Synthesis of Diversely Functionalized 2 H-Chromenes through Pd-Catalyzed Cascade Reactions of 1,1-Dibromoolefin Derivatives with Arylboronic Acids

Article abstract of DOI:10.1021/acs.joc.8b02456

In this work, an unprecedented synthesis of (2H-chromen-2-ylidene)acetates and (2H-chromen-2-ylidene)ethanones with controlled stereoselectivity via Pd-catalyzed cascade reactions of 3-(2-(2,2-dibromovinyl)phenoxy)acrylates or 3-(2-(2,2-dibromovinyl)pheno

Full text of DOI:10.1021/acs.joc.8b02456

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Article
Synthesis of Diversely Functionalized 2H-Chromenes through Pd-Catalyzed
Cascade Reactions of 1,1-Dibromoolefin Derivatives with Arylboronic Acids
Xia Song, Cai Gao, Xinying Zhang, and Xuesen Fan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02456 • Publication Date (Web): 22 Nov 2018
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Synthesis of Diversely Functionalized 2H-Chromenes through Pd-Catalyzed Cascade Reactions
of 1,1-Dibromoolefin Derivatives with Arylboronic Acids
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Xia Song, Cai Gao, Xinying Zhang,* and Xuesen Fan*
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Henan Key Laboratory of Organic Functional Molecules and Drug Innovation, Collaborative
Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of
Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical
Engineering, Henan Normal University, Xinxiang, Henan 453007, China
E-mail: xinyingzhang@htu.cn; xuesen.fan@htu.cn
Abstract: In this paper, an unprecedented synthesis of (2H-chromen-2-ylidene)acetates and
(2H-chromen-2-ylidene)ethanones with controlled stereoselectivity via Pd-catalyzed cascade reactions
of 3-(2-(2,2-dibromovinyl)phenoxy)acrylates or 3-(2-(2,2-dibromovinyl)phenoxy)enones with aryl
boronic acids has been established. This protocol combines two C–C bond forming reactions (an
intermolecular Suzuki coupling followed by an intramolecular Heck coupling) in one pot under the
catalysis of the same catalyst. Compared with literature methods for the preparation of 2H-chromene
derivatives, it has advantages such as easily obtainable or commercially available substrates, diverse
substitution pattern of products, simple procedure, and excellent stereoselectivity. Interestingly, this
cascade reaction could distinguish the subtle difference of the electron withdrawing capacity and the
size of various functional groups, and thus resulted in different chemoselectivity. In addition, the
utility of the (2H-chromen-2-ylidene)acetate thus obtained was showcased by its facile transformation
into the synthetically and photophysically significant 3H-xanthen-3-one derivative.
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INTRODUCTION
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The 2H-chromene unit exists in a wide range of natural products and man-made compounds
exhibiting a broad spectrum of biological activities such as antibacterial, antitumor, antioxidant,
antiviral, antileishmanial, and antiprotozoal.1 Therefore, it is deemed as a privileged scaffold in
medicinal chemistry. In addition, many 2H-chromene derivatives demonstrate unique photo-physical
properties, and have thus been extensively utilized in the development of powerful laser dyes, organic
light emitting devices (OLEDs) and fluorescence probes.1,2 As a further aspect, functionalized
2H-chromenes are frequently used as indispensable synthetic intermediates in the preparation of a
plethora of natural products and fine chemicals.1,2 Due to their importance, some reliable methods for
the synthesis of 2H-chromene derivatives have been developed.1,3 Meanwhile, it was also noticed by
us that efficient methods applicable for the preparation of 2H-chromenes containing an elongated
conjugate system attached on the pyranyl moiety, which is structurally and synthetically highly
interesting, had only appeared sporadically in literature reports.4
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In recent decades, 1,1-dibromoolefin derivatives are rapidly emerging as highly important synthetic
intermediates owing to their easy accessibility and versatile reactivity.5 In particular, they have been
routinely used as effective precursors toward various kinds of heterocycle and carbocycle through
transition-metal-catalyzed tandem C–N and/or C–C coupling reactions.6 In this aspect, we have
recently developed an alternative synthesis of functionalized indoles via copper-catalyzed one-pot
multi-component cascade reactions of 1-bromo-2-(2,2-dibromovinyl)benzenes with aldehydes and
aqueous ammonia (Scheme 1, (1)).7 Inspired by those pioneering studies and as a continuation of our
own interest in this regard, we have studied the reaction of 3-(2-(2,2-dibromovinyl)phenoxy)acrylate
with organoboronic acid under the catalysis of Pd catalyst.8 We anticipated that in the presence of a
coupling partner such as arylboronic acid, the 1,1-dibromovinyl moiety in 3-(2-(2,2-dibromovinyl)
phenoxy)acrylate would undergo cascade coupling reactions to access 3-substituted 2H-chromenes
bearing an extended conjugate system on the pyranyl moiety (Scheme 1, (2)).9 Herein, we report our
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detailed study in this aspect.
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Our previous work, ref. 7
CuI
CN
Ph
Br
(1)
(2)
NH3 H2O
+ PhCHO +
Br
Br
Br
N
9
H
This work
PhB(OH)2
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Br
Ph
Pd(OAc)2, PPh3, K2CO3
dioxane, 80 o
O
C
CO2Et
CO2Et
O
Scheme 1. Transformations of 1,1-Dibromoolefin Derivatives
RESULTS AND DISCUSSION
Our study was commenced by treating ethyl (E)-3-(2-(2,2-dibromovinyl)phenoxy)acrylate (1a) with
phenylboronic acid (2a) in the presence of Pd(OAc)2, PPh3, Cs2CO3 in THF at 80 °C for 24 h. To our
delight, the envisioned cascade reaction took place smoothly to give the desired product, ethyl
(Z)-2-(3-phenyl-2H-chromen-2-ylidene)acetate (3a), in a yield of 50% (Table 1, entry 1). To improve
the reaction efficiency, several parameters possibly affecting this cascade transformation were
investigated. First, different bases such as Na2CO3, K2CO3, Li2CO3 and KH2PO4 were tried (entries
2-5). Among them, K2CO3 turned out to be the most efficient (entry 3). Second, several solvents
including DME, toluene, dioxane and DMF were tried to replace THF. Delightfully, the yield of 3a
increased to 70% when the reaction was carried out in dioxane (entry 8). Third, the effect of different
palladium catalysts such as PdCl2, PdCl2(PPh3)2, Pd(PPh3)4, Pd(OTFA)2, Pd(dppf)Cl2 were tested
(entries 10-14). Among them, Pd(TFA)2 showed a comparable efficiency as Pd(OAc)2 in promoting
this reaction while other Pd catalysts were much less effective than Pd(OAc)2. Fourth, different
ligands including 1,10-phenanthroline (1,10-phen), tri-(tert-butyl)phosphonium tetrafluoroborate
(TBPF), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos), tris(2-furanyl)phosphine
(TFP) and tricyclohexylphosphine (TCHP), were tried to replace PPh3 (entries 15-19), but they were
found to be much less effective. Finally, control experiments showed that in the absence of either
catalyst, ligand or base, the formation of 3a was not observed (entries 20-22).
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Table 1. Optimization Studies on the Formation of 3a a
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Entry
1
Catalyst
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Ligand
PPh3
Base
Cs2CO3
Na2CO3
K2CO3
Li2CO3
KH2PO4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Solvent
THF
Yield (%)b
50
2
PPh3
THF
23
3
PPh3
THF
63
4
PPh3
THF
trace
23
5
PPh3
THF
6
PPh3
DME
33
7
PPh3
toluene
dioxane
DMF
trace
70
8
PPh3
9
PPh3
trace
29
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PPh3
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
PdCl2(PPh3)2
Pd(PPh3)4
Pd(TFA)2
Pd(dppf)Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PPh3
53
PPh3
24
PPh3
69
PPh3
24
1,10-Phen
TBPF
X-Phos
TFP
34
22
trace
30
TCHP
PPh3
24
ND
ND
ND
Pd(OAc)2
Pd(OAc)2
PPh3
a Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), catalyst (0.03 mmol), ligand
(0.18 mmol), base (1.2 mmol), solvent (3 mL), 80 C, 24 h. b Isolated yields.
With the optimized reaction conditions in hand, the scope and generality of this novel cascade
process was explored. It was firstly found that the reactions of diversely substituted phenylboronic
acids (2) with 1a proceeded smoothly to give 3a-3m in moderate to good yields, and various
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functional groups such as alkyl, aryl, halides and nitro group tolerated the reaction conditions very
well (Table 2). Meanwhile, the reaction showed some electronic effect in that phenylboronic acids
bearing an electron-donating functional group on the phenyl ring gave the corresponding products in
higher yields than those bearing an electron-withdrawing group (3c, 3h vs 3e, 3g), and this is in
agreement with previous observations.8j In addition, the reaction also showed some steric effect in that
ortho-substituted phenylboronic acids resulted in reduced yields compared with their para- or
meta-substituted counterparts as exemplified in the formation of 3l and 3m. Interestingly, in addition
to phenylboronic acids, thiophen-2-ylboronic acid could also participate in this reaction, albeit the
yield of the corresponding product (3n) was lower. Finally, it is also worth to be noted herein that the
structure of 3g was unambiguously confirmed by its single crystal X-ray diffraction analysis.10
Table 2. Substrate Scope for the Preparation of 3 (I)a
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Ph(4-Et)
O
CO2Et
3a, 70%
3e, 60%
3i, 70%
3b, 72%
3c, 75%
3g, 46%
3k, 56%
3d, 59%
3h, 75%
3l, 44%
Ph(4-Cl)
O
CO2Et
3f, 60%
3j, 60%
3n, 38%
Ph(2-Cl)
O
CO2Et
3m, 45%
a
Reaction conditions: 1a (0.3 mmol), 2 (0.45 mmol), Pd(OAc)2 (0.03 mmol), PPh3 (0.18 mmol), K2CO3 (1.2
mmol), dioxane (3 mL), 80 C, 24 h. b Isolated yields.
