MW-Assisted P-C Coupling Reaction Using P-Ligand-Free Pd(OAc) 2 Catalyst

Article abstract of DOI:10.1080/10426507.2014.984023

P-C coupling reactions of a variety of >P(O)H species with aryl bromides were found to take place under P-ligand-free microwave conditions.

Full text of DOI:10.1080/10426507.2014.984023

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Phosphorus, Sulfur, and Silicon and the Related
Elements
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Mw-Assisted P-C coupling reaction using P-ligand-free
Pd(oAc)2 catalyst
Erzsébet Jablonkaia, László B. Balázsa & György Keglevicha
a Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, 1521 Budapest, Hungary
Accepted author version posted online: 06 Dec 2014.
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To cite this article: Erzsébet Jablonkai, László B. Balázs & György Keglevich (2014): Mw-Assisted P-C coupling
reaction using P-ligand-free Pd(oAc)2 catalyst, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2014.984023
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MW-ASSISTED P-C COUPLING REACTION USING P-LIGAND-FREE Pd(OAc)2
CATALYST
Erzsébet Jablonkai*, László B. Balázs, György Keglevich
Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, 1521 Budapest, Hungary
Abstract P-C coupling reactions of a variety of >P(O)H species with aryl bromides were found
to take place under P-ligand-free microwave conditions.

