A "green" variation of the Hirao reaction: The P-C coupling of diethyl phosphite, alkyl phenyl-H-phosphinates and secondary phosphine oxides with bromoarenes using a P-ligand-free Pd(OAc)2 catalyst under microwave and solvent-free conditions

Article abstract of DOI:10.1039/c4ra03292f

The P-C coupling of diethyl phosphite, alkyl phenyl-H-phosphinates, diphenylphosphine oxide and dialkylphosphine oxides with bromoarenes may be performed in the presence of a P-ligand-free Pd(OAc)₂ catalyst and triethylamine under microwave-assisted (MW) and, in almost all cases, solvent-free conditions to afford diethyl arylphosphonates, alkyl diphenylphosphinates, aryldiphenylphosphine oxides and dialkylphenylphosphine oxides, respectively. This is the "greenest" accomplishment of the well-known Hirao reaction that has now been found to have general application for a broad spectrum of >P(O)H species with different reactivity and a great variety of substituted bromobenzenes. The alkyl phenyl-H-phosphinates were prepared by the MW-promoted alkylation of phenyl-H-phosphinic acid in the absence of any solvent. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra03292f

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PAPER
A “green” variation of the Hirao reaction: the P–C
coupling of diethyl phosphite, alkyl phenyl-H-
phosphinates and secondary phosphine oxides with
bromoarenes using a P-ligand-free Pd(OAc)2
catalyst under microwave and solvent-free
conditions†
Cite this: RSC Adv., 2014, 4, 22808
*
Gyorgy Keglevich, Erzsebet Jablonkai and Laszlo B. Balazs
¨
´
´
´
´
The P–C coupling of diethyl phosphite, alkyl phenyl-H-phosphinates, diphenylphosphine oxide and
dialkylphosphine oxides with bromoarenes may be performed in the presence of a P-ligand-free
Pd(OAc)2 catalyst and triethylamine under microwave-assisted (MW) and, in almost all cases, solvent-free
conditions to afford diethyl arylphosphonates, alkyl diphenylphosphinates, aryldiphenylphosphine oxides
and dialkylphenylphosphine oxides, respectively. This is the “greenest” accomplishment of the well-
known Hirao reaction that has now been found to have general application for a broad spectrum of
>P(O)H species with different reactivity and a great variety of substituted bromobenzenes. The alkyl
phenyl-H-phosphinates were prepared by the MW-promoted alkylation of phenyl-H-phosphinic acid in
the absence of any solvent.
Received 11th April 2014
Accepted 30th April 2014
DOI: 10.1039/c4ra03292f
www.rsc.org/advances
accelerating effect. It was a milestone, when attempts were
made to replace Pd(PPh3)4 with Pd(dba)2 (dba ¼ dibenzylide-
Introduction
neacetone), Pd(OAc)2 or PdCl2. The most efficient catalytic
system was formed from Pd(OAc)2 in the presence of triphe-
nylphosphine as the P-ligand.15 There have been attempts to
apply bidentate P-ligands, such as dppf [1,10-bis(diphenyl-
phosphino)ferrocene], xantphos [4,5-bis(diphenylphosphino)-
9,9-dimethylxanthene], dppp [1,3-bis(diphenylphosphino)-
propane], dppb [1,4-bis(diphenylphosphino)butane], and
BINAP [2,20-bis(diphenylphosphino)-1,10-binaphthyl] together
with Pd(OAc)2, instead of triphenylphosphine, to establish in
situ catalysts.16–18 In another variation, a Pd(II) salt was used with
triphenylphosphine, but the base was K2CO3, and the reaction
was performed in the presence of triethylbenzylammonium
chloride (TEBAC) as the phase transfer catalyst.19–22 It was
observed that the phosphinylation of aryl iodides took place in
the presence of ‘phosphine-free Pd’, but aryl bromides under-
went the coupling reaction only in the presence of triphenyl-
phosphine as the P-ligand.19–22 Diphenylphosphine may also be
the subject of an analogous coupling reaction using Pd(OAc)2
catalyst under MW irradiation. However, this kind of P–C
coupling has been limited only to iodobenzene as the reactant.23
The high ability of Ph2PH towards oxidation means another
disadvantage, and this reaction was not described as a general
method. It is noteworthy that reductive Hirao couplings were
also described using NiBr2 and Mg,24 or NiCl2 and Zn along with
2,20-bipyridine and K3PO4 in a suitable solvent.25
The synthesis of aryl phosphonates and related derivatives is a
focus of interest these days.2 The preparation of aryl phospho-
nates by the Arbuzov reaction of trialkyl phosphites and aryl
halides is possible only under special conditions due to the
lower reactivity of aryl halides.3,4 The most suitable method for
the synthesis of aryl phosphonates is the Hirao reaction
comprising a P–C coupling between a dialkyl phosphite
(H-phosphonate) and an aryl or vinyl halide (or another aryl
derivative) in the presence of Pd(PPh3)4 as the catalyst, and in
most cases, triethylamine as the base in different solvents.5–12
The rst examples of the Hirao reaction included also the
preparation of vinyl phosphates from vinyl halides. Many vari-
ations and applications of the Hirao reaction have been
described; the coupling was extended to H-phosphinates,
secondary phosphine oxides and other P-reactants, as well as to
other Pd(0) complexes and Pd(II) salts applied in the presence of
suitable P-ligands.2 According to one method, the P–C coupling
was enhanced by microwave (MW) irradiation, but this method
did not bring a breakthrough, as Pd(PPh3)4 and THF had to be
used.13 In another case,14 MW irradiation also had only an
Department of Organic Chemistry and Technology, Budapest University of Technology
and Economics, 1521 Budapest, Hungary. E-mail: gkeglevich@mail.bme.hu; Fax: +36
1 463 3648; Tel: +36 1 463 1111/5883
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra03292f
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We experienced that in certain alkylation reactions, the (Table 1, entries 7 and 8). It is obvious that the 4-methoxy-
catalysts could be substituted by MW irradiation,26–30 or it bromobenzene is signicantly less reactive in the reaction
inuenced positively the effect of a catalyst.4,31,32 For this reason, under discussion than bromobenzene. The 3-methoxy-
we wished to investigate the role of MW irradiation in the Hirao bromobenzene was, however, somewhat more reactive than the
reaction. We envisaged that the catalyst system may be simpli- 4-methoxy substituted analogue, as measuring in 10 mol% of
ꢀ
ꢀ
ed. It was a question of whether it might be possible to omit the catalyst and applying conditions of 150 C/5 min, 175 C/5
the P-ligand under certain conditions in the coupling reaction min and 200 ꢀC/2 min, the conversions were 78%, 81% and
of bromoarenes. If the simplication of the catalytic system is 93%, respectively (Table 1, entries 9–11). The preparative yield
possible, for which >P(O)H reagents might it be relevant? Our of 3-methoxyphenylphosphonate 1c from the best experiment
preliminary results on a limited scope of the P–C coupling was 79% (Table 1, entry 11). At 150/175 ꢀC, the conversions
reactions have been published in a communication.1
remained incomplete even on prolonged heating, while at
200 C, decomposition was observed aer a reaction time of 2
ꢀ
min. In the next experiments 4-alkyl substituted bromo-
benzenes were the model compounds in reaction with 1.5
equivalents of DEP. First, 4-propylbromobenzene was used as
the starting material. Aꢀpplying a combination of 150 ꢀC/15 min,
Results and discussion
Our model reaction was the P–C coupling between bromoarenes
and, in most cases, 1.5–1 equivalents of diethyl phosphite, alkyl
phenyl-H-phosphinates and secondary phosphine oxides using
Pd(OAc)2 as the catalyst without any P-ligand and 1.1 equiva-
lents of triethylamine as the base in the absence of any solvent
on MW irradiation. The basic model was the coupling of diethyl
phosphite with bromoarenes (Scheme 1).
