Practical way for the synthesis of phosphine oxides and phosphine sulfides from benzyl alcohol derivatives

Article abstract of DOI:10.1016/j.tetlet.2016.04.035

The reaction of benzyl alcohol derivatives with Ph₂PI generated in situ from Ph₂PCl and NaI provides a facile way to the synthesis of pentavalent phosphine compounds with moderate to excellent yields.

Full text of DOI:10.1016/j.tetlet.2016.04.035

Tetrahedron Letters 57 (2016) 2465–2467
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Practical way for the synthesis of phosphine oxides and phosphine
sulfides from benzyl alcohol derivatives
Yutao Ma a, Feng Chen a, Jifeng Bao d, Hao Wei b, , Min Shi a,c, Feijun Wang a,
⇑
⇑
a Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 MeiLong Road, Shanghai 200237, PR China
b School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, PR China
d Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of benzyl alcohol derivatives with Ph2PI generated in situ from Ph2PCl and NaI provides a
facile way to the synthesis of pentavalent phosphine compounds with moderate to excellent yields.
Ó 2016 Elsevier Ltd. All rights reserved.
Received 2 March 2016
Revised 8 April 2016
Accepted 12 April 2016
Available online 20 April 2016
Keywords:
Ph2PI
Michaelis–Arbuzov reaction
Phosphine oxides
Phosphine sulfoxides
Oxophilic Lewis acid
Introduction
achievements, the MA reaction still suffered the difficult isolation
of R1R2POR3 from the reaction of alcohol HOR3 with phosphine
Phosphorus compounds have emerged as a preeminent class of
organic compounds which hold ubiquitous applications serving as
versatile ligands for transition metal catalyzed reactions,1 Lewis
basic organocatalysts to promote various organocatalytic transfor-
mations such as Morita–Baylis–Hillman reaction,2 and useful
reagents in a wide array of organic transformations.3 Therefore,
there are a steadily increasing number of reports on the application
of phosphorus compounds.4 Given their high importance, there is
an ongoing interest in the development of convenient and general
protocols for the synthesis of phosphorus compounds.5
Michaelis–Arbuzov (MA) reaction as one of the most important
reactions for the preparations of phosphorus compounds such as
phosphonates, phosphinates, and phosphane oxides has received
wide attention from both academia and industry.6 Considering
the low efficiency with the selectivity of R1R2P(O)R4 and R1R2P(O)R3
and required strict reaction conditions of classic version of a
trivalent phosphorus ester R1R2POR3 with alkyl halide R4X
(Scheme 1), more optimized strategies such as the use of ionic
reagent, especially for these R1R2POR3 with a high boiling point.
Therefore, practical and flexible synthetic strategies leading to
phosphorus compounds directly from easily available reactants
such as alcohol HOR3 are still in high demanding.
Recently, the reaction of aldehydes with Ph2PI reported in our
previous work provides a facile way to the synthesis of pentavalent
phosphine compounds with moderate to good yields.8 Ph2PI was
used as an efficient phosphine reagent, and was also used as a
reduction reagent to promote the reduction of pentavalent
phosphine to tervalent phosphine and oxophilic Lewis acid catalyst
to promote the MA rearrangement. Therefore, we reasoned that
phosphination of HOR3 with R1R2PI to give R1R2POR3 could be
subjected to MA rearrangement using R1R2PI as oxophilic Lewis
acid to afford pentavalent phosphine which was further reduced
by R1R2PI to furnish trivalent phosphine intermediate8 (Scheme 1).
However, due to its easy oxidation, this intermediate can be easily
converted to the corresponding stable pentavalent phosphine com-
pound by a simple oxidation in work-up procedures. Herein we
wish to report a highly convergent and concise method to the syn-
thesis of phosphine oxides and sulfoxides by the Ph2PI-promoted
reaction of HOR3.
7
liquid solvents, microwave-assisted heating, and I2 or oxophilic
Lewis acid catalysts were developed. In spite of all these
Initially, benzyl alcohol was chosen as a model substrate to
prepare its phosphine oxide 3a under the presence of Ph2PCl and
NaI. From the optimization of the employed amounts of Ph2PI
⇑
Corresponding authors.
