Stereoselective synthesis of vinylphosphonates and phosphine oxides via silver-catalyzed phosphorylation of styrenes

Article abstract of DOI:10.1039/c5cc04826e

An efficient and stereoselective synthesis of vinylphosphonates and phosphine oxides was developed starting from styrenes using AgNO₃ as the catalyst and K₂S₂O₈ as the oxidant. The success of the reaction was fo

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Stereoselective synthesis of vinylphosphonates and phosphine oxides via
silver-catalyzed phosphorylation of styrenes
Qingwen Gui,a Liang Hu,a Xiang Chen,a Jidan Liu,a and Ze Tan*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Later on, Han was able to effect the same transformation with a
cheaper Ni-catalyst.9 Complementary to these metal catalyzed
processes, some radical initiated processes were also developed.10
Although these approaches provided useful access to substituted
vinylphosphonates, most of them suffered from some drawbacks
such as lack of stereoselectivity (a mixture of E/Z products) or
the need to use rather expensive catalyst. As a result, there
remains much room to be improved for the stereoselective
synthesis of vinylphosphonates.
An
efficient
and
stereoselective
synthesis
of
vinylphosphonates and phosphine oxides was developed
starting from styrenes using AgNO3 as the catalyst and
K2S2O8 as the oxidant. The success of the reaction was found
to be critically dependent on the use of TEMPO as the
additive.
Vinylphosphonates are a group of important compounds in
synthetic chemistry and are commonly used to prepare
biologically active molecules,1 flame retardants,2 polymer
additives.3 In addition, vinylphosphonates are frequently used in
organic transformations such as Michael additions,4a Horner-
Wadsworth-Emmons reactions.4b For these reasons, the
development of simple and stereoselective methods to prepare
vinylphosphonates has become important in organic synthesis.
Even though there are numerous methods for their syntheses,5
those relying on the formation of vinylic carbon-phosphorous
bonds by transition metal catalyzed cross coupling or addition
reactions are particularly noteworthy due to their overall
efficiency and selectivity.6 Though transition metal catalyzed
coupling of alkenyl halides or pseudo halides with H-
phosphonate does provide useful ways of synthesizing
vinylphosphonates (Eq. 1), the addition of H-phosphonates to
alkynes is a 100% atom economical reaction since no waste is
generated in the process and all the atoms in the starting materials
are incorporated in the final products (Eq. 2). Consequently
considerable efforts have been spent by scientists on this research
front and significant progresses have been made.7-10 For example,
Han and Tanaka in 1996 have reported an efficient Pd-catalyzed
hydrophosphorylation of terminal alkynes, leading to the
selective formation of Markovnikov addition product.7 By
changing the catalyst from Pd to Rd and using a cyclic H-
phosphonate, they were able to reverse the regioselectivity
completely and (E)-alkenylphosphonates were obtained instead.8
O
P(OR)2
O
Br
metal catalyst
Eq. 1
HP(OR)2
O
Eq. 2
Rh, Ni, Pd
P(OR)2
P(OR)2
O
O
HP(OR)2
O
P(OR)2
Eq. 3
Eq. 4
O
HP(OR)2
O
this work
P(OR)2
Olefins are basic building blocks in organic chemistry and the use
of them as starting materials would be highly advantageous.
However, the reaction of olefins with phosphite catalyzed by
transition metal catalyst or radically initiated, as reported by
many chemists, usually gave the addition product (Eq. 3).10e,11
Recently, Maiti reported a series of efficient nitration of olefins
with silver nitrite,12a Fe(NO3)312b or tert-butylnitrite12c via a nitro
radical addition process. With the aid of TEMPO, they were able
to obtain nitroalkenes instead of the saturated alkanes. Inspired by
Maiti's results and the knowledge that phosphite could be utilized
as phosphoryl radical precursor, we wonder that
vinylphosphonates can be synthesized directly from styrenes.13
Herein we report vinylphosphonates can indeed be efficiently and
stereoselectively synthesized from styrenes in good yields (Eq. 4).
