C-H hydroxylation of phosphonates with oxygen in [bmIm]OH to produce quaternary α-hydroxy phosphonates

Article abstract of DOI:10.1021/jo502883q

A highly efficient and mild [bmIm]OH-catalyzed α-hydroxylation of phosphonates using O₂ as the oxygen source is described. The employment of ionic liquid under mild reaction conditions makes this transformation green and practical. Especially, this reaction provided a novel and convenient methodology for the construction of quaternary α-hydroxy phosphonates.

Full text of DOI:10.1021/jo502883q

Note
pubs.acs.org/joc
C−H Hydroxylation of Phosphonates with Oxygen in [bmIm]OH To
Produce Quaternary α‑Hydroxy Phosphonates
Xiangguang Li,† Cheng Jin,§ and Lijun Gu*,‡
†Chemical Science and Technology Department, Kunming University, Kunming 650214, China
‡Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan
Minzu University, Kunming 650500, China
§New United Group Company Limited, Changzhou, Jiangsu 213166, China
S
* Supporting Information
ABSTRACT: A highly efficient and mild [bmIm]OH-catalyzed α-hydroxylation of
phosphonates using O2 as the oxygen source is described. The employment of ionic
liquid under mild reaction conditions makes this transformation green and practical.
Especially, this reaction provided a novel and convenient methodology for the
construction of quaternary α-hydroxy phosphonates.
−H bonds are ubiquitous in bioactive molecules,
bility.6 There have been many reports describing the successful
Cpharmaceuticals, natural products, and industrial materi- use of ILs as environmentally friendly or “green” solvents. ILs
have also been used as catalysts or promoters in synthetic
reactions, including Mannich reactions,7 Friedel−Crafts reac-
tions,8 Knoevenagel condensations,9 and Henry reactions.10 ILs
can be tailor-made for specific purposes by modifying the
cations and anions, providing them with greater potential. To
our knowledge, however, IL-catalyzed direct hydroxylation of
phosphonates remains unknown. On the basis of our previous
work on dioxygen activation and the use of molecular oxygen as
the terminal oxidant,11 we set out to explore the use of
molecular oxygen for the IL-catalyzed direct hydroxylation of
phosphonates (Scheme 1).12 This reaction represents a rare
example of direct hydroxylation of phosphonates and allows the
highly regioselective preparation of quaternary α-hydroxy
phosphonates.
als. Although catalytic activation and subsequent functionaliza-
tion of C−H bonds is very challenging, the formation of C−X
(X = C, N, O, etc.) bonds by activation of C−H bonds is one of
the most useful methods in organic synthesis, including the
total synthesis of natural products.1 This type of reaction is
favorable, both economically and ecologically, when compared
with more traditional approaches. Much current interest is
focused on the direct hydroxylation of unactivated C(sp3)−H
bonds, and significant progress has been achieved in recent
years.2
α-Hydroxy phosphonates, which have physical and structural
similarities to biologically important phosphate esters, possess
intriguing biological activities and have widespread applications
in many areas, including the biological and pharmaceutical
industries.3 As analogues of quaternary α-hydroxy acids,
quaternary α-hydroxy phosphonates, particularly, are of
considerable value. Incorporation of α,α-disubstituted α-
hydroxy phosphonates into peptides can alter the proteolytic
stability of the peptides and can also alter the secondary
structure of the corresponding proteins, which may give
valuable information on enzymatic mechanisms.4 The synthesis
of quaternary α-hydroxy phosphonates has thus become a topic
of great interest. Of the numerous methods that have been
developed, the most straightforward and atom-economical
approach is the Pudovic reaction, i.e., the nucleophilic addition
of phosphites to ketones.5 An alternative approach is the
reaction of acyl phosphonates with organoaluminum reagents
at low temperatures.3f
We first investigated the IL-catalyzed aerobic oxidation of
dimethyl 1-phenylethylphosphonate 1a (0.3 mmol) in the
presence of 1-n-butyl-3-methylimidazolium hydroxide
([bmIm]OH) (1.0 mmol) and P(OEt)3 (2.0 equiv), at 25 °C
under an O2 atmosphere for 6 h. These conditions afforded the
desired quaternary α-hydroxy phosphonate 2a in 77% yield
(Table 1, entry 1). We were surprised to find that the
hydroxylation reaction also proceeded well in air (Table 1,
entry 2). Other reagents, including PPh3, Na2S2O3, and
P(OMe)3, were tested and found to be less effective than
P(OEt)3 (Table 1, entries 3−5). The amount of P(OEt)3 was
found to influence the reaction; a good yield was achieved at a
loading of 2.5 equiv P(OEt)3 (Table 1, entries 6−8). Both
P(OEt)3 and O2 are essential for the reaction to take place
(Table 1, entries 9−10). No benefit was obtained by increasing
the reaction time (Table 1, entry 11). Interestingly, the reaction
also proceeded well in the dark (Table 1, entry 12).
