Synthesis of 5-(trifluoromethyl)-2,5-dihydro-1,2λ5- oxaphospholes by a one-pot three-component reaction

Article abstract of DOI:10.1055/s-0032-1316799

A series of trifluoromethyl-substituted 1,2λ⁵- oxaphospholes were prepared in yields of up to 95% by a one-pot three-component reaction under mild conditions. The zwitterionic intermediate generated by attack of triphenylphosphine on an alkyl propiolate reacts with an aryl or styryl trifluoromethyl ketone to form the 1,2λ⁵-oxaphosphole ring. All the new products were characterized by IR, NMR, and mass spectroscopy and the structure of one of them, ethyl 2,2,2-triphenyl-5-[(E)-2-phenylvinyl]-5- (trifluoromethyl)-2,5-dihydro-1,2λ⁵-oxaphosphole-4- carboxylate, was confirmed by X-ray single-crystal diffraction analysis. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0032-1316799

PAPER
▌3315
5
paper
Synthesis of 5-(Trifluoromethyl)-2,5-dihydro-1,2λ -oxaphospholes by a
One-Pot Three-Component Reaction
5-(Trifluoromethyl)-2,5-dihydro-1,2λ5-oxaphospholes
Hua-Fang Fan,a,b Xiao-Wei Wang,b Jing-Wei Zhao,b Xin-Jin Li,b Jin-Ming Gao,*a Shi-Zheng Zhu*b
a
Shaanxi Engineering Center of Bioresource Chemistry and Sustainable Utilization, College of Science, Northwest A & F University, Yangling,
Shaanxi 712100, P. R. of China
b
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road,
Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: zhusz@mail.sioc.ac.cn
Received: 10.07.2012; Accepted after revision: 18.09.2012
pholes.11 As part of our current studies on the develop-
ment of new routes to fluorinated heterocycles,12 we now
report a simple synthesis of 5-(trifluoromethyl)-2,5-di-
hydro-1,2λ5-oxaphospholes in good yields through the
Abstract: A series of trifluoromethyl-substituted 1,2λ5-oxaphos-
pholes were prepared in yields of up to 95% by a one-pot three-
component reaction under mild conditions. The zwitterionic inter-
mediate generated by attack of triphenylphosphine on an alkyl pro-
piolate reacts with an aryl or styryl trifluoromethyl ketone to form multicomponent one-pot reaction of triphenylphosphine,
the 1,2λ5-oxaphosphole ring. All the new products were character-
ized by IR, NMR, and mass spectroscopy and the structure of one
an alkyl propiolate, and an aryl or styryl trifluoromethyl
ketone.
of them, ethyl 2,2,2-triphenyl-5-[(E)-2-phenylvinyl]-5-(trifluoro-
methyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate, was con-
To test the reaction conditions, we selected the reaction of
ethyl propiolate (2a) with (3E)-1,1,1-trifluoro-4-phenyl-
but-3-en-2-one (3a), and triphenylphosphine as a model
reaction. When the reaction mixture was stirred in toluene
at room temperature, thin-layer chromatography showed
that the reaction was complete within 24 hours. The de-
sired product 5a was obtained in 71% yield (Table 1, entry
1). When the reaction was carried out at 100 °C, it was
complete within three hours, but the yield was slightly
lower (entry 2). A slightly lower yield was also obtained
in xylene (entry 8) and similar yields were obtained in di-
ethyl ether and in tetrahydrofuran (entries 9 and 10, re-
spectively). Polar solvents such as acetonitrile or ethanol
gave very low yields, even with longer reaction times (en-
tries 11 and 12, respectively). Fortunately, when ethyl
acetate was used as the solvent, the yield improved to 77%
(entry 7). We therefore, conducted the remainder of the
reactions in ethyl acetate at room temperature.
firmed by X-ray single-crystal diffraction analysis.
Key words: heterocycles, phosphorus, fluorine, oxaphospholes, al-
kynes, ketones
Organophosphorus compounds are widely used in organic
synthesis.1 Recently, a great deal of attention has been
paid to organophosphorus compounds because of their
potential biological, industrial, and synthetic applications,
and many novel methods have been developed for the
synthesis of such compounds.2–4
The introduction of fluoro or fluoroalkyl groups into an
organic molecule can profoundly affect its physical,
chemical, and biological properties, and fluorine-contain-
ing heterocycles are now widely used in medicine and ag-
riculture.5 One of the most important strategies for the
synthesis of fluorine-containing heterocycles involves the
use of multicomponent reactions, which have long been
recognized as effective, economic, convenient, and envi-
ronmental benign.6 Triphenylphosphine has been exten-
sively studied as a nucleophilic species. As early as 1961,
Tebby and co-workers found that the addition of triphe-
nylphosphine to various activated alkynes, such as 1,4-di-
The product 5a was fully characterized by means of NMR
(1H, 13C, 19F, and 31P), IR, and mass spectroscopy, and its
configuration was confirmed by X-ray crystallographic
analysis (Figure 1).
