Synthesis of Functionalized Chromene and Chroman Derivatives via Cesium Carbonate Promoted Formal [4 + 2] Annulation of 2′-Hydroxychalcones with Allenoates

Article abstract of DOI:10.1021/acs.joc.8b02627

A new strategy has been established for the synthesis of functionalized chromene and chroman derivatives via a Cs₂CO₃-catalyzed domino addition of 2′-hydroxychalcone derivatives with allenoates, which can serve as a general avenue for the construction of multireplaced chromene derivatives. Chemoselectivity of this synthesis was found to depend on substituents on substrates. Good to excellent yields were achieved under simple and mild conditions at room temperature.

Full text of DOI:10.1021/acs.joc.8b02627

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Article
Synthesis of Functionalized Chromene and Chroman
Derivatives via Cesium Carbonate Promoted Formal [4
+ 2] Annulation of 2'-Hydroxychalcones with Allenoates
Hossein Rouh, Yangxue Liu, Nandakumar Katakam, Lilian Pham, Yi-Long Zhu, and Guigen Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02627 • Publication Date (Web): 27 Nov 2018
Downloaded from http://pubs.acs.org on November 27, 2018
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The Journal of Organic Chemistry
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Synthesis of Functionalized Chromene and Chroman Derivatives via
Cesium Carbonate Promoted Formal [4 + 2] Annulation of 2'-
†
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Hydroxychalcones with Allenoates
Hossein Rouh#, Yangxue Liu#, Nandakumar Katakam#, Lilian Pham#, Yi-Long Zhu#,$ and Guigen Li*#,‡
#Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061, USA
‡Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University,
Nanjing, 210093, China
$College of Pharmacy, Nanjing Tech University, Nanjing 211816, P. R. China
*E-mail: guigen.li@ttu.edu.
† We would like to dedicate this work to Professor Victor J. Hruby on occasion of his 80th birthday.
Ar
Ar
O
O
H
R4
R2
O
O
O
O
R4
Ar
O
R3
R3
O
R2
R3
Cs2CO3
CH3CN, r.t.
Cs2CO3
CH3CN, r.t.
O
R2
R1
R1
+
R1
O
O
OH
R4 = Me, Et, Bn,
CH2CO2Et
R2 = H
R4 = H
ABSTRACT: A new strategy has been established for the synthesis of functionalized chromene and chroman derivatives via a
Cs2CO3-catalyzed domino addition of 2'-hydroxychalcone derivatives with allenoates, which can serve as a general avenue for the
construction of multi-replaced chromene derivatives. Chemoselectivity of this synthesis was found to depend on substituents on
substrates. Good to excellent yields were achieved under simple and mild conditions at the room temperature.
INTRODUCTION
preferences. For example, the allenoates can behave as
electrophiles when electron-withdrawing groups are present.8
It also has been reported that allenoate can react with
nucleophiles in the presence of carbonate catalysts.9,10-12 Shi
and co-workers first reported carbonate-catalyzed reactions of
ethyl
Chromene and chroman rings are important classes of
oxygenated heterocycles and present in
a variety of
biologically active natural products.1 Many molecules
containing these frameworks gracefully exhibit superior
biological activities, such as antirhinovirus2, anticancer3,
antifungal4 and so on. Therefore, the development of efficient
synthetic methods to access these motifs has received a
tremendous amount of attention, and many strategies have
been reported in literature.5 Over the past decades, a
significant progress in allenes chemistry has been made by
many research labs.6 In particular, the transformations of
allenoate under nucleophilic Lewis base catalysis and
phosphine catalysis have received considerable interest due to
their modifying flexibility of molecular complexity.7 What
they have in common is that they heavily rely on the key
zwitterionic intermediate (Scheme 1a). Allenes can react as
either nucleophiles or electrophiles, depending on the
substituents on the parent framework for altering the reactivity
Scheme 1. Strategies for the reactions of allenoates with
nucleophiles or electrophiles.
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OR
7
8
2.0
2.0
Cs2CO3 (60%)
Cs2CO3 (100%)
CH3CN
CH3CN
r.t.
r.t.
92%
78%
OR
O
OR
Structurally
Diverse
Products
NR3
PR3
O
or
Nu
E
O
1
OR
O
(a)
or

NR3/PR3
NR3/PR3
NR3/PR3
2
3
4
5
6
7
8
9
9
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
DBU (60%)
CH3CN
CH3CN
CH3CN
CH3CN
ethanol
H2O
DCM
THF
toluene
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
15%
17%
45%
43%
8%
N.R.
23%
39%
27%
10
11
12
13
14
15
16
17
DABCO (60%)
K2CO3 (60%)
Na2CO3 (60%)
Cs2CO3 (60%)
Cs2CO3 (60%)
Cs2CO3 (60%)
Cs2CO3 (60%)
Cs2CO3 (60%)
O
O
O
O
O
E
OR
OR
OR
Ar
OR
OR
E
(b)
or
Nu

+
Nu
E
Nu
Nu
Nu
Our reaction
Ar
O
O
R4
R2
O
O
O
O
R4
Ar
O
R3
R3
O
R2
R3
aTo a mixture of 1a (1.0 equiv., 0.5 mmol) and 2a (n equiv.) in anhydrous
solvent, catalyst (n mol%) was added. The resulting solution was stirred at
room temperature. bIsolated yield based on 1a.
(c)
O
R2
R1

R1
or
+
R1
O
3
O
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60
H
O
1
2
4
Ar
Ar
load of 2a could significantly improve the yield (entry 6 vs
entries 3-5). With the increase of the amount of cesium
carbonate, the yield of the reaction has been significantly
improved, and up to 92% yield was obtained (entry 7 vs entry
6). As the amount of catalyst continues to increase, it is not
conducive to the progress of the reaction. (entry 7 vs entry 8).
Next, several bases commonly used in the annulate reactions
were investigated, like DBU, DABCO, K2CO3, and Na2CO3,
all showed poor catalytic activities. Afterward, we adjusted
other solvents, such as ethanol, H2O, dichloromethane (DCM),
tetrahydrofuran (THF) and toluene, which were inferior to
acetonitrile in terms of reaction yields (entry 7 vs entry 13-
17).With the optimized reaction conditions in hand, a wide
range of intramolecular cyclization reactions, using different
substituted 2'-hydroxychalcone derivatives and allenoates
were examined for this transformation (Scheme 2). Both
aromatic moieties in 2'-hydroxychalcone structures could be
varied, regardless of the electronic nature and substitution
patterns of the aryl structures, and annulation products were
obtained in good to excellent yields (Scheme 2, 3a-s).
