A convenient and applicable route to synthesize 2-(1-alkynyl) phenylphosphonates

Article abstract of DOI:10.1002/hc.20156

A convenient and applicable route has been developed to synthesize various 2-(1-alkynyl)-phenylphosphonates starting from easily available phenols via palladium-catalyzed alkynyl dehydroxylation of 2-hydroxylphenylphosphonates.

Full text of DOI:10.1002/hc.20156

Heteroatom Chemistry
Volume 16, Number 6, 2005
A Convenient and Applicable Route to
Synthesize 2-(1-Alkynyl)phenylphosphonates
Ai-Yun Peng, Xin-Ying Zhang, and Yi-Xiang Ding
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai, 200032, People’s Republic of China
Received 16 May 2005; revised 19 June 2005
a convenient method to synthesize 2-(1-alkynyl)-
ABSTRACT: A convenient and applicable route has
phenylphosphonates. In this paper, we wish to report
in detail our results to prepare them.
been developed to synthesize various 2-(1-alkynyl)-
phenylphosphonates starting from easily available
phenols via palladium-catalyzed alkynyl-dehydroxy-
ꢀ
C
lation of 2-hydroxylphenylphosphonates. 2005 Wiley
RESULTS AND DISCUSSION
Periodicals, Inc. Heteroatom Chem 16:529–534, 2005; Pub-
lished online in Wiley InterScience (www.interscience.
wiley.com). DOI 10.1002/hc.20156
Two probable methods to synthesize our aim alkynes
were considered. We initially had tried to prepare the
alkynes 3 through the Sonogashira cross-coupling
reaction [3,5] of 2-halophenylphosphonates 1 and
terminal alkynes 2 (Scheme 1). But after consulting
the corresponding literature, we found that prepara-
tion of 2-halophenylphosphonate 1 (R1 = H, X = I or
Br) usually starts from the unstable and expensive
2-iodophenylamine and needs strong basic and irra-
diation conditions [6]. Furthermore, 2-iodophenyl-
amines with other substituents in the benzene ring
are not commercially available, herein it is difficult
to synthesize various 2-halophenylphosphonates.
Taking into account of these drawbacks, we gave up
this method.
We then turned our attention to the Heck
alkynylation of 2-(diethylphosphonyl)phenyl per-
fluoroalkanesulfonates 4 with terminal alkynes 2
(Scheme 2). It has been reported that aryl triflates
[7] and aryl perfluoroalkanesulfonates [8] can un-
dergo palladium-catalyzed cross-coupling reaction
with terminal alkynes, but these procedures have
not been extended to the corresponding 2-phos-
phonyl-substituted aryl substrates. We thought this
method was feasible and applicable in the follow-
ing two aspects. On the one hand, 2-hydroxyphenyl-
phosphonates, the key starting materials to pre-
pare compounds 4, can be easily obtained from the
INTRODUCTION
Since conjugated alkynes are found in a wide range
of natural and unnatural materials [1], as well as ver-
satile synthetic intermediates [2], much effort has
been paid to develop methods to construct organic
molecules bearing alkynyl moieties. Over the last few
decades, the palladium-catalyzed alkynylation reac-
tion has been extensively studied and become one of
the most general and reliable methods to form con-
jugated alkynes [3].
We became interested in palladium-catalyzed
alkynylation reaction during the course of preparing
phosphaisocoumarins via intramolecular cycliza-
tion of phosphonates to alkynes [4]. It was essen-
tial to prepare 2-(1-alkynyl)phenylphosphonates as
the cyclization substrates. However, to our knowl-
edge, there were no reports about the synthesis
and application of 2-(1-alkynyl)phenylphosphonates
prior to our studies. Thus, we decided to develop
Correspondence to: Yi-Xiang Ding: e-mail: dingyx@mail.sioc.
ac.cn.
c
ꢀ
2005 Wiley Periodicals, Inc.
529

530 Peng, Zhang, and Ding
SCHEME 1
SCHEME 3
rearrangement of aryl phosphates according to the
literature [9]. On the other hand, compared with
the moisture-sensitive and rather expensive triflat-
ing agent (e.g. triflic anhydride) to prepare aryl
triflates, perfluoroalkanesulfonyl fluoride, which is
used to synthesize aryl perfluoroalkanesulfonates,
is not only commercially available but also cheap
and insensitive to moisture. After examination, in
the end we developed a convenient route to synthe-
size the alkynes 3 via palladium-catalyzed alkynyl-
dehydroxylation of 2-hydroxylphenylphosphonates.
We first prepared several 2-hydroxyphenylphos-
phonates 7 from the corresponding phenols 5 ac-
cording to the literature [9] (Scheme 3). It is worth
mentioning that the rearrangement of diethyl 4-
nitrophenyl phosphate 6d is not a literature proce-
dure, which, we found, needs lower reaction temper-
ature (below −85◦C) and requires about 2.0 equiv.
LDA.