phenylbut-2-yne-1,4-dione,
but-2-ynedinitrile,
or
dimethyl acetylenedicarboxylate, gave zwitterionic inter-
mediates.7,8 Recently, groups led by Esmaeili9 and by
Yavari10 have reported that the reactions of acetylenic
compound with triphenylphosphine in the presence of ke-
tones give the corresponding 2,5-dihydro-1,2-oxaphos-
pholes. However, to the best of our knowledge, there are
few reports of preparations of fluorinated oxaphos-
SYNTHESIS 2012, 44, 3315–3320
Advanced online publication: 02.10.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1316799; Art ID: SS-2012-H0575-OP
© Georg Thieme Verlag Stuttgart · New York
Figure 1 The structure of compound 5a

3316
H.-F. Fan et al.
PAPER
Table 1 Screening of Reaction Conditions for the Three-Component Reaction
CF3
O
Ph3P
O
Ph
Ph3P
+
+
COOEt
Ph
CF3
COOEt
1
2a
3a
5a
Entrya
Solvent
Temp (°C)
Time (h)
Yieldb (%)
1
2
toluene
toluene
toluene
toluene
CH2Cl2
CHCl3
EtOAc
xylene
THF
25
100
25
25
25
25
25
25
25
25
25
25
24
3
71
69
66
60
58
60
77
69
70
70
30
47
3c
4d
5
24
24
24
24
10
24
10
16
40
30
6
7
8
9
10
11
12
Et2O
EtOH
MeCN
a Unless otherwise noted, the reaction was carried out with 1 (0.3 mmol), 2a (0.25 mmol), and 3a (0.2 mmol) in the appropriate solvent (1.0 mL).
b Isolated yield.
c The reaction was carried out with 1 (0.25 mmol), 2a (0.25 mmol), and 3a (0.2 mmol).
d The reaction was carried out with 1 (0.2 mmol), 2a (0.2 mmol), and 3a (0.2 mmol).
Having determined the optimized condition, we explored A possible reaction pathway is shown in Scheme 1. Ini-
the scope of the reaction, and some of the results that we tially, a 1,3-dipolar intermediate A is formed by the reac-
obtained are listed in Table 2. Generally, when the reac- tion of triphenylphosphine and the propiolate.13
tion was carried out with 1, 2a, and a styrenyl ketone 3a– Subsequently, the carbonyl carbon of the trifluoromethyl
h, the corresponding product 5a–h was obtained in about ketone 3 or 4 is attacked by the intermediate A to form in-
80% yield, irrespective of the electronic nature of the sub- termediate A′ which then cyclizes to form the desired
stituents on the benzene ring (Table 2, entries 1–7). We product 5 or 6.
then examined the reactions of various aryl trifluorometh-
yl ketones 4a–e under similar reaction conditions. Both
electron-donating and electron-withdrawing substituents
on the benzene rings were tolerated and the desired prod-
In summary, we have developed a simple method for syn-
thesizing a series of 5-(trifluoromethyl)-2,5-dihydro-
1,2λ5-oxaphospholes through the three-component reac-
tion of triphenylphosphine, an alkyl propiolate, and an
aryl or styryl trifluoromethyl ketone. The desired products
ucts 6a–f were obtained in high yields (entries 9–14).
When other acetylenic compounds such as ethyl 3-phen-
were obtained in up to 95% yields under mild conditions.
ylpropiolate or ethynylbenzene were investigated, no cor-
Further research on the reaction and its applications are in
responding reaction was observed and the starting
progress at our laboratories.
materials were recovered.
