Synthesis of heterocyclic-fused benzopyrans via the Pd(II)-catalyzed C-H alkenylation/C-O cyclization of flavones and coumarins

Article abstract of DOI:10.1039/c4ob00180j

An efficient and practical method for effecting a tandem C-H alkenylation/C-O cyclization has been achieved via the C-H functionalization of flavone derivatives. The synthetic utility of the one-pot sequence was demonstrated by obtaining convenient access to coumarin-annelated benzopyrans. The reaction scope for the transformation was found to be fairly broad, affording good yields of a wide range of flavone- or coumarin-fused benzopyran motifs, which are privileged structures in many biologically active compounds. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00180j

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
Synthesis of heterocyclic-fused benzopyrans via
the Pd(II)-catalyzed C–H alkenylation/C–O
cyclization of flavones and coumarins†
Cite this: Org. Biomol. Chem., 2014,
12, 3413
Yechan Kim, Youngtaek Moon, Dahye Kang and Sungwoo Hong*
An efficient and practical method for effecting a tandem C–H alkenylation/C–O cyclization has been
achieved via the C–H functionalization of flavone derivatives. The synthetic utility of the one-pot
sequence was demonstrated by obtaining convenient access to coumarin-annelated benzopyrans. The
reaction scope for the transformation was found to be fairly broad, affording good yields of a wide range
of flavone- or coumarin-fused benzopyran motifs, which are privileged structures in many biologically
active compounds.
Received 23rd January 2014,
Accepted 24th March 2014
DOI: 10.1039/c4ob00180j
www.rsc.org/obc
Introduction
Substantial advances have been made toward enhancing the
efficiency of direct C–H bond activation in (hetero)arenes for
the C–C and C–heteroatom bond forming reactions of high
synthetic utility. C–H functionalization is advantageous in that
it enables the construction of complicated target molecules in
lesser reaction steps without pre-functionalizing the starting
materials. The direct transition metal-catalyzed functionali-
zation of C–H bonds in heterocycles is an extremely valuable
process in the research field of synthetic applications and
medicinal chemistry.1 Since the discovery of the direct olefina-
tion of arenes by Fujiwara et al.,2 impressive progress has been
made toward improving the efficiency of oxidative C–H alkenyl-
ation of heterocycles as promising alternatives to the conven-
tional approach.3,4
Flavone-fused benzopyran is an important structural motif
in many naturally occurring products and has been shown to
display a diverse range of biological activities (Fig. 1).5 In this
regard, the benzopyran motif continues to attract the attention
of synthetic chemists.6 In our ongoing studies toward the con-
struction of scaffold focused chemical libraries, we were inter-
ested in developing an efficient and practical method for
synthesizing a variety of heterocyclic-fused benzopyrans.
Driven by the need for a concise and general synthetic route
to flavone- or coumarin-fused benzopyrans, we were particu-
Fig. 1 Examples of biologically active compounds bearing a flavone-
fused benzopyran motif.
larly interested in exploring efficient approaches to these
derivatives through a one-pot process. From the viewpoint of
synthetic and environmental considerations, one-pot reactions
are advantageous for conducting multistep reactions in one
synthetic operation. These approaches ideally generate mole-
cular complexity from relatively simple starting materials in a
single reaction vessel, thereby minimizing undesired waste.7
Over the course of developing efficient flavone synthetic
methods, our group recently reported efficient and versatile
methods for effecting the direct C–O cyclization of the pheno-
lic hydroxyl group onto the C–H bond at the C3 position of
flavone derivatives, permitting the construction of a variety
of flavone-fused benzopyrans (Scheme 1a).8 This finding
prompted us to explore the feasibility of an expeditious syn-
thetic approach to flavone-fused benzopyrans through a one-
pot alkenylation/C–O cyclization sequence. C–H bond
functionalization that involves the use of the innate nucleophi-
licity of chromones or coumarins could provide a useful strat-
egy for cross-coupling reactions with high site selectivities.9
Department of Chemistry, Korea Advanced Institute of Science and Technology
(KAIST), Daejeon, 305-701, Korea. E-mail: hongorg@kaist.ac.kr;
Fax: (+82) 42-350-2810; Tel: (+82) 42-350-2811
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4ob00180j
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 3413–3422 | 3413

