N-heterocyclic carbene catalyzed intramolecular hydroacylation of alkynylphosphonates

Article abstract of DOI:10.1055/s-0031-1290976

Two exocyclic and endocyclic olefin tautomers of chromone phosphonates were obtained in good to excellent yields at different temperatures by utilizing an N-heterocyclic carbene catalyst in the intramolecular reactions between the formyl group and alkynylphosphonates. The exocyclic olefins can isomerize to the endocyclic derivatives completely when treated with a thiazolium salt precatalyst and potassium carbonate at 30C for three to fivehours. In addition, the chromone phosphonate derivatives were also applied in the one-pot synthesis of benzopyranopyridine phosphonates in moderated yields.

Full text of DOI:10.1055/s-0031-1290976

PAPER
▌1559
paper
N-Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation of
Alkynylphosphonates
Intramolecular Hydroacylation of Alkynylphosphonates
Zhenqiang Wang, Zhihua Yu, Ying Wang, Deqing Shi*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University,
Wuhan 430079, P. R. of China
Fax +86(27)67862041; E-Mail: chshidq@mail.ccnu.edu.cn
Received: 13.01.2012; Accepted after revision: 24.03.2012
of NHCs in catalysis in umpolung strategies has been no-
tably adopted in both intra- and intermolecular transfor-
mations in the Stetter reaction,6 and the electrophilic
acceptors of these transformations contain both activated
Abstract: Two exocyclic and endocyclic olefin tautomers of chro-
mone phosphonates were obtained in good to excellent yields at dif-
ferent temperatures by utilizing an N-heterocyclic carbene catalyst
in the intramolecular reactions between the formyl group and al-
kynylphosphonates. The exocyclic olefins can isomerize to the en- olefins and unactivated derivatives. Recently, Enders et
docyclic derivatives completely when treated with a thiazolium salt
precatalyst and potassium carbonate at 30 °C for three to five hours.
In addition, the chromone phosphonate derivatives were also ap-
functionalized chromones by an intramolecular Stetter re-
plied in the one-pot synthesis of benzopyranopyridine phospho-
nates in moderated yields.
al. and Rovis et al. pioneered the development of a pow-
erful NHC-catalyzed approach to the formation of highly
action. The NHC-catalyzed hydroacylation of unactivated
alkynes led to the formation of α,β-unsaturated chromone,
Key words: Stetter reaction, N-heterocyclic carbenes, hydroacyla-
which was first reported by Frank Glorius et al. in 2009.6m
tion, one-pot synthesis, chromone, phosphonate
According to examples that exploit nucleophilic acyl an-
ion equivalents, acceptors of the Stetter reaction were
mainly limited to α,β-unsaturated ketones, α,β-unsaturat-
Organic phosphorus compounds are attractive to chemists
ed esters or phosphonates, and alkynes.7 We envisaged
that alkynylphosphonates would act as excellent accep-
tors for the intramolecular Stetter reaction because of their
highly electrophilic nature at the β-position.8 This prompt-
ed us to investigate the possibility of developing a new
carbon–carbon bond forming reaction to construct the po-
tentially biologically relevant α,β-unsaturated chromone
phosphonates at room temperature, which are useful in
many fields including agrochemical and medicinal
chemistry9 (Scheme 1, equation 1). During the prepara-
tion of this manuscript, Liu et al. reported the NHC-cata-
lyzed intramolecular hydroacylation of activated alkynes
(Scheme 1, equation 2).6p
because of their wide range of biological activities1 and
catalytic properties in organic synthesis.2 Moreover, phos-
phonyl heterocycles and related compounds have been
widely used in the field of pharmaceuticals and agrochem-
icals as bactericides, insecticides, fungicides, and plant
growth regulators.3 On the other hand, over the past few
decades, the broad application of N-heterocyclic carbenes
(NHCs) in organic synthesis has been impressively dem-
onstrated.4 Such compounds play a vital role not only as
ubiquitous ligands in organometallic chemistry, but also
as efficient nucleophilic organocatalysts in a variety of or-
ganic reactions,5 including benzoin condensation, the
Stetter reaction, and a3 to d3 umpolung reactions. The use
O
O
O
O
P
O
P
OR2
OR2
OR2
OR2
NHCs
(1)
(2)
H
+
O
P
O
O
O
OR2
R1
R1
R1
1
2
2'
OR2
O
O
O
O
O
NHCs
COOEt
H
COOEt
O
H
COOEt
Scheme 1 NHC-Catalyzed intramolecular Stetter reaction of activated alkynes
SYNTHESIS 2012, 44, 1559–1568
Advanced online publication: 02.05.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290976; Art ID: SS-2012-F0043-OP
© Georg Thieme Verlag Stuttgart · New York

1560
Z. Wang et al.
PAPER
We decided to employ a series of alkynylphosphonates as (Scheme 2).10 Aerial oxidative coupling of terminal al-
electrophilic acceptors in the intramolecular Stetter reac- kynes with H-phosphonates was efficiently catalyzed by
tion. Alkynylphosphonates 1 were prepared by using a copper acetate to generate alkynylphosphonates in high
modified procedure described by Zhao and colleagues
Table 1 Optimization of the Reaction Conditionsa
O
OEt
O
O
O
O
P
O
P
OEt
NHCs-HX (5 mol%)
K2CO3 (10 mol%)
OEt
OEt
CHO
+
O
O
P
CH2Cl2, r.t.
OEt
OEt
1a
2a
2a'
S
N
S
N
OH
ClO4
ClO4
S
N
Cl
C
A
B
N
N
N
N
N
N
N
N
Cl
ClO4
Cl
E
D
F
Yield (%)b
Entry
NHC-HX
Base
Solvent
2a
2a′
0
1
2
A
B
C
D
E
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DBU
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
90
88
89
0
0
3
0
4
0
5
72
0
26
40
0
6
F
7
A
A
A
A
A
A
A
A
A
A
A
A
A
1,4-dioxane
n-BuOH
toluene
THF
85
0
8
23
0
9
86
87
0
10
11
12
13
14
15
16
17
18
19
0
MeCN
DMF
0
0
0
EtOH
0
29
14
43
21
20
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
82
51
74
0
t-BuOK
Cs2CO3
NaH
DABCO
Et3N
17
19
77
a Reaction conditions: 1a (0.5 mmol), NHC-HX (5 mol%), base (10 mol%), solvent (2.0 mL), r.t. (17 °C), 3 h.
b Isolated yield.
Synthesis 2012, 44, 1559–1568
© Georg Thieme Verlag Stuttgart · New York

PAPER
Intramolecular Hydroacylation of Alkynylphosphonates
1561
O
S
1) Cu(OAc)2 (10 mol%), Et3N
HP(O)(OR2)2, DMSO
S
R1
R1
O
P
2) Fe(NO3)3·9H2O–SiO2
hexane
O
O
OR2
OR2
1
Scheme 2 Copper-catalyzed coupling of alkynes and H-phosphonates
yields. Deprotection of the 1,2-dithiane using ferric nitrate and 6). Because of the higher yield, the convenient purifi-
provided 1 in excellent yields.
cation operation, and the higher catalytic activity of A, we
chose this carbene precursor as the catalyst in subsequent
reactions. At this stage, the effects of various solvents in
the reaction were examined with catalyst A as a control
(Table 1, entries 7–13). With increasing solvent polarity,
the yields of the products were found to be reduced. Sur-
prisingly, no product was detected when polar nonprotonic
solvents such as acetonitrile or N,N-dimethylformamide
(DMF) were used, however, use of a moderately polar sol-
vent such as dichloromethane was more effective. Using
catalyst A and dichloromethane as solvent, we explored
the use of a range of bases (Table 1, entries 14–19) and
found that potassium carbonate afforded the products in
highest yield.
