Mild and efficient oxidation of phosphorus(III) compounds with Selectfluor

Article abstract of DOI:10.1016/j.tetlet.2016.06.078

A novel and efficient oxidation of phosphorus(III) compounds with Selectfluor is described. The reactions smoothly led to the formation of tertiary phosphine oxides, phosphinates, and phosphonates in up to 99% yield under mild conditions in minutes.

Full text of DOI:10.1016/j.tetlet.2016.06.078

Accepted Manuscript
Mild and efficient oxidation of phosphorus(III) compounds with Selectfluor
Qian Chen, Jiekun Zeng, Xinxing Yan, Yulin Huang, Zhiyun Du, Kun Zhang,
Chunxiao Wen
PII:
S0040-4039(16)30747-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.078
TETL 47805
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
10 May 2016
13 June 2016
17 June 2016
Please cite this article as: Chen, Q., Zeng, J., Yan, X., Huang, Y., Du, Z., Zhang, K., Wen, C., Mild and efficient
oxidation of phosphorus(III) compounds with Selectfluor, Tetrahedron Letters (2016), doi: http://dx.doi.org/
10.1016/j.tetlet.2016.06.078
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phosphorus(III) compounds with Selectfluor
Qian Chen, Jiekun Zeng, Xinxing Yan, Yulin Huang, Zhiyun Du, Kun Zhang, Chunxiao Wen

1
Tetrahedron Letters
Mild and efficient oxidation of phosphorus(III) compounds with Selectfluor
Qian Chen, Jiekun Zeng†, Xinxing Yan†, Yulin Huang, Zhiyun Du, Kun Zhang, Chunxiao Wen
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, Guangdong 510006, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel and efficient oxidation of phosphorus(III) compounds with Selectfluor is described. The
reactions smoothly led to the formation of tertiary phosphine oxides, phosphinates and
phosphonates in up to 99% yield under mild conditions in minutes.
© 2016 Published by Elsevier Ltd.
Available online
Keywords:
Phosphines
Phosphine oxides
Oxidation
Selectfluor
Organophosphorus compounds have been widely used in
organic synthesis,1 materials,2 bioorganic and medical
chemistry,3 coordination chemistry and catalysis,4 and flame
retardants.5 Phosphine oxides, phosphinates and phosphonates
are popularly introduced into the synthesis of organophosphorus
compounds,6 which shows that the oxygen atom of P=O bonds
serves as a protecting group for phosphorus because of the strong
nucleophilicity of phosphorus(III) compounds. Trivalent
phosphines, which are the most important class of ligands in
metal-catalyzed reactions,7 are usually synthesized by the
reduction of phosphine oxides.8 On the other hand, phosphine
oxides are also applied as reagents in Wittig–Horner reactions,9
as ligands10 and Lewis bases.11 A variety of methods are used for
the oxidation of P(III) compounds: (1) the use of oxidants
Recently, electrophilic fluorinating reagents with the general
structure R2N–F or R3N+–F have been of particular interest to
fluorination
reactions.18
For
example,
NFSI
(N-
fluorobenzenesulfonimide) or Selectfluor (1-chloromethyl-4-
fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate))
(Figure 1) provides
a convenient entry to site-selective
monofluorination.18,19 On the other hand, electrophilic
fluorinating reagents can also play an important role in a variety
of reactions as oxidants.18,20 In comparison with the previous
oxidants,12-16 NFSI and Selectfluor were milder, user-friendly,
safer, and more stable. With the above background and our recent
investigations on the synthesis of arylphosphonates and tertiary
phosphine oxides,21 we became interested in studying the
oxidation of P(III) compounds with electrophilic fluorinating
reagents. Herein, we report a novel and efficient oxidation of
P(III) compounds with Selectfluor to afford P(V) compounds in
high yields under mild conditions in minutes.
including
chromium(VI)
compounds,12
H2O2,13
dimesityldioxirane,14 oxone,15 and HOF;16 and (2) photocatalytic
electron-transfer oxidations.17 The efficient oxidation of P(III)
compounds under milder conditions is still a demand to fulfill the
modern synthesis.
First we carried out the reaction of triphenylphosphine 1a with
NFSI (2 equiv) in CH3CN/H2O (v/v = 100/1) at room
temperature (Table 1, entry 1), and triphenylphosphine oxide 2a
was obtained in 40% yield. To our delight, switching the oxidant
from NFSI to Selectfluor led to the formation of 2a in
quantitative yield in 5 minutes, and no purification was needed
(entry 2). To elucidate the oxygen source of 2a, we carried out
the reaction in anhydrous CD3CN under air, and only trace
amounts of 2a were detected (entry 3), which indicates that water
served as the oxygen source. We then turned to screen other
moist solvents (entries 4–9). The use of EtOH or acetone
decreased the yield, while 2a was obtained in quantitative yield
in DMSO, DMF, or CH3CN/H2O (v/v = 1/1). When 1 equiv of
Figure 1. Structures of NFSI and Selectfluor
———
 Corresponding author. Tel.: +86-20-3932-2231; fax: +86-20-3932-2235; E-mail address: qianchen@gdut.edu.cn (Q. Chen).
† These two authors contributed equally to this work.