First, the reaction of diethyl phosphite (DEP) with bromo-
benzene was investigated. The coupling was complete in the
presence of 5 mol% of Pd(OAc)2 at 150 ꢀC, aer an irradiation of
5 min, and diethyl phenylphosphonate 1a was obtained in a
yield of 93% (Table 1, entry 1).1 The comparative thermal reac-
tion led to a conversion of only 47% (Table 1, entry 2).
ꢀ
175 C/5 min and 200 C/2 min in the presence of 10 mol% of
Pd(OAc)2, the conversions were 70%, 77% and 86%, respectively
(Table 1, entries 12–14). The conversions were incomplete and
the prolonged heating had a negative effect on the yield. From
the best experiment, the 4-propylphenylphosphonate (1d) was
isolated in a yield of 71% (Table 1, entry 14). In respect of the
4-ethyl- and 4-methylbromobenzenes, a reaction temperature of
175 ꢀC seemed to be the optimum to afford products 1e and 1f
in conversions of 93% and 86%, respectively, aer reaction
times of 15 min and 10 min, respectively (Table 1, entries 16 and
17). The 4-ethylphenylphosphonate (1e) was isolated in a yield
of 85%, while the 4-methyl counterpart (1f) in a yield of 73%
(Table 1, entries 16 and 17). It can be seen that the 4-alkyl
substituted bromobenzenes are also less reactive than bromo-
benzene. Above 175 ꢀC, the phosphonates with electron-
donating substituents in the aromatic ring (e.g. 1b–f) were not
entirely stable and decomposed partially to give the corre-
sponding benzene derivative as a minor by-product.
The next experiments embraced the reactions of halogeno-
substituted bromobenzenes. The coupling reactions of 4-
chlorobromobenzene and the 3-chloro analogue were quite
efficient in the presence of 10 mol% of the catalyst at 175 ꢀC
aer an irradiation of 10 min, as chlorophenylphosphonates 1g
and 1h were obtained in conversions of 95% for both cases, and
in yields of 83% and 87%, respectively (Table 1, entries 18 and
20). At 150 ꢀC, the conversion was lower (73%), while at 200 ꢀC it
remained practically the same (92%) as that detected at 175 ꢀC
(Table 1, entries 19 and 21). The uoro-substituted bromo-
benzenes were the most efficient reagents aer bromobenzene.
Both the 4-uoro- and the 3-uorobromobenzene took part in a
quantitative reaction with DEP in the presence of 5 mol% of
Pd(OAc)2 as the catalyst at 175 ꢀC aer a reaction time of 5 min
and 10 min, respectively, to furnish uorophenylphosphonates
1i and 1j in 91% and 88% yields, respectively (Table 1, entries 22
and 24). In respect of the 3-uoro starting material, the coupling
was incomplete at 150 ꢀC for 5 min, while using more (10 mol%)
of the catalyst, the shorter reaction time of 5 min was enough
(Table 1, entries 23 and 25). It was a noteworthy observation that
the coupling reaction of the bromo-function of the dihaloge-
nobenzenes with the >P(O)H species was entirely selective, the
Then, DEP was reacted with a series of substituted aryl
bromides. Using 4-methoxybromobenzene at 150 ꢀC in the
presence of 5 mol% and 10 mol% Pd(OAc)2, incomplete
conversions of 57% and 67%, respectively, were observed and
the compositions did not change on extending the reaction
times of 10/5 min (Table 1, entries 3 and 4). A comparative
thermal experiment carried out in the presence of 10 mol% of
ꢀ
Pd(OAc)2 at 150 C for 5 min led to a conversion of only 38%
(Table 1, entry 5), that was increased to 62% aer a heating of
15 min, but than the conversion could not be increased further
(Table 1, entry 6). Increasing the temperature to 175 ꢀC and
200 ꢀC, and applying reaction times of 5 min and 2 min, the
conversions were 77% and 80%, respectively, and decomposi-
tion was observed on further irradiation (Table 1, entries 7 and
8). Hence, the last two experiments were the best giving diethyl
arylphosphonates 1b in yields of 66% and 69%, respectively
Scheme
1 P–C coupling reaction of bromoarenes with diethyl
phosphite.
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Table 1 P–C coupling reaction of bromoarenes with diethyl phosphite
Entry
Y
Pd(OAc)2 (%)
T (ꢀC)
t (min)
Mode of heating
Conversiona (%)
Yield (%)
Ref.
1
1
2
3
4
5
6
7
8
H
H
5
5
5
150
150
150
150
150
150
175
200g
150
175
200g
150
175
200g
150
175
175
175
150
175
200g
175
150
175
175
175
150
175
200g
175
150
175
175
200g
5
5
10
5
5
15
5
2
5
5
2
15
5
2
15
15
10
10
10
10
2
MW
Dc
99
47
93 (1a)
27 (1a)
50
56
30
53
66
69 (1b)
4-MeOb
4-MeO
4-MeO
4-MeO
4-MeO
4-MeO
3-MeOb
3-MeO
3-MeO
4-Pr
MW
MW
Dc
Dc
57d,e
67d,e
38d
62e
77d,f
80f
78e
81e
93f
70
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
MW
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
73
79 (1c)
4-Pr
4-Pr
4-Et
4-Et
4-Me
4-Cl
3-Cl
3-Cl
3-Cl
4-F
3-F
3-F
77f
86f
61
71 (1d)
93f
86f
95
85 (1e)
73 (1f)
83 (1g)
1
1
73e
95
87 (1h)
91 (1i)
88 (1j)
89 (1k)
92
99
70
100
95
100
66e
83f
93f
96h
76
81
100
100
5
5
1
1
1
5
5
10
5
15
15
5
2
5
15
10
5
3-F
10
5
10
10
10
5
10
5
10
5
4-CO2Et
3-CO2Et
3-CO2Et
3-CO2Et
4-C(O)Me
3-C(O)Me
3-C(O)Me
3-C(O)Me
3-C(O)Me
74
81 (1l)
71 (1m)
92
89 (1n)
2
I
ðEtOÞ2PðOÞAr
a
b
c
d
On the basis of GC analysis conversion ¼
:
In this case 3 equiv. DEP were used. Conventional heating. Average of two
IðEtOÞ PðOÞAr þ IArBr
2
e
f
g
reactions. The deviation is ꢁ1.5%. No change on further irradiation. On further irradiation, the product decomposed. Quasi-isothermal
reaction. h The starting material was partially.