O
COOR1
R2
CF3
Ph3P
COOR1
CO2R1
5 or 6
R2
Ph3P
Ph3P
3 or 4
O
CF3
2
A
A'
Scheme 1 Possible mechanism for the formation of the products
Synthesis 2012, 44, 3315–3320
© Georg Thieme Verlag Stuttgart · New York

PAPER
5-(Trifluoromethyl)-2,5-dihydro-1,2λ5-oxaphospholes
3317
Table 2 Synthesis of a Series of Dihydro-1,2λ5-oxaphospholes
CF3
O
Ph3P
O
R2
R2
CF3
COOR1
3a–h
5a–h
EtOAc
r.t
COOR1
Ph3P
+
+
or
or
CF3
O
Ph3P
2a,b
O
1
Ar
COOR1
6a–f
Ar
CF3
4a–e
Entrya
R1
R2 or R3
Time (h)
Product
Yield b (%)
1
2
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Me (2b)
Ph (3a)
20
20
24
24
30
30
30
20
8
5a
5b
5c
5d
5e
5f
77
81
79
78
82
79
79
71
92
90
89
92
93
95
4-ClC6H4 (3b)
4-BrC6H4 (3c)
4-FC6H4 (3d)
3
4
5
4-MeOC6H4 (3e)
2-MeOC6H4 (3f)
3-MeOC6H4 (3g)
2-thienyl (3h)
Ph (4a)
6
7
5g
5h
6a
6b
6c
6d
6e
6f
8
9
10
11
12
13
14
4-ClC6H4 (4b)
4-BrC6H4 (4c)
4-FC6H4 (4d)
4-Tol (4e)
8
8
8
8
Ph (4f)
8
a The reaction was carried out with 1 (0.3 mmol), 2 (0.25 mmol), and 3 (0.2 mmol) or 4 (0.2 mmol) in EtOAc (1.0 mL) at room temperature.
b Isolated yield.
Ethyl 2,2,2-Triphenyl-5-[(E)-2-phenylvinyl]-5-(trifluorometh-
yl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate (5a)
Yield: 86.2 mg (77%); white solid; mp 161–162 °C. X-ray crystal
data are summarized in Table 3.
Purifications were performed by flash chromatography with EtOAc
and PE on silica gel. Melting points were measured on a Temp-Melt
apparatus and are uncorrected. IR spectra were recorded on a
1
Perkin-Elmer 983 spectrophotometer. H and 19F NMR spectra
IR (CH2Cl2, film): 1728, 1433, 1258, 1082, 972, 748 cm–1.
were recorded in CDCl3 on a Bruker AM-300 instrument with TMS
or CFCl3 (upfield negative) as the internal and external standards,
respectively. 13C NMR spectra were recorded in CDCl3 with a Bruker
AMX spectrometer at 100 MHz, and chemical shifts are reported in
ppm relative to TMS. High-resolution mass spectra were obtained
with a Bruker Apex III 7.0 TESLA FTMS spectrometer. The single-
crystal X-ray structure analysis was performed on a Bruker P4 in-
strument.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.39 (m, 6 H), 7.27–7.25 (m,
9 H), 7.20–7.16 (m, 3 H), 7.06–7.01 (m, 3 H), 6.66 (d, J = 16 Hz, 1
H), 5.85 (d, J = 16 Hz, 1 H), 4.36 (q, J = 4.8 Hz, 2 H), 1.39 (t,
J = 8.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, 3JCP = 28 Hz), 155.8 (d,
1
1
2JCP = 13 Hz), 143.9 (d, JCP = 106 Hz), 135.7 (d, JCP = 127 Hz),
133.6, 131.2 (d, 2JCP = 9 Hz), 128.6 (d, 3JCP = 3 Hz), 128.2, 128.0,
127.8, 127.6, 126.9, 124.3 (q, J = 289 Hz), 122.7, 81.3 (q, J = 29
Hz), 62.1, 14.1.
Alkyl 2,2,2-Triphenyl-5-(trifluoromethyl)-2,5-dihydro-1,2λ5-
oxaphosphole-4-carboxylates 5 and 6; General Procedure
Ph3P (0.3 mmol) was added to a soln of propiolate 2 (0.25 mmol)
and styryl ketone 3 or aryl ketone 4 (0.2 mmol) in EtOAc (1.0 mL)
at r.t. The mixture was stirred until the reaction was complete
(TLC), then concentrated under reduced pressure. The resulting
crude product was purified directly by column chromatography [sil-
ica gel, hexanes–EtOAc (30:1 to 20:1)].
19F NMR (282 MHz, CDCl3): δ = –74.4 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –49.3 (s).
MS (ESI): m/z = 561 [M + H]+.
HRMS: m/z calcd for C33H29F3O3P: 561.1806; found: 561.1801.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3315–3320

3318
H.-F. Fan et al.