E-mail addresses: haowei@sjtu.edu.cn (H. Wei), feijunwang@ecust.edu.cn
(F. Wang).
http://dx.doi.org/10.1016/j.tetlet.2016.04.035
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

2466
Y. Ma et al. / Tetrahedron Letters 57 (2016) 2465–2467
Table 2
Previous Work (Michaelis-Arbuzov reaction):
The reaction of Ph2PI and alcohol to generate phosphine oxidesa
R3
O
P
R1
O
P
R1
O
P
R3
R2
R4X
R4
R2
R3X
+
+
(1) NaI (6.0 equiv)
CH
CN, 80 o
(2) 30% H2O2, or air
R1 R2
3
C
R
PPh2
+
ClPPh
2
R
OH
O
3
1
2
This Work:
(6.0 equiv)
X
P
R1
R1R2PI (R1 = R2 = Ph)
X = O, S
R3
R2
R3 OH
Entry Substrate
Yieldb
(%)
Entry Substrate
Yieldb
(%)
R1R2PI
phosphination
oxidation
R2
OH
OH
R3
MA
O
P
1
3b, 91
3c, 67
8
9
3i, 86
3j, 95
1b
O
R3
P
R1
1i
rearrangement
R1R2PI
reduction
R1R2PI
Cl
Me
Me
R3
R2
Me
P
R1 R2
R1
OH
1c
Me
OH
1j
2
F
Scheme 1. Methods to the synthesis of phosphorus compounds.
Me
OH
1k
OH
3
4
3d, 49
3e, 94
10
11
3k, 87
3l, 86
1d
and reaction temperature (Table 1), it was found that higher
employed amounts of Ph2PI and reaction temperature could afford
the higher yield of 3a. Up to 99% yield of 3a was obtained using
6 equiv of Ph2PCl and NaI at 80 °C (entry 5).
NC
CF3
OH
1e
F3C
1l
OH
With the optimized reaction conditions in hand,9 various sub-
stituted alcohols were tested to demonstrate the generality of this
Ph2PI-mediated reaction. The results are summarized in Table 2.
Benzyl alcohol derivatives bearing either an electron-donating or
electron-withdrawing group led to the corresponding phosphine
oxides 3 in good to high yields, with an exception of alcohol 1d.
Alcohol 1d having a cyano group at 4-position of benzene ring gave
the desired product in only 49% yield (entry 3), probably due to
decomposition of the cyano group under these acidic conditions.
In order to prepare the analogues of these phosphine ligands devel-
oped by Buchwald and co-workers, alcohols 1l and 1m with a
biaryl framework were used to react with Ph2PI, affording products
3l and 3m in 86% and 62% yields, respectively (entries 11 and 12).
Alkyl alcohols such as ethanol 1q were also tested in this
Ph2PI-mediated reaction, however, 71% yield of desired product
3n was afforded (entry 13).
MeO
OH
1f
5
3f, 53
12
13
3m, 62
3n, 71c
Br
1m
OH
OH
6
7
3g, 99
3h, 73
EtOH 1n
1g
MeO
Me
OH
1h
a
Reaction conditions: (1) 1 (1.0 mmol), 2 (6.0 equiv) and NaI (6.0 equiv), CH3CN,
80 °C, 12 h; (2) 30% H2O2 or air in the work-up procedure.
b
Isolated yield.
c
Sealed reaction at 80 °C.
Table 3
The reaction of Ph2PI and alcohol to generate phosphine sulfoxidesa
Subsequently, these benzyl alcohol derivatives 1 were also used
to prepare their corresponding phosphine sulfoxides 4 using the
Sat. Na2S2O3 solution instead of 30% H2O2 in their work-up proce-
dure.10 As shown in Table 3, relatively low yields of phosphine sul-
foxides 4 were obtained by comparison of the yields of the
corresponding phosphine oxides 3.