chloro- and uoro-moieties remained intact under the MW- partial dehalogenation of the starting material was also
assisted P-ligand-free and solvent-free conditions.
observed (Table 1, entry 30). At the same time, the reaction of
The next experiments involved a study with the ethyl 4- and the 3-bromoacetophenone took place quantitatively in the
3-bromobenzoates. The 4-ethoxycarbonyl- and 3-(ethoxycar- presence of 10 mol% of catalyst at 175 ꢀC aer 5 min, or
bonyl)bromobenzene could be involved in quite efficient applying 5 mol% of catalyst at 200 ꢀC aer 2 min (Table 1/
couplings using 5 mol% of Pd(OAc)2 at 175 ꢀC for 15 min and 10 entries 33 and 34). At 150 ꢀC/15 min in the presence of 10 mol%
mol% of the catalyst at 200 ꢀC for 2 min, respectively, to provide of Pd(OAc)2, or 175 ꢀC/10 min using 5 mol% of the catalyst, the
products 1k and 1l in yields of 89% and 81%, respectively conversions were 76% and 81%, respectively (Table 1, entries 31
(Table 1, entries 26 and 29). Regarding the reaction of ethyl and 32). The 3-acetylbromobenzene was found to reveal a
3-bromobenzoate, lower temperatures than 200 ꢀC were less comparable reactivity with that of the 4-bromobenzoate.
efficient (Table 1, entries 27 and 28). At 150 ꢀC incomplete
It is worthy to mention that the reaction mixtures formed a
conversions occurred, while at 175 ꢀC/200 ꢀC decomposition of homogeneous liquid phase. Due to the stirring, there could not
the product (1l) was observed (Table 1, entries 27–29). It can be have been a temperature gradient in the mixtures.
seen that the ethyl bromobenzoates are less reactive than
bromobenzene.
It was found that the addition of 10 mol% of PPh3 (1
equivalent to the catalyst) to the reaction mixture was without
Finally, the 4- and 3-bromoacetophenones were tested. The any effect. Repeating the experiment marked by entry 4 of
coupling reaction of 4-bromoacetophenone with DEP was Table 1 in the presence of PPh3, the yield of arylphosphonate
ꢀ
complete using 5 mol% of Pd(OAc)2 at 175 C for 5 min, but a 1b was 57%.
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It can be seen that with the exception of 4-methoxy-
bromobenzene, all bromoarenes investigated could be con-
verted into the corresponding diethyl arylphosphonates (1) in
conversions $86%, although the optimum conditions were
somewhat different. The overall reactivity of the aromatic
substrates was the following:
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Table 2 Alkylating esterification of phenyl-H-phosphinic acid with
alkyl halides
Entry
RX
t (min)
Mode of heating
Yield (%)
1
2
3
4
5
6
7
8
9
EtI
5
12
15
15
30
15
15
30
15
15
MW
MW
MW
Da
97 (2a)
94 (2b)
76 (2c)
26 (2c)
53 (2c)
96 (2d)
69 (2d)
94 (2d)
79 (2e)
91 (2f)
nPrBr
iPrBr
iPrBr
iPrBr
nBuBr
nBuBr
nBuBr
iBuBr
iPentBr
Da
MW
Da
Da
MW
MW
10
a
Conventional heating.
One may conclude that the presence of substituents in
general decreases the reactivity of the bromoarenes and that
electron-donating (methoxy and alkyl) substituents have a more
signicant effect in this respect than electron-withdrawing
(halogeno, acetyl and ethoxycarbonyl) substituents. In the case
of electron-donating substituents, the conversions were
incomplete and the best yields were 69–85%. 4-Methoxy-
bromobenzene revealed the lowest reactivity among the
aromatic substrates used.
The main message of our nding is that, rst in the litera-
ture, the Hirao reaction of bromoarenes could be performed in
the presence of P-ligand-free Pd(OAc)2 that now proved to be
general for a wide variety of substituted bromobenzenes. This
was possible only under MW irradiation, as shown by the result
of comparative thermal experiments. Moreover, our procedure
can be carried out under solvent-free conditions. The explana-
tion for the benecial inuence of MW irradiation may be that
the statistically occurring local overheating effect promotes the
P–C coupling in the absence of P-ligands.33 This experience
augments the number of cases, when MW irradiation simplies
the realization of catalytic reactions.4,26–32
80 ꢀC for 5–15 min with MW irradiation without the use of any
solvent (Scheme 2, Table 2). In our original procedure, K2CO3
was used as the base together with a phase transfer catalyst.40,41
Now, triethylamine was applied in a homogeneous medium for
the synthesis of never representatives.
One may see from Table 2 that using ethyl iodide, n-propyl
bromide, isopropyl bromide, n-butyl bromide, isobutyl bromide
and isopentyl bromide, the corresponding alkyl phenyl-H-
phosphinates (2a–f) were obtained in yields of 76–97% aer
ash column chromatography. In these O-alkylation reactions
the effect of MW is noteworthy, if the results are compared with
those of the comparative thermal experiments. In the alkylation
ꢀ
with isopropyl bromide at 80 C for 15 min, the MW-assisted
reaction gave phenylphosphinate 2c in a yield of 76% (Table 2,
entry 3). As the same time, the outcome of the comparative
thermal experiment was only 26% (Table 2, entry 4). Increasing
the reaction time to 30 min, the yield was doubled (53%) (Table
2, entry 5). In the alkylation with butyl bromide, the effect of
MW was also considerable, but aer a prolonged reaction time,
almost the same yield (94%) could be achieved on conventional
heating, as that in the MW variation (96%) (Table 2, entries 6–8).
From among the H-phosphinates (2a–e) prepared, the isopentyl
ester (2f) was new.
From among the diethyl arylphosphonates (1a–n) synthe-
sized, 1a–c, 1e–g, 1i–k, 1m and 1n prepared are known
compounds.1,3,34–39 All arylphosphonates (1) were characterized
1
by 31P, 13C, H NMR, and HR-MS.
Then, the alkyl phenyl-H-phosphinates 2a–f were tested in
In the next part of our work, we wished to utilize alkyl phenyl-
H-phosphinates in the Hirao reaction. First we had to prepare
the phenylphosphinates (2). This was done essentially on the
basis of our previous method involving the alkylating esteri-
cation of phosphinic acids under MW- and solvent-free condi-
tions.40,41 According to this, phenyl-H-phosphinic acid was
reacted with alkyl halides in the presence of triethylamine at
ꢀ
reaction with bromobenzene at 150 C using 5 mol% Pd(OAc)2
as the catalyst and triethylamine as the base under solvent-free
conditions (Scheme 3 and Table 3).