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 1 Optimization of the C–H alkenylation/C–O cyclization in a
flavone substratea
Additive
(0.2 equiv.) (h)
Time Yield
Entry Pd
Solvent
Base
(%)
1
2
3
4
5
6
7
8
Pd(OAc)2 MeCN
Pd(OAc)2 MeCN
Pd(OAc)2 MeCN
Pd(OAc)2 MeCN
Pd(OAc)2 1,4-Dioxane Cs2CO3
Pd(OAc)2 DME
Pd(OAc)2 t-BuOH
Pd(acac)2 t-BuOH
Pd(acac)2 t-BuOH
Pd(acac)2 t-BuOH
Pd(acac)2 t-BuOH
Pd(acac)2 t-BuOH
Na2CO3
Ag2CO3
Cs2CO3
CsOPiv
—
24
24
24
24
12
12
12
4
4
4
4
4
10%
12%
27%
26%
48%
54%
56%
63%
67%
65%
62%
74%
—
—
—
—
—
—
—
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3 Zn(OTf)2
Cs2CO3 Li(OTf)2
Cs2CO3 Al(OTf)3
Cs2CO3 Al2O3
Scheme 1 Proposed flavone-fused benzopyran synthesis by the C–H
alkenylation/C–O cyclization.
9
10
11
12
a Reactions were conducted with flavone, butyl acrylate (2 equiv.), Pd
catalyst (0.2 equiv.), Cu(OAc)2 (3 equiv.), and base (2 equiv.) in a
solvent at 120 °C. MeCN = acetonitrile, Piv = pivaloyl, DME =
dimethoxyethane, acac = acetoacetyl.
If the installed olefin contains an electron-withdrawing group,
the cyclization reaction might take place, generating the
desired product. In this context, we anticipated that the C3
alkenylated enolones generated in situ from a Pd(II)-catalyzed
alkenylation reaction could undergo C–O cyclization by
employing the phenolic hydroxyl group as a nucleophile to
afford flavonoids bearing benzopyrans in an atom-economical
approach (Scheme 1b). This strategy would present opportu-
nities for the construction of flavone-fused benzopyrans which
resemble the core structures of biologically active natural pro-
ducts (Fig. 1). Herein we report an efficient and practical C–H
alkenylation/C–O cyclization process that is broadly applicable
to the readily accessible flavone and coumarin systems10
and enables the construction of heterocyclic-annelated
benzopyrans.
tion oxidants (see the ESI† for additional data). Both the base
and the solvent were found to fundamentally influence
the efficiency of the reaction, in the presence of Cs2CO3 and
t-BuOH as the optimal base and solvent, respectively. Among
the palladium sources tested, Pd(acac)2 displayed the best cata-
lytic efficiency. In an effort to enhance the electrophilic charac-
ter of the α,β-unsaturated ketone system and optimize the
conjugate addition step, a series of Lewis acids was intensively
screened. When the reaction was subjected to treatment with
catalytic amounts of Al2O3 as a Lewis acid, an enhanced reac-
tivity was obtained. Under the optimized reaction conditions
(entry 12), the C–H alkenylation/C–O cyclization of 1 with
n-butyl acrylate (2) proceeded to provide the best isolated
yield, 74% (entry 12). Under the reaction conditions, only
trace amounts (<5%) of the flavone-annelated benzofuran
were observed from the direct intramolecular C–O
cyclization.
With the optimized reaction conditions as shown for entry
12 (Table 1), we set up a series of experiments to investigate
the substrate scope of both the alkene and the flavone sub-
strates for the one-pot reaction (Table 2). The catalytic syn-
thesis smoothly proceeded with substrates in the presence of a
variety of functional groups. For example, alkene substrates
were extended to a variety of alkenes conjugated with methyl
ester, tert-butyl, n-butyl, methyl ketone, phenyl ketone, amide,
or phosphonate groups to afford the desired products. The
substrate scope of the flavones was subsequently examined,
and a relatively broad range of functional groups (e.g., alkyl,
fluoro, chloro, and bromo) was found to be compatible with
the reaction conditions. Encouraged by the successful results
Results and discussion
At the outset, the feasibility of this strategy was tested by inves-
tigating a one-pot alkenylation/C–O cyclization of 2-(2-hydroxy-
phenyl)-4H-chromen-4-one (1) with n-butyl acrylate (2) as
model substrates; representative results of a catalyst screen for
this conversion are listed in Table 1. The oxidizing agent was
critical to the efficiency of this type of cross-coupling reaction
as it facilitated the re-oxidation of Pd(0) to Pd(II). We therefore
surveyed the capabilities of a variety of oxidizing agents,
including Cu(II), Ag(II), K2S2O8, 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ), MnO2, (2,2,6,6-tetramethyl-piperidin-
t
1-yl)oxy (TEMPO), and PhCO3 Bu (see the ESI† for additional
data). We were pleased to observe that benzopyran 3a was
obtained under a catalytic system comprising both Pd(OAc)2
and Cu(OAc)2 in acetonitrile, albeit in a 10% yield (entry 1).
Among the Cu species screened, Cu(OAc)2 was found to be the
most effective and economical oxidant for promoting the reac-
3414 | Org. Biomol. Chem., 2014, 12, 3413–3422
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 2 Scope of the C–H alkenylation/C–O cyclization of flavonesa
Table 2 (Contd.)
a Reactions were conducted with flavone (1 equiv.), alkene (2 equiv.),
Pd(acac)2 (0.2 equiv.), Cu(OAc)2 (3 equiv.), Cs2CO3 (2 equiv.), and Al2O3
(0.2 equiv.) in t-BuOH at 120 °C for 4 h. Yields are reported after
isolation and purification by flash silica gel chromatography.
in the sequential reactions, we further investigated the C–N
cyclization and were pleased to observe that the N-sulfonyl
group could be readily utilized, demonstrating that the process
was flexible with respect to the substrate type to afford the
corresponding cyclization product 3r in 62% yield.
A proposed mechanism describing the catalytic cycle is
illustrated in Fig. 2. The cyclization reaction appeared to follow
the initial C–H olefination event. Thus, the electrophilic palla-
dation by the Pd(II) species of the flavone derivative at the C3
position is favorable because the 3-position of the flavone is
electron-rich to afford the intermediate I. At this point, it
remains uncertain whether the phenolic hydroxyl group co-
ordinates as a ligand during the electrophilic palladation of
the flavone derivative. Subsequent olefin insertion into the
C3-palladated species I, followed by C–Pd β-hydride
elimination of an intermediate II would lead to the C3
alkenylated product III. Al2O3 is then proposed to coordinate
to the carbonyl oxygen and activate the electrophilicity of
the α,β-unsaturated ketone system of 2 and III to facilitate the
alkenylation/C–O cyclization, thereby furnishing the corres-
ponding cyclized product 3. Furthermore, the enhanced
activity observed with Al2O3