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Next, the scope and generality of (E)-3-(2-(2,2-dibromovinyl)phenoxy)acrylates 1 was investigated
by using 2a as a model substrate. The results listed in Table 3 showed that 1 with either a methyl,
chloro or bromo group attached on the 4-position, a methoxy unit on the 5-position, two bromo or
tert-butyl groups on the 4,6-positions of the linking phenyl scaffold reacted with 2a smoothly to afford
3o-3t with good efficiency. Notably, different functional groups were well tolerated, and the reactions
did not show either an obvious electronic or steric effect. To our delight, the reaction of ethyl
(E)-3-((1-(2,2-dibromovinyl)naphthalen-2-yl)oxy)acrylate with 2a also took place smoothly to give
3u in a yield of 45%. Interestingly, this cascade reaction took place efficiently when the ethyl unit of
the acrylate moiety was replaced by a methyl or tert-butyl unit as demonstrated in the formation of
3v-3y.
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Table 3. Substrate Scope for the Preparation of 3 (II)a
3o, 68%
3s, 67%
3p, 74%
3t, 62%
3x, 71%
3q, 71%
3u, 45%
3y, 75%
3r, 60%
3v, 75%
Me
Ph
O
CO2Me
3w, 69%
a
Reaction conditions: 1 (0.3 mmol), 2a (0.45 mmol), Pd(OAc)2 (0.03 mmol), PPh3 (0.18 mmol), K2CO3 (1.2
mmol), dioxane (3 mL), 80 C, 24 h. b Isolated yields.
After having established an efficient synthesis of (2H-chromen-2-ylidene)acetates 3 from the
cascade reactions of 3-(2-(2,2-dibromovinyl)phenoxy)acrylates 1 with arylboronic acids 2, the scope
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of the 1,1-dibromoolefin substrate was extended from acrylate derivatives 1 to enone derivatives 4.
Thus, (E)-4-(2-(2,2-dibromovinyl)phenoxy)but-3-en-2-one (4a) was treated with 2a under the
optimum reaction conditions as described above. From this reaction, the desired cascade coupling
product, (Z)-1-(3-phenyl-2H-chromen-2-ylidene)propan-2-one (5a), was obtained in a yield of 58%.
Meanwhile, 1-(3-phenyl-2H-chromen-2-yl)propan-2-one (6a) was also isolated in a yield of 15%
(Scheme 2).
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Scheme 2. Formation of 5a and 6a from the Reaction of 4a with 2a
To improve the reaction efficiency and selectivity, different catalysts, additives, bases and solvents
were then screened.11 However, no better result was obtained under these reaction conditions (see SI).
As a further effort, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was added to the mixture
resulting from the reaction of 4a with 2a to assist the dehydrogenation of 6a to form 5a. Unfortunately,
the yield of 5a could not be improved under this circumstance. Since it was so, we then moved our
focus to exploring the substrate generality for the preparation of 5. It was firstly found that in addition
to 2a, p-tolylboronic acid and (4-chlorophenyl)boronic acid participated in this reaction effectively to
give 5b, 5d and 5e in reasonably good yields (Table 4). As for the scope of 4, it was observed that 4
with either a methyl, chloro or methoxy group attached on the 4-position, or a methoxy group on the
5-position of the linking phenyl scaffold reacted with 2 to give 5c-5h in yields ranging from 53% to
68%. In another aspect, the R4 unit in 4 could be varied from methyl to benzyl, cyclohexyl, phenyl or
p-chlorophenyl group, thus resulting in a versatile and convenient formation of 2H-chromenes bearing
structurally diverse enone units attached on the pyranyl moiety. Meanwhile, it was also noticed that
when the R4 unit was varied from methyl to benzyl, cyclohexyl or phenyl, the selectivity for the
formation of 5 over 6 decreased obviously (5i-5l), most likely owing to electronic and steric effect.
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Table 4. Substrate Scope for the Preparation of 5 a,b,c
4
5
Br
Br
R3
Pd(OAc)2, PPh3, K2CO3
dioxane, 80 o
R1
+ R3-B(OH)2
6
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R1
C
COR4
O
2
O
4
COR4
5 (6)
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Ph(4-Me)
COMe
O
5a, 58% (15%)
5b, 57% (14%)
5c, 66% (16%)
5d, 68% (16%)
Cl
Ph
O
COMe
5e, 65% (14%)
5i, 42% (22%)
5f, 57% (17%)
5g, 55% (14%)
5k, 42% (35%)
5h, 53% (14%)
5l, 23% (30%)
5j, 44% (27%)
a
Reaction conditions: 4 (0.3 mmol), 2 (0.45 mmol), Pd(OAc)2 (0.03 mmol), PPh3 (0.18 mmol), K2CO3 (1.2
mmol), dioxane (3 mL), 80 C, 24 h. b Isolated yields. c The yields in parentheses are for products 6.
Interestingly, our further study showed that while direct addition of DDQ to the mixture resulting
from the reaction of 4a with 2a did not have an obvious effect in promoting the dehydrogenation of 6a
to form 5a as described above, treating 6a isolated and purified from the original reaction system with
o
DDQ in dioxane at 80 C for 5 h afforded 5a in 38% yield (Scheme 3). More promisingly, treating
isolated 6k with DDQ gave 5k in an excellent yield of 85% (Scheme 3). These transformations could
be used complementarily to the reaction shown in Table 4 for the preparation of the targeted
(2H-chromen-2-ylidene)ethanones 5.
Scheme 3. Transformation of 6 into 5 under the Promotion of DDQ
Based on the above described experimental results and literature reports, a plausible mechanism
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accounting for the formation of 3a from the reaction of 1a with 2a is proposed in Scheme 4. Initially,
an oxidative addition of Pd(0) into the C–Br bond in 1a gives intermediate A. Subsequent
transmetallation of A with 2a affords B, which then undergoes a reductive elimination to give C along
with the concurrent release of Pd(0). Subsequently, oxidative addition of Pd(0) into the vinyl C–Br
bond in C affords intermediate D. The following palladium coordination and insertion form
intermediates E and F, respectively. Next, rotation around the Cα–C single bond, which is necessary
to attain the conformation required for a syn elimination, occurs with F to give intermediate G.
Finally, elimination of HPdBr from G produces 3a and regenerates Pd(0) for the next catalytic cycle.
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Scheme 4. Plausible Reaction Pathway Accounting for the Formation of 3a
As for the formation of 5a and 6a from the reaction of 4a with 2a, it should firstly involve a
cascade process including oxidative addition of Pd(0) into the C–Br bond in 4a, subsequent
transmetallation with 2a and reductive elimination, second oxidative addition of Pd(0) into the vinyl
C–Br bond, and palladium coordination and insertion to form the key intermediate H (Scheme 5).
From H, 5a is formed through elimination of HPdBr. On the other hand, the formation of 6a is
believed to go through a C–Pd bond heterolytic cleavage to afford an anion intermediate I. Finally,
protonation of the anionic moiety in I affords 6a.12
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Ph
Ph
Pd(0)
elimination
4a
2a
+
PdBr
O
O
HPdBr
Pd(0)
H
COMe
COMe
5a
PPh3
heterolytic cleavage
[PdBr]
Ph
Ph
protonation
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O
O
6a
COMe
I
COMe
Scheme 5. Plausible Reaction Pathway Accounting for the Formation of 5a and 6a
Based on the reaction mechanism described above, the different chemoselectivity shown by the
reactions of 1 with 2 and 4 with 2 in that the former exclusively gave the vinylic substitution product
while the later afforded a mixture of vinylic substitution product and conjugate addition type product
might be explained as owing to the inherently different electronic nature of 1 and 4. To be specific,
since the electron withdrawing capacity of an acyl group is generally stronger than that of an ester
group, the acyl unit embedded in 4 should be more favorable than the ester unit embedded in 1 for the
generation of the proposed anionic intermediate as shown in Scheme 5, from which the conjugate
addition product is formed.
Moreover, the examples included in Table 4 showed that an increase in the electron-withdrawing
capacity of R4 tends to increase the ratio of the conjugate addition product over the vinylic substitution
product. This could be seen by comparing the ratio of 6a over 5a with the ratio of 6k over 5k, and the
ratio of 6k over 5k with the ratio of 6l over 5l. Meanwhile, the size of R4 also makes a difference. To
be specific, a more hindered R4 tends to favor the formation of the conjugate addition product
presumably through restricting the rotation around the Cα-C single bond required to attain the
conformation suitable for -H elimination. This could be demonstrated by comparing the ratio of 6a
over 5a with the ratio of 6j over 5j.
To showcase the usability of the products obtained above, 3a was treated with PPA at 135 oC for 4
h. From this reaction, benzo 3H-xanthen-3-one (7) was obtained in a yield of 80% (Scheme 6). Given
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the fact that 3H-xanthen-3-one derivatives posses unique photophysical properties and have thus been
used widely in the development of new dyes and pigments,13 this efficient synthetic pathway toward
3H-xanthen-3-one derivatives is expected to find practical applications in related areas.
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Scheme 6. Synthesis of Benzo 3H-xanthen-3-one (7) from 3a
Finally, to study whether this newly developed method is suitable for large scale synthetic missions,
the preparations of 3a and 5a were carried out in an enlarged scale of 5 mmol. It turned out that the
corresponding reactions proceeded smoothly to afford 3a and 5a in yields of 64% and 52%,
respectively (Scheme 7).
Scheme 7. Gram-scale Synthesis of 3a and 5a
In summary, an efficient and convenient synthesis of the biologically and synthetically important
(2H-chromen-2-ylidene)acetates and (2H-chromen-2-ylidene)ethanones has been established. Notable
features such as use of easily accessible 1,1-dibromoolefin derivatives and the commercially available
arylboronic acids as the substrates, high efficiency of one catalyst for two couplings in one pot, simple
process and broad substrate scope make this novel approach an attractive and practical method for the
preparation of the title compounds. Further investigations on the detailed reaction mechanism and
applications of the synthetic methods presented herein in synthetic and medicinal chemistry are in
progress in our laboratory.