The P–C couplings were complete aer a 5 min reaction
time. Flash chromatography afforded alkyl diphenylphosphi-
nates 3a, 3b and 3d–f in yields of 76–92% (Table 3, entries 1, 2,
Scheme 2 Alkylating esterification of phenyl-H-phosphinic acid with Scheme 3 P–C coupling reaction of alkyl phenyl-H-phosphinates
alkyl halides.
(2a–f) with bromobenzene.
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Table 3 P–C coupling reaction of alkyl phenyl-H-phosphinates (2a–f)
with bromobenzene
Entry
R
Yield (%)
1
2
3
4
5
6
Et
85 (3a)
91 (3b)
68 (3c)
87 (3d)
76 (3e)
92 (3f)
nPr
iPr
Scheme 5 P–C coupling of dialkylphosphine oxides (5a–c) with
bromobenzene.
nBu
iBu
iPent
acetonitrile as the solvent to avoid the decomposition observed
under solvent-free conditions. Using acetonitrile, completion of
the reactions required 1.5 h.
4–6). The sterically hindered isopropyl derivative (3c) was
obtained only in a yield of 68% (Table 3, entry 3).
This series of couplings proves the more general value of the
P-ligand-free P–C coupling reaction developed by us.
It is noted that the starting secondary phosphines oxides
(5a–c)52–55 were also prepared by us.
It can be seen, that the alkyl phenyl-H-phosphinates (with
the exception of the isopropyl derivative 3c) were as reactive, as
dialkyl phosphites in the Pd(OAc)2-catalyzed, P-ligand-free
Hirao reaction with bromobenzene. Hence, the P-ligand-free
coupling seems to be rather general.
The dialkylphenylphosphine oxides (6a–c)56–59 prepared are
known compounds.
Most of the alkyl diphenylphosphinates (3a, 3c, 3d and 3f)
prepared have been described in the literature.1,42–47 All phos-
phinates (3a–f) were identied by 31P, 13C, 1H NMR, and HR-MS.
As another extension, the coupling of diphenylphosphine
oxide with bromobenzene and a few 4-substituted derivatives
was also investigated under the standard conditions applied
above (Scheme 4). Due to the enhanced reactivity of Ph2P(O)H,
The most striking feature of the newer developments of our
work is the broad scope of the possible applications of the new
method, since an impressive range of >P(O)H reagents could be
used with similar efficiencies. It can be said that the hydrogen
atom on the P]O moiety of diphenylphosphine oxide is
signicantly more acidic, than the similar proton in diethyl
phosphite, as suggested by the pKa values of 14.5 (predicted by
the program Marvin Sketch, Version 5.4.1.1) and 20.8,60
respectively. At the same time, the acidity of the P–H of dia-
lkylphosphine oxides is comparable with that of diethyl phos-
phite or in general dialkyl phosphites. However, the acidity of
the P–H has not much role in the efficiency of the couplings
studied.
In conclusion, the rst P-ligand-free accomplishment of the
Hirao reaction has been developed and extended to the
synthesis of a wider range of derivatives, such as diethyl aryl-
phosphonates, alkyl diphenylphosphinates and different
tertiary phosphine oxides demonstrating the general value of
the MW-assisted, P-ligand-free and, in almost all cases, solvent-
free conditions for this reaction. The omission of the P-ligand in
the Pd-catalyzed Hirao coupling under MW conditions means
an enormous advantage from the point of view environmentally
friendly conditions and costs. It can be expected that this
novel method will have further impact on the development of
P-ligand-free methodologies including also other model
compounds, such as, among others, (2-bromovinyl)benzenes.
ꢀ
the reactions were complete at 120 C aer 15 min, or, using
ꢀ
bromobenzene, at 150 C within 5 min, to afford aryldiphenyl-
phosphine oxides (4a–d) in yields of 83–90% (Table 4). All
aryldiphenylphosphine oxides (4a–d) have been known from
the literature.48–51
Finally, a few dialkylphenylphosphine oxides (6a–c) were
synthesized by the reaction of dialkylphosphine oxides (5a–c)
with bromobenzene under the conditions of the P-ligand-free
Hirao reaction at 175 ꢀC (Scheme 5). It was advantageous to use
Scheme 4 P–C coupling reaction of diphenylphosphine oxide with
bromoarenes.
Experimental
General
Table 4 P–C coupling reaction of diphenylphosphine oxide with
The reactions were carried out in a 300 W CEM Discover focused
microwave reactor equipped with a pressure controller applying
30–50 W under isothermal conditions. Standard 5 mL glass
reaction vessels were used distributed by the supplier of the CEM
reactor, and the reaction mixtures were stirred magnetically.
bromoarenes
Entry
Y
T (ꢀC)
t (min)
Yield (%)
1
2
3
4
5
H
H
4-Me
4-Cl
4-F
120
150
150
150
150
15
<5
5
5
5
90 (4a)
88 (4a)
83 (4b)
89 (4c)
87 (4d)
1
The 13C and H NMR spectra were obtained in CDCl3 solu-
tion on a Bruker DRX-500 spectrometer operating at 125.7, and
500.1 MHz, respectively. The 13C and 1H chemical shis are
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referred to TMS. 31P NMR spectra were obtained on a Bruker AV- (CDCl3)55 35.5; [M + H]+ ¼ 231.0937, C14H16OP requires
300 spectrometer. Chemical shis are downeld relative to 85% 231.0933.
H3PO4. Mass spectrometry was performed on a ZAB-2SEQ
instrument.
2. General procedures for P–C couplings
2.1. General procedure for the reaction of bromoarenes and
diethyl phosphite. To the bromoarene (2.0 mmol: 0.21 mL of
1. Synthesis of the non-commercial starting materials
1.1. General procedure for the preparation alkyl-phenyl-H- bromobenzene, 0.25 mL of 4-bromoanisole, 0.25 mL of 3-bro-
phosphinates. To phenyl-H-phosphinic acid (0.28 g, 2.0 mmol) moanisole, 0.31 mL of 4-propyl bromobenzene, 0.28 mL of
was added the alkyl bromide (2.4 mmol: 0.19 mL of ethyl iodide, 4-ethyl bromobenzene, 0.34 g of 4-bromotoluene, 0.38 g of
0.22 mL of propyl bromide, 0.23 mL of isopropyl bromide, 4-bromo-chlorobenzene, 0.24 mL of 3-bromo-chlorobenzene,
0.26 mL of butyl bromide, 0.26 mL of isobutyl bromide or 0.22 mL of 4-bromo-uorobenzene, 0.22 mL of 3-bromo-
0.29 mL of isopentyl bromide) and TEA (0.31 mL, 2.2 mmol) and uorobenzene, 0.32 mL of ethyl 4-bromobenzoate, 0.32 mL of
the resulting mixture was irradiated in a closed vial in the ethyl 3-bromobenzoate, 0.40 g of 4-bromoacetophenone and
ꢀ
microwave reactor at 80 C for the time shown in Table 2. The 0.26 mL of 3-bromoacetophenone) was added diethyl phosphite
reaction mixture was passed through a thin (ca. 1–1.5 cm) layer 0.39 mL (3.0 mmol) [or in the case of bromoanisoles, diethyl
of silica gel using ethyl acetate as the eluent. The products (2a–f) phosphite (6.0 mmol, 0.79 mL)] triethylamine (0.31 mL, 2.2
were obtained as colourless oils.