(1) NaI (6.0 equiv)
CH
CN, 80 oC
3
R
PPh2
+
ClPPh
2
(6.0 equiv)
2
R
OH
(2) sat. Na2S2O3
S
4
1
Entry Substrate
Yieldb
(%)
Entry Substrate
Yieldb
(%)
A possible mechanism for the reaction of benzyl alcohol 1a and
Ph2PI is proposed in Scheme 2. Ph2PI was used as an oxophilic
Lewis acid catalyst to promote the Michaelis–Arbuzov rearrange-
ment of intermediate A through a bimolecular process, affording
the corresponding product B. Ph2PI with its oxophilic ability fur-
ther reacted with oxide B to give zwitterionic intermediate C,
which was further converted into tervalent phosphine D with the
OH
OH
1
4a, 69
8
4h, 71
4i, 53
1a
1h
Me
OH
OH
2
4b, 44
4c, 67
9
1b
1i
Cl
Me
Me
Me
OH
1c
OH
3
10
4j, 38
F
1j
Me
Me
OH
1k
OH
Table 1
Screening of reaction conditionsa
4
5
4d, 44
4e, 47
11
4k, 49
4l, 37
1d
NC
CF3
ClPPh2, NaI
(x equiv.)
OH
OH
PPh2
1e
12
F3C
CH3CN, 12 h
O
3a
1a
1l
OH
OH
MeO
OH
Entry
X (equiv)
Temp (oC)
Yield of
1f
3ab (%)
6
7
4f, 35
4g, 34
13
14
4m, 51
4n, 65c
Br
1m
1
2
3
4
5
1.0
3.0
3.0
3.0
6.0
rt
rt
60
80
80
Trace
56
85
91
99
OH
EtOH 1n
1g
MeO
a
Reaction conditions: (1) 1 (1.0 mmol), 2 (6.0 equiv) and NaI (6.0 equiv), CH3CN,
80 °C, 12 h; (2) Saturated Na2S2O3 used in the work-up procedure.
a
Reaction conditions: (1) 1a (1.0 mmol), 2 and NaI (X equiv), CH3CN, 12 h; (2)
b
Isolated yield.
30% H2O2 in the work-up procedure.
c
b
Sealed reaction at 80 °C.
Isolated yield.

Y. Ma et al. / Tetrahedron Letters 57 (2016) 2465–2467
2467
Ph
Ph
Ph Ph
References and notes
P
O
+
P
Ph2PI
-HI
Ph2PI
Ph
O
Ph
OPPh2
I-
Ph
OH
+
1. Selected reviews, see: (a) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029; (b)
Grushin, V. V. Chem. Rev. 2004, 104, 1629; (c) Fernández-Pérez, H.; Etayo, P.;
Panossian, A.; Vidal-Ferran, A. Chem. Rev. 2011, 111, 2119.
P
A
Ph
Ph
Ph
2. Selected a book, see: (a) Shi, M.; Wang, F.; Zhao, M.; Wei, Y. RSC Catal. Ser. 2011.
Selected reviews, see:; (b) Langer, P. Angew. Chem., Int. Ed. 2000, 39, 3049; (c)
Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811; (d)
Kataoka, T.; Kinoshita, H. Eur. J. Org. Chem. 2005, 45; (e) Basavaiah, D.; Rao, K.
V.; Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581; (f) Masson, G.; Housseman, C.;
Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 4614; (g) Singh, V.; Batra, S. Tetrahedron
2008, 64, 4511; (h) Ma, G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y. Chem. Commun. 2009,
5496.
Ph
Ph
+
+
I-
Ph
I-
Ph
Ph
Ph
P
O
Ph
P
Ph
Ph
Ph2PI
-Ph2PI
P
Ph
P
Ph
Ph
O
P
O
P
O
Ph
Ph
Ph
B
Ph
C
3. Selected a review, see: Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–
927.
4. Selected reviews, see: (a) Majoral, J.-P. New Aspects in Phosphorus Chemistry I;
Springer: Berlin Heidelberg, 2002; (b) Majoral, J.-P. New Aspects in Phosphorus
Chemistry II; Springer: Berlin Heidelberg, 2002; (c) Kaur, P.; Pindi, S.; Wever,
W.; Rajale, T.; Li, G. Chem. Commun. 2010, 4330.
5. Selected reviews, see: (a) Clarke, M. L.; Williams, M. J. In Organophosphorus
Reagents; Murphy, P. J., Ed.; Oxford University Press: New York, 2004. Chapter
2; (b) Gilheany, D. G.; Mitchell, C. M. In The Chemistry of Organophosphorus
Compounds; Hartley, F. R., Ed.; John Wiley and Sons: Chichester, UK, 1990; Vol.
