Pd-catalyzed P-arylation of triarylantimony dicarboxylates with dialkyl H-phosphites without a base: Synthesis of arylphosphonates

Article abstract of DOI:10.1248/cpb.c14-00727

The reaction of triarylantimony diacetates [Ar3Sb(OAc)2] with dialkyl H-phosphites [H-PO(OR)2] in the presence of a Pd(PPh3)4 (5 mol%) catalyst led to the formation of arylphosphonates in moderate to excellent yield under base-free conditions. This reaction is the first example of carbon-phosphorus bond formation by using an organoantimony compound as a pseudo-halide.

Full text of DOI:10.1248/cpb.c14-00727

1
30
Chem. Pharm. Bull. 63, 130–133 (2015)
Vol. 63, No. 2
Note
Pd-Catalyzed P-Arylation of Triarylantimony Dicarboxylates with
Dialkyl H-Phosphites without a Base: Synthesis of Arylphosphonates
a
b
b
,a
Mio Matsumura, Yuqiang Dong, Naoki Kakusawa, and Shuji Yasuike*
a
School of Pharmaceutical Sciences, Aichi Gakuin University; 1–100 Kusumoto-cho, Chikusa-ku, Nagoya 464–8650,
b
Japan: and Faculty of Pharmaceutical Sciences, Hokuriku University; Kanagawa-machi, Kanazawa 920–1181,
Japan.
Received October 20, 2014; accepted November 25, 2014
The reaction of triarylantimony diacetates [Ar Sb(OAc) ] with dialkyl H-phosphites [H-PO(OR) ] in the
3
2
2
presence of a Pd(PPh ) (5mol%) catalyst led to the formation of arylphosphonates in moderate to excellent
3
4
yield under base-free conditions. This reaction is the first example of carbon–phosphorus bond formation by
using an organoantimony compound as a pseudo-halide.
Key words Hirao-type P-arylation; triarylantimony diacetate; arylphosphonate; dialkyl H-phosphite; base-
free reaction
Phosphorus–carbon (P–C) bond formation for the synthe- diethyl phosphite (9a) without using a base. The results in-
sis of organophosphorus compounds is a fundamental and cluding the search for active substrates, optimum amount
significant research topic in organic synthesis, materials, and of phosphorus reagent and suitable catalysts for the reaction
1–6)
biology.
Among these, the transition-metal-catalyzed cross- are summarized in Table 1. The progress of the reaction was
coupling reaction is one of the most practical methods in monitored by gas–liquid chromatography (GLC) and the reac-
7
–9)
modern organic syntheses.
With regard to the synthesis of tion time was determined when the yields of products 10, 11,
arylphosphonates, the Pd-catalyzed cross-coupling reactions of and Ph M (12, 13) showed a maximum value because it is
3
aryl halides with dialkyl H-phosphites (i.e., Hirao P-arylation) impossible to detect the disappearance of the starting mate-
10–21)
have proved to be a powerful method.
The general proce- rial and phosphorus reagent by thin-layer chromatography or
dure of these P-arylations involves a Pd-phosphine complex GLC. First, we performed the reactions of 9a (1.2eq) with a
as the catalyst with the use of a stoichiometric or an excess variety of antimony reagents (1a–6) to compare the reactiv-
amount of a base. Recently, different aryl substances were ity using 5mol% of Pd(PPh ) as catalyst in 1,4-dioxane at
3
4
investigated for their reactivity with phosphorus agents. Sulfo- 60°C under argon atmosphere (entries 1–8). In comparison
2
2,23)
24)
25)
nates,
diaryliodonium salts, arylboronic acids, aryldi- with these results, triphenylantimony dicarboxylates (1a, 2)
2
6)
27)
azonium salts, and triarylbismuthanes have been reported and pentavalent bismuth(V) compounds (7, 8) afforded the
to be useful for P–C bond formation as the arylating reagents expected diethyl phenylphosphonate (10) in good to high
with dialkyl H-phosphites; however, a base and/or an additive yields along with homo-coupling product (11) and reductive
was required for the transformation.
products (12, 13). Among these, triphenylantimony diacetate
On the other hand, Pd-catalyzed cross-coupling reactions (1a) appeared to be the best substrate for this reaction in terms
using organoantimony compounds have recently been the of the yield (77%) of the cross-coupling product (10) and reac-
focus of attention. Triarylantimony dicarboxylates act as ef- tion time (6h). Next, optimum amount of phosphorus reagent
fective arylating agents in Pd-catalyzed C–C(Ar) bond forma- was determined by the reaction of 1a with 9a because 1a had
2
8–30)
31)
32)
tion reactions such as Heck-,
Stille-, and Hiyama-type
three phenyl groups (entries 1, 9–11). The reaction of 1a with
reactions. Over the past few years, we have also found that 9a in the ratio 1:0.9 was proved to be the best, affording the
they are an efficient aryl donors in base-free Suzuki-type cross-coupling product (10) in the highest yield (94%) and
reactions and copper- and base-free Sonogashira-type reac- with extremely small amounts the by-products (entry 11). The
33–35)
tions.
Moreover, base-free Miyaura-type cross-coupling reaction of 1a with an excess amount diethyl phosphite (9a)
reactions for boron–carbon (B–C) bond formation using tri- afforded the reductive by-product (12) in 10–45% yields (en-
arylantimony diacetates and tetra(alkoxo)diborons afforded tries 1, 9, 10). Thus, this reaction is sensitive to the amount of
36)
the corresponding arylboronates. As a continuation of our dialkyl H-phosphite. These results show that one of the three
studies on heteroatom–carbon bond formation, we now report phenyl groups on antimony is involved in the present carbon-
a novel Pd-catalyzed Hirao-type P-arylation of a pentavalent phosphours bond formation. We also examined a similar reac-
organoantimony compound, triarylantimony diacetate, with tion using other catalytic systems such as Pd(dba) , Pd(dba) -
2
2
dialkyl H-phosphites afford to the corresponding arylphospho- dppf, PdCl , Pd(OAc) , and PdCl (PPh ) . They were inferior
2
2
2
3 2
nates without using any base.
to Pd(PPh ) in the terms of the reaction time and yield of the
3 4
cross-coupling product (entries 12–16). The screening of sol-
vent showed that the reaction proceeded effectively in dioxane
Results and Discussion
We initially focused our attention on the determina- (94%), 1,2-dichloroethane (DCE) (78%), 1,2-dimethoxyethane
tion of the optimum conditions for the P-arylation of (DME) (75%) and tetrahydrofuran (THF) (71%) whereas
organoantimony(V) and bismuth(V) compounds (1a–8) with toluene, CH CN, N-methylpyrrolidone (NMP) and EtOH gave
3
*
To whom correspondence should be addressed. e-mail: s-yasuik@dpc.agu.ac.jp
©
2015 The Pharmaceutical Society of Japan