PAPER
Table 3 X-ray Data for Oxaphosphole 5a
Empirical formula
C33H28F3O3P
Formula weight
560.52
Temperature
293(2) K
Wavelength
0.71073 Å
Crystal system, space group
Unit cell dimensions
triclinic, P1
a = 9.5067(6) Å, α = 97.1890(10)°
b = 10.0271(6) Å, β = 91.5000(10)°
c = 15.6189(10) Å, γ = 107.4710(10)°
1405.82(15) Å3
Volume
Z, Calculated density
Absorption coefficient
F(000)
2, 1.324 Mg/m3
0.151 mm–1
584
Crystal size
0.450 × 0.387 × 0.301 mm
2.15–25.50°
θ range for data collection
Limiting indices
–11 ≤ h ≤ 11, –11 ≤ k ≤ 12, –18 ≤ l ≤ 15
7376/5136 [R(int) = 0.0238]
98.5%
Reflections collected/unique
Completeness to θ = 25.50°
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
empirical
1.0000 and 0.8172
full-matrix least-squares on F2
5136/0/363
1.037
R1 = 0.0416, wR2 = 0.1125
R1 = 0.0450, wR2 = 0.1159
0.037(3)
Extinction coefficient
Largest diff. peak and hole
0.372 and –0.268 e·Å–3
Ethyl 5-[(E)-2-(4-Chlorophenyl)vinyl]-2,2,2-triphenyl-5-(tri-
fluoromethyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate
(5b)
HRMS: m/z calcd for C33H28ClF3O3P: 595.1417; found: 595.1411.
Ethyl 5-[(E)-2-(4-Bromophenyl)vinyl]-2,2,2-triphenyl-5-(tri-
fluoromethyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate
(5c)
Yield: 100.8 mg (79%); white solid; mp 149–150 °C.
IR (CH2Cl2, film): 1731, 1438, 1260, 1072, 980, 738 cm–1.
Yield: 96.2 mg (81%); white solid; mp 167–168 °C.
IR (CH2Cl2, film): 1724, 1433, 1265, 1082, 969, 739 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.43–7.37 (m, 6 H), 7.28–7.27 (m,
10 H), 7.17–7.14 (m, 2 H), 6.95–6.92 (m, 2 H), 6.65 (d, J = 15 Hz,
1 H), 5.85 (d, J = 15 Hz, 1 H), 4.36 (m, J = 6.9 Hz, 2 H), 1.39 (t,
J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, J = 28 Hz), 155.7 (d,
J = 13 Hz), 143.3 (d, J = 106 Hz), 135.7 (d, J = 128 Hz), 134.9,
133.3, 132.4, 131.2 (d, J = 9 Hz), 128.6 (d, J = 3 Hz), 128.4, 128.1,
127.9 (d, J = 12 Hz), 124.7 (q, J = 288 Hz), 123.4, 81.3 (q, J = 29
Hz), 62.1, 14.1.
19F NMR (282 MHz, CDCl3): δ = –75.1 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –46.4 (s).
MS (ESI): m/z = 595 [M + H]+.
1H NMR (300 MHz, CDCl3): δ = 7.43–7.38 (m, 6 H), 7.32–7.24 (m,
11 H), 7.10 (d, J = 40 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 2 H), 6.65 (d,
J = 15 Hz, 1 H), 5.85 (d, J = 16 Hz, 1 H), 4.36 (m, J = 3.6 Hz, 2 H),
1.38 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, J = 28 Hz), 155.6 (d,
J = 13 Hz), 143.3 (d, J = 106 Hz), 135.7 (d, J = 128 Hz), 135.4,
132.5, 131.2 (d, J = 9 Hz), 128.6 (d, J = 3 Hz), 128.4, 128.0, 127.9,
124.2 (q, J = 288 Hz), 123.6, 121.5, 81.3 (q, J = 29 Hz), 62.1, 14.1.
19F NMR (282 MHz, CDCl3): δ = –75.1 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –48.3 (s).
MS (ESI): m/z = 641 [M + H]+.
Synthesis 2012, 44, 3315–3320
© Georg Thieme Verlag Stuttgart · New York

PAPER
5-(Trifluoromethyl)-2,5-dihydro-1,2λ5-oxaphospholes
3319
HRMS: m/z calcd for C33H28BrF3O3P: 639.0912; found: 639.0906.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.38 (m, 6 H), 7.27–7.23 (m,
9 H), 7.18–7.05 (m, 2 H), 6.73–6.64 (m, 3 H), 6.53 (s, 1 H), 5.80 (d,
J = 15 Hz, 1 H), 4.36 (m, J = 6.9 Hz, 2 H), 3.76 (s, 3 H), 1.39 (t,
J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, J = 28 Hz), 159.5, 155.8
(d, J = 14 Hz), 143.5 (d, J = 106 Hz), 137.9, 135.9 (d, J = 128 Hz),
133.5, 131.2 (d, J = 9 Hz), 129.1, 128.6 (d, J = 3 Hz), 127.9 (d,
J = 13 Hz), 124.3 (q, J = 288 Hz), 123.1, 119.5, 113.4, 112.3, 81.3
(q, J = 29 Hz), 62.0, 55.2, 14.1.
