Iodocyclization of trifluoromethylallenic phosphonates: An efficient approach to trifluoromethylated oxaphospholenes

Article abstract of DOI:10.1016/j.tet.2010.10.040

α-Trifluoromethylallenic phosphonates were prepared by the reaction of diethyl chlorophosphite (DECP) and 4,4,4-trifluorobut-2-yn-1-ols in the presence of Et₃N. The iodocyclization of these fluorine-containing allenic phosphonates was achieved

Full text of DOI:10.1016/j.tet.2010.10.040

Tetrahedron 66 (2010) 9729e9732
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Iodocyclization of trifluoromethylallenic phosphonates: an efficient approach
to trifluoromethylated oxaphospholenes
*
Peng Li, Zhen-Jiang Liu, Jin-Tao Liu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 July 2010
Received in revised form 20 September 2010
Accepted 15 October 2010
Available online 10 November 2010
a
-Trifluoromethylallenic phosphonates were prepared by the reaction of diethyl chlorophosphite (DECP)
and 4,4,4-trifluorobut-2-yn-1-ols in the presence of Et3N. The iodocyclization of these fluorine-con-
taining allenic phosphonates was achieved with iodine under mild conditions to give the corresponding
trifluoromethylated oxaphospholenes in moderate to good yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Iodocyclization
Trifluoromethylallenic phosphonate
Phosphorus heterocycles
1. Introduction
framework would offer effective modification toward the original
properties of the resulted compounds. However, despite such in-
Organophosphorus compounds continue to receive widespread
attention due to the recognition of their potential use as novel
pharmaceutical, agricultural, and chemical agents.1,2 Among them,
a number of phosphorus heterocycles displaying potent biological
activities have emerged. 1,2-Oxaphospholane 2-oxides (_), as a no-
table example, have attracted much attention as sugar surrogates
since analogues with phosphorus atoms replacing the anomeric
carbons could potentially serve as carbohydrate mimics.3
terests, few reports have been found for the construction of these
types of molecules.5 In continuation of our earlier work on fluorine-
containing allenes, and in connection with our ongoing interest in
construction of biologically active fluorine-containing compounds,6
we represent herein a facile synthesis of trifluoromethylated 1,2-
oxaphosphol-3-ene 2-oxide (
P
, R3¼CF3), a divergent intermediate
for various trifluoromethylated oxaphospholanes.
O
P
O
P
2. Results and discussion
OR
R3
R4
OR
R3
I
O
R1
O
Synthetic investigation of the target oxaphospholenes was ini-
tiated by the preparation of allenic phosphonates 2 (Table 1). It is
well known that allenic phosphonates are readily available from
alk-2-yn-l-ols.7 Using this method, the rearrangement reaction of
3-trifluoromethylalk-2-yn-1-ols (1), prepared according to the lit-
erature,8 was studied first. As shown in Table 1, the reaction went
smoothly and afforded the corresponding allenic phosphonates 2 in
good yields with 1,1-disubstituted or phenyl substituted substrates
under mild conditions (entries 1e3 and 6e9). In the case of sec-
ondary aliphatic alk-2-yn-l-ols, however, the reaction became
complicated and gave relatively lower yields (entries 4e5). No
elimination of HF was observed in these reactions as Commeyras
reported about the rearrangement of perfluorobutyl substituted
prop-2-ynyl diethylphosphites.9 The trifluoromethyl acetylenic
carbon atom probably has a lower electrophilic character than
those of nonfluorinated acetylenes, which would make attack by
the phosphorus atom less likely. Bulky 1,1-disubstituents or phenyl
R2 R1
R2
1,2-oxaphospholane 2-oxide
1,2-oxaphosphol-3-ene 2-oxide
I
II
Meanwhile, the presence of fluorine atoms in a potentially bio-
active molecule can dramatically change not only its physical but
also its chemical properties,4 accordingly might give rise to en-
hancement or alteration of the native biological activity of the sub-
strate. This has been particularly true for fluoroheterocycles. Taking
the biological importance of phosphorus heterocycles into consid-
eration, introduction of fluorineatoms or fluoroalkylgroups intothis
* Corresponding author. Tel.: þ86 21 54925188; fax: þ86 21 64166128; e-mail
address: jtliu@mail.sioc.ac.cn (J.-T. Liu).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.040

9730
P. Li et al. / Tetrahedron 66 (2010) 9729e9732
Table 3
substituents, however, could decrease the CeCeO angle and favor
hybridization at the initially saturated carbon atom, thus facilitate
the rearrangement reaction.