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EXPERIMENTAL SECTION
1. General experimental information
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All commercial reagents and solvents were used without further purification. Melting points were
recorded with a micro melting point apparatus and uncorrected. The 1H NMR spectra were recorded at
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400 MHz or 600 MHz, the C NMR spectra were recorded at 100 MHz or 150 MHz, and the F
NMR spectra were recorded at 376 MHz. Chemical shifts were expressed in parts per million (δ), and
were reported as s (singlet), d (doublet), t (triplet), m (multiplet), etc. The coupling constants J were
given in Hz. High resolution mass spectra (HRMS) were obtained via ESI mode by using a
MicrOTOF mass spectrometer. All the reactions were monitored by thin-layer chromatography (TLC)
using silica gel plates (silica gel 60 F254 0.25 mm), and components were visualized by observation
under UV light (254 and 365 nm).
2. Typical procedure for the synthesis of 1a and spectroscopic data of substrates 1a-1l and 4a-4i
To a flask containing a solution of PPh3 (4721 mg, 18 mmol) in DCM (5 mL) was slowly added
CBr4 (2985 mg, 9 mmol) in DCM (5 mL) at 0 ºC. Then, Et3N (2.9 mL, 18 mmol) and a solution of
2-hydroxybenzaldehyde (366 mg, 3 mmol) in DCM (5 mL) were added sequentially and dropwisely at
0 ºC with stirring. The resulting mixture was stirred at room temperature for 1 h. Upon completion, it
was concentrated under reduced pressure. The residue was purified by column chromatography on
silica gel with petroleum ether/dichoromethane (2:1) as the eluent to give 2-(2,2-dibromovinyl)phenol
(667 mg, 80%).
To a flask containing a solution of 2-(2,2-dibromovinyl)phenol (556 mg, 2 mmol) in DCM (6 mL)
were added ethyl propiolate (216 mg, 2.2 mmol) and DABCO (23 mg, 0.2 mmol). It was then stirred
at 0 ºC for 30 min. The resulting mixture was concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel using petroleum ether/ethyl acetate (20:1) as eluent
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to afford ethyl (E)-3-(2-(2,2-dibromovinyl)phenoxy)acrylate (1a, 673 mg, 89%). 1b-1l and 4a-4i were
obtained in a similar manner.
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(E)-Ethyl 3-(2-(2,2-dibromovinyl)phenoxy)acrylate (1a)
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1
White solid (673 mg, 89%), mp: 40-41 °C. H NMR (400 MHz, CDCl3) δ: 1.29 (t, J = 7.2 Hz, 3H),
4.20 (q, J = 7.2 Hz, 2H), 5.52 (d, J = 12.4 Hz, 1H), 7.05 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.22 (td, J1
= 7.6 Hz, J2 = 0.8 Hz, 1H), 7.38 (td, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 7.48 (s, 1H), 7.72-7.75 (m, 2H). 13C
NMR (150 MHz, CDCl3) δ: 14.3, 60.2, 92.4, 102.8, 118.2, 125.0, 126.8, 129.8, 130.2, 131.4, 152.6,
158.7, 167.0. HRMS calcd for C13H12Br2O3Na: 396.9045 [M+Na]+, found: 396.9050.
(E)-Ethyl 3-(2-(2,2-dibromovinyl)-4-methylphenoxy)acrylate (1b)
Yellow liquid (721.6 mg, 93%). 1H NMR (400 MHz, CDCl3) δ: 1.28 (t, J = 7.2 Hz, 3H), 2.36 (s, 3H),
4.19 (q, J = 7.2 Hz, 2H), 5.46 (d, J = 12.4 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 7.17 (dd, J1 = 8.4 Hz, J2
= 2.0 Hz, 1H), 7.43 (s, 1H), 7.51 (d, J = 2.0 Hz,, 1H), 7.70 (d, J = 12.0 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ: 14.3, 20.9, 60.2, 92.2, 102.3, 118.2, 126.6, 130.1, 130.7, 131.5, 134.8, 150.4, 159.3, 167.1.
HRMS calcd for C14H14Br2O3Na: 410.9202 [M+Na]+, found: 410.9201.
(E)-Ethyl 3-(4-chloro-2-(2,2-dibromovinyl)phenoxy)acrylate (1c)
White solid (673.2 mg, 82%), mp: 65-66 °C. 1H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 7.2 Hz, 3H),
4.18 (q, J = 7.2 Hz, 2H), 5.51 (d, J = 12.4 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H),
7.39 (s, 1H), 7.66 (d, J = 12.0 Hz, 1H), 7.71 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.3, 60.3, 93.9,
103.4, 119.4, 128.2, 129.5, 130.0, 130.1, 130.3, 151.1, 158.2, 166.6. HRMS calcd for
C13H11Br2ClO3Na: 430.8656 [M+Na]+, found: 430.8650.
(E)-Ethyl 3-(4-bromo-2-(2,2-dibromovinyl)phenoxy)acrylate (1d)
Yellow solid (686.8 mg, 75%), mp: 76-77 °C. 1H NMR (400 MHz, CDCl3) δ: 1.29 (t, J = 7.6 Hz, 3H),
4.20 (q, J = 7.2 Hz, 2H), 5.53 (d, J = 12.0 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 7.40 (s, 1H), 7.48 (d, J =
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8.4 Hz, 1H), 7.67 (d, J = 12.0 Hz, 1H), 7.86 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.3, 60.3, 94.0,
103.5, 117.7, 119.7, 128.6, 130.0, 132.5, 133.0, 151.6, 158.1, 166.7. HRMS calcd for C13H11Br3O3Na:
474.8151 [M+Na]+, found: 474.8152.
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(E)-Ehyl 3-(2-(2,2-dibromovinyl)-5-methoxyphenoxy)acrylate (1e)
Yellow liquid (533.2 mg, 66%). 1H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 7.2 Hz, 3H), 3.80 (s, 3H),
4.18 (q, J = 7.2 Hz, 2H), 5.52 (d, J = 12.4 Hz, 1H), 6.55 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 7.39 (s, 1H),
7.67-7.72 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 14.3, 55.7, 60.2, 90.4, 103.0, 104.3, 110.3, 119.0,
130.3, 130.8, 153.7, 158.5, 161.0, 166.9. HRMS calcd for C14H14Br2O4Na: 426.9151 [M+Na]+, found:
426.9149.
(E)-Ethyl 3-(2,4-dibromo-6-(2,2-dibromovinyl)phenoxy)acrylate (1f)
White solid (794.6 mg, 74%), mp: 51-52 °C. 1H NMR (400 MHz, CDCl3) δ: 1.18 (t, J = 7.2 Hz, 3H),
4.09 (q, J = 7.2 Hz, 2H), 5.06 (d, J = 12.4 Hz, 1H), 7.21 (s, 1H), 7.53 (d, J = 12.0 Hz, 1H), 7.68 (s,
1H), 7.71 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.3, 60.3, 95.8, 101.5, 117.2, 119.4, 129.6, 131.81,
131.84, 136.1, 147.8, 158.8, 166.2. HRMS calcd for C13H10Br4O3Na: 552.7256 [M+Na]+, found:
552.7261.
(E)-Ethyl 3-(2,4-di-tert-butyl-6-(2,2-dibromovinyl)phenoxy)acrylate (1g)
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White solid (767.9 mg, 79%), mp: 102-103 °C. H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 6.8 Hz,
3H), 1.32 (s, 9H), 1.35 (s, 9H), 4.15 (q, J = 6.8 Hz, 2H), 5.32 (d, J = 12.4 Hz, 1H), 7.31(s, 1H), 7.39 (s,
13
1H), 7.41, (s, 1H), 7.51 (d, J = 12.4 Hz, 1H). C NMR (100 MHz, CDCl3) δ: 14.4, 30.7, 31.4, 34.8,
35.1, 59.9, 93.4, 100.9, 124.8, 125.6, 128.6, 133.8, 141.0, 147.9, 149.4, 161.7, 166.9. HRMS calcd for
C21H28Br2O3Na: 509.0297 [M+Na]+, found: 509.0297.
(E)-Ethyl 3-((1-(2,2-dibromovinyl)naphthalen-2-yl)oxy)acrylate (1h)
Colorless liquid (678.3 mg, 80%). 1H NMR (400 MHz, CDCl3) δ: 1.26 (t, J = 7.2 Hz, 3H), 4.18 (q, J =
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7.2 Hz, 2H), 5.50 (d, J = 12.0 Hz, 1H), 7.23 (d, J = 8.8 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.52-7.57 (m,
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2H), 7.80-7.87 (m, 4H). C NMR (150 MHz, CDCl3) δ: 14.4, 60.2, 96.2, 102.4, 118.4, 123.0, 125.0,
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126.0, 127.6, 128.5, 131.0, 131.12, 131.14, 131.3, 149.7, 159.4, 167.0. HRMS calcd for
C17H14Br2O3Na: 446.9202 [M+Na]+, found: 446.9187.
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(E)-Methyl 3-(2-(2,2-dibromovinyl)phenoxy)acrylate (1i)
White solid (676.6 mg, 93%), mp: 71-72 °C. 1H NMR (600 MHz, CDCl3) δ: 3.75 (s, 3H), 5.55 (d, J =
12.0 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 7.24 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.49 (s, 1H),
7.75-7.77 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 51.5, 92.5, 102.5, 118.0, 125.0, 126.8, 129.8,
130.3, 131.4, 152.6, 158.9, 167.4. HRMS calcd for C12H10Br2O3Na: 382.8889 [M+Na]+, found:
382.8892.