19F NMR (282 MHz, CDCl3): δ = –75.0 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.3 (s).
MS (ESI): m/z = 591 [M + H]+.
Ethyl 5-[(E)-2-(4-Fluorophenyl)vinyl]-2,2,2-triphenyl-5-(tri-
fluoromethyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate
(5d)
Yield: 90.2 mg (78%); white solid; mp 165–166 °C.
IR (CH2Cl2, film): 1724, 1433, 1286, 1082, 970, 741 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.43–7.37 (m, 6 H), 7.28–7.27 (m,
10 H), 7.00–6.85 (m, 4 H), 6.59 (d, J = 15 Hz, 1 H), 5.78 (d, J = 15
Hz, 1 H), 4.36 (m, J = 7.2 Hz, 2 H), 1.39 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, J = 29 Hz), 162.8 (d,
J = 245 Hz), 155.8 (d, J = 13 Hz), 143.3 (d, J = 106 Hz), 135.8 (d,
J = 128 Hz), 132.6 (d, J = 3 Hz), 132.4, 131.2 (d, J = 9 Hz), 128.6
(d, J = 3 Hz), 128.4 (d, J = 8 Hz), 128.0, 127.8, 124.2 (q, J = 288
Hz), 115.1 (d, J = 22 Hz), 81.3 (q, J = 29 Hz), 62.1, 14.1.
HRMS: m/z calcd for C34H31F3O4P: 591.1912; found: 591.1907.
19F NMR (282 MHz, CDCl3): δ = –75.1 (s, 3 F), –114.8 (s, 1 F).
31P NMR (75 MHz, CDCl3): δ = –51.5 (s).
MS (ESI): m/z = 579 [M + H]+.
Ethyl 2,2,2-Triphenyl-5-[(E)-2-(2-thienyl)vinyl]-5-(trifluoro-
methyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate (5h)
Yield: 80.4 mg (71%); white solid; mp 161–162 °C.
IR (CH2Cl2, film): 1727, 1436, 1259, 1080, 963, 739 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.45–7.37 (m, 7 H), 7.28–7.23 (m,
9 H), 7.08–7.04 (m, 1 H), 6.85–6.82 (m, 1 H), 6.53–6.52 (m, 1 H),
6.47 (d, J = 15 Hz, 1 H), 5.87 (d, J = 15 Hz, 1 H), 4.36 (m, J = 7.2
Hz, 2 H), 1.39 (t, J = 7.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, J = 28 Hz), 155.8 (d,
J = 13 Hz), 142.3 (d, J = 106 Hz), 141.6, 135.8 (d, J = 129 Hz),
131.2 (d, J = 9 Hz), 128.6 (d, J = 3 Hz), 128.0, 127.1, 126.8, 126.3,
124.6, 123.9 (q, J = 288 Hz), 122.2, 81.1 (q, J = 29 Hz), 62.1, 14.1.
HRMS: m/z calcd for C33H28F4O3P: 579.1712; found: 579.1707.
Ethyl 5-[(E)-2-(4-Methoxyphenyl)vinyl]-2,2,2-triphenyl-5-(tri-
fluoromethyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate
(5e)
Yield: 96.8 mg (82%); white solid; mp 114–115 °C.
IR (CH2Cl2, film): 1731, 1437, 1251, 1081, 971, 741 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.45–7.37 (m, 6 H), 7.27–7.23 (m,
10 H), 6.97 (d, J = 8.7 Hz, 2 H), 6.73 (d, J = 8.7 Hz, 2 H), 6.52 (d,
J = 15 Hz, 1 H), 5.78 (d, J = 15 Hz, 1 H), 4.36 (m, J = 6.9 Hz, 2 H),
3.75 (s, 3 H), 1.38 (t, J = 7.2 Hz, 3 H).
19F NMR (282 MHz, CDCl3): δ = –75.1 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –50.3 (s).