Iodocyclization of allenic phosphonates 2aei
CF3
F3C
I
I2
O
EtO
EtO
Table 1
•
P
P
R2
R1
R1
Preparation of allenic phosphonates 2 from 3-trifluoromethylalk-2-yn-1-ols 1
OEt
O
O
CH3CN
R2
F3C
DECP, Et3N
OH
R2
3
2
EtO
EtO
F3C
•
P
R2
R1
R1
CH2Cl2, -78oC to 0oC
O
Entry
2
Product
Yielda (%)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
1
2
83
48; 30b
Entry
1
R1
R2
Product
Yielda (%)
dc
dc
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
Et
Me
Et
Me
Et
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
85
68
74
37
35
78
80
77
86
61d
70d
82
Me
nPr
tBu
87
Ph
Ph
eCH2)5e
e(CH2)4e
a
Isolated yield.
Me
b
c
Two diastereomers were isolated.
I2 or ICl was used as the electrophile, the substrate was recovered.
Total isolated yield of two diastereomers.
d
a
Isolated yield.
A similar mechanism as Angelov10b reported was proposed for
With intermediates 2 in hand, the construction of oxaphos-
pholenes 3 via iodocyclization reaction6c,10 was next studied. Using
the reaction of diethyl 1-trifluoromethyl-3-ethyl-1,2-pentadien-1-
ylphosphonate (2a) and iodine as the model reaction, various
conditions were examined (Table 2). The amount of iodine had an
important effect on the reaction. With 3 equiv of iodine, 2a was
converted to 3a completely within 3 h in CH3CN or CH2Cl2 (entries 1
and 4). A longer time (27 h) was needed for the reaction to go to
completion in CH3CN when 2 equiv of iodine was used (entry 2).
Further decreasing the amount of iodine made the reaction become
much slower (entry 3). In other solvents, such as toluene, DMF, and
THF the reaction was also very slow (entries 5e7).
the formation of 3 as illustrated in Scheme 1. Allenic phosphonates
2 reacted with polarized I2 to form iodonium A and release an io-
dine anion at the same time. With the assistance of iodine anion,
intramolecular nucleophilic attack of oxygen in phosphonyl group
on the terminal carbon of allene in the 5-endo mode afforded the
cyclization product 3 accompanied by the elimination of ethyl io-
dine. Therefore, substituents which can stabilize the iodonium in-
termediate A facilitate the cyclization as demonstrated by the
results above.
F3C
Table 2
I
O
O
CF3
Condition optimization for the iodocyclization of 2a
F3C
R2
I2
•
P
I
O
O
O
O
O
R2
R1
P
•
R1
P
O
R1
OEt
OEt
CF3
O
F3C
P
I3
R2
O
P
n equiv I2, solvent
O
•
ambient temperature
I
3
EtO
Et
Et
Et
A
OEt
2
Et
3a
Scheme 1. Proposed mechanism for the iodocyclization reaction.
2a
Entry
n
Solvent
Time (h)
Conversiona (%)
3. Conclusion
1
2
3
4
5
6
7
3
2
1.5
3
3
CH3CN
CH3CN
CH3CN
CH2Cl2
DMF
3
27
52
3
18
18
18
100
100
87
100
95
In summary, the synthesis and iodocyclization of tri-
fluoromethylallenic phosphonates have been achieved under mild
conditions for the first time, providing a convenient method for the
synthesis of trifluoromethylated oxaphospholenes. The presence of
vinyl iodine in the resulted fluorine-containing oxaphospholenes
makes it possible to incorporate this novel subunit into other
molecules to prepare various carbohydrate mimics with potential
bioactivities.
