DABCO-catalyzed regioselective cyclization reactions of β,γ-unsaturated α-ketophosphonates or β,γ- unsaturated α-ketoesters with allenic esters

Article abstract of DOI:10.1039/c1ob06507f

Highly efficient DABCO-catalyzed [4 + 2] cycloaddition of β,γ-unsaturated α-ketophosphonates or β,γ- unsaturated α-ketoesters with allenic esters gives the corresponding highly functionalized tetrahydropyran and dihydropyran derivatives in good to excelle

Full text of DOI:10.1039/c1ob06507f

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PAPER
DABCO-catalyzed regioselective cyclization reactions of b,c-unsaturated
a-ketophosphonates or b,c-unsaturated a-ketoesters with allenic esters†
Cheng-Kui Pei,a Lei Wu,b Zhong Lianb and Min Shi*a,b
Received 2nd September 2011, Accepted 20th September 2011
DOI: 10.1039/c1ob06507f
Highly efficient DABCO-catalyzed [4 + 2] cycloaddition of b,g-unsaturated a-ketophosphonates or
b,g-unsaturated a-ketoesters with allenic esters gives the corresponding highly functionalized
tetrahydropyran and dihydropyran derivatives in good to excellent yields and moderate to good
regioselectivities under mild conditions.
Table 1 Optimization of the reaction conditions of (E)-dimethyl cin-
Introduction
namoylphosphonate 1a and ethyl 2,3-butadienoate 2aa
Heterocycles are of great value in the design and discovery of
new biologically active compounds.1 The development of efficient
processes to construct heterocycles, using metal-free catalysts, has
been drawing much attention over the past decades.2 Recently,
nitrogen-containing Lewis base (LB) catalyzed cyclization reac-
tions of allenoates have emerged as powerful synthetic tools in
the rapid construction of cyclic molecular complexity.3 To our
surprise, examples of b,g-unsaturated a-ketophosphonates4 or
b,g-unsaturated a-ketoesters5 as the electrophiles were seldom
mentioned in the construction of heterocycles. Herein, we wish
Entry LB
T/◦C
Solvent
Yield (%)b
3aa : 4aa (%)c
to report a novel DABCO-catalyzed regioselective [4 + 2] cycload-
dition of b,g-unsaturated a-ketophosphonates or b,g-unsaturated
a-ketoesters with allenic esters to give the corresponding highly
functionalized tetrahydropyran and dihydropyran derivatives,
which are structural subunits in many natural products and
biologically active molecules.6
1
2
3
4
5
6
7
8
DABCO
DMAP
DBU
Et3N
DIEA
PPh3
PBu3
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
THF
THF
THF
THF
THF
THF
THF
DCM
Et2O
Dioxane
CH3CN
Toluene
DCE
CHCl3
DMSO
DMF
DCM
DCM
DCM
DCM
87
84
2 : 1
1 : 1
—
—
—
—
—
3 : 1
1 : 1
2 : 1
2 : 1
1 : 1
2 : 1
3 : 1
—
NR
NR
NR
NR
NR
90
80
82
81
78
80
82
trace
trace
85
85
86
85
Results and discussion
9
10
11
12
13
14
15
16
17
18
19
20
We initially utilized (E)-dimethyl cinnamoylphosphonate 1a
(0.1 mmol, 1.0 equiv) and ethyl 2,3-butadienoate 2a (0.12 mmol,
1.2 equiv) as the substrates to investigate their cyclization behavior
in tetrahydrofuran (THF) at room temperature in the presence of
20 mol% 1,4-diazabicyclo[2,2,2]octane (DABCO). It was found
that the desired [4 + 2] cycloaddition reaction took place smoothly
to give the corresponding cyclic products 3aa and 4aa in 87%
combined yield but with low regioselectivity as the ratio of
—
0
3 : 1
4 : 1
5 : 1
3 : 1
-20
-40
-60
a All reactions were carried out using 1a (0.10 mmol) and 2a (0.12 mmol)
in solvent (1.00 mL) for 24 h. b Isolated combined yield. c Determined by
1H NMR spectroscopic data, and these regioisomers can not be easily
separated by column chromatography.
aKey Laboratory for Advanced Materials and Institute of Fine Chemicals,
East China University of Science and Technology, 130 Mei Long Road,
Shanghai, 200237, China
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai,
200032, China. E-mail: Mshi@mail.sioc.ac.cn; Fax: 86-21-64166128
3aa : 4aa was 2 : 1 within 24 h (Table 1, entry 1). Subsequently,
we screened various nitrogen-containing Lewis base catalysts for
this reaction, and the results are summarized in Table 1 (entries 2–
7). 4-N,N-dimethylpyridine (DMAP) can also efficiently catalyze
† Electronic supplementary information (ESI) available: Experimental
procedures, NMR charts for all compounds and X-ray crystal data of
6ea. CCDC reference numbers 833190. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c1ob06507f
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this reaction to give the product mixture of 3aa and 4aa in 84%
combined yield with a ratio of 1 : 1 (Table 1, entry 2). Other weak
nucleophilic nitrogen-containing Lewis base catalysts, such as 1,8-
diazabicyclo[5,4,0]-7-undecene (DBU), Et3N and diisopropylethy-
lamine (DIEA) did not catalyze this reaction (Table 1, entries
3–5). We next attempted to screen phosphane-containing Lewis
base catalysts, such as PPh3 and tributylphosphine (PBu3), in this
reaction, but it was found that no reactions occurred either (Table
1, entries 6 and 7). Of the catalysts examined, DABCO was found
to be the best one. Using DABCO as the catalyst, various solvents
were examined and dichloromethane (DCM) was found to be the
solvent of choice, affording 3aa and 4aa in 90% combined yield
with the ratio of 3 : 1 (Table 1, entries 8–16). Lowering the reaction
temperature to 0 ◦C or -20 ◦C, similar results were obtained (Table
1, entries 17 and 18). At -40 ◦C, the corresponding cyclic adducts
3aa and 4aa were obtained in 86% combined yield along with a 5 : 1
ratio of 3aa : 4aa (Table 1, entry 19). Further reducing the reaction
temperature did not improve the reaction outcomes (Table 1, entry
20). Thus, we have established the optimal reaction conditions for
this reaction: using 20 mol % DABCO as a catalyst and DCM as
a solvent to perform the reaction at -40 ◦C.
Under the optimized reaction conditions, the reaction generality
was investigated by using various cinnamoylphosphonates 1 in
the reaction with several allenic esters 2, and the results of these
experiments are summarized in Table 2. As can be seen from Table
2, changing the ester moiety of allenic esters 2 from OEt to OMe
or OiPr provided similar reaction outcomes, affording the desired
products in good combined yields (up to 90%) along with moderate
regioselectivities (3 : 4 = 3 : 1) (Table 2, entries 2 and 3). However,
we found that the R2 substituent in the phosphonate moiety of
cinnamoylphosphonates 1 can significantly affect the reaction
outcomes, as that R2 group can improve the regioselectivity of the
products (up to 3 : 4 = 10 : 1) if it had a sterically bulky group, such
as OiPr or OtBu (Table 2, entries 4 and 5). As for substrates 1d–
1h, electron-withdrawing or electron-donating substituents at the
meta- or para-positions of the benzene ring of 1 were equally well-
tolerated in the reaction, giving the corresponding products 3 and
4 in good combined yields along with high regioselectivities (up
to 3 : 4 > 20 : 1) (Table 2, entries 6–10). The substrate 1i, in which
R1 is a 1-naphthyl group, was also able in this reaction to give the
corresponding products in 85% combined yield along with good
regioselectivity (3ia : 4ia = 14 : 1) (Table 2, entry 11). When R1 is an
alkyl group (1j, R1 = Me), the reaction also proceeded smoothly
to give the desired products 3ja and 4ja in 75% combined yield
but with moderate regioselectivity (3ja : 4ja = 4 : 1) (Table 2, entry
12). The structures of 3 and 4 were determined by the 2-D NMR
spectroscopic data (HMQC, HMBC, DEPT and NOESY spectra)
of compounds 3ca and 4ca (see the Supporting Information for
the details†).
Encouraged by the above results, b,g-unsaturated a-ketoesters
were also examined under the optimal reaction conditions.
Initially, we utilized (E)-ethyl 2-oxo-4-phenylbut-3-enoate 5a
(0.10 mmol, 1.0 equiv) and ethyl 2,3-butadienoate 2a (0.12 mmol,
1.2 equiv) as the substrates in DCM (2.00 mL, 0.05 M) at
room temperature in the presence of 20 mol% DABCO. We were
pleased to find that the reaction proceeded smoothly to give
the desired products 6aa and 7aa in 82% combined yield along
with good regioselectivity (7aa : 6aa = 8 : 1) (Table 3, entry 1),
which was contrary to the above results in Table 2. Reducing
the concentration to 0.03 M by increasing the amount of solvent
(DCM) employed to 3.00 mL can improve the reaction outcome,
affording the corresponding products in 85% combined yield along
with the 13 : 1 ratio of 7aa : 6aa (Table 3, entry 1). Inspired by
this result, we next screened various nitrogen-containing Lewis
base catalysts for this reaction in the optimized amount of
solvent (3.00 mL, 0.03 M). DMAP can efficiently catalyze this
reaction as well but with low regioselectivity. However, DBU
and DIEA did not catalyze this reaction (Table 3, entries 2–4).
Accordingly, DABCO was then used as the best catalyst for further
investigation of solvent and temperature effects in this reaction.
It was found that THF was the solvent of choice in comparison
with those reactions carried out in other organic solvents, such
as toluene, Et2O, 1,2-dichloroethane (DCE), chloroform, 1,4-
dioxane, CH3CN, N,N-dimethylformamide (DMF) and dimethyl
sulfoxide (DMSO) (Table 3, entries 5–13). The low temperature
(-10 ◦C) can improve the combined yield of 6aa and 7aa (Table 3,
entry 15), but further lowering the reaction temperature to -40 ◦C
reduced the combined yield (Table 3, entry 16). Thus, we have
identified the optimal reaction conditions for this reaction: using
20 mol% of DABCO as a catalyst and THF as a solvent to perform
the reaction at -10 ◦C.