90◦C for several hours (Scheme 5), and the results
are shown in Table 2. Most of the examined sub-
strates gave the desired products 3 in moderate to
high yields. Lower yields are associated with the use
of electron-rich sulfonate 4c (Table 2, entry 13) and
electron-withdrawing terminal alkyne (Table 2, en-
try 7). It has been reported that LiCl can improve the
coupling yields by acting as ligand exchanger in the
initially formed organopalladium triflates [7b], and
the presence of copper co-catalyst is essential for the
cross-coupling reaction to proceed at room temper-
ature [10]. Indeed, for our reaction, the yield of the
reaction of 4c with phenyl acetylene has been im-
proved considerably from 36 to 79% by the addition
of LiCl and CuI (Table 2, entries 13 and 14). Under the
same conditions, the reaction of 4c with propynl-1-
ol gave the desired product 3n in 72% yield (Table 2,
entry 15).
Compounds 7 were then converted to the cor-
responding perfluoroalkanesulfonates 4 (Scheme 4).
Compounds 7a–c can react with perfluoroalkane-
sulfonyl fluoride in Et3N at room temperature to
afford 4a–c in good yields (Table 1, entries 1–3).
However, the reaction of 7d under the above con-
ditions gave 4d only in 7% isolated yield, and most
of the starting material 7d was recovered (Table 1,
entry 4). When this reaction was carried out in
anhydrous CH2Cl2 by addition of 1.5 equiv. anhy-
drous Et3N at room temperature, the isolated yield
of 4d has been improved to 47% (Table 1, entry
5). A probable explanation is that the nitro group’s
strong electron-withdrawing effect might make the
formed 4d easy to hydrolysis to 7d under aqueous
conditions.
CONCLUSIONS
In conclusion, we have developed a convenient
and applicable route to synthesize 2-(1-alkynyl)-
phenylphosphonates starting from easily available
phenols via the palladium-catalyzed cross-coupling
reaction of 2-(diethylphosphonyl)phenyl perfluo-
roalkanesulfonates 4 and terminal alkynes. Since
compounds 4 have the potential to react with many
reagents, such as alkenes [8,11] and a variety of
organometallic reagents [12], the present route may
also be very useful to prepare other 2-substituted
phenylphosphonates.
EXPERIMENTAL
Compounds 4 reacted with a variety of terminal
alkynes in the presence of PdCl2(PPh3)2 and Et3N at
NMR spectra were all recorded on a Varian
Mercury300 spectrometer using CDCl3 as a solvent
SCHEME 2
SCHEME 4

A Convenient and Applicable Route to Synthesize 2-(1-Alkynyl)phenylphosphonates 531
TABLE 1 The Synthesis of the Perfluoroalkansulfonates 4a
TABLE 2 The Synthesis of 2-(1-Alkynyl)phenylphospho-
nates 3a
Entry
Product
R1
Solvent
Base
Yield (%)b
Entry
R1
R 2
Product
Yield (%)b
1
2
3
4a
4b
4c
4d
4d
H
Cl
MeO
NO2
NO2
Et3N
Et3N
Et3N
Et3N
CH2Cl2
Et3N
Et3N
Et3N
Et3N
Et3N
78
75
70
7
1
2
3
4
5
6
7
8
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
NO2
MeO
MeO
MeO
Ph
n-Bu
H
n-Bu
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3m
3n
73
50
52c
77
81
83
47
78
80
73
79
78
36
79
72
4
5c
47
aGeneral reaction conditions otherwise specified: 7: RfSO2F: Et3N =
1 mmol: 1.2 mmol : 1 mL, at room temperature for 12 h.
bIsolated yield.
p -EtC6H4
p -O2NC6H4
CH2OH
CH2OCH3
SiMe3
Cyclopropyl
p -EtC6H4
Ph
c 7d (4.50 mmol), RfSO2F (6.67 mmol), Et3N (6.83 mmol), CH2Cl2
(10.0 mL), at room temperature for 12 h.
9
10
11
12
13
14d
15d
1
unless stated. The H NMR spectra and 13C NMR
Ph
CH2OH
spectra used CDCl3 (with TMS) as the internal ref-
erence at 7.27 ppm and 77.0 ppm, respectively. 19F
NMR spectra used CFCl3 as the external reference,
and 31P NMR spectra used the 85% H3PO4 as the
external reference. MS spectra were determined us-
ing a HP5989A mass spectrometer. IR spectra were
measured on a Y-Zoom Cursor instrument. HRMS
were determined by Kratos Concept 1H series mass
spectrometer. Starting materials 7a–c were formed
from the corresponding phenols as reported [9].
Fluoroalkanesulfonyl fluorides and terminal alkynes
were commercially obtained. All reagents and sol-
vents were used as received unless Et3N and DMF
used to prepare compounds 3 were distilled from
calcium hydride.
aGeneral reaction conditions: molar ratio of 4: 2: PdCl2(PPh3)2: Et3N
is 1: 1.5: 0.03: 4, in DMF at 90◦C for 4 h.
bIsolated yield.
cThe total yield of 3c by desilylation of the product of 4a and trimethyl-
silyl acetelyne.
dBy addition of 300 mol% LiCl and 10 mol% CuI.