O
O
O
O
O
R3
O
R2
R3
R1
R1
R2
O
O
allenoate with salicylic aldehydes to access the functionalized
chromenes in good yields.10 Selig and co-workers reported a
method for the synthesis of 2,3-disubstituted quinolines via
carbonate-catalyzed reaction of allenoates with N-protected o-
aminobenzaldehydes.11 Recently, Zhou and co-workers
reported a carbonate-catalyzed reaction of allenoates and 2-(2-
hydroxyphenyl) isoindoline-1,3-dione for the construction of
functionalized
benzooxazepino-[5,4-a]
isoindolone
derivatives.12 However, a cesium carbonate promoted reaction
of allenoates with 2'-hydroxychalcone derivatives has not been
reported yet. Herein, we report the cyclization reactions of 2'-
hydroxychalcone
derivatives
with
allenoate
to
chemoselectively give new types of highly functionalized
chromene and chroman derivatives in good to excellent yields
in the presence of cesium carbonate at room temperature. On
the basis of this facile synthetic protocol, a variety of
interesting chromene and chroman derivatives can be obtained
in a simple way.
Scheme 2. Substrate Scope for the Synthesis of 3a
Ar
O
O
O
O
Ar
O
R3
O
R3
Cs2CO3 (60 mol%)
CH3CN, r.t.
R1
RESULTS AND DISCUSSION
+
R2
R1
O
R2
H
OH
1a-s
3a-z
At the outset of our study, 3-(2-hydroxyphenyl)-1-phenylprop-
2-en-1-one 1a and benzyl buta-2,3-dienoate 2a were selected
for the initial reaction in the presence of 40 mol % cesium
carbonate in DMSO at 60 °C gave the desired product 3a in
43% isolated yield (Table 1, entry 1). When we use the
combination of Cs2CO3 with DMSO at room temperature, we
can also get a good result in 48% yield (entry 2). So, we chose
to let the reaction proceed at room temperature. An increased
2a-h
Ar
O
3a, Ar = Ph, 91%
3b, Ar = 4-MeC6H4, 86%
3c, Ar = 4-OMeC6H4, 84%
3d, Ar = 4-tBuC6H4, 81%
3e, Ar = 4-ClC6H4, 85%
3f, Ar = 4-BrC6H4, 84%
3g, Ar = 4-FC6H4, 84%
3h, Ar = 2-MeC6H4, 81%
3i, Ar = 2-MeOC6H4, 81%
3j, Ar = 3-MeOC6H4, 83%
3k, Ar = 3,4-(Me)2C6H3, 84%
3l, Ar = Ph, 77%
3m, Ar = 4-MeC6H4, 79%
3n, Ar = 4-ClC6H4, 74%
CO2Bn
CO2Bn
Ar
O
Br
Cl
O
CO Bn
2
Ph
4-MeC6H4
O
O
O
CO2Bn
O
O
3p, 85%
3o, 72%
Table 1. Condition optimization for the [4 + 2] Annulation
4-MeC6H4
Ph
O
Ph
O
O
CO2Bn
CO2Bn
CO2Bn
O
MeO
Ph
O
O
Ph
MeO
O
O
CO2Bn
2a
3s, 86%
3r, 86%
3q, 88%
conditions
CO2Bn
+
Ph
3t, R3 = 4-ClC6H4, 89%
3u, R3 = 4-OMeC6H4, 90%
3v, R3 = 2-ClC6H4, 84%
3w, R3 = 3,4-(OMe)2C6H4, 84%
3x, R3 = Me, 81%
OH
1a
O
O
O
O
O
3y, R2 = Me, 88%
3z, R2 = Ph, 88%
3a
CO2Bn
R2
R3
O
O
entry
2a (equiv.)
Cat. (mol%.)
Cs2CO3 (40%)
Cs2CO3 (40%)
Cs2CO3 (40%)
Cs2CO3 (40%)
Cs2CO3 (40%)
Cs2CO3 (40%)
Solvent
DMSO
DMSO
CH3CN
CH3CN
CH3CN
CH3CN
Temp. Yieldb
1
2
3
4
5
6
1.0
1.0
1.0
1.2
1.5
2.0
60 0C
r.t.
43%
48%
55%
61%
62%
73%
aReaction conditions: 2'-hydroxychalcone 1 (0.5 mmol), allenoate 2 (1.0
mmol), CS2CO3 (0.3 mmol, 60 mol%), acetonitrile (4.0 mL), Ar
conditions. bIsolated yield based on substrates 1.
r.t.
r.t.
r.t.
r.t.
Scheme 3. Regioselective synthesis of products 4a.
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O
Ph
O
O
R3
R4
O
O
O
O
Ph
O
Ph
Ph
O
Ph
1
O
R4
R4
Ph
R4
CO2Bn
Cs2CO3 (60 mol%)
CH3CN, r.t.
O
Ph
cycloaddition
OR3
CsCO3
+
2
3
O
O
R4
O
2
O
C
O
OH
1a
OH
1
OR3
2i-l
4a-d
A
B
4
5
6
7
8
9
O
O
O
Ph
Ph
Ph
O
Ph
Ph
O
Ph
O
Ph
O
1
A
R4
H
=
OR3
OR3
O
O
OR3
O
CH2CO2Et
CO2Bn
Et
CO2Bn
Bn
CO2Bn
Me
CO2Bn
1,3-proton
transfer
path a
O
O
3
O
E
D
O
O
O
O
O
O
OH
4a, 66%
4d, 60%
4c, 61%
4b, 64%
Ph
O
Ph
O
Ph
O
A
R4
1
R4
R4 Me, Et, Bn
R4
=
10
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OR3
OR3
CH2COOEt
path b
OR3
aReaction conditions: 2'-hydroxychalcone 1 (0.5 mmol), allenoate 2 (1.0
mmol), CS2CO3 (0.3 mmol, 60 mol%), acetonitrile (4.0 mL), Ar
conditions. bIsolated yield based on substrates 1.
O
4
O
F
O
G
Additionally, the multiple substitution of the aromatic groups
was an adaptable substrate in this transformation, allowing its
[4+2] annulation to the corresponding γ-chromene in 84%
yield. With a phenyl group on the 2'-hydroxychalcone (Ar)
motif, the variant of substituents on the phenolic hydroxyl
moiety(R1), including MeO, Me, Cl, and Br, were successful
engaged in these transformations under the above conditions.
The presence of electron donating groups at the para-position
of the phenyl ring (R1) seemed to improve the reaction
efficiency, as the corresponding products 3p, 3q, 3r and 3s
could be obtained in higher yields than those with electron
withdrawing groups (Scheme 2, 3l vs. 3q, 3m vs. 3s). In
general, the nature of the substituent on the benzene ring of
the 2'-hydroxychalcone had a slight impact on the yields.
Next, we decided to change the ester group of allenoates and
use the non-terminal allenoates to expand its synthetic utility.
As we had expected, a large variety of different substituents,
including 4-ClC6H4, 4-OMeC6H4, 2-ClC6H4, 3,4-(MeO)2C6H4
and Me would be accommodated, confirming the efficiency of
the reaction, as the corresponding products 3t-3x were
generated in 81–90% yields. Similarly, non-terminal
allenoates also show good tolerance (Scheme 2, 3y and 3z).
