulfur Silicon Relat. Elem. 1982, 12, 217. (b) Poh,
S.; Hernandez, R.; Inagaki, M.; Jessop, P. G. Org. Lett. 1999, 1, 583. (c) Yasui, S.;
Tojo, S.; Majima, T. J. Org. Chem. 2005, 70, 1276. (d) Yasui, S.; Yamazaki, S.
Chem. Lett. 2015, 44, 422. (e) Yamada, T.; Suzuki, K.; Hashimoto, K.; Ikeno, T.
Chem. Lett. 1999, 10, 1043. (f) Bergin, E.; O’Connor, C. T.; Robinson, S. B.;
McGarrigle, E. M.; O’Mahony, C. P.; Gilheany, D. G. J. Am Chem. Soc. 2007,
1
29, 9566. (g) Elson, K. E.; Jenkinsb, I. D.; Loughlin, W. A. Tetrahedron Lett.
004, 45, 2491.
2
(
7) (a) Zhang, D.; Celaje, J. A.; Agua, A.; Doan, C.; Stewart, T.; Bau, R.; Selke, M.
Org. Lett. 2010, 12, 3100. (b) Gao, R.; Ho, D. G.; Dong, T.; Khuu, D.; Franco, N.;
Sezer, O.; Selke, M. Org. Lett. 2001, 3, 3719. (c) Zhang, D.; Ye, B.; Ho, D. G.;
Gao, R.; Selke, M. Tetrahedron 2006, 62, 10729.
(
(
8) Ye, C.; Zhang, Y.; Ding, A.; Hu, Y.; Guo, H. Sci. Rep. 2018, 8, 2205.
9) Ding, A.; Wang, Y.; Rios, R.; Sun, J.; Li, H.; Guo, H. J. Saudi Chem. Soc. 2015,
1
9, 706.
(
(
10) Guo, J.; Yang, D.; Guan, Z.; He, Y. J. Org. Chem. 2017, 82, 1888.
11) Kim, S.; Liu, Y.; Nash, K. M.; Zweier, J. L.; Rockenbauer, A.; Villamena, F. A. J.
Am. Chem. Soc. 2010, 132, 17157.
(
(
12) (a) Tsuji, S.; Hondo, M.; Ishiguro, K.; Sawaki, Y. J. Org. Chem. 1993, 58, 5055.
(
b) Li, W.; Xie, Z.; Jing, X. Catal. Commun. 2011, 16, 94.
13) (a) Herder, M.; Schmidt, B. M.; Grubert, L.; Pätzel, M.; Schwarz, J.; Hecht, S. J.
Am. Chem. Soc. 2015, 137, 2738. (b) Zhou, J.; Guo, X.; Katz, H. E.; Bragg, A. E.
J. Am. Chem. Soc. 2015, 137, 10841.
(
14) The UV-vis absorption spectrum of 4-phenylthioxanthone in CH OH indicated
3
that the absorption wavelength is intense at 382 nm, which is in visible
wavelength rang (380-780 nm). For more information, see Supplementary
Material.
Research highlights
10

1
2
3
. 4-Phenylthioxanthone-catalyzed aerobic oxidation of triarylphosphines.
. Good functional groups compatibility.
. Green oxidation method.
11

Research highlights
1
2
3
. 4-Phenylthioxanthone-catalyzed aerobic oxidation of triarylphosphines.
. Good functional groups compatibility.
. Green oxidation method.
12