General Procedure for the Preparation
of 2-(Phosphonyl)phenyl
Perfluoroalkanesulfonates 4
To a mixture of the corresponding phenol 3
(5.5 mmol) and fluoroalkanesulfonyl fluoride
(5 mmol) was added dropwise Et3N (5 mL) at 0◦C.
After stirring at room temperature for 8 h, the
reaction mixture was concentrated in vacuo and the
residue was then dissolved in water (15 mL) and
extracted with EtOAc. The organic extracts were
washed with brine, dried (Na2SO4), and evaporated
in vacuo. The residue was chromatographed on
silica gel using hexane/EtOAc as an eluent to give
the corresponding product 4a–c. 4d was prepared
as in Table 1 (entry 5). The isolated yield and the
physical data for 4a–d are as follows.
Diethyl 2-hydroxy-5-nitrophenylphosphonate 7d
7d was prepared according to a modified process
of the literature [9]: the reaction of diethyl 4-nitro-
phenyl phosphate 6d with 2.0 equiv. LDA under be-
low −85◦C gave 7d as a yellow solid. Yield: 77%. 1H
NMR (300 MHz, CDCl3): δ 11.15 (br s, 1H), 8.29–
8.38 (m, 2H), 7.03–7.09 (m, 1H), 4.08–4.28 (m, 4H),
1.38 (t, J = 7.2 Hz, 6H). MS (EI): m/z: 275 (M+, 36),
247 (12), 231 (13), 219 (100), 203 (31), 189 (21), 171
(42), 109 (6); IR (KBr, cm−1): 3400, 2985, 1608, 1494,
1346, 1304, 1209, 1069, 1030, 987; Anal. Calcd for
C10H14NO6P: C, 43.64; H, 5.13; N, 5.09. Found: C,
43.71; H, 5.17; N, 5.12.
2-(Diethoxyphosphonyl)phenyl 1,1,2,2-tetra-
fluoro-2-(1,1,2,2-tetrafluoroethoxy)ethanesulfonate
1
4a. Oil. Yield: 78%. H NMR (300 MHz, CDCl3): δ
8.02–8.10 (m, 1H), 7.62–7.68 (m, 1H), 7.38–7.51 (m,
2H), 5.91 (tt, J1 = 52.5 Hz, J2 = 3.0 Hz, 1H), 4.10–
4.28 (m, 4H), 1.34 (t, J = 6.9 Hz, 6H); 31P NMR (121
MHz, CDCl3): δ 12.14; 19F NMR (300 MHz, CDCl3): δ
−81.77 (t, J = 12.9 Hz, 2F), −88.71 (m, 2F), −113.77
(s, 2F), −137.83 (dt, J1 = 55.7 Hz, J2 = 3.3 Hz, 2F);
MS (EI): m/z: 510 (M+, 2), 483 (10), 455 (14), 390 (7),
229 (5), 156 (100), 92 (9), 65 (22); IR (film, cm−1):
2991, 1602, 1572, 1474, 1428, 1331, 1256, 1145,
1080, 1024, 977, 887; Anal. Calcd for C14H15F8O7PS:
C, 32.95; H, 2.97. Found: C, 32.92; H, 3.07.
SCHEME 5

532 Peng, Zhang, and Ding
4-Chloro-2-(diethoxyphosphonyl)phenyl 1,1,2,2-
tetra-fluoro-2-(1,1,2,2-tetrafluoroethoxy)ethanesul-
fonate 4b. Oil. Yield: 75%. 1H NMR (300 MHz,
CDCl3): δ 8.00–8.06 (m, 1H), 7.58–7.62 (m, 1H),
7.31–7.36 (m, 1H), 5.91 (tt, J1 = 52.5 Hz, J2 = 3.0
Hz, 1H), 4.15–4.26 (m, 4H), 1.36 (t, J = 6.9 Hz, 6H);
31P NMR (121 MHz, CDCl3): δ 10.20; 19F NMR (300
MHz, CDCl3): δ −81.74 (t, J = 12.9 Hz, 2F), −88.57
(m, 2F), −113.62 (s, 2F), −137.78 (dt, J1 = 55.5 Hz,
J2 = 3.6 Hz, 2F); MS (EI): m/z: 544 (M+, 7), 488 (2),
424 (10), 263 (2), 247 (18), 190 (100), 173 (15), 101
(25), 79 (6); IR (film, cm−1): 2990, 1716, 1594, 1462,
1430, 1380, 1257, 1149, 1106, 1077, 1023, 979, 888;
Anal. Calcd for C14H14ClF8O7PS: C, 30.87; H, 2.59.
Found: C, 31.41; H, 2.51.
added dropwise the terminal alkyne (1.5 mmol) at
room temperature. After stirring at 80◦C for 5 h un-
der nitrogen, the reaction mixture was diluted with
EtOAc and washed with aqueous NH4Cl until neutral
and brine, dried (Na2SO4), and evaporated in vacuo.