To our delight, α-substituted allenoate also reacted smoothly
with 1a, but we didn’t get the same product as previous. A
new class of chroman derivates can be successfully
synthesized by this method in moderate yields (Scheme 3, 4a-
d). Therefore, a multi-substituted chromene and chroman
derivates can be achieved, by controlling the α-substituents of
the allenoate. The resultant functionalized 3 and 4 were fully
characterized by their NMR spectroscopy and HRMS. The
structure of the product was undeniably confirmed by X-ray
crystallographic analysis of compound 3a (see the Supporting
Information).
On the basis of our investigations6-12 and the earlier reports13, a
plausible mechanism for the reaction is shown in scheme 4.
Initially the non-nucleophilic base cesium carbonate
deprotonates 1 to generate oxy-anionic intermediate A. The
intermediate A then undergoes conjugate addition with
allenoate 2 to form the intermediate B. The following
intramolecular cycloaddition reaction produces the
intermediate C. When the substituents of α-position of
allenoate (R4) are different, two proton transfer modes of
intermediate C could occur to formed intermediate D (path a)
and
F (path b), respectively. Subsequent resonate of
intermediate D leads to the formation of intermediate E, which
abstracts a proton from 1 to afford compound 3 and
regenerates intermediate A to accomplish the catalytic cycle.
Because of the group of α-position (R4 = Me, Et, Bn, and
CH2COOEt), intermediate F through the abstract proton and
tautomerization processes form chroman derivates 4.
CONCLUSION
In summary, we have discovered a new a strategy for the
construction of densely functionalized 4H-chromene and
chroman derivatives via a highly efficient [4+2] annulation of
2'-Hydroxychalcone with allenoates. By adjusting the
substituent of α-substituents of allenoate, we can selectively
synthesize chromene or chroman derivates in a good to
excellent yield. This method complements with any other
ways for the access to functional chromene or chroman
derivatives for potential applications in biological activity
screening.
EXPERIMENTAL SECTION
Scheme 4. Proposed Mechanism for Forming 3 and 4
General Information. All melting points are uncorrected.
NMR spectra were recorded in CDCl3 or DMSO-d6 on a 400
MHz instrument with TMS as internal standard. Chemical
shifts (δ) are reported in ppm with respect to TMS. Data are
represented as follows: chemical shift, mutiplicity (s = singlet,
d = doublet, t = triplet, and m = multiplet), coupling constant
(J, Hz), and integration. HRMS analyses were carried out
using a TOF-MS instrument with an ESI source. X-ray
crystallographic analysis was performed with a SMART CCD
and a P4 diffractometer.
General Procedure for the Preparation of 2'-
hydroxychalcone.14 To a solution of various acetophenones
(1.00 eq) and salicylaldehyde (1.25 eq) in Ethanol
(2.5mL/mmol), potassium hydroxide 40% (3 eq) is added
3
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drop-wise at room temperature. After 24 hours, the mixture is
Page 4 of 8
128.9, 128.7, 128.4, 128.3, 128.2, 127.8, 124, 124.6, 116.1,
105.4, 66.3, 48.2, 31.8, 21.7, 19.9. IR (film, ν, cm−1) 3054,
2986, 2305, 1708, 1685, 1420, 1265, 738, 705; HRMS (ESI-
TOF) m/z: [M+Na]+ calcd for C27H24O4Na 435.1572; found
435.1560.
1
2
3
4
5
6
7
8
cooled with ice and neutralized carefully using 2N
hydrochloric acid. The crude mixture was extracted with ethyl
acetate, washed with water and brine afforded the chalcones
which were purified by column chromatography using hexane:
ethyl acetate (30%) as eluent to give pure chalcones (50%-
92%).
Benzyl
4-(2-(4-methoxyphenyl)-2-oxoethyl)-2-methyl-4H-
chromene-3-carboxylate (3c). White solid, 180 mg, 84% yield;
mp 92-94 ºC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80 (d, J
= 8.6 Hz, 2H), 7.38-7.25 (m, 5H), 7.12 (t, J = 7.2 Hz, 2H),
6.96 (t, J = 7.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 5.20 (s, 2H),
4.57 (dd, J = 8.8, 3.6 Hz, 1H), 3.82 (s, 3H), 3.22-3.04 (m, 2H),
2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 196.7,
166.9, 163.4, 163.3, 150.6, 136.3, 130.6, 130.2, 128.81, 128.7,
128.3, 128.2, 127.8, 124.9, 124.5, 116.1, 113.7, 105.4, 66.3,
55.5, 48.0, 31.0, 19.9. IR (film, ν, cm−1) 3054, 2986, 2305,
1684, 1508, 1265, 738, 705; HRMS (ESI-TOF) m/z: [M+Na]+
calcd for C27H24O5Na 451.1521; found 451.1504.
General Procedure for the Preparation of γ -substituted
allenoates.15 A flask was charged with stabilized ylide and
CH2Cl2, and Et3N. After 10 minutes the appropriate acid
chloride was added as a solution (5 mL) in CH2Cl2 slowly
such that the temperature of the reaction remained constant.
After 30 minutes, the color of the reaction mixture changes to
clear yellow. After completion of the reaction (TLC), the
solution was concentrated to afford a gummy residue. This
was treated with hexane (25 mL), stirred well, and allowed to
sit undisturbed for 2 hours. The mixture was filtered, and the
filtrate was evaporated, and product was separated with
column chromatography (Ethyl acetate/ Petroleum Ether 5%).
General Procedure for the Preparation of α-substituted
allenoates.15 Alkyl halide (1.00 eq.) was added to a stirred
solution of the ylide (1.00 eq) in CHCl3 at room temperature.
The mixture was reflux overnight. The solvent was evaporated
under reduced pressure and CH2Cl2 follow by triethylamine
(2.00 eq). were added to the resulting phosphonium salt. After
stirring for 1 h, acetyl chloride (1.1 equiv.) dissolved in
CH2Cl2 (5 mL) was added dropwise over 30 min. After
completion of the reaction (TLC), the solution was
concentrated to afford a gummy residue. This was treated with
hexane/Ethyl acetate (10:1), stirred well, and allowed to sit
undisturbed for 2 hours. The mixture was filtered, and the
filtrate was evaporated, and product was separated with
column chromatography (Ethyl acetate/ Petroleum Ether 5%).
General procedure for the synthesis Products 3 and 4. In
an oven dried and argon flushed round bottom flask, 2'-
hydroxychalcone (1, 1.0 eq, 0.5 mmol) is dissolved in 2 ml
acetonitrile. After 5 minutes, 60% cesium carbonate is added,
and the reaction continued for 5 more minutes. Then allenoate
(2, 2.0 eq, 1.0 mmol) dissolved in 2 ml acetonitrile is added
drop-wise and over 5 minutes. The reaction is continued for 4
hours and after completion of reaction (confirmed by TLC),
the solvent is concentrated, and the product is separated
directly by column chromatography (EA/PE 5%) to afford
pure products 3 and 4.
