Ph2PI as a reduction/phosphination reagent: Providing easy access to phosphine oxides

Article abstract of DOI:10.1039/c2cc33908k

The reaction of aldehydes with Ph₂PI provides a facile way to the synthesis of pentavalent phosphine compounds with moderate to good yields.

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Ph2PI as a reduction/phosphination reagent: providing easy access to
phosphine oxidesw
Feijun Wang,*a Mingliang Qu,a Feng Chen,a Qin Xu*a and Min Shi*ab
Received 31st May 2012, Accepted 4th July 2012
DOI: 10.1039/c2cc33908k
The reaction of aldehydes with Ph2PI provides a facile way to
the synthesis of pentavalent phosphine compounds with moderate
to good yields.
Phosphorus compounds have emerged as a preeminent class of
organic compounds that hold ubiquitous applications serving
as versatile ligands for transition metal catalyzed reactions,1
Scheme 1 The reaction of aldehyde with monohalogenophosphine.
Lewis basic organocatalysts to promote various organocatalytic
transformations, such as Morita–Baylis–Hillman reaction,2 and
oxides, which were further reduced by Ph2PI to afford phosphine
useful reagents in a wide array of organic transformations.3 There-
oxides in a one-pot operation.
Initially, the reaction mixture of benzaldehyde 2a with 3 equiv
fore, there is a steadily increasing number of reports on the
application of phosphorus compounds4 and the development of
Ph2PI generated in situ from Ph2PCl 1a and NaI in CH3CN was
stirred at 80 1C for 24 h, resulting a brown reaction solution with
the formation of I2. In order to eliminate the I2 in the work-up
procedure, sat. Na2S2O3 solution was added. However, 45%
yield of unexpected benzyldiphenylphosphine sulfide 4a was
obtained, and its structure was undoubtedly confirmed by a
single-crystal X-ray diffraction.w12 The formation of 4a suggested
that tervalent benzyldiphenylphosphine should be afforded in
this reaction, and subsequently reacted with S derived from the
reaction of I2 with Na2S2O3 in work-up procedures to give the
compound 4a. The formation of tervalent phosphine was further
confirmed by mass spectrometry analysis of the reaction mixture
(see the ESIw). Therefore, 30% H2O2 was used to quench this
reaction before the addition of Na2S2O3 solution.
convenient and general protocols for the synthesis of phosphorus
compounds.5
Compared with the reactivity of Me3SiCl, Me3SiI has showed
special reactivities to promote a variety of useful synthetic trans-
formations.6 For example, Me3SiI can promote the reaction of
salicylic aldehydes with carbonyl compounds providing a facile way
to construct 4H-benzopyranic scaffold in our previous work.7
Therefore, we reasoned that Ph2PI may also have more special
reactivities than Ph2PCl, which has been widely used as a phosphine
reagent in organic synthesis. However, Ph2PI-mediated reactions
received less attention.8 Herein, we wish to report a novel and
practical synthetic method for the synthesis of phosphorus-
containing compounds using Ph2PI as a multifunctional agent.
The reaction of aldehydes 2 with Ph2PCl 1 has been a well-
known reaction to give 1-chloroalkylphosphine oxides at elevated
temperature (Scheme 1).9 However, in order to prepare phosphine
oxides, which are key intermediates for the synthesis of E-alkenes10
and tervalent phosphines,4,5 these 1-chloroalkylphosphine oxides
should be treated with reduction systems, such as NaBH4/
DMSO.11 Inspired by the reduction of alkyl iodide with IÀ reagent
to give the reductive product with elimination of I2,7 the reaction of
aldehydes with Ph2PI was envisioned to give 1-iodoalkylphosphine
As expected, phosphine oxide 3a was obtained in 70% yield.
Further optimization of the employed amounts of Ph2PI and
reaction temperature was carried out. As shown in Table 1, up
to 99% yield of 3a was obtained in the presence of 4.5 equiv. of
Ph2PCl and NaI at 80 1C (Table 1, entry 3). Using KBr instead
of NaI could also afford 3a in 66% yield (Table 1, entry 7).
Next, we examined the substrate scope of this Ph2PI-mediated
reaction under the optimized conditions (4.5 equiv. of Ph2PCl
and NaI, CH3CN, 80 1C). The results are shown in Table 2. For
aldehydes 2b–d, the different position of the fluorine substituent
on the phenyl ring showed little influence on the yields of
corresponding phosphine oxides (Table 2, entries 1–3). However,
aldehydes with different electronic properties of substituents
showed the significant influence on the reaction outcomes
(Table 2, entries 3–8). For instance, aldehydes 2 with electron
donating groups, such as Me and OMe, gave higher yields of their
corresponding products than those of aldehydes 2 with electron-
withdrawing groups, such as F and CF3. This effect was also found
in the oxophilic Lewis acid catalyzed Michaelis–Arbuzov reaction.13
a Key Laboratory for Advanced Materials and Institute of Fine
Chemicals, East China University of Science and Technology, and
130 MeiLong Road, Shanghai 200237, P. R. China.
E-mail: feijunwang@ecust.edu.cn, qinxu@ecust.edu.cn
b State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, P. R. China.