Over the past decades, ionic liquids (ILs) have been
extensively studied and successfully applied in many areas,
including organic synthesis, electrochemistry, materials chem-
istry, and chemical separations. ILs have distinct physical and
chemical properties, which include low melting point, negligible
vapor pressure, excellent solvating ability, and good recycla-
Received: December 19, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/jo502883q
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The Journal of Organic Chemistry
Note
a b
,
Scheme 1. Synthetic Route to Quaternary α-Hydroxy
Table 2. Scope of Phosphonates
Phosphonates
a
Table 1. Screening Optimal Conditions
b
entry
additive
time
yield (%)
1
2
3
4
5
P(OEt)3
P(OEt)3
PPh3
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
6 h
7 h
6 h
70
59
62
Na2S2O3
P(OMe)3
P(OEt)3
P(OEt)3
P(OEt)3
none
trace
44
c
6
63
d
7
e
79
8
77
9
trace
0
f
10
P(OEt)3
P(OEt)3
P(OEt)3
11
79
g
12
71
a
Reaction conditions: 1a (0.3 mmol), additive (2.0 equiv), [bmIm]-
b
OH (1.0 mmol), 25 °C in O2 atmosphere for 6 h. Isolated yield.
c
d
e
f
P(OEt)3 (1.5 equiv). P(OEt)3 (2.5 equiv). P(OEt)3 (3.0 equiv). In
g
Ar atmosphere. The reaction was carried out in the dark.
With the standard reaction conditions defined, we next
investigated the substrate scope of the reaction by employing a
variety of phosphonates 1. The standard reaction conditions
were found to be compatible with a wide range of
phosphonates 1 (Table 2). Several aromatic substituents,
including Me, MeO, F, and Cl, were well-tolerated under the
standard conditions; substituents at the ortho-, meta-, or para-
positions had no distinct influence on the reaction. For
example, substrates 1c and 1g with a MeO group were
transformed into products 2c and 2g with similar yields. It is
noteworthy that halogen groups, F and Cl, were compatible
with the optimized reaction conditions, thereby enabling
subsequent modifications at the halogenated positions (Table
2, entries 2d−2f). Importantly, the polysubstituted phospho-
nate 1h gave the desired product 2h in good yield (Table 2,
entry 2h). The introduction of heterocyclic groups would make
this methodology to be more useful for the preparation of
pharmaceuticals and other commercially important materials
(Table 2, entry 2i). Gratifyingly, this direct hydroxylation
protocol could also be applied to substrate 1j, providing
product 2j in 74% yield. Reaction of substrate 1k, with two
phenyl groups, delivered the desired product in 62% yield
a
Reaction conditions: 1 (0.3 mmol), P(OEt)3 (2.5 equiv), [bmIm]OH
b
(1.0 mmol), 25 °C in O2 atmosphere for 6 h. Isolated yield.
(Table 2, entry 1k). Satisfyingly, the reaction was also
successful with aliphatic phosphonates (Table 2, entries 2l−
2m).
B
DOI: 10.1021/jo502883q
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The Journal of Organic Chemistry
Note
To gain an insight into the course of the reaction, we
conducted a series of control experiments.2j Addition of a
radical-trapping reagent, 2,2,6,6-tetramethylpiperidine-1-oxyl
(TEMPO) (1.0 equiv), did not inhibit the reaction, suggesting
that free radical intermediates are not involved. The results of
18O labeling demonstrated that the oxygen atom in the hydroxy
group originates from molecular oxygen. When a singlet oxygen
inhibitor, 1,4-diazabicyclo[2,2,2]octane (DABCO), was added
to the model reaction, the desired quaternary α-hydroxy
phosphonate 2a was obtained in 70% yield, suggesting little
involvement of singlet molecular oxygen in the transformation
(Scheme 2).13
a pressure of 1 atm. The new process thus provides a practical
and preferable, alternative to the existing procedures.