Our present study commenced with simple phenyl deriv-
ative 1a as a model substrate with which to optimize the
reaction conditions. Treatment of 1a with the N-heterocy-
clic carbene generated from the deprotonation of thiazoli-
um salt A by potassium carbonate resulted in the
formation of chromone phosphonate derivative 2a at
room temperature (17 °C) in three hours, which is a syn-
thetically valuable exocyclic olefin, as a single isomer in
90% yield (Table1, entry 1).
A survey of carbene precursors showed that the use of thi-
azolium salts A, B, and C gave a single isomer of exocy-
clic olefin in excellent yields (Table 1, entries 1, 2, and 3).
To our surprise, the phenyl-substituted carbene precursor
D was completely ineffective (Table 1, entry 4). Interest-
ingly, imidazolium salt E and triazolium salt F provided
another isomer; the endocyclic olefin (Table 1, entries 5
With these optimized conditions in hand, we then turn our
attention to the influence of the substituents of the salicyl-
aldehyde-derived alkynylphosphonates on the formation
of tautomers (Table 2, entries 4–11). Remarkably, sub-
Table 2 Hydroacylation of Activated Alkynesa
O
OR2
O
O
O
P
NHCs-HX (5 mol%)
OR2
O
OR2
OR2
K2CO3 (10 mol%)
CHO
O
P
+
CH2Cl2, r.t., 3 h
R1
O
O
P
R1
R1
OR2
OR2
1
2
2'
(endocyclic olefin)
(exocyclic olefin)
R1
R2
Et
Yield (%)b
90 (2a)c
81 (2b)
Entry
91 (2a′)c
1
2
H
H
n-Bu
i-Pr
Et
3
H
79 (2c)
4
4-NO2
4-F
6-Br
91 (2d′)
89 (2e′)
87 (2f′)
94 (2g′)
85 (2h′)
89 (2i′)
80 (2j′)
90 (2k′)
5
Et
93 (2e)
92 (2g)
6
Et
7
4-OMe
Et
8
4-t-Bu
Et
9
6-Me
Et
10
11
4,6-di-t-Bu
naphthalethyl
Et
Et
a Reaction conditions: 1 (0.5 mmol), NHC-HX A (5 mol%), base (10 mol%), solvent (2.0 mL).
b Isolated yield.
c The exocyclic olefin products were obtained at 17 °C for 3 h; and endocyclic olefin products at 30 °C for 3 h.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1559–1568

1562
Z. Wang et al.
PAPER
strates with either electron-donating or electron-with- The first intramolecular hydroacylation of an electron-
drawing substituents on the aromatic rings were effective. neutral triple bond was reported by Frank Glorius, which
Competition experiments with different phenyl moieties was followed by the intramolecular hydroacylation of ac-
revealed that the electron-withdrawing substituents could tivated alkynes in which the electron-withdrawing groups
accelerate the reaction rates; in particular, the reaction have mainly been the carbonyl group. Although the ability
reached completion within 30 minutes with the nitro-con- of the phosphonyl group to withdraw electrons is inferior
taining reactant (Table 2, entry 4). Finally, we examined to that of the carbonyl group, and it might also introduce
the effects of steric hindrance of the phosphonates (R = Et, a certain degree of steric hindrance, the hydroacylation
n-Bu, or i-Pr) on this Stetter type intramolecular hydroac- products can be obtained in excellent yield at room tem-
ylation reaction (Table 2, entries 1–3). The results showed perature, which can be due to a suitable selection of
that the yields decreased slightly with increasing steric NHCs. The defined electronic effects and steric hindrance
hindrance. To establish whether the temperature had an of NHCs11 will be very useful in catalysts for this type of
effect on the formation of the tautomers, catalyst A, di- reaction. In contrast to our reaction system, the formation
chloromethane, and potassium carbonate were used at a of exocyclic products or its endocyclic tautomers can de-
range of temperatures; isomer 2a was found to be the ma- pend on the reaction temperature.
jor product at lower temperature (17 °C), and isomer 2a′
was formed as the major product at 30 °C.
Based on our system and on literature reports,6p a possible
mechanism is shown in Scheme 3. The reaction might
In view of these interesting results, we wondered whether proceed through different routes at different temperatures.
we could use the exocyclic olefin as a Michael receptor All of the pathways involve tetrahedral intermediates,
and the α-pyridylmethyl ketone salt as a nucleophile to which are generated by carbene nucleophilic attack on the
provide benzopyranopyridine derivatives by the applica- carbonyl carbon of the aldehyde. The reaction is terminat-
tion of Kröhnke method11 through a one-pot synthesis. To ed in the exocyclic Stetter type product at a lower temper-
test our hypothesis, we employed the α-pyridylmethyl ke- ature (17 °C). Alternatively, the substrate alkynyl group
tone salt12 as the Michael partner for 1 to yield polycyclic can isomerize to the allene, followed by proton transfer
phosphonate derivatives 3a–f. A series of substrates with and carbene release to generate the endo isomers at higher
various substituents on the aromatic ring of the salt were temperature (30 °C). Moreover, the exocyclic olefins 2
examined (Table 3).
are not more stable than the aromatized tautomers 2′, in
Table 3 Preparation of Benzopyranopyridine by the Kröhnke Methoda
R
1) NHCs-HX (5 mol%)
K2CO3 (10 mol%), CH2Cl2, r.t.
CHO
N
O
OR2
P
O
O
P
2)
OR2
OR2
OR2
O
O
N
I
1
3a–f
R
MeOH, NH4OAc
reflux
R2
Yield (%)b
Entry
R
Product
1
2
3
4
5
6
7
H
Et
3a
3b
3c
3d
3e
3f
52
50
48
53
51
55
0
H
n-Bu
i-Pr
Et
H
OMe
Me
F
Et
Et
NO2
Et
3g
a Reaction conditions: (1) 1 (0.5 mmol), NHC-HX A (5 mol%), base (10 mol%), solvent (2.0 mL), r.t. (17 °C), 3 h; (2) -pyridylmethyl ketone
salt (0.5 mmol), NH4Ac (5 equiv), MeOH (3 mL), reflux, 6 h; no prospective product was detected when nitro-substituted substrate was used
as reactant (Table 3, entry 7).
b Isolated yield.
Synthesis 2012, 44, 1559–1568
© Georg Thieme Verlag Stuttgart · New York

PAPER
Intramolecular Hydroacylation of Alkynylphosphonates
1563
R3
R4
R3
R4
R4
S
R5
S
N
N
R5
R3
S
N
R5
H
••
O
O
P
OR2
OR2
O
R3
R4
O
O
P
OR2
OR2
O
R1
R3
R4
R1
O
S
N
S
R5
H
O
N
R5
OR2
OR2
••
low temp
P
O
1
O
exo
R1
O
O
R1
OR2
OR2
P
O
P
OR2
OR2
OR2
O
R3
R4
N
higher temp
R5
P
OR2
H
R4
O
S
R5
N
R5
••
O
R4
R3
OH
N
S
R3
O
S
R1
O
O
P
OR2
OR2
R1
O
endo
R1
Scheme 3 Proposed catalytic cycle for the NHC-catalyzed intramolecular hydroacylation of alkynylphosphonates
ppm). 31P NMR spectra were recorded on the same instrument with
85% H3PO4 as external standard. Mass spectra (ESI) were obtained
with an Applied Biosystems API 2000 LC/MS/MS (ESI-MS) spec-
trometer. Elemental analyses were performed with an Elementar
Vario ELШ CHNSO elemental analyzer.
fact, 2 can isomerize to 2′ completely when the former is
treated with catalyst A and potassium carbonate at 30 °C
for three to five hours; however, without catalyst A and
potassium carbonate, the isomerization of 2 cannot occur.
