The synthesis of vicinal halohydrin phosphates via highly regioselective ring opening of epoxides with dialkyl halophosphate

Article abstract of DOI:10.1039/a909613b

The synthesis of vicinal halohydrin phosphates was carried out via highly regioselective ring opening of epoxides using dialkyl halophosphate (DAHP). The effect of temperature on the yield and regioselectivity of the reaction were also studied. The experi

Full text of DOI:10.1039/a909613b

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The synthesis of vicinal halohydrin phosphates via highly
regioselective ring opening of epoxides with dialkyl halophosphate
Yixiang Ding* and Jun Hu
1
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, China
Received (in Cambridge, UK) 6th December 1999, Accepted 1st March 2000
Published on the Web 19th April 2000
Various titanium() reagents catalyze the ring opening of epoxides by dialkyl halophosphates (added or formed
in situ) under mild conditions to give the corresponding vicinal halohydrin phosphates in good yields with high
regioselectivity.
Introduction
Results
The facile ring opening of epoxides makes them extremely ver-
satile intermediates for organic synthesis.1 Although a myriad
reagents employed in the cleavage of epoxides have been
reported, very little is known concerning the ring opening of
epoxides with dialkyl halophosphates (DAHPs).2
Two models for the ring opening of epoxides with halo-
phosphates were studied: DAHPs were used directly as the
reagent in the ring opening (method A); DAHPs were formed
in situ (methods B and C).
Recently, Rotella3 suggested a mechanism-based phos-
phatase inhibitor model. In this hypothesis, vicinal halohydrin
phosphates would undergo a phosphatase catalytic hydrolytic
reaction to give a reactive intermediate epoxide that could
irreversibly deactivate the phosphatase by forming a covalent
bond to an active site residue (i.e. OH, SH and NH2 groups)4 as
shown in Scheme 1.
Method A: chlorophosphate used directly as a reagent
The epoxide was added to a solution of TiCl4 and dialkyl
chlorophosphate in CH2Cl2 at room temperature (Scheme 2).
After 0.5–4 h, the reaction afforded the desired product in
good yield with high regioselectivity. The results of the ring
opening of various representative epoxides by this process are
compiled in Table 1. The presence of only one regioisomer was
determined by 1H NMR, 31P NMR and TLC of both crude and
isolated products.
Many catalysts normally used in epoxide ring-opening
reactions, such as LiCl, ZnCl2, AlCl3, BF3ؒEt2O, NH4Cl, HCl
and several Ti() compounds,7 were investigated. Among the
catalysts examined, titanium() compounds emerged as the
most effective promoter; LiCl gave 3c in very low yield (<5%),
ZnCl2, AlCl3, NH4Cl and HCl gave only halohydrin, and
BF3ؒEt2O caused decomposition of the substrate. We found
that 0.5–1 mol% TiCl4 was the appropriate catalyst stoichio-
metry. Higher concentration of TiCl4 led to more by-products.
There was no reaction without the catalyst.
The effect of temperature on the yield and regioselectivity of
the reaction was also investigated. At Ϫ78 ЊC, there was no
reaction as monitored by TLC. The temperature was raised to
room temperature, we found that the reaction took place at
around Ϫ30 ЊC. At a reaction temperature higher than 40 ЊC,
the products were very complex and the yields were very low
(20–30%).
The success of the TiCl4-catalyzed reaction encouraged us to
examine the ring opening of epoxides with other DAHPs.
Moreover, the reaction that is carried out directly with the pure
dialkyl iodophosphate in method A seems impractical since it is
impossible to isolate the dialkyl iodophosphate.8 This prompted
us to examine the possibility of developing other methods in
which halophosphates are formed in situ as intermediates.
Scheme 1
By taking the stereochemistry of the enzyme into consider-
ation, the ring opening of the epoxides with DAHPs will pro-
vide the most attractive methods for the synthesis of this kind
of molecule because two contiguous centers of defined stereo-
chemistry may be generated from the readily obtained chiral
epoxides.5,6
In this paper we wish to report the details of the ring-opening
reaction of epoxides with DAHPs to provide the halohydrin
phosphates in the presence of catalytic amounts of titanium()
compounds.
Method B: chloro- and bromophosphate formed in situ via the
Atherton–Todd reaction
In situ oxidation of the dialkyl phosphite via the Atherton–
Todd reaction9 afforded the chlorophosphate or bromo-
phosphate 2c. Subsequent ring opening of the epoxide in the
Scheme 2 Method A.