9
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Benzyl 4-(2-(4-(tert-butyl) phenyl)-2-oxoethyl)-2-methyl-4H-
chromene-3-carboxylate (3d). White solid, 184 mg, 81% yield,
mp 60-62 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.79 (d, J =
8.4 Hz, 2H), 7.40-7.29 (m, 7H), 7.15 (dd, J = 15.4, 6.4 Hz,
2H), 6.98 (t, J = 7.6 Hz, 2H), 5.22 (s, 2H), 4.62 (dd, J = 8.4,
3.5 Hz, 1H), 3.29-3.11 (m, 2H), 2.45 (s, 3H), 1.32 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 197.8, 166.9, 163.4,
156.7, 150.6, 136.3, 134.5, 128.9, 128.7, 128.4, 128.3, 128.2,
127.8, 125.6, 124.9, 124.5, 116.1, 105.3, 66.3, 48.4, 35.2, 31.8,
31.2, 20.0. IR (film, ν, cm−1) 3054, 2986, 2305, 1707, 1684,
1265, 738, 705; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C30H30O4Na 477.2041; found 477.2028.
Benzyl
4-(2-(4-chlorophenyl)-2-oxoethyl)-2-methyl-4H-
chromene-3-carboxylate (3e). White solid, 184 mg, 85% yield,
mp 89-91 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.73 (d, J =
8.6 Hz, 2H), 7.40-7.25 (m, 7H), 7.14 (t, J = 7.2 Hz, 2H), 7.02-
6.92 (m, 2H), 5.26-5.14 (m, 2H), 4.56 (dd, J = 8.0, 3.6 Hz,
1H), 3.23-3.08 (m, 2H), 2.43 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3; δ, ppm) 196.8, 166.6, 163.1, 151.2, 139.7, 136.0,
135.2, 130.1, 129.7, 129.0, 128.8, 128.45, 128.4, 127.7, 123.8,
120.8, 119.5, 105.4, 66.5, 47.9, 31.3, 19.9. IR (film, ν, cm−1)
3054, 2986, 2305, 1685, 1420, 1265, 738, 705; HRMS (ESI-
TOF) m/z: [M+Na]+ calcd for C26H21ClO4Na 455.1026; found
455.1009.
Benzyl
2-methyl-4-(2-oxo-2-phenylethyl)-4H-chromene-3-
Benzyl
4-(2-(4-bromophenyl)-2-oxoethyl)-2-methyl-4H-
carboxylate (3a). Yellow solid, 182 mg, 91% yield; mp 91-93
ºC; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (dd, J = 8.4, 1.2
Hz, 2H), 7.49-7.50 (m, 1H), 7.39-7.26 (m, 7H), 7.18-7.10 (m,
2H), 7.00-6.92 (m, 2H), 5.27-5.12 (m, 2H), 4.60 (dd, J = 7.8,
4.2 Hz, 1H), 3.28-3.13 (m, 2H), 2.42 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3; δ, ppm) 198.2, 166.9, 163.4, 150.6, 137.1,
136.2, 133, 128.8, 128.7, 128.6, 128.3, 128.2, 127.8, 124.9,
124.5, 116.1, 105.3, 66.2, 48.3, 31.7, 19.9. IR (film, ν, cm−1)
3054, 2986, 2305, 1708, 1685, 1265, 738, 704. IR (film, ν,
cm−1) 3054, 2986, 2305, 1708, 1685, 1265, 738, 704; HRMS
(ESI-TOF) m/z: [M+Na]+ calcd for C26H22O4Na 421.1415;
found 421.1398.
chromene-3-carboxylate (3f). Yellow solid, 200 mg, 84%
yield, mp 104-107 ºC. H NMR (400 MHz, CDCl3; δ, ppm)
1
7.65 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.37-7.27
(m, 5H), 7.17 -7.09 (m, 2H), 7.01-6.93 (m, 2H), 5.26-5.13 (m,
2H), 4.55 (dd, J = 8.4, 3.6 Hz, 1H), 3.23-3.06 (m, 2H), 2.42 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 196.8, 166.6,
163.13, 151.2, 139.7, 136.0, 135.2, 130.1, 129.7, 129.0, 128.8,
128.4, 128.4, 127.7, 123.8, 120.8, 119.5, 105.4, 66.5, 47.9,
31.3, 19.8. IR (film, ν, cm−1) 3054, 2986, 2305, 1708, 1685,
1420, 1265, 738, 704; HRMS (ESI-TOF) m/z: [M+Na]+ calcd
for C26H21BrO4Na 499.0520; found 499.0506.
Benzyl
2-methyl-4-(2-oxo-2-(p-tolyl)ethyl)-4H-chromene-3-
Benzyl
4-(2-(4-fluorophenyl)-2-oxoethyl)-2-methyl-4H-
carboxylate (3b). White solid, 178 mg, 86% yield, Mp 85-87
chromene-3-carboxylate (3g). White solid, 175mg, 84% yield,
mp 55-57 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.85-7.79
(m, 2H), 7.37-7.27 (m, 5H), 7.13 (t, J = 7.2 Hz, 2H), 7.02-6.93
(m, 4H), 5.24-5.15 (m, 2H), 4.56 (dd, J = 8.4, 3.6 Hz, 1H),
3.23-3.07 (m, 2H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3; δ, ppm) 196.6, 167.0, 166.9, 164.4, 163.5, 150.6,
1
ºC. H NMR (400 MHz, CDCl3; δ, ppm) 7.72 (d, J = 8.2 Hz,
2H), 7.37-7.27 (m, 5H), 7.18-7.11 (m, 4H), 7.00-6.93 (m, 2H),
5.19 (s, 2H), 4.59 (dd, J = 8.0, 4.1 Hz, 1H), 3.23-3.11 (m, 2H),
2.42 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3; δ,
ppm) 197.8, 166.9, 163.3, 150.6, 143.8, 136.3, 134.7, 129.3,
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136.2, 133.5, 133.5, 131.0, 130.9, 128.7, 128.3, 128.3, 127.9,
124.6, 124.6, 116.2, 115.8, 115.6, 105.1, 66.4, 48.2, 31.9, 20.0.
IR (film, ν, cm−1) 3053, 2984, 2305, 1708, 1685, 1598, 1420,
1265, 738, 704; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C26H21FO4Na 439.1321; found 439.1310.
