Base-mediated tandem reaction of α-aryloxyacetophenones with phosphonates: Selective synthesis of enol phosphates

Article abstract of DOI:10.1055/s-0031-1289717

A new, simple method for the synthesis of enol phosphates by base-mediated tandem reaction of α-aryloxyacetophenones with phosphonates is described. In the presence of Cs₂CO₃, a variety of -aryloxyacetophenones smoothly underwent the sequential O-P bond-forming/C-O bond cleavage/isomerization tandem reaction with phosphonates at room temperature, providing the corresponding enol phosphates in moderate to excellent yields. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289717

PAPER
1119
Base-Mediated Tandem Reaction of a-Aryloxyacetophenones with
Phosphonates: Selective Synthesis of Enol Phosphates
S
elective Synthes
e
is of
E
nol
n
Jin-Heng Li*a
a
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University,
Changsha 410082, P. R. of China
Fax +86(731)88872531; E-mail: jhli@hnu.edu.cn; E-mail: xieyexiang520@126.com
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), Hunan Normal University,
Changsha 410081, P. R. of China
b
Received 21 December 2011; revised 20 January 2012
As a consequence, the preparation of enol phosphates oc-
cupies a place of particular importance in organic chemis-
try. The general method for enol phosphate preparation
includes the quenching of lithium enolates with dialkyl
Abstract: A new, simple method for the synthesis of enol phos-
phates by base-mediated tandem reaction of a-aryloxyacetophe-
nones with phosphonates is described. In the presence of Cs2CO3, a
variety of a-aryloxyacetophenones smoothly underwent the se-
quential O–P bond-forming/C–O bond cleavage/isomerization tan- phosphorochloridates.7,8 However, the method suffers
dem reaction with phosphonates at room temperature, providing the
from harsh reaction conditions including use of strong
corresponding enol phosphates in moderate to excellent yields.
bases (often LDA or KHMDS) and instable phosphoryl
Key words: base, tandem reaction, a-aryloxyacetophenone, phos-
phonate, enol phosphate
chlorides, which significantly limits its application in or-
ganic synthesis. Herein, we wish to report a new, simple
method for the synthesis of enol phosphates by sequential
O–P bond-forming/C–O bond cleavage/isomerization
Phosphonate-containing compounds are important be- tandem reaction of a-aryloxyacetophenones with phos-
cause they often display a multitude of robust biologically phonates and Cs2CO3 at room temperature under mild
important properties serving as pharmacological agents, conditions (Equation 1).9,10
as well as they have found widespread applications as ver-
satile intermediates in organic synthesis.1 Among the
known phosphonate-containing compounds, enol phos-
R1
O
R3
phates are particularly attractive and have proven their
worth in organic synthesis: for example, in the cross-
coupling reactions, such as the Stille,1l,2 Negishi,1f,n,3
Kumada,1c,m,4 Suzuki–Miyaura,1f,1i–k,5 and Heck couplings
(Scheme 1).1e,h,6
R2
R4
R2
O
+
Cs2CO3
R3
R4
R1OH
+
CH2Cl2, r.t.
OR5
OR5
O
O
P
OR5
OR5
H
P
O
Equation 1
R1
R3
R1
R3
Suzuki–Miyaura
coupling
Our investigation began with the reaction between 1-phe-
nyl-2-(o-tolyloxy)ethanone (1a) and dimethyl phospho-
nate (2a) under basic conditions to screen the optimal
reaction conditions, and the results are summarized in
Table 1. Initially, a series of bases were tested (Table 1,
entries 1–7). Screening revealed that while either KHCO3,
KF, or KHMDS has no effect on the reaction in dichlo-
romethane at room temperature (entries 1–3), the other
bases, such as LDA, CsF, t-BuOK, K2CO3, K3PO4, and
Cs2CO3, displayed some activities (entries 4–9). For ex-
ample, treatment of 1-phenyl-2-(o-tolyloxy)ethanone (1a)
with dimethyl phosphonate (2a) and CsF afforded the de-
sired product 3 in 26% yield (entry 5). To our delight, the
yield of 3 was enhanced sharply to 93% in the presence of
2 equivalents of Cs2CO3 (entry 9). Subsequently, the
amount of Cs2CO3 was examined, and it turned out that
two equivalents of Cs2CO3 were the most suitable for the
reaction (entries 9–11). In the light of the above results,
the effect of solvents was next evaluated (entries 9 and
R
Negishi coupling
ZnX
O
R1
OP(OR2)2
R1
R3
R1
R3
R5
Stille coupling
Kumada coupling
R5
R1
or
R1
Heck coupling
R5
Scheme 1 The cross-coupling reactions of enol phosphates
SYNTHESIS 2012, 44, 1119–1125
Advanced online publication: 17.02.2012
x
x.
x
x.
