International Journal of Organic Chemistry, 2011, 1, 1-5
Published Online March 2011 (http://www.SciRP.org/journal/ijoc)
An Efficient α-Phosphoryloxylation of Ketones
Ye Pu, Jie Yan*
College of Chemical Engineering and Materials Sciences, Zhejiang University of Technology, Hangzh ou, P. R. China
Received February 10, 2011; revised February 28, 2011; accepted March 4, 2011
Abstract
An efficient α-phosphoryloxylation of ketones has been developed. When ketones were treated with (diace-
toxyiodo)benzene and phosphates in CH2Cl2 at room temperature, the α-phosphoryloxylaction of ketones
was easily be carried out, providing the ketol phosphates in good yields.
Keywords: α-Phosphoryloxylation, Ketol Phosphate, (Diacetoxyiodo)benzene, Synthesis
1. Introduction
Hypervalent iodine reagents have found broad applica-
tion in organic chemistry and nowadays frequently used
in synthesis due to they are nonmetallic oxidation re-
agents and avoid the issues of toxicity of many transition
metals commonly involved in such processes [1-10].
They offer high potential for the improvement of known
reactions not only from the environmental point of
view，they are also potentially interesting reagents for
the development of completely new synthetic transfor-
mations. Among hypervalent iodine reagents, [hydroxy
(tosyloxy)iodo]benzene (Koser’s reagent) is the most
popular and useful reagent for the direct α-tosyloxylation
of ketones, and with which the α-tosyloxylation of ke-
tones has been extensively studied especially in recent
years [11-17]. However, to our knowledge, the analogue
reaction of ketones for α-phosphoryloxylation has been
rather limited and only two methods for preparation of
the important ketol phosphates have been known. Using
the hypervalent iodine reagent, [hydroxyl ((bis(phenyloxy)
phphoryl)-oxy)iodo]benzene to react with ketones was
the main method which was reported by Koser’s group in
1988, in this process hypervalent iodine reagent must be
pre-prepared from (diacetoxyiodo)benzene and diphenyl
phosphate [18-19]. The reaction of the prepared hyper-
valent iodine reagent with terminal alkynes in aqueous
MeCN was another protocol for preparation of ketol-
phosphates [20]. In order to extend the scope of α-
phosphoryloxylation of ketones and to prepare more ke-
tol phosphates, the development of a simple, mild and
efficient α-phosphoryloxylation of ketones is a much-
sought process. Herein we would like to report an effi-
cient one-pot α-phosphoryloxylation of ketones and a
series of ketol phosphates have been prepared in good
yields.
2. Results and Discussions
At the beginning, we investigated the “one pot” proce-
dure to improve Koser’s method due to the preparation
of [hydroxyl((bis(phenyloxy)phosphoryl)oxy)iodo]bezene
and its reaction with ketones were separated in two steps.
When one equivalent of (diacetoxyiodo)benzene (DIB),
diphenyl phosphate and acetophenone were mixed in
CH2Cl2 at room temperature and stirred for 24 h, the de-
sired product of α-phosphoryloxyl acetophenone was
separated in 38% yield after separation. Then, a series of
experiments were performed on the reaction of (diace-
toxyiodo)benzene, diphenyl phosphate and acetophenone
to determine the suitable reaction conditions (Scheme 1),
the results are summarized in Table 1.
The results indicate that the yield depended on solvent
and CH2Cl2 was found to be the most preferred (entries
1-5). When (diacetoxyiodo)benzene and diphenyl phos-
phate reached to two equivalents, the yield was increased
to 43% (entry 6); while two equivalents of acetophenone
were used to reacted with one equivalent of (diacetoxy-
iodo)benzene and diphenyl phosphate, the reaction got
the higher yield of 48% (entry 7). We found that the
RT
PhI(OAc)2HOPO(OPh)2 PhCOCH3PhCOCH2OPO(OPh)2
Scheme 1

2 Y. PU ET AL.
Table 1. Optimization of the α-phosphoryloxylation of acetophenone.