2
Tetrahedron
Selectfluor was introduced, the oxidation reaction was still
noteworthy that the oxidation of dimethyl phenylphosphonite
afforded dimethyl phenylphosphonate in 54% yield (entry 16),
while triethyl phosphite and tribenzyl phosphite did not gave the
desired products (entries 17 and 18).
completed smoothly in 5 minutes (entry 10). When 0.5 equiv of
Selectfluor was used, the desired product was obtained in 50%
yield (entry 11), which suggests that Selectfluor cannot catalyze
this oxidation reaction. Thus, we concluded that the optimized
combination for the oxidation of P(III) compounds was to use 1
equiv of Selectfluor as the oxidant, CH3CN/H2O (v/v = 100/1) as
the solvent, and the reaction was set at room temperature (entry
10).
Table 2
Scope of the oxidation reactions of phosphorus(III) compounds with
Selectfluora
Table 1
Optimzation of the reaction conditionsa
Entry
Product
Time
Yieldb
Entry
1
Oxidant (equiv)
NFSI (2)
Solvent
Time
Yieldb (2a)
CH3CN/H2O
30 min
40%
1
2
3
4
5
6
5 min
5 min
5 min
5 min
5 min
60 min
99%
99%
93%
91%
99%
98%
CH3CN/H2O
CD3CN
quant.
trace
2
Selectfluor (2)
Selectfluor (2)
Selectfluor (2)
Selectfluor (2)
Selectfluor (2)
Selectfluor (2)
Selectfluor (2)
Selectfluor (2)
Selectfluor (1)
Selectfluor (0.5)
5 min
30 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
12 h
3c
4
EtOH/H2O
acetone/H2O
DMSO/H2O
DMF/H2O
THF/H2O
15%
7
10 min
36%
45%
5
6
quant.
quant.
quant.
quant.
quant.
50%
7
8
9
10
11
12
10 min
10 min
10 min
10 min
10 min
88%
98%
99%
99%
84%
8
9d
10
11
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
13c
10 min
10 min
80%
95%
a The reaction of 1a (0.2 mmol) and Selectfluor was carried out in 2 mL of
organic solvent/H2O (v/v = 100/1) at room temperature.
b
Yield based on 1a was determined by 1H NMR analysis of crude
14
products using an internal standard.
c
The reaction of 1a (0.05 mmol) and Selectfluor (0.1 mmol) was carried
out in anhydrous CD3CN (0.5 mL) under air in a sealed NMR tube.
d CH3CN/H2O (v/v = 1/1) was used as the solvent.
15
16
17
10 min
30 min
30 min
30 min
99%
To investigate the scope of the oxidation protocol, we applied
the optimized reaction conditions to a variety of P(III)
compounds 1 and the results are illustrated in Table 2.
Triarylphosphines 1a–f were all tolerated for the oxidation
reaction to smoothly give triarylphosphine oxides 2a–f in 91–
99% isolated yields (entries 1–6). It is noteworthy that the
oxidation of electron-poor tris(4-fluorophenyl)phosphine
required 60 minutes (entry 6). For the oxidation of tris(2-
furanyl)phosphine, the desired product 2g was isolated in only
36% yield (entry 7). When one of phenyl groups on PPh3 was
replaced by an electron-poor pyridyl group, the reaction also
afforded the desired product 2h in 88% yield in minutes (entry 8).
For the oxidation of alkyldiphenylphosphines, the desired
products 2i–k were obtained in high yields (entries 9–11). To our
delight, ethyl diphenylphosphinite can also smoothly react with
Selectfluor to afford ethyl diphenylphosphinate 2l in 84% yield
in 10 min (entry 12). Similarly, the reaction of dppe, Bu2PPh or
PCy3 with Selectfluor gave diphosphine oxide 2m, phosphine
oxide 2n or 2o in good yield, respectively (entries 13–15). It is
54%
-
-
18
a
All reactions were carried out with 1 (0.2 mmol) and Selectfluor (0.2
mmol) in 2 mL of CH3CN/H2O (v/v = 100/1) at room temperature.
b Isolated yield based on 1.
c The reaction of dppe (0.2 mmol) and Selectfluor (0.4 mmol) was carried
out in 4 mL of CH3CN/H2O (v/v = 100/1).