In conclusion, we have developed an effective organocat-
alytic intramolecular hydroacylation reaction between
phosphonylation alkynyl and compounds containing a
formyl group, by utilizing N-heterocyclic carbene cataly-
sis. In addition, the chromone derivatives can also be ap-
plied in the one-pot synthesis of benzopyranopyridine
phosphonates 3 in moderate yields.
Dialkyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1);
General Procedure
H-Phosphonates (10 mmol), 2-[2-(prop-2-ynyloxy)phenyl]-1,3-di-
thiolane (12 mmol, 2.95 g), Cu(OAc)2 (10 mol%, 0.19 g), and Et3N
(20 mol%, 0.2 g) were dissolved in commercial DMSO (20 mL) and
stirred at 50 °C for 24 h under a dry air atmosphere. The resulting
mixture was poured into 50 mL H2O and extracted with EtOAc
(3 × 50 mL). The organic layer was washed with brine (3 × 50 mL),
dried over MgSO4 and concentrated under vacuum and the crude
product was purified by silica gel chromatography (petroleum
ether–EtOAc, 1:1) to give a yellow oil. The 1,2-dithiane was depro-
tected by stirring the mixture of the yellow oil (1.0 mmol), ferric ni-
trate nonahydrate (1.0 mmol), hexane (10 mL), and silica gel (1 g)
at ambient temperature under an N2 atmosphere (reaction monitored
by TLC). The crude reaction mixture was purified by column chro-
matography on silica gel (petroleum ether–EtOAc 1:1). Evapora-
tion of solvent afforded the pure product.
All reagents and solvents were used as received with the following
exceptions: THF, toluene, and dioxane were distilled from sodium/
benzophenone. CH2Cl2, MeCN, and DMF were distilled from CaH.
EtOH and n-BuOH were distilled from Mg turnings. K2CO3 was
dried by heating at 110 °C for 12 h and left to cool under argon. N-
Heterocyclic carbene (NHC) precursors A–F were prepared accord-
ing to the literature.13 Substituted salicylaldehyde were synthesized
according to the reported method.14 All other commercially avail-
able solvents and reagents were used without further purification.
All reactions were performed in oven-dried apparatus under an N2
or argon atmosphere. Reactions were monitored by thin layer chro-
matography (TLC) and visualized by short-wave UV light or
Diethyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1a)
Yield: 153.9 mg (87%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.88 (d, J = 9.0 Hz,
1 H), 7.59 (t, J = 8.4 Hz, 1 H), 7.14 (t, J = 10.8 Hz, 1 H), 7.08 (d,
J = 12.6 Hz, 1 H), 4.95 (d, J = 3.6 Hz, 2 H), 4.16–4.09 (m, 4 H),
1.33 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.2 (d, J = 167.4 Hz), 159.1,
135.7, 128.8 (d, J = 17.5 Hz), 125.5, 122.2, 112.9, 93.2 (d, J =
48.6 Hz), 78.0 (d, J = 288 Hz), 63.4 (d, J = 3.9 Hz), 56.1, 15.9.
1
KMnO4 staining solution followed by heating. H, 13C, and 31P
NMR spectra were obtained with either a Varian Mercury PLUS
400 or a Varian Mercury PLUS 600 spectrometer. Chemical shifts
are reported in parts per million (δ, ppm) from an internal standard
[tetramethylsilane (TMS) or chloroform (CHCl3)], multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, and m = multiplet), inte-
gration, and coupling constant (Hz). 13C NMR chemical shifts are
reported in ppm relative to the signal of CDCl3 (taken as δ = 77.0
MS (ESI): m/z = 297 [M + H]+, 319 [M + Na]+.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1559–1568

1564
Z. Wang et al.
PAPER
Dibutyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1b)
1H NMR (600 MHz, CDCl3): δ = 10.42 (s, 1 H), 7.35 (d, J = 3.6 Hz,
1 H), 7.15 (dd, J =9.0, 3.0 Hz, 1 H), 7.04 (d, J = 9.6 Hz, 1 H), 4.90
(d, J = 3.6 Hz, 2 H), 4.14–4.11 (m, 4 H), 3.82 (s, 3 H), 1.35 (t, J =
7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 188.8 (d, J = 27.6 Hz), 154.7,
153.8, 126.1, 123.0, 115.3, 110.6, 93.5 (d, J = 48.3 Hz), 78.9 (d, J =
282.9 Hz), 63.4 (d, J = 4.65 Hz), 57.0 (d, J = 4.65 Hz), 55.7, 15.9
(d, J = 6.9 Hz).
Yield: 214.7 mg (91%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.88 (d, J = 7.2 Hz,
1 H), 7.58 (t, J = 7.8 Hz, 1 H), 7.13 (t, J = 7.2 Hz, 1 H), 7.08 (d, J =
8.4 Hz, 1 H), 4.96 (d, J = 3.0 Hz, 2 H), 4.70–4.03 (m, 4 H), 1.67–
1.62 (m, 4 H), 1.37 (q, J = 7.2 Hz, 4 H), 0.90 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.0 (t, J = 89.7 Hz), 159.0,
135.6, 128.7 (d, J = 16.2 Hz), 125.3, 122.1, 112.7, 93.2 (d, J =
51 Hz), 79.1, 67.0, 56.0, 31.9, 18.5, 13.4.
MS (ESI): m/z = 327 [M + H]+, 349 [M + Na]+.
31P NMR (CDCl3, 243 MHz): δ = –8.48.
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+.
Diethyl 3-(4-tert-Butyl-2-formylphenoxy)prop-1-ynylphospho-
nate (1h)
Yield: 225.3 mg (92%); yellow oil.
Diisopropyl 3-(2-Formylphenoxy)prop-1-ynylphosphonate (1c)
Yield: 236.5 mg (89%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.45 (s, 1 H), 7.88 (s, 1 H), 7.61
(d, J = 8.4 Hz, 1 H), 7.02 (d, J = 9.0 Hz, 1 H), 4.93 (d, J = 3.0 Hz,
2 H), 4.14–4.11 (m, 4 H), 1.38–1.29 (m, 15 H).
13C NMR (150 MHz, CDCl3): δ = 188.8 (q, J = 55.2 Hz), 157.1,
145.1, 132.8, 125.3, 124.7, 112.7, 93.5 (d, J = 50.5 Hz), 78.9 (d, J =
264.5 Hz), 63.4 (d, J = 4.65 Hz), 56.1 (d, J = 4.5 Hz), 34.3, 31.2 (d,
J = 25.4 Hz), 15.8 (d, J = 6.9 Hz).