Our investigation began with the reaction of styrene with
diethyl H-phosphonate in the presence of 5 mol% of Ag2CO3,
o
K2S2O8 (2 equiv) and TEMPO (0.4 equiv) in toluene at 100 C
for 6 hours. Much to our delight, the desired product 2a was
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indeed obtained even though the yield is very low (Table 1,
entry 1). This result encouraged us to optimize the reaction
parameters further. After a series of trials of silver catalysts, we
were pleased to find that the yield of vinylphosphonate could be
improved up to 73% in the presence of 0.05 equiv of AgNO3.
derivatives were found to undergo dehydrogenative
phosphonation in good to excellent yields ranging from 51-73%
with high stereoselectivity. It is gratifying to see that our reaction
not only worked with dialkyl H-phosphonates but also with
diphenylphosphine oxide as well. Thus a series of vinylphosphine
oxides were synthesized stereoselectively using our standard
condition in 53-81% yield (Table 2, entries 2n-2u, 2w, 2x, 2af).
Substituents such as methyl, methoxy, ethoxy, tert-butyl, fluoro,
chloro, bromo, iodo, cyano and acetyl group are well tolerated on
the aromatic ring and their reactions afforded the target products
in good to excellent yields, showing the broad scope of this
reaction. Styrenes with electron-donating groups could give
slightly better yields than analogues with electron-withdrawing
groups. Notably, sterically demanding substrate like 2,4,6-
trimethylstyrene could be phosphorylated in 65% yield (2h).
When the benzene ring of the substrates was changed to
naphthalene, the reaction successfully provided the desired
vinylphosphonate product 2i in 68% yield.
1
Analysis of the H NMR of the final product indicated that the
configuration of the double bond was trans, showing the reaction
is highly stereoselective. Among the organic and inorganic
oxidant examined, K2S2O8 turned out to the best choice while the
use of oxidant such as TBHP and benzoquinone gave very low
yields ( Table 1, entries 4-5). Subsequently, a number of
solvents including toluene, DMF, CH3CN and CH2Cl2 were
examined, and tests revealed toluene to be the best solvent (Table
1, entries 3 and 6–8). Control reaction also indicated that the
silver catalyst played a key role in the reaction and no desired
product was formed in the absence of Ag catalyst (Table 1, entry
9). The yields are very low when either K2S2O8 or TEMPO was
absent, showing both oxidant and additive are indispensable for
obtaining high yields (Table 1, entries 10 and 11). The reaction
could be carried out under nitrogen atmosphere, and 2a was
isolated in slightly lower yield, showing air is not essential for the
reaction to proceed (Table 1, entry 12). On the basis of the above
results, we decided to set reacting styrene with 1.5 equiv of
diethyl H-phosphonates with 5 mol% of AgNO3, 2 equiv of
K2S2O8 and 0.4 equiv TEMPO in toluene at 100 oC as our
standard condition.
We were pleased to find styrenes with a methyl group on the β-
position can afford the corresponding (E)-vinylphosphonate 2v
and vinylphosphine oxide 2w in yields above 50%. More
impressively, ɑ-methyl substituted styrene yielded the desired
products 2x-2ab in good to excellent yields as well. It is
worthwhile to point out that, unlike the results reported by
Maiti,12c only E products were obtained in all cases irrespective
With the optimized condition in hand, we next set out to
examine the scope of H-phosphonates and styrenes, and the
results were summarized in Table 2. A range of styrene
2
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of the position of the methyl group (ɑ or β). Under the standard
of the reaction mechanism and application to other substrates are
underway and the results will be reported in due course.
conditions, cyclic olefins of different complexity also reacted
smoothly to give 2ac, 2ad and 2ae in good yields. In addition, a
thiophene derivative could also afford the desired product 2af in
64% yield. Unfortunately, the reactions of aliphatic olefins and
conjugated dienes with diethyl H-phosphonate or phosphine
oxides turned out to be messy.
Notes and references
a State Key Laboratory of Chemo/Biosensing and Chemometrics, College
of Chemistry and Chemical Engineering, Hunan University, Changsha
410082, P. R. China. E-mail: ztanze@gmail.com
† Electronic Supplementary Information (ESI) available: [Detail
experimental procedures, analytical data]. See DOI: 10.1039/b000000x/
Control experiments were designed to investigate the
mechanism of this transformation. Since a pioneering report has
shown that silver salts can react with Ph2P(O)H to form the
corresponding active Ph2P(O)Ag complexes which subsequently
1
2
(a) T. Minami, J. Motoyoshiya, Synthesis, 1992, 333; (b) M. R.