E-mail: mshi@mail.sioc.ac.cn
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization data of new compounds and CCDC
883288. See DOI: 10.1039/c2cc33908k
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.

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Table 1 Screening of reaction conditionsa
Table 2 The reaction of Ph2PI and aldehydesa
Entry Aldehyde
Chlorophosphine Product Yieldb (%)
Entry
X (equiv.)
T/1C
Yield of 3aab (%)
1
2
3
4
5
6
7c
3.0
1.5
4.5
6.0
4.5
4.5
4.5
80
80
80
80
25
50
80
70
8
1
1a
3ab
76
99
96
25
79
66
2
1a
3ac
64
3
4
5
6
7
2d: R = F
2e: R = Cl
1a
1a
1a
1a
1a
3ad
3ae
3af
3ag
3ah
66
68
67
60
69
a
Reaction conditions: (1) 2a (1.0 mmol, 1a and NaI (x equiv.),
CH3CN, 24 h; (2) 30% H2O2 used in the work-up procedure.
b
c
Isolated yield. KBr instead of NaI was used.
8
9
2i: R = OMe
1a
1a
3ai
3aj
99
99
Up to 99% yield of 3ai was obtained. 2,4-Dimethyl benzalde-
hyde 2j and 2,4,6-trimethyl benzaldehyde 2k afforded the
corresponding products in up to 99% yield, respectively
(Table 2, entries 10–11). In order to synthesize the analogues
of these phosphine ligands developed by Buchwald and
co-workers,14 aldehydes 2m and 2n with a biaryl framework
were used to react with Ph2PI, affording products 3am and 3an in
99% and 74% yields, respectively (Table 2, entries 12 and 13).
Phosphine oxide 3ao containing a ferrocenyl framework was also
prepared from aldehyde 2o in 46% yield under the standard
conditions (Table 2, entry 14). Salicylic aldehyde 2p also furnished
the corresponding functional phosphine oxide 3ap in 80% yield
(Table 2, entry 15). Alkyl aldehyde 2q can also afford the product
3aq in 40% yield (Table 2, entry 16). Moreover, using Et2PCl 1b
as a phosphine reagent could furnish trialkyl phosphine oxides
3ba and 3bq in up to 99% yields (Table 2, entries 17 and 18).
Subsequently, different work-up procedures were investigated
to prepare other pentavalent phosphines. Benzyldiphenyl-
phosphine sulfide 4a and selenide 4b were successfully synthesized
(Scheme 2).
10
11
1a
1a
3ak
3al
99
99
12
1a
3am
99
13
14
1a
1a
3an
3ao
74
46
Other substrates instead of aldehyde 2 were also examined.
As shown in Scheme 3, ketone 5a, benzyl ether 5b, 2-phenyl-
oxirane 5c and benzyloxydiphenylphosphine 5d could also
afford their corresponding phosphine oxides in moderate yields.
Moreover, the reaction of 5d with Et2PCl in the presence of NaI
afforded the main product 3ba in 60% yield and the minor
product 3aa in 6% yield.
15
16
1a
1a
3ap
3aq
80
40
17
18
1b: R2 = Et
3ba
3bq
95
99
1b
In order to further prove the Ph2PI-mediated reduction of
pentavalent phosphine to tervalent phosphine, the mutual
transformation between phosphine oxide and sulfide was
investigated. With the treatment of Ph2PI, the transformations
of 3aa/4a into 4a/3aa can be successfully achieved (Scheme 4).
Sulfoxide 7 can also be reduced to sulfur compound 8 by
Ph2PI in 63% yield. Moreover, a deuterium experiment was
carried out. Deuterium water was added into this Ph2PI-mediated
reaction and deuterated phosphine oxide 3aa was formed in 65%
yield (D content 48% determined by ESI-MS).
a
Reaction conditions: (1) 2 (1.0 mmol), 1 and NaI (4.5 equiv.),
CH3CN, 24 h; (2) 30% H2O2 or air used in the work-up procedure.
b
Isolated yield.