EXPERIMENTAL SECTION
■
Instrumentation and Chemicals. Reagents were obtained
commercially and used as received. Solvents were purified and dried
by standard methods. Substrates 1 were prepared according to the
literature methods.14 [bmIm]OH was prepared according to our
previous reported method.6e All title products were characterized by
1
infrared (IR), MS, H NMR, 13C NMR, and high-resolution mass
spectrometry (HRMS). IR spectra were reported in frequency of the
1
absorption (cm−1). H NMR spectra were recorded on 400 MHz in
CDCl3, and 13C NMR spectra were recorded on 100 MHz in CDCl3
using tetramethylsilane (TMS) as an internal standard or 85% H3PO4
as external standard for 31P NMR. Chemical shift values (δ) are given
in ppm. Coupling constants (J) were measured in Hz. Mass spectra
were obtained with ionization voltages of 70 eV. HRMS spectra were
obtained by ESI on a TOF mass.
Scheme 2. Experiments for Mechanistic Studies
Typical Experimental Procedure for Synthesis of α-Hydroxy
Phosphonates 2. An oven-dried Schlenk tube was charged with a
magnetic stir-bar, phosphonates 1 (0.3 mmol), [bmIm]OH (1.0
mmol), and P(OEt)3 (0.75 mmol). The tube was sealed, and oxygen
was purged through syringe. The reaction was stirred at 25 °C for 6 h.
After the reaction was finished, the reaction mixture was extracted with
30 mL of ethyl acetate. The extract was washed with brine, dried
(Na2SO4), and concentrated in vacuum, and the resulting residue was
purified by silica gel column chromatography (hexane/ethyl acetate)
to afford the desired products 2. The ionic liquid left in the reaction
vessel was rinsed with ether (2 mL) and dried under vacuum at 95 °C
for 3.5 h to eliminate any water trapped from moisture and reused for
subsequent reactions.
On the basis of these preliminary results, and those of
previous studies,2j we propose the catalytic cycle for this
transformation shown in Scheme 3. Carbanion A is initially
Dimethyl 1-Hydroxy-1-phenylethylphosphonate (2a).15 Yield:
1
79%, 54.5 mg; H NMR (400 MHz, CDCl3) δ: 7.59−7.55 (m, 2H),
7.40−7.28 (m, 3H), 4.41 (br, 1H), 3.71 (d, J = 10.4 Hz, 3H), 3.58 (d, J
= 10.0 Hz, 3H), 1.79 (d, J = 15.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 141.2 (d, J = 0.8 Hz), 128.3 (d, J = 2.0 Hz), 127.1 (d, J =
2.6 Hz), 125.4 (d, J = 4.1 Hz), 73.5 (d, J = 159.7 Hz), 54.3 (d, J = 7.3
Hz), 53.4 (d, J = 7.4 Hz), 26.2 (d, J = 3.2 Hz); 31P NMR (161 MHz,
CDCl3) δ: 26.21; IR (neat cm−1): 3251, 3031, 2921,1226, 1066, 1021,
990, 766; LRMS (EI 70 ev) m/z (%): 230 (M+, 100); HRMS m/z
(ESI) calcd for C10H16O4P (M + H)+ 231.0787, found 231.0784.
Dimethyl 1-Hydroxy-1-p-tolylethylphosphonate (2b).15 Yield:
Scheme 3. Possible Mechanism
1
70%, 51.2 mg; H NMR (400 MHz, CDCl3) δ: 7.48 (dd, J = 8.0
Hz, J = 2.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 4.46 (br, 1H), 3.77 (d, J
= 10.0 Hz, 3H), 3.63 (d, J = 10.0 Hz, 3H), 2.32 (d, J = 1.2 Hz, 3H),
1.83 (d, J = 15.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 138.3 (d, J
= 8.0 Hz), 136.4, 128.1, 125.2 (d, J = 4.2 Hz), 73.3 (d, J = 163.4 Hz),
54.1 (d, J = 7.7 Hz), 53.5 (d, J = 7.7 Hz), 25.7 (d, J = 3.3 Hz), 21.0; 31P
NMR (161 MHz, CDCl3) δ: 26.64; IR (neat cm−1): 3269, 2937, 1447,
1221, 1020, 941; LRMS (EI 70 ev) m/z (%): 244 (M+, 100); HRMS
m/z (ESI) calcd for C11H18O4P (M + H)+ 245.0943, found 245.0939.