13C NMR (100 MHz, CDCl3): δ = 163.4 (d, J = 29 Hz), 159.3, 156.0
(d, J = 13 Hz), 143.5 (d, J = 105 Hz), 135.7 (d, J = 128 Hz), 133.0,
131.2 (d, J = 8 Hz), 129.3, 128.6, 128.1, 127.9 (d, J = 12 Hz), 124.3
(q, J = 287 Hz), 120.3, 113.6, 81.3 (q, J = 29 Hz), 62.0, 55.2, 14.2.
19F NMR (282 MHz, CDCl3): δ = –75.1 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –51.1 (s).
MS (ESI): m/z = 591 [M + H]+.
MS (ESI): m/z = 567 [M + H]+.
HRMS: m/z calcd for C31H27F3O3PS: 567.1371; found: 567.1365.
Ethyl 2,2,2,5-Tetraphenyl-5-(trifluoromethyl)-2,5-dihydro-
1,2λ5-oxaphosphole-4-carboxylate (6a)
Yield: 98.3 mg (92%); white solid; mp 176–177 °C.
IR (CH2Cl2, film): 1731, 1438, 1259, 1072, 980, 738 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.35–7.31 (m, 7 H), 7.23–7.10 (m,
12 H), 7.04–6.99 (m, 2 H), 4.41 (m, J = 6.9 Hz, 2 H), 1.39 (t, J = 6.9
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.3 (d, J = 28 Hz), 156.9 (d,
J = 12 Hz), 143.5 (d, J = 106 Hz), 138.5 (d, J = 127 Hz), 136.9,
131.3 (d, J = 9 Hz), 128.4 (d, J = 3 Hz), 127.8, 127.7, 127.6, 127.4,
122.0 (q, J = 286 Hz), 82.0 (q, J = 30 Hz), 62.2, 14.1.
19F NMR (282 MHz, CDCl3): δ = –72.4 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.8 (s).
MS (ESI): m/z = 535 [M + H]+.
HRMS: m/z calcd for C34H31F3O4P: 591.1912; found: 591.1907.
Ethyl 5-[(E)-2-(2-Methoxyphenyl)vinyl]-2,2,2-triphenyl-5-(tri-
fluoromethyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate
(5f)
Yield: 93.2 mg (79%); white solid; mp 145–146 °C.
IR (CH2Cl2, film): 1729, 1435, 1276, 1080, 973, 741 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.44–7.38 (m, 6 H), 7.27–7.23 (m,
10 H), 7.17–7.08 (m, 2 H), 6.82–6.74 (m, 3 H), 6.33 (d, J = 15 Hz,
1 H), 4.36 (m, J = 6.9 Hz, 2 H), 3.73 (s, 3 H), 1.38 (t, J = 7.2 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 163.6 (d, J = 29 Hz), 157.1, 156.1
(d, J = 14 Hz), 143.7 (d, J = 106 Hz), 136.1 (d, J = 128 Hz), 131.2
(d, J = 9 Hz), 129.2, 128.7, 128.3 (d, J = 3 Hz), 128.2, 127.8 (d,
J = 13 Hz), 125.5, 124.4 (q, J = 288 Hz), 123.7, 120.2, 110.7, 81.5
(q, J = 29 Hz), 62.0, 55.1, 14.1.
19F NMR (282 MHz, CDCl3): δ = –75.1 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.5 (s).
MS (ESI): m/z = 591 [M + H]+.
HRMS: m/z calcd for C31H27F3O3P: 535.1650; found: 535.1644.
Ethyl 5-(4-Bromophenyl)-2,2,2-triphenyl-5-(trifluoromethyl)-
2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate (6b)
Yield: 102.3 mg (90%); white solid; mp 194–195 °C.
IR (CH2Cl2, film): 1731, 1436, 1260, 1101, 930, 703 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.33–7.17 (m, 16 H), 7.09–7.00
(m, 4 H), 4.38 (m, J = 7.2 Hz, 2 H), 1.35 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.2 (d, J = 28 Hz), 156.5 (d,
J = 12 Hz), 143.0 (d, J = 106 Hz), 138.5 (d, J = 127 Hz), 136.1,
131.3 (d, J = 9 Hz), 130.4, 129.6, 128.5 (d, J = 3 Hz), 127.8 (d,
J = 13 Hz), 124.2 (q, J = 288 Hz), 122.0, 81.6 (q, J = 30 Hz), 62.3,
14.1.
HRMS: m/z calcd for C34H31F3O4P: 591.1912; found: 591.1907.
Ethyl 5-[(E)-2-(3-Methoxyphenyl)vinyl]-2,2,2-triphenyl-5-(tri-
fluoromethyl)-2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate
(5g)
Yield: 93.2 mg (79%); white solid; mp 146–147 °C.