3
3
PhCH3
THF
90
84
a
Determined by 19F NMR.
Using the optimized conditions in Table 2, entry 2, the iodo-
cyclization reactions of other allenic phosphonates were in-
vestigated. As shown in Table 3, the reaction was strongly
influenced by the substitution pattern on the allenic skeleton: C-
terminal aryl or dialkyl substituted allenic phosphonates (2aec and
4. Experimental section
4.1. General
2fei) investigated could afford the desired g-phosphonate lactones
in moderate to good yields (entries1e3 and 6e9). In the case of
allenic phosphonates with one C-terminal alkyl substituent (2dee),
however, no desired cyclization products were obtained, even if
stronger electrophile ICl6c was used (entries 4and 5), probably due
to the difficulty to form the iodonium intermediates. The ratio of
two isomers was about 1:1 to 8:5 with allenic phosphonates with
different C-terminal substituents (entries 3, 6, and 7).
Melting points were measured with a Temp-Melt apparatus and
uncorrected. 1H NMR spectra were recorded in CDCl3 on Bruker
AM-300 instruments with TMS as the internal standard. 19F NMR
and 31P NMR spectra were recorded on the same spectrometer
using CFCl3 and 85% H3PO4 as external standards, respectively. IR
spectra were obtained with a Nicolet AV-360 spectrophotometer.

P. Li et al. / Tetrahedron 66 (2010) 9729e9732
9731
Mass spectra and high resolution mass spectra (HRMS) were
obtained on a Finnigan GCeMS 4021 and a Finnigan MAT-8430
spectrometer, respectively. Elemental analyses were performed by
this institute. Dichloromethane was freshly distilled from sodium
before use. Diethyl chlorophosphite was prepared according to
literature.11 All other chemicals were commercially available and
were used as received.
m/z 286.0946, found 286.0945. Anal. Calcd for C11H18F3O3P: C,
46.16; H, 6.34. Found: C, 45.98; H, 6.62.
4.2.5. Diethyl 1-trifluoromethyl-4,4-dimethylpenta-1,2-dien-1-ylphos-
phonate (2e). Colorless oil. IR (thin film, cmꢀ1): 2966, 2910, 1960,
1737, 1479, 1464, 1398,1369,1280,1216,1180, 1138, 978, 587. 1H NMR
(300 MHz, CDCl3):
d
5.91 (dq, J¼11.1, 3.0 Hz, 1H), 4.23e4.14 (m, 4H),
1.37 (t, J¼7.2 Hz, 6H),1.17 (s, 9H).19F NMR (282 MHz, CDCl3):
ꢀ58.19
d
4.2. Typical procedure for the preparation of 2
(s). 31P NMR (162 MHz, CDCl3): 9.33 (s). EI-MS m/z (%): 300 (Mþ,
d
12.93), 243 (100.00), 209 (89.85), 188 (64.31), 81 (26.18), 57 (22.74).
Anal. Calcd for C12H20F3O3P: C, 48.00; H, 6.71. Found: C, 47.98; H,
6.88.
To a mixture of alkynol 1a (0.45 g, 2.5 mmol) and Et3N (0.36 mL,
2.6 mmol) in CH2Cl2 (8 mL) was added slowly a solution of diethyl
chlorophosphite (0.42 g, 2.7 mmol) in CH2Cl2 (2 mL) at ꢀ78 ꢁC.
After stirred at that temperature for 10 min, the reaction mixture
was warmed to ambient temperature and stirred for 2 h, then
quenched with H2O (10 mL) and extracted with Et2O (3ꢂ10 mL).
The organic layer was dried over Na2SO4 and concentrated under
vacuum. The residue was purified by silica gel chromatography to
give 0.64 g of 2a as a colorless oil (isolated yield: 85%).