7.50 (t, J = 7.2 Hz, 1H), 7.40-7.24 (m, 7H), 7.14 (d, J = 1.6 Hz,
1H), 7.12-7.06 (m, 2H), 5.25-5.15 (m, 2H), 4.56 (dd, J = 8.0,
4.0 Hz, 1H), 3.25-3.12 (m, 2H), 2.41 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3; δ, ppm) 197.9, 166.6, 163.0, 151.2, 136.9,
136.1, 133.2, 130.2, 128.7, 128.7, 128.3, 128.2, 127.6, 124.5,
124.0, 120.6, 119.4, 105.5, 66.4, 47.9, 31.1, 19.8. IR (film, ν,
cm−1) 3054, 2986, 2305, 1710, 1685, 1420, 1265, 738, 705;
HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C26H21BrO4Na
499.0520; found 499.0507.
1
2
3
4
5
6
7
8
Benzyl
2-methyl-4-(2-oxo-2-(o-tolyl)ethyl)-4H-chromene-3-
1
carboxylate (3h). Yellow oil, 167 mg, 81% yield. H NMR
(400 MHz, CDCl3; δ, ppm) 7.41-7.24 (m, 7H), 7.21-7.11 (m,
3H), 7.05 (t, J = 7.6 Hz, 1H), 7.02-6.96 (m, 1H), 6.95 (d, J =
8.0 Hz, 1H), 5.29-5.15 (m, 2H), 4.60 (t, J = 6.0 Hz, 1H), 3.13
(d, J = 5.6 Hz, 2H), 2.39 (s, 3H), 2.36 (s, 3H); 13C{1H} (100
MHz, CDCl3; δ, ppm) 202.1, 166.9, 163.3, 150.6, 138.2, 137.9,
136.3, 132.0, 131.3, 128.8, 128.7, 128.4, 129.0, 127.8, 127.6,
125.6, 125.0, 124.55, 116.2, 105.2, 66.3, 50.9, 31.6, 21.2, 19.9.
IR (film, ν, cm−1) 3053, 2986, 2305, 1708, 1685, 1421, 1265,
895, 738, 704; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C27H24O4Na 435.1572; found 435.1562.
9
Benzyl
7-bromo-2-methyl-4-(2-oxo-2-(p-tolyl)ethyl)-4H-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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55
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58
59
60
chromene-3-carboxylate (3m). White solid, 194 mg, 79%
yield, mp 100-102 ºC. H NMR (400 MHz, CDCl3; δ, ppm)
1
7.77-7.66 (m, 2H), 7.36-7.27 (m, 5H), 7.18-7.11 (m, 3H),
7.10-7.05 (m, 2H), 5.25-5.15 (m, 2H), 4.55 (dd, J = 8.0, 4.0
Hz, 1H), 3.24-3.08 (m, 2H), 2.41 (s, 3H), 2.37 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 197.5, 166.6, 162.9, 151.1,
144.0, 136.1, 134.4, 130.2, 129.3, 128.7, 128.3, 128.3, 127.6,
124.4, 124.1, 120.6, 119.4, 105.6, 66.4, 47.9, 31.2, 21.7, 19.8.
IR (film, ν, cm−1) 3054, 2986, 2305, 1709, 1684, 1420, 1265,
738, 705; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C27H23BrO4Na 513.0677; found 513.0672.
Benzyl
4-(2-(2-methoxyphenyl)-2-oxoethyl)-2-methyl-4H-
chromene-3-carboxylate (3i). Yellow oil, 174 mg, 81% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.51 (dd, J = 7.6, 1.8 Hz,
1H), 7.40-7.26 (m, 7H), 7.11 (t, J = 7.0 Hz, 1H), 6.99 (t, J =
7.6 Hz, 1H), 6.91 (t, J = 8.0 Hz, 2H), 6.82 (d, J = 8.4 Hz, 1H),
5.18 (s, 2H), 4.64 (dd, J = 7.9, 3.6 Hz, 1H), 3.70 (s, 3H), 3.36
(dd, J = 16.6, 8.0 Hz, 1H), 3.14 (dd, J = 16.6, 3.6 Hz, 1H),
2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 200.5,
167.0, 162.8, 158.4, 150.5, 136.4, 133.4, 130.3, 128.9, 128.7,
128.6, 128.040, 127.5, 125.5, 124.4, 120.6, 115.9, 111.4,
105.4, 66.0, 55.4, 53.5, 52.9, 31.3, 19.8. IR (film, ν, cm−1)
3054, 2986, 2305, 1707, 1685, 1437, 1265, 737, 704; HRMS
(ESI-TOF) m/z: [M+Na]+ calcd for C27H24O5Na 451.1521;
found 451.1511.
Benzyl 7-bromo-4-(2-(4-chlorophenyl)-2-oxoethyl)-2-methyl-
4H-chromene-3-carboxylate (3n). White solid, 190 mg, 74%
1
yield, mp 98-100 ºC. H NMR (400 MHz, CDCl3; δ, ppm)
7.73 (d, J = 8.6 Hz, 2H), 7.35-7.27 (m, 7H), 7.13 (d, J = 2.0
Hz, 1H), 7.10 (dd, J = 8.4, 2.0 Hz, 1H), 7.03 (d, J = 8.0 Hz,
1H), 5.25-5.13 (m, 2H), 4.51 (dd, J = 8.4, 3.6 Hz, 1H), 3.21-
3.05 (m, 2H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3;
δ, ppm) 196.7, 166.6, 163.1, 151.1, 139.7, 136.0, 135.1, 130.1,
129.63, 129.0, 128.7, 128.4, 128.4, 127.6, 123.8, 120.7, 119.5,
105.3, 66.5, 47.9, 31.3, 19.8. IR (film, ν, cm−1) 3054, 2986,
2305, 1708, 1421, 1265, 895, 738, 705; HRMS (ESI-TOF)
m/z: [M+Na]+ calcd for C26H20BrClO4Na 533.013; found
533.0130.
Benzyl
4-(2-(3-methoxyphenyl)-2-oxoethyl)-2-methyl-4H-
chromene-3-carboxylate (3j). Yellow oil, 178 mg, 83% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.42-7.37 (m, 2H), 7.36-
7.27 (m, 5H), 7.25-7.09 (m, 3H), 7.07-7.02 (m, 1H), 7.02-6.94
(m, 2H), 5.20 (d, J = 1.6 Hz, 2H), 4.60 (dd, J = 7.8, 4.0 Hz,
1H), 3.81 (s, 3H), 3.25-3.12 (m, 2H), 2.43 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 198.0, 166.9, 163.3, 159.9,
150.6, 138.4, 136.2, 129.6, 128.8, 128.7, 128.2, 128.2, 127.8,
124.8, 124.6, 121.0, 119.7, 116.1, 112.2, 105.2, 66.2, 55.5,
48.3, 31.7, 20.0. IR (film, ν, cm−1) 3054, 2986, 2305, 1707,
1685, 1458, 1421, 1265, 738, 705; HRMS (ESI-TOF) m/z:
[M+Na]+ calcd for C27H24O5Na 451.1521; found 451.1504.