Vol. 63, No. 2 (2015)
Chem. Pharm. Bull.
131
a)
Table 1. Pd-Catalyzed P-Arylation of Organoantimony and Bismuth Reagents (1a–8) with Diethyl Phosphite (9a)
b)
Entry
M
X
Ratio
Pd catalyst
Pd(PPh3)4
Solvent
Time (h)
10 (%)
11 (%)
12 or 13 (%)
c)
1
1a
2
Sb
OAc
OBz
OTs
Cl
1:1.2
Dioxane
6
6
77
58
46
<1
<1
36
66
57
19
37
3
3
10
8
c)
2
c)
3
3
24
24
24
24
24
24
6
<1
14
11
4
10
1
c)
4
4
c)
5
5
Br
9
c)
6
6
Ph
37
3
c)
7
7
Bi
OAc
Cl
20
2
c)
8
8
2
c)
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
Sb
OAc
1:3
1:2
<1
4
45
24
3
c)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
6
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
e)
1:0.9
6
94 (89)
24
2
Pd(dba)2
24
24
24
24
24
24
6
6
15
5
Pd(dba) +dppf
70
3
2
PdCl2
<1
<1
<1
78
<1
<1
<1
15
13
17
5
38
25
14
6
Pd(OAc)2
PdCl (PPh )
3 2
2
Pd(PPh3)4
1,2-DCE
DME
75
7
THF
3
71
5
Toluene
NMP
24
24
24
24
22
7
18
35
<1
<1
8
CH CN
<1
<1
2
3
EtOH
<1
a) 1a–8 (0.5mmol), Pd(PPh3)4 (0.025mmol), b) 1a–8:9a, c) GC yield using octadecane as internal standard. The yield 100% corresponds to the formation of 0.5mmol of
1
0, 0.75mmol of 11 and 0.5mmol of Ph M (12, 13), d) the yield 100% corresponds to the formation of 0.45mmol of 10 and 12, 0.675mmol of 11, e) isolated yield is shown
3
in parenthesis.
Table 2. Pd-Catalyzed Hirao-Type Coupling Reaction of Triarylantimony
Diacetates (1) with Dialkyl H-Phosphites (9)
inferior results (entries 17–23). The addition of a base such
as triethylamine to facilitate the Hirao reaction decreased the
yield of the coupling product (10) (38%). We have previously
reported that the B-arylation of triarylantimony diacetates
with diboron reagents in the presence of PdCl (PPh ) under
a)
2
3 2
an aerobic conditions, affording arylboronates in which two
of the three aryl groups on the antimony participated in the
36)
formation of coupling products. Unfortunately, the yield of
0 in this P-arylation decreased to 30% in an aerobic condi-
b)
Entry
Ar
R
Yield (%)
1
tions. Consequently, the best result was obtained when 1a was
treated with 9a (0.9eq) by using Pd(PPh ) (5mol%) in 1,4-di-
oxane at 60°C under an argon atmosphere (entry 11).
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1c
1d
1e
1f
Phenyl
9b i-Pr
9c n-Bu
9d Me
9a Et
9a
14
15
16
17
18
19
20
21
22
98
93
90
95
93
45
76
97
3
3
4
To study the substrate scope and limitation of this P-
arylation, we carried out the coupling reaction of triarylanti-
mony diacetates (1) with dialkyl H-phosphites (9) using the
optimized reaction conditions (Table 1, entry 11). The reaction
time was fixed at 6h because the endpoint of reaction was
not clear. The results are summarized in Table 2. The reac-
tion of dialkyl H-phosphites (9b–d) affored the correspond-
ing arylphosphonates (14–16) in high yields (entries 1–3).
We also examined a similar reaction using other phosphorus
4-Methoxyphenyl
4-Methylphenyl
2-Methylphenyl
4-Bromophenyl
4-Trifluoromethylphenyl
Mesityl
9a
9a
9a
1g
9a
a) 1 (0.5mmol), 9 (0.45mmol), Pd(PPh ) (0.025mmol). b) Isolated yield.
3
4
The reactions of various triarylantimony diacetates (1b–f),
compounds, such as HPPh , HPCy and P(OEt) . However, all bearing electron-donating and -withdrawing groups on the
2
2
3
these compounds gave the cross-coupling products in misera- phenyl ring, with 9a under the same reaction conditions af-
bly poor yields (<4% yields), and provided the homo-coupling forded the corresponding products in excellent to good yields
and reduction products of 1a.
except 1d (entries 4–8). The reaction could be applied to a