2
0
1
2
DOI: 10.1055/s-0031-1289717; Art ID: H117411SS
© Georg Thieme Verlag Stuttgart · New York

1120
R.-J. Song et al.
PAPER
12–15). Although the yield of 3 was reduced to some ex- group were employed to further screen the scope of the re-
tent, solvents such as MeCN, toluene, and THF still action (entries 9–21). To our delight, treatment of 2-phen-
showed high activity for the reaction (entries 12–14). oxy-1-phenylethanone (1b) with diethyl phosphonate
However, DMF was less effective, lowering the yield to (2b) and diisopropyl phosphonate (2c) was carried out
52% (entry 15). It is noteworthy that the optimal reaction smoothly to afford the corresponding enol phosphates 4
conditions are amenable to large-scale reaction: 92% and 5 in 99% and 88% yield, respectively (entries 9 and
yield of 3a was still obtained when 2 mmol of 1a was add- 10). Screening disclosed that substituents, such as methyl,
ed (entry 16).
methoxy, or fluoro groups, on the aromatic ring of the
arylethanone moiety were uniformly well tolerated under
the optimal conditions (entries 11–14). For example, sub-
strate 1l bearing a bulky o-MeO group was reacted with
phosphonate 2a and Cs2CO3 to form the desired product 8
in 87% yield (entry 13). It was noted that 1-(naphthalen-
1-yl)-2-phenoxyethanone (1n) was also suitable for the
reaction resulting in quantitative yields (entry 15). En-
couraged by the above results, a variety of a-substituted
substrates 1o–t were subsequently examined in the pres-
ence of phosphonate 2a and Cs2CO3 (entries 16–21). In-
terestingly, one or two substituents, even containing
active CN or PhSO2 functional groups, on the a-position
of the 1-aryl-2-phenoxyethanone moiety were perfectly
tolerated. Substrate 1o with a methyl group, for instance,
underwent the reaction with phosphonate 2a and Cs2CO3
to form the target product 11 in 91% yield with the 1:1 ra-
tio of Z/E-isomers (entry 16). Two other a-monosubstitut-
ed substrates 1p and 1q with a CN or a PhSO2 group also
provided a mixture of Z/E-isomers in excellent yields (en-
tries 17 and 18). Notably, unsymmetric a-disubstituted
substrate 1r, bearing both a methyl group and a 2-cyano-
ethyl group, was successfully reacted with phosphonate
2a and Cs2CO3 leading to the desired product 14 in 88%
yield (the ratio of Z/E-isomers = 1:1, entry 19). We were
pleased to find that the optimized conditions were consis-
tent with the symmetric a-disubstituted substrates 1s and
1t, providing the corresponding products 15 and 16 in
84% and 43% yield, respectively (entries 20 and 21).
Table 1 Screening Optimal Conditionsa
O
Ph
O
OMe
OMe
base
Ph
O
O
OMe
OMe
P
+
HP
2a
solvent
O
1a
3a
Entry
1
Base (equiv)
KHCO3 (2)
KF (2)
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
toluene
THF
Yield (%)b
trace
trace
trace
9
2
3
KHMDS (2)
LDA (2)
4
5
CsF (2)
26
6
t-BuOK (2)
K2CO3 (2)
K3PO4 (2)
Cs2CO3 (2)
Cs2CO3 (1.2)
Cs2CO3 (3)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
25
7
45
8
64
9
93
10
11
12
13
14
15
16c
61
94
88
82
70
A possible mechanism for the present transformation as
outlined in Scheme 2 is proposed.7,8 In the presence of a
base, deprotonation of the a-position in substrate 1a can
take place readily to form the enol form B. Subsequently,
the addition of phosphate 2a to intermediate B affords in-
termediate C. Finally, sequential the C–O bond cleavage
and isomerization of intermediate C take place to give the
desired enol phosphate 3 and PhOH with the aid of a base.
DMF
52
CH2Cl2
92
a Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), base (2.0 equiv),
and solvent (2 mL) at r.t.
b Isolated yield.
c Compounds 1a (2.0 mmol) and 2a (2.5 mmol) were used.