(E)-Methyl 3-(2-(2,2-dibromovinyl)-4-methylphenoxy)acrylate (1j)
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Yellow solid (688.0 mg, 91%), mp: 54-55 °C. H NMR (400 MHz, CDCl3) δ: 2.28 (s, 3H), 3.65 (s,
3H), 5.40 (d, J = 12.4 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 7.09 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.35
(s, 1H), 7.43 (d, J = 1.6 Hz, 1H), 7.64 (d, J = 12.4 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ: 20.9, 51.4,
92.2, 101.9, 118.1, 126.5, 130.1, 130.7, 131.5, 134.8, 150.4, 159.4, 167.5. HRMS calcd for
C13H12Br2O3Na: 396.9045 [M+Na]+, found: 396.9041.
(E)-Methyl 3-(4-chloro-2-(2,2-dibromovinyl)phenoxy)acrylate (1k)
White liquid (669.6 mg, 85%). 1H NMR (400 MHz, CDCl3) δ: 3.74 (s, 3H), 5.54 (d, J = 12.4 Hz, 1H),
6.99 (d, J = 8.8 Hz, 1H), 7.35 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 7.41 (s, 1H), 7.68 (d, J = 12.4 Hz,
1H), 7.73 (d, J = 2.0 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ: 51.5, 93.9, 103.0, 119.3, 128.2, 129.6,
130.0, 130.1, 130.4, 151.0, 158.4, 167.1. HRMS calcd for C12H9Br2ClO3Na: 416.8499 [M+Na]+,
found: 416.8494.
(E)-tert-Butyl 3-(2-(2,2-dibromovinyl)phenoxy)acrylate (1l)
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Colorless liquid (635.1 mg, 79%). 1H NMR (400 MHz, CDCl3) δ: 1.49 (s, 9H), 5.45 (d, J = 12.4 Hz,
1H), 7.05 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.21 (td, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 7.37 (td, J1 = 8.0
Hz, J2 = 1.6 Hz, 1H), 7.48 (s, 1H), 7.63 (d, J = 12.4 Hz, 1H), 7.74 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H).
13C NMR (150 MHz, CDCl3) δ: 28.3, 80.4, 92.3, 104.6, 118.1, 124.8, 126.8, 129.8, 130.2, 131.5,
152.7, 158.0, 166.3. HRMS calcd for C15H16Br2O3Na: 424.9358 [M+Na]+, found: 424.9350.
(E)-4-(2-(2,2-Dibromovinyl)phenoxy)but-3-en-2-one (4a)
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Colorless liquid (650.5 mg, 94%). 1H NMR (400 MHz, CDCl3) δ: 2.20 (s, 3H), 5.84 (dd, J1 = 12.8 Hz,
J2 = 2.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 7.18-7.22 (m, 1H), 7.34-7.38 (m, 1H), 7.44 (s, 1H),
7.62-7.71 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 28.5, 92.6, 112.1, 118.2, 125.2, 126.9, 129.9,
130.3, 131.4, 152.5, 158.7, 197.0. HRMS calcd for C12H10Br2O2Na: 366.8940 [M+Na]+, found:
366.8940.
(E)-4-(2-(2,2-Dibromovinyl)-4-methylphenoxy)but-3-en-2-one (4b)
White solid (691.2 mg, 96%), mp: 63-64 °C. 1H NMR (400 MHz, CDCl3) δ: 2.22 (s, 3H), 2.37 (s, 3H),
5.82 (d, J = 12.4 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 7.18 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.42 (s,
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1H), 7.51 (d, J = 1.6 Hz, 1H), 7.64 (d, J = 12.4 Hz, 1H). C NMR (150 MHz, CDCl3) δ: 20.9, 28.5,
92.4, 111.6, 118.3, 126.7, 130.2, 130.8, 131.6, 135.1, 150.4, 159.3, 197.2. HRMS calcd for
C13H12Br2O2Na: 380.9096 [M+Na]+, found: 380.9094.
(E)-4-(4-Chloro-2-(2,2-dibromovinyl)phenoxy)but-3-en-2-one (4c)
Yellow solid (646.8 mg, 85%), mp: 94-95 °C. 1H NMR (400 MHz, CDCl3) δ: 2.24 (s, 3H), 5.88 (d, J
= 12.4 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 7.36 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz 1H), 7.40 (s, 1H), 7.61 (d,
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J = 12.4 Hz, 1H), 7.72 (d, J = 2.4 Hz, 1H). C NMR (150 MHz, CDCl3) δ: 28.7, 94.1, 112.3, 119.6,
128.4, 129.7, 130.07, 130.15, 130.6, 151.0, 158.1, 196.9. HRMS calcd for C12H9Br2ClO2Na: 400.8550
[M+Na]+, found: 400.8554.
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(E)-4-(2-(2,2-Dibromovinyl)-4-methoxyphenoxy)but-3-en-2-one (4d)
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Colorless liquid (526.5 mg, 70%). 1H NMR (400 MHz, CDCl3) δ: 2.22 (s, 3H), 3.82 (s, 3H), 5.76 (d, J
= 12.4 Hz, 1H), 6.91-6.92 (m, 1H), 6.96-6.98 (m, 1H), 7.27 (d, J = 2.8 Hz, 1H), 7.42 (s, 1H), 7.63 (d,
J = 12.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ: 28.4, 55.8, 92.8, 111.3, 114.6, 115.6, 119.9, 127.9,
131.2, 146.2, 156.7, 160.0, 197.2. HRMS calcd for C13H12Br2O3Na: 396.9045 [M+Na]+, found:
396.9038.
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(E)-4-(2-(2,2-Dibromovinyl)-5-methoxyphenoxy)but-3-en-2-one (4e)
White solid (646.7 mg, 86%), mp: 86-87 oC. 1H NMR (600 MHz, CDCl3) δ: 2.24 (s, 3H), 3.83 (s, 3H),
5.89 (d, J = 12.6 Hz, 1H), 6.57 (s, 1H), 6.77 (d, J = 8.4 Hz, 1H), 7.39 (s, 1H), 7.64 (d, J = 12.6 Hz,
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1H), 7.71 (d, J = 9.0 Hz, 1H). C NMR (150 MHz, CDCl3) δ: 28.5, 55.7, 90.7, 104.5, 110.5, 112.2,
119.2, 130.5, 130.9, 153.6, 158.5, 161.1, 197.1. HRMS calcd for C13H12Br2O3Na: 396.9045 [M+Na]+,
found: 396.9045.
(E)-4-(2-(2,2-Dibromovinyl)phenoxy)-1-phenylbut-3-en-2-one (4f)
Colorless liquid. (726.0 mg, 86%). 1H NMR (600 MHz, CDCl3) δ: 3.80 (s, 2H), 5.97 (d, J = 12.0 Hz,
1H), 7.00 (d, J = 8.4 Hz, 1H), 7.23-7.27 (m, 3H), 7.29-7.31 (m, 1H), 7.36-7.40 (m, 3H), 7.45 (s, 1H),
7.73-7.75 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 49.5, 92.6. 110.2, 117.9, 125.1, 126.7, 127.1,
128.8, 129.5, 129.9, 130.3, 131.4, 134.4, 152.7, 158.6, 196.9. HRMS calcd for C18H14Br2O2Na:
442.9253 [M+Na]+, found: 442.9249.
(E)-1-Cyclohexyl-3-(2-(2,2-dibromovinyl)phenoxy)prop-2-en-1-one (4g)
Yellow liquid (662.6 mg, 80%). 1H NMR (400 MHz, CDCl3) δ: 1.26-1.45 (m, 5H), 1.68-1.71 (m, 1H),
1.80-1.88 (m, 4H), 2.37-2.44 (m, 1H), 5.99 (d, J = 12.0 Hz, 1H), 7.06 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz,
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1H), 7.24 (td, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.38-7.42 (m, 1H), 7.49 (s, 1H), 7.70-7.75 (m, 2H). C
NMR (150 MHz, CDCl3) δ: 25.7, 25.9. 28.6. 50.3. 92.4. 109.5. 118.0. 124.9. 126.8. 129.8. 130.3.
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131.5. 152.8, 157.7, 202.8. HRMS calcd for C17H18Br2O2Na: 434.9566 [M+Na]+, found: 434.9549.
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White solid (767.2 mg, 94%), mp: 62-63 °C. 1H NMR (400 MHz, CDCl3) δ: 6.72 (d, J = 11.6 Hz, 1H),
7.12 (d, J = 8.4 Hz, 1H), 7.23-7.26 (m, 1H), 7.39-7.56 (m, 5H), 7.76 (d, J = 8.0 Hz, 1H), 7.90-7.93 (m,
3H). 13C NMR (100 MHz, CDCl3) δ: 92.6, 107.4, 117.8, 125.1, 126.7, 128.2, 128.6, 129.9, 130.4,
131.5, 132.8, 138.1, 152.9, 159.7, 190.2. HRMS calcd for C17H12Br2O2Na: 428.9096 [M+Na]+, found:
428.9096.
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(E)-1-(4-Chlorophenyl)-3-(2-(2,2-dibromovinyl)phenoxy)prop-2-en-1-one (4i)
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White solid (391.5 mg, 89%), mp: 107-108 °C. H NMR (600 MHz, CDCl3) δ: 6.66 (d, J = 11.4 Hz,
1H), 7.09 (d, J = 7.8 Hz, 1H), 7.24 (t, J = 7.8 Hz, 1H), 7.39-7.43 (m, 3H), 7.52 (m, 1H), 7.74 (d, J =
13
7.8 Hz, 1H), 7.85 (d, J = 7.8 Hz, 2H), 7.91 (d, J = 12.0, 1H). C NMR (150 MHz, CDCl3) δ: 92.7,
106.9, 117.8, 125.2, 126.7, 128.9, 129.6, 129.9, 130.4, 131.4, 136.4, 139.2, 152.8, 160.0, 188.7.