DOI: 10.1039/a909613b
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This journal is © The Royal Society of Chemistry 2000
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Table 1 Titanium() catalyzed ring opening of epoxides with DAHPs
Main
products
Isolated
yield (%)
Entry
1
Epoxide
Halophosphate
Time/h
2
Methoda
A
α:βb
2b
65
71
<5:95
<5:95
2
3
2b
2a
2
1
A
A or B
82 (A)
85 (B)
>95:5
>95:5
4
5
1c
2c
2a
1.5
0.5
B
80
A or B
87 (A)
90 (B)
<5:95
6
1d
1d
2c
1
B
92
<5:95
<5:95
7
8
2d
2a
1
C
A
85
85
0.5
<5:95
>95:5
9
10
11
2a
2a
2a
1
1
2
A
80
77
A
>95:5
A or B
75 (A)
75 (B)
12
13
1h
1h
2c
2d
2
2
B
C
77
74
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Table 1 (Contd.)
Main
products
Isolated
yield (%)
Entry
Epoxide
Halophosphate
Time/h
2
Methoda
α:βb
14
2d
C
87
a A, B and C represent methods A, B, and C. b The ratios were determined by 1H and 31P NMR.
presence of a catalytic amount of Ti() led to the desired halo-
hydrin phosphates. If TiCl4 was used as the catalyst there
was always some trace amount of chlorohydrin phosphate as a
contaminant in the reaction product of the bromophosphate
because the initial chloride ion could come from TiCl4.10 We
found that Ti(OPr-i)4 readily catalyzes the ring opening reac-
tion to give the clean products in good yields (Scheme 3).11 The
results are also shown in Table 1.
Scheme 5
We chose to test disodium 2-chloro-2-phenylethyl phosphate
(4a) and disodium 2-chlorocyclohexyl phosphate (4b) as inhib-
itors of orthophosphoric monoester phosphohydrolase because
they were the simplest molecules that contained this struc-
ture; they were obtained by removing the phosphoric acid
protecting group CH3 from compounds 3c and 3m with
BrSiMe3.13 The IC50 value of compound 4b is 2.46 × 10Ϫ3
M
and with 4-nitrophenyl phosphate compound 4b is a compet-
itive inhibitor of the phosphohydrolase.
Discussion
Two regioisomers are distinguished easily by comparing the dif-
ferent couplings of the methylene or methyl group to the phos-
phorus atom. Surprisingly, the methylene resonances of the
Scheme 3 Method B.
Compared with method A, method B gave a higher yield
(Table 1, entries 3, 4 and 7) and was experimentally more con-
venient. In method A it was essential to carry out the experi-
ment with the freshly distilled halophosphates since acid (an
obvious contaminant) is known to open epoxides with ease.
However, in method B, the presence of NEt3 efficiently pre-
vented acid-catalyzed ring opening.
products 3c-ꢀ, 3d-ꢀ, 3i-ꢀ and 3j-ꢀ are triplets because JPH = JHH
.
The methine resonances are also triplets. The compounds 3e–
h-ꢁ have two methylene groups that have a doublet signal. All
the methylene groups in these compounds show deceptively
simple splitting patterns (at 90 MHz) and no diastereotopicity,
but these peaks are broadened in some of the compounds.
Based on experimental observations, a possible mechanism
involves the precomplexation between TiCl4, an epoxide and a
phosphoryl group, as shown in Scheme 6.
Method C: iodophosphate formed in situ by the reaction of
trimethyl phosphite with iodine
In the reaction with TiCl4 the mechanism of ring opening is
thought to be a borderline SN2.10 We might expect nucleophilic
attack to occur at the more highly substituted and more
electrophilic carbon. In the present case, the possible precom-
plexation with the phosphoryl group may weaken the Lewis
acidity of TiCl4, and so lower the polarization of the C–O
bond and decrease the positive charge on the carbon. Thus,
the reaction occurs by a mechanism in which there is less SN1
character in the transition state. In this case, the positive
charge on the carbon atom could be efficiently stabilized by the
conjugated aryl group, so that the chloride ion would attack the
benzylic carbon atom. The reaction pathway a (Scheme 6), via a
carbonium ion-like transition state, was favored and followed
the borderline SN2 mechanism with considerable SN1 character.