The residue was chromatographed on silica gel us-
ing hexane/EtOAc as eluent to give the correspond-
ing product 3. The preparation of 3c, 3m, and 3n
was a little different from the above procedures (see
Table 2). The isolated yield and the physical data for
3a–n are as follows.
(2-Phenylethynyl-phenyl)-phosphonic Acid Di-
ethyl Ester 3a. Oil. Yield: 73%. 1H NMR (300 MHz,
CDCl3): δ 7.99–8.07 (m, 1H), 7.35–7.66 (m, 8H), 4.07–
4.28 (m, 4H), 1.32 (t, J = 6.9 Hz, 6H); 13C NMR (75.4
MHz, CDCl3): δ 134.18 (d, J = 9.1 Hz), 133.14 (d,
J = 12.3 Hz), 131.91 (d, J = 2.7 Hz), 131.37, 129.71
(d, J = 186.2 Hz), 128.23, 128.21, 127.54 (d, J = 14.3
Hz), 125.64 (d, J = 6.6 Hz), 122.89, 94.44 (d, J = 0.5
Hz), 87.66 (d, J = 6.2 Hz), 62.10 (d, J = 5.5 Hz),
16.20 (d, J = 6.8 Hz); 31P NMR (121 MHz, CDCl3): δ
16.73; MS (EI): m/z: 314 (M+, 100), 285 (27), 258 (30),
242 (34), 226 (23), 178 (21), 165 (37), 105 (16), 77 (7);
IR (film, cm−1): 2983, 2219, 1598, 1492, 1391, 1244,
1139, 1025, 970; HRMS (EI): Calcd for C18H19O3P
(M+): 314.10719. Found: 314.11061.
2-(Diethoxyphosphonyl)-4-methoxyphenyl 1,1,2,2-
tetrafluoro-2-(1,1,2,2-tetrafluoroethoxy)-ethanesulfo-
nate 4c. Oil. Yield: 70%. 1H NMR (300 MHz,
CDCl3): δ 7.50–7.56 (m, 1H), 7.26–7.31 (m, 1H),
7.08–7.12 (m, 1H), 5.90 (tt, J1 = 52.5 Hz, J2 = 3.0
Hz, 1H), 4.08–4.30 (m, 4H), 3.87 (s, 3H), 1.35 (dt,
J1 = 6.9 Hz, J2 = 0.6 Hz, 6H); 31P NMR (121 MHz,
CDCl3): δ 12.09; 19F NMR (300 MHz, CDCl3): δ
−81.81 (t, J = 13.8 Hz, 2F), −88.66 (m, 2F), −113.91
(s, 2F), −137.88 (dt, J1 = 56.7 Hz, J2 = 5.7 Hz, 2F);
MS (EI): m/z: 540 (M+, 10), 259 (55), 231 (10), 215
(17), 187 (100), 171 (12), 123 (8), 65 (5); IR (film,
cm−1): 2988, 1738, 1582, 1477, 1371, 1254, 1150,
1074, 1029, 977, 855; Anal. Calcd for C15H17F8O8PS:
C, 33.34; H 3.18. Found: C, 33.30; H, 3.21.
(2-Hex-1-ynyl-phenyl)-phosphonic Acid Diethyl
Ester 3b. Oil. Yield: 50%. 1H NMR (300 MHz,
CDCl3): δ 7.92–7.99 (m, 1H), 7.33–7.52 (m, 3H), 4.03–
4.24 (m, 4H), 2.46 (t, J = 6.9 Hz, 2H), 1.47–1.68 (m,
4H), 1.34 (t, J = 6.9 Hz, 6H), 0.95 (t, J = 6.9 Hz, 3H);
13C NMR (75.4 MHz, CDCl3): δ 134.04 (d, J = 9.9
Hz), 133.62 (d, J = 12.5 Hz), 131.86 (d, J = 2.6 Hz),
129.44 (d, J = 185.8 Hz), 126.98, 126.77 (d, J = 1.8
Hz), 96.21, 78.87, 62.07 (d, J = 4.8 Hz), 30.51, 21.94,
19.34, 16.31 (d, J = 4.8 Hz), 13.60; 31P NMR (121
MHz, CDCl3): δ 20.13; MS (EI): m/z: 294 (M+, 22),
265 (19), 252 (87), 224 (35), 209 (33), 196 (100), 115
(22), 77 (9); IR (film, cm−1): 2982, 2232, 1589, 1469,
1386, 1247, 1141, 1055, 1027, 966; HRMS (EI): Calcd
for C16H23O3P (M+): 294.13848. Found: 294.13606.