mmol) and palladium acetate (0.022 g, 0.10 mmol or 0.044 g,
0.20 mmol – see Table 1.) and the resulting mixture was irra-
diated in a closed vial in the microwave reactor at the temper-
ature and for the time shown in Table 1. The reaction mixture
was passed through a thin (ca. 1.5–2 cm) layer of silica gel using
ethyl acetate as the eluent. The products 1a–n were obtained as
colourless oils.
Selected spectral data for alkyl phenyl-H-phosphinates
dP (CDCl3) d (ref. 46)
Entry Product (ppm)
(ppm)
[M + H]+found [M + H]r+equires
1
2
3
4
5
2a
2b
2c
2d
2e
22.7
25.7
20.6
25.1
25.7
24.7
24.9
22.3
24.9
25.0
171.0575
185.0733
185.0733
199.0888
199.0887
171.0575
185.0731
185.0731
199.0888
199.0888
Diethyl 4-methoxyphenylphosphonate (1b). 31P NMR (CDCl3) d
19.8, dP (CDCl3)34 18.8; 13C NMR (CDCl3) d 16.3 (d, J ¼ 6.6,
CH2CH3), 55.3 (OCH3), 62.9 (d, J ¼ 5.3, OCH2), 114.0 (d, J ¼ 16.0,
C2)*, 119.6 (d, J ¼ 194.9, C1), 133.8 (d, J ¼ 11.4, C3)*, 162.8 (d, J ¼
Isopentyl phenyl-H-phosphinate (2f). 31P NMR (CDCl3) d 24.9; 3.3, C4), * may be reversed; 1H NMR (CDCl3) d 1.31 (t, 6H, J ¼ 7.0,
13C NMR (CDCl3) d 22.4 (CH3), 24.6 (CH), 39.2 (d, J ¼ 6.4, CH3), 3.83 (OCH3), 3.96–4.21 (m, 4H, OCH2), 6.89–7.02 (m, 2H,
OCH2CH2), 64.5 (d, J ¼ 6.6, OCH2), 128.8 (d, J ¼ 13.8, C2)*, 130.0 ArH), 7.65–7.85 (m, 2H, ArH); [M + H]+ ¼ 245.0945, C11H18O4P
(d, J ¼ 132.1, C1), 130.9 (d, J ¼ 11.8, C3)*, 133.1 (d, J ¼ 2.9, C4), * requires 245.0943.
1
may be reversed; H NMR (CDCl3) d 0.87 (t, 6H, J ¼ 6.1, 2 ꢂ
Diethyl 3-methoxyphenylphosphonate (1c). 31P NMR (CDCl3) d
CH3), 1.50–1.61 (m, 2H, OCH2CH2), 1.62–1.79 (m, 1H, CH), 18.8; dP (CDCl3)35 18.7; 13C NMR (CDCl3) d 16.3 (d, J ¼ 6.5,
4.00–4.15 (m, 2H, OCH2), 7.54 (d, 1H, J ¼ 562.5, P–H), 7.41–7.61 CH2CH3), 55.4 (OCH3), 62.2 (d, J ¼ 5.4, OCH2), 116.4 (d, J ¼ 11.4,
(m, 3H, ArH), 7.69–7.80 (m, 2H, ArH); [M + H]+ ¼ 213.1042, C2), 118.8 (d, J ¼ 3.2, C4), 124.0 (d, J ¼ 9.2, C6), 129.6 (d, J ¼
C
11H18O2P requires 213.1044.
186.8, C1), 129.8 (d, J ¼ 17.6, C5), 159.5 (d, J ¼ 18.9, C3); 1H NMR
1.2. General procedure for the preparation of the dia- (CDCl3) d 1.30 (t, 6H, J ¼ 7.1, CH3), 3.82 (OCH3), 3.96–4.20
lkylphosphine oxides (5a–c). The Grignard reagent (40.0 mmol) (m, 4H, OCH2), 7.00–7.10 (m, 1H, ArH), 7.26–7.41 (m, 3H, ArH);
formed from (0.97 g, 40.0 mmol) of magnesium and alkyl halide [M + H]+ ¼ 245.0939, C11H18O4P requires 245.0943.
(40.0 mmol: 3.6 mL of bromopropane, 4.2 mL chlorobutane or
Diethyl 4-propylphenylphosphonate (1d). 31P NMR (CDCl3) d
4.6 mL of benzyl chloride) in diethyl ether (50 mL) was added 20.5; 13C NMR (CDCl3) d 13.8 (CH2CH2CH3), 16.4 (d, J ¼ 6.5,
dropwise to the diethyl phosphite (1.7 mL, 13.0 mmol) in CH2CH3), 24.3 (C4–CH2CH2), 38.1 (C4–CH2), 62.0 (d, J ¼ 5.4,
diethyl ether (10 mL) at 0 ꢀC. The resulting mixture was stirred OCH2), 125.4 (d, J ¼ 189.9, C1), 128.7 (d, J ¼ 15.4, C2)*, 131.9 (d, J
1
ꢀ
at 26 C for 1.5 hours. The mixture was hydrolyzed with 10% ¼ 10.3, C3)*, 147.6 (d, J ¼ 3.1, C1), * may be reversed; H NMR
HCl solution (40 mL) and the aqueous phase was extracted with (CDCl3) d 0.95 (t, 3H, J ¼ 7.3, CH2CH2CH3), 1.32 (t, 6H, J ¼ 7.0,
diethyl ether (2 ꢂ 50 mL). The combined organic phases were OH2CH3), 1.57–1.75 (m, 2H, C4–CH2CH2), 2.63 (t, 2H, J ¼ 7.6,
dried (Na2SO4). Evaporation of the solvent provided a residue C4–CH2), 4.00–4.23 (m, 4H, OCH2), 7.23–7.30 (m, 2H, ArH),
that was puried by column chromatography using silica gel, 7.65–7.78 (m, 2H, ArH); [M + H]+ ¼ 257.1302, C13H22O3P
1% methanol in dichloromethane as the eluent to give products requires 257.1301.
5a–c as white crystals.