4.2.6. Diethyl 1-trifluoromethyl-3-phenylpropa-1,2-dien-1-ylphospho-
nate (2f). Colorless oil. IR (thin film, cmꢀ1): 2986, 1961, 1731, 1459,
1392, 1262, 1197, 1020, 974, 584. 1H NMR (300 MHz, CDCl3):
d
7.29e7.40 (m, 5H), 6.90 (dq, J¼11.4, 3.0 Hz, 1H), 4.27e4.13 (m, 4H),
1.34 (dt, J¼8.4, 7.5 Hz, 6H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.02 (s).
31P NMR (162 MHz, CDCl3): 7.36 (s). EI-MS m/z (%): 320 (Mþ, 29.18),
d
272 (14.56), 244 (55.14), 228 (37.14), 182 (11.89), 164 (100.00), 75
(12.75), 65 (11.97). Anal. Calcd for C14H16F3O3P: C, 52.51; H, 5.04.
Found: C, 52.17; H, 5.18.
4.2.1. Diethyl 1-trifluoromethyl-3-ethylpenta-1,2-dien-1-ylphospho-
nate (2a). Colorless oil. IR (thin film, cmꢀ1): 2976, 1966, 1461, 1401,
1378, 1271, 1172, 1133, 1054, 1025, 976, 585. 1H NMR (300 MHz,
CDCl3):
d
4.21e4.10 (m, 4H), 2.21e2.12 (m, 4H), 1.35 (t, J¼6.9 Hz,
4.2.7. Diethyl 1-trifluoromethyl-3-phenylbuta-1,2-dien-1-ylphosph-
onate (2g). Colorless oil. IR (thin film, cmꢀ1): 2990, 2935, 2912,
1955, 1716, 1497, 1460, 1446, 1373, 1264, 1170, 1135, 1053, 587. 1H
6H), 1.08 (t, J¼7.4 Hz, 6H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.56 (d,
J¼2.0 Hz). 31P NMR (162 MHz, CDCl3):
d
9.71 (s). 13C NMR (75 MHz,
CDCl3): 209.6 (m), 120.2 (qd, JCeF¼272.2 Hz, JCeP¼16.4 Hz), 110.3 (d,
JCeP¼13.1 Hz), 91.2 (m), 62.8 (d, JCeP¼5.6 Hz), 24.9 (d, JCeP¼5.1 Hz),
16.1 (d, JCeP¼6.8 Hz), 11.6 (d, JCeP¼1.9 Hz). EI-MS m/z (%): 300 (Mþ,
12.29), 231 (16.16), 163 (13.96), 138 (71.06), 111 (100.00), 81 (64.36).
HRMS: calcd for C12H20F3O3P requires m/z 300.1102, found
300.1107.
NMR (300 MHz, CDCl3): d 7.33e7.40 (m, 5H), 4.16 (m, 4H), 2.28 (d,
J¼5.7 Hz, 3H), 1.33 (dt, J¼7.2, 6.9 Hz, 6H). 19F NMR (282 MHz,
CDCl3):
d
ꢀ58.11 (s). 31P NMR (162 MHz, CDCl3):
d 8.20 (s). EI-MS m/
z (%): 334 (Mþ, 4.38), 265 (2.57), 197 (36.48), 104 (17.94), 81
(100.00), 77 (40.28), 69 (14.61). Anal. Calcd for C15H18F3O3P: C,
53.90; H, 5.43. Found: C, 53.63; H, 5.49.
4.2.2. Diethyl 1-trifluoromethyl-3-methylbuta-1,2-dien-1-ylphosph-
onate (2b). Colorless oil. IR (thin film, cmꢀ1): 2990, 1974, 1448,
1384, 1263, 1175, 1134, 1025, 979, 585. 1H NMR (300 MHz, CDCl3):
4.2.8. Diethyl 1-trifluoromethyl-2-cyclohexylidene-1-vinylphosphonate
(2h). Colorless oil. IR (thin film, cmꢀ1): 2988, 2938, 2860, 1967, 1448,
1409, 1271, 1164, 1137, 1053, 1025, 973, 584. 1H NMR (300 MHz,
d
4.22e4.09 (m, 4H), 1.89 (s, 3H), 1.87 (s, 3H), 1.35 (t, J¼6.9 Hz, 6H).