Ph
O
O
Ph
Ph
O
O Ph
Ph
O Ph
As shown in Table 2, the scope of both a-aryloxyace-
tophenones and phosphonates was explored under the op-
timal reaction conditions. In the presence of Cs2CO3, the
R1O leaving groups in a-aryloxyacetophenones 1b–i were
first investigated (Table 2, entries 1–8). The results dem-
onstrated that numerous leaving groups, such as ArO and
AcO, were perfectly compatible with the optimal condi-
tions (entries 1–8), and three groups, PhO, p-MeOC6H4O,
and o-IC6H4O, are more efficient giving the desired prod-
uct 3 in quantitative yields (entries 1, 3, and 6). As a con-
sequence, a-aryloxyacetophenones with a PhO as leaving
base
– H+
–
–
O
A
1a
B
O
P
H
MeO
OMe
2a
base
Ph
Ph
O Ph
O
O
+
MeO
P
O
MeO
MeO
P OH
MeO
PhOH
C
3
Scheme 2 Possible mechanism for the formation of enol phosphates
Synthesis 2012, 44, 1119–1125
© Thieme Stuttgart · New York

PAPER
Selective Synthesis of Enol Phosphates
1121
Table 2 Cs2CO3-Mediated Synthesis of Enol Phosphatesa
Table 2 Cs2CO3-Mediated Synthesis of Enol Phosphatesa
(continued)
R2
R2
R1
O
R1
O
O
Cs2CO3
O
R3
Cs2CO3
OR5
OR5
R3
R4
OR5
OR5
R4
+
+
H
P
R3
H
P
R3
OR5
OR5
CH2Cl2, r.t.
R4
OR5
OR5
CH2Cl2, r.t.
R4
O
O
R2
R2
P
P
2
2
O
1
O
1
O
O
O
O
O
O
O
O
OMe
OMe
OEt
OEt
Oi-Pr
Oi-Pr
OMe
OMe
OEt
OEt
Oi-Pr
Oi-Pr
H
P
H
P
H P
H
P
H
P
H P
2a
2b
2c
2a
2b
2c
Product, yieldb (%)
Entry Substrate 1
2
Product, yieldb (%)
Entry Substrate 1
2
Ph
Ph
O
O
O
OMe
OMe
Ph
O
O
O
O
O
O
O
O
P
1
2
3
4
5
6
2a
2a
2a
2a
2a
2a
O
P
OMe
OMe
11
2a
2a
2a
2a
O
O
3, 99
O
O
1b
6, 98
1j
MeO
Ph
OMe
OMe
Ph
Ph
MeO
P
O
O
O
OMe
12
13
14
O
P
3, 82
OMe
1c
O
O
Ph
OMe
OMe
1k
7, 96
Ph
OMe
P
Ph
OMe
O
O
O
O
OMe
3, ~100
1d
P
OMe
OMe
O
O
Ph
O
OMe
OMe
Ph
P
1l
F
8, 87
F
O
Ph
O
OMe
O
3, 88
1e
O
OMe
OMe
P
Ph
O
O
OMe
OMe
Ph
Cl
O
O
P
1m
9, 77
O
O
Ph
3, 82
O
1f
O
OMe
OMe
15
16
17
2a
2a
2a
P
Ph
OMe
OMe
Ph
P
O
O
O
O
O
I
10, 99
1n
1o
3, 98
1g
Ph
O
P
O
OMe
OMe
Ph
O
Ph
O
O
OMe
OMe
P
7
8
2a
2a
O
O
O
3, 95
11, 91 (1:1)
1h
Ph
Ph
O
O
O
O
Ph
OMe
OMe
O
OMe
OMe
Ph
O
O
O
P
P
CN
O
O
NC
3, 91
1p
1q
1i
12, 70 (2:3)
Ph
O
O
OEt
OEt
Ph
O
P
9
2b
2c
O
OMe
P
O
18
2a
SO2Ph
O
OMe
4, 99
O
1b
PhO2S
13, 92 (2:3)
Ph
Oi-Pr
Oi-Pr
Ph
P
10
O
O
5, 81
1b
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1119–1125

1122
R.-J. Song et al.
PAPER
Table 2 Cs2CO3-Mediated Synthesis of Enol Phosphatesa
(continued)
the reaction mixture was diluted with Et2O (5 mL), and washed with
brine (3 × 1 mL). The aqueous phase was extracted with Et2O (3 × 2
mL). The combined organic layers were dried (Na2SO4) and con-
centrated in vacuo. The resulting residue was purified by column
chromatography on silica gel (hexane–EtOAc, 2:1) to afford the de-
sired product (Table 2).
R2
R1
O
O
Cs2CO3
R3
OR5
OR5
R4
+
H
P
R3
OR5
OR5
R4
CH2Cl2, r.t.
O
R2
P
2
O
1
Dimethyl 1-Phenylvinyl Phosphate (3)1g
Yield: 42.9 mg (94%); colorless oil.
IR (KBr): 1708, 1491, 1454, 1234, 1181, 1042 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.60–7.58 (m, 2 H), 7.39–7.35 (m,
3 H), 5.31 (t, J = 2.5 Hz, 1 H), 5.22 (t, J = 2.5 Hz, 1 H), 3.87 (s, 3
H), 3.84 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 152.2 (d, JC,P = 6.4 Hz, 1 C),
134.0 (d, JC,P = 6.9 Hz, 1 C), 129.2, 128.4, 125.1, 97.4 (d, JC,P = 3.6
Hz, 1 C), 54.9 (d, JC,P = 5.9 Hz, 1 C).