2-(Diethoxyphosphonyl)-4-nitrophenyl 1,1,2,2-
tetrafluoro-2-(1,1,2,2-tetrafluoroethoxy)-ethanesulfo-
nate 4d. Oil. Yield: 47%. 1H NMR (300 MHz,
CDCl3): δ 8.85–8.92 (m, 1H), 8.48–8.52 (m, 1H),
7.58–7.63 (m, 1H), 5.93 (tt, J1 = 51.6 Hz, J2 = 3.0
Hz, 1H), 4.17–4.34 (m, 4H), 1.38 (t, J = 6.9 Hz,
6H); 31P NMR (121 MHz, CDCl3): δ 11.65; 19F NMR
(300 MHz, CDCl3): δ −81.61 (t, J = 11.1 Hz, 2F),
−88.41 (m, 2F), −113.21 (s, 2F), −137.90 (dd,
J1 = 55.5 Hz, J2 = 3.6 Hz, 2F); MS (EI): m/z: 556
[(M + 1)+, 2], 528 (27), 500 (55), 257 (100), 201
(84), 171 (62), 101 (60), 63 (32); IR (film, cm−1):
2991, 1620, 1540, 1465, 1433, 1355, 1262, 1193,
1069, 1020, 862; Anal. Calcd for C14H14F8NO9PS:
C, 30.28, H 2.54, N, 2.52. Found: C, 30.43, H, 2.57,
N, 2.58.
Ethynyl-phenylphosphonic Acid Diethyl Ester 3c.
1
Oil. Yield: 52%. H NMR (300 MHz, CDCl3): δ 7.96–
8.04 (m, 1H), 7.41–7.65 (m, 3H), 4.06–4.27 (m, 4H),
3.39 (d. J = 2.7 Hz, 1H), 1.34 (dt, J1 = 7.2 Hz, J2 =
2.7 Hz, 6H); 13C NMR (75.4 MHz, CDCl3): δ 134.35 (d,
J = 12.3 Hz), 134.04 (d, J = 9.5 Hz), 131.86 (d, J =
2.5 Hz), 130.39 (d, J = 186.1 Hz), 128.18 (d, J = 15.0
Hz), 124.49 (d, J = 6.6 Hz), 82.51, 81.47 (d, J = 6.7
General Procedure for the Preparation of
o-Ethynylphenylphosphonic Acid Diethyl
Esters 3
Hz), 62.29 (d, J = 5.4 Hz), 16.14 (d, J = 6.3 Hz); 31
P
To a mixture of 4 (1.0 mmol), PdCl2(PPh3)2 (0.03
mmol), Et3N (4.0 mmol), and DMF (3 mL) was
NMR (121 MHz, CDCl3): δ 19.05; MS (EI): m/z: 238
(M+, 100), 209 (76), 182 (67), 166 (47), 137 (29), 129

A Convenient and Applicable Route to Synthesize 2-(1-Alkynyl)phenylphosphonates 533
(4), 77 (3); HRMS (EI): Calcd for C20H22ClO3P (M+):
376.09951. Found: 376.09696.
(51), 118 (51), 75 (33); IR (film, cm−1): 3283, 2983,
2101, 1589, 1468, 1392, 1243, 1142, 1026, 966; HRMS
(EI): Calcd for C12H15O3P (M+): 238.07588. Found:
238.07819.
[5-Chloro-2-(4-nitro-phenylethynyl)-phenyl]-phos-
phonic Acid Diethyl Ester 3g. A red solid, mp: 123–
1
124◦C. Yield: 47%. H NMR (300 MHz, CDCl3): δ
(5-Chloro-2-hex-1-ynyl-phenyl)-phosphonic Acid
Diethyl Ester 3d. Oil. Yield: 77%. 1H NMR (300
MHz, CDCl3): δ 7.79–7.84 (m, 1H), 7.47–7.49 (m, 2H),
4.17–4.25 (m, 4H), 2.45 (t, J = 6.9 Hz, 2H), 1.44–1.63
(m, 4H), 1.38 (t, J = 6.9 Hz, 6H), 0.95 (t, J = 6.9
Hz, 3H); 13C NMR (75.4 MHz, CDCl3): δ 134.76 (d,
J = 14.0 Hz), 133.74 (d, J = 10.3 Hz), 133.00 (d,
J = 19.8 Hz), 131.47 (d, J = 185.3 Hz), 131.81 (d,
J = 2.8 Hz), 125.00 (d, J = 6.0 Hz), 97.16 (d, J = 0.5
Hz), 77.86 (d, J = 6.0 Hz), 62.24 (d, J = 5.8 Hz),
30.29, 21.81, 19.23, 16.15 (d, J = 6.6 Hz), 13.45; 31P
NMR (121 MHz, CDCl3): δ 15.01; MS (EI): m/z: 328
(M+, 19), 299 (15), 286 (81), 258 (32), 230 (100), 165
(10), 149 (13), 115 (12), 75 (5); IR (film, cm−1): 2959,
2231, 1463, 1381, 1250, 1150, 1104, 1025, 971; HRMS
(EI): Calcd for C16H22ClO3P (M+): 328.09951. Found:
328.10115.