1,. selected papers, see (c) Ohmiya, H.; Yorimitsu, H.; Oshima, K. Angew. Chem.,
Int. Ed. 2005, 44, 2368; (d) Jérôme, F.; Monnier, F.; Lawicka, H.; Dérien, S.;
Dixneuf, P. H. Chem. Commun. 2003, 696; (e) Caiazzo, A.; Dalili, S.; Yudin, A. K.
Org. Lett. 2002, 4, 2597.
6. Selected papers, see: (a) Renard, P.-Y.; Vayron, P.; Leclerc, E.; Valleix, A.;
Mioskowski, C. Angew. Chem., Int. Ed. 2003, 42, 2389; (b) Renard, P.-Y.; Vayron,
P.; Mioskowski, C. Org. Lett. 2003, 5, 1661; (c) Dabkowski, W.; Ozarek, A.;
Olejniczak, S.; Cypryk, M.; Chojnowski, J.; Michalski, J. Chem. Eur. J. 2009, 15,
1747.
Ph
Ph
Ph
- IP(O)Ph2
[X]
X = O, S
Ph
P
X
E
Ph
Ph
P
D
Scheme 2. A possible mechanism for the Ph2PI-mediated reaction.
elimination of diphenylphosphinic iodide. Due to the instability of
phosphine D for its easy oxidation, oxide E was obtained in its
work-up procedure.
In conclusion, we reported a practical method to prepare phos-
phorus compounds using Ph2PI as a multifunctional agent. The
unusual reactivity of Ph2PI generated in situ from the reaction of
Ph2PCl with NaI was disclosed in this work, such as its oxophilic
ability to promote the transformations of a series of oxo-containing
compounds and reducing the ability to achieve the reduction of
7. (a) Buss, A.; Warren, D. S. J. Chem. Soc., Perkin Trans. 1 1985, 2307; (b) Asuncion,
L.; Baldwin, A. J. E. Croat. Chem. Acta 1996, 69, 1421–1436.
pentavalent phosphine which usually required more than
a
8. Wang, F.; Qu, M.; Chen, F.; Xu, Q.; Shi, M. Chem. Commun. 2012, 8580.
9. General procedure for the synthesis of phosphine oxides 3: To a stirred mixture
of Ph2PCl (6.0 mmol), NaI (6.0 mmol), and anhydrous CH3CN (5.0 mL) was
added alcohol 2 (1.0 mmol) at room temperature under argon atmosphere. The
reaction mixture was stirred at 80 °C in oil bath for 12 h. When the reaction
temperature was cooled to room temperature, 30% H2O2 aqueous (0.5 mL) was
slowly added, and stirred for another 10 min. The organic layer was extracted
with dichloromethane, washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by chromatography on silica
gel to obtain the corresponding phosphine oxide 3.
stoichiometric amount of expensive, explosive, and/or not easy to
handle reducing agents. Moreover, a possible mechanism for the
reaction of benzyl alcohol with Ph2PI was proposed. Further
exploration of Ph2PI-mediated reactions and the application of
phosphorus compounds are ongoing.
Acknowledgment
10. General procedure for the synthesis of phosphine sulfoxide 4: To a stirred
mixture of Ph2PCl (6.0 mmol), NaI (6.0 mmol) and anhydrous CH3CN (5 mL)
was added alcohol 2 (1.0 mmol) at room temperature under argon atmosphere.
The reaction mixture was stirred at 80 °C in oil bath for 12 h. When the
reaction temperature was cooled to room temperature, aqueous Na2S2O3
(2.0 mL) was added to the reaction mixture, and stirred for another 10 minutes.
The organic layer was extracted with dichloromethane, washed with brine,
dried over MgSO4, and concentrated under reduced pressure. The residue was
purified by chromatography on silica gel to obtain the corresponding
phosphine sulfoxide 4.
The authors acknowledge the National Natural Science
Foundation of China (21372075 and 61376003) and the Medical-
Engineering Crossover Fund of Shanghai Jiao Tong University
(YG2015MS23) for financial support.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.04.
035.