Benzyl
6-chloro-2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3o). White solid, 156 mg, 72% yield,
mp 114-116 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (dd,
J = 8.4, 1.2 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.39-7.26 (m,
7H), 7.22 (d, J = 2.4 Hz, 1H), 7.08 (dd, J = 8.8, 2.4 Hz, 1H),
6.89 (d, J = 8.6 Hz, 1H), 5.23-5.14 (m, 2H), 4.56 (t, J = 5.6 Hz,
1H), 3.21 (d, J = 6.0 Hz, 2H), 2.41 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3; δ, ppm) 197.7, 166.6, 163.1, 149.2, 136.9,
136.1, 133.2, 129.3, 128.7, 128.7, 128.6, 128.4, 128.3, 128.2,
127.9, 126.7, 117.5, 105.0, 66.4, 48.0, 31.3, 19.8. IR (film, ν,
cm−1) 3054, 2986, 2305, 1708, 1420, 1265, 738, 705; HRMS
(ESI-TOF) m/z: [M+Na]+ calcd for C26H21ClO4Na 455.1026;
found 455.1041.
Benzyl
4-(2-(3,4-dimethylphenyl)-2-oxoethyl)-2-methyl-4H-
chromene-3-carboxylate (3k). Colorless oil, 180 mg, 84%
1
yield. H NMR (400 MHz, CDCl3; δ, ppm) 7.62 (s, 1H), 7.56
(dd, J = 7.9, 1.7 Hz, 1H), 7.37-7.26 (m, 5H), 7.21 (dd, J = 7.6,
1.6 Hz, 1H), 7.13 (td, J = 7.6, 1.6 Hz, 1H), 7.09 (d, J = 8.0 Hz,
1H), 7.01-6.94 (m, 2H), 5.20 (s, 2H), 4.62 (dd, J = 6.8, 5.2 Hz,
1H), 3.23-3.13 (m, 2H), 2.44 (s, 3H), 2.27 (s, 3H), 2.25 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 198.0, 166.9, 163.2,
150.6, 142.5, 136.9, 136.3, 135.1, 129.8, 129.4, 128.9, 128.7,
128.2, 128.2, 127.7, 126.1, 125.1, 124.5, 116.1, 105.4, 66.2,
48.2, 31.6, 20.1, 19.9, 19.9. IR (film, ν, cm−1) 3054, 2983,
2305, 1709, 1682, 1488, 1265, 738, 703; HRMS (ESI-TOF)
m/z: [M+Na]+ calcd for C28H26O4Na 449.1728; found
449.1712.
Benzyl 2,7-dimethyl-4-(2-oxo-2-(p-tolyl)ethyl)-4H-chromene-
3-carboxylate (3p). Yellow solid, 181 mg, 85% yield, mp 79-
82 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.75 (d, J = 8.4 Hz,
2H), 7.39-7.27 (m, 5H), 7.14 (d, J = 8.2 Hz, 2H), 7.04 (d, J =
8.4 Hz, 1H), 6.83-6.77 (m, 2H), 5.21 (s, 2H), 4.57 (dd, J = 8.4,
3.6 Hz, 1H), 3.25-3.08 (m, 2H), 2.43 (s, 3H), 2.37 (s, 3H),
2.27 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 198.0,
167.0, 163.4, 150.4, 143.8, 137.8, 136.3, 134.7, 129.3, 128.7,
128.5, 128.4, 128.3, 128.2, 125.4, 121.8 116.5, 105.4, 66.2,
48.4, 31.5, 21.7, 21.1, 20.0. IR (film, ν, cm−1) 3054, 2986,
2305, 1708, 1684, 1421, 1265, 738, 705; HRMS (ESI-TOF)
m/z: [M+Na]+ calcd for C28H26O4Na 449.1728; found
449.1717.
Benzyl
7-bromo-2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3l). Yellow oil, 184 mg, 77% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 7.8 Hz, 2H),
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Benzyl 2,7-dimethyl-4-(2-oxo-2-phenylethyl)-4H-chromene-3-
carboxylate (3q). Yellow oil, 182 mg, 88% yield. H NMR
1265, 738, 704; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C27H24O5Na 451.1521; found 451.1511.
1
1
2
3
4
5
6
7
8
9
(400 MHz, CDCl3; δ, ppm) 7.83 (d, J = 7.2 Hz, 2H), 7.49 (t, J
= 7.4 Hz, 1H), 7.39-7.27 (m, 7H), 7.04 (d, J = 8.4 Hz, 1H),
6.79 (d, J = 6.6 Hz, 2H), 5.25-5.16 (m, 2H), 4.57 (dd, J = 8.4,
3.6 Hz, 1H), 3.28-3.10 (m, 2H), 2.42 (s, 3H), 2.26 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 198.3, 167.0, 163.4,
150.4, 138.0, 137.1, 136.3, 133.0, 128.7, 128.6, 128.5, 128.4,
128.3, 128.2, 125.4, 121.8, 116.5, 105.3, 66.2, 48.4, 31.5, 21.1,
20.0. IR (film, ν, cm−1) 3054, 2986, 2305, 1707, 1685, 1421,
1265, 738, 705; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C27H24O4Na 435.1572; found 435.1550.
2-Chlorobenzyl
2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3v). Yellow Oil, 182 mg, 84% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.82 (d, J = 7.0 Hz, 2H),
7.51-7.41 (m, 2H), 7.34 (t, J = 8.0 Hz, 3H), 7.25-7.17 (m, 3H),
7.13 (td, J = 7.8, 1.6 Hz, 1H), 6.98 (t, J = 7.6 Hz, 2H), 5.36-
5.24 (m, 2H), 4.62 (dd, J = 8.0, 3.8 Hz, 1H), 3.31-3.17 (m,
2H), 2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm)
198.1, 166.7, 163.7, 150.6, 137.1, 133.9, 133.0, 130.3, 129.7,
129.6, 128.9, 128.6, 128.3, 127.8, 127.1, 124.9, 124.6, 124.5,
116.1, 105.1, 63.8, 48.3, 31.6, 20.0. IR (film, ν, cm−1) 3054,
2986, 2305, 1708, 1685, 1420, 1265, 739, 705; HRMS (ESI-
TOF) m/z: [M+Na]+ calcd for C26H21ClO4Na 455.1026; found
455.1010.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Benzyl
7-methoxy-2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3r). Yellow solid, 187 mg, 87%
yield, mp 73-76 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81
(d, J = 8.2 Hz, 2H), 7.48 (t, J = 6.8 Hz, 1H), 7.39 -7.25 (m,
7H), 7.04 (d, J = 8.4 Hz, 1H), 6.54 (dd, J = 8.6, 1.8 Hz, 1H),
6.50 (d, J = 2.2 Hz, 1H), 5.24-5.14 (m, 2H), 4.53 (dd, J = 8.4,
3.7 Hz, 1H), 3.72 (s, 3H), 3.25-3.07 (m, 2H), 2.40 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 198.4, 167.0, 163.2,
159.3, 151.2, 137.1, 136.2, 133.0, 129.3, 128.7, 128.6, 128.4,
128.3, 128.2, 116.9, 111.0, 105.6, 101.4, 66.3, 55.5, 48.4, 31.2,
19.9. IR (film, ν, cm−1) 3054, 2985, 2305, 1708, 1686, 1506,
1265, 739, 704; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for
C27H24O5Na 451.1521, found 451.1504.