1H NMR (400 MHz, CDCl3): δ = 10.46 (s, 1 H), 7.87 (d, J = 7.6 Hz,
1 H), 7.58 (t, J = 8.0 Hz, 1 H), 7.14–7.07 (m, 2 H), 4.95 (d, J =
1.6 Hz, 2 H), 4.76–4.66 (m, 2 H), 1.37 (t, J = 6.4 Hz, 6 H), 1.32 (t,
J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 188.9 (m), 159.1, 135.6 (d,
J =20.7 Hz), 128.5 (d, J =11.5 Hz), 125.2, 121.9, 112.7 (d, J =
6.9 Hz), 92.4 (d, J = 50.5 Hz), 78.9 (d, J =287.4 Hz), 72.6 (d, J =
18.4 Hz), 55.9 (dd, J =13.8, 18.4 Hz), 23.4 (t, J = 41.4 Hz).
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+.
Diethyl 3-(2-Formyl-6-methylphenoxy)prop-1-ynylphospho-
nate (1i)
Yield: 164.3 mg (93%); yellow oil.
MS (ESI): m/z = 325 [M + H]+, 347 [M + Na]+.
Diethyl 3-(2-Formyl-4-nitrophenoxy)prop-1-ynylphosphonate
1H NMR (600 MHz, CDCl3): δ = 10.36 (s, 1 H), 7.71 (d, J = 7.8 Hz,
1 H), 7.48 (d, J = 7.2 Hz, 1 H), 7.22 (t, J = 7.8 Hz, 1 H), 4.83 (d, J =
3.0 Hz, 2 H), 4.11–4.09 (m, 4 H), 2.39 (d, J = 3.0 Hz, 3 H), 1.33 (t,
J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.6, 157.9, 137.6, 132.4, 129.6,
127.5, 125.2 (d, J = 52.1 Hz), 93.8 (d, J = 50.5 Hz), 77.5 (d, J =
289.5 Hz), 63.3 (d, J = 5.7 Hz), 60.9 (d, J = 108.3 Hz), 42.5, 15.9 (t,
J = 82.8 Hz).
(1d)
Yield: 276.2 mg (79%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.45 (s, 1 H), 8.74 (d, J = 3.0 Hz,
1 H), 8.47 (dd, J =9.0, 3.0 Hz, 1 H), 7.23 (d, J = 9.0 Hz, 1 H), 5.08
(d, J = 3.6 Hz, 2 H), 4.17–4.14 (m, 4 H), 1.35 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 187.3, 162.7, 142.5, 130.3 (d, J =
11.7 Hz), 125.2, 124.6 (d, J = 6.0 Hz), 113.2 (d, J = 5.8 Hz), 91.2
(d, J = 48.6 Hz), 78.9 (d, J = 289.9 Hz), 63.5 (d, J = 5.85 Hz), 56.7,
15.9.
MS (ESI): m/z = 311 [M + H]+, 333 [M + Na]+.
MS (ESI): m/z = 342 [M + H]+, 364 [M + Na]+.
Diethyl 3-(4,6-Di-tert-butyl-2-formylphenoxy)prop-1-ynylphos-
phonate (1j)
Diethyl 3-(4-Fluoro-2-formylphenoxy)prop-1-ynylphosphonate
Yield: 224.4 mg (90%); yellow oil.
(1e)
1H NMR (600 MHz, CDCl3): δ = 10.26 (s, 1 H), 7.69 (s, 1 H), 7.65
(s, 1 H), 4.79 (d, J = 3.6 Hz, 2 H), 4.18–4.15 (m, 4 H), 1.45 (s, 9 H),
1.38 (t, J = 7.2 Hz, 6 H), 1.33 (s, 9 H).
13C NMR (150 MHz, CDCl3): δ = 190.3, 157.2, 147.4, 143.2, 131.1,
129.0, 126.1, 94.2, 93.9, 79.1, 77.0, 63.5 (t, J = 35.7 Hz), 35.3, 34.7,
31.2 (d, J = 41.4 Hz), 16.0 (d, JC–P = 6.6 Hz).
Yield: 181.5 mg (83%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.40 (s, 1 H), 7.54 (dd, J =8.4,
3.6 Hz, 1 H), 7.31–7.28 (m, 1 H), 7.08 (dd, J = 9.0, 3.6 Hz, 1 H),
4.93 (d, J = 3.6 Hz, 2 H), 4.16–4.09 (m, 4 H), 1.33 (t, J = 7.2 Hz,
6 H).
13C NMR (150 MHz, CDCl3): δ = 189.0 (t, J =97.0 Hz), 158.4,
156.8, 155.3, 126.4, 122.3 (d, J = 23.8 Hz), 114.5 (t, J = 50.5 Hz),
92.9 (d, J = 46.3 Hz), 79.1, 63.5 (d, J = 5.5 Hz), 56.8, 15.9 (d, J =
5.7 Hz).
MS (ESI): m/z = 409 [M + H]+, 431 [M + Na]+.
Diethyl 3-(2-Formylnaphthalen-1-yloxy)prop-1-ynylphospho-
nate (1k)
Yield: 207.6 mg (82%); yellow oil.
MS (ESI): m/z = 314 [M + H]+, 336 [M + Na]+.
1H NMR (600 MHz, CDCl3): δ = 10.61 (s, 1 H), 8.22 (d, J = 8.4 Hz,
1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.89 (d, J = 8.4 Hz, 1 H), 7.74 (d, J =
8.4 Hz, 1 H), 7.68 (t, J = 7.2 Hz, 1 H), 7.65 (t, J = 7.2 Hz, 1 H), 5.08
(d, J = 3.6 Hz, 2 H), 4.07–4.03 (m, 4 H), 1.32 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 189.4 (t, J = 111.2 Hz), 158.6,
137.9, 129.5, 128.5, 127.3, 127.2, 125.7 (d, J = 11.3 Hz), 122.8 (d,
J = 19.7 Hz), 93.2 (d, J =49.2 Hz), 79.0 (d, J = 288.2 Hz), 63.5 (t,
J = 33.7 Hz), 42.6, 15.9.
Diethyl3-(6-Bromo-2-formylphenoxy)prop-1-ynylphosphonate
(1f)
Yield: 201.9 mg (86%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 10.41 (s, 1 H), 7.86 (d, J = 1.8 Hz,
1 H), 7.84 (d, J = 2.4 Hz, 1 H), 7.22 (t, J = 7.8 Hz, 1 H), 5.02 (d, J =
3.6 Hz, 2 H), 4.13–4.08 (m, 4 H), 1.34 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 188.8 (d, J = 167.4 Hz), 156.5,
139.4 (d, J = 16.8 Hz), 131.8, 127.7 (d, J = 15.6 Hz), 126.7, 117.8,
92.8 (d, J = 49.2 Hz), 79.5 (d, J = 289.1 Hz), 63.4 (d, J = 5.7 Hz),
61.5, 15.9.
MS (ESI): m/z = 347 [M + H]+, 369 [M + Na]+.
Synthesis of Dialkyl (4-Oxo-2H-chromen-3(4H)-ylidene)meth-
ylphosphonates 2; General Procedure
MS (ESI): m/z = 375 [M + H]+, 397 [M + Na]+.
To an oven-dried, round-bottom flask equipped with a magnetic bar
was added dialkyl 3-(2-formylphenoxy)prop-1-ynylphosphonate 1
(0.5 mmol, 1.0 equiv), pre-catalyst A (9 mg, 0.025 mmol, 0.05
equiv) and anhydrous K2CO3 (6.9 mg, 0.05 mmol, 0.10 equiv) at r.t.