1
32
Chem. Pharm. Bull.
Vol. 63, No. 2 (2015)
13
as an internal standard) and C-NMR (CDCl : δ: 77.00 as an
3
internal standard) spectra were recorded on a JEOL JNM-
ECA400 (400MHz and 100MHz) spectrometers in CDCl un-
3
less otherwise stated. Mass spectra (MS) were obtained on a
JEOL JMP-DX300 instrument (70eV, 300µA). All chromato-
graphic separations were accomplished with Silica Gel 60N
(
(
Kanto Chemical Co., Inc., Japan). Thin-layer chromatography
TLC) was performed with Macherey-Nagel Pre-coated TLC
plates Sil G25 UV254
.
Materials Dialkyl H-phosphites (9a–d) were purchased
from Wako Pure Chemical Industries, Ltd. and TCI Fine
Chemicals, Japan. Triphenylantimony diacetate (1a) was
purchased from TCI Fine Chemicals, Japan, and other triary-
2
9)
36)
34)
29)
lantimony diacetates such as 1b–d, 1e, 1f, 1g were
prepared according to the reported procedures.
Typical Procedure for P-Arylation of Triarylantimony
Dicarboxylates with Dialkyl H-Phosphites A solution of
triaryantimony diacetate (1) (0.5mmol), dialkyl H-phosphite
(
(
9) (0.45mmol), and tetrakis(triphenylphosphine)palladium
5mol%, 0.025mmol) in dioxane (5mL) was heated at 60°C
for 6h under an argon atmosphere. After dilution with ether
30mL) and saturated aqueous NH Cl (20mL), the reaction
Chart 1. Possible Mechanism
(
4
highly reactive substrate, tris(4-bromophenyl)antimony diace- mixture was separated and the aqueous layer was extracted
tate (1e), whose carbon–bromine bond remained intact and with ether (30mL×2). The combined organic layer was
other by-products were not observed (entry 7). In the methyl- washed with brine, dried over anhydrous MgSO and concen-
4
substituted antimony agents (1c, d, g), the influence of the ste- trated under reduced pressure. The crude residue was purified
ric hindrance of antimony reagents 1 was remarkable (entries by column chromatograph (hexane–ethyl acetate) on silica
3
7)
5
, 6, 9). The most bulky mesityl derivative [(Mes) Sb(OAc) ] gel to give arylphosphonates (10, 14–22). The products [10,
3 2
37)
24)
37)
19)
37)
38)
was practically inactive (entry 9).
14, 15, 16–19, 20, 21, 22 ] were colorless oil, and
A plausible reaction mechanism of this P-arylation is shown were confirmed by comparison of NMR data and MS spectra
in Chart 1. The catalytic cycle of this reaction would be simi- with that in the literature.
lar to that of the Heck-type C-arylation of alkenes reported
by Moiseev et al. and the Pd-catalyzed base-free B-arylation
Acknowledgments This work was supported by
Grant-in-Aid for Scientific Research (C) from the Ministry
a
2
9,36)
of Ar Sb(OAc) with tetra(alkoxo)diboron reported by us.
3
2
The initial step of the reaction would be oxidative addition Education, Culture, Sports, Sciences and Technology of Japan.
of the Ar–Sb bond of 1 onto the Pd(0) species (A) to form Financial was support by Institute of Pharmaceutical Life
ArPdSb complex (B). The complex (B) thus formed is trans- Sciences, Aichi Gakuin University and the Special Research
formed to ArPdOAc complex (C) accompanied by elimination Found from Hokuriku University.
of Ar SbOAc. The Pd-catalyzed P-arylation of aryl halides
2
with dialkyl H-phosphites is promoted by acetate ions, and
ArPdOAc (C) is the key intermediate for reaction mecha- interest.
Conflict of Interest The authors declare no conflict of
12,13,19)
nism.
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