Table 2 Substrate scope of the reactions of phosphonates 1 and allenic
esters 2a
Entry No R1
R2
R3 (2)
Yield (%)b No
3 : 4c
1
2
3
4
5
6
7
8
1a C6H5
OMe Et (2a) 86
OMe iPr (2b) 82
OMe Me (2c) 90
OtBu Et (2a) 70
OiPr Et (2a) 85
OiPr Et (2a) 87
3aa : 4aa 5 : 1
3ab : 4ab 3 : 1
3ac : 4ac 3 : 1
3ba : 4ba 9 : 1
3ca : 4ca 10 : 1
3da : 4da 10 : 1
3ea : 4ea >20 : 1
3fa : 4fa 13 : 1
3ga : 4ga 10 : 1
3ha : 4ha 8 : 1
1a C6H5
1a C6H5
1b C6H5
1c C6H5
1d 4-ClC6H4
1e 4-NO2C6H4 OiPr Et (2a) 80
1f 4-BrC6H4
1g 3-MeC6H4
OiPr Et (2a) 85
OiPr Et (2a) 85
Having identified the optimal reaction conditions, we next
set out to examine the scope and limitations of the [4 + 2]
cycloaddition reaction catalyzed by DABCO using various
b,g-unsaturated a-ketoesters 5 with different substituents on the
R4 group, and the results are summarized in Table 4. As can
be seen from Table 4, when R4 is an aromatic group, whether
they have electron-withdrawing or electron-donating substituents
at the ortho-, meta- or para-positions on the benzene rings, the
9
10
11
12
1h 4-MeOC6H4 OiPr Et (2a) 75
1i 1-naphthyl
1j Me
OiPr Et (2a) 85
OiPr Et (2a) 75
3ia : 4ia
3ja : 4ja
14 : 1
4 : 1
a All reactions were carried out using 1 (0.10 mmol) and 2 (0.12 mmol) in
DCM (1.00 mL) at -40 ◦C for 24 h. b Isolated combined yield. c Determined
by 1H NMR spectroscopic data, and these regioisomers cannot be easily
separated by column chromatography.
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Table 3 Optimization of the reaction conditions of (E)-ethyl 2-oxo-4-
phenylbut-3-enoate 5a and ethyl 2,3-butadienoate 2aa
reactions proceeded smoothly to give the desired products
in good yields along with good regioselectivities (Table 4, entries
2–7). Heterocyclic substrates 5h and 5l were also suitable in
this reaction to give the corresponding products in moderate
combined yields and regioselectivities (Table 4, entries 8 and 9).
The substrate 5j, in which R4 is a 2-naphthyl group, was also
tolerable in this reaction to give the corresponding products in
82% combined yield along with good regioselectivity (7ja : 6ja =
8 : 1) (Table 4, entry 10). For substrate 5k, in which R4 is a
cyclopropyl group, the reaction also proceeded smoothly to give
the desired products in high combined yield (up to 90%) along
with high regioselectivity (up to 7ka : 6ka = >20 : 1). The structure
of 6ea was unambiguously determined by X-ray diffraction.
The ORTEP drawing is shown in Fig. 1 and its CIF data are
summarized in the Supporting Information.†7 The structure of
7 and the E-configuration of the double bond were assigned
by the 2-D NMR spectroscopic data (HMQC, HMBC, DEPT
and NOESY spectra) of compound 7aa (see the Supporting
Information for the details†).
Entry LB
T/◦C
Solvent
Yield (%)b 7aa : 6aa (%)c
1
2
3
4
5
6
7
8
DABCO
DMAP
DIEA
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
-10
-40
DCM
DCM
DCM
DCM
THF
Toluene
Et2O
85 (82)d
80
NR
NR
90
75
88
86
90
89
50
trace
trace
91
95
92
13 : 1 (8 : 1)d
2 : 1
—
—
>20 : 1
5 : 1
13 : 1
8 : 1
6 : 1
14 : 1
>20 : 1
—
DBU
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DCE
9
CHCl3
Dioxane
CH3CN
DMSO
DMF
THF
10
11
12
13
14
15
16
—
>20 : 1
>20 : 1
>20 : 1
THF
THF
a All reactions were carried out using 5a (0.10 mmol) and 2a (0.12 mmol) in
solvent (3.00 mL, 0.03 M) for 24 h. b Isolated combined yield. c Determined
by 1H NMR spectroscopic data, and these regioisomers can not be easily
separated by column chromatography. d The reaction was carried out in
DCM (2.00 mL, 0.05 M).
Fig. 1 An ORTEP drawing of 6ea.
The mechanism for the reactions has not been unequivocally
established, but one reasonable explanation is shown in Scheme
1 based on earlier reports and our own investigations. Addition
of DABCO to allenoate 2a delivers zwitterionic intermediate A,
which coexists with its resonance form B.3a,3c The zwitterionic
intermediate A reacts with 1 or 5 to give intermediate C,
which undergoes enolization to give intermediate E. Subsequent
cyclization produces cyclic product G and regenerates the DABCO
catalyst. Finally, G isomerizes to give the more stable adducts 3 or
6. At the same time, the zwitterionic intermediate B can also react
with 1 or 5 to give intermediate D, which undergoes enolization
to give intermediate F. Subsequent cyclization produces cyclic
product 4 or 7 and regenerates the DABCO catalyst. We also
assumed that the major products in the reaction might be mainly
due to the steric interaction between intermediates C and D. When
EWG = PO(OiPr)2, which is sterically more bulky than an aromatic
ring, the steric repulsion between CO2Et and EWG is larger than
that of CO2Et and an aromatic ring. Therefore, intermediate C is
more stable than intermediate D, affording 3 as the major product.
When EWG = CO2Et, which is sterically smaller than aromatic
ring, the steric repulsion between CO2Et and EWG is less than
that of CO2Et and aromatic ring. Therefore, intermediate D is
more stable than intermediate C, leading to 7 as the major product.
In conclusion, we have established a novel DABCO-catalyzed
[4 + 2] cycloaddition of b,g-unsaturated a-ketophosphonates
or b,g-unsaturated a-ketoesters with allenic esters to give the
corresponding highly functionalized tetrahydropyran and dihy-
dropyran derivatives in good to excellent yields and moderate
Table 4 Substrate scope of the reactions of b,g-unsaturated a-ketoesters
5 and ethyl 2,3-butadienoate 2aa
Entry
No
R1
Yield (%)b
No
7 : 6c
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
C6H5
95
86
87
83
85
87
85
60
57
82
90
7aa : 6aa
7ba : 6ba
7ca : 6ca
7da : 6da
7ea : 6ea
7fa : 6fa
7ga : 6ga
7ha : 6ha
7ia : 6ia
>20 : 1
14 : 1
10 : 1
8 : 1
8 : 1
7 : 1
12 : 1
3 : 1
6 : 1
8 : 1
>20 : 1
4-ClC6H4
4-BrC6H4
3-BrC6H4
2-BrC6H4
2,4-Cl2C6H3
4-MeC6H4
2-furyl
2-thiophene
2-naphthyl
cyclopropyl
9
10
11
5j
5k
7ja : 6ja
7ka : 6ka
a All reactions were carried out using 5 (0.10 mmol) and 2a (0.12 mmol) in
solvent (3.00 mL, 0.03 M) for 24 h. b Isolated combined yield. c Determined
by 1H NMR spectroscopic data, and these regioisomers can not be easily
separated by column chromatography.
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in cm-1. THF, toluene and Et2O were distilled from sodium
(Na) under argon (Ar) atmosphere. CH3CN, 1,2-dichloroethane
and dichloromethane were distilled from CaH2 under argon
(Ar) atmosphere. Commercially obtained reagents were used
without further purification. All reactions were monitored by
TLC with Huanghai GF254 silica gel coated plates. Flash column
chromatography was carried out using 300–400 mesh silica gel at
increased pressure. All the b,g-unsaturated a-ketophosphonates
and b,g-unsaturated a-ketoesters were prepared according to the
literature.4b,8
General procedure for the preparation of 3 and 4 from the reaction
of 1a with 2a using 3aa and 4aa as an example in the presence of
DABCO
To a mixture of 1a (0.10 mmol, 24.0 mg), 2a (0.12 mmol,
13.6 mL) and DABCO (2.2 mg, 0.02 mmol) was added 2.0 mL of
dichloromethane at -40 ◦C. The reaction solution was monitored
by TLC. After the reaction was complete, the solution was
concentrated under reduced pressure and the residue was further
purified by silica gel column chromatography (EtOAc/PE = 1/6)
to give the target products 3aa and 4aa.
Ethyl 6-(dimethoxyphosphoryl)-2-methyl-4-phenyl-4H-pyran-3-
carboxylate 3aa. A colorless oil (16.7 mg, 70%); 1H NMR (400
MHz, CDCl3, TMS) d 1.09 (t, J = 7.2 Hz, 3H), 2.39 (s, 3H), 3.78
(d, J = 11.2 Hz, 3H), 3.80 (d, J = 11.2 Hz, 3H), 3.96–4.07 (m, 2H),
4.45 (d, J = 5.2 Hz, 1H), 6.12 (dd, J = 10.0 Hz, 5.2 Hz, 1H), 7.19–
7.22 (m, 3H), 7.29–7.31 (m, 2H); 13C NMR (100 MHz, CDCl3) d
13.8, 19.0, 38.1 (d, J = 10.4 Hz), 53.3 (d, J = 6.7 Hz), 53.4 (d, J = 5.9
Hz), 60.1, 104.8, 122.0 (d, J = 20.9 Hz), 126.9, 127.8, 128.5, 137.4,
139.8, 144.0 (d, J = 2.2 Hz), 159.7 (d, J = 8.2 Hz), 166.6; 31P NMR
(161.93 MHz, CDCl3, 85% H3PO4): d 9.734;. IR (CH2Cl2) n 2966,
2902, 1715, 1659, 1473, 1373, 1260, 1176, 1105, 1026, 947, 800,
741, 700 cm-1; MS (ESI) m/z 353.0 (M+H+). HRMS (ESI) Calcd
for C17H22O6P requires (M+H+): 353.1149, found: 353.1156.
(E)-Ethyl
2-(6-(dimethoxyphosphoryl)-4-phenyl-3,4-dihydro-
Scheme 1 A plausible reaction mechanism.
2H-pyran-2-ylidene)acetate 4aa. A colorless oil (5.5 mg, 16%);
1H NMR (400 MHz, CDCl3, TMS) d 1.23 (t, J = 7.2 Hz, 3H),
3.10 (dd, J = 10.4 Hz, 6.8 Hz, 1H), 3.67–3.73 (m, 2H), 3.84 (d,
J = 11.2 Hz, 3H), 3.85 (d, J = 11.2 Hz, 3H), 4.08–4.14 (m, 2H),
5.67 (s, 1H), 6.28 (dd, J = 10.4 Hz, 2.8 Hz, 1H), 7.19–7.22 (m,
2H), 7.26–7.28 (m, 1H), 7.31–7.35 (m, 2H); 13C NMR (100 MHz,
CDCl3) d 14.1, 29.8, 35.6 (d, J = 11.9 Hz), 53.39 (d, J = 3.7 Hz),
53.40 (d, J = 6.2 Hz), 59.8, 100.8, 122.0 (d, J = 19.3 Hz), 127.0,
127.2, 128.8, 141.0 (d, J = 11.2 Hz), 143.4, 164.6 (d, J = 9.7 Hz),
166.6; 31P NMR (161.93 MHz, CDCl3, 85% H3PO4): d 9.180; IR
(neat) n 2966, 2902, 1712, 1656, 1494, 1449, 1374, 1261, 1172,
1111, 1026, 824, 764, 700 cm-1; MS (ESI) m/z 353.1 (M+H+);
HRMS (ESI) Calcd for C17H22O6P requires (M+H+): 353.1149,
found: 353.1159.
to good regioselectivities under mild conditions. The obtained
multiple functionalized tetrahydropyran and dihydropyran deriva-
tives are useful building blocks in the organic synthesis of
biologically useful compounds. A plausible reaction mechanism
has been also proposed on the basis of previous literature and our
own investigations. Efforts are in progress to elucidate further
mechanistic details of these reactions and to understand their
scope and limitations.