O
O
O
O
OMe
OMe
OEt
OEt
Oi-Pr
Oi-Pr
H
P
H
P
H P
2a
2b
2c
Entry Substrate 1
2
Product, yieldb (%)
Ph
O
O
O
OMe
19
20
2a
2a
P
LRMS (EI, 70 eV): m/z (%) = 228 (M+, 16), 213 (7), 116 (20), 102
(100).
CN
OMe
CN
O
O
1r
14, 88 (1:1)
Diethyl 1-Phenylvinyl Phosphate (4)1g
Yield: 50.7 mg (99%); colorless oil.
IR (KBr): 1712, 1490, 1448, 1232, 1177, 1038 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.60–7.58 (m, 2 H), 7.38–7.34 (m,
3 H), 5.29 (t, J = 2.5 Hz, 1 H), 5.23 (t, J = 2.5 Hz, 1 H), 4.25–4.17
(m, 4 H), 1.36–1.33 (m, 6 H).
13C NMR (125 MHz, CDCl3): d = 152.3 (d, JC,P = 8.0 Hz, 1 C),
134.3, 129.1, 128.4, 125.2, 97.3 (d, JC,P = 3.6 Hz, 1 C), 64.5 (d,
JC,P = 6.1 Hz, 1 C), 16.1 (d, JC,P = 6.6 Hz, 1 C).
Ph
O
O
P
O
OMe
OMe
CN
CN
NC
CN
15, 84
1s
1t
Ph
O
O
SO2Ph
O
OMe
P
21
2a
OMe
SO2Ph
LRMS (EI, 70 eV): m/z (%) = 256 (M+, 10), 199 (7), 130 (81), 102
(100).
O
PhO2S
SO2Ph
16, 43
Diisopropyl 1-Phenylvinyl Phosphate (5)1g
Yield: 46.0 mg (81%); colorless oil.
IR (KBr): 1715, 1556, 1446, 1232, 1143, 1039 cm–1.
a Reaction conditions: 1 (0.2 mmol), phosphonate 2 (0.3 mmol),
Cs2CO3 (2 equiv), CH2Cl2 (2 mL) at r.t. under air atmosphere.
b Isolated yield. The Z/E ratio is given in parentheses.
1H NMR (500 MHz, CDCl3): d = 7.60–7.58 (m, 2 H), 7.38–7.33 (m,
3 H), 5.27 (t, J = 2.5 Hz, 1 H), 5.24 (t, J = 2.5 Hz, 1 H), 4.78–4.72
(m, 2 H), 1.37 (s, 3 H), 1.33 (s, 3 H), 1.32 (s, 3 H), 1.26 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 152.4 (d, JC,P = 7.4 Hz, 1 C),
134.6 (d, JC,P = 7.3 Hz, 1 C), 128.9, 128.3, 125.2, 97.0 (d, JC,P = 3.4
Hz, 1 C), 73.4 (d, JC,P = 6.0 Hz, 1 C), 23.7 (d, JC,P = 4.8 Hz, 1 C),
23.5 (d, JC,P = 5.3 Hz, 1 C).
In summary, we have developed a new, simple method for
the synthesis of enol phosphates under mild conditions. In
the presence of Cs2CO3, a variety of a-aryloxyacetophe-
none compounds selectively underwent the sequential
O–P bond-forming/C–O bond-cleavage/isomerization
tandem reaction with phosphonates leading to enol phos-
phates in moderate to excellent yields. Importantly, this
method is simple and mild with a wide range of substrates
compatibility, which makes the applications of enol phos-
phates more attractive in organic synthesis.
LRMS (EI, 70 eV): m/z (%) = 284 (M+, 10), 144 (61), 102 (100).
Dimethyl 1-p-Tolylvinyl Phosphate (6)
Yield: 47.4 mg (98%); colorless oil.
IR (KBr): 1716, 1555, 1183, 1095 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.48 (d, J = 8.0 Hz, 2 H), 7.17 (d,
J = 8.5 Hz, 2 H), 5.25 (t, J = 2.5 Hz, 1 H), 5.16 (t, J = 2.5 Hz, 1 H),
3.85 (s, 3 H), 3.83 (s, 3 H), 2.36 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 152.3 (d, JC,P = 7.8 Hz, 1 C),
139.2, 131.2 (d, JC,P = 6.6 Hz, 1 C), 129.0, 125.0, 96.5 (d, JC,P = 3.5
Hz, 1 C), 54.8 (d, JC,P = 6.1 Hz, 1 C), 21.1.