CDCl3): d 4.23e4.08 (m, 4H), 2.36e2.23 (m, 4H), 1.54e1.75 (m, 6H),
19F NMR (282 MHz, CDCl3):
(162 MHz, CDCl3):
d
ꢀ58.61 (d, J¼1.7 Hz). 31P NMR
1.35 (t, J¼7.2 Hz, 6H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.61 (s). 31P
d
9.06 (s). EI-MS m/z (%): 272 (Mþ, 2.68), 203
NMR (162 MHz, CDCl3):
d
9.53 (s). EI-MS m/z(%): 313 (Mþþ1, 22.56),
(16.36), 147 (49.37), 109 (57.67), 81 (100.00), 69 (15.74), 65 (63.38).
Anal. Calcd for C10H16F3O3P: C, 44.12; H, 5.92. Found: C, 44.06; H,
5.97.
312 (Mþ, 9.01), 243 (13.76), 158 (100.00), 137 (13.03), 82 (76.84), 69
(13.26). Anal. Calcd for C13H20F3O3P: C, 50.00; H, 6.46. Found: C,
49.87; H, 6.54.
4.2.3. Diethyl 1-trifluoromethyl-3-methylpenta-1,2-dien-1-ylphospho-
nate (2c). Colorless oil. IR (thin film, cmꢀ1): 2981, 2938, 2913, 1959,
1457, 1442, 1392, 1378, 1268, 1174, 1134, 1024, 974, 799, 747, 710, 586.
4.2.9. Diethyl 1-trifluoromethyl-2-cyclopentylidene-1-vinylphospho-
nate (2i). Colorless oil. IR (thin film, cmꢀ1): 2964, 1962, 1726, 1394,
1288, 1256, 1172, 1133, 1053, 1024, 979, 585. 1H NMR (300 MHz,
1H NMR (300 MHz, CDCl3):
d
4.21e4.10 (m, 4H), 2.20e2.11 (m, 2H),
CDCl3): d 4.21e4.08 (m, 4H), 2.67e2.58 (m, 4H), 1.83e1.76 (m, 4H),
1.88 (d, J¼5.7 Hz, 3H), 1.35 (t, J¼7.2 Hz, 6H), 1.09 (t, J¼7.2 Hz, 3H). 19F
1.35 (t, J¼7.2 Hz, 6H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.40 (s). 31P
NMR (282 MHz, CDCl3):
d
ꢀ58.60 (s). 31P NMR (162 MHz, CDCl3):
NMR (162 MHz, CDCl3):
d
9.89 (s). EI-MS m/z (%): 299 (Mþþ1,
d
9.65 (s). 13C NMR (100 MHz, CDCl3): 209.4 (m), 122.0 (qd,
46.39), 298 (Mþ, 14.13), 230 (14.22), 161 (14.66), 137 (12.12), 91
(100.00), 137 (13.03), 69 (16.54). Anal. Calcd for C12H18F3O3P: C,
48.33; H, 6.08. Found: C, 48.28; H, 6.21.
JCeF¼272.2 Hz, JCeP¼16.2 Hz), 110.53 (d, JCeP¼13.3 Hz), 91.2 (dq,
JCeP¼200.3 Hz, JCeF¼37.0 Hz), 65.4 (d, JCeP¼6.0 Hz), 32.3 (d,
JCeP¼5.4 Hz), 26.2 (d, JCeP¼5.1 Hz), 18.6 (d, JCeP¼4.8 Hz), 17.3 (d,
JCeP¼5.5 Hz), 16.0 (d, JCeP¼6.5 Hz), 13.4 (d, JCeP¼3.4 Hz), 11.4 (d,
JCeP¼1.8 Hz). EI-MS m/z (%): 286 (Mþ, 7.37), 217 (8.30), 149 (11.99),
109 (100.00), 57 (69.29). HRMS: calcd for C11H18F3O3P requires m/z
286.0946, found 286.0947.