When R1 is an aliphatic chain which cannot sufficiently stabilize
the positive charge on the substituted carbon atom as the aryl
group did, the reaction occurs by pathway b and follows an SN2
mechanism in which the halogen atom becomes attached to the
less substituted carbon atom.
The iodohydrin phosphates were prepared in good yields by the
ring opening of epoxides with iodophosphate 2d formed in situ
from trimethyl phosphite and elemental iodine at Ϫ10 ЊC as
shown in Table 1 and Scheme 4. Ti(OPr-i)4 was used as the
Scheme 4 Method C.
catalyst for the same reasons given above. Tetrahydrofuran
(THF) used as solvent can also be ring opened by iodophos-
phate 2d (Table 1, entry 14).
The fact that only one regioisomer was obtained is similar to
the results reported by Eisch et al.10 They reported that the ring
opening of epoxides became extremely regioselective by adding
a stoichiometric amount of a tertiary amine as a ligand on the
metal halide. Recently, Iranpoor and Zeynizadeh14 proposed a
similar mechanism for the highly regioselective conversion of
epoxides into vicinal chloroesters.
Unfortunately, the ring opening of 1,2-disubstituted
epoxides failed with the exception of cyclohexene oxide
(Scheme 5). 2-Halocyclohexyl phosphates can be prepared by
1
method A, B or C. H NMR spectroscopy of the hydrolytic
products proved the phosphates derived from cyclohexene oxide
to be trans in structure by comparison with reference data.12
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Scheme 6
AlCl3 and other catalysts lack the additional valencies
POCH2), 3.93 (d, J 5 Hz, 4H, 2ClCH2), 1.50 (t, J 6 Hz, 6H,
2CH3).
required to complex with the phosphoryl group to promote
substitution at the phosphorus atom, so ring opening of
epoxides occurred, but halohydrin phosphates were not formed.
In conclusion, TiCl4 is a versatile catalyst for the cleavage of
a variety of epoxides with chlorophosphates. Using Ti(OPr-i)4,
the bromohydrin phosphates and iodohydrin phosphates were
also obtained cleanly by ring opening with 2b and 2c formed
in situ. The good yields, excellent regioselectivity, small amount
of catalyst required and the mild experimental conditions
make the procedure useful for the synthesis of the multi-
functionalized synthons. The experimental observations sup-
ported the precomplexation hypothesis for the mechanism.
2-Chloro-2-phenylethyl dimethyl phosphate 3c-ꢀ. Colorless
oil. δH (CCl4) 7.20–7.50 (m, 5H, PhH), 5.07 (t, J 7 Hz, 1H,
ClCH), 4.29 (t, JHH = JPH 7 Hz, 2H, POCH2), 3.66 (d, J 10 Hz,
6H, 2POCH3); m/z 267 (M ϩ 1, 6.48%), 229 (19.66), 138
(100.00), 127 (37.08), 103 (48.63); δP 1.0820; IR(neat) 1282,
1037 cmϪ1. Found: C, 45.50; H, 5.40; C10H14O4ClP requires C,
45.39; H, 5.33%.
3-Chloro-1-phenoxypropan-2-yl dimethyl phosphate 3e-ꢁ.
Colorless oil. δH (CCl4) 7.36–6.80 (m, 5H, Ph), 4.96–4.50 (m,
1H, POCH), 4.16 (d, J 5 Hz, 2H, PhOCH2), 3.93–3.50 (m, 8H,
ClCH2 and 2POCH3); m/z 295 (M ϩ 1, 100.00%), 201 (15.62),
105 (8.60), 133 (93.64), 127 (45.18), 77 (12.38); δP 0.6956;
IR(neat) 1282, 1048 cmϪ1. Found: C, 44.51; H, 5.50; C11H16-
O5ClP requires C, 44.84; H, 5.47%.
Experimental section
1H-NMR spectra were recorded on an FX-90Q spectrometer in
carbon tetrachloride (TMS as the internal reference) or in
CDCl3. 31P-NMR spectra were recorded in CDCl3 on a
DRX-400 spectrometer (161.97 MHz, 85% H3PO4 as the
external reference). Mass spectra were determined on a
Finnigan 4021 instrument. IR spectra were recorded on
a Y-Zoom CURSOR spectrometer. Elemental analyses were
performed on a Rapid CHN-O-S instrument at Shanghai
Institute of Organic Chemistry. CH2Cl2 was distilled from
CaH2, THF from sodium–benzophenone. All the reaction
vessels were flame-dried under vacuum and back-filled with N2,
and all reactions were carried out under a N2 atmosphere. The
epoxides 1a, 1b, 1c, and 1h were obtained commercially and
purified prior to use (distilled from CaH2). The epoxides 1d, 1e,
1f and 1g were prepared from the literature.15 Compounds 3a-ꢁ,
3b-ꢁ, and 3k are known compounds, which were identified in
agreement with the literature data and only the 1H-NMR data
are reported here.