Experimental section
General remarks
1H NMR spectra were recorded on a Bruker AM-300 or AM-
400 spectrometer for solution in CDCl3 with tetramethylsilane
(TMS) as internal standard; J-values are in Hz. Mass spectra
were recorded with a HP-5989 instrument. All of the compounds
reported in this paper gave satisfactory HRMS analytic data.
Melting points were determined on a digital melting point ap-
paratus and temperatures were uncorrected. Infrared spectra were
recorded on a Perkin-Elmer PE-983 spectrometer with absorption
Isopropyl
6-(dimethoxyphosphoryl)-2-methyl-4-phenyl-4H-
pyran-3-carboxylate 3ab. A slightly yellow liquid (22.0 mg,
60%); 1H NMR (CDCl3, 400 MHz, TMS) d 0.91 (d, J = 6.0 Hz,
3H), 1.16 (d, J = 6.0 Hz, 3H), 2.39 (s, 3H), 3.78 (d, J = 11.2 Hz,
3H), 3.81 (d, J = 11.2 Hz, 3H), 4.44 (d, J = 4.8 Hz, 1H), 4.88 (sept,
J = 6.0 Hz, 1H), 6.11 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 7.18–7.31 (m,
5H); 13C NMR (100 MHz, CDCl3) d 19.0, 21.3, 21.8, 38.3 (d, J =
10.6 Hz), 53.29 (d, J = 6.0 Hz), 53.35 (d, J = 6.0 Hz), 67.6, 105.0,
174 | Org. Biomol. Chem., 2012, 10, 171–180
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121.9 (d, J = 20.4 Hz), 126.9, 128.0, 128.5, 137.6, 139.9, 144.3,
159.5 (d, J = 9.1 Hz), 166.2; 31P NMR (CDCl3, 161.93 MHz, 85%
H3PO4) d 9.795; IR (CH2Cl2) n 3061, 2980, 2902, 1713, 1659,
1628, 1374, 1262, 1177, 1104, 1047, 953, 803, 739, 701 cm-1; MS
(ESI) m/z 367.1 (M+H+); HRMS (ESI) Calcd for C18H23O6PNa
requires (M+Na+): 389.1125, found: 389.1110.
700 cm-1; MS (ESI) m/z 459.3 (M+Na+); HRMS (ESI) Calcd for
C23H33O6PNa requires (M+Na+): 459.1907, found: 459.1919.
(E)-ethyl 2-(6-(di-tert-butoxyphosphoryl)-4-phenyl-3,4-dihydro-
2H-pyran-2-ylidene)acetate 4ba. A slightly yellow liquid (3.1 mg,
7%); 1H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t, J = 7.2 Hz, 3H),
1.54 (s, 18H), 3.05 (dd, J = 13.6 Hz, 6.8 Hz, 1H), 3.61–3.70 (m,
2H), 4.09–4.14 (m, 2H), 5.65 (s, 1H), 6.19 (dd, J = 11.2 Hz, 2.8 Hz,
(E)-Isopropyl 2-(6-(dimethoxyphosphoryl)-4-phenyl-3,4-dihydro-
2H-pyran-2-ylidene)acetate 4ab. A slightly yellow liquid (8.1 mg,
22%); 1H NMR (CDCl3, 400 MHz, TMS) d 1.19 (d, J = 6.4 Hz,
3H), 1.22 (d, J = 6.4 Hz, 3H), 3.10 (dd, J = 17.2 Hz, 10.4 Hz, 1H),
3.68–3.72 (m, 2H), 3.84 (d, J = 11.2 Hz, 3H), 3.85 (d, J = 11.2 Hz,
3H), 4.98 (sept, J = 6.4 Hz, 1H), 5.64 (s, 1H), 6.29 (dd, J = 10.0 Hz,
2.8 Hz, 1H), 7.20–7.27 (m, 3H), 7.31–7.34 (m, 2H). 13C NMR (100
MHz, CDCl3) d 21.8, 29.9, 35.7 (d, J = 11.9 Hz), 53.4 (d, J = 4.4
Hz), 67.1, 101.4, 121.5 (d, J = 19.3 Hz), 127.1, 127.2, 128.8, 141.1
(d, J = 16.4 Hz), 143.6, 164.4 (d, J = 9.7 Hz), 166.2; 31P NMR
(CDCl3, 161.93 MHz, 85% H3PO4) d 9.206; IR (CH2Cl2) n 3062,
2979, 2905, 1706, 1655, 1452, 1374, 1260, 1170, 1100, 1023, 800,
761, 700 cm-1; MS (ESI) m/z 367.2 (M+H+); HRMS (ESI) Calcd
for C18H23O6PNa requires (M+Na+): 389.1125, found: 389.1112.
1H), 7.19–7.21 (m, 2H), 7.22–7.26 (m, 1H), 7.30–7.33 (m, 2H); 31
P
NMR (CDCl3, 121 MHz, 85% H3PO4) d -3.003; IR (CH2Cl2) n
2977, 2903, 1713, 1655, 1373, 1261, 1170, 1114, 1042, 1014, 801,
739, 700 cm-1; MS (ESI) m/z 459.2 (M+Na+); HRMS (ESI) Calcd
for C23H33O6PNa requires (M+Na+): 459.1907, found: 459.1915.
Ethyl 6-(diisopropoxyphosphoryl)-2-methyl-4-phenyl-4H-pyran-
1
3-carboxylate 3ca. A slightly yellow liquid (31.4 mg, 77%); H
NMR (CDCl3, 400 MHz, TMS) d 1.09 (t, J = 6.8 Hz, 3H), 1.31
(d, J = 6.4 Hz, 6H), 1.35 (d, J = 6.4 Hz, 3H), 1.37 (d, J = 6.4 Hz,
3H), 2.40 (s, 3H), 3.97–4.06 (m, 2H), 4.44 (d, J = 4.8 Hz, 1H),
4.65–4.73 (m, 2H), 6.10 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 7.18–7.22
(m, 3H), 7.28–7.30 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS)
d 13.8, 19.0, 23.60 (d, J = 3.8 Hz), 23.65 (d, J = 4.4 Hz), 23.9
(d, J = 4.5 Hz), 38.2 (d, J = 9.9 Hz), 60.1, 71.8 (d, J = 4.9 Hz),
104.8, 120.7 (d, J = 19.8 Hz), 126.8, 127.9, 128.0, 128.4, 139.7,
142.0, 144.3, 159.9 (d, J = 9.4 Hz), 166.8; 31P NMR (CDCl3,
161.93 MHz, 85% H3PO4) d 4.537; IR (CH2Cl2) n 2982, 2905,
2876, 1769, 1720, 1658, 1376, 1261, 1098, 1009, 800, 701 cm-1; MS
(ESI) m/z 409.2 (M+H+); HRMS (ESI) Calcd for C21H29O6PNa
requires (M+Na+): 431.1594, found: 431.1595.
Methyl 6-(dimethoxyphosphoryl)-2-methyl-4-phenyl-4H-pyran-
1
3-carboxylate 3ac. A slightly yellow liquid (21.6 mg, 64%); H
NMR (CDCl3, 400 MHz, TMS) d 2.39 (s, 3H), 3.57 (s, 3H), 3.78
(d, J = 11.2 Hz, 3H), 3.80 (d, J = 11.2 Hz, 3H), 4.45 (d, J =
4.8 Hz, 1H), 6.13 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 7.20–7.22 (m,
3H), 7.28–7.32 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d
19.1, 38.1 (d, J = 10.4 Hz), 51.3, 53.27 (d, J = 6.0 Hz), 53.34 (d, J =
5.9 Hz), 104.8, 121.9 (d, J = 20.0 Hz), 127.0, 127.8, 128.6, 137.8,
140.2, 144.0, 160.0 (d, J = 8.9 Hz), 167.2; 31P NMR (CDCl3, 161.93
MHz, 85% H3PO4) d 9.654. IR (CH2Cl2) n 3062, 2963, 2904, 1717,
1660, 1627, 1437, 1375, 1262, 1174, 1037, 840, 803, 702 cm-1; MS
(ESI) m/z 339.1 (M+H+); HRMS (ESI) Calcd for C16H19O6PNa
requires (M+Na+): 361.0812, found: 361.0801.
(E)-Ethyl 2-(6-(diisopropoxyphosphoryl)-4-phenyl-3,4-dihydro-
2H-pyran-2-ylidene)acetate 4ca. A slightly yellow liquid (3.2 mg,
1
8%); H NMR (CDCl3, 300 MHz, TMS) d 1.23 (t, J = 7.2 Hz,
3H), 1.35 (d, J = 6.3 Hz, 6H), 1.39 (d, J = 6.3 Hz, 6H), 3.10 (dd,
J = 16.8 Hz, 9.9 Hz, 1H), 3.64–3.71 (m, 2H), 4.07–4.16 (m, 2H),
4.71–4.80 (m, 2H), 5.65 (s, 1H), 6.27 (dd, J = 10.2 Hz, 6.9 Hz,
1H), 7.19–7.26 (m, 3H), 7.30–7.35 (m, 2H); 13C NMR (CDCl3,
75 MHz, TMS) d 14.2, 23.7 (d, J = 4.6 Hz), 24.0 (d, J = 3.5
Hz), 29.9, 35.6 (d, J = 11.4 Hz), 59.8, 71.9 (d, J = 5.7 Hz), 100.4,
120.6 (d, J = 19.4 Hz), 127.1, 127.2, 128.7, 141.3, 142.8, 145.9,
165.1 (d, J = 9.7 Hz), 166.8; 31P NMR (CDCl3, 121.453 MHz,
85% H3PO4) d 5.107; IR (CH2Cl2) n 3063, 2980, 2937, 2902, 1711,
1654, 1352, 1259, 1170, 1110, 1044, 985, 886, 762, 700 cm-1; MS
(ESI) m/z 409.2 (M+H+); HRMS (ESI) Calcd for C21H29O6PNa
requires (M+Na+): 431.1594, found: 431.1579.