Diethyl 3-(2-Formyl-4-methoxyphenoxy)prop-1-ynylphospho-
nate (1g)
Yield: 166.3 mg (95%); yellow oil.
Synthesis 2012, 44, 1559–1568
© Georg Thieme Verlag Stuttgart · New York

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Intramolecular Hydroacylation of Alkynylphosphonates
1565
under a nitrogen atmosphere. The mixture was dissolved in anhy-
drous CH2Cl2 (2.0 mL) under a nitrogen atmosphere and the result-
ing mixture was stirred for 3 h at the stated temperature (17 or
30 °C). The progress of the reaction was monitored by TLC. Upon
completion, the reaction mixture was pre-absorbed on silica gel and
purified by flash column chromatography on silica gel (hexane–
EtOAc, 1:1) to afford 2 (the appearance of exocyclic olefins is a yel-
low oil, and the appearance of endocyclic olefins is a white solid).
13C NMR (150 MHz, CDCl3): δ = 180.1, 162.1, 147.1, 136.7, 128.1
(d, J = 23.1 Hz), 122.7, 122.2, 121.0 (d, J = 78.2 Hz), 118.3, 67.9,
66.1, 32.3, 18.6, 13.5.
31P NMR (CDCl3, 243 MHz): δ = 13.39.
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+, 391 [M + K].
Anal. Calcd for C18H25O5P: C, 61.36; H, 7.15. Found: C, 61.23; H,
7.29.
Isomerization of Exocyclic Olefins 2 to Endocyclic Derivatives
2′; General Procedure
(E)-Diisopropyl (4-Oxo-2H-chromen-3(4H)-ylidene)methyl-
phosphonate (2c)
To an oven-dried, round-bottom flask equipped with a magnetic bar
was added 2 (0.5 mmol, 1.0 equiv), pre-catalyst A (9 mg, 0.025
mmol, 0.05 equiv) and anhydrous K2CO3 (6.9 mg, 0.05 mmol, 0.10
equiv) at r.t. under a nitrogen atmosphere. The mixture was dis-
solved in anhydrous CH2Cl2 (2.0 mL) under a nitrogen atmosphere
and the resulting mixture was stirred at 30 °C for 3–5 h until the re-
action was complete. The reaction mixture was pre-absorbed on sil-
ica gel and purified by flash column chromatography on silica gel
(hexane–EtOAc, 1:1) to afford 2′ as a white solid in nearly quanti-
tative yields.
The title compound was prepared according to the general proce-
dure.
Yield: 127.9 mg (79%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.98 (d, J = 7.8 Hz, 1 H), 7.53 (t,
J = 7.2 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1 H),
6.84 (d, JH–P = 15.0 Hz, 1 H), 5.54 (d, J = 1.8 Hz, 2 H), 4.73 (q, J =
6.6 Hz, 2 H), 1.37 (d, J = 6.0 Hz, 6 H), 1.33 (d, J = 6.6 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 180.2 (d, J = 21.45 Hz), 162.1,
146.0 (d, J = 7.8 Hz), 136.6 (d, J = 7.6 Hz), 128.1 (d, J = 23.3 Hz),
124.6 (d, J = 180.9 Hz), 123.3, 122.1, 121.1, 118.3, 71.4 (d, J =
11.7 Hz), 68.0, 24.0 (d, J = 5.7 Hz).
(E)-Diethyl (4-Oxo-2H-chromen-3(4H)-ylidene)methylphos-
phonate (2a)
The title compound was prepared according to the general proce-
dure.
MS (ESI): m/z = 325 [M + H]+, 347 [M + Na]+, 363 [M + K].
Anal. Calcd for C16H21O5P: C, 59.26; H, 6.53. Found: C, 59.15; H,
6.31.
Yield: 133.2 mg (90%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.98 (d, J = 7.8 Hz, 1 H), 7.54 (t,
J = 7.2 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1 H),
6.83 (d, JH–P = 15.0 Hz, 1 H), 5.55 (d, J = 1.2 Hz, 2 H), 4.18–4.14
(m, 4 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 179.9 (d, J = 21.3 Hz), 161.9,
146.9 (d, J = 7.6 Hz), 136.6, 128.0, 122.9, 122.1, 121.1 (d, J =
24.4 Hz), 118.2, 67.7 (d, J = 6.1 Hz), 62.2 (d, J = 5.7 Hz), 16.1 (d,
J = 6.5 Hz).
Diethyl (6-Nitro-4-oxo-4H-chromen-3-yl)methylphosphonate
(2d′)
The title compound was prepared according to the general proce-
dure.
Yield: 155.2 mg (91%); white solid; mp 75 °C.
1H NMR (600 MHz, CDCl3): δ = 9.10 (d, J = 2.4 Hz, 1 H), 8.51 (dd,
J = 3.0, 9.0 Hz, 1 H), 8.19 (d, J = 3.6 Hz, 1 H), 7.62 (d, J = 9.6 Hz,
1 H), 4.16–4.13 (m, 4 H), 3.11 (d, JH–P = 20.4 Hz, 2 H), 1.31 (t, J =
7.2 Hz, 6 H).
MS (ESI): m/z = 297 [M + H]+, 319 [M + Na]+, 335 [M + K].
Anal. Calcd for C14H17O5P: C, 56.76; H, 5.78. Found: C, 56.57; H,
5.84.
13C NMR (150 MHz, CDCl3): δ = 175.6, 160.3, 158.6, 154.5, 152.5,
124.4 (d, J = 7.8 Hz), 122.0 (d, J = 25.65 Hz), 120.3, 115.3 (d, J =
7.8 Hz), 110.6 (t, J = 16.65 Hz), 62.3 (d, J = 6.75 Hz), 21.1 (d, J =
140.7 Hz), 16.3.
Diethyl (4-Oxo-4H-chromen-3-yl)methylphosphonate (2a′)
The title compound was prepared according to the general proce-
dure.
MS (ESI): m/z = 342 [M + H]+, 364 [M + Na]+, 380 [M + K].
Yield: 134.7 mg (91%); white solid; mp 56 °C.
1H NMR (600 MHz, CDCl3): δ = 8.23 (d, J = 7.8 Hz, 1 H), 8.13 (d,
J = 3.6 Hz, 1 H), 7.68 (t, J = 7.2 Hz, 1 H), 7.45 (d, J = 8.4 Hz, 1 H),
7.41 (t, J = 7.8 Hz, 1 H), 4.15–4.10 (m, 4 H), 3.12 (d, JH–P
20.4 Hz, 2 H), 1.30 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.3, 156.2, 154.3 (d, J =
7.8 Hz), 133.6, 125.9, 125.2, 123.4, 118.1, 115.9, 62.2 (d, J =
7.8 Hz), 20.9 (d, J = 142.1 Hz), 16.2 (d, J = 5.9 Hz).
Anal. Calcd for C14H16NO7P: C, 49.27; H, 4.73. Found: C, 49.34; H,
4.65.
(E)-Diethyl (6-Fluoro-4-oxo-2H-chromen-3(4H)-ylidene)meth-
ylphosphonate (2e)
The title compound was prepared according to the general proce-
dure.