Entry Acetophenone (equiv.) DIB (equiv.) Diphenyl phosphate (equiv.) Solvent (2 mL) Time (h) Yield (%)a
1 1 1 1 CH3CN 24 10
2 1 1 1 THF 24 20
3 1 1 1 CH3OH 24 9
4 1 1 1 CF3CH2OH 24 9
5 1 1 1 CH2Cl2 24 38
6 1 2 2 CH2Cl2 24 43
7 2 1 1 CH2Cl2 24 48
8 2 1 1 CH2Cl2 2 8b
9 2 1 1 CH2Cl2 4 13b
10 2 1 1 CH2Cl2 8 45b
11 2 1 1 CH2Cl2 12 69b
12 2 1 1 CH2Cl2 16 72b
13 2 1 1 CH2Cl2 24 80b
aIsolated yield; bMeasured by 1H NMR.
product of α-phosphoryloxyl acetophenone was partly
decomposed in separation and the yield was decreased
much, then we used 1H NMR technique to show the true
yield and after 24 h the reaction reached the highest yield
of 80% (entries 8-13).
Under the optimum reaction conditions, the reaction of
a series of ketones (1) with (diacetoxyiodo)benzene and
phosphate (2) in CH2Cl2 at room temperature was inves-
tigated (Scheme 2), and several ketol phosphates (3)
were obtained which all were characterized by 1H NMR,
13C NMR, IR and MS spectra, the results are summarized
in Table 2. It is shown that the α-phosphoryloxylaction
of ketones was easily carried out at room temperature
and complete in 24 h, most provided the corresponding
ketol phosphates in good to excellent yields. In com-
parison with other ketones, β-diketone 1e and 1f usually
needed much less time in the reaction and got the pro-
ducts in excellent yields due to the high activity of
α-hydrogen (entries 5-6,8).
The proposed mechanism for the α-phosphoryloxy-
laction of ketones is similar to the literature procedure
[21], which is shown as follows (Scheme 3).
3. Experimental
IR spectra were recorded on a Thermo-Nicolet 6700 in-
strument, NMR spectra were measured on a Bruker
ANANCE Ⅲ (500 MHz) spectrometer, and Mass spec-
tra were determined on Thermo-ITQ 1100 mass spec-
trometer. Ketones, (diacetoxyiodo)benzene and phos-
phate are commercially available.
4. A Typical Procedure for
α-Phosphoryloxylation of Ketones
A mixture of acetophenone (1a) (0.5 mmol), (diacetoxy
iodo)benzene (0.25 mmol) and diphenyl phosphate (2a)
(0.25 mmol) in CH2Cl2 (2 mL) was stirred at room tem-
perature for 24 h, then H2O (5 ml) and sat. aq Na2CO3
RCCH2R' + PhI(OAc)2 + (R''O)2PO2H RCCH(R')OP(OR'')2
OO O
CH2 Cl2
RT
123
1a: R=Ph, R'=H
1b: R=Me, R'=H
1c: R=p-NO2-C6H4, R'=H
1d: R, R'=-(CH2)4-
1e: R=Ph, R'=PhCO
1f: R=Ph, R'=MeCO
3a: R=Ph, R'=H, R''=Ph
3b: R=Me, R'=H, R''=Ph
3c: R=p-NO2-C6H4, R'=H, R''=Ph
3d: R, R'=-(CH2)4-, R''=Ph
3e: R=Ph, R'=PhCO, R''=Ph
3f: R=Ph, R'=MeCO, R''=Ph
3g: R=Ph, R'=H, R''=Bz
3h: R=Ph, R'=MeCO, R''=Bz
4
2a: R''=Ph
2b: R''=Bz
2c: R''=p-NO2-C6H4
3i: R=Ph, R'=H, R''=p-NO2-C6H
Scheme 2

Y. PU ET AL.
3
Table 2. The result of the α-phosphoryloxylation of ketone.
Entry Ketone (1) Phosphate (2) Ketol phosphate (3) Time (h) Yield (%)a
1 1a 2a 3a 24 80
2 1b 2a 3b 24 70
3 1c 2a 3c 28 68
4 1d 2a 3d 24 92
5 1e 2a 3e 45 (min) 90
6 1f 2a 3f 45 (min) 91
7 1a 2b 3g 24 50
8 1f 2b 3h 45 (min) 92
9 1a 2c 3i 24 69
a Measured by 1H-NMR.
R
R'
OH+
IOAcPh
R
R'
O
R
R'
OH
R
OPO(OR'')2
O
R'
OPO(OR'')2
R
R'
O
IPh
OPO(OR'')2
-PhI
-AcOH
PhI(OAc)2
HOPO(OR'')2
Scheme 3
(1 mL) were added. After separation, the water layer was
extracted with CH2Cl2 (2 × 5 mL). The combined or-
ganic layer was dried over anhydrous MgSO4, filtered
and concentrated under reduced pressure to give the
residue with which the yield of α-phosphoryloxyl aceto-
phenone (3a) was determined in 80% by 1H NMR tech-
nique. The residue was purified on a silica gel plate using
(4:1 hexane-ethyl acetate) as eluant to give 3a in the
yield of 48%.