(E)-Methyl 2-(6-(dimethoxyphosphoryl)-4-phenyl-3,4-dihydro-
2H-pyran-2-ylidene)acetate 4ac. (8.8 mg, 26%): a slightly yellow
liquid. 1H NMR (CDCl3, 400 MHz, TMS) d 3.11 (dd, J = 17.6 Hz,
10.4 Hz, 1H), 3.65 (s, 3H), 3.68–3.73 (m, 2H), 3.85 (d, J = 11.2 Hz,
6H), 5.68 (s, 1H), 6.29 (dd, J = 10.4 Hz, 3.2 Hz, 1H), 7.19–7.27
(m, 3H), 7.33–7.35 (m, 2H); 13C NMR (100 MHz, CDCl3) d 19.1,
29.9, 35.6 (d, J = 11.9 Hz), 51.1, 53.4 (d, J = 5.2 Hz), 100.4, 122.1
(d, J = 19.4 Hz), 127.1, 127.3, 128.8, 141.1 (d, J = 20.0 Hz), 143.5,
164.5 (d, J = 9.7 Hz), 167.1; 31P NMR (CDCl3, 161.93 MHz, 85%
H3PO4) d 9.165; IR (CH2Cl2) n 3061, 2963, 2904, 1714, 1655,
1372, 1262, 1168, 1114, 1028, 803, 764, 701, 651 cm-1; MS (ESI)
m/z 339.2 (M+H+); HRMS (ESI) Calcd for C16H20O6P requires
(M+H+): 339.1001, found: 339.0992.
Ethyl 4-(4-chlorophenyl)-6-(diisopropoxyphosphoryl)-2-methyl-
4H-pyran-3-carboxylate 3da. A slightly yellow liquid (34.9 mg,
1
79%); H NMR (CDCl3, 400 MHz, TMS) d 1.11 (t, J = 7.2 Hz,
3H), 1.31 (d, J = 6.0 Hz, 6H), 1.36 (d, J = 6.0 Hz, 3H), 1.37 (d,
J = 6.0 Hz, 3H), 2.40 (s, 3H), 4.00–4.08 (m, 2H), 4.43 (d, J =
4.8 Hz, 1H), 4.64–4.75 (m, 2H), 6.06 (dd, J = 10.0 Hz, 4.8 Hz,
1H), 7.14 (d, J = 7.2 Hz, 2H), 7.28 (d, J = 7.2 Hz, 2H); 13C NMR
(CDCl3, 100 MHz, TMS) d 14.2, 19.1, 23.0–24.5 (m, 4C), 37.6 (d,
J = 10.4 Hz), 60.2, 71.8 (d, J = 5.2 Hz), 71.9 (d, J = 5.2 Hz), 104.4,
119.9 (d, J = 20.0 Hz), 128.6, 129.2, 132.6, 140.1, 142.4, 142.9,
160.2 (d, J = 8.9 Hz), 166.6; 31P NMR (CDCl3, 161.93 MHz, 85%
H3PO4) d 4.175; IR (CH2Cl2) n 2980, 2942, 2904, 1714, 1663, 1625,
1488, 1376, 1259, 1176, 1104, 986, 946, 804, 685 cm-1; MS (ESI)
m/z 443.3 (M+H+); HRMS (ESI) Calcd for C21H28O6PNa requires
(M+Na+): 465.1204, found: 465.1193.
Ethyl
6-(di-tert-butoxyphosphoryl)-2-methyl-4-phenyl-4H-
pyran-3-carboxylate 3ba. A slightly yellow liquid (27.5 mg,
1
63%); H NMR (CDCl3, 400 MHz, TMS) d 1.08 (t, J = 7.2 Hz,
3H), 1.46 (s, 9H), 1.51 (s, 9H), 2.40 (s, 3H), 3.96–4.06 (m, 2H), 4.42
(d, J = 4.8 Hz, 1H), 5.99 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 7.17–7.20
(m, 3H), 7.26–7.29 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS)
d 13.7, 19.2, 29.6–31.0 (m, 6C), 38.2 (d, J = 10.4 Hz), 60.1, 83.5,
104.6, 118.3 (d, J = 21.5 Hz), 126.7, 128.0, 128.3, 142.6, 144.6,
144.9, 160.2 (d, J = 8.2 Hz), 167.1; 31P NMR (CDCl3, 161.93
MHz, 85% H3PO4) d -2.515; IR (CH2Cl2) n 2980, 2902, 2884,
1714, 1659, 1626, 1476, 1372, 1262, 1171, 1108, 1041, 992, 804,
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(E)-Ethyl 2-(4-(4-chlorophenyl)-6-(diisopropoxyphosphoryl)-3,4-
dihydro-2H-pyran-2-ylidene)acetate 4da. A slightly yellow liquid
(3.5 mg, 8%); H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t, J =
Ethyl
6-(diisopropoxyphosphoryl)-2-methyl-4-m-tolyl-4H-
pyran-3-carboxylate 3ga. A slightly yellow liquid (32.6 mg,
1
1
77%); H NMR (CDCl3, 400 MHz, TMS) d 1.11 (t, J = 7.2 Hz,
7.2 Hz, 3H), 1.34 (d, J = 6.4 Hz, 3H), 1.35 (d, J = 6.4 Hz, 3H), 1.39
(d, J = 6.0 Hz, 6H); 3.16 (dd, J = 15.2 Hz, 7.6 Hz, 1H), 3.55 (dd, J =
15.2 Hz, 6.0 Hz, 1H); 3.64–3.67 (m, 1H), 4.09–4.13 (m, 2H), 4.73–
4.79 (m, 2H), 5.65 (s, 1H), 6.22 (dd, J = 10.0 Hz, 4.0 Hz, 1H), 7.13
(d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H); 31P NMR (CDCl3,
161.93 MHz, 85% H3PO4) d 3.723; IR (CH2Cl2) n 2980, 2942,
2902, 1713, 1657, 1492, 1375, 1261, 1172, 1116, 1045, 994, 820,
739, 703 cm-1; MS (ESI) m/z 443.2 (M+H+); HRMS (ESI) Calcd
for C21H28O6PNa requires (M+Na+): 465.1204, found: 465.1213.
3H), 1.32 (d, J = 6.4 Hz, 6H), 1.35 (d, J = 6.4 Hz, 3H), 1.37 (d,
J = 6.4 Hz, 3H), 2.31 (s, 3H), 2.39 (s, 3H), 4.00–4.07 (m, 2H), 4.40
(d, J = 4.8 Hz, 1H), 4.66–4.73 (m, 2H), 6.09 (dd, J = 10.0 Hz,
4.8 Hz, 1H), 7.00–7.02 (m, 3H), 7.17 (t, J = 8.0 Hz, 1H); 13C
NMR (CDCl3, 100 MHz, TMS) d 13.9, 19.0, 21.3, 23.6 (d, J =
5.2 Hz), 23.7 (d, J = 5.9 Hz), 24.0 (d, J = 3.7 Hz), 38.1 (d, J =
9.7 Hz), 60.1, 71.7 (d, J = 5.2 Hz), 104.9, 120.8 (d, J = 20.1 Hz),
125.0, 127.6, 128.3, 128.7, 138.0, 139.7, 142.0, 144.3, 159.8 (d, J =
8.2 Hz), 166.9; 31P NMR (CDCl3, 161.93 MHz, 85% H3PO4) d
5.259; IR (CH2Cl2) n 2979, 2901, 2884, 1715, 1660, 1626, 1475,
1376, 1261, 1171, 1107, 1011, 801, 739, 703 cm-1; MS (ESI) m/z
423.3 (M+H+); HRMS (ESI) Calcd for C22H31O6PNa requires
(M+Na+): 445.1751, found: 445.1743.
Ethyl 6-(diisopropoxyphosphoryl)-2-methyl-4-(4-nitrophenyl)-
4H-pyran-3-carboxylate 3ea. A slightly yellow liquid (36.2 mg,
1
80%); H NMR (CDCl3, 400 MHz, TMS) d 1.11 (t, J = 7.2 Hz,
3H), 1.32 (d, J = 6.4 Hz, 6H), 1.36 (d, J = 6.4 Hz, 3H), 1.38 (d, J =
6.4 Hz, 3H), 2.43 (s, 3H), 4.00–4.06 (m, 2H), 4.58 (d, J = 4.8 Hz,
1H), 4.67–4.74 (m, 2H), 6.04 (dd, J = 10.0 Hz, 4.8 Hz, 1H), 7.38
(d, J = 8.8 Hz, 2H), 8.17 (d, J = 8.8 Hz, 2H); 13C NMR (CDCl3,
100 MHz, TMS) d 14.0, 19.3, 23.7 (d, J = 4.6 Hz), 23.9 (d, J = 2.3
Hz), 38.3 (d, J = 9.9 Hz), 60.5, 72.1 (d, J = 5.3 Hz), 103.8, 118.6
(d, J = 19.5 Hz), 123.9, 128.7 141.1, 143.5, 146.9, 151.6, 161.2 (d,
J = 8.3 Hz), 166.3; 31P NMR (CDCl3, 161.93 MHz, 85% H3PO4)
d 3.597; IR (CH2Cl2) n 3074, 2981, 2906, 2874, 1715, 1662, 1626,
1521, 1375, 1347, 1176, 1105, 988, 854, 806, 700 cm-1; MS (ESI)
m/z 454.2 (M+H+); HRMS (ESI) Calcd for C21H28NO8PNa
requires (M+Na+): 476.1445, found: 476.1461.
(E)-Ethyl 2-(6-(diisopropoxyphosphoryl)-4-m-tolyl-3,4-dihydro-
2H-pyran-2-ylidene)acetate 4ga. A slightly yellow liquid (3.3 mg,
8%); 1H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t, J = 7.2 Hz, 3H),
1.35 (d, J = 6.4 Hz, 3H), 1.36 (d, J = 6.4 Hz, 3H), 1.39 (d, J = 6.4 Hz,
6H), 2.33 (s, 3H), 3.03 (dd, J = 15.2 Hz, 8.4 Hz, 1H), 3.62–3.64
(m, 1H), 3.70 (dd, J = 15.2 Hz, 6.0 Hz, 1H), 4.08–4.14 (m, 2H),
4.73–4.79 (m, 2H), 5.64 (s, 1H), 6.26 (dd, J = 10.4 Hz, 3.6 Hz, 1H),
6.99–7.00 (m, 2H), 7.06 (d, J = 7.6 Hz, 1H), 7.21 (t, J = 7.6 Hz,
1H); 31P NMR (CDCl3, 161.93 MHz, 85% H3PO4) d 4.008; IR
(CH2Cl2) n 2979, 2903, 1713, 1656, 1375, 1260, 1175, 1112, 1044,
1013, 800, 739, 703 cm-1; MS (ESI) m/z 423.3 (M+H+); HRMS
(ESI) Calcd for C22H31O6PNa requires (M+Na+): 445.1751, found:
445.1744.