=
Yield: 139.7 mg (89%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.61 (d, J = 8.4 Hz, 1 H), 7.24 (d,
J = 7.8 Hz, 1 H), 7.01 (d, J = 9.0 Hz, 1 H), 6.84 (d, JH–P = 15 Hz,
1 H), 5.52 (d, J = 3.6 Hz, 2 H), 4.17–4.14 (m, 4 H), 1.36 (t, J =
7.2 Hz, 6 H).
MS (ESI): m/z = 297 [M + H]+, 319 [M + Na]+, 335 [M + K].
Anal. Calcd for C14H17O5P: C, 56.76; H, 5.78. Found: C, 56.90; H,
5.56.
13C NMR (150 MHz, CDCl3): δ = 179.85, 158.93, 146.28, 124.46,
123.50 (d, J =25.95 Hz), 122.2 (d, J = 25.2 Hz), 112.82 (d, J =
13.8 Hz), 68.09, 62.5 (d, J = 19.25 Hz), 16.3 (d, J = 8.20 Hz).
(E)-Dibutyl (4-Oxo-2H-chromen-3(4H)-ylidene)methylphos-
phonate (2b)
The title compound was prepared according to the general proce-
dure.
MS (ESI): m/z = 315 [M + H]+, 337 [M + Na]+, 353 [M + K].
Yield: 142.6 mg (81%); yellow oil.
Anal. Calcd for C14H16FO5P: C, 53.51; H, 5.13. Found: C, 53.37; H,
5.24.
1H NMR (600 MHz, CDCl3): δ = 7.98 (d, J = 7.8 Hz, 1 H), 7.53 (t,
J = 7.2 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.01 (d, J = 8.4 Hz, 1 H),
6.84 (d, JH–P = 15.0 Hz, 1 H), 5.54 (d, J = 1.2 Hz, 2 H), 4.10–4.07
(m, 4 H), 1.70–1.66 (m, 4 H), 1.44–1.40 (m, 4 H), 0.93 (t, J =
7.8 Hz, 6 H).
Diethyl (6-Fluoro-4-oxo-4H-chromen-3-yl)methylphosphonate
(2e′)
The title compound was prepared according to the general proce-
dure.
Yield: 146.1 mg (93%); yellow solid; mp 78 °C.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1559–1568

1566
Z. Wang et al.
PAPER
1H NMR (600 MHz, CDCl3): δ = 8.20 (d, J = 3.6 Hz, 1 H), 8.17 (d,
J = 7.8 Hz, 1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.30 (d, J = 7.8 Hz, 1 H),
4.15–4.13 (m, 4 H), 3.11 (d, JH–P = 20.4 Hz, 2 H), 1.31 (t, J =
7.2 Hz, 6 H).
Diethyl (6-tert-Butyl-4-oxo-4H-chromen-3-yl)methylphospho-
nate (2h′)
The title compound was prepared according to the general proce-
dure.
13C NMR (150 MHz, CDCl3): δ = 175.7, 154.2, 152.8, 137.1, 125.7,
125.3, 124.6, 116.3 (d, J = 9.0 Hz), 111.6, 62.3 (d, J = 6.75 Hz),
20.9 (d, J = 141.75 Hz), 16.2 (d, J = 6.75 Hz).
Yield: 149.6 mg (85%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.20 (d, J = 1.8 Hz, 1 H), 8.12 (d,
J = 3.0 Hz, 1 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.40 (d, J = 9.0 Hz, 1 H),
4.15–4.12 (m, 4 H), 3.13 (d, JH–P = 20.4 Hz, 2 H), 1.38 (s, 9 H), 1.30
(t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.6, 154.5, 148.5, 131.6, 122.7,
121.6, 117.7, 115.5, 62.3 (d, J = 6.75 Hz), 34.8, 31.2, 21.1 (d, J =
140.7 Hz), 16.3.
MS (ESI): m/z = 315 [M + H]+, 337 [M + Na]+, 353 [M + K].
Anal. Calcd for C14H16FO5P: C, 53.51; H, 5.13. Found: C, 53.67; H,
5.20.
Diethyl (8-Bromo-4-oxo-4H-chromen-3-yl)methylphosphonate
(2f′)
The title compound was prepared according to the general proce-
dure.
MS (ESI): m/z = 353 [M + H]+, 375 [M + Na]+, 391 [M + K].
Anal. Calcd for C18H25O5P: C, 61.36; H, 7.15. Found: C, 61.27; H,
7.31.
Yield: 163.1 mg (87%); white solid; mp 90 °C.
1H NMR (600 MHz, CDCl3): δ = 8.14 (d, J = 3.6 Hz, 1 H), 7.85 (dd,
J = 3.0, 8.4 Hz, 1 H), 7.49–7.47 (m, 1 H), 7.41–7.39 (m, 1 H), 4.16–
4.11 (m, 4 H), 3.11 (d, JH–P = 20.4 Hz, 2 H), 1.29 (q, J = 7.2 Hz,
6 H).
Diethyl (8-Methyl-4-oxo-4H-chromen-3-yl)methylphosphonate
(2i′)
The title compound was prepared according to the general proce-
dure.
13C NMR (150 MHz, CDCl3): δ = 176.3, 156.2, 154.3 (d, J =
7.8 Hz), 133.6, 125.9, 125.2, 123.4, 118.1, 115.9, 62.2 (d, J =
7.8 Hz), 20.9 (d, J = 142.1 Hz), 16.3 (d, J = 5.85 Hz).
Yield: 137.9 mg (89%); white solid; mp 97 °C.
1H NMR (600 MHz, CDCl3): δ = 8.11 (s, 1 H), 7.99 (d, J = 7.8 Hz,
1 H), 7.43 (d, J = 6.0 Hz, 1 H), 7.22 (t, J = 6.6 Hz, 1 H), 4.08–4.03
(m, 4 H), 3.04 (t, JH–P = 20.4 Hz, 2 H), 2.39 (s, 3 H), 1.24 (t, J =
7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.6, 154.8, 154.1, 134.5, 127.6,
124.7, 123.2 (d, J = 19.95 Hz), 115.5 (d, J = 7.8 Hz), 62.3 (d, J =
6.75 Hz), 20.9 (d, J = 140.7 Hz), 16.2, 15.5.
MS (ESI): m/z = 376 [M + H]+, 398 [M + Na]+, 414 [M + K].
Anal. Calcd for C14H16BrO5P: C, 44.82; H, 4.30. Found: C, 44.96;
H, 4.23.
(E)-Diethyl (6-Methoxy-4-oxo-2H-chromen-3(4H)-yli-
dene)methylphosphonate (2g)
The title compound was prepared according to the general proce-
dure.
MS (ESI): m/z = 311 [M + H]+, 333 [M + Na]+, 349 [M + K].
Anal. Calcd for C15H19O5P: C, 58.06; H, 6.17. Found: C, 58.15; H,
6.09.
Yield: 150.0 mg (92%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 7.35 (d, J = 3.6 Hz, 1 H), 7.14 (dd,
Diethyl (6,8-Di-tert-butyl-4-oxo-4H-chromen-3-yl)methylphos-
phonate (2j′)
J =9.0, 3.0 Hz, 1 H), 6.94 (d, J = 9.0 Hz, 1 H), 6.78 (d, JH–P
=
The title compound was prepared according to the general proce-
dure.