4.3. Typical procedure for the cyclization reaction of allenic
phosphonates 2 with iodine
To a solution of 2a (136 mg, 0.5 mmol) in 5 mL of CH3CN was
added I2 (250 mg, 1.0 mmol). The mixture was stirred at room
temperature for 27 h. The resulting mixture was diluted with ether,
washed with saturated Na2S2O3 solution and brine, and the organic
layer was dried over Na2SO4. After the removal of solvents under
vacuum, the residue was purified by flash chromatography on silica
gel to give 3a as a white solid (170 mg, 92% yield).
4.2.4. Diethyl 1-trifluoromethylhexa-1,2-dien-1-ylphosphonate (2d).
Colorless oil. IR (thin film, cmꢀ1): 2968, 1972, 1396, 1277, 1195, 1138,
1053, 1023, 975, 584. 1H NMR (300 MHz, CDCl3):
d 5.95e5.87 (m,
1H), 4.24e4.10 (m, 4H), 2.24e2.14 (m, 2H), 1.58e1.47 (m, 2H), 1.36
(t, J¼7.2 Hz, 6H), 0.98 (t, J¼7.5 Hz, 3H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.48 (s). 31P NMR (162 MHz, CDCl3):
d 8.99 (s). EI-MS m/z (%):
286 (Mþ, 3.58), 257 (6.94), 230 (9.71), 149 (3.47), 109 (100.00), 81
(85.27), 77 (30.17), 69 (9.18). HRMS: calcd for C11H18F3O3P requires
4.3.1. 5,5-Diethyl-2-ethoxy-4-iodo-3-trifluoromethyl-1,2-oxaphos-
phol-3-ene 2-oxide (3a). Mp 102e103 ꢁC. IR (KBr, cmꢀ1): 2972,

9732
P. Li et al. / Tetrahedron 66 (2010) 9729e9732
2939, 1610, 1299, 1251, 1173, 1146, 1054, 1037, 981, 831, 582. 1H NMR
(d, J¼7.8 Hz, 3g00). 31P NMR (162 MHz, CDCl3):
d
26.30 (s, 3g0), 25.88
(300 MHz, CDCl3):
d
4.38e4.25 (m, 2H), 1.92 (q, J¼7.2 Hz, 4H), 1.37
(s, 3g00). 13C NMR (100 MHz, CDCl3): 133.9, 130.3 (m), 129.4, 128.7,
127.6, 126.6, 120.5 (qd, JCeF¼273.5 Hz, JCeP¼16.4 Hz), 90.5, 65.1 (d,
JCeP¼6.6 Hz), 25.2, 16.4 (d, JCeP¼5.4 Hz). EI-MS m/z (%): 432 (Mþ,
22.66), 305 (10.69), 257 (27.46), 149 (100.00), 77 (48.25). HRMS:
calcd for C13H13F3IO3P requires m/z 431.9599, found 431.9598.
(t, J¼6.9 Hz, 3H), 0.90 (t, J¼7.5 Hz, 3H), 0.85 (t, J¼8.4 Hz, 3H). 19F
NMR (282 MHz, CDCl3):
d
ꢀ59.11 (d, J¼6.8 Hz). 31P NMR (162 MHz,
CDCl3):
d
26.45 (d, J¼7.2 Hz). EI-MS m/z (%): 399 (Mþþ1, 11.09), 398
(Mþ, 9.13), 369 (81.06), 341 (100.00), 271 (49.12), 194 (65.33), 92
(3.19), 69 (5.21). Anal. Calcd for C10H15F3IO3P: C, 30.17; H, 3.80.
Found: C, 30.26; H, 3.88.