HRMS calcd for C17H11Br2ClO2Na: 462.8707 [M+Na]+, found: 462.8700.
3. Typical procedure for the synthesis of 3a and spectroscopic data of 3a-3y
To a reaction tube equipped with a stir bar were added ethyl 3-(2-(2,2-dibromovinyl)phenoxy)
acrylate (1a, 112.8 mg, 0.3 mmol), phenylboronic acid (2a, 54.9 mg, 0.45 mmol), PPh3 (47.2 mg, 0.18
mmol), K2CO3 (165.9 mg, 1.2 mmol) and dioxane (3 mL). It was stirred at room temperature for 3
min. Then, Pd(OAc)2 (6.7 mg, 0.03 mmol) was added, and the resulting mixture was stirred at 80 °C
(oil bath) for 24 h. Upon completion, it was diluted with ethyl acetate (20 mL), and washed with water
and brine. The organic layer was dried over anhydrous Na2SO4, and evaporated under reduced
pressure. The residue was purified by column chromatography on silica gel with petroleum ether/ethyl
acetate (30:1) as the eluent to give 3a in a yield of 70%. 3b-3y were obtained in a similar manner.
(Z)-Ethyl 2-(3-phenyl-2H-chromen-2-ylidene)acetate (3a)
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Yellow solid (61.4 mg, 70%), mp: 98-99 °C. 1H NMR (400 MHz, CDCl3) δ: 1.25 (t, J = 7.2 Hz, 3H),
4.15 (q, J = 7.2 Hz, 2H), 5.07 (s, 1H), 6.77 (s, 1H), 7.04 (t, J = 7.2 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H),
7.25-7.30 (m, 2H), 7.32-7.40 (m, 5H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 59.4, 94.2, 116.1, 120.4,
123.8, 127.1, 128.6, 128.7, 128.8, 130.4, 130.6, 133.5, 136.9, 152.3, 160.3, 165.7. HRMS calcd for
C19H16O3Na: 315.0992 [M+Na]+, found: 315.0987.
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(Z)-Ethyl 2-(3-(p-tolyl)-2H-chromen-2-ylidene)acetate (3b)
Yellow solid (66.2 mg, 72%), mp: 78-79 °C. 1H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 7.2 Hz, 3H),
2.39 (s, 3H), 4.16 (q, J = 7.2 Hz, 2H), 5.09 (s, 1H), 6.82 (s, 1H), 7.09 (t, J = 7.2 Hz, 1H), 7.20-7.30 (m,
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6H), 7.34 (t, J = 8.0 Hz, 1H). C NMR (100 MHz, CDCl3) δ: 14.5, 21.3, 59.4, 94.0, 116.0, 120.4,
123.7, 127.0, 128.6, 129.5, 130.2, 130.5, 133.5, 134.0, 138.5, 152.2, 160.5, 165.8. HRMS calcd for
C20H18O3Na: 329.1148 [M+Na]+, found: 329.1140.
(Z)-Ethyl 2-(3-(4-ethylphenyl)-2H-chromen-2-ylidene)acetate (3c)
Yellow liquid (72.1 mg, 75%). 1H NMR (600 MHz, CDCl3) δ: 1.191 (t, J = 7.2 Hz, 3H), 1.194 (t, J =
7.8 Hz, 3H), 2.61 (q, J = 7.8 Hz, 2H), 4.09 (q, J = 7.2 Hz, 2H), 5.02 (s, 1H), 6.74 (s, 1H), 7.01 (td, J1
= 7.8 Hz, J2 = 1.2 Hz, 1H), 7.12 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.21 (d, J
= 7.8 Hz, 3H), 7.24-7.27 (m, 1H). 13C NMR (150 MHz, CDCl3) δ: 14.5, 15.5, 28.7, 59.4, 93.9, 116.1,
120.5, 123.8, 127.1, 128.3, 128.7, 130.3, 130.5, 133.5, 134.2, 144.8, 152.2, 160.6, 165.9. HRMS calcd
for C21H20O3Na: 343.1305 [M+Na]+, found: 343.1298.
(Z)-Ethyl 2-(3-([1,1'-biphenyl]-4-yl)-2H-chromen-2-ylidene)acetate (3d)
Yellow solid (65.2 mg, 59%), mp: 152-153 °C. 1H NMR (600 MHz, CDCl3) δ: 1.31 (t, J = 7.2 Hz, 3H),
4.21 (q, J = 7.2 Hz, 2H), 5.17 (s, 1H), 6.92 (s, 1H), 7.13-7.16 (m, 1H), 7.27 (dd, J1 = 7.8 Hz, J2 = 1.8
Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.38-7.42 (m, 2H), 7.48-7.51 (m, 4H), 7.64-7.69 (m, 4H). 13C NMR
(150 MHz, CDCl3) δ: 14.5, 59.5, 94.1, 116.1, 120.4, 123.8, 127.1, 127.6, 127.7, 128.9, 129.2, 130.5,
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130.7, 133.2, 135.8, 140.4, 141.6, 152.3, 160.3, 165.8. HRMS calcd for C25H20O3Na: 391.1305
[M+Na]+, found: 391.1294.
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(Z)-Ethyl 2-(3-(4-fluorophenyl)-2H-chromen-2-ylidene)acetate (3e)
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Yellow solid (55.9 mg, 60%), mp: 119-120 °C. 1H NMR (400 MHz, CDCl3) δ: 1.29 (t, J = 7.2 Hz, 3H),
4.19 (q, J = 7.2 Hz, 2H), 5.01 (s, 1H), 6.84 (s, 1H), 7.10-7.15 (m, 3H), 7.23 (dd, J1 = 7.6 Hz, J2 = 1.6
Hz, 1H), 7.29-7.31 (m, 1H), 7.35-7.39 (m, 3H). 13C NMR (150 MHz, CDCl3) δ: 14.4, 59.4, 94.1,
115.8, 116.0 (d, 3JC-F = 16.5 Hz), 120.2, 123.8, 127.1, 130.6, 130.67, 130.71 (d, 2JC-F = 26.3 Hz), 132.4,
132.8 (d, 4JC-F = 3.2 Hz), 152.2, 160.2, 162.8 (d, 1JC-F = 247.2 Hz), 165.6. 19F NMR (376 MHz, CDCl3)
δ: -112.6. HRMS calcd for C19H15FO3Na: 333.0897 [M+Na]+, found: 333.0890.
(Z)-Ethyl 2-(3-(4-chlorophenyl)-2H-chromen-2-ylidene)acetate (3f)
Yellow solid (58.8 mg, 60%), mp: 116-117 °C. 1H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 7.2 Hz, 3H),
4.17 (q, J = 7.2 Hz, 2H), 4.99 (s, 1H), 6.83 (s, 1H), 7.09-7.13 (m, 1H), 7.22 (d, J = 7.6 Hz, 1H),
7.26-7.36 (m, 4H), 7.38-7.42 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 14.4, 59.5, 94.2, 116.1, 120.1,
123.9, 127.2, 129.1, 130.2, 130.7, 130.9, 132.3, 134.6, 135.3, 152.3, 159.9, 165.5. HRMS calcd for
C19H15ClO3Na: 349.0602 [M+Na]+, found: 349.0593 .
(Z)-Ethyl 2-(3-(4-nitrophenyl)-2H-chromen-2-ylidene)acetate (3g)
Yellow solid (46.6 mg, 46%), mp: 192-193 °C. 1H NMR (600 MHz, CDCl3) δ: 1.29 (t, J = 7.2 Hz, 3H),
4.19 (q, J = 7.2 Hz, 2H), 4.92 (s, 1H), 6.92 (s, 1H), 7.16 (td, J1 = 7.8 Hz, J2 = 0.6 Hz, 1H), 7.27-7.28
(m, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.41-7.44 (m, 1H), 7.61 (d, J = 9.0 Hz, 2H), 8.32 (d, J = 8.4 Hz,
2H). 13C NMR (150 MHz, CDCl3) δ: 14.4, 59.6, 94.5, 116.3, 119.7, 124.1, 124.2, 127.5, 129.9, 131.3,
131.5, 131.6, 143.5, 147.9, 152.4, 159.1, 165.2. HRMS calcd for C19H15O5NNa: 360.0842 [M+Na]+,
found: 360.0842 .
(Z)-Ethyl 2-(3-(4-methoxyphenyl)-2H-chromen-2-ylidene)acetate (3h)
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Yellow solid (72.5 mg, 75%), mp: 109-110 °C. 1H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 7.2 Hz, 3H),
3.84 (s, 3H), 4.16 (q, J = 7.2 Hz, 2H), 5.09 (s, 1H), 6.80 (s, 1H), 6.94 (d, J = 8.0 Hz, 2H), 7.08 (t, J =
7.2 Hz, 1H), 7.20 (d, J = 7.2 Hz, 1H), 7.27-7.35 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 55.3,
59.3, 94.0, 114.2, 116.0, 120.5, 123.7, 127.0, 129.2, 129.96, 130.04, 130.4, 133.2, 152.2, 159.8, 160.6,
165.7. HRMS calcd for C20H18O4Na: 345.1097 [M+Na]+, found: 345.1093.
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(Z)-Ethyl 2-(3-(m-tolyl)-2H-chromen-2-ylidene)acetate (3i)
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Yellow liquid (64.3 mg, 70%). H NMR (600 MHz, CDCl3) δ: 1.30 (t, J = 7.2 Hz, 3H), 2.41 (s, 3H),
4.19 (q, J = 7.2 Hz, 2H), 5.09 (s, 1H), 6.84 (s, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.18-7.19 (m, 2H), 7.23 (d,
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J = 6.6 Hz, 2H), 7.31-7.38 (m, 3H). C NMR (150 MHz, CDCl3) δ: 14.5, 21.5, 59.4, 94.1, 116.1,
120.4, 123.8, 125.8, 127.1, 128.7, 129.3, 130.3, 130.6, 133.6, 136.8, 138.6, 152.2, 160.4, 165.8.