3,4-Dimethoxybenzyl 2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3w). Yellow Oil, 193 mg, 84% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.79 (d, J = 7.2 Hz, 2H),
7.48 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.8 Hz, 2H), 7.20-7.08 (m,
2H), 6.96 (td, J = 8.4, 2.0 Hz, 2H), 6.89 (d, J = 7.6 Hz, 2H),
6.75 (d, J = 8.2 Hz, 1H), 5.18-5.05 (m, 2H), 4.60 (t, J = 6.0 Hz,
1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.18 (s, 1H), 3.17 (d, J = 2.0
Hz, 1H), 2.42 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3; δ,
ppm) 198.1, 166.9, 163.2, 150.5, 149.0, 137.00, 133.1, 128.8,
128.7, 128.7, 128.6, 128.2, 127.8, 124.9, 124.7, 121.2, 116.1,
111.7, 111.0, 105.3, 66.3, 55.9, 55.9, 48.4, 31.5, 19.9. IR (film,
ν, cm−1) 3054, 2986, 2305, 1706, 1685, 1518, 1420, 1265, 738,
704; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C28H26O6Na
481.1627; found 481.1612.
Benzyl
7-methoxy-2-methyl-4-(2-oxo-2-(p-tolyl)ethyl)-4H-
chromene-3-carboxylate (3s). Yellow oil, 190 mg, 86% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.73 (d, J = 8.2 Hz, 2H),
7.37-7.27 (m, 5H), 7.13 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.6
Hz, 1H), 5.19 (s, 2H), 4.53 (dd, J = 8.6, 3.6 Hz, 1H), 3.72 (s,
3H), 3.22-3.06 (m, 2H), 2.41 (s, 3H), 2.36 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 198.1, 167.0, 163.1, 159.3,
151.2, 143.8, 136.3, 134.7, 129.4, 129.3, 128.7, 128.4, 128.3,
128.2, 116.9, 111.0, 105.7, 101.3, 66.3, 55.5, 48.4, 31.2, 21.7,
19.9. IR (film, ν, cm−1) 3054, 2986, 2305, 1707, 1684, 1637,
1421,1265, 738, 705; HRMS (ESI-TOF) m/z: [M+Na]+ calcd
for C28H26O5Na 465.1677; found 465.1668.
Ethyl
2-methyl-4-(2-oxo-2-phenylethyl)-4H-chromene-3-
1
carboxylate (3x). Yellow oil, 136 mg, 81% yield. H NMR
(400 MHz, CDCl3; δ, ppm) 7.88 (dd, J = 7.8, 1.3 Hz, 2H),
7.51 (t, J = 7.4 Hz, 1H), 7.44-7.37 (m, 2H), 7.18 (dd, J = 7.6,
1.7 Hz, 1H), 7.13 (td, J = 7.8, 1.6 Hz, 1H), 7.02-6.92 (m, 2H),
4.56 (dd, J = 8.2, 4.0 Hz, 1H), 4.24-4.13 (m, 2H), 3.28-3.13
(m, 2H), 2.42 (s, 3H), 1.25 (t, J = 7.2, 0.8 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 198.2, 167.1, 162.8, 150.7,
137.1, 133.1, 128.8, 128.6, 128.3, 127.8, 125.0, 124.5, 116.08,
105.6, 60.4, 48.3, 31.7, 19.8, 14.4. IR (film, ν, cm−1) 3054,
2986, 2305, 1701, 1685, 1448, 1265, 739, 705; HRMS (ESI-
TOF) m/z: [M+Na]+ calcd for C21H20O4Na 359.1259; found
359.1240.
4-Chlorobenzyl
2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3t). Yellow solid, 193 mg, 89%
yield, mp 96-98 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.83-
7.78 (m, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.8 Hz, 2H),
7.29-7.19 (m, 5H), 7.14 (td, J = 7.8, 1.6 Hz, 1H), 7.02-6.94 (m,
2H), 5.18-5.09 (m, 2H), 4.61 (dd, J = 6.8, 5.0 Hz, 1H), 3.25-
3.14 (m, 2H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3;
δ, ppm) 198.1, 166.7, 163.5, 150.5, 137.0, 134.7, 134.1, 133.1,
129.7, 128.9, 128.8, 128.6, 128.2, 127.9, 124.9, 124.7, 116.1,
105.1, 65.4, 48.4, 31.4, 19.93. IR (film, ν, cm−1) 3053, 2986,
2305, 1687, 1421, 1265, 738, 705; HRMS (ESI-TOF) m/z:
[M+Na]+ calcd for C26H21ClO4Na 455.1026; found 455.1012.
Benzyl
2-ethyl-4-(2-oxo-2-phenylethyl)-4H-chromene-3-
carboxylate (3y). Yellow solid, 182 mg, 88% yield, mp 100-
1
103 ºC. H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 7.6
Hz, 2H), 7.48 (t, J = 7.4 Hz, 1H), 7.39-7.24 (m, 7H), 7.20-7.10
(m, 2H), 6.98 (dd, J = 7.4, 4.0 Hz, 2H), 5.25-5.15 (m, 2H),
4.59 (dd, J = 8.4, 3.8 Hz, 1H), 3.28-3.12 (m, 2H), 2.96 (dq, J =
14.8, 7.4 Hz, 1H), 2.76-2.65 (m, 1H), 1.18 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3; δ, ppm) 198.2, 168.0, 166.6, 150.9,
137.1, 136.2, 133.0, 128.8, 128.7, 128.6, 128.3, 128.2, 127.8,
125.0, 124.5, 116.0, 104.7, 66.3, 48.2, 31.9, 26.3, 11.8. IR
(film, ν, cm−1) 3054, 2986, 2305, 1708, 1685, 1265,1420, 738,
705; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C27H24O4Na
435.1572; found 435.1562.