4.3.6. 2-Ethoxy-4-iodo-5,5-pentamethylene-3-trifluoromethyl-1,2-
oxaphosphol-3-ene 2-oxide (3h). White solid, mp 102e104 ꢁC. IR
(KBr, cmꢀ1): 2943, 1604, 1452, 1445, 1299, 1262, 1245, 1180, 1147,
1049, 1033, 963, 910, 818, 686, 580. 1H NMR (300 MHz, CDCl3):
4.3.2. 5,5-Dimethyl-2-ethoxy-4-iodo-3-trifluoromethyl-1,2-ox-
aphosphol-3-ene 2-oxide (3b). White solid, mp 93e94 ꢁC. IR (KBr,
cmꢀ1): 2995, 1607, 1458, 1397, 1385, 1369, 1299, 1257, 1167, 1140,
1046, 1031, 982, 806, 788, 585. 1H NMR (300 MHz, CDCl3):
d
4.32e4.19 (m, 2H), 2.04e1.97 (m, 2H), 1.81e1.68 (m, 6H),
1.60e1.21 (m, 2H), 1.37 (t, J¼7.2 Hz, 3H). 19F NMR (282 MHz, CDCl3):
d
4.32e4.21 (m, 2H), 1.64 (s, 3H), 1.59 (s, 3H), 1.38 (t, J¼7.2 Hz, 3H).
d
ꢀ59.12 (d, JFeP¼6.2 Hz). 31P NMR (162 MHz, CDCl3):
d 24.66 (q,
19F NMR (282 MHz, CDCl3):
d
ꢀ59.71 (d, J¼6.2 Hz). 31P NMR
JFeP¼6.2 Hz). EI-MS m/z (%): 410 (Mþ, 2.08), 341 (3.05), 327 (29.98),
283 (100.00), 69 (6.74). Anal. Calcd for C11H15F3IO3P: C, 32.22; H,
3.69. Found: C, 32.25; H, 3.79.
(162 MHz, CDCl3):
d
24.63 (s). ESI-MS m/z: 370.9 [MþH]þ, 392.9
[MþNa]þ, 402.9 [MþMeOHþH]þ. EI-MS m/z (%): 371 (Mþþ1,
24.20), 355 (21.27), 301 (6.08), 243 (45.16), 196 (51.04), 108 (0.77),
69 (19.57), 43 (100.00). Anal. Calcd for C8H11F3IO3P: C, 25.97; H,
3.00. Found: C, 25.98; H, 3.23.
4.3.7. 5,5-Butamethylene-2-ethoxy-4-iodo-3-trifluoromethyl-1,2-ox-
aphosphol-3-ene 2-oxide (3i). White solid, mp 90e91 ꢁC. IR (KBr,
cmꢀ1): 2988, 1603, 1331, 1299, 1259, 1169, 1144, 1048, 1032, 977,
4.3.3. 2-Ethoxy-5-ethyl-4-iodo-5-methyl-3-trifluoromethyl-1,2-ox-
aphosphol-3-ene 2-oxide (3c). Less polar isomer: white solid, mp
191e193 ꢁC. IR (KBr, cmꢀ1): 2987, 2939, 1610, 1291, 1254, 1180, 1143,
945, 815, 790, 578. 1H NMR (300 MHz, CDCl3):
d 4.29e4.19 (m, 2H),
2.23e2.18 (m, 2H), 2.06e1.89 (m, 6H) 1.36 (t, J¼7.2 Hz, 3H). 19F NMR
(282 MHz, CDCl3):
d
ꢀ59.15 (d, JFeP¼6.2 Hz). 31P NMR (162 MHz,
1054, 1029, 970, 820, 580. 1H NMR (300 MHz, CDCl3):
d
4.34e4.23
CDCl3):
d
24.73 (q, JFeP¼6.2 Hz). EI-MS m/z (%): 397 (Mþþ1, 0.90),
(m, 2H), 1.96e1.88 (m, 2H), 1.56 (s, 3H), 1.36 (t, J¼7.2 Hz, 3H), 0.91 (t,
339 (4.56), 327 (11.77), 269 (69.91), 221 (100.00), 69 (23.01). Anal.