3
5.
6.
(a) Cho, C.-S.; Chen, L.-W.; Chiu, Y.-S. Polym. Bull. 1998, 41, 4552;
Based on the experimental results, a plausible mechanism of
the oxidation of P(III) compounds with Selectfluor is proposed as
shown in Scheme 1. P(III) compound 1 interacts with Selectfluor
to form the fluoro-phosphonium cation 3,22 which reacts with
water to form the unstable intermediate 4. Subsequent HF
elimination gives the desired oxidation product 2.
(b) Cho, C.-S.; Fu, S.-C.; Chen, L.-W.; Wu, T.-R. Polym. Int. 1998, 47,
203209.
For selected examples, see: (a) Jeulin, S.; de Paule, S. D.;
Ratovelomanana-Vidal, V.; Genêt, J.-P.; Champion, N.; Dellis, P.
Angew. Chem. 2004, 116, 324329; (b) Shintani, R.; Yashio, K.;
Nakamura, T.; Okamoto, K.; Shimada, T.; Hayashi, T. J. Am. Chem.
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H.; Chan, S.; Yu, W.-Y.; Li, Y.-M.; Guo, R.; Zhou, Z.; Chan, A. S. C. J.
Am. Chem. Soc. 2006, 128, 59555965; (d) Punniyamurthy, T.; Mayr,
M.; Dorofeev, A. S.; Bataille, C. J. R.; Gosiewska, S.; Nguyen, B.;
Cowley, A. R.; Brown, J. M. Chem. Commun. 2008, 41, 50925094; (e)
Itoh, H.; Yamamoto, E.; Masaoka, S.; Sakai, K.; Tokunaga, M. Adv.
Synth. Catal. 2009, 351, 17961800; (f) Shen, X.; Jones, G. O.; Watson,
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Scheme 1. Plausible mechanism of the oxidation of phosphorus(III)
compounds with Selectfluor
7.
8.
(a) de Meijere, A.; Diederich, F. Metal-Catalyzed Cross-Coupling
Reactions; Wiley-VCH: Weinheim, 2004; (b) Börner, A. Phosphorus
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Synthesis; Wiley-VCH: Chichester, U.K., 2012.
In summary, we have developed an efficient oxidation
protocol for phosphorus(III) compounds with Selectfluor, which
provides a facile methodology for the synthesis of tertiary
phosphine oxides, phosphinates and phosphonates under mild
conditions in minutes. To the best of our knowledge, only the
oxidation of PPh3 with Selectfluor was simply mentioned in gold-
catalyzed oxidative cross-coupling reactions by Zhang and co-
workers.23 This property of Selectfluor should lead to new and
useful applications in organophosphorus chemistry. Further
investigations on the transformations of phosphorus compounds
with electrophilic fluorinating reagents are ongoing and will be
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Acknowledgments
This work was supported by the National Natural Science
Foundation of China (Project No. 21242002), Science and
Technology Planning Project of Guangdong Province (Project
No. 2015A020211026), and 100 Young Talents Programme of
Guangdong University of Technology (Project No. 220413506).
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1
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4
Tetrahedron
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5
Highlights
1. The oxidation of P(III) compounds with
Selectfluor smoothly affords P(V) compounds
in high yields.
2. The reactions give tertiary phosphine oxides,
phosphinates and phosphonates at room
temperature in minutes.
3. The oxidation conditions are mild, user-
friendly, and safe.