HRMS calcd for C20H18O3Na: 329.1148 [M+Na]+, found: 329.1140.
(Z)-Ethyl 2-(3-(3-fluorophenyl)-2H-chromen-2-ylidene)acetate (3j)
White solid (55.9 mg, 60%), mp: 120-121 °C. 1H NMR (400 MHz, CDCl3) δ: 1.28 (t, J = 7.2 Hz, 3H),
4.17 (q, J = 7.2 Hz, 2H), 5.02 (s, 1H), 6.84 (s, 1H), 7.08-7.12 (m, 3H), 7.16 (d, J = 7.6 Hz, 1H), 7.22
(d, J = 7.6 Hz, 1H), 7.28 (d, J = 8.8 Hz, 1H), 7.34-7.40 (m, 2H). 13C NMR (100 MHz, CDCl3) δ: 14.4,
59.5, 94.2, 115.6 (d, 2JC-F = 20.3 Hz), 115.9 (d, 2JC-F = 21.9 Hz), 116.1, 120.1, 123.9, 124.5 (d, 4JC-F
=
2.9 Hz), 127.2, 130.5 (d, 3JC-F = 8.0 Hz), 130.8, 131.0, 132.2 (d, 4JC-F = 2.2 Hz), 138.9 (d, 3JC-F = 7.3
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Hz), 152.3, 159.7, 162.8 (d, JC-F = 245.8 Hz), 165.5. 19F NMR (376 MHz, CDCl3) δ: -112.1. HRMS
calcd for C19H15O3FNa: 333.0897 [M+H]+, found: 333.0887.
(Z)-Ethyl 2-(3-(3-chlorophenyl)-2H-chromen-2-ylidene)acetate (3k)
Yellow solid (54.9 mg, 56%), mp: 109-110 °C. 1H NMR (400 MHz, CDCl3) δ: 1.28 (t, J = 7.2 Hz, 3H),
4.17 (q, J = 7.2 Hz, 2H), 4.98 (s, 1H), 6.84 (s, 1H), 7.11 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 7.6 Hz, 1H),
7.26-7.30 (m, 2H), 7.37-7.39 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 59.5, 94.3, 116.1, 120.0,
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123.9, 127.0, 127.2, 128.8, 128.9, 130.1, 130.9, 131.0, 132.1, 134.7, 138.6, 152.3, 159.7, 165.5.
HRMS calcd for C19H15ClO3Na: 349.0602 [M+Na]+, found: 349.0593.
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(Z)-Ethyl 2-(3-(o-tolyl)-2H-chromen-2-ylidene)acetate (3l)
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Yellow solid (40.4 mg, 44%), mp: 100-101 °C. 1H NMR (600 MHz, CDCl3) δ: 1.28 (t, J = 7.2 Hz, 3H),
2.29 (s, 3H), 4.16-4.19 (m, 2H), 4.69 (s, 1H), 6.82 (s, 1H), 7.13-7.18 (m, 2H), 7.23-7.25 (m, 1H), 7.28
(t, J = 7.8 Hz, 2H), 7.32-7.35 (m, 2H), 7.39 (t, J = 7.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ: 14.4,
19.5, 59.4, 93.6, 116.2, 120.2, 123.8, 126.3, 127.1, 128.7, 129.6, 130.5, 130.67, 130.70, 133.2, 136.0,
136.5, 152.3, 160.0, 165.8. HRMS calcd for C20H18O3Na: 329.1148 [M+Na]+, found: 329.1137.
(Z)-Ethyl 2-(3-(2-chlorophenyl)-2H-chromen-2-ylidene)acetate (3m)
Yellow solid (44.1 mg, 45%), mp: 102-103 °C. 1H NMR (400 MHz, CDCl3) δ: 1.27 (t, J = 7.2 Hz, 3H),
4.16 (q, J = 7.2 Hz, 2H), 4.65 (s, 1H), 6.85 (s, 1H), 7.12 (t, J = 7.2 Hz, 1H), 7.23 (d, J = 7.2 Hz, 1H),
7.26-7.38 (m, 5H), 7.47-7.49 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 59.4, 93.7, 116.2, 119.9,
123.8, 127.2, 127.3, 130.0, 130.1, 130.9, 131.0, 131.2, 131.7, 133.7, 135.3, 152.4, 159.2, 165.6.
HRMS calcd for C19H15ClO3Na: 349.0602 [M+Na]+, found: 349.0593.
(Z)-Ethyl 2-(3-(thiophen-2-yl)-2H-chromen-2-ylidene)acetate (3n)
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Yellow liquid (34.0 mg, 38%). H NMR (400 MHz, CDCl3) δ: 1.29 (t, J = 7.2 Hz, 3H), 4.19 (q, J =
7.2 Hz, 2H), 5.49 (s, 1H), 6.99 (s, 1H), 7.08-7.12 (m, 2H), 7.21-7.23 (m, 2H), 7.26-7.28 (m, 1H),
7.34-7.37 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 14.4, 59.5, 94.0, 116.1, 120.0, 123.8, 126.2, 126.3,
127.2, 127.5, 127.6, 131.0, 131.5, 137.5, 152.2, 159.5, 165.7. HRMS calcd for C17H14SO3Na:
321.0556 [M+Na]+, found: 321.0546.
(Z)-Ethyl 2-(6-methyl-3-phenyl-2H-chromen-2-ylidene)acetate (3o)
Yellow solid (62.5 mg, 68%), mp: 88-89 °C. 1H NMR (400 MHz, CDCl3) δ: 1.26 (t, J = 7.2 Hz, 3H),
2.33 (s, 3H), 4.16 (q, J = 7.2 Hz, 2H), 5.03 (s, 1H), 6.79 (s, 1H), 7.00 (s, 1H), 7.14-7.20 (m, 2H),
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7.35-7.43 (m, 5H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 20.7, 59.3, 93.7, 115.8, 120.1, 127.2, 128.5,
128.77, 128.81, 130.6, 131.5, 133.3, 133.4, 137.1, 150.4, 160.5, 165.8. HRMS calcd for C20H18O3Na:
329.1148 [M+Na]+, found: 329.1137.
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(Z)-Ethyl 2-(6-chloro-3-phenyl-2H-chromen-2-ylidene)acetate (3p)
Yellow solid (72.5 mg, 74%), mp: 134-135 °C. 1H NMR (400 MHz, CDCl3) δ: 1.26 (t, J = 7.2 Hz, 3H),
4.16 (q, J = 7.2 Hz, 2H), 5.08 (s, 1H), 6.74 (s, 1H), 7.19-7.22 (m, 2H), 7.26-7.30 (m, 1H), 7.35-7.44
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(m, 5H). C NMR (150 MHz, CDCl3) δ: 14.4, 59.5, 95.2, 117.4, 121.6, 126.4, 128.6, 128.7, 128.86,
128.91, 129.0, 130.3, 134.8, 136.4, 150.7, 159.6, 165.4. HRMS calcd for C19H15ClO3Na: 349.0602
[M+Na]+, found: 349.0598.
(Z)-Ethyl 2-(6-bromo-3-phenyl-2H-chromen-2-ylidene)acetate (3q)
Yellow solid (79.1 mg, 71%), mp: 136-137 °C. 1H NMR (400 MHz, CDCl3) δ: 1.26 (t, J = 7.2 Hz, 3H),
4.15 (q, J = 7.2 Hz, 2H), 5.08 (s, 1H), 6.73 (s, 1H), 7.15 (d, J = 8.8 Hz, 1H), 7.32-7.36 (m, 3H),
7.41-7.43 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 59.6, 95.2, 116.0, 117.8, 122.2, 128.6,
128.85, 128.88, 128.9, 129.4, 133.2, 134.7, 136.4, 151.1, 159.6, 165.4. HRMS calcd for
C19H15BrO3Na: 393.0097 [M+Na]+, found: 393.0097.
(Z)-Ethyl 2-(7-methoxy-3-phenyl-2H-chromen-2-ylidene)acetate (3r)
Yellow solid (58.0 mg, 60%), mp: 132-133 °C. 1H NMR (400 MHz, CDCl3) δ: 1.26 (t, J = 7.2 Hz, 3H),
3.84 (s, 3H), 4.16 (q, J = 7.2 Hz, 2H), 5.04 (s, 1H), 6.68 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 6.80 (s,
1H), 6.85-6.86 (m, 1H), 7.12 (d, J = 8.4 Hz, 1H), 7.35-7.43 (m, 5H). 13C NMR (100 MHz, CDCl3) δ:
14.5, 55.8, 59.2, 93.0, 100.5, 111.8, 113.8, 127.9, 128.4, 128.8, 128.9, 130.4, 130.6, 137.2, 153.7,
160.8, 162.0, 165.8. HRMS calcd for C20H18O4Na: 345.1097 [M+Na]+, found: 345.1088.
(Z)-Ethyl 2-(6,8-dibromo-3-phenyl-2H-chromen-2-ylidene)acetate (3s)
Yellow solid (90.5 mg, 67%), mp: 155-156 °C. 1H NMR (400 MHz, CDCl3) δ: 1.28 (t, J = 7.2 Hz, 3H),
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4.22 (q, J = 7.2 Hz, 2H), 5.16 (s, 1H), 6.68 (s, 1H), 7.27 (s, 1H), 7.34-7.36 (m, 2H), 7.43-7.44 (m, 3H),
7.68 (s, 1H). 13C NMR (150 MHz, CDCl3) δ: 14.5, 59.9, 97.2, 110.6, 115.9, 123.2, 128.0, 128.50,
128.54, 129.0, 129.1, 135.6, 135.9, 136.0, 148.5, 158.4, 165.1. HRMS calcd for C19H14Br2O3Na:
470.9202 [M+Na]+, found: 470.9205.