Diethyl 4-ethylphenylphosphonate (1e). 31P NMR (CDCl3) d
Dipropylphosphine oxide (5a). Yield: 71%; white crystals; mp.: 19.6, dP (MeOH)3 19.4; 13C NMR (CDCl3) d 15.2 (C4–CH2CH3),
47–48 ꢀC, mp.:52 48–50 ꢀC; 31P NMR (CDCl3) d 35.3, dP (CDCl3)53 16.4 (d, J ¼ 6.5, OCH2CH3), 24.3 (C4–CH2CH3), 61.0 (d, J ¼ 5.3,
32.5; [M + H]+ ¼ 135.0930, C6H16OP requires 135.0933.
OCH2), 125.3 (d, J ¼ 190.0, C1), 128.1 (d, J ¼ 15.4, C2)*, 131.9 (d, J
1
Dibutylphosphine oxide (5b). Yield: 65%; white crystals; mp.: ¼ 10.3, C3)*, 149.1 (d, J ¼ 3.1, C4), * may be reversed; H NMR
55–56 ꢀC, mp.:54 55–56 ꢀC; 31P NMR (CDCl3) d 33.9, dP (CDCl3)54 (CDCl3) d 1.24 (t, 3H, J ¼ 7.6, C4–CH2CH3), 1.30 (t, 6H, J ¼ 7.0,
36.09; [M + H]+ ¼ 163.1249, C8H20OP requires 163.1246.
OH2CH3), 2.68 (q, 2H, J ¼ 7.6, C4–CH2), 3.97–4.20 (m, 4H,
Dibenzylphosphine oxide (5c). Yield: 78%; white crystals; mp.: OCH2), 7.21–7.35 (m, 2H, ArH), 7.64–7.80 (m, 2H, ArH); [M + H]+
109–110 ꢀC, mp.:55 106–107 ꢀC; 31P NMR (CDCl3) d 36.2, dP ¼ 243.1146, C12H20O3P requires 243.1145.
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Diethyl 3-chlorophenylphosphonate (1h). 31P NMR (CDCl3) d
17.5; 13C NMR (CDCl3) d 16.2 (d, J ¼ 6.4, CH3), 62.3 (d, J ¼ 5.5,
CH2), 129.69 (d, J ¼ 9.2, C5), 129.74 (d, J ¼ 16.3, C6), 130.7 (d, J ¼
187.9, C1), 131.6 (d, J ¼ 10.7, C3), 132.4 (d, J ¼ 3.0, C4), 134.7 (d, J
(CDCl3) d 1.36 (t, 3H, J ¼ 7.1, CH3), 4.01–4.16 (m, 2H, OCH2),
7.39–7.58 (m, 6H, ArH), 7.75–7.88 (m, 4H, ArH); [M + H]+
¼
247.0888, C14H16O2P requires 247.0888.
Propyl diphenylphosphinate (3b). White crystals; mp.: 92–
93 ꢀC, mp.:44 89–91 ꢀC; 31P NMR (CDCl3) d 33.5; 13C NMR
(CDCl3) d 10.3 (CH2CH3), 24.0 (d, J ¼ 6.7, OCH2CH2), 66.4 (d, J ¼
6.1, OCH2), 128.6 (d, J ¼ 13.1, C2)*, 131.7 (d, J ¼ 10.1, C3)*, 131.8
1
¼ 20.3, C2); H NMR (CDCl3) d 1.30 (t, 6H, J ¼ 7.1, CH3), 3.96–
4.20 (m, 4H, OCH2), 7.40–7.31 (m, 1H, ArH), 7.43–7.51 (m, 1H,
ArH), 7.59–7.81 (m, 2H, ArH); [M
10H15O3P35Cl requires 249.0447.
Diethyl 3-uorophenylphosphonate (1j). 31P NMR (CDCl3) d
+
H]+
¼
249.0448,
1
(d, J ¼ 137.2, C1), 132.2 (d, J ¼ 2.8, C4), * may be reversed; H
C
NMR (CDCl3) d 0.94 (t, 3H, J ¼ 7.4, CH3), 1.71–1.80 (m, 2H,
OCH2CH2), 3.99 (q, 2H, J ¼ 6.7, OCH2), 7.39–7.53 (m, 6H, ArH),
7.79–7.88 (m, 4H, ArH); [M + H]+ ¼ 261.1040, C15H18O2P
requires 261.1039.
16.7 (d, J ¼ 8.7); dP (CDCl3)37 17.4; 13C NMR (CDCl3) d 16.3 (d, J1
¼ 6.4, CH3), 62.4 (d, J1 ¼ 5.5, CH2), 118.6 (dd, J1 ¼ 10.5, J2 ¼ 22.3,
C2), 119.5 (dd, J1 ¼ 3.1, J2 ¼ 21.1, C4), 127.5 (dd, J1 ¼ 9.2, J2 ¼ 3.3,
C6), 130.5 (dd, J1 ¼ 17.5, J2 ¼ 7.5, C5), 131.0 (dd, J1 ¼ 188.9, J2 ¼
6.2, C1), 162.4 (dd, J1 ¼ 21.4, J2 ¼ 249.4, C3); 1H NMR (CDCl3) d
1.29 (t, 6H, J ¼ 7.0, CH3), 3.99–4.20 (m, 4H, OCH2), 7.13–7.23 (m,
1H, ArH), 7.33–7.60 (m, 3H, ArH); [M + H]+ ¼ 233.0743,
Isopropyl diphenylphosphinate (3c). White crystals; mp.: 101–
31
102 C, mp.: 98–100 C; P NMR (CDCl3) d 30.0, dP (CDCl3)43
31.4; 13C NMR (CDCl3) d 24.4 (d, J ¼ 4.2, CH3), 70.3 (d, J ¼ 6.0,
OCH), 128.5 (d, J ¼ 13.1, C2)*, 131.7 (d, J ¼ 10.1, C3)*, 132.0 (d, J
ꢀ
43
ꢀ
1
¼ 2.8, C4), 132.4 (d, J ¼ 137.3, C1), * may be reversed; H NMR
C
10H15O3PF requires 233.0743.
Diethyl 3-ethoxycarbonylphenylphosphonate (1l). 31P NMR
(CDCl3) d 1.34 (d, 6H, J ¼ 6.1, CH3), 4.57–4.74 (m, 1H, OCH),
7.36–7.56 (m, 6H, ArH), 7.75–7.90 (m, 4H, ArH); [M + H]+
¼
(CDCl3) d 17.4; 13C NMR (CDCl3) d 14.4 (COCH2CH3), 16.4 (d, J ¼
6.4, POCH2CH3), 61.4 (COCH2), 62.4 (d, J ¼ 5.5, POCH2), 128.7
(d, J ¼ 15.0, C2), 129.3 (d, J ¼ 189.7, C1), 130.9 (d, J ¼ 15.1, C6),
132.8 (d, J ¼ 10.9, C5), 133.3 (d, J ¼ 3.0, C4), 135.9 (d, J ¼ 10.0,
C3), 165.7 (d, J ¼ 2.2, C]O); 1H NMR (CDCl3) d 1.33 (t, 6H, J ¼
7.1, POCH2CH3), 1.40 (t, 3H, J ¼ 7.1, COCH2CH3), 4.00–4.28 (m,
4H, POCH2), 4.35–4.46 (m, 2H, COCH2), 7.49–7.60 (m, 1H, ArH),
7.94–8.08 (m, 1H, ArH), 8.22 (d, 1H, J ¼ 7.8, C4–H), 8.46 (d, 1H, J
¼ 13.8, C2–H), [M + H]+ ¼ 287.1048, C13H20O5P requires
287.1048.