Dimethyl 1-Hydroxy-1-(4-methoxyphenyl)ethylphosphonate
(2c).15 Yield: 64%, 49.9 mg; H NMR (400 MHz, CDCl3) δ: 7.43
1
generated from phosphonate 1a in basic IL [bmIm]OH. The
resulting carbanion A is rapidly trapped by O2 to give
superoxide anion B that, in turn, abstracts a hydrogen atom
from phosphonate 1a to form superoxide C. Reduction of
intermediate C by P(OEt)3 then gives the desired product 2a.
In summary, the procedure described, which uses a readily
available ionic liquid, [bmIm]OH, provides an efficient and
convenient procedure for direct hydroxylation of phosphonates
with molecular oxygen, without a requirement for any other
catalyst or organic solvent. This method offers marked
improvements in terms of operational simplicity, reaction
time, reaction conditions, general applicability, and good
isolated yields of products. The procedure is also environ-
mentally friendly, avoiding hazardous organic solvents and toxic
catalysts, and using molecular oxygen, the “greenest” oxidant, at
(dd, J = 2.0 Hz, J = 8.0 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H),
3.69 (d, J = 10.0 Hz, 3H), 3.57 (d, J = 10.0 Hz, 3H), 1.76 (d, J = 15.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.2 (d, J = 2.5 Hz),
132.1, 127.4 (d, J = 4.3 Hz), 113.4 (d, J = 2.0 Hz), 73.2 (d, J = 159.2
Hz), 55.4, 54.4 (d, J = 7.3 Hz), 53.2 (d, J = 7.3 Hz), 25.5 (d, J = 4.1
Hz); 31P NMR (161 MHz, CDCl3) δ: 26.51; IR (neat cm−1): 3313,
2988, 1561, 1451, 1233, 1041, 1014, 864. LRMS (EI 70 ev) m/z (%):
260 (M+, 100); HRMS m/z (ESI) calcd for C11H18O5P (M + H)+
261.0893, found 261.0890.
Dimethyl 1-(4-Fluorophenyl)-1-hydroxyethylphosphonate (2d).15
1
Yield: 61%, 45.4 mg; H NMR (400 MHz, CDCl3) δ: 7.60−7.53 (m,
2H), 7.04 (t, J = 10.0 Hz, 2H), 4.47 (br, 1H), 3.77 (d, J = 10.4 Hz,
3H), 3.64 (d, J = 10.4 Hz, 3H), 1.83 (d, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 161.6, 159.8, 159.1, 137.18, 137.15, 137.13,
137.12, 127.4, 127.39, 127.37, 127.32, 114.3, 114.1, 114.05, 114.03,
73.9 (d, J = 159.8 Hz), 54.7 (d, J = 7.6 Hz), 53.6 (d, J = 7.4 Hz), 26.1
C
DOI: 10.1021/jo502883q
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The Journal of Organic Chemistry
Note
(d, J = 4.4 Hz); 31P NMR (161 MHz, CDCl3) δ: 25.76; IR (neat
cm−1): 3401, 2992, 1500, 1426, 1221, 1125, 1067, 1023. LRMS (EI 70
ev) m/z (%): 248 (M+, 100); HRMS m/z (ESI) calcd for C10H15FO4P
(M + H)+ 249.0693, found 249.0699.