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(Z)-Ethyl 2-(6,8-di-tert-butyl-3-phenyl-2H-chromen-2-ylidene)acetate (3t)
Yellow solid (75.2 mg, 62%), mp: 126-127 °C. 1H NMR (400 MHz, CDCl3) δ: 1.24 (t, J = 7.2 Hz, 3H),
1.32 (s, 9H), 1.60 (s, 9H), 4.18 (q, J = 7.6 Hz, 2H), 4.99 (s, 1H), 6.83 (s, 1H), 7.05 (s, 1H), 7.36-7.42
(m, 6H). 13C NMR (100 MHz, CDCl3) δ: 14.5, 29.4, 31.4, 34.5, 35.1, 59.2, 93.5, 120.3, 122.2, 125.8,
128.3, 128.8, 128.9, 132.0, 132.6, 137.1, 137.5, 145.9, 148.8, 159.4, 165.4. HRMS calcd for
C27H32O3Na: 427.2244 [M+Na]+, found: 427.2241.
(Z)-Ethyl 2-(2-phenyl-3H-benzo[f]chromen-3-ylidene)acetate (3u)
Colorless liquid (46.2 mg, 45%). 1H NMR (400 MHz, CDCl3) δ: 1.29 (t, J = 7.2 Hz, 3H), 4.19 (q, J =
7.6 Hz, 2H), 5.12 (s, 1H), 7.43-7.51 (m, 7H), 7.55-7.59 (m, 2H), 7.83-7.87 (m, 2H), 8.08 (d, J = 8.4
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Hz, 1H). C NMR (100 MHz, CDCl3) δ: 14.5, 59.3, 92.9, 113.9, 116.9, 121.2, 125.3, 126.5, 127.6,
128.7, 128.8, 128.92, 128.95, 130.3, 131.4, 133.1, 137.2, 151.2, 160.6, 165.9. HRMS calcd for
C23H18O3Na: 365.1148 [M+Na]+, found: 365.1148.
(Z)-Methyl 2-(3-phenyl-2H-chromen-2-ylidene)acetate (3v)
Yellow liquid (62.6 mg, 75%). 1H NMR (400 MHz, CDCl3) δ: 3.61 (s, 3H), 4.99 (d, J = 0.4 Hz, 1H),
6.78 (s, 1H), 7.03 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.15 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 7.23 (d, J
= 8.0 Hz, 1H), 7.27-7.37 (m, 6H). 13C NMR (150 MHz, CDCl3) δ: 50.8, 93.7, 116.1, 120.4, 123.8,
127.1, 128.6, 128.7, 128.8, 130.5, 130.7, 133.5, 136.9, 152.2, 160.5, 166.0. HRMS calcd for
C18H14O3Na: 301.0835 [M+Na]+, found: 301.0826.
(Z)-Methyl 2-(6-methyl-3-phenyl-2H-chromen-2-ylidene)acetate (3w)
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Yellow solid (60.5 mg, 69%), mp: 107-108 °C. H NMR (400 MHz, CDCl3) δ: 2.31 (s, 3H), 3.67 (s,
3H), 5.04 (s, 1H), 6.78 (s, 1H), 6.99 (d, J = 1.2 Hz, 1H), 7.14 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 7.20
(d, J = 8.4 Hz, 1H), 7.33-7.43 (m, 5H). 13C NMR (150 MHz, CDCl3) δ: 20.7, 50.7, 93.2, 115.8, 120.1,
127.2, 128.6, 128.75, 128.82, 130.7, 131.5, 133.32, 133.33, 137.0, 150.3, 160.7, 166.1. HRMS calcd
for C19H16O3Na: 315.0992 [M+Na]+, found: 315.0980.
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(Z)-Methyl 2-(6-chloro-3-phenyl-2H-chromen-2-ylidene)acetate (3x)
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Yellow solid (66.6 mg, 71%), mp: 124-126 °C. H NMR (600 MHz, CDCl3) δ: 3.70 (s, 3H), 5.11 (s,
1H), 6.77 (s, 1H), 7.20 (s, 1H), 7.24 (d, J = 9.0 Hz, 1H), 7.28-7.31 (m, 1H), 7.37 (d, J = 7.2 Hz, 2H),
7.42-7.46 (m, 3H). 13C NMR (100 MHz, CDCl3) δ: 50.8, 94.7, 117.4, 121.6, 126.4, 128.6, 128.8,
128.89, 128.92, 129.1, 130.4, 134.7, 136.4, 150.6, 159.8, 165.8. HRMS calcd for C18H13ClO3Na:
335.0445 [M+Na]+, found: 335.0435.
(Z)-3,3-Dimethyl-1-(3-phenyl-2H-chromen-2-ylidene)butan-2-one (3y)
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Yellow liquid (68.5 mg, 75%). H NMR (400 MHz, CDCl3) δ: 1.49 (s, 9H), 4.97 (d, J = 0.8 Hz 1H),
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6.77 (s, 1H), 7.05-7.09 (m, 1H), 7.17-7.20 (m, 1H), 7.27-7.34 (m, 2H), 7.35-7.44 (m, 5H). C NMR
(150 MHz, CDCl3) δ: 28.4, 79.3, 96.3, 116.0, 120.4, 123.6, 127.0, 128.5, 128.78, 128.80, 130.0, 130.5,
133.7, 137.1, 152.3, 159.4, 165.3. HRMS calcd for C21H20O3Na: 343.1305 [M+Na]+, found: 343.1293.
4. Typical procedure for the synthesis of 5a and 6a and spectroscopic data of 5a-5l, 6a-6l
To a reaction tube equipped with a stir bar were added (E)-4-(2-(2,2-dibromovinyl)phenoxy)but-
3-en-2-one (4a, 103.8 mg, 0.3 mmol), phenylboronic acid (2a, 54.9mg, 0.45 mmol), PPh3 (47.2 mg,
0.18 mmol), K2CO3 (165.9 mg, 1.2 mmol) and dioxane (3 mL). It was stirred at room temperature for
3 min. Then, Pd(OAc)2 (6.7 mg, 0.03 mmol) was added, and the resulting mixture was stirred at 80 °C
(oil bath) for 24 h. Upon completion, it was diluted with ethyl acetate (20 mL), and washed with water
and brine. The organic layer was dried over anhydrous Na2SO4, and evaporated under reduced
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pressure. The residue was purified by column chromatography on silica gel with petroleum ether/ethyl
acetate (50:1) as the eluent to give 5a in 58% yield. Meanwhile, 6a was obtained in a yield of 15%.
5b-5l and 6b-6l were obtained in a similar manner.
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(Z)-1-(3-Phenyl-2H-chromen-2-ylidene)propan-2-one (5a)
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Yellow solid (45.6 mg, 58%), mp: 132-133 °C. H NMR (400 MHz, CDCl3) δ: 2.49 (s, 3H), 5.35 (s,
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1H), 6.87 (s, 1H), 7.13 (d, J = 7.6 Hz, 1H), 7.21-7.26 (m, 2H), 7.34-7.41 (m, 6H). C NMR (100
MHz, CDCl3) δ: 31.8, 106.2, 115.6, 120.6, 124.2, 127.4, 128.69, 128.72, 128.9, 130.7, 130.9, 133.9,
136.7, 152.1, 158.9, 196.9. HRMS calcd for C18H14O2Na: 285.0886 [M+Na]+, found: 285.0877.
1-(3-Phenyl-2H-chromen-2-yl)propan-2-one (6a)
Yellow liquid (11.9 mg, 15%). 1H NMR (400 MHz, CDCl3) δ: 2.10 (s, 3H), 2.29 (dd, J1 = 16.0 Hz, J2
= 2.4 Hz, 1H), 3.08 (dd, J1 = 16.0 Hz, J2 = 10.4 Hz, 1H), 5.87 (dd, J1 = 10.4 Hz, J2 = 2.4 Hz, 1H), 6.74
(s, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.87 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.04-7.11 (m, 2H), 7.23-7.27
(m, 1H), 7.30-7.34 (m, 2H), 7.42-7.44 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 31.1, 46.0, 72.7,
116.7, 120.0, 121.9, 122.5, 125.4, 127.1, 128.3, 129.0, 129.5, 134.5, 136.1, 150.8, 206.2. HRMS calcd
for C18H16O2Na: 287.1043 [M+Na]+, found: 287.1034.
(Z)-1-(3-(p-Tolyl)-2H-chromen-2-ylidene)propan-2-one (5b)
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Yellow solid (47.3 mg, 57%), mp: 107-108 °C. H NMR (400 MHz, CDCl3) δ: 2.38 (s, 3H), 2.48 (s,
3H), 5.38 (s, 1H), 6.84 (s, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.20-7.26 (m, 6H), 7.35 (t, J = 7.6 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ: 21.3, 31.8, 106.1, 115.5, 120.7, 124.1, 127.3, 128.6, 129.5, 130.61,
130.65, 133.8, 133.9, 138.6, 152.0, 159.1, 196.9. HRMS calcd for C19H16O2Na: 299.1043 [M+Na]+,
found: 299.1039.
1-(3-(p-Tolyl)-2H-chromen-2-yl)propan-2-one (6b)
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Yellow solid (11.7 mg, 14%), mp: 98-99 °C. H NMR (400 MHz, CDCl3) δ: 2.17 (s, 3H), 2.33-2.36
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(m, 4H), 3.13 (dd, J1 = 16.0 Hz, J2 = 10.4 Hz, 1H), 5.92 (dd, J1 = 10.0 Hz, J2 = 2.4 Hz, 1H), 6.78 (s,
1H), 6.85 (d, J = 8.0 Hz, 1H), 6.93 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.09-7.17 (m, 2H), 7.20 (d, J =
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8.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H). C NMR (150 MHz, CDCl3) δ: 21.2, 31.1, 46.0, 72.7, 116.6,
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119.1, 121.8, 122.6, 125.2, 126.9, 129.3, 129.7, 133.1, 134.5, 138.3, 150.7, 206.2. HRMS calcd for
C19H18O2Na: 301.1199 [M+Na]+, found: 301.1198.