3a: Oil (Lit.18); 1H NMR (500 MHz, CDCl3): 7.89 -
7.87 (m, 2H), 7.62 - 7.59 (m, 1H), 7.49 - 7.46 (m, 2H),
7.37 - 7.34 (m, 4H), 7.30 - 7.26 (m, 4H), 7.22 - 7.19 (m,
2H), 5.46 (d, J = 10.0 Hz, 2H); 13C NMR (125 MHz,
CDCl3): 191.20(d, J = 5.0 Hz), 150.40 (d, J = 7.5 Hz),
134.04, 133.72, 129.78, 128.88, 127.78, 125.51, 120.18
(d, J = 5.0 Hz), 69.90 (d, J = 5.0 Hz); IR (film, cm–1):
1709, 1594, 1489, 1291, 1222, 1189, 1102, 1026; MS (EI,
m/z, %): 369 (M+1, 3.5), 275 (100).
3b: Oil (Lit.18); 1H NMR (500 MHz, CDCl3): 7.38 -
7.34 (m, 4H), 7.28 - 7.26 (m, 2H), 7.23 - 7 .22 (m, 4H),
4.72 (d, J = 9.5 Hz, 2H), 2.16(s, 3H); 13C NMR (125
MHz, CDCl3): 201.39 (d, J = 6.3 Hz), 150.17 (d, J = 6.3
Hz), 129.72, 125.50, 119.94 (d, J = 5.0 Hz), 71.54 (d, J
= 6.3 Hz), 25.78; IR (film, cm–1): 1739, 1194, 1092,
1024; MS (EI, m/z, %): 307 (M+1, 2), 250 (100).
3c: Oil; 1H NMR (500 MHz, CDCl3): 8.31 (d, J = 9.0
Hz, 2H), 8.04 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 7.5 Hz,
4H), 7.28 - 7.22 (m, 6H), 5.44 (d, J = 10.5 Hz, 2H); 13C
NMR (125 MHz, CDCl3): 196.26, 150.30, 141.33,
136.46, 134.89, 130.90, 129.04, 125.66, 123.98, 120.07
(d, J = 5.0 Hz), 69.99 (d, J = 5.0 Hz); IR (film, cm–1):
1693, 1527, 1346, 1261, 1188, 1101; MS (EI, m/z, %):
413 (M, 2), 94 (100); HRMS: C20H16NO7P calcd.:
413.0664, found: 413.0632.
3d: Oil (Lit.18); 1H NMR (500 MHz, CDCl3): 7.37 -
7.32 (m, 6H), 7.25 - 7.19 (m, 4H), 5.03 - 4.98 (m, 1H),
2.59 - 2.55 (m, 1H), 2.37 - 2.31 (m, 2H), 2.0 - 2.02 (m,
1H), 1.95 - 1.92 (m, 1H), 1.86 - 1.80 (m, 1H), 1.75 - 1.60
(m, 2H); 13C NMR (125 MHz, CDCl3): 203.58, 150.62 (d,
J = 6.3 Hz), 150.44 (d, J = 7.5 Hz), 129.72 (d, J = 10.0
Hz), 129.58, 125.45, 120.43 (d, J = 3.8 Hz), 120.28 (d, J
= 5.0 Hz), 81.36 (d, J = 7.5 Hz), 40.51, 35.03 (d, J = 5.0
Hz), 26.88, 23.34; IR (film, cm–1): 1734, 1284, 1221,
1190, 1069, 1026; MS (EI, m/z, %): 346 (M+, 1), 94
(100).
3e: Oil (Lit.18); 1H NMR (500 MHz, CDCl3): 8.09 -
8.04 (m, 4H), 7.55 - 7.52 (m, 2H), 7.41 - 7.38 (m, 4H),
7.33 - 7.27 (m, 4H), 7.24 - 7.242 (m, 4H), 7.19 - 7.15 (m,
2H), 6.90 (d, J = 9.0 Hz, 1H); 13C NMR (125 MHz,
CDCl3): 190.35 (d, J = 5.0 Hz), 150.22 (d, J = 7.5 Hz),
134.29 (d, J = 12.5 Hz), 133.73, 129.76 (d, J = 16.3 Hz),
129.42, 128.80 (dd, J = 10.0, 3.8 Hz), 127.50, 125.70,

4 Y. PU ET AL.
120.21 (d, J = 5.0 Hz), 84.06 (d, J = 6.3 Hz); IR (film,
cm–1): 1711, 1682, 1294, 1230, 1186, 1163, 1091, 1011;
MS (EI, m/z, %): 472 (M+, 2), 94 (100).