Dimethyl Hydroxydiphenylmethylphosphonate (2k).17 Yield:
62%, 54.3 mg; H NMR (400 MHz, CDCl3) δ: 7.56 (d, J = 7.6 Hz,
1
4H), 7.37−7.31 (m, 4H), 7.23−7.20 (m, 2H), 4.51 (br, 1H), 3.71 (d, J
= 10.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 141.4 (d, J = 1.4
Hz), 127.7 (d, J = 2.3 Hz), 127.0 (d, J = 3.1 Hz), 126.5 (d, J = 4.2 Hz),
75.8 (d, J = 254.6 Hz), 54.8 (d, J = 7.0 Hz), 53.4 (d, J = 7.8 Hz); 31P
NMR (161 MHz, CDCl3) δ: 23.53; IR (neat cm−1): 3260, 2959, 1444,
1235, 1120, 1043, 761. LRMS (EI 70 ev) m/z (%): 292 (M+, 100);
HRMS m/z (ESI) calcd for C15H18O4P (M + H)+ 293.0944, found
293.0947.
Dimethyl 1-(4-Chlorophenyl)-1-hydroxyethylphosphonate (2e).15
Yield: 56%, 44.3 mg; 1H NMR (400 MHz, CDCl3) δ: 7.44 (dd, J = 2.0
Hz, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 4.49 (br, 1H), 3.69 (d, J
= 10.0 Hz, 3H), 3.58 (d, J = 10.0 Hz, 3H), 1.71 (d, J = 15.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 139.1, 133.0 (d, J = 3.1 Hz), 128.6
(d, J = 2.2 Hz), 127.9 (d, J = 4.0 Hz), 73.1 (d, J = 159.5 Hz), 54.7 (d, J
= 7.8 Hz), 53.5 (d, J = 7.6 Hz), 25.7 (d, J = 7.8 Hz); 31P NMR (161
MHz, CDCl3) δ: 25.80; IR (neat cm−1): 3411, 2962, 1487, 1226, 1073,
1027, 867. LRMS (EI 70 ev) m/z (%): 264 (M+, 78); HRMS m/z
(ESI) calcd for C10H15ClO4P (M + H)+ 265.0397, found 265.0399.
Dimethyl 1-(2-Chlorophenyl)-1-hydroxyethylphosphonate (2f).15
Dimethyl 1-Hydroxycyclohexylphosphonate (2l).18 Yield: 58%,
36.2 mg; 1H NMR (400 MHz, CDCl3) δ: 4.48 (br, 1H), 3.71 (s, 3H),
3.68 (s, 3H), 1.85 (t, J = 10.2 Hz, 2H), 1.68−1.31 (m, 8H); 13C NMR
(100 MHz, CDCl3) δ: 71.8 (d, J = 164.0 Hz), 53.3 (d, J = 7.5 Hz),
31.1 (d, J = 2.8 Hz), 25.1, 19.7 (d, J = 11.3 Hz); 31P NMR (161 MHz,
CDCl3) δ: 26.43; IR (neat cm−1): 3331, 2987, 1230, 1144, 1065, 1034,
1019. LRMS (EI 70 ev) m/z (%): 208 (M+, 100); HRMS m/z (ESI)
calcd for C8H18O4P (M + H)+ 209.0945, found 209.0947.
1
Yield: 54%, 42.8 mg; H NMR (400 MHz, CDCl3) δ: 7.66−7.62 (m,
1H), 7.24 (dd, J = 1.2 Hz, J = 7.6 Hz, 1H), 7.19−7.14 (m, 2H), 4.46
(br, 1H), 3.68 (d, J = 10.4 Hz, 6H), 1.88 (d, J = 15.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 137.1 (d, J = 3.1 Hz), 131.8 (d, J = 5.3
Hz), 131.0 (d, J = 1.9 Hz), 129.4 (d, J = 3.5 Hz), 128.6 (d, J = 2.6 Hz),
126.3 (d, J = 1.7 Hz), 74.7 (d, J = 158.7 Hz), 54.4 (d, J = 7.0 Hz), 53.5
(d, J = 6.8 Hz), 25.3; 31P NMR (161 MHz, CDCl3) δ: 25.31; IR (neat
cm−1): 3381, 2949, 1448, 1402, 1225, 1118, 1054, 1037. LRMS (EI 70
ev) m/z (%): 264 (M+, 86); HRMS m/z (ESI) calcd for C10H15ClO4P
(M + H)+ 265.0397, found 265.0400.