15.6 Hz, 1 H), 5.48 (d, J = 3.6 Hz, 2 H), 4.17–3.82 (m, 4 H), 3.82
(s, 3 H), 1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.7, 154.2, 152.8, 137.1, 125.7,
125.3, 124.6, 116.3 (d, J = 9.0 Hz), 111.6, 67.9 (d, J = 6.75 Hz),
62.4 (d, J = 21.9 Hz), 55.7 (d, J = 26.5 Hz), 16.2 (d, J = 6.75 Hz).
Yield: 163.2 mg (80%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.13 (d, J = 3.0 Hz, 1 H), 8.03 (d,
J = 1.8 Hz, 1 H), 7.63 (d, J = 1.8 Hz, 1 H), 4.08–4.06 (m, 4 H), 3.06
(d, JH–P = 20.4 Hz, 2 H), 1.42 (s, 9 H), 1.30 (s, 9 H), 1.24 (t, J =
7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.9, 153.2 (d, J = 12.3 Hz),
147.5, 138.5, 128.7, 123.5, 119.7, 114.9 (d, J = 7.8 Hz), 62.3 (d, J =
6.75 Hz), 34.9 (d, J = 35.7 Hz), 31.3, 30.5 (t, J = 78 Hz), 20.9 (d, J =
140.5 Hz), 16.3 (d, J = 5.85 Hz).
MS (ESI): m/z = 327 [M + H]+, 349 [M + Na]+, 365 [M + K].
Anal. Calcd for C15H19O6P: C, 55.22; H, 5.87. Found: C, 55.11; H,
5.97.
Diethyl (6-Methoxy-4-oxo-4H-chromen-3-yl)methylphospho-
nate (2g′)
The title compound was prepared according to the general proce-
dure.
MS (ESI): m/z = 409 [M + H]+, 431 [M + Na]+, 447 [M + K].
Anal. Calcd for C22H33O5P: C, 64.69; H, 8.14. Found: C, 64.55; H,
8.31.
Yield: 146.7 mg (90%); white solid; mp 83 °C.
1H NMR (600 MHz, CDCl3): δ = 8.12 (d, J = 4.2 Hz, 1 H), 7.57 (d,
J = 3.0 Hz, 1 H), 7.41 (d, J = 9.0 Hz, 1 H), 7.27 (d, J = 9.0 Hz, 1 H),
4.16–4.11 (m, 4 H), 3.98 (s, 3 H), 3.13 (d, JH–P = 20.4 Hz, 2 H), 1.32
(t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 176.0 (d, J = 18.6 Hz), 156.8,
154.1, 151.1, 123.8 (d, J = 82.8 Hz), 119.5, 114.9 (d, J = 7.5 Hz),
104.7, 62.2 (d, J = 7.5 Hz), 55.7, 20.9 (d, J = 140.3 Hz), 16.3 (d, J =
6.9 Hz).
Diethyl (4-Oxo-4H-benzo[h]chromen-3-yl)methylphosphonate
(2k′)
The title compound was prepared according to the general proce-
dure.
Yield: 155.7 mg (90%); white solid; mp 86 °C.
1H NMR (600 MHz, CDCl3): δ = 8.44 (d, J = 8.4 Hz, 1 H), 8.32 (d,
J = 3.6 Hz, 1 H), 8.13 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 1 H),
7.74 (d, J = 9.0 Hz, 1 H), 7.69 (t, J = 7.2 Hz, 1 H), 7.67 (t, J =
7.8 Hz, 1 H), 4.18–4.13 (m, 4 H), 3.19 (d, JH–P = 21.0 Hz, 2 H), 1.31
(t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 175.9, 153.6, 153.4, 135.6, 129.2,
127.9, 127.1, 125.3, 123.8, 122.1, 120.7, 119.5, 117.2 (d, J =
7.8 Hz), 62.3 (d, J = 7.8 Hz), 20.9 (d, J = 140.7 Hz), 16.2 (d, J =
5.85 Hz).
MS (ESI): m/z = 327 [M + H]+, 349 [M + Na]+, 365 [M + K].
Anal. Calcd for C15H19O6P: C, 55.22; H, 5.87. Found: C, 55.13; H,
5.94.
Synthesis 2012, 44, 1559–1568
© Georg Thieme Verlag Stuttgart · New York

PAPER
Intramolecular Hydroacylation of Alkynylphosphonates
1567
MS (ESI): m/z = 347 [M + H]+, 369 [M + Na]+, 385 [M + K].
8.4 Hz, 1 H), 5.51 (s, 2 H), 4.81–4.77 (m, 2 H), 1.38 (d, J = 7.2 Hz,
6 H), 1.24 (d, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 156.3 (t, J = 16.05 Hz), 149.0,
138.2, 135.8, 134.6, 131.6, 129.5, 128.7, 126.9, 125.8, 125.3, 122.9,
122.3, 122.0, 116.8, 72.0, 66.4, 24.0 (d, J = 16.2 Hz).
Anal. Calcd for C18H19O5P: C, 62.43; H, 5.53. Found: C, 62.58; H,
5.60.
Synthesis of Dialkyl 2-Aryl-5H-chromeno[4,3-b]pyridin-4-yl
Phosphonate 3; General Procedure
MS (ESI): m/z = 424 [M + H]+, 446 [M + Na]+ 462 [M + K]+.
To an oven-dried, round-bottom flask equipped with a magnetic bar
was added the diethyl 3-(2-formylphenoxy)prop-1-ynylphospho-
nate derivative 1 (0.5 mmol, 1.0 equiv), pre-catalyst A (9 mg, 0.025
mmol, 0.05 equiv) and anhydrous K2CO3 (6.9 mg, 0.05 mmol, 0.10
equiv) at r.t. (17 °C) under a nitrogen atmosphere. The mixture was
dissolved in anhydrous CH2Cl2 (2.0 mL) under nitrogen and the re-
sulting mixture was then stirred at r.t. (17 °C) for 3 h. The α-pyri-
dylmethyl ketone salt (0.5 mmol) and excess NH4OAc (5 equiv) in
MeOH (4 mL) was added and the mixture was heated at reflux for
6 h. Upon cooling to r.t., the mixture was filtered and washed with
EtOAc (3 × 10 mL). The filtrate was collected and purified by flash
column chromatography on silica gel (hexane–EtOAc, 1:1) to give
3.
Anal. Calcd for C24H26NO4P: C, 68.07; H, 6.19; N, 3.31. Found: C,
67.95; H, 6.33; N, 3.47.
Diethyl 2-(4-Methoxyphenyl)-5H-chromeno[4,3-b]pyridin-4-
ylphosphonate (3d)
The title compound was prepared according to the general proce-
dure.
Yield: 112.6 mg (53%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.40 (dd, J = 1.8, 7.2 Hz, 1 H),
8.15 (d, J = 8.4 Hz, 2 H), 8.07 (d, J = 15.0 Hz, 1 H), 7.34 (t, J =
7.2 Hz, 1 H), 7.14 (t, J = 7.2 Hz, 1 H), 7.02 (d, J = 9.0 Hz, 2 H), 6.98
(d, J = 8.4 Hz, 1 H), 5.49 (s, 2 H), 4.28–4.11 (m, 4 H), 3.88 (s, 3 H),
1.37 (t, J = 7.2 Hz, 6 H).
13C NMR (150 MHz, CDCl3): δ = 160.9, 156.4, 156.1, 148.9, 134.1,
133.0, 131.6, 130.8, 128.3, 125.0, 123.0, 122.3, 119.0, 116.8, 114.1,
66.3, 62.8, 55.3, 16.3.