O
MW/
PZ1Z2
Br
120-200°C, 2-90 min
Pd(OAc)2
O
P
TEA
+
Z1
Z2
H
Y
Y
Y= H, 4-MeO, 3-MeO, 4-tBu, 4-Pr, 4-Et, 4-Me, 3-Me, 4-F, 3-F, 4-Cl, 3-Cl, 4-CO2Et,
3-CO2Et, 4-C(O)Me, 3-C(O)Me
Z1
OR Ph R Ph
R = Et, Pr, iPr, Bu, iBu, iPent, Bn
Z2
OR OR R Ph
Keywords Microwave; P-C coupling; arylphosphonates; diphenylphosphinates; phosphine
oxides
1
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Nowadays, the P-C coupling reaction is in the focus. In general, the P-C coupling reaction
was carried out in the presence of Pd(PPh3)4 as the catalyst using triethylamine or other bases in
toluene.1,2 Many alternative approaches (other catalysts, microwave(MW)-assisted and phase
2,3
transfer-catalyzed accomplishments) were described in the last three decades
We tried to
elaborate a new P-ligand-free P-C coupling for the synthesis of dialkyl arylphosphonates, alkyl
diphenylphosphinates and tertiary phosphine oxides.5,6 In our experiments different >P(O)H
species were reacted with aryl bromides using Pd(OAc)2 as the catalyst and triethylamine as the
base, in almost all cases, under solvent-free MW conditions.
The first model reaction was the coupling of diethyl phosphite with bromobenzene
(Scheme 1), and the coupling reaction was efficient at 120 °C after 0.5 h and 150 °C after 5 min
using 5% Pd(OAc)2 (Table 1/ Entries 1 and 2). Dibutyl phosphite was less reactive, and
conversions of 94% and 91% could be attained after prolonged reaction times (Table 1/ Entry 3
and 4). The P-C coupling reactions were also tested under conventional heating. Comparative
thermal experiments were not so efficient and they required longer reaction times to achieve
good conversions.
Then, the reactions of diethyl phosphite with 4- and 3-substituted aryl bromides were also
investigated (Scheme 2). In all cases, the transformations required more forcing conditions
(higher temperature, longer reaction time, using a larger amount of Pd(OAc)2) (Table 2).
It was found that both the electron-donating and the electron-withdrawing substituents in
positions 4 and 3 decrease the reactivity of aryl bromides. 3-Bromotoluene and 4-
fluorobromobenzene were somewhat more reactive than the other aryl derivatives, and the
2
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corresponding diethyl arylphosphonates (2) were formed in both cases in a yield of 91% at 175
°C in the presence of 5% Pd(OAc)2 (Table 2/ Entries 8 and 11).
Finally, we studied the P–C couplings of phenyl-H-phosphinates with bromobenzene, and
the corresponding products (3) were obtained in acceptable yields (68-92%) using 5% Pd(OAc)2
at 150 °C for 5 min (Scheme 3). The coupling reaction of diphenylphosphine oxide with aryl
bromides, such as bromobenzene, bromotoluene, 4-chlorobromobenzene and 4-
fluorobromobenzene, was efficient in the presence of 5% Pd(OAc)2 at 150°C after 5 min and
triarylphosphine oxides (3) were formed in high yields (83-90%) (Scheme 3). Furthermore, we
found that the reaction of dialkylphosphine oxides with bromobenzene gave the corresponding
products (3) in yield of 80-95% at 175 °C after 1.5 h in acetonitrile (Scheme 3). In this case, the
use of solvent was necessary to avoid decomposition.
It was found that diphenylphosphine oxide have higher reactivity than dialkyl phosphite and
alkyl phenyl-H-phosphinates.
In conclusion, the P-ligand-free Hirao reaction has been elaborated by us for the P-C
coupling of different aryl bromides and a wide range of >P(O)H species, such as dialkyl
phosphite, phenyl-H-phosphinates and secondary phosphine oxides. In most of the cases, the
corresponding products were formed in high yields (73-93%). We showed that the novel method
is of general value and it is an environmentally friendly approach for the P-C coupling reactions.
3
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REFERENCES
1. Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Tetrahedron Lett. 1980, 21, 3595-3598.
2. Hirao, T.; Masunaga, T.; Yamada, N.; Ohshiro, Y.; Agawa, T. Bull. Chem. Soc. Jpn. 1982,
55, 909-913.
3. Jablonkai, E.; Keglevich, Gy. Curr. Org. Chem. 2014, 11, 429-453.
4. Jablonkai, E.; Keglevich, Gy. Org. Prep. Proc. Int. 2014, 46, 281-316.
5. Jablonkai, E.; Keglevich, Gy. Tetrahedron Lett. 2013, 54, 4185-4188.
6. Keglevich, Gy.; Jablonkai, E.; Balázs, L. B. RSC Adv. 2014, 4, 22808-22816.
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MW/
T, t
5% Pd(OAc)2
TEA
no solvent
O
O
PhBr + (RO)2P
H
(RO)2P
Ph
(1.5 equiv.)
R = Et, Bu
1
Scheme 1
O
MW
T,t
Br
P(OEt)2
Pd(OAc)2
O
TEA
no solvent
(EtO) P
+
2
H
Y
Y
2
Y= 4-MeO, 3-MeO, 4-tBu, 4-Pr, 4-Et, 4-Me, 3-Me, 4-Cl, 3-Cl, 4-F, 3-F,
4-CO2Et, 3-CO2Et, 4-C(O)Me, 3-C(O)Me
Scheme 2
O
PZ1Z2
MW
T, t
Br
Y
5% Pd(OAc)2
TEA
solvent-free
or MeCN
O
Z1 P
Z2
+
H
Y
3
Y = H, Me, Cl, F
(68-95%)
i
Z1
Z2
OiBu OiPent
OPr
Bn
Bn
OEt
Ph
O Pr OBu
Ph Pr Bu
Ph Bu
Pr
Ph Ph
Ph
Ph Ph
Scheme 3
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Table 1 P-C coupling of dialkyl phosphite with bromobenzene under MW conditions
T
t
[min]
30
Conversiona,b
Yield
[%]
90
R
Entry
[°C]
120
150
120
150
[%]
97
Et
Et
1
2
3
4
5
99
93
Bu
Bu
90
94
84
20
91
77
aOn the basis of GC analysis. bAverage from 3 parallel reactions.
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Table 2 The coupling reaction of aryl bromides with diethyl phosphite
Pd(OAc)2
T
t
[min]
5
Conversiona
[%]
99
Yield
[%]
93
Y
Entry
[%]
5
[°C]
150
200
200
200
200
175
175
175
200
175
175
175
175
200
175
H
4-MeOb
3-MeOb
4-tBu
1
2
5
2
80c
69
10
10
10
10
10
5
2
93c
79
3
2
68c
60
4
4-Pr
2
86c
71
5
4-Et
15
10
10
2
93c
85
6
4-Me
86c
73
7
3-Me
100
100
95
91
8
4-Cl
10
10
5
83
9
3-Cl
10
5
87
10
11
12
13
14
15
16
4-F
99
91
3-F
10
5
5
100
100
93
88
4-CO2Et
3-CO2Et
4-C(O)Me
3-C(O)Me
15
2
89
10
5
81
15
5
100
100
71
10
175
92
b
c
aOn the basis of GC analysis. In the presence of 3 equiv. of diethyl phosphite. No
change on the further irradiation.
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