Dimethyl 2-Hydroxybutan-2-ylphosphonate (2m).15 Yield: 70%,
38.2 mg; 1H NMR (400 MHz, CDCl3) δ: 4.49 (br, 1H), 3.74 (s, 3H),
3.71 (s, 3H), 1.85−1.81 (m, 1H), 1.69−1.62 (m, 1H), 1.33 (d, J = 15.6
Hz, 3H), 0.97 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
73.3 (d, J = 161.2 Hz), 54.5 (d, J = 6.8 Hz), 53.1 (d, J = 5.9 Hz), 29.2
(d, J = 5.0 Hz), 21.5 (d, J = 4.4 Hz), 7.1 (d, J = 8.0 Hz); 31P NMR
(161 MHz, CDCl3) δ: 30.10; IR (neat cm−1): 3300, 2939, 1452, 1227,
1132, 1057, 1020; LRMS (EI 70 ev) m/z (%): 182 (M+, 100); HRMS
m/z (ESI) calcd for C6H16O4P (M + H)+ 183.0791, found 183.0797.
Diethyl 1-Hydroxycyclohexylphosphonate (2n).19 Yield: 56%, 39.6
Dimethyl 1-Hydroxy-1-(3-methoxyphenyl)ethylphosphonate
(2g).16 Yield: 60%, 46.8 mg; H NMR (400 MHz, CDCl3) δ: 7.31−
1
7.28 (m, 1H), 7.23−7.19 (m, 2H), 6.88−6.85 (m, 1H), 4.44 (br, 1H),
3.87 (s, 3H), 3.79 (d, J = 10.4 Hz, 3H), 3.66 (d, J = 10.4 Hz, 3H), 1.81
(d, J = 15.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.1 (d, J =
2.0 Hz), 142.3 (d, J = 1.2 Hz), 129.1 (d, J = 2.6 Hz), 118.7 (d, J = 4.6
Hz), 113.2 (d, J = 2.8 Hz), 110.9 (d, J = 4.3 Hz), 73.5 (d, J = 158.2
Hz), 55.7, 54.3 (d, J = 7.7 Hz), 53.2 (d, J = 7.7 Hz), 25.1 (d, J = 3.5
Hz); IR (neat cm−1): 3291, 2921, 1441, 1231, 1129, 1044, 789; 31P
NMR (161 MHz, CDCl3) δ: 25.99; IR (neat cm−1): 3306, 2993, 1222,
1051, 1021, 771. LRMS (EI 70 ev) m/z (%): 260 (M+, 100); HRMS
m/z (ESI) calcd for C11H18O5P (M + H)+ 261.0893, found 261.0898.
Dimethyl 1-(2,4-Dichlorophenyl)-1-hydroxyethylphosphonate
1
mg; H NMR (400 MHz, CDCl3) δ: 4.16−4.09 (m, 4H), 3.37 (br,
1H), 1.86 (t, J = 9.5 Hz, 2H), 1.68−1.60 (m, 5H), 1.52−1.49 (m, 2H),
1.31−1.27 (m, 6H), 1.20−1.14 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ: 71.7 (d, J = 163.9 Hz), 62.6 (d, J = 7.4 Hz), 31.4, 25.2, 20.0
(d, J = 11.0 Hz), 16.4 (d, J = 5.4 Hz); 31P NMR (161 MHz, CDCl3) δ:
26.73; IR (neat cm−1): 3310, 2983, 2911, 1371, 1232, 1133, 1050,
1026. LRMS (EI 70 ev) m/z (%): 236 (M+, 100); HRMS m/z (ESI)
calcd for C10H22O4P (M + H)+ 237.1257, found 237.1261.
Methyl 1-(Ethoxyphosphono)-1-hydroxyethanoate (2o). Yield:
1
51%, 36.7 mg; H NMR (400 MHz, CDCl3) δ: 4.50 (br, 1H), 4.19−
(2h).17 Yield: 51%, 45.6 mg; H NMR (400 MHz, CDCl3) δ: 7.81
1
4.11 (m, 4H), 3.89 (s, 3H), 1.77 (d, J = 15.2 Hz, 3H), 1.33−1.29 (m,
6H); 13C NMR (100 MHz, CDCl3) δ: 169.8 (d, J = 3.8 Hz), 79.9 (d, J
= 139.3 Hz), 61.8 (d, J = 6.9 Hz), 61.6 (d, J = 7.4 Hz), 52.0 (d, J = 7.2
Hz), 16.2 (d, J = 3.2 Hz), 16.1 (d, J = 3.2 Hz), 11.7 (d, J = 5.9 Hz); 31P
NMR (161 MHz, CDCl3) δ: 23.33; IR (neat cm−1): 3307, 2981, 1725,
1240, 1113, 1048, 1014. LRMS (EI 70 ev) m/z (%): 240 (M+, 100);
HRMS m/z (ESI) calcd for C8H18O6P (M + H)+ 241.0767, found
241.0764.