(Z)-1-(6-Methyl-3-phenyl-2H-chromen-2-ylidene)propan-2-one (5c)
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Yellow solid (54.7 mg, 66%), mp: 109-111 °C. H NMR (400 MHz, CDCl3) δ: 2.37 (s, 3H), 2.50 (s,
3H), 5.36 (s, 1H), 6.86 (s, 1H), 7.07 (s, 1H), 7.15 (d, J = 8.4 Hz, 1H), 7.19-7.21 (m, 1H), 7.35-7.37 (m,
2H), 7.40-7.44 (m, 3H). 13C NMR (150 MHz, CDCl3) δ: 20.7, 31.7, 105.9, 115.3, 120.3, 127.5, 128.6,
128.75, 128.83, 131.0, 131.5, 133.7, 133.8, 136.9, 150.2, 159.2, 196.8. HRMS calcd for C19H16O2Na:
299.1043 [M+Na]+, found: 299.1039.
1-(6-Methyl-3-phenyl-2H-chromen-2-yl)propan-2-one (6c)
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Yellow liquid (13.4 mg, 16%). H NMR (400 MHz, CDCl3) δ: 2.09 (s, 3H), 2.22-2.28 (m, 4H), 3.07
(dd, J1 = 16.0 Hz, J2 = 10.4 Hz, 1H), 5.82 (dd, J1 = 10.4 Hz, J2 = 2.4 Hz, 1H), 6.68-6.70 (m, 2H),
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6.86-6.91 (m, 2H), 7.22-7.26 (m, 1H), 7.29-7.33 (m, 2H), 7.40-7.43 (m, 2H). C NMR (150 MHz,
CDCl3) δ: 20.6, 31.1, 45.8, 72.6, 116.4, 120.0, 122.3, 125.3, 127.5, 128.2, 129.0, 130.1, 131.1, 134.6,
136.2, 148.5, 206.3. HRMS calcd for C19H18O2Na: 301.1199 [M+Na]+, found: 301.1192.
(Z)-1-(6-Methyl-3-(p-tolyl)-2H-chromen-2-ylidene)propan-2-one (5d)
Yellow liquid (59.2 mg, 68%). 1H NMR (400 MHz, CDCl3) δ: 2.26 (s, 3H), 2.30 (s, 3H), 2.39 (s, 3H),
5.28 (s, 1H), 6.73 (s, 1H), 6.96 (s, 1H), 7.04 (d, J = 8.4 Hz, 1H), 7.07-7.09 (m, 1H), 7.11-7.18 (m, 4H).
13C NMR (150 MHz, CDCl3) δ: 20.7, 21.3, 31.7, 105.8, 115.2, 120.4, 127.4, 128.6, 129.5, 130.8,
131.4, 133.7, 133.8, 134.0, 138.5, 150.2, 159.3, 196.8. HRMS calcd for C20H18O2Na: 313.1199
[M+Na]+, found: 313.1189 .
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Yellow solid (14.0 mg, 16%), mp: 78-79 °C. H NMR (400 MHz, CDCl3) δ: 2.09 (s, 3H), 2.21-2.82
(m, 7H), 3.05 (dd, J1= 16.0 Hz, J2 = 10.0 Hz, 1H), 5.80 (dd, J1 = 10.4 Hz, J2 = 2.4 Hz, 1H), 6.67 (d, J
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= 7.6 Hz, 2H), 6.83-6.89 (m, 2H), 7.11 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H). C NMR (150
MHz, CDCl3) δ: 20.6, 21.2, 31.1, 45.8, 72.7, 116.4, 119.2, 122.4, 125.2, 127.4, 129.7, 129.8, 131.1,
133.2, 134.5, 138.3, 148.5, 206.3. HRMS calcd for C20H20O2Na: 315.1356 [M+Na]+, found:
315.1347.
(Z)-1-(3-(4-Chlorophenyl)-6-methyl-2H-chromen-2-ylidene)propan-2-one (5e)
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Yellow solid (60.6 mg, 65%), mp: 190-191 °C. H NMR (400 MHz, CDCl3) δ: 2.38 (s, 3H), 2.49 (s,
3H), 5.28 (s, 1H), 6.84 (s, 1H), 7.08 (d, J = 0.8 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 7.20-7.22 (m, 1H),
7.29-7.33 (m, 2H), 7.41-7.43 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 20.7, 31.7, 105.8, 115.3, 120.0,
127.5, 129.1, 130.2, 131.3, 131.8, 132.6, 133.9, 134.7, 135.3, 150.2, 158.8, 196.7. HRMS calcd for
C19H15ClO2Na: 333.0653 [M+Na]+, found: 333.0645.
1-(3-(4-Chlorophenyl)-6-methyl-2H-chromen-2-yl)propan-2-one (6e)
Yellow solid (13.1 mg, 14%), mp: 107-108 °C. 1H NMR (400 MHz, CDCl3) δ: 2.10 (s, 3H), 2.20-2.24
(m, 4H), 3.07 (dd, J1 = 16.0 Hz, J2 = 10.4 Hz, 1H), 5.77 (dd, J1 = 10.0 Hz, J2 = 2.4 Hz, 1H), 6.68-6.70
(m, 2H), 6.85-6.86 (m, 1H), 6.91 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.27-7.30 (m, 2H), 7.33-7.36 (m,
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2H). C NMR (150 MHz, CDCl3) δ: 20.6, 31.2, 45.6, 72.4, 116.5, 120.5, 122.0, 126.6, 127.6, 129.2,
130.4, 131.3, 133.3, 134.0, 134.6, 148.5, 206.1. HRMS calcd for C19H17ClO2Na: 335.0809 [M+Na]+,
found: 335.0791.
(Z)-1-(6-Chloro-3-phenyl-2H-chromen-2-ylidene)propan-2-one (5f)
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Yellow solid (50.7 mg, 57%), mp: 166-167 °C. H NMR (400 MHz, CDCl3) δ: 2.46 (s, 3H), 5.37 (s,
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NMR (100 MHz, CDCl3) δ: 31.8, 106.8, 116.9, 121.8, 126.6, 128.6, 129.0, 129.1, 129.4, 130.4, 135.2,
136.3, 150.5, 158.2, 196.6. HRMS calcd for C18H13ClO2Na: 319.0496 [M+Na]+, found: 319.0497.
1-(6-Chloro-3-phenyl-2H-chromen-2-yl)propan-2-one (6f)
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White solid (15.2 mg, 17%), mp: 78-79 °C. 1H NMR (400 MHz, CDCl3) δ: 2.07 (s, 3H), 2.28 (dd, J1 =
16.4 Hz, J2 = 2.4 Hz, 1H), 3.02 (dd, J1 = 16.4 Hz, J2 = 10.0 Hz, 1H), 5.86 (dd, J1 = 10.4 Hz, J2 = 2.4
Hz, 1H), 6.64 (s, 1H), 6.69-6.71 (m, 1H), 7.00-7.03 (m, 2H), 7.23-7.27 (m, 1H), 7.29-7.33 (m, 2H),
7.38-7.41 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 31.0, 45.9, 72.8, 117.9, 118.9, 123.9, 125.4, 126.5,
126.6, 128.7, 129.06, 129.09, 135.6, 136.0, 149.4, 205.6. HRMS calcd for C18H15ClO2Na: 321.0653
[M+Na]+, found: 321.0653.
(Z)-1-(6-Methoxy-3-phenyl-2H-chromen-2-ylidene)propan-2-one (5g)
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Yellow solid (48.2 mg, 55%), mp: 124-125 °C. H NMR (400 MHz, CDCl3) δ: 2.46 (s, 3H), 3.80 (s,
3H), 5.33 (s, 1H), 6.73 (d, J = 2.8 Hz, 1H), 6.83 (s, 1H), 6.93 (dd, J1 = 8.8 Hz, J2 = 3.2 Hz, 1H), 7.15
(d, J = 9.2 Hz, 1H), 7.32-7.36 (m, 2H), 7.37-7.43 (m, 3H). 13C NMR (150 MHz, CDCl3) δ: 31.7, 55.8,
105.7, 110.6, 116.4, 117.3, 121.0, 128.67, 128.72, 128.8, 130.9, 134.4, 136.8, 146.4, 155.9, 159.1,
196.6. HRMS calcd for C19H16O3Na: 315.0992 [M+Na]+, found: 315.0992.
1-(6-Methoxy-3-phenyl-2H-chromen-2-yl)propan-2-one (6g)
Yellow liquid (12.4 mg, 14%). 1H NMR (400 MHz, CDCl3) δ: 2.17 (s, 3H), 2.32 (dd, J1 = 16.0 Hz, J2
= 2.4 Hz, 1H), 3.14 (dd, J1 = 16.0 Hz, J2 = 10.4 Hz, 1H), 3.79 (s, 3H), 5.88 (dd, J1 = 10.0 Hz, J2 = 2.4
Hz, 1H), 6.69-6.81 (m, 4H), 7.32-7.34 (m, 1H), 7.37-7.41 (m, 2H), 7.48-7.51 (m, 2H). 13C NMR (100
MHz, CDCl3) δ: 31.1, 45.5, 55.8, 72.6, 111.9, 114.8, 117.2, 120.0, 123.1, 125.4, 128.4, 129.0, 135.5,
136.0, 144.5, 154.6, 206.2. HRMS calcd for C19H18O3Na: 317.1148 [M+Na]+, found: 317.1146.
(Z)-1-(7-Methoxy-3-phenyl-2H-chromen-2-ylidene)propan-2-one (5h)
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Yellow solid (46.5 mg, 53%), mp: 143-145 °C. H NMR (400 MHz, CDCl3) δ: 2.39 (s, 3H), 3.83 (s,
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