3f: Oil; 1H NMR (500 MHz, CDCl3): 7.94 (dd, J = 8.0,
1.0 Hz, 2H), 7.61 - 7.58 (m, 1H), 7.45 - 7.42 (m, 2H),
7.37 - 7.31 (m, 2H), 7.28 - 7.20 (m, 5H), 7.17 - 7.14 (m,
3H), 6.11 (d, J = 8.5 Hz, 1H), 2.22 (s, 3H); 13C NMR
(125 MHz, CDCl3): 190.35 (d, J = 5.0 Hz), 150.22 (d, J
= 7.5 Hz), 134.29 (d, J = 12.5 Hz), 133.73, 129.76 (d, J
= 16.3 Hz), 129.42, 128.80 (dd, J = 10.0, 3.8 Hz),
127.50, 125.70, 120.21 (d, J = 5.0 Hz), 84.06 (d, J = 6.3
Hz); IR (film, cm–1): 1730, 1688, 1218, 1024; MS (EI,
m/z, %): 410 (M+, 1), 105 (100); HRMS: C22H19O6P
calcd.: 410.0919, found: 410.0889.
3g: Oil; 1H NMR (500 MHz, CDCl3): 7.84 (d, J = 8.0
Hz, 2H), 7.58 - 7.52 (m, 1H), 7.47 (d, J = 8.0 Hz, 2H),
7.34 - 7.30 (m, 10H), 5.22 (d, J = 10.0 Hz, 2H), 5.18 (dd,
J = 8.0, 6.0 Hz, 4H); 13C NMR (125 MHz, CDCl3):
191.99 (d, J = 5.0 Hz), 135.67 (d, J = 6.3 Hz), 133.89,
128.80, 128.51, 128.02, 127.68, 69.70 (d, J = 5.0 Hz),
68.67 (d, J = 5.0 Hz); IR (film, cm–1): 1708, 1279, 1234,
1116, 1014; MS (EI, m/z, %): 397 (M+, 1), 199 (100);
HRMS: C22H21O5P calcd.: 396.1127, found: 396.1121.
3h: Oil; 1H NMR (500 MHz, CDCl3): 7.98 (d, J = 7.5
Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.42 (t, J = 8.0 Hz,
2H), 7.38 - 7.29 (m, 10H), 5.97 (d, J = 8.0 Hz, 1H), 5.15
(d, J = 9.0 Hz, 2H), 5.10 - 5.01 (m, 2H), 2.22 (s, 3H);
13C NMR (125 MHz, CDCl3): 191.99 (d, J = 5.0 Hz),
135.67 (d, J = 6.3 Hz), 133.89, 128.80, 128.51, 128.02,
127.68, 69.70 (d, J = 5.0 Hz), 68.67 (d, J = 5.0 Hz); IR
(film, cm–1): 1708, 1279, 1234, 1116, 1014; MS (EI, m/z,
%): 439 (M+1, 2), 105 (100); HRMS: C24H23O6P calcd.:
438.1232, found: 438.1201.
3i: Oil; 1H NMR (500 MHz, CDCl3): 8.28 (d, J = 9.0
Hz, 4H), 7.87 (d, J = 7.5 Hz, 2H), 7.64 - 7.62 (m,1H),
7.52 - 7.45 (m, 6H), 5.57 (d, J = 12.5Hz, 2H); 13C NMR
(125 MHz, CDCl3): 190.55 (d, J = 3.8 Hz), 154.55 (d, J
= 6.3 Hz), 145.19, 134.41, 132.98, 128.98, 127.62,
125.72, 120.86 (d, J = 2.5 Hz), 70.79 (d, J = 6.3 Hz); IR
(film, cm–1): 1713, 1614, 1591, 1518, 1491, 1344, 1290,
1248, 1215, 1109; MS (EI, m/z, %): 458 (M+, 1), 105
(100); HRMS: C20H15N2O9P calcd.: 458.0515, found:
458.0488.
5. Acknowledgements
Financial supports from the Natural Science Foundation
of China (Project 21072176) and Zhejiang Province
Natural Science Foundation of China (Project Y4100231)
are gratefully acknowledged.
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