(d, J = 7.2 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 6.4 Hz, 1H),
4.475(br, 1H), 3.69 (d, J = 10.4 Hz, 3H), 3.57 (d, J = 10.8 Hz, 3H),
1.85 (d, J = 15.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 139.3 (d, J
= 4.4 Hz), 133.4 (d, J = 3.9 Hz), 132.5 (d, J = 2.0 Hz), 131.8 (d, J =
5.8 Hz), 129.9 (d, J = 3.1 Hz), 127.1 (d, J = 2.6 Hz), 73.4 (d, J = 161.9
Hz), 54.4 (d, J = 7.1 Hz), 53.6 (d, J = 7.4 Hz), 24.8 (d, J = 3.3 Hz); 31P
NMR (161 MHz, CDCl3) δ: 25.33; IR (neat cm−1): 3284, 2960, 1469,
1247, 1108, 1053, 1019, 870. LRMS (EI 70 ev) m/z (%): 298 (M+,
31); HRMS m/z (ESI) calcd for C10H14Cl2O4P (M + H)+ 299.0007,
found 299.0011.
ASSOCIATED CONTENT
* Supporting Information
Spectral and analytical data. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
Dimethyl 1-Hydroxy-1-(thiophen-2-yl)ethylphosphonate (2i).17
Yield: 77%, 54.5 mg; 1H NMR (400 MHz, CDCl3) δ: 7.31−7.27
(m, 1H), 7.12−7.08 (m, 1H), 6.95−6.92 (m, 1H), 4.51 (br, 1H), 3.66
(d, J = 10.4 Hz, 3H), 3.58 (d, J = 10.4 Hz, 3H), 1.74 (d, J = 15.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 155.1, 142.3 (d, J = 10.1 Hz),
111.0, 108, 71.1 (d, J = 162.9 Hz), 54.3 (d, J = 7.5 Hz), 53.1 (d, J = 7.1
Hz), 23.1 (d, J = 2.8 Hz); 31P NMR (161 MHz, CDCl3) δ: 24.67; IR
(neat cm−1): 3266, 2930, 1440, 1224, 1151, 1042, 1020, 862. LRMS
(EI 70 ev) m/z (%): 236 (M+, 100); HRMS m/z (ESI) calcd for
C8H14O4PS (M + H)+ 237.0350, found 237.0354.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gulijun2005@126.com (L.G.).
■
Notes
The authors declare no competing financial interest.
Dimethyl 1-Hydroxy-1-phenylpropylphosphonate (2j).16 Yield:
1
ACKNOWLEDGMENTS
74%, 54.2 mg; H NMR (400 MHz, CDCl3) δ: 7.52−7.49 (m, 2H),
■
7.31 (t, J = 7.8 Hz, 2H), 7.23−7.20 (m, 1H), 4.43 (br, 1H), 3.69 (d, J
= 10.0 Hz, 6H), 2.61−2.27 (m, 2H), 0.87 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 138.7, 127.8 (d, J = 3.0 Hz), 127.0 (d, J =
3.3 Hz), 125.8 (d, J = 4.3 Hz), 75.7 (d, J = 158.6 Hz), 54.6 (d, J = 7.5
Hz), 53.1 (d, J = 7.3 Hz), 29.6 (d, J = 4.3 Hz), 9.1 (d, J = 8.9 Hz); 31P
NMR (161 MHz, CDCl3) δ: 25.29; IR (neat cm−1): 3256, 2969, 1429,
1231, 1052, 1017, 827. LRMS (EI 70 ev) m/z (%): 244 (M+, 100);
HRMS m/z (ESI) calcd for C11H18O4P (M + H)+ 245.0943, found
245.0944.
We are grateful for the financial support from the Program for
Innovative Research Team (in Science and Technology) in
University of Yunnan Province (IRTSTYN 2014-11) and the
State Ethnic Affairs Commission (12YNZ05).
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