IR spectra of the liquid products were recorded as neat films be-
tween KBr plates on a Bruker vertex 70 spectrophotometer. NMR
spectroscopy was performed on a Bruker advanced spectrometer
operating at 500 MHz (1H NMR) and 125 MHz (13C NMR). Mass
spectrometric analysis was performed on GC-MS analysis (Shimadzu
GCMS-QP2010) and ESI-Q-TOF (Bruker MicroQTOF-II).
LRMS (EI, 70 eV): m/z (%) = 242 (M+, 26), 227 (16), 127 (33), 116
(100).
Base-Catalyzed Synthesis of Vinyl Phosphates; General Proce-
dure
HRMS (EI): m/z calcd for C11H15O4P (M+): 242.0708; found:
To a Schlenk tube were added a-aryloxyacetophenone 1 (0.2
mmol), phosphonate 2 (0.3 mmol), Cs2CO3 (130 mg, 0.4 mmol),
and CH2Cl2 (2 mL). Then the contents of the tube were stirred at r.t.
under air atmosphere for the indicated time until complete con-
sumption of starting material as monitored by TLC (eluent: hexane–
EtOAc, 1:1) and GC-MS analysis. After completion of the reaction,
242.0705.
1-(4-Methoxyphenyl)vinyl Dimethyl Phosphate (7)
Yield: 49.5 mg (96%); colorless oil.
IR (KBr): 1725, 1568, 1195, 1103 cm–1.
Synthesis 2012, 44, 1119–1125
© Thieme Stuttgart · New York

PAPER
Selective Synthesis of Enol Phosphates
1123
1H NMR (500 MHz, CDCl3): d = 7.53–7.52 (m, 2 H), 6.89–6.88 (m,
2 H), 5.17 (t, J = 2.5 Hz, 1 H), 5.10 (t, J = 2.5 Hz, 1 H), 3.86 (s, 3
H), 3.84 (s, 3 H), 3.82 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 160.3, 152.1 (d, JC,P = 8.0 Hz, 1
C), 126.6 (d, JC,P = 9.3 Hz, 1 C), 113.8, 95.6 (d, JC,P = 3.5 Hz, 1 C),
55.3, 54.8 (d, JC,P = 6.3 Hz, 1 C).
LRMS (EI, 70 eV): m/z (%) = 258 (M+, 30), 227 (4), 131 (100).
HRMS (EI): m/z calcd for C11H15O5P (M+): 258.0657; found:
5.78–5.73 (m, 1 H), 5.70–5.65 (m, 1 H), 3.75 (s, 3 H), 3.73 (s, 3 H),
3.72 (s, 3 H), 3.71 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 146.7 (d, JC,P = 9.0 Hz, 1 C),
146.2 (d, JC,P = 8.9 Hz, 1 C), 135.5, 133.8 (d, JC,P = 4.3 Hz, 1 C),
128.5 (d, JC,P = 9.5 Hz, 1 C), 128.2 (d, JC,P = 10.5 Hz, 1 C), 128.1,
125.2, 112.2 (d, JC,P = 6.4 Hz, 1 C), 111.8 (d, JC,P = 5.1 Hz, 1 C),
54.7 (d, JC,P = 6.1 Hz, 1 C), 54.5 (d, JC,P = 6.0 Hz, 1 C), 12.9, 11.6.
LRMS (EI, 70 eV): m/z (%) = 242 (M+, 19), 127 (100), 115 (66).
HRMS (EI): m/z calcd for C11H15O4P (M+) 242.0708; found:
258.0654.
242.0705.
1-(2-Methoxyphenyl)vinyl Dimethyl Phosphate (8)
Yield: 44.9 mg (87%); colorless oil.
IR (KBr): 1703, 1497, 1450, 1228, 1178, 1044 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.53–7.51 (m, 1 H), 7.33–7.30 (m,
1 H), 6.89–6.92 (m, 2 H), 5.46 (t, J = 2.5 Hz, 1 H), 5.37 (t, J = 2.0
Hz, 1 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 3.80 (s, 3 H).
(Z/E)-4-Cyano-1-phenylbut-1-enyl Dimethyl Phosphate (12)
Yield: 39.3 mg (70%); Z/E = 3:2; Z-isomer: 15.7 mg, E-isomer:
23.6 mg.
Z-Isomer
Colorless oil.
13C NMR (125 MHz, CDCl3): d = 157.1, 149.2 (d, JC,P = 8.0 Hz, 1
C), 130.1, 128.8, 123.2 (d, JC,P = 6.0 Hz, 1 C), 120.3, 111.1, 102.7
(d, JC,P = 4.0 Hz, 1 C), 55.4, 54.6 (d, JC,P = 6.1 Hz, 1 C).
LRMS (EI, 70 eV): m/z (%) = 258 (M+, 29), 227 (3), 131 (100), 127
(65).
HRMS (EI): m/z calcd for C11H15O5P (M+): 258.0657; found:
258.0656.