Diethyl 2-Phenyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate
(3a)
The title compound was prepared according to the general proce-
dure.
Yield: 102.7 mg (52%); yellow oil.
MS (ESI): m/z = 426 [M + H]+, 448 [M + Na]+, 464 [M + K].
1H NMR (600 MHz, CDCl3): δ = 8.42 (d, J = 7.2 Hz, 1 H), 8.18 (d,
J = 7.8 Hz, 2 H), 8.13 (d, J = 7.2 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 2 H),
7.46 (d, J = 7.2 Hz, 1 H), 7.35 (t, J = 7.8 Hz, 1 H), 7.15 (t, J =
7.8 Hz, 1 H), 6.98 (d, J = 7.8 Hz, 1 H), 5.25 (s, 2 H), 4.30–4.16 (m,
4 H), 1.38 (t, J = 7.2 Hz, 6 H).
Anal. Calcd for C23H24NO5P: C, 64.94; H, 5.69; N, 3.29. Found: C,
64.79; H, 5.50; N, 3.07.
Diethyl2-p-Tolyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate
(3e)
The title compound was prepared according to the general proce-
dure.
13C NMR (150 MHz, CDCl3): δ = 156.4 (d, J = 18.45 Hz), 149.2 (d,
J = 11.55 Hz), 138.1, 134.4, 133.2, 131.6, 129.5, 128.7, 126.9,
126.0 (d, J = 9.15 Hz), 125.2 (d, J = 9.15 Hz), 122.8, 122.3, 121.9,
116.7, 66.3, 62.8, 16.3.
Yield: 104.3 mg (51%); yellow oil.
1H NMR (600 MHz, CDCl3): δ = 8.40 (dd, J = 1.2, 7.8 Hz, 1 H),
8.12–8.08 (m, 3 H), 7.35 (t, J = 7.2 Hz, 1 H), 7.31 (d, J = 7.8 Hz,
2 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.98 (d, J = 7.8 Hz, 1 H), 5.51 (d, J =
1.8 Hz, 2 H), 4.27–4.16 (m, 4 H), 2.43 (s, 3 H), 1.37 (t, J = 7.2 Hz,
6 H).
MS (ESI): m/z = 396 [M + H]+, 418 [M + Na]+, 434 [M + K].
Anal. Calcd for C22H22NO4P: C, 66.83; H, 5.61; N, 3.54. Found: C,
66.90; H, 5.73; N, 3.52.
13C NMR (150 MHz, CDCl3): δ = 156.4, 149.1 (d, J = 12.3 Hz),
139.7, 135.4, 134.2, 133.0, 131.6, 129.5, 128.5 (d, J = 7.8 Hz),
126.7, 125.5, 125.2, 122.9, 122.3, 116.7, 66.3, 62.8 (d, J = 5.55 Hz),
21.3, 16.3.
Dibutyl2-Phenyl-5H-chromeno[4,3-b]pyridin-4-ylphosphonate
(3b)
The title compound was prepared according to the general proce-
dure.
Yield: 112.8 mg (50%); yellow oil.
MS (ESI): m/z = 410 [M + H]+, 432 [M + Na]+, 447 [M + K].
1H NMR (600 MHz, CDCl3): δ = 8.42 (d, J = 7.8 Hz, 1 H), 8.18 (t,
J = 7.8 Hz, 2 H), 8.13 (d, J = 14.4 Hz, 1 H), 7.52 (t, J = 7.2 Hz, 2 H),
7.46 (t, J = 7.2 Hz, 1 H), 7.35 (t, J = 7.8 Hz, 1 H), 7.15 (t, J = 7.8 Hz,
1 H), 6.99 (d, J = 7.8 Hz, 1 H), 5.51 (s, 2 H), 4.21–4.16 (m, 2 H),
4.12–4.07 (m, 2 H), 1.72–1.67 (m, 4 H), 1.45–1.39 (m, 4 H), 0.93 (t,
J = 7.2 Hz, 6 H).
13C NMR (CDCl3, 150 MHz): δ = 156.4, 149.2, 138.2, 134.4, 133.2,
131.7, 129.5, 128.7, 126.9, 125.9, 125.2, 122.9, 122.3, 122.0, 116.8,
66.4, 62.8, 31.2, 19.2, 16.4.
Anal. Calcd for C23H24NO4P: C, 67.47; H, 5.91; N, 3.42. Found: C,
67.60; H, 5.79; N, 3.53.
Diethyl 2-(4-Fluorophenyl)-5H-chromeno[4,3-b]pyridin-4-
ylphosphonate (3f)
The title compound was prepared according to the general proce-
dure.
Yield: 103.3 mg (50%); white solid; mp 78 °C.
1H NMR (600 MHz, CDCl3): δ = 8.38 (dd, J = 1.2, 7.2 Hz, 1 H),
8.19–8.16 (m, 2 H), 8.09 (d, J = 15.0 Hz, 1 H), 7.37–7.34 (m, 1 H),
7.18 (t, J = 8.4 Hz, 2 H), 7.13 (q, J = 7.2 Hz, 1 H), 6.98 (d, J =
7.8 Hz, 1 H), 5.51 (s, 2 H), 4.27–4.16 (m, 4 H), 1.37 (t, J = 7.2 Hz,
6 H).
13C NMR (150 MHz, CDCl3): δ = 164.5, 162.9, 156.4, 155.3 (d, J =
13.8 Hz), 149.1 (d, J = 13.8 Hz), 134.3 (d, J = 34.5 Hz), 133.3,
131.8, 128.7 (d, J = 6.9 Hz), 125.8 (d, J = 9.15 Hz), 125.2, 122.5 (d,
J = 57.45 Hz), 121.6 (d, J = 9.15 Hz), 116.8, 115.6 (d, J = 20.7 Hz),
66.3, 62.9, 16.3.
31P NMR (CDCl3, 243 MHz): δ = 14.59.
MS (ESI): m/z = 452 [M + H]+, 474 [M + Na]+, 490 [M + K].
Anal. Calcd for C26H30NO4P: C, 69.17; H, 6.70; N, 3.10. Found: C,
69.03; H, 6.59; N, 3.05.
Diisopropyl 2-Phenyl-5H-chromeno[4,3-b]pyridin-4-ylphos-
phonate (3c)
The title compound was prepared according to the general proce-
dure.
Yield: 101.5 mg (48%); yellow oil.
MS (ESI): m/z = 414 [M + H]+, 436 [M + Na]+, 452 [M + K].
1H NMR (600 MHz, CDCl3): δ = 8.41 (d, J = 7.8 Hz, 1 H), 8.19–
7.16 (m, 3 H), 7.51 (t, J = 7.2 Hz, 2 H), 7.45 (t, J = 7.8 Hz, 1 H),
7.35 (t, J = 7.2 Hz, 1 H), 7.14 (t, J = 7.8 Hz, 1 H), 6.98 (d, J =
Anal. Calcd for C22H21FNO4P: C, 63.92; H, 5.12; N, 3.39. Found:
C, 64.11; H, 5.04; N, 3.27.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1559–1568

1568
Z. Wang et al.
PAPER
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Acknowledgment
This work was supported by the Natural Science Foundation of Chi-
na (No. 20872046) and the Fundamental Research Funds for the
Central Universities (No. CCNU09A02013).
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Synthesis 2012, 44, 1559–1568
© Georg Thieme Verlag Stuttgart · New York