3-Chloro-1-(2-methoxyphenoxy)propan-2-yl dimethyl phos-
phate 3h-ꢁ. Colorless oil. δH (CCl4) 6.80 (s, 4H, Ph), 5.03–4.50
(m, 1H, POCH), 4.13 (d, J 5 Hz, 2H, ClCH2), 3.92–3.42 (m,
11H, 2POCH3, CH3OPh and PhOCH2); m/z 325 (M ϩ 1,
81.55%), 203 (36.03), 201 (100.00), 165 (22.25), 163 (8.32), 127
(14.81), 109 (4.66); δP 0.6419; IR(neat) 1257, 1046 cmϪ1. Found:
C, 44.41; H, 5.70; C12H18O6ClP requires C, 44.39; H, 5.59%.
2-Chloro-2-(2,4-dichlorophenyl)ethyl diethyl phosphate 3i-ꢀ.
Colorless oil. δH (CCl4) 7.60–7.32 (m, 3H, Ph), 5.63 (t, J 6 Hz,
1H, ClCH), 4.42 (t, JHH = JPH 6 Hz, 2H, POCH2CHCl), 4.40–
3.70 (m, 4H, 2POCH2), 1.40 (t, J 6 Hz, 6H, 2CH3); m/z 360 (M,
33.21%), 327 (54.25), 325 (77.04), 208 (100.00), 206 (96.84), 193
(13.61), 171 (37.24), 155 (54.88), 137 (24.52), 109 (37.88); δP
Ϫ1.187; IR(neat) 1276, 1031 cmϪ1. Found: C, 39.78; H, 4.57;
C12H16Cl13O4P requires C, 39.86; H, 4.46%.
General procedure for the ring opening of epoxides with 2a or 2b
(method A)
2-Chloro-2-(4-methylphenyl)ethyl dimethyl phosphate 3j-ꢀ.
Colorless oil. δH (CDCl3) 7.20 (m, 4H, Ph), 5.05 (t, J 7.0 Hz,
1H, ClCH), 4.40–4.20 (t, 2H, JHH = JPH 7 Hz, POCH2), 3.66 (d,
JPH 11 Hz, 2CH3), 2.31 (s, 3H, CH3Ph); m/z 279 (M ϩ 1,
15.68%), 243 (100.00), 152 (69.63), 139 (32.18), 127 (37.54), 117
(53.24), 91 (15.30), 77 (10.69); δP 1.0611; IR(neat) 1282, 1037
cmϪ1. Found: C, 47.41; H, 5.91; C11H16O4ClP requires C, 47.41;
H, 5.79%.
A solution of TiCl4 (0.05 mmol) in CH2Cl2 (2 ml) was added to
the stirred solution of 2a or 2b (5 mmol) in CH2Cl2 (10 ml) at
room temperature via syringe. Then, a solution of epoxide (5
mmol) in CH2Cl2 (10 ml) was added dropwise during 15 min to
the above mixture. The progress of the reaction was monitored
by TLC. After complete disappearance of the starting material
(0.5–4 h), water (1 ml) was added to the reaction mixture, and
the mixture was left to stir at room temperature, then dried,
filtered and concentrated. The residue was purified by flash
chromatography on silica gel.
2-Chlorocyclohexyl dimethyl phosphate 3k.2b Colorless oil.
δH (CDCl3) 4.32–4.23 (m, 1H), 3.90–3.78 (m, 1H), 3.80, 3.76
(2d, 6H, JPH 11.20 Hz, 2POCH3), 2.38–1.20 (m, 8H).
3-Chloropropan-2-yl diethyl phosphate 3a-ꢁ.2a Colorless oil.
δH (CCl4) 4.93–4.33 (m, POCH), 4.43–3.76 (m, 4H, POCH2),
3.42 (d, J 4 Hz, 2H, ClCH2), 1.10 (m, 9H, 3CH3).