IR (KBr): 1717, 1711, 1658, 1558, 1193, 1036 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.53 (d, J = 7.0 Hz, 2 H), 7.38–
7.35 (m, 3 H), 5.68–5.65 (m, 1 H), 3.74 (s, 3 H), 3.72 (s, 3 H), 2.74–
2.70 (m, 2 H), 2.57 (t, J = 7.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 148.0 (d, JC,P = 8.5 Hz, 1 C),
134.5, 129.0, 128.4, 125.6, 119.2, 112.9 (d, JC,P = 6.4 Hz, 1 C), 54.9
(d, JC,P = 5.8 Hz, 1 C), 22.3, 17.0 (d, JC,P = 2.6 Hz, 1 C).
LRMS (EI, 70 eV): m/z (%) = 281 (M+, 1), 155 (45), 127 (100), 115
(59).
HRMS (EI): m/z calcd for C13H16NO4P (M+): 281.0817; found:
281.0820.
1-(4-Fluorophenyl)vinyl Dimethyl Phosphate (9)
Yield: 37.9 mg (77%); colorless oil.
IR (KBr): 1700, 1487, 1455, 1043 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.58–7.56 (m, 2 H), 7.07–7.04 (m,
2 H), 5.24 (t, J = 2.5 Hz, 1 H), 5.20 (t, J = 2.5 Hz, 1 H), 3.87 (s, 3
H), 3.84 (s, 3 H).
E-Isomer
Colorless oil.
13C NMR (125 MHz, CDCl3): d = 162.2, 151.4, 129.7, 127.1 (d,
JC,P = 8.0 Hz, 1 C), 115.4 (d, JC,P = 21.9 Hz, 1 C), 97.2, 54.8 (d,
JC,P = 4.9 Hz, 1 C).
LRMS (EI, 70 eV): m/z (%) = 246 (M+, 14), 231 (9), 120 (100), 109
(23).
HRMS (EI): m/z calcd for C10H12FO4P (M+): 246.0457; found:
246.0453.
IR (KBr): 1718, 1708, 1659, 1550, 1199, 1044 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.43–7.40 (m, 5 H), 5.69–5.66 (m,
1 H), 3.75 (s, 3 H), 3.73 (s, 3 H), 2.50 (t, J = 7.0 Hz, 2 H), 2.43 (t,
J = 7.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 148.7 (d, JC,P = 8.5 Hz, 1 C),
133.1 (d, JC,P = 4.5 Hz, 1 C), 129.4, 128.5 (d, JC,P = 1.5 Hz, 1 C),
118.7, 112.6 (d, JC,P = 4.9 Hz, 1 C), 54.7 (d, JC,P = 6.1 Hz, 1 C),
23.6, 17.6.
LRMS (EI, 70 eV): m/z (%) = 281 (M+, 1), 155 (45), 127 (100), 115
(59).
HRMS (EI): m/z (EI) calcd for C13H16NO4P (M+): 281.0817; found:
281.0820.
Dimethyl 1-(Naphthalen-1-yl)vinyl Phosphate (10)
Yield: 55.0 mg (99%); colorless oil.
IR (KBr): 1709, 1488, 1465, 1040 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.06 (s, 1 H), 7.88–7.86 (m, 1 H),
7.84–7.81 (m, 2 H), 7.67–7.65 (m, 1 H), 7.52–7.48 (m, 2 H), 5.45 (t,
J = 2.5 Hz, 1 H), 5.32 (t, J = 2.5 Hz, 1 H), 3.89 (s, 3 H), 3.87 (s, 3
H).
Dimethyl (Z/E)-1-Phenyl-4-(phenylsulfonyl)but-1-enyl Phos-
phate (13)
13C NMR (125 MHz, CDCl3): d = 152.2 (d, JC,P = 7.9 Hz, 1 C),
133.5, 133.0, 131.2 (d, JC,P = 6.6 Hz, 1 C), 128.4 (d, JC,P = 46.9 Hz,
1 C), 127.6, 126.6 (d, JC,P = 27.6 Hz, 1 C), 124.6, 122.7, 98.0 (d,
JC,P = 3.3 Hz, 1 C), 54.9 (d, JC,P = 6.0 Hz, 1 C).
LRMS (EI, 70 eV): m/z (%) = 278 (M+, 39), 263 (9), 166 (26), 152
(100).
Yield: 72.9 mg (92%); Z/E = 2:3; Z-isomer: 29.1 mg, E-isomer:
43.8 mg.
Z-Isomer
Colorless oil.