Ethyl 4-(4-bromophenyl)-6-(diisopropoxyphosphoryl)-2-methyl-
4H-pyran-3-carboxylate 3fa. A slightly yellow liquid (38.3 mg,
1
79%); H NMR (CDCl3, 400 MHz, TMS) d 1.11 (t, J = 6.8 Hz,
Ethyl
6-(diisopropoxyphosphoryl)-4-(4-methoxyphenyl)-2-
3H), 1.31 (d, J = 6.4 Hz, 6H), 1.35 (d, J = 6.4 Hz, 3H), 1.37 (d, J =
6.4 Hz, 3H), 2.39 (s, 3H), 4.00–4.06 (m, 2H), 4.41 (d, J = 4.8 Hz,
1H), 4.65–4.73 (m, 2H), 6.05 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 7.08
(d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3,
100 MHz, TMS) d 14.0, 19.1, 23.64 (d, J = 2.3 Hz), 23.68 (d, J =
2.3 Hz), 23.9 (d, J = 3.8 Hz), 37.7 (d, J = 10.6 Hz), 60.3, 71.9
(d, J = 5.3 Hz), 104.4 (d, J = 1.5 Hz), 119.8 (d, J = 19.8 Hz),
120.8, 129.6, 131.6, 140.2, 142.5, 143.5 (d, J = 2.3 Hz), 160.2 (d,
J = 8.4 Hz), 166.6; 31P NMR (CDCl3, 161.93 MHz, 85% H3PO4)
d 4.165; IR (CH2Cl2) n 2979, 2934, 2906, 1713, 1657, 1488, 1448,
1261, 1170, 1111, 1010, 802, 740, 702, 668 cm-1; MS (ESI) m/z
487.3 (M+H+); HRMS (ESI) Calcd for C21H28O6PBrNa requires
(M+Na+): 509.0699, found: 509.0705.
methyl-4H-pyran-3-carboxylate 3ha. A slightly yellow liquid
(29.2 mg, 67%); H NMR (CDCl3, 400 MHz, TMS) d 1.12 (t,
1
J = 7.2 Hz, 3H), 1.30 (d, J = 6.4 Hz, 3H), 1.32 (d, J = 6.4 Hz,
3H), 1.35 (d, J = 6.4 Hz, 3H), 1.37 (d, J = 6.4 Hz, 3H), 2.37 (s,
3H), 3.78 (s, 3H), 4.00–4.08 (m, 2H), 4.38 (d, J = 4.8 Hz, 1H),
4.65–4.73 (m, 2H), 6.08 (dd, J = 10.0 Hz, 4.8 Hz, 1H), 6.82 (d,
J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100
MHz, TMS) d 14.0, 19.0, 23.6 (d, J = 1.4 Hz), 23.7 (d, J = 1.4
Hz), 24.0 (d, J = 4.6 Hz), 37.3 (d, J = 9.9 Hz), 55.2, 60.1, 71.7
(d, J = 5.3 Hz), 105.1 (d, J = 2.3 Hz), 113.8, 120.8 (d, J = 19.8
Hz), 129.0, 136.7 (d, J = 2.3 Hz), 139.6, 141.9, 158.5, 159.6 (d,
J = 9.2 Hz), 167.0; 31P NMR (CDCl3, 161.93 MHz, 85% H3PO4)
d 4.631; IR (CH2Cl2) n 2980, 2937, 2906, 1714, 1626, 1510, 1376,
1259, 1176, 1106, 1070, 991, 946, 805, 745 cm-1; MS (ESI) m/z
439.3 (M+H+); HRMS (ESI) Calcd for C22H31O7PNa requires
(M+Na+): 461.1700, found: 461.1699.
(E)-Ethyl
2-(4-(4-bromophenyl)-6-(diisopropoxyphosphoryl)-
3,4-dihydro-2H-pyran-2-ylidene)acetate 4fa. A slightly yellow
1
liquid (3.1 mg, 6%); H NMR (CDCl3, 400 MHz, TMS) d 1.24
(t, J = 7.2 Hz, 3H), 1.35 (d, J = 6.4 Hz, 3H), 1.36 (d, J = 6.4 Hz,
3H), 1.39 (d, J = 6.4 Hz, 6H); 3.16 (dd, J = 15.2 Hz, 7.6 Hz, 1H),
3.57 (dd, J = 15.2 Hz, 6.4 Hz, 1H), 3.62–3.66 (m, 1H), 4.09–4.14
(m, 2H), 4.72–4.79 (m, 2H), 5.65 (s, 1H), 6.21 (dd, J = 10.0 Hz,
(E)-ethyl 2-(6-(diisopropoxyphosphoryl)-4-(4-methoxyphenyl)-
3,4-dihydro-2H-pyran-2-ylidene)acetate 4ha. A slightly yellow
liquid (3.7 mg, 8%); 1H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t,
J = 7.2 Hz, 3H), 1.35 (d, J = 6.4 Hz, 3H), 1.36 (d, J = 6.4 Hz, 3H),
1.38 (d, J = 6.0 Hz, 6H), 3.11 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 3.57–
3.63 (m, 2H), 3.79 (s, 3H), 4.08–4.14 (m, 2H), 4.72–4.78 (m, 2H),
5.64 (s, 1H), 6.24 (dd, J = 10.4 Hz, 4.4 Hz, 1H), 6.85 (d, J = 8.4 Hz,
2H), 7.12 (d, J = 8.4 Hz, 2H); 31P NMR (CDCl3, 161.93 MHz, 85%
H3PO4) d 4.061; IR (CH2Cl2) n 2968, 2902, 2839, 1713, 1657, 1513,
1474, 1447, 1375, 1172, 1109, 1046, 1016, 803, 738, 702 cm-1; MS
4.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H); 31
P
NMR (CDCl3, 161.93 MHz, 85% H3PO4) d 3.697; IR (CH2Cl2) n
2980, 2939, 2902, 1714, 1661, 1626, 1485, 1376, 1260, 1176, 1106,
992, 805, 740, 664 cm-1; MS (ESI) m/z 487.3 (M+H+); HRMS
(ESI) Calcd for C21H28O6PBrNa requires (M+Na+): 509.0699,
found: 509.0708.
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(ESI) m/z 439.3 (M+H+); HRMS (ESI) Calcd for C22H31O7PNa
4.66–4.74 (m, 2H), 5.61 (s, 1H), 6.08 (dd, J = 10.4 Hz, 4.0 Hz, 1H);
31P NMR (CDCl3, 161.93 MHz, 85% H3PO4) d 4.380; IR (CH2Cl2)
n 2978, 2906, 1713, 1657, 1375, 1351, 1261, 1114, 1048, 1014, 803,
739, 703 cm-1; MS (ESI) m/z 347.2 (M+H+); HRMS (ESI) Calcd
for C16H27O6PNa requires (M+Na+): 369.1438, found: 369.1421.
requires (M+Na+): 461.1700, found: 461.1694.
Ethyl 6-(diisopropoxyphosphoryl)-2-methyl-4-(naphthalen-1-yl)-
4H-pyran-3-carboxylate 3ia. A slightly yellow liquid (36.2 mg,
1
79%); H NMR (CDCl3, 400 MHz, TMS) d 0.74 (t, J = 7.2 Hz,
3H), 1.25 (d, J = 6.4 Hz, 3H), 1.29 (d, J = 5.2 Hz, 3H), 1.30 (d,
J = 6.0 Hz, 3H), 1.36 (d, J = 6.4 Hz, 3H), 2.49 (s, 3H), 3.85 (q,
J = 7.2 Hz, 2H), 4.53–4.62 (m, 1H), 4.65–4.73 (m, 1H), 5.34 (d,
J = 4.8 Hz, 1H), 6.21 (dd, J = 10.4 Hz, 4.8 Hz, 1H), 7.32 (d, J =
6.8 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 7.47–7.56 (m, 2H), 7.71 (d,
J = 8.0 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H);
13C NMR (CDCl3, 100 MHz, TMS) d 13.6, 18.9, 23.5 (d, J = 4.4
Hz), 23.6 (d, J = 5.2 Hz), 23.87 (d, J = 4.4 Hz), 23.91 (d, J = 4.4
Hz), 33.1 (d, J = 10.5 Hz), 60.0, 71.66 (d, J = 5.2 Hz), 71.72 (d,
J = 6.0 Hz), 104.3 (d, J = 1.5 Hz), 120.2 (d, J = 21.1 Hz), 122.5,
125.60, 125.61, 126.3, 127.3, 128.7, 130.4, 133.7, 139.5, 140.8 (d,
J = 2.2 Hz), 141.8, 160.4 (d, J = 8.2 Hz), 166.8; 31P NMR (CDCl3,
161.93 MHz, 85% H3PO4) d 4.637; IR (CH2Cl2) n 3059, 2980,
2939, 1713, 1665, 1627, 1375, 1327, 1258, 1106, 984, 798, 776, 740,
702 cm-1; MS (ESI) m/z 459.3 (M+H+); HRMS (ESI) Calcd for
C25H31O6PNa requires (M+Na+): 481.1751, found: 481.1760.
General procedure for the preparation of 6 and 7 from the reaction
of 5a with 2a using 6aa and 7aa as an example in the presence of
DABCO
To a mixture of 1a (0.10 mmol, 20.4 mg), 2a (0.12 mmol, 13.6 mL)
and DABCO (2.2 mg, 0.02 mmol) was added 3.0 mL of THF
at -10 ◦C. The reaction solution was monitored by TLC. After
the reaction was complete, the solution was concentrated under
reduced pressure and the residue was further purified by silica
gel column chromatography (EtOAc/PE = 1/6) to give the target
products 6aa and 7aa.
Diethyl 6-methyl-4-phenyl-4H-pyran-2,5-dicarboxylate 6aa.
A
slightly yellow liquid (2.7 mg, 7%); 1H NMR (CDCl3, 400 MHz,
TMS) d 1.08 (t, J = 7.2 Hz, 3H), 1.30 (t, J = 7.2 Hz, 3H), 2.44 (s,
3H), 3.99–4.06 (m, 2H), 4.21–4.30 (m, 2H), 4.51 (d, J = 5.2 Hz,
1H), 6.26 (d, J = 5.2 Hz, 1H), 7.20–7.24 (m, 3H), 7.29–7.33 (m,
2H); 13C NMR (CDCl3, 100 MHz, TMS) d 13.9, 14.1, 19.1, 38.9,
60.2, 61.5, 104.6, 116.2, 127.0, 128.1, 128.6, 138.9, 144.4, 159.8,
161.1, 166.9; IR (CH2Cl2) n 2980, 2903, 1736, 1714, 1658, 1448,
1374, 1260, 1118, 1018, 860, 802, 761, 739, 700 cm-1; MS (ESI)
m/z 317.2 (M+H+); HRMS (ESI) Calcd for C18H20O5Na requires
(M+Na+): 339.1203, found: 339.1206.