4-Methoxybenzyl
2-methyl-4-(2-oxo-2-phenylethyl)-4H-
chromene-3-carboxylate (3u). Yellow solid, 193 mg, 90%
yield, mp 78-81 ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81
(d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.35 (t, J = 7.6 Hz,
2H), 7.27 (d, J = 8.6 Hz, 2H), 7.20-7.09 (m, 2H), 7.01-6.92 (m,
2H), 6.81 (d, J = 8.6 Hz, 2H), 5.19-5.06 (m, 2H), 4.59 (dd, J =
7.8, 4.2 Hz, 1H), 3.76 (s, 3H), 3.24-3.12 (m, 2H), 2.41 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 198.2, 166.9, 163.1,
159.6, 150.6, 137.1, 133.0, 130.1, 128.8, 128.6, 128.4, 128.3,
127.8, 124.9, 124.5, 116.1, 114.0, 105.3, 66.0, 55.3, 48.3, 31.6,
19.8. IR (film, ν, cm−1) 3054, 2986, 2305, 1707, 1685, 1488,
Benzyl
2-benzyl-4-(2-oxo-2-phenylethyl)-4H-chromene-3-
carboxylate (3z). White solid, 209 mg, 88% yield, mp 71-74
ºC. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (dd, J = 8.4, 1.2
Hz, 2H), 7.54-7.46 (m, 1H), 7.38-7.08 (m, 14H), 7.00-6.91 (m,
2H), 5.27-5.17 (m, 2H), 4.66 (dd, J = 8.4, 3.8 Hz, 1H), 4.37 (d,
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J = 14.2 Hz, 1H), 4.06 (d, J = 14.4 Hz, 1H), 3.31-3.15 (m, 2H);
60.8, 49.4, 43.3, 40.2, 38.4, 14.1. IR (film, ν, cm−1) 3054, 2986,
2305,1739, 1708, 1685, 1488, 1457, 1265, 739, 704; HRMS
(ESI-TOF) m/z: [M+Na]+ calcd for C30H28O6Na 507.1783;
found 507.1768.
13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 198.1, 166.6, 164.2,
150.7, 137.4, 137.0, 136.0, 133.1, 129.0, 128.7, 128.7, 128.6,
128.5, 128.4, 128.3, 128.3, 127.9, 126.6, 124.9, 124.6, 116.2,
106.4, 66.5, 48.2, 38.1, 32.0. IR (film, ν, cm−1) 3053, 2986,
2305, 1687, 1421,1265, 738, 704; HRMS (ESI-TOF) m/z:
[M+Na]+ calcd for C32H26O4Na 497.1728; found 497.1717.
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ASSOCIATED CONTENT
Supporting Information
Spectroscopic data for all new compounds 3a-3z, 4a-4d, and X-
ray crystal data (CIF) for 3a. This material is available free of
charge via the Internet at http://pubs.acs.org.
Benzyl
3-methyl-2-methylene-4-(2-oxo-2-phenylethyl)
chromane-3-carboxylate (4a). Yellow oil, 136 mg, 66% yield.
1H NMR (400 MHz, CDCl3; δ, ppm) 7.86 (d, J = 7.8 Hz, 2H),
7.54 (t, J = 8.0 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.26 (t, J =
4.8 Hz, 3H), 7.20-7.11 (m, 3H), 6.94 (d, J = 7.6 Hz, 1H), 6.85
(dd, J = 17.2, 8.2 Hz, 2H), 5.11-5.00 (m, 2H), 4.87 (d, J = 1.6
Hz, 1H), 4.70 (d, J = 1.6 Hz, 1H), 3.89 (dd, J = 7.6, 3.8 Hz,
1H), 3.42 (dd, J = 18.2, 3.8 Hz, 1H), 3.17 (dd, J = 18.2, 7.6 Hz,
1H), 1.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm)
197.8, 172.3, 156.0, 151.5, 136.7, 135.5, 133.3, 128.7, 128.6,
128.3, 128.3, 128.2, 128.2, 128.2, 124.8, 121.9, 115.7, 92.6,
67.1, 47.9, 42.1, 38.8, 22.8. IR (film, ν, cm−1) 3054, 2986,
2305, 1729, 1685, 1490, 1456, 1265, 746, 704; HRMS (ESI-
TOF) m/z: [M+Na]+ calcd for C27H24O4Na 435.1572; found
435.1561.
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AUTHOR INFORMATION
Corresponding Authors
*(G.L.) E-mail: Guigen.Li@ttu.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We would like to acknowledge the financial support from the
National Natural Science Foundation of China (No. 21332005,
21672100) and Robert A. Welch Foundation (D-1361, USA).
Benzyl
3-ethyl-2-methylene-4-(2-oxo-2-phenylethyl)
chromane-3-carboxylate (4b). Yellow oil, 137 mg, 137 mg,
1
64% yield. H NMR (400 MHz, CDCl3; δ, ppm) 7.78 (d, J =
7.2 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.41-7.29 (m, 4H), 7.28-
7.21 (m, 3H), 7.18-7.09 (m, 2H), 6.83 (td, J = 8.4, 2.2 Hz, 2H),
5.19-5.00 (m, 4H), 4.01 (dd, J = 8.2, 3.8 Hz, 1H), 3.19 (dd, J =
17.6, 3.6 Hz, 1H), 3.02 (dd, J = 17.6, 8.4 Hz, 1H), 1.80 (dq, J
= 14.6, 7.4 Hz, 1H), 1.67 (dq, J = 14.6, 7.4 Hz, 1H), 0.81 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 197.5, 171.5,
152.5, 151.2, 136.9, 135.5, 133.1, 129.5, 128.7, 128.6, 128.6,
128.6, 128.4, 128.1, 124.8, 121.7, 115.5, 95.2, 77.5, 77.1, 76.8,
67.0, 53.1, 43.8, 37.7, 28.3, 9.0. IR (film, ν, cm−1) 3054, 2986,
2305, 1734, 1685, 1458, 1117, 1265, 738, 704; HRMS (ESI-
TOF) m/z: [M+Na]+ calcd for C28H26O4Na 449.1728; found
449.1710.
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7.69 (m, 2H), 7.52-7.45 (m, 1H), 7.34 (t, J = 7.8 Hz, 2H),
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133.1, 130.2, 130.1, 128.9, 128.7, 128.6, 128.6, 128.1, 128.1,
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3-(2-ethoxy-2-oxoethyl)-2-methylene-4-(2-oxo-2-
phenylethyl)chromane-3-carboxylate (4d). colorless oil, 148
mg, 61% yield. 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80 (dd,
J = 8.4, 1.2 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.40-7.35 (m,
2H), 7.34-7.23 (m, 5H), 7.17-7.11 (m, 2H), 6.90-6.83 (m, 2H),
5.14-5.06 (m, 2H), 5.05 (s, 2H), 4.05-3.94 (m, 3H), 3.50 (dd, J
= 17.6, 4.8 Hz, 1H), 2.94 (dd, J = 17.6, 7.2 Hz, 1H), 2.87 (d, J
= 16.8 Hz, 1H), 2.68 (d, J = 16.8 Hz, 1H), 1.12 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3; δ, ppm) 197.1, 170.6,
170.0, 151.8, 150.9, 136.8, 135.3, 133.2, 129.3, 128.8, 128.8,
128.7, 128.6, 128.6, 128.4, 128.1, 122.1, 115.8, 96.2, 67.5,
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