8.24–8.28 (m, 2H), 7.99–8.05 (m, 1H), 7.55–7.75
(m, 4H), 4.09–4.30 (m, 4H), 1.34 (dt, J1 = 6.9 Hz,
J2 = 2.1 Hz, 6H); 13C NMR (75.4 MHz, CDCl3): δ
146.36, 145.89 (d, J = 17.4 Hz), 133.96 (d, J = 12.8
Hz), 133.34, 132.57 (d, J = 6.7 Hz), 131.83 d, J = 1.6
Hz), 129.47 (d, J = 204.2 Hz), 129.08 (d, J = 11.6
Hz), 126.48 (d, J = 1.9 Hz), 119.05, 100.85, 86.24
(d, J = 6.1 Hz), 62.85 (d, J = 6.1 Hz), 28.79, 16.30
(d, J = 6.3 Hz), 15.16; 31P NMR (121 MHz, CDCl3):
δ 17.03; MS (EI): m/z: 393 (M+, 100), 365 (17), 337
(45), 321 (28), 273 (12), 244 (8), 210 (16), 199 (23),
163 (29), 105 (6), 77 (7); IR (KBr, cm−1): 2981, 2323,
1593, 1456, 1340, 1249, 1106, 1043, 972; Anal. Calcd
for C18H17ClNO5P: C, 54.90; H, 4.35; N, 3.56. Found:
C, 55.31; H, 4.25; N, 3.63.
[5-Chloro-2-(3-hydroxy-prop-1-ynyl)-phenyl]-
phosphonic Acid Diethyl Ester 3h. Oil. Yield: 78%.
1H NMR (300 MHz, DMSO): δ 7.57–7.79 (m, 3H),
5.39 (t, J = 6.0 Hz, 1H), 4.33 (d, J = 6.0 Hz, 2H),
4.05–4.13 (m, 4H), 1.26 (t, J = 6.9 Hz, 6H); 31P NMR
(300 MHz, DMSO): δ 16.16; MS (EI): m/z: 302 (M+,
7), 273 (7), 245 (24), 217 (49), 199 (25), 165 (10), 136
(21), 75 (11), 43 (100); IR (film, cm−1): 3377, 2983,
2239, 1463, 1392, 1240, 1152, 1045, 1025, 953; Anal.
Calcd for C13H16ClO4P: C, 51.58; H, 5.34. Found: C,
51.76; H, 5.50.
(5-Chloro-2-phenylethynyl-phenyl)-phosphonic
Acid Diethyl Ester 3e. Oil. Yield: 81%. 1H NMR
(300 MHz, CDCl3): δ 7.99–8.04 (m, 1H), 7.36–7.60
(m, 7H), 4.09–4.30 (m, 4H), 1.33 (dt, J1 = 6.9 Hz,
J2 = 0.6 Hz, 6H); 13C NMR (75.4 MHz, CDCl3): δ
134.27 (d, J = 13.4 Hz), 133.98 (d, J = 10.0 Hz),
133.79 (d, J = 19.6 Hz), 131.92 (d, J = 3.1 Hz),
131.79 (d, J = 185.4 Hz), 131.28, 128.62, 128.21,
123.94 (d, J = 6.0 Hz), 122.50, 95.32 (d, J = 0.7
Hz), 86.66 (d, J = 6.3 Hz), 62.32 (d, J = 5.5 Hz),
16.17 (d, J = 6.7 Hz); 31P NMR (121 MHz, CDCl3):
δ 14.96; MS (EI): m/z: 348 (M+, 100), 319 (19), 292
(30), 276 (48), 212 (17), 199 (23), 176 (46), 77 (11);
IR (film, cm−1): 2983, 2219, 1597, 1493, 1460, 1391,
1253, 1152, 1106, 1024, 972; HRMS (EI): Calcd for
C18H18ClO3P (M+): 348.06821. Found: 348.07295.
[5-Chloro-2-(3-methoxy-prop-1-ynyl)-phenyl]-
phosphonic Acid Diethyl Ester 3i. Oil. Yield: 80%.
1H NMR (300 MHz, CDCl3): δ 7.92–7.98 (m, 1H),
7.42–7.52 (m, 2H), 4.36 (s, 2H), 4.08–4.24 (m, 4H),
3.48 (d. J = 1.2 Hz, 3H), 1.32 (t, J = 7.2 Hz, 6H); 31
P
NMR (121 MHz, CDCl3): δ 17.28; MS (EI): m/z: 316
(M+, 2), 286 (62), 273 (5), 245 (39), 230 (100), 165
(9), 136 (16), 101 (10), 75 (7); IR (film, cm−1): 2984,
2229, 1463, 1382, 1250, 1153, 1101, 1022, 963; Anal.
Calcd for C14H18ClO4P: C, 53.08; H, 5.74. Found: C,
53.02; H, 5.86.
[5-Chloro-2-(4-ethyl-phenylethynyl)-phenyl]-phos-
phonic Acid Diethyl Ester 3f. Oil. Yield: 83%.