261.1040, C15H18O2P requires 261.1039.
Butyl diphenylphosphinate (3d). White crystals; mp.: 95–96 ꢀC,
mp.:45 90–92 C; P NMR (CDCl3) d 31.2, dP (CDCl3)46 31.2; 13C
31
ꢀ
NMR (CDCl3) d 13.7 (CH3), 18.9 (CH2CH3), 32.7 (d, J ¼ 6.6,
OCH2CH2), 64.8 (d, J ¼ 6.1, OCH), 128.5 (d, J ¼ 13.1, C2)*, 131.7
(d, J ¼ 10.1, C3)*, 131.8 (d, J ¼ 2.8, C4), 132.1 (d, J ¼ 137.0, C1), *
1
may be reversed; H NMR (CDCl3) d 0.92 (t, 3H, J ¼ 7.3, CH3),
1.35–1.55 (d, 2H, CH2CH3), 1.62–1.80 (m, 2H, OCH2CH2), 4.03 (t,
2H, J ¼ 6.6, OCH2), 7.35–7.61 (m, 6H, ArH), 7.71–7.94 (m, 4H,
ArH); [M + H]+ ¼ 275.1196, C16H20O2P requires 275.1195.
Isobutyl diphenylphosphinate (3e). White crystals; mp.: 82–
83 ꢀC, mp.:44 79–80 ꢀC; 31P NMR (CDCl3) d 31.0; 13C NMR
(CDCl3) d 19.0 (CH3), 29.4 (d, J ¼ 6.9, CH), 70.9 (d, J ¼ 6.3,
OCH2), 128.6 (d, J ¼ 13.1, C2)*, 131.8 (d, J ¼ 10.1, C3)*, 131.9 (d, J
Diethyl 3-acetylphenylphosphonate (1n). 31P NMR (CDCl3) d
18.1, dP (CDCl3)39 18.1; 13C NMR (CDCl3) d 16.4 (d, J ¼ 6.4,
CH2CH3), 26.0 (C(O)CH3), 62.4 (d, J ¼ 5.6, OCH2), 129.0 (d, J ¼
14.8, C6), 129.5 (d, J ¼ 189.4, C1), 131.7 (d, J ¼ 10.6, C5), 131.9 (d,
J ¼ 3.0, C4), 136.0 (d, J ¼ 10.0, C3), 137.2 (d, J ¼ 13.9, C2), 197.2
(d, J ¼ 1.4, C]O); 1H NMR (CDCl3) d 1.35 (t, 6H, J ¼ 7.0,
CH2CH3), 2.65 (3H, C(O)CH3), 4.07–4.28 (m, 4H, OCH2), 7.55–
7.66 (m, 1H, ArH), 7.94–8.03 (m, 1H, ArH), 8.15 (d, 1H, J ¼ 7.5,
C4–H), 8.38 (d, 1H, J ¼ 13.8, C2–H); [M + H]+ ¼ 257.0943,
1
¼ 2.8, C4), 132.2 (d, J ¼ 137.2, C1), * may be reversed; H NMR
(CDCl3) d 0.96 (d, 6H, J ¼ 6.7, CH3), 1.89–2.07 (m, 1H, CH), 3.78
(t, 2H, J ¼ 6.3, OCH2), 7.34–7.56 (m, 6H, ArH), 7.65–7.88 (m, 4H,
ArH); [M + H]+ ¼ 275.1197, C16H20O2P requires 275.1195.
Isopentyl diphenylphosphinate (3f). White crystals; mp.: 55–
56 ꢀC, mp.:47 55–57 ꢀC; 31P NMR (CDCl3) d 31.2, dP (CDCl3)47
30.1; 13C NMR (CDCl3) d 22.3 (CH3), 24.6 (CH), 39.2 (d, J ¼ 6.6,
OCH2CH2), 63.4 (d, J ¼ 6.1, OCH2), 128.4 (d, J ¼ 13.1, C2)*, 131.5
(d, J ¼ 10.1, C3)*, 131.6 (d, J ¼ 137.0, C1), 132.0 (d, J ¼ 2.8, C4), *
C
12H18O4P requires 257.0943.
2.2. General procedure for the reaction of bromobenzene and
alkyl phenyl-H-phosphinates (2a–f). To the bromobenzene (0.11
mL, 1.0 mmol) was added alkyl phenyl-H-phosphinate [1.0
mmol: 0.15 mL of ethyl phenylphosphinate (2a), 0.17 mL of
propyl phenylphosphinate (2b), 0.17 mL of isopropyl phenyl-
phosphinate (2c), 0.18 mL of butyl phenylphosphinate (2d), 0.19
mL of isobutyl phenylphosphinate (2e), 0.21 g isopentyl phe-
nylphosphinate (2f)], triethylamine (0.16 mL, 1.1 mmol) and
Pd(OAc)2 (0.011 g, 0.05 mmol) and the resulting mixture was
irradiated by microwave as above (2.1) at 150 ꢀC for 5 min. The
mixture was puried as above using hexane–ethyl acetate 1 : 1
as the eluent. The products (3a–f) were obtained as white
crystals.
1
may be reversed; H NMR (CDCl3) d 0.88 (d, 6H, J ¼ 6.5, CH3),
1.60 (q, 2H, J ¼ 6.7, OCH2CH2), 1.68–1.85 (m, 1H, CH), 4.04 (q,
2H, J ¼ 6.5, OCH2), 7.34–7.56 (m, 6H, ArH), 7.65–7.85 (m, 4H,
ArH); [M + H]+ ¼ 289.1353, C17H22O2P requires 289.1352.