General procedure for the ring opening of epoxides with 2a–c
formed in situ (method B)
To a stirred solution of dimethyl or diethyl phosphonate (5.1
mmol) and CCl4 or CBr4 (5.1 mmol) in CH2Cl2 was added
dropwise NEt3 (0.5 mmol) in CH2Cl2 (2 ml) at 0 ЊC. After 10
1,3-Dichloropropan-2-yl diethyl phosphate 3b-ꢁ.2a Colorless
oil. δH (CCl4) 4.96–4.60 (m, 1H, POCH), 4.46–4.06 (m, 4H,
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min, Ti(OPr-i)4 (0.05 mmol) in CH2Cl2 (1 ml) was added. Then,
the epoxide (5 mmol) in CH2Cl2 (10 ml) was added dropwise to
the above mixture. The work up procedure was the same as
for method A.
(10.50), 81 (13.90), 79 (8.50); δP Ϫ0.006; IR(neat) 1280, 1028
cmϪ1. Found: C, 29.00; 4.69; C8H16IO4P requires C, 28.76; H,
4.83%.
4-Iodobutyl dimethyl phosphate 3n. Pale yellow oil. δH (CCl4)
4.13–4.80 (m, 2H, POCH2), 3.66 (d, J 12 Hz, 6H, 2POCH3),
3.36–3.20 (t, 2H, ICH2), 2.03–1.53 (m, 4H, CH2CH2); m/z
309 (M ϩ 1, 7.45%), 235 (5.37), 183 (100.00), 127 (56.35),
2-Bromo-2-phenylethyl diethyl phosphate 3d-ꢀ. Colorless oil.
δH (CCl4) 7.43 (s, 5H, Ph), 5.16 (t, J 8 Hz, 1H, BrCH), 4.50 (t,
JHH = JPH
8 Hz, 2H, POCH2CHBr), 4.32–3.83 (m, 4H,
109 (22.70), 55 (16.04); δP 1.9111; IR(neat) 1278, 1045 cmϪ1
.
2POCH2), 1.32 (t, J 6 Hz, 6H, 2CH3); m/z 257 (M, 35.65%), 229
(23.58), 201 (55.60), 184 (61.35), 182 (56.39), 155 (20.91), 103
Found: C, 23.66; H, 4.25; C6H14IO4P requires C, 23.40; H,
4.58%.
(100.00), 99 (24.65); δP Ϫ1.311; IR(neat) 1273, 1028 cmϪ1
.
Found: C, 42.42; H, 5.30; C12H18BrO4P requires C, 42.75; H,
5.38%.
Acknowledgements
3-Bromo-1-phenoxypropan-2-yl diethyl phosphate 3f-ꢁ. Color-
less oil. δH (CDCl3) 7.36–6.72 (m, 5H, Ph), 4.90–4.62 (m, 1H,
POCH), 4.20 (d, 2H, J 5 Hz, PhOCH2), 4.30–3.82 (m, 4H,
2POCH2), 3.66 (d, J 5 Hz, 2H, BrCH2), 1.30, 1.25 (2t, J 5 Hz,
6H, 2CH3); m/z 369 (M ϩ 1, 37.20%), 367 (35.85), 155 (47.84),
133 (100.00), 105 (19.35), 77 (13.10); δP Ϫ1.586; IR(neat) 1246,
1032 cmϪ1. Found: C, 42.48; H, 5.49; C13H20O5BrP requires C,
42.53; H, 5.49%.
The project was supported by the National Nature Science
Foundation of China. We thank Professor Q. Q. Zhuang,
Mr W. J. Xie and Mr F. Qin of Shanghai Medical University for
their preliminary biochemical evaluation.
References and notes
1 (a) S. E. Denmark, P. A. Barsanti, K. T. Wong and R. A. Stavenger,
J. Org. Chem., 1998, 63, 2428; (b) H. Sharghi, A. R. Massah,
E. Eshghi and K. Niknam, J. Org. Chem., 1998, 63, 1455.
2 (a) E. T. McBee and J. G. Damrath, US Pat., 1965, 3206495
(Chem. Abstr., 1965, 63, 14705a); (b) D. Arlt and K. Ley, Ger. Pat.,
1974, 2417143 (Chem. Abstr., 1976, 84, 89602c).
3 D. P. Rotella, Chemtracts: Org. Chem., 1996, 9, 190.
4 A. Albeck, S. Fluss and R. Persky, J. Am. Chem. Soc., 1996, 118,
3591.