A possible mechanism for the reaction of benzaldehyde and
Ph2PI is proposed in Scheme 5. Like the formation of a-iodo
trimethylsilyl ethers from the reaction of Me3SiI and aldehydes,15
intermediate A was obtained from the addition of Ph2PI to
benzaldehyde, and subsequently reduced by HI to give intermediate
B with elimination of I2. Ph2PI was used as an oxophilic Lewis acid
Scheme 2 The preparation of phosphine sulfide and selenide from 2a.
catalyst to promote the Michaelis–Arbuzov rearrangement of
intermediate B through a bimolecular process,13 affording
the corresponding product 3aa. Ph2PI with its oxophilic
ability further reacted with oxide 3aa to give zwitterionic
c
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the Fundamental Research Funds for the Central Universities
is gratefully acknowledged.
Notes and references
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2 For a book, see: M. Shi, F. Wang, M. Zhao and Y. Wei, The
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Series, 2011.
3 B. E. Maryanoff and A. B Reitz, Chem. Rev., 1989, 89, 863.
4 Selected books: (a) J.-P. Majoral, New Aspects in Phosphorus
Chemistry I, Springer, Berlin Heidelberg, 2002; (b) J.-P. Majoral,
New Aspects in Phosphorus Chemistry II, Springer, Berlin Heidel-
berg, 2002. Selected papers: (c) S. Pindi, P. Kaur, G. Shakya and
G. Li, Chem. Biol. Drug Des., 2011, 77, 20; (d) P. Kaur, S. Pindi,
W. Wever, T. Rajale and G. Li, Chem. Commun., 2010, 46, 4330;
(e) A. Kattuboina and G. Li, Tetrahedron Lett., 2008, 49, 1573.
5 Selected books: (a) M. L. Clarke and M. J. Williams, in Organo-
phosphorus Reagents, ed. P. J. Murphy, Oxford University Press,
New York, 2004, ch. 2; (b) D. G. Gilheany and C. M. Mitchell, in
The Chemistry of Organophosphorus Compounds, ed. F. R. Hartley,
John Wiley and Sons, Chichester, UK, 1990, vol. 1. Selected
papers: (c) H. Ohmiya, H. Yorimitsu and K. Oshima, Angew.
Scheme 3 Ph2PI promoted the transformations of
a series of
oxo-containing compounds.
´
Chem., Int. Ed., 2005, 44, 2368; (d) F. Jerome, F. Monnier,
H. Lawicka, S. Derien and P. H. Dixneuf, Chem. Commun.,
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M. Shi, Chem. Commun., 2012, 48, 6259–6261.
Scheme 4 Controlled experiments in the Ph2PI-mediated reaction.
8 Selected papers: (a) V. P. Morgalyuk, P. V. Petrovskii,
K. A. Lysenko and E. E. Nifant’, Russ. J. Gen. Chem., 2010,
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Obshch. Khim., 1992, 62, 1667; (d) N. D. Gomelya and
N. G. Feshchenko, Zh. Obshch. Khim., 1988, 58, 709.
Scheme 5 A possible mechanism for the Ph2PI-mediated reaction.
9 Selected papers: (a) K. Sasse, in Methoden der Organischen Chemie,
ed. E. Muller, Georg Thieme Verlag, Stuttgart, 1963, vol. 12/1;
¨
(b) N. J. De’, J. A. Miller, M. J. Nunn and D. Stewart, J. Chem.
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intermediate C, which was further converted into tervalent
phosphine D with the elimination of diphenylphosphinic
iodide. Due to the instability of phosphine D for its easy
oxidation, oxide 3aa was obtained in the work-up procedure.
In conclusion, we have developed efficient methods to prepare
phosphorus compounds using Ph2PI as a multifunctional agent.
The unusual reactivities of Ph2PI were disclosed in this work, such
as its oxophilic ability to promote the transformations of a series of
oxo-containing compounds and reducing ability to achieve the
reduction of pentavalent phosphine which usually required more
than a stoichiometric amount of expensive, explosive and/or not
easy to handle reducing agents. Moreover, a possible mechanism
for the reaction of benzaldehyde with Ph2PI was proposed. Further
exploration of Ph2PI-mediated reactions and the application of
phosphorus compounds are ongoing.
10 (a) B. E. Maryanoff and A. B. Reitz, Chem. Rev., 1989, 89, 863;
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L. A. Hepworth, J. A. Hadfield, A. T. McGown and R. G. Pritchard,
Synthesis, 1999, 1656.
12 CCDC 883288 4a 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.
13 (a) P.-Y. Renard, P. Vayron, E. Leclerc, A. Valleix and C. Mioskowski,
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Financial support from the Shanghai Municipal Committee
of Science and Technology (11JC1402600), the National Natural
Science Foundation of China (21072206, 20902019, 20472096,
20872162, 20672127, 21121062 and 20732008), the National
Basic Research Program of China (973)-2010CB833302 and
14 R. Martin and S. L. Buchwald, Acc. Chem. Res., 2008, 41, 1461.
15 M. E. Jung, A. B. Mossman and M. A. Lyster, J. Org. Chem.,
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c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.