Calcd for C10H13F3IO3P: C, 30.32; H, 3.31. Found: C, 30.27; H, 3.43.
J¼7.5 Hz, 3H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.78 (d, J¼7.9 Hz). 31
P
NMR (162 MHz, CDCl3):
d
25.51 (q, J¼5.8 Hz). EI-MS m/z (%): 369
(MþꢀCH3, 0.98), 355 (24.43), 327 (28.54), 315 (1.15), 257 (49.12),
127 (24.94), 69 (11.93), 44 (100.00). Anal. Calcd for C9H13F3IO3P: C,
28.14; H, 3.41. Found: C, 27.90; H, 3.45. More polar isomer: white
solid, mp 186e187 ꢁC. IR (KBr, cmꢀ1): 2987, 2939, 1610, 1291, 1254,
1180, 1143, 1054, 1029, 970, 820, 580. 1H NMR (300 MHz, CDCl3):
Acknowledgements
We thank the National Natural Science Foundation of China for
financial support (No. 20872166).
d
4.34e4.23 (m, 2H), 1.91 (q, J¼7.2 Hz, 2H), 1.61 (s, 3H), 1.37 (t,
References and notes
J¼6.9 Hz, 3H), 0.87 (t, J¼7.2 Hz, 3H). 19F NMR (282 MHz, CDCl3):
d
ꢀ59.11 (d, J¼6.8 Hz). 31P NMR (162 MHz, CDCl3):
d 25.27 (q,
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4.3.4. 2-Ethoxy-4-iodo-5-phenyl-3-trifluoromethyl-1,2-oxa-phos-
phol-3-ene 2-oxide (3f). A 1:1 mixture of two diastereomers. IR
(KBr, cmꢀ1): 2966, 2910, 2873, 1960, 1737, 1479, 1464, 1398, 1369,
1280, 1216, 1180, 1138, 1039, 978, 587. 1H NMR (300 MHz, CDCl3):
d
7.47e7.31 (m, 5H), 5.73e5.66 (m, 1H), 4.41e4.29 (m, 2H), 1.42 (t,
J¼7.2 Hz, 3H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.52 (s, 3f0), ꢀ58.41
(d, J¼7.6 Hz, 3f00). 31P NMR (162 MHz, CDCl3):
d
26.07 (s, 3f0), 26.44
(s, 3f00). 13C NMR (125 MHz, CDCl3): 133.9, 130.3 (m), 129.1, 128.2,
128.1, 122.8 (qd, JCeF¼271.6 Hz, JCeP¼16.3 Hz), 87.9, 65.4 (d,
JCeP¼7.5 Hz), 16.4 (d, JCeP¼12.6 Hz). EI-MS m/z (%): 389 (MþꢀC2H5,
100.00), 369 (88.77), 254 (51.82), 133 (68.44), 105 (60.48), 77
(43.26), 51 (26.81). HRMS: calcd for C12H11F3IO3P requires m/z
417.9443, found 417.9442. Anal. Calcd for C12H11F3IO3P: C, 34.47; H,
2.65. Found: C, 34.07; H, 2.58.
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4.3.5. 2-Ethoxy-4-iodo-5-methyl-5-phenyl-3-trifluoromethyl-1,2-ox-
aphosphol-3-ene 2-oxide (3g). A 1:1.2 mixture of two di-
astereomers. IR (KBr, cmꢀ1): 2993, 2939, 1606, 1301, 1255, 1141,
1039, 983, 952, 759, 695. 1H NMR (300 MHz, CDCl3):
d 7.52e7.40 (m,
5H), 4.42e4.34 (m, 2H), 2.00 (s, 1.25H), 2.07 (s, 1.75H), 1.42 (t,
J¼7.2 Hz, 3H). 19F NMR (282 MHz, CDCl3):
d
ꢀ58.60 (s, 3g0), ꢀ58.64
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