1H NMR (300 MHz, CDCl3): δ 7.98–8.04 (m, 1H),
7.48–7.57 (m, 4H), 7.19–7.21 (m, 2H), 4.07–4.29 (m,
4H), 2.67 (q, J = 7.5 Hz, 2H), 1.33 (t, J = 7.2 Hz,
6H), 1.24 (dt, J1 = 7.5 Hz, J2 = 1.2 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): δ 145.34, 134.40 (d, J = 6.6
Hz), 134.03 (d, J = 20.3 Hz), 132.09 (d, J = 2.8
Hz), 131.81 (d, J = 185.2 Hz), 131.59 (d, J = 5.5
Hz), 131.51, 127.98, 124.41 (d, J = 6.2 Hz), 119.90,
95.84, 86.32, 62.52 (d, J = 5.7 Hz), 28.84, 16.31 (d,
J = 6.8 Hz), 15.25; 31P NMR (121 MHz, CDCl3): δ
15.13; IR (film, cm−1): 2968, 2218, 1512, 1461, 1390,
1253, 1152, 1025, 970; MS (EI): m/z: 376(M+, 100),
347 (16), 319 (12), 287 (38), 239 (7), 189 (23), 105
(5-Chloro-2-trimethylsilanylethynyl-phenyl)-phos-
phonic Acid Diethyl Ester 3j. Oil. Yield: 73%. 1H
NMR (300 MHz, CDCl3): δ 7.94–8.00 (m, 1H), 7.41–
7.53 (m, 2H), 4.04–4.26 (m, 4H), 1.35 (dt, J1 = 7.2
Hz, J2 = 1.5 Hz, 6H), 0.26 (d, J = 2.4 Hz, 9H); 31P
NMR (121 MHz, CDCl3): δ 14.72; MS (EI): m/z: 344
(M+, 10), 329 (40), 301 (6), 273 (100), 257 (13), 205
(5), 195 (16), 105 (1), 75 (25); IR (film, cm−1): 2981,
2162, 1459, 1391, 1251, 1150, 1105, 1026, 973; Anal.

534 Peng, Zhang, and Ding
Calcd for C15H22ClO3P: C, 52.24; H, 6.43. Found: C,
52.56; H, 6.69.
6.96–7.00 (m, 1H), 4.48 (s, 2H), 4.13–4.21 (m, 4H),
3.84 (s, 3H), 3.50 (br s, 1H), 1.34 (t, J = 7.2 Hz, 6H);
13C NMR (75.4 MHz, CDCl3): δ 158.62 (d, J = 17.9
Hz), 134.97 (d, J = 15.1 Hz), 131.12 (d, J = 187.3
Hz), 118.57 (d, J = 10.0 Hz), 117.60 (d, J = 2.8 Hz),
117.30 (d, J = 6.7 Hz), 91.76, 82.81 (d, J = 6.1 Hz),
62.54 (d, J = 5.6 Hz), 55.34, 29.49, 16.21 (d, J = 6.1
Hz); 31P NMR (121 MHz, CDCl3): δ 16.47; MS (EI):
m/z: 298 (M+, 37), 269 (47), 241 (79), 213 (100),
195 (39), 161 (30), 77 (5); IR (film, cm−1): 3404,
2985, 2239, 1598, 1479, 1394, 1296, 1146, 1026, 971;
HRMS (EI): Calcd for C14H19O5P (M+): 298.09786.
Found: 298.09743.
(5-Chloro-2-cyclopropylethynyl-phenyl)-phos-
phonic Acid Diethyl Ester 3k. Oil. Yield: 79%.
1H NMR (300 MHz, CDCl3): δ 7.88–7.95 (m, 1H),
7.39–7.41 (m, 2H), 4.04–4.25 (m, 4H), 1.43–1.52
(m, 1H), 1.36 (dt, J1 = 7.2 Hz, J2 = 2.1 Hz, 6H),
0.86–0.92 (m, 4H); 31P NMR (121 MHz, CDCl3): δ
17.95; MS (EI): m/z: 312 (M+, 38), 283 (36), 255
(100), 237 (10), 220 (34), 175 (21), 139 (46), 99 (12),
75 (11); IR (film, cm−1): 2983, 2234, 1464, 1383,
1249, 1152, 1025, 953; Anal. Calcd for C15H18ClO3P:
C, 57.60; H, 5.81. Found: C, 57.77; H, 6.05.
REFERENCES
[2-(4-Ethyl-phenylethynyl)-5-nitro-phenyl]-phos-
phonic Acid Diethyl Ester 3l. A yellow solid, mp:
[1] (a) Lam, J.; Breteler, H.; Arnason, T.; Hansen, L.
(Eds.). Chemistry and Biology of Naturally-Occurring
Acetylenes and Related Compounds; Elsevier:
Amsterdam, 1988; (b) Banthorpe, D. V. In Chemistry
of Triple-Bonded Functional Groups; Patai, S. (Ed.);
Wiley: New York, 1994; p. 689.
[2] Stang, P. J.; Diederich, F. (Eds.). Modern Acetylene
Chemistry; VCH: Weinheim, Germany, 1995.