IR (KBr): 1720, 1650, 1556, 1144, 1042 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.95 (d, J = 7.0 Hz, 2 H), 7.65 (t,
J = 7.5 Hz, 1 H), 7.57 (t, J = 7.5 Hz, 2 H), 7.45–7.43 (m, 2 H), 7.35–
7.31 (m, 3 H), 5.57–5.54 (s, 1 H), 3.68 (s, 3 H), 3.65 (s, 3 H), 3.32
(t, J = 7.5 Hz, 2 H), 2.80–2.75 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 147.8 (d, JC,P = 8.9 Hz, 1 C),
139.0, 134.6, 133.7, 129.3, 128.9, 128.2 (d, JC,P = 26.8 Hz, 1 C),
125.5, 112.3 (d, JC,P = 6.4 Hz, 1 C), 54.9 (d, JC,P = 2.5 Hz, 1 C), 54.8
(d, JC,P = 6.0 Hz, 1 C), 19.9.
HRMS (EI): m/z calcd for C14H15O4P (M+): 278.0708; found:
278.0706.
Dimethyl (Z/E)-1-Phenylprop-1-enyl Phosphate (11)
Yield: 44.0 mg (91%); Z/E = 1:1; colorless oil.
IR (KBr): 1716, 1699, 1654, 1552, 1184, 1099, 1033 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.51–7.49 (m, 2 H), 7.47–7.45 (m,
2 H), 7.40–7.37 (m, 2 H), 7.35–7.32 (m, 3 H), 7.30–7.27 (m, 1 H),
LRMS (EI, 70 eV): m/z (%) = 396 (M+, 1), 155 (22), 127 (100).
© Thieme Stuttgart · New York
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1124
R.-J. Song et al.
PAPER
HRMS (EI): m/z calcd for C18H21O6PS (M+): 396.0797; found:
396.0795.
13C NMR (125 MHz, CDCl3): d = 145.8 (d, JC,P = 8.1 Hz, 1 C),
139.0, 138.3, 133.8 (d, JC,P = 6.0 Hz, 1 C), 133.3, 129.4 (d,
JC,P = 3.6 Hz, 1 C), 129.3, 128.9, 128.5, 128.1, 127.9, 119.9 (d,
JC,P = 8.1 Hz, 1 C), 54.5 (d, JC,P = 6.1 Hz, 1 C), 53.8 (d, JC,P = 40.6
Hz, 1 C), 24.3, 22.1.
E-Isomer
Colorless oil.
IR (KBr): 1722, 1648, 1559, 1148, 1043 cm–1.
LRMS (EI, 70 eV): m/z (%) = 564 (M+, 1), 423 (12), 297 (73), 155
(100), 127 (33).
1H NMR (500 MHz): d = 7.84 (d, J = 7.5 Hz, 2 H), 7.64 (t, J = 7.5
Hz, 1 H), 7.53 (t, J = 7.5 Hz, 2 H), 7.36–7.32 (m, 5 H), 5.59–5.56
(s, 1 H), 3.71 (s, 3 H), 3.69 (s, 3 H), 3.18–3.15 (m, 2 H), 2.60–2.54
(m, 2 H).
HRMS (EI): m/z calcd for C26H29O8PS2 (M+): 564.1042; found:
564.1040.
13C NMR (125 MHz): d = 148.0 (d, JC,P = 8.5 Hz, 1 C), 138.6, 133.8,
133.0 (d, JC,P = 4.3 Hz, 1 C), 129.3 (d, JC,P = 2.4 Hz, 1 C), 128.3 (d,
JC,P = 20.8 Hz, 1 C), 128.0, 112.2 (d, JC,P = 4.8 Hz, 1 C), 55.5, 54.6
(d, JC,P = 6.3 Hz, 1 C), 21.1.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
LRMS (EI, 70 eV): m/z (%) = 396 (M+, 1), 155 (22), 127 (100).
Acknowledgment
HRMS (EI): m/z calcd for C18H21O6PS (M+): 396.0797; found:
396.0795.
We thank the National Natural Science Foundation of China (No.
21172060) and Fundamental Research Funds for the Central Uni-
versities (Hunan University) for financial support.
(Z/E)-4-Cyano-2-methyl-1-phenylbut-1-enyl Dimethyl Phos-
phate (14)
Yield: 51.9 mg (88%); Z/E = 1:1; colorless oil.
References
IR (KBr): 1716, 1698, 1556, 1552, 1507, 1185, 1031 cm–1.
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(b) Hayashi, T.; Fujiwa, T.; Okamoto, Y.; Katsuro, Y.;
Kumada, M. Synthesis 1981, 1001.
1H NMR (500 MHz, CDCl3): d = 7.41–7.37 (m, 10 H), 3.80 (s, 3 H),
3.78 (s, 3 H), 3.56 (s, 6 H), 3.53 (s, 6 H), 2.69 (t, J = 7.5 Hz, 1 H),
2.64–2.61 (m, 1 H), 2.43–2.39 (m, 3 H), 2.37–2.35 (m, 3 H).