2.3. General procedure for the reaction of secondary phosphine
oxides with bromoarenes. The tertiary phosphine oxides (4a–d
and 6a–c) were prepared from the corresponding bromoarene
(2.0 mmol: 0.21 mL of bromobenzene, 0.34 g of 4-bromoto-
luene, 0.38 g 4-bromo-chlorobenzene and 0.22 mL 4-bromo-
uorobenzene) and the secondary phosphine oxide [2.0 mmol:
0.40 g of diphenylphosphine oxide, 0.27 g of dipropylphosphine
oxide (5a), 0.32 g of dibutylphosphine oxide (5b) and 0.46 g of
dibenzylphosphine oxide (5c)] [in the case of dialkylphosphine
oxides in acetonitrile (1 mL)], as above (2.1). The only difference
is that, in the case of dialkylphosphine oxides (5a–c), the solvent
Ethyl diphenylphosphinate (3a). White crystals; mp.: 43–44 ꢀC,
31
mp.:42 39–41 C, P NMR (CDCl3) d 32.2, dP (CDCl3)43 31.5; 13C
ꢀ
NMR (CDCl3) d 16.5 (d, J ¼ 6.6, CH3), 61.1 (d, J ¼ 5.9, OCH2),
128.4 (d, J ¼ 13.1, C2)*, 131.6 (d, J ¼ 10.1, C3)*, 131.7 (d, J ¼
1
137.0, C1), 132.0 (d, J ¼ 2.8, C4), * may be reversed; H NMR
22814 | RSC Adv., 2014, 4, 22808–22816
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was removed aer the reaction. The products 4a–d and 6a–c
were obtained as white or pale yellow crystals.
Acknowledgements
Triphenylphosphine oxide (4a). White crystals; mp.: 156–157
ꢀC, mp.:48 156–157 ꢀC; 31P NMR (CDCl3) d 30.6, dP (CDCl3)48 29.5.
[M + H]+ ¼ 279.0941, C18H16OP requires 279.0939.
The above project was supported by the Hungarian Scientic
and Research Fund (OTKA no. K83118).
4-Methylphenyl diphenylphosphine oxide (4b). White crystals;
References
mp.: 118–119 ꢀC, mp.:49 119–123 C; 31P NMR (CDCl3) d 29.3, dP
ꢀ
(CDCl3)49 29.1; 13C NMR (CDCl3) d 21.6 (CH3), 128.4 (d, J ¼ 12.1,
C20 )a, 129.1 (d, J ¼ 106.4, C1), 129.2 (d, J ¼ 12.6, C2)b, 131.8 (d, J ¼
2.7, C40 ), 132.0 (d, J ¼ 9.9, C30 )a, 132.1 (d, J ¼ 10.2, C3)b, 132.8 (d, J ¼
1 Preceding communication: E. Jablonkai and G. Keglevich,
Tetrahedron Lett., 2013, 54, 4185.
2 E. Jablonkai and G. Keglevich, Curr. Org. Synth., 2014, 11,
429.
105.9, C10 ), 142.4 (d, J ¼ 2.8, C4),
may be reversed; H NMR
a,b
1
(CDCl3) d 2.40 (s, 3H, CH3), 7.11–7.29 (m, 2H, ArH), 7.40–7.80 (m,
12H, ArH); [M + H]+ ¼ 293.1085, C19H18OP requires 293.1090.
4-Chlorophenyl diphenylphenylphosphine oxide (4c). Pale
3 C. Yuan and H. Feng, Synthesis, 1990, 140.
¨
¨
4 G. Keglevich, A. Grun, A. Bolcskei, L. Drahos, M. Kraszni and
G. T. Balogh, Heteroat. Chem., 2012, 23, 574.
5 T. Hirao, T. Masunaga, Y. Ohshiro and T. Agawa, Tetrahedron
Lett., 1980, 21, 3595.
yellow crystals; mp.: 142–143 C, mp.:49 141–142 C; 31P NMR
(CDCl3) d 28.5, dP (CDCl3)49 28.8; 13C NMR (CDCl3) d 128.6 (d, J ¼
12.2, C20 )a, 128.8 (d, J ¼ 12.7, C2)b, 131.1 (d, J ¼ 104.7, C1), 131.96
(d, J ¼ 10.0, C30 )a, 132.02 (d, J ¼ 105.0, C10 ), 132.1 (d, J ¼ 2.7, C40 ),
133.4 (d, J ¼ 10.7, C3)b, 138.5 (d, J ¼ 3.4, C4), a, b may be reversed;
1H NMR (CDCl3) d 7.20–7.87 (m, ArH); [M + H]+ ¼ 313.0551,
ꢀ
ꢀ
6 T. Hirao, T. Masunaga, N. Yamada, Y. Ohshiro and T. Agawa,
Bull. Chem. Soc. Jpn., 1982, 55, 909.
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C
18H15OP35Cl requires 313.0544.
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4-Fluorophenyl diphenylphosphine oxide (4d). Pale yellow
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a,b
1
¼ 3.2, J2 ¼ 253.6, C4),
may be reversed; H NMR (CDCl3) d
1749.
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297.0846, C18H15OPF requires 297.0839.
4637.
Dipropylphenylphosphine oxide (6a). Yield: 80%; pale yellow 14 D. Villemin, P.-A. Jaffres and F. Simeon, Phosphorus, Sulfur
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ꢀ
ꢀ
13C NMR (CDCl3) d 15.4 (d, J ¼ 4.1, CH3), 15.9 (d, J ¼ 14.9, 15 M. Kalek and J. Stawinski, Organometallics, 2007, 26, 5840.
CH2CH3), 32.3 (d, J ¼ 68.3, PCH2), 128.8 (d, J ¼ 11.1, C2)*, 130.6 16 Y. Belabassi, S. Alzghari and J.-L. Montchamp, J. Organomet.
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1
may be reversed; H NMR (CDCl3) d 0.95 (t, 6H, J ¼ 7.3, CH3), 17 E. L. Deal, C. Petit and J.-L. Montchamp, Org. Lett., 2011, 13,
1.37–1.69 (m, 4H, CH2CH3), 1.75–2.01 (m, 4H, PCH2), 7.40–7.51
3270.
(m, 3H, ArH), 7.61–7.73 (m, 2H, ArH); [M + H]+ ¼ 211.1247, 18 M. Kalek, M. Jezowska and J. Stawinski, Adv. Synth. Catal.,
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12H20OP requires 211.1246.
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CH2CH3), 24.0 (d, J ¼ 14.5, PCH2CH2), 29.6 (d, J ¼ 68.5, PCH2),
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(m, 4H, PCH2), 7.37–7.54 (m, 3H, ArH), 7.59–7.75 (m, 2H, ArH); 22 I. P. Beletskaya and M. A. Kazankova, Russ. J. Org. Chem.,
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Dibenzylphenylphosphine oxide (6c). Yield: 95%; white crys- 23 A. Stadler and C. O. Kappe, Org. Lett., 2002, 4, 3541.
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¼ 8.5, C3)a, 131.4 (d, J ¼ 7.6, C1), 131.6 (d, J ¼ 2.7, C4), a, b may be 26 G. Keglevich, T. Novak, L. Vida and I. Greiner, Green Chem.,
´
reversed; 1H NMR (CDCl3) d 3.49 (d, 4H, J ¼ 13.9, PCH2), 7.20–
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7.71 (m, 15H, ArH); [M + H]+ ¼ 307.1241, C20H20OP requires 27 G. Keglevich, K. Majrik, L. Vida and I. Greiner, Lett. Org.
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