2-Bromocyclohexyl diethyl phosphate 3l. Colorless oil.
δH (CCl4) 4.50–3.86 (m, 6H, 2POCH2 and POCH, BrCH), 2.53–
1.40 (m, 8H, 4CH2), 1.36 (t, 6H, J 8 Hz, 2CH3); m/z 317
(M ϩ 1, 7.93%), 315 (7.79), 155 (100.00), 127 (45.80), 99
(45.70), 81 (24.77); δP 1.994; IR(neat) 1269, 1031 cmϪ1. Found:
C, 38.00; H, 6.54; C10H20O4BrP requires C, 38.11; H, 6.40%.
5 Z. Wang, W. Zhou and G. Ling, Tetrahedron Lett., 1985, 26, 6221.
6 Y. Gao, R. M. Hanson, T. M. Klunder, S. Y. Ko, H. Masamune and
K. B. Sharpless, J. Am. Chem. Soc., 1987, 109, 5765.
7 For a review, see: C, Bonini and G. Gighi, Synthesis, 1994, 225.
8 H. McCombie, B. C. Saunders and G. J. Stacey, J. Chem. Soc., 1945,
921.
9 F. R. Atherton and A. R. Todd, J. Chem. Soc., 1947, 647.
10 J. J. Eisch, Z. Liu, X. Ma and G. Zhen, J. Org. Chem., 1992, 57,
5140.
11 During the course of the experiment we observed an interesting
phenomenon that Ti(OPr-i)4 readily reacts with DAHPs to give the
isopropyl dialkyl phosphate, but we do not know which form of
Ti(OPr-i)4 Ϫ nXn is the true catalyst.
General procedure for the ring opening of epoxides with 2d
formed in situ (method C)
To a stirred suspension of I2 (5.0 mmol) in CH2Cl2 (10 ml) was
added dropwise trimethyl phosphite (5 mmol) in CH2Cl2 (5 ml)
at Ϫ10 ЊC. After 10 min, Ti(OPr-i)4 (0.05 mmol) in CH2Cl2
(1 ml) was added. Then, the epoxide (5 mmol) in CH2Cl2 (10
ml) was added dropwise to the above mixture. The workup
procedure was the same as for method A.
3-Iodo-1-phenoxypropan-2-yl dimethyl phosphate 3g-ꢁ. Color-
less oil. δH (CCl4) 7.43–6.80 (m, 5H, Ph), 4.70–4.32 (m, 1H,
POCH), 4.28–4.13 (m, 2H, PhOCH2), 3.72, 3.78 (2d, JPH 11 Hz,
6H, 2POCH3), 3.50 (d, J 5 Hz, 2H, ICH2); m/z 386 (M, 10.55%),
292 (3.14), 133 (100.00), 127 (19.59), 109 (18.72), 105 (26.16), 77
(18.11); δP 0.4542; IR(neat) 1280, 1048 cmϪ1. Found: C, 34.20;
H, 4.20; C11H16IO4P requires C, 34.22; H, 4.18%.
(RO)2P(᎐O)X ϩ Ti(Oi-Pr)4 →
᎐
Ti(Oi-Pr)4 Ϫ nXn ϩ (RO)2P(᎐O)(Oi-Pr)
᎐
X = Cl, Br, I
12 S. Bruns and G. Haufe, Tetrahedron: Asymmetry, 1999, 10,
1563.
13 J. K. Stowell and T. S. Widlanski, J. Org. Chem., 1995, 60, 6930.
14 N. Iranpoor and B. Zeynizadeh, J. Chem. Res. (S), 1998, 582.
15 (a) H. Schwarz and W. Franke, Tetrahedron, 1979, 35, 1969;
(b) D. Gravel, J. Hebert and D. Thoraval, Can. J. Chem., 1983, 61,
400.
2-Iodocyclohexyl diethyl phosphate 3m. Colorless oil.
δH (CCl4) 4.50–3.96 (m, 2H, POCHCHI), 3.82, 3.77 (2d, 6H,
JPH 11 Hz, 2POCH3), 2.53–1.10 (m, 8H, 4CH2); m/z 335
(M ϩ 1, 27.61%), 243 (7.64), 207 (7.24), 127 (100.00), 109
J. Chem. Soc., Perkin Trans. 1, 2000, 1651–1655
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