13C NMR (125 MHz, CDCl3): d = 143.9 (d, JC,P = 8.6 Hz, 1 C),
134.2, 129.4 (d, JC,P = 22.0 Hz, 1 C), 128.9 (d, JC,P = 31.4 Hz, 1 C),
128.2 (d, JC,P = 35.4 Hz, 1 C), 120.4 (d, JC,P = 7.8 Hz, 1 C), 118.8,
54.4 (d, JC,P = 6.1 Hz, 1 C), 54.3 (d, JC,P = 6.1 Hz, 1 C), 52.0 (d,
JC,P = 5.5 Hz, 1 C), 29.0, 27.8, 17.6, 15.8 (d, JC,P = 2.9 Hz, 1 C),
15.4, 14.8.
LRMS (EI, 70 eV): m/z (%) = 295 (M+, 1), 249 (27), 216 (8), 155
(36), 127 (73).
HRMS (EI): m/z calcd for C14H18NO4P (M+): 295.0973; found:
295.0970.
4-Cyano-2-(2-cyanoethyl)-1-phenylbut-1-enyl Dimethyl Phos-
phate (15)
Yield: 56.1 mg (84%); colorless oil.
IR (KBr): 1720, 1658, 1546, 1279, 1184, 1049 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.47–7.42 (m, 5 H), 3.55 (s, 3 H),
3.53 (m, 3 H), 2.70 (t, J = 5.0 Hz, 4 H), 2.43–2.38 (m, 4 H).
13C NMR (125 MHz, CDCl3): d = 147.1 (d, JC,P = 8.3 Hz, 1 C),
133.2, 129.5 (d, JC,P = 23.6 Hz, 1 C), 128.6, 121.2 (d, JC,P = 8.5 Hz,
1 C), 119.2, 118.4, 54.5 (d, JC,P = 6.1 Hz, 1 C), 26.6, 24.5, 16.0 (d,
JC,P = 2.6 Hz, 1 C), 15.7 (d, JC,P = 2.3 Hz, 1 C).
LRMS (EI, 70 eV): m/z (%) = 334 (M+, 1), 253 (2), 208 (53), 168
(100), 127 (73).
HRMS (EI): m/z calcd for C16H29N2O4P (M+): 334.1082; found:
334.1080.
(5) (a) Larsen, U. S.; Martiny, L.; Begtrup, M. Tetrahedron Lett.
2005, 46, 4261. (b) Campbell, I. B.; Guo, J.; Jones, E.; Steel,
P. G. Org. Biomol. Chem. 2004, 2, 2725. (c) Lepifre, F.;
Clavier, S.; Bouyssou, P.; Coudert, G. Tetrahedron 2001,
57, 6969. (d) Nan, Y.; Yang, Z. Tetrahedron Lett. 1999, 40,
3321.
Dimethyl 1-Phenyl-4-(phenylsulfonyl)-2-[2-(phenyl-
sulfonyl)ethyl]but-1-enyl Phosphate (16)
Yield: 48.5 mg (43%); colorless oil.
IR (KBr): 1716, 1699, 1650, 1556, 1503, 1307, 1042 cm–1.
(6) Coe, J. W. Org. Lett. 2000, 2, 4205.
1H NMR (500 MHz, CDCl3): d = 7.95 (d, J = 7.5 Hz, 2 H), 7.72–
7.67 (m, 3 H), 7.64–7.59 (m, 3 H), 7.48 (t, J = 7.5 Hz, 2 H), 7.36–
7.28 (m, 3 H), 7.19 (d, J = 7.0 Hz, 2 H), 3.46 (s, 3 H), 3.44 (s, 3 H),
3.33–3.30 (m, 2 H), 3.05–3.01 (m, 2 H), 2.70–2.67 (m, 2 H), 2.37–
2.34 (m, 2 H).
(7) (a) Carruthers, W.; Coldham, I. Modern Methods of Organic
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Synthesis 2012, 44, 1119–1125
© Thieme Stuttgart · New York

PAPER
(8) For selected papers, see: (a) Satterthwait, A. C.; Westheher,
Selective Synthesis of Enol Phosphates
1125
(9) For a paper on Rh-catalyzed C–O bond cleavage of
2-aryloxy-1-arylethanols, see: Nichols, J. M.; Bishop,
F. H. J. Am. Chem. Soc. 1980, 102, 4464. (b) Grzegorz, B.;
Ralph, M. P. Synthesis 1988, 109. (c) Tatsuoka, G. A.;
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L. M.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc.
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(10) For a paper on base-mediated reaction from our group, see:
Lei, Y.; Wang, Z.-Q.; Xie, Y.-X.; Yu, S.-C.; Tang, B.-X.; Li,
J.-H. Adv. Synth. Catal. 2011, 353, 31.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1119–1125