[3] Negishi, E.-i.; Anastasia, L. Chem Rev 2003, 103,
1979.
1
72–74◦C. Yield: 78%. H NMR (300 MHz, CDCl3): δ
8.81–8.87 (m, 1H), 8.33–8.37 (m, 1H), 7.75–7.80 (m,
1H), 7.53–7.57 (m, 2H), 7.23–7.27 (m, 2H), 4.16–4.32
(m, 4H), 2.71 (q, J = 7.5 Hz, 2H), 1.36 (t, J = 7.2 Hz,
6H), 1.27 (t, J = 7.2 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3): δ 146.36, 145.89 (d, J = 17.4 Hz), 133.96 (d,
J = 12.8 Hz), 133.34, 132.57 (d, J = 6.7 Hz), 131.83
(d, J = 1.6 Hz), 129.47 (d, J = 204.2 Hz), 129.08 (d,
J = 11.6 Hz), 126.48 (d, J = 1.9 Hz), 119.05, 100.85,
86.24, 62.85 (d, J = 6.1 Hz), 28.79, 16.30 (d, J =
6.3 Hz), 15.16; 31P NMR (121 MHz, CDCl3): δ 16.11;
MS (EI): m/z: 387 (M+, 100), 358 (25), 330 (20), 300
(34), 221 (10), 189 (50), 143 (35), 105 (8); IR (KBr,
cm−1): 2968, 2211, 1597, 1515, 1385, 1343, 1255,
1145, 1020, 975; HRMS (EI): Calcd for C20H22NO5P
(M+ + 1): 388.13280. Found: 388.13084.
[4] (a) Peng, A.-Y.; Ding, Y.-X. J Am Chem Soc 2003, 125,
15006; (b) Peng, A.-Y.; Ding, Y.-X. Org Lett 2004, 6,
1119.
[5] Sonogashira, K. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-i. (Ed.);
Wiley-Interscience: New York, 2002; p. 493.
[6] (a) Bunnett, J. F.; Mitchell, E.; Galli, C. Tetrahe-
dron 1985, 41, 4119; (b) Beugelmans, R.; Chbani, M.
Bull Soc Chim Fr 1995, 132, 290; (c) Defacqz, N.;
de Bueger, B.; Touillaux, R.; Cordi, A.; Marchand-
Brynaert, J. Synthesis 1999, 1368.
[7] (a) Scott, W. J.; Pen˜ a, M. R.; Swa¨rd, K.; Stoessel, S. J.;
Stille, J. K. J Org Chem 1985, 50, 2302; (b) Cacchi, S.
Synthesis 1986, 320.
[8] (a) Chen, Q.-Y.; Yang, Z.-Y. Tetrahedron Lett 1986,
27, 1171; (b) Chen, Q.-Y.; Li, Z.-T. J Chem Soc, Perkin
Trans 1 1992, 2931.
[9] (a) Kenner, W. J Chem Soc 1955, 522; (b) Dhawan, B.;
Redmore, D. J Org Chem 1984, 49, 4018.
[10] Scott, W. J.; Pen˜a, M. R.; Swa¨rd, K.; Stoessel, S. J.;
Stille, J. K. J Org Chem 1985, 50, 2302.
[11] (a) Cacchi, S.; Ciattini, P. G.; Ortar, G. Tetrahedron
Lett 1987, 28, 3039; (b) Tilley, J. W.; Zawoiski, S.
J Org Chem 1988, 53, 386; (c) Arcadi, A.; Cacchi, S.;
Marinelli, F. Tetrahedron Lett 1989, 30, 2581.
[12] (a) Chen, Q.-Y.; He, Y.-B. Tetrahedron Lett 1987,
28, 2387; (b) Cook, G. K.; Hornback, W. J.;
McDonald, J. H.; Munroe, J. E. J Org Chem 1989,
54, 5828.
(5-Methoxy-2-phenylethynyl-phenyl)-phosphonic
Acid Diethyl Ester 3m. Oil. Yield: 79%. 1H NMR
(300 MHz, CDCl3): δ 7.53–7.60 (m, 4H), 7.33–7.35
(m, 3H), 7.01–7.05 (m, 1H), 4.09–4.26 (m, 4H), 3.86
(d. J = 1.5 Hz, 3H), 1.32 (t, J = 6.9 Hz, 6H); 31P
NMR (121 MHz, CDCl3): δ 20.846; MS (EI): m/z:
344 (M+, 100), 316 (11), 270 (15), 209 (5), 193 (4),
163 (14), 105 (6), 77 (3); IR (film, cm−1): 2982, 1593,
1497, 1392, 1292, 1236, 1163, 1027, 971; Anal. Calcd
for C19H21O4P: C, 66.26; H, 6.16. Found: C, 66.20; H,
6.22.
[5-Methoxy-2-(3-hydroxy-prop-1-ynyl)-phenyl]-
phosphonic Acid Diethyl Ester 3n. Oil. Yield: 72%.
1H NMR (300 MHz, CDCl3): δ 7.38–7.47 (m, 2H),