(E)-Ethyl 2-(6-(diisopropoxyphosphoryl)-4-(naphthalen-1-yl)-
3,4-dihydro-2H-pyran-2-ylidene)acetate 4ia. A slightly yellow
liquid (2.6 mg, 6%); 1H NMR (CDCl3, 400 MHz, TMS) d 1.16 (t,
J = 7.2 Hz, 3H), 1.38 (d, J = 6.0 Hz, 6H), 1.40 (d, J = 6.0 Hz, 6H),
3.22 (dd, J = 15.2 Hz, 8.4 Hz, 1H), 3.87 (dd, J = 15.2 Hz, 5.6 Hz,
1H), 4.00–4.08 (m, 2H), 4.47–4.50 (m, 1H), 4.77–4.84 (m, 2H),
5.68 (s, 1H), 6.38 (dd, J = 10.4 Hz, 3.6 Hz, 1H), 7.32 (d, J = 6.8 Hz,
1H), 7.42 (t, J = 7.6 Hz, 1H), 7.49–7.58 (m, 2H), 7.77 (d, J =
(E)-Ethyl 2-(2-ethoxy-2-oxoethylidene)-4-phenyl-3,4-dihydro-
2H-pyran-6-carboxylate 7aa. A slightly yellow liquid (30.0 mg,
7.6 Hz, 1H), 7.89 (d, J = 7.6 Hz, 1H), 8.04 (d, J = 8.4 Hz, 1H); 31
P
1
95%); H NMR (CDCl3, 400 MHz, TMS) d 1.23 (t, J = 7.2 Hz,
NMR (CDCl3, 161.93 MHz, 85% H3PO4) d 3.937; IR (CH2Cl2) n
2981, 2901, 1712, 1657, 1474, 1374, 1261, 1175, 1116, 1046, 1013,
88, 801, 739 cm-1; MS (ESI) m/z 459.3 (M+H+); HRMS (ESI)
Calcd for C25H31O6PNa requires (M+Na+): 481.1751, found:
481.1743.
3H), 1.34 (t, J = 7.2 Hz, 3H), 3.11 (dd, J = 8.0 Hz, 4.8 Hz, 1H),
3.68–3.72 (m, 2H), 4.07–4.14 (m, 2H), 4.28–4.34 (m, 2H), 5.75
(s, 1H), 6.45 (d, J = 4.8 Hz, 1H), 7.20–7.22 (m, 2H), 7.26–7.28
(m, 1H), 7.31–7.35 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS)
d 14.1, 14.2, 29.7, 35.8, 59.8, 61.6, 101.0, 116.5, 127.2, 128.8,
141.3, 141.7, 161.1, 164.6, 166.9; IR (CH2Cl2) n 2981, 2903, 2875,
1736, 1711, 1660, 1493, 1373, 1258, 1170, 1118, 1046, 1015, 821,
760 cm-1; MS (ESI) m/z 317.2 (M+H+). HRMS (ESI) Calcd for
C18H20O5 requires (M+Na+): 339.1203, found: 339.1206.
Ethyl
6-(diisopropoxyphosphoryl)-2,4-dimethyl-4H-pyran-3-
carboxylate 3ja. A slightly yellow liquid (20.8 mg, 60%); 1H
NMR (CDCl3, 400 MHz, TMS) d 1.16 (d, J = 6.4 Hz, 3H), 1.30
(t, J = 7.2 Hz, 3H), 1.30 (d, J = 6.0 Hz, 3H), 1.34 (d, J = 6.0 Hz,
3H), 1.36 (d, J = 6.0 Hz, 3H), 1.38 (d, J = 6.0 Hz, 3H), 2.27 (s,
3H), 3.29–3.35 (m, 1H), 4.16–4.26 (m, 2H), 4.64–4.76 (m, 2H),
6.07 (dd, J = 10.0 Hz, 5.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz,
TMS) d 14.2, 19.1, 23.4 (d, J = 2.7 Hz), 23.6 (d, J = 4.5 Hz),
24.0 (d, J = 3.8 Hz), 26.7 (d, J = 10.2 Hz), 60.1, 71.6 (d, J = 5.3
Hz), 71.7 (d, J = 5.3 Hz), 106.4, 122.6 (d, J = 20.1 Hz), 140.5,
142.8, 160.0 (d, J = 8.4 Hz), 167.3; 31P NMR (CDCl3, 161.93
MHz, 85% H3PO4) d 4.672; IR (CH2Cl2) n 2980, 2937, 2905,
2874, 1713, 1665, 1625, 1375, 1259, 1163, 1056, 989, 945, 801,
662, 611 cm-1; MS (ESI) m/z 347.2 (M+H+); HRMS (ESI) Calcd
for C16H27O6PNa requires (M+Na+): 369.1438, found: 369.1439.
Diethyl 4-(4-chlorophenyl)-6-methyl-4H-pyran-2,5-dicarboxy-
late 6ba. A slightly yellow liquid (2.0 mg, 6%); 1H NMR (CDCl3,
400 MHz, TMS) d 1.11 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 7.2 Hz,
3H), 2.44 (s, 3H), 4.00–4.08 (m, 2H), 4.22–4.31 (m, 2H), 4.49 (d,
J = 4.8 Hz, 1H), 6.21 (d, J = 4.8 Hz, 1H), 7.16 (d, J = 8.8 Hz,
2H), 7.27 (d, J = 8.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz, TMS)
d 14.00, 14.04, 19.2, 38.4, 60.3, 61.6, 104.3, 115.5, 128.7, 129.4,
132.8, 139.1, 142.9, 160.1, 161.0, 166.7; IR (CH2Cl2) n 2981, 2904,
1739, 1715, 1629, 1488, 1372, 1327, 1268, 1106, 1049, 1015, 946,
805, 739 cm-1; MS (ESI) m/z 373.2 (M+Na+); HRMS (ESI) Calcd
for C18H19ClNaO5 requires (M+Na+): 373.0816, found: 373.0813.
(E)-Ethyl 2-(6-(diisopropoxyphosphoryl)-4-methyl-3,4-dihydro-
2H-pyran-2-ylidene)acetate 4ja. A slightly yellow liquid (5.2 mg,
(E)-Ethyl 4-(4-chlorophenyl)-2-(2-ethoxy-2-oxoethylidene)-3,4-
dihydro-2H-pyran-6-carboxylate 7ba. A slightly yellow liquid
1
1
15%); H NMR (CDCl3, 400 MHz, TMS) d H NMR (CDCl3,
400 MHz, TMS) d 1.13 (d, J = 7.2 Hz, 3H), 1.28 (t, J = 7.2 Hz,
3H), 1.32 (d, J = 6.4 Hz, 3H), 1.33 (d, J = 6.4 Hz, 3H), 1.37 (d,
J = 5.6 Hz, 6H), 2.45–2.92 (m, 1H), 2.68 (dd, J = 14.8 Hz, 8.4 Hz,
1H), 3.44 (dd, J = 14.8 Hz, 5.6 Hz, 1H), 4.16 (q, J = 7.2 Hz, 2H),
1
(28.1 mg, 80%); H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t,
J = 7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 3H), 3.18 (dd, J = 15.2 Hz,
7.6 Hz, 1H), 3.57 (dd, J = 15.2 Hz, 6.0 Hz, 1H), 3.68–3.72 (m,
1H), 4.08–4.14 (m, 2H), 4.29–4.35 (m, 2H), 5.75 (s, 1H), 6.40 (d,
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J = 4.0 Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 8.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.1, 14.2, 29.5, 35.2,
59.9, 61.7, 101.3, 115.6, 128.6, 128.9, 133.1, 139.7, 142.0, 161.0,
164.0, 166.8; IR (CH2Cl2) n 2981, 2903, 2875, 1736, 1711, 1660,
1493, 1373, 1258, 1170, 1118, 1046, 1015, 821, 760 cm-1; MS (ESI)
m/z 373.2 (M+Na+); HRMS (ESI) Calcd for C18H19ClO5 requires
(M+Na+): 373.0813, found: 373.0821.
Diethyl 4-(2-bromophenyl)-6-methyl-4H-pyran-2◦,5-dicarboxy-
late 6ea. A white solid (3.7 mg, 9%); m.p. 122–124 C; 1H NMR
(CDCl3, 400 MHz, TMS) d 1.00 (t, J = 7.2 Hz, 3H), 1.30 (t,
J = 7.2 Hz, 3H), 2.50 (s, 3H), 3.93–4.03 (m, 2H), 4.20–4.29 (m,
2H), 5.06 (d, J = 4.8 Hz, 1H), 6.27 (d, J = 4.8 Hz, 1H), 7.05–
7.10 (m, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.27–7.30 (m, 1H), 7.53
(d, J = 8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz, TMS) d 13.8,
14.1, 19.0, 38.3, 60.2, 61.6, 103.6, 114.4, 122.7, 128.2, 128.4, 130.0,
132.7, 139.2, 143.4, 161.0, 161.2, 166.5; IR (CH2Cl2) n 3058, 2980,
2873, 1714, 1627, 1590, 1472, 1328, 1267, 1096, 964, 839, 764, 739,
696 cm-1; MS (ESI) m/z 395.2 (M+H+); HRMS (ESI) Calcd. for
C18H19BrO5Na requires (M+Na+): 417.0308, Found: 417.0315.
Diethyl 4-(4-bromophenyl)-6-methyl-4H-pyran-2,5-dicarboxy-
late 6ca. A slightly yellow liquid (3.1 mg, 8%); 1H NMR (CDCl3,
400 MHz, TMS) d 1.12 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 7.2 Hz, 3H),
2.44 (s, 3H), 3.99–4.08 (m, 2H), 4.23–4.30 (m, 2H), 4.48 (d, J =
5.2 Hz, 1H), 6.21 (d, J = 5.2 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H), 7.43
(d, J = 8.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.0,
14.1, 19.2, 38.4, 60.3, 61.6, 104.2, 115.4, 120.9, 129.8, 131.7, 139.1,
143.4, 160.1, 160.9, 166.6; IR (CH2Cl2) n 2979, 2902, 1716, 1660,
1373, 1263, 1173, 1107, 1048, 1013, 803, 762, 738, 703 cm-1; MS
(ESI) m/z 395.2 (M+H+); HRMS (ESI) Calcd for C18H19BrO5Na
requires (M+Na+): 417.0308, found: 417.0320.