IR (CH2Cl2, film): 1732, 1436, 1248, 1083, 963, 721 cm–1.
19F NMR (282 MHz, CDCl3): δ = –72.2 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.1 (s).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3315–3320

3320
H.-F. Fan et al.
PAPER
MS (ESI): m/z = 613 [M + H]+.
13C NMR (100 MHz, CDCl3): δ = 164.5 (d, J = 28 Hz), 156.9 (d,
J = 13 Hz), 143.3 (d, J = 106 Hz), 139.2 (d, J = 127 Hz), 136.8,
131.3 (d, J = 10 Hz), 128.4, 127.8, 127.7, 127.6, 127.5 (d, J = 15
Hz), 124.4 (q, J = 287 Hz), 82.0 (q, J = 30 Hz), 52.9.
19F NMR (282 MHz, CDCl3): δ = –71.7 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.7 (s).
MS (ESI): m/z = 521 [M + H]+.
HRMS: m/z calcd for C31H26BrF3O3P: 613.0755; found: 613.0750.
Ethyl 5-(4-Fluorophenyl)-2,2,2-triphenyl-5-(trifluoromethyl)-
2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate (6c)
Yield: 108.9 mg (89%); white solid; mp 174–175 °C.
IR (CH2Cl2, film): 1731, 1438, 1260, 1081, 930, 744 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.33–7.10 (m, 18 H), 6.64 (t,
J = 8.7 Hz, 2 H), 4.38 (m, J = 7.5 Hz, 2 H), 1.37 (t, J = 7.2 Hz, 3 H).
HRMS: m/z calcd for C30H25F3O3P: 521.1493; found: 521.1488.
13C NMR (100 MHz, CDCl3): δ = 164.3 (d, J = 29 Hz), 161.7 (d,
J = 245 Hz), 156.7 (d, J = 13 Hz), 143.1 (d, J = 106 Hz), 138.6 (d,
J = 126 Hz), 132.8, 131.2 (d, J = 9 Hz), 129.7 (d, J = 8 Hz), 128.5
(d, J = 3 Hz), 127.7 (d, J = 12 Hz), 124.2 (q, J = 286 Hz), 114.1 (d,
J = 21 Hz), 81.5 (q, J = 30 Hz), 62.3, 14.1.
Acknowledgment
The authors thank the National Natural Science Foundation of Chi-
na (NNSFC) (No. 21032006 and No. 21102163).
19F NMR (282 MHz, CDCl3): δ = –73.0 (s, 3 F), –115.3 (s, 1 F).
31P NMR (75 MHz, CDCl3): δ = –52.5 (s).
MS (ESI): m/z = 553 [M + H]+.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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HRMS: m/z calcd for C31H26F4O3P: 553.1556; found: 553.1550.
References
Ethyl 5-(4-Chlorophenyl)-2,2,2-triphenyl-5-(trifluoromethyl)-
2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate (6d)
Yield: 101.6 mg (92%); white solid; mp 179–180 °C.
(1) Organic Phosphorus Compounds, 2nd ed.; Kosolapoff, G.
M.; Maier, L., Eds.; Wiley-Interscience: New York, 1976.
(2) Hudson, H. R. In The Chemistry of Organophosphorus
Compounds: Primary, Secondary and Tertiary Phosphines,
Polyphosphines, and Heterocyclic Organophosphorus(III)
Compounds; Vol. 1; Hartley, F. R., Ed.; Wiley: New York,
1990, 386.
IR (CH2Cl2, film): 1731, 1436, 1298, 1081, 971, 738 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.36–7.24 (m, 16 H), 7.10 (d,
J = 8.1 Hz, 2 H), 6.94 (d, J = 8.4 Hz, 2 H), 4.39 (m, J = 6.9 Hz, 2
H), 1.37 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.2 (d, J = 28 Hz), 156.6 (d,
J = 12 Hz), 143.0 (d, J = 106 Hz), 138.6 (d, J = 127 Hz), 135.6,
133.7, 131.3 (d, J = 9 Hz), 129.3, 128.5 (d, J = 3 Hz), 127.8, 127.4,
124.2 (q, J = 287 Hz), 81.6 (q, J = 30 Hz), 62.3, 14.1.
19F NMR (282 MHz, CDCl3): δ = –72.9 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.2 (s).
MS (ESI): m/z = 569 [M + H]+.
(3) Synthesis of Carbon–Phosphorus Bonds; Engel, R., Ed.;
CRC Press: Boca Raton, 1988.