Harnden, A. Parkin, M. J. Parratt, R. M. Perkins, J. Med. Chem.,
1993, 36, 1343; (c) H. B. Lazrek, A. Rochdi, H. Khaider, J.-L.
Barascut, J.-L. Imbach, J. Balzrini, M. Witvrouw, C. Pannecouque, E.
De Clerca, Tetrahedron, 1998, 54, 3807.
(a) M. Ruiz, M. C. Fernández, S. Conde, A. Diaz, J. M. Quintela,
Synlett, 1999, 12, 1903; (b) J. A. Russell, F. A. Ching, H. I.
Tashtoush, J. E. Russell, D. F. Dedolph, J. Org. Chem., 1991, 56, 663.
S. Jin, K. E. Gonsalves, Macromolecules, 1998, 31, 1010.
(a) D. Enders, H. Wahl, K. Papadopoulos, Tetrahedron, 1997, 53,
13961; (b) H. Inoue, H. Tsubouchi, Y. Nagaoka, K. Tomioka,
Tetrahedron, 2002, 58, 83.
(a) L. Coudray, J.-L. Montchamp, Eur. J. Org. Chem., 2008, 3601; (b)
W. Al-Maksoud, J. Mesnager, F. Jaber, C. Pinel, L. Djakovitch, J.
Organomet. Chem., 2009, 694, 3222; (c) H.-Q. Wang, Z.-J. Liu, Chin.
J. Org. Chem., 2003, 23, 321; (d) A. A. A. Quntar, M. Srebnik, Chem.
Commun., 2003, 58; (e) X. Huang, C.-G. Liang, Q. Xu, Q.-W. He, J.
Org. Chem., 2001, 66, 74; (f) J. M. Gil, D. Y. Oh, J. Org. Chem.,
1999, 64, 2950; (g) F. Palacios, C. Alonso, J. M. de los Santos, Chem.
Rev., 2005, 105, 899; (h) J.-A. Ma, Chem. Soc. Rev., 2006, 35, 630.
(a) G. W. Kabalka, S. K. Guchhait, Org. Lett., 2003, 5, 729; (b) S.
Thielges, P. Bisseret, J. Eustache, Org. Lett., 2005, 7, 681; (c) L. Liu,
Y. Wang, Z. Zeng, P. Xu, Y. Gao, Y. Yin, Y. Zhao, Adv. Synth.
Catal., 2013, 355, 659; (d) L. Liu, Y. Lv, X. Gao, Z. Zeng, Y. Gao,
G. Tang, Y. Zhao, RSC Adv., 2014, 4, 2322; (e) G. Hu, Y. Gao, Y.
Zhao, Org. Lett., 2014, 16, 4464; (f) J. Hu, N. Zhao, B. Yang, G.
Wang, L.-N. Guo. Y.-M. Liang, S.-D. Yang, Chem. Eur. J., 2011, 17,
5516; (g) Y. Wu, L. Liu, K. Yan, P. Xu, Y. Zhao, J. Org. Chem.,
2014, 79, 8118.
.
generate the Ph2P(O) radical,14 we surmise that Ph2P(O)Ag may
have played a critical role in our syntheses of vinylphosphine
oxides. Indeed, when the Ph2P(O)Ag complex was used in a
stoichiometric fashion in our reaction, the phosphorylated styrene
was isolated in 72% yield. Thus, it is reasonable to assume a
phosphoryl radical is an active intermediate in our reaction.
Based on this result and literature precedents,12,14 the following
plausible mechanism can be proposed for the transformation. The
Phosphoryl radical B may be generated from the complex A
which itself is formed by the reaction of Ag catalyst with the
phosphite under the reaction conditions. The resultant
intermediate B subsequently adds to the styrene to form a carbon-
centered radical C which was trapped by TEMPO to form
intermediate D. With the assistance of another molecule of
TEMPO, intermediate D undergoes elimination to form the
desired vinylphosphonate product12 and TEMPOH and Ag(0)
could be oxidized back to TEMPO and Ag(I) by K2S2O8
respectively, thus closing the catalytic cycle. The high E-
selectivity observed with most products indicated that the
reaction is a thermodynamically controlled process.
3
4
5
6
7
8
L.-B. Han, M. Tanaka, J. Am. Chem. Soc., 1996, 118, 1571.
(a) C.-Q. Zhao, L.-B. Han, M. Goto, M. Tanaka, Angew. Chem. Int.
Ed., 2001, 50, 1983; (b) L.-B. Han, C.-Q. Zhao, M. Tanaka, J. Org.
Chem., 2001, 66, 5929.
L.-B. Han, C. Zhang, H. Yazawa, S. Shimada, J. Am. Chem. Soc.,
2004, 126, 5080.
9
10 (a) E. E. Nifantev, R. K. Magdeeva, A. V. Dolidze, K. V. Ingorokva,
L. O. Samkharadze, L. K. Vasyanina, A. R. Bekker, J. Gen. Chem.
USSR, 1991, 61, 83; (b) O. Tayama, A. Nakano, T. Iwahama, S.
Sakaguchi, Y. Ishii, J. Org. Chem., 2004, 69, 5494; (c) C. M. Jessop,
A. F. Parsons, A. Routledge, D. J. Irvine, Tetrahedron Lett., 2003, 44,
479; (d) C. M. Jessop, A. F. Parsons, A. Routledge, D. J. Irvine, Eur.
J. Org. Chem., 2006, 1547; (e) R. A. Braun, J. L. Bradfield, C. B.
Henderson, N. Mobarrez, Y. Sheng, R. A. OˊBrien, A. C. Stenson, J.
H. Davis Jr., A. Mirjafari, Green. Chem., 2015, 17, 1259.
Scheme 2. Proposed reaction mechanism
PO(OEt)2
Ag(0)
TEMPOH
Oxidant
Oxidant
Ag-PO(OEt)2
PO(OEt)2
B
A
TEMPO
11 (a) L.-B. Han, F. Mirzaei, C. Q. Zhao, M. Tanaka, J. Am. Chem. Soc.,
2000, 122, 5407; (b) J. F. Reichwein, M. C. Patel, B. L. Pagenkopf,
Org. Lett., 2001, 3, 4303; (c) Q. Xu, L.-B. Han, Org. Lett., 2006, 8,
2099; (d) M. O. Shulyupin, G. Franciò, I. P. Pagenkopf, Adv. Synth.
Catal., 2005, 347, 667; (e) A. N. Reznikov, N. K. Skvortsov, Russ. J.
Gen. Chem., 2007, 77, 1170.
Ag(I)
TEMPO
HPO(OEt)2
PO(OEt)2
TEMPO
PO(OEt)2
C
D
In summary, we have developed
a novel and highly
12 (a) S. Maity, S. Manna, S. Rana, T. Naveen, A. Mallick, D. Maiti, J.
Am. Chem. Soc., 2013, 135, 3355; (b) T. Naveen, S. Maity, U.
Sharma, D. Maiti, J. Org. Chem., 2013, 78, 5949; (c) S. Maity, T.
Naveen, U. Sharma, D. Maiti, Org. Lett., 2013, 15, 3384.
13 L. Zhu, H. Yu, Q. Guo, Q. Chen, Z. Xu, R. Wang, Org. Lett., 2015, 17,
1978.
stereoselectivity protocol for the synthesis of vinylphosphonates
and phosphine oxides starting form styrenes. This process
features a broad substrate scope and excellent functional-group
tolerance. The yields of the reaction are generally high and the
reaction is very simple to run. Further studies on the clarification
14 (a) Y.-M. Li, M. Sun, H.-L. Wang, Q.-P. Tian, S.-D. Yang, Angew.
Chem. Int. Ed., 2013, 52, 3972; (b) W. Kong, E. Merino, C. Nevado,
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Angew. Chem. Int. Ed., 2014, 53, 5078; (c) D. Sheberla, B.
Tumanskii, A. C. Tomasik, A. Mitra, N. J. Hill, R. West, Y. Apeloig,
Chem. Sci., 2010, 1, 234; (d) J. Ke, Y. Tang, H. Yi, Y. Li, Y. Cheng,
C. Liu, A. Lei, Angew. Chem. Int. Ed., 2015, 54, 6604.
4
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