(E)-Ethyl 4-(2-bromophenyl)-2-(2-ethoxy-2-oxoethylidene)-3,4-
dihydro-2H-pyran-6-carboxylate 7ea. A slightly yellow liquid
1
(29.8 mg, 76%); H NMR (CDCl3, 400 MHz, TMS) d 1.23 (t,
J = 7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 3H), 3.20 (dd, J = 15.6 Hz,
7.6 Hz, 1H), 3.59 (dd, J = 15.6 Hz, 6.4 Hz, 1H), 4.07–4.14 (m, 2H),
4.18–4.23 (m, 1H), 4.29–4.35 (m, 2H), 5.75 (s, 1H), 6.42 (d, J =
4.4 Hz, 1H), 7.13–7.17 (m, 2H), 7.27–7.30 (m, 1H), 7.58 (d, J =
8.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.09, 14.14,
28.1, 35.2, 59.9, 61.7, 101.5, 115.1, 124.0, 127.9, 128.4, 128.8, 133.1,
140.0, 142.4, 161.1, 163.8, 166.6; IR (CH2Cl2) n 3060, 2980, 2902,
1711, 1659, 1470, 1372, 1298, 1258, 1197, 1108, 1022, 856, 803,
754, 670 cm-1; MS (ESI) m/z 395.0 (M+H+); HRMS (ESI) Calcd
for C18H19BrO5Na requires (M+Na+): 417.0308, found: 417.0312.
(E)-Ethyl 4-(4-bromophenyl)-2-(2-ethoxy-2-oxoethylidene)-3,4-
dihydro-2H-pyran-6-carboxylate 7ca. A slightly yellow liquid
1
(31.2 mg, 80%); H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t,
J = 7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 3H), 3.18 (dd, J = 15.2 Hz,
7.2 Hz, 1H), 3.56 (dd, J = 15.2 Hz, 6.4 Hz, 1H), 3.66–3.71 (m,
1H), 4.09–4.13 (m, 2H), 4.30–4.34 (m, 2H), 5.75 (s, 1H), 6.40 (d,
J = 5.2 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H);
13C NMR (CDCl3, 100 MHz, TMS) d 14.1, 14.2, 29.4, 35.3, 59.9,
61.7, 101.3, 115.4, 121.1, 129.0, 131.9, 140.2, 142.0, 161.0, 164.0,
166.8; IR (CH2Cl2) n 3084, 2982, 2904, 1736, 1711, 1659, 1489,
1394, 1300, 1167, 1117, 1011, 859, 818, 760 cm-1; MS (ESI) m/z
417.2 (M+Na+); HRMS (ESI) Calcd for C18H19BrO5Na requires
(M+Na+): 417.0308, found: 417.0315.
Diethyl 4-(2,4-dichlorophenyl)-6-methyl-4H-pyran-2,5-dicarbo-
1
xylate 6fa. A slightly yellow liquid (4.2 mg, 11%); H NMR
(CDCl3, 400 MHz, TMS) d 1.05 (t, J = 7.2 Hz, 3H), 1.31 (t, J =
7.2 Hz, 3H), 2.49 (s, 3H), 3.97–4.03 (m, 2H), 4.22–4.29 (m, 2H),
5.03 (d, J = 4.8 Hz, 1H), 6.22 (d, J = 4.8 Hz, 1H), 7.14 (d, J = 8.4 Hz,
1H), 7.22 (d, J = 8.4 Hz, 1H), 7.37 (s, 1H). 13C NMR (CDCl3,
100 MHz, TMS) d 13.8, 14.1, 19.1, 35.1, 60.4, 61.7, 103.0, 113.9,
127.8, 129.1, 130.7, 132.8, 133.2, 139.4, 140.4, 160.8, 161.6, 166.3;
IR (CH2Cl2) n 3086, 2982, 2906, 1716, 1630, 1586, 1561, 1372,
1270, 1189, 1172, 1097, 1074, 964, 918, 767 cm-1; MS (ESI) m/z
385.3. (M+H+); HRMS (ESI) Calcd for C18H18Cl2NaO5 requires
(M+Na+): 407.0424, found: 407.0435.
Diethyl 4-(3-bromophenyl)-6-methyl-4H-pyran-2,5-dicarboxy-
late 6da. A slightly yellow liquid (3.6 mg, 9%); 1H NMR (CDCl3,
400 MHz, TMS) d 1.12 (t, J = 7.2 Hz, 3H), 1.32 (t, J = 7.2 Hz,
3H), 2.44 (s, 3H), 4.00–4.09 (m, 2H), 4.25–4.30 (m, 2H), 4.48 (d,
J = 5.2 Hz, 1H), 6.21 (d, J = 5.2 Hz, 1H), 7.16–7.18 (m, 2H),
7.34–7.26 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.0,
14.1, 19.2, 38.7, 60.3, 61.7, 104.1, 115.3, 122.7, 126.8, 130.1, 130.2,
131.2, 139.3, 146.7, 160.4, 160.9, 166.5; IR (CH2Cl2) n 3058, 2980,
2873, 1714, 1627, 1590, 1472, 1328, 1267, 1096, 964, 839, 764, 739,
696 cm-1; MS (ESI) m/z 395.2 (M+H+); HRMS (ESI) Calcd for
C18H19BrO5Na requires (M+Na+): 417.0308, found: 417.0315.
(E)-Ethyl 4-(2,4-dichlorophenyl)-2-(2-ethoxy-2-oxoethylidene)-
3,4-dihydro-2H-pyran-6-carboxylate 7fa. A slightly yellow liquid
(29.2 mg, 76%); 1H NMR (CDCl3, 400 MHz, TMS) d 1.23 (t, J =
7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 3H), 3.30 (dd, J = 15.2 Hz, 6.8 Hz,
1H), 3.47 (dd, J = 15.2 Hz, 6.4 Hz, 1H), 4.07–4.19 (m, 3H), 4.30–
4.36 (m, 2H), 5.76 (s, 1H), 6.37 (d, J = 4.4 Hz, 1H), 7.09 (d, J =
8.4 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H); 13C NMR
(CDCl3, 100 MHz, TMS) d 14.11, 14.15, 27.7, 32.2, 60.0, 61.8,
101.8, 114.2, 127.5, 129.1, 129.6, 133.7, 134.1, 136.9, 142.7, 160.9,
163.5, 166.6; IR (CH2Cl2) n 3086, 2982, 2905, 1660, 1587, 1561,
1474, 1372, 1299, 1256, 1170, 1104, 1020, 861, 818, 760 cm-1; MS
(ESI) m/z 385.3. (M+H+); HRMS (ESI) Calcd for C18H18Cl2NaO5
requires (M+Na+): 407.0424, found: 407.0435.
(E)-Ethyl 4-(3-bromophenyl)-2-(2-ethoxy-2-oxoethylidene)-3,4-
dihydro-2H-pyran-6-carboxylate 7da. A slightly yellow liquid
1
(29.2 mg, 74%); H NMR (CDCl3, 400 MHz, TMS) d 1.24 (t,
J = 7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 3H), 3.12 (dd, J = 14.8 Hz,
6.8 Hz, 1H), 3.61–3.69 (m, 2H), 4.09–4.14 (m, 2H), 4.29–4.35
(m, 2H), 5.76 (s, 1H), 6.39 (d, J = 3.6 Hz, 1H), 7.13–7.16 (m,
1H), 7.21 (t, J = 8.0 Hz, 1H), 7.35 (s, 1H), 7.39–7.41 (m, 1H);
13C NMR (CDCl3, 100 MHz, TMS) d 14.1, 14.2, 29.5, 35.6, 59.9,
61.8, 101.4, 115.3, 122.8, 126.0, 130.38, 130.41, 130.5, 142.1, 143.6,
161.0, 164.0, 166.8; IR (CH2Cl2) n 3082, 2981, 2903, 2873, 1710,
1658, 1593, 1475, 1393, 1349, 1256, 1111, 1045, 1021, 855, 790,
676 cm-1; MS (ESI) m/z 419.1 (M+Na+); HRMS (ESI) Calcd for
C18H19BrO5Na requires (M+Na+): 417.0308, found: 417.0307.
Diethyl 6-methyl-4-p-tolyl-4H-pyran-2,5-dicarboxylate 6ga.
A
slightly yellow liquid (2.2 mg, 7%); 1H NMR (CDCl3, 400 MHz,
TMS) d 1.11 (t, J = 7.2 Hz, 3H), 1.29 (t, J = 7.2 Hz, 3H), 2.31
(s, 3H), 2.43 (s, 3H), 3.98–4.07 (m, 2H), 4.21–3.31 (m, 2H), 4.46
(d, J = 4.8 Hz, 1H), 5.74 (s, 1H), 6.25 (d, J = 4.8 Hz, 1H), 7.08–
7.13 (m, 4H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.0, 14.1,
19.1, 21.0, 38.5, 60.2, 61.5, 104.8, 116.4, 128.0, 129.3, 136.7, 138.9,
178 | Org. Biomol. Chem., 2012, 10, 171–180
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141.5, 159.6, 161.2, 167.0; IR (CH2Cl2) n 2979, 2902, 1715, 1659,
1629, 1511, 1446, 1373, 1324, 1263, 1172, 1106, 1021, 865, 803,
739 cm-1; MS (ESI) m/z 353.1 (M+Na+); HRMS (ESI) Calcd for
C19H22O5Na requires (M+Na+): 353.1359, found: 353.1371.
8.0 Hz, 1H), 3.56 (dd, J = 15.2 Hz, 5.2 Hz, 1H), 3.99–4.03 (m,
1H), 4.13 (q, J = 7.2 Hz, 2H), 4.31 (q, J = 7.2 Hz, 2H), 5.77 (s, 1H),
6.48 (d, J = 4.0 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 6.95 (dd, J =
4.8 Hz, 3.6 Hz, 1H), 7.20 (d, J = 4.8 Hz, 1H); 13C NMR (CDCl3,
100 MHz, TMS) d 14.15, 14.24, 29.8, 31.2, 59.9, 61.7, 101.7,
115.7, 124.4, 124.5, 126.9, 141.5, 144.1, 161.2, 163.9, 166.8; IR
(CH2Cl2) n 3075, 2966, 2934, 1736, 1713, 1660, 1373, 1259, 1173,
1259, 1119, 1046, 1020, 802, 762, 738, 701 cm-1; MS (ESI) m/z
345.2 (M+Na+); HRMS (ESI) Calcd for C16H18O5SNa requires
(M+Na+): 345.0767, found: 345.0777.
(E)-Ethyl 2-(2-ethoxy-2-oxoethylidene)-4-p-tolyl-3,4-dihydro-
2H-pyran-6-carboxylate 7ga. A slightly yellow liquid (25.9 mg,
1
78%); H NMR (CDCl3, 400 MHz, TMS) d 1.23 (t, J = 7.2 Hz,
3H), 1.34 (t, J = 7.2 Hz, 3H), 2.33 (s, 3H), 3.06–3.13 (m, 1H),
3.62–3.69 (m, 2H), 4.08–4.14 (m, 2H), 4.27–4.33 (m, 2H), 5.74
(s, 1H), 6.43 (d, J = 4.4 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 7.14
(d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.1,
14.2, 21.0, 29.7, 35.5, 59.8, 61.6, 100.9, 116.8, 127.1, 129.5, 136.9,
138.3, 141.6, 161.2, 164.8, 166.9; IR (CH2Cl2) n 2980, 2902, 1736,
1712, 1658, 1514, 1373, 1297, 1167, 1113, 1045, 1020, 847, 808,
762 cm-1; MS (ESI) m/z 353.1 (M+Na+); HRMS (ESI) Calcd for
C19H22O5Na requires (M+Na+): 353.1359, found: 353.1371.