(4) Organophosphorus Reagents in Organic Synthesis;
Cadogan, J. I. G., Ed.; Academic Press: New York, 1979.
(5) (a) Filler, R.; Kobayashi, Y. Biomedicinal Aspects of
Fluorine Chemistry; Elsevier Biomedical Press:
Amsterdam, 1982. (b) Organofluorine Chemicals and Their
Industrial Applications; Banks, R. E., Ed.; Ellis Horwood:
Chichester, 1979. (c) Welch, J. T. Tetrahedron 1987, 43,
3123. (d) Organofluorine Compounds in Medicinal
Chemistry and Biomedical Applications; Filler, R.;
Kobayashi, Y.; Yagupolskii, L. M., Eds.; Elsevier:
Amsterdam, 1993.
HRMS: m/z calcd for C31H26ClF3O3P: 569.1260; found: 569.1255.
Ethyl 5-(4-Methylphenyl)-2,2,2-triphenyl-5-(trifluoromethyl)-
2,5-dihydro-1,2λ5-oxaphosphole-4-carboxylate (6e)
Yield: 102.0 mg (93%); white solid; mp 173–174 °C.
IR (CH2Cl2, film): 1731, 1437, 1256, 1099, 931, 702 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.36–7.22 (m, 16 H), 7.03 (d,
J = 8.1 Hz, 2 H), 6.82 (d, J = 7.2 Hz, 2 H), 4.39 (m, J = 6.9 Hz, 2
H), 2.24 (s, 3 H), 1.37 (t, J = 6.9 Hz, 3 H).
(6) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3168.
(7) Johnson, A. W.; Tebby, J. C. J. Chem. Soc. 1961, 2126.
(8) Tebby, J. C.; Wilson, I. F.; Griffiths, D. V. J. Chem. Soc.,
Perkin Trans. 1 1979, 2133.
(9) Esmaeili, A.; Amini, S.; Bodaghi, A. Synlett 2007, 1452.
(10) (a) Yavari, I.; Hossaini, Z.; Alizadeh, A. Monatsh. Chem.
2006, 137, 1083. (b) Yavari, I.; Mohtat, B.; Zare, H.
Mendeleev Commun. 2006, 15, 102. (c) Alizadeh, A.;
Yavari, I. Mendeleev Commun. 2005, 14, 154. (d) Yavari, I.;
Alizadeh, A. Synthesis 2004, 237. (e) Yavari, I.; Alizadeh,
A.; Anary-Abbasinejad, M. Tetrahedron Lett. 2003, 44,
2877. (f) Yavari, I.; Anary-Abbasinejad, M.; Hossaini, Z.
Org. Biomol. Chem. 2003, 1, 560. (g) Yavari, I.; Hossaini,
Z.; Sabbaghan, M.; Ghazanfarpour-Darjani, M. Tetrahedron
2007, 63, 9423.
13C NMR (100 MHz, CDCl3): δ = 164.3 (d, J = 29 Hz), 159.9 (d,
J = 13 Hz), 143.5 (d, J = 106 Hz), 138.1 (d, J = 127 Hz), 137.4,
134.0, 131.3 (d, J = 8 Hz), 128.3 (d, J = 3 Hz), 128.1, 127.7 (d,
J = 13 Hz), 127.5, 124.4 (q, J = 287 Hz), 81.9 (q, J = 30 Hz), 62.1,
21.0, 14.1.
19F NMR (282 MHz, CDCl3): δ = –72.5 (s, 3 F).
31P NMR (75 MHz, CDCl3): δ = –52.4 (s).
MS (ESI): m/z = 549 [M + H]+.
HRMS: m/z calcd for C32H29F3O3P: 549.1806; found: 549.1801.
(11) (a) Ratner, V. G.; Lork, E.; Pashkevich, K. I.; Röschenthaler,
G.-V. J. Fluorine Chem. 2000, 102, 73. (b) Gerus, I. I.;
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Methyl 2,2,2,5-Tetraphenyl-5-(trifluoromethyl)-2,5-dihydro-
1,2λ5-oxaphosphole-4-carboxylate (6f)
Yield: 98.8 mg (95%); white solid; mp 163–164 °C.
IR (CH2Cl2, film): 1736, 1435, 1256, 1081, 943, 745 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.72–7.63 (m, 7 H), 7.59–7.54 (m,
10 H), 7.50–7.45 (m, 3 H), 7.35–7.33 (m, 1 H), 4.27 (s, 3 H).
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Synthesis 2012, 44, 3315–3320
© Georg Thieme Verlag Stuttgart · New York