Diethyl 6-methyl-4-(naphthalen-2-yl)-4H-pyran-2,5-dicarboxy-
late 6ja. A slightly yellow liquid (3.3 mg, 9%); 1H NMR (CDCl3,
400 MHz, TMS) d 1.07 (t, J = 7.2 Hz, 3H), 1.29 (t, J = 7.2 Hz, 3H),
2.48 (s, 3H), 3.98–4.00 (m, 2H), 4.24–4.27 (m, 2H), 4.68 (d, J =
5.2 Hz, 1H), 6.31 (d, J = 5.2 Hz, 1H), 7.38 (dd, J = 8.4 Hz, 1.6 Hz,
1H), 7.44–7.47 (m, 2H), 7.65 (s, 1H), 7.78–7.80 (m, 3H); 13C NMR
(CDCl3, 100 MHz, TMS) d 14.0, 14.1, 19.2, 39.1, 60.2, 61.6, 104.6,
116.0, 125.8, 126.1, 126.3, 126.9, 127.6, 127.8, 128.3, 132.6, 133.5,
139.0, 141.8, 159.9, 161.1, 166.9; IR (CH2Cl2) n 3057, 2980, 2902,
1715, 1474, 1373, 1262, 1106, 1048, 1021, 956, 859, 801, 746, 702,
667 cm-1; MS (ESI) m/z 389.2 (M+Na+); HRMS (ESI) Calcd for
C22H22O5Na requires (M+Na+): 389.1359, found: 389.1374.
Diethyl
4-(furan-2-yl)-6-methyl-4H-pyran-2,5-dicarboxylate
1
6ha. A slightly yellow liquid (4.6 mg, 15%); H NMR (CDCl3,
400 MHz, TMS) d 1.18 (t, J = 7.2 Hz, 3H), 1.32 (t, J = 7.2 Hz,
3H), 2.41 (s, 3H), 4.06–4.18 (m, 2H), 4.25–4.31 (m, 2H), 4.67 (d,
J = 5.2 Hz, 1H), 6.05 (d, J = 5.2 Hz, 1H), 6.28–6.29 (m, 2H),
7.27–7.29 (m, 1H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.06,
14.12, 19.1, 32.3, 60.3, 61.6, 102.2, 106.1, 110.5, 112.9, 140.1,
141.6, 156.1, 160.5, 160.9, 166.7; IR (CH2Cl2) n 2980, 2903, 2857,
1738, 1716, 1660, 1475, 1372, 1266, 1173, 1107, 1048, 1020, 798,
763, 739 cm-1; MS (ESI) m/z 329.1 (M+Na+); HRMS (ESI) Calcd
for C16H18O6Na requires (M+Na+): 329.0996, found: 329.1000.
(E)-ethyl 2-(2-ethoxy-2-oxoethylidene)-4-(naphthalen-2-yl)-3,4-
dihydro-2H-pyran-6-carboxylate 7ja. A slightly yellow liquid
1
(26.7 mg, 73%); H NMR (CDCl3, 400 MHz, TMS) d 1.21 (t,
J = 7.2 Hz, 3H), 1.36 (t, J = 7.2 Hz, 3H), 3.27 (dd, J = 14.8 Hz,
8.4 Hz, 1H), 3.71 (dd, J = 14.8 Hz, 5.2 Hz, 1H), 3.86–3.89 (m,
1H), 4.05–4.12 (m, 2H), 4.31–4.36 (m, 2H), 5.76 (s, 1H), 6.54 (d,
J = 4.0 Hz, 1H), 7.34 (dd, J = 8.4 Hz, 1.2 Hz, 1H), 7.46–7.49
(m, 2H), 7.64 (s, 1H), 7.78–7.83 (m, 3H); 13C NMR (CDCl3, 100
MHz, TMS) d 14.17, 14.20, 29.6, 36.0, 59.8, 61.7, 101.3, 116.3,
125.5, 125.8, 125.9, 126.3, 127.6, 127.7, 128.7, 132.6, 133.4, 138.6,
142.0, 161.2, 164.5, 166.9; IR (CH2Cl2) n 3056, 2982, 2904, 1734,
1709, 1659, 1508, 1474, 1445, 1372, 1298, 1254, 1172, 1115, 854,
817, 760 cm-1; MS (ESI) m/z 389.2 (M+Na+); HRMS (ESI) Calcd
for C22H22O5Na requires (M+Na+): 389.1359, found: 389.1364.
(E)-Ethyl
2-(2-ethoxy-2-oxoethylidene)-4-(furan-2-yl)-3,4-
dihydro-2H-pyran-6-carboxylate 7ha. A slightly yellow liquid
1
(13.8 mg, 45%); H NMR (CDCl3, 400 MHz, TMS) d 1.27 (t,
J = 7.2 Hz, 3H), 1.34 (t, J = 7.2 Hz, 3H), 3.36 (dd, J = 15.2 Hz,
8.0 Hz, 1H), 3.56 (dd, J = 15.2 Hz, 5.2 Hz, 1H), 3.78–3.83 (m,
1H), 4.15 (q, J = 7.2 Hz, 2H), 4.30 (q, J = 7.2 Hz, 2H), 5.76 (s,
1H), 6.13–6.14 (m, 1H), 6.30–6.31 (m, 1H), 6.45 (d, J = 4.0 Hz,
1H), 7.35–7.36 (m, 1H); 13C NMR (CDCl3, 100 MHz, TMS) d
14.1, 14.3, 26.3, 29.7, 59.9, 61.7, 101.4, 105.7, 110.3, 113.4, 141.8,
142.1, 153.4, 161.1, 164.1, 166.9; IR (CH2Cl2) n 2980, 2906, 2874,
1737, 1712, 1660, 1446, 1373, 1298, 1174, 1120, 1046, 1017, 801,
761, 739 cm-1; MS (ESI) m/z 329.1 (M+Na+); HRMS (ESI) Calcd
for C16H18O6Na requires (M+Na+): 329.0996, found: 329.1007.
(E)-Ethyl
4-cyclopropyl-2-(2-ethoxy-2-oxoethylidene)-3,4-
dihydro-2H-pyran-6-carboxylate 7ka. A slightly yellow liquid
(27.3 mg, 90%); 1H NMR (CDCl3, 400 MHz, TMS) d 0.23–0.26
(m, 2H), 0.52–0.56 (m, 2H), 0.70–0.76 (m, 1H), 1.28 (t, J = 7.2 Hz,
3H), 1.35 (t, J = 7.2 Hz, 3H), 1.72–1.79 (m, 1H), 2.92 (dd, J =
15.2 Hz, 8.4 Hz, 1H), 3.48 (dd, J = 15.2 Hz, 5.6 Hz, 1H), 4.16
(q, J = 7.2 Hz, 2H), 4.27–4.32 (m, 2H), 5.70 (s, 1H), 6.32 (d, J =
4.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz, TMS) d 3.2, 3.6, 14.1,
14.3, 15.3, 27.7, 34.9, 59.8, 61.5, 100.4, 117.1, 141.1, 161.3, 165.7,
167.2. IR (CH2Cl2) n 3081, 2982, 2903, 1737, 1713, 1659, 1372,
1335, 1298, 1256, 1120, 1048, 1021, 854, 761, 740 cm-1. MS (ESI)
m/z 281.1 (M+H+). HRMS (ESI) Calcd for C15H20O5Na requires
(M+Na+): 303.1203, found: 303.1209.
Diethyl 6-methyl-4-(thiophen-2-yl)-4H-pyran-2,5-dicarboxylate
1
6ia. A slightly yellow liquid (2.6 mg, 8%); H NMR (CDCl3,
400 MHz, TMS) d 1.19 (t, J = 7.2 Hz, 3H), 1.32 (t, J = 7.2 Hz,
3H), 2.41 (s, 3H), 4.07–4.17 (m, 2H), 4.25–4.31 (m, 2H), 4.83 (d,
J = 5.2 Hz, 1H), 6.34 (d, J = 5.2 Hz, 1H), 6.86–6.87 (m, 1H),
6.91 (dd, J = 4.8 Hz, 3.2 Hz, 1H), 7.17 (dd, J = 4.8 Hz, 1.2 Hz,
1H); 13C NMR (CDCl3, 100 MHz, TMS) d 14.03, 14.1, 19.1, 33.4,
60.4, 61.6, 104.8, 115.1, 124.6, 124.9, 126.9, 139.4, 148.3, 159.7,
161.0, 166.7; IR (CH2Cl2) n 2980, 2903, 2857, 1738, 1716, 1660,
1475, 1372, 1266, 1173, 1107, 1048, 1020, 798, 763, 739 cm-1; MS
(ESI) m/z 345.1 (M+Na+); HRMS (ESI) Calcd for C16H18O5SNa
requires (M+Na+): 345.0767, found: 345.0775.
Acknowledgements
(E)-Ethyl 2-(2-ethoxy-2-oxoethylidene)-4-(thiophen-2-yl)-3,4-
dihydro-2H-pyran-6-carboxylate 7ia. A slightly yellow liquid
(15.7 mg, 49%); H NMR (CDCl3, 400 MHz, TMS) d 1.25 (t,
Financial support from the National Basic Research Program of
China (973)-2010CB833302, the Fundamental Research Funds
for the Central Universities and the National Natural Science
Foundation of China for financial support (21072206, 20472096,
1
J = 7.2 Hz, 3H), 1.34 (t, J = 7.2 Hz, 3H), 3.41 (dd, J = 15.2 Hz,
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and 20702059) is greatly acknowledged.
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7 The crystal data of compound 6ea have been deposited in CCDC
with number 833190. Empirical Formula: C18H19BrO5; Formula Weight:
395.24; Crystal Color, Habit: colorless; Crystal Dimensions: 0.28 ¥ 0.15
¥ 0.10 mm; Crystal System: Triclinic; Lattice Type: Primitive; Lattice
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˚
˚
˚
Paramete◦rs: a = 8.5579(17) A, b = 9.7◦108(19) A, c = 11.568(3) A, =
◦
3
˚
73.985(4) , b = 68.692(3) , g = 73.448(3) , V = 842.4(3) A ; Space group:
P1; Z = 2; Dc = 1.558 g cm ; F000 = 404; Final R indices [I > 2s(I)]: R1 =
-3
¯
0.0438; wR2 = 0.1321.
8 (a) A. Kumar, S. Sharma, V. D. Tripathi, R. A. Maurya, S. P. Srivastava,
G. Bhatia, A. K. Tamrakar and A. K. Srivastava, Bioorg. Med. Chem.,
2010, 18, 4138.
180 | Org. Biomol. Chem., 2012, 10, 171–180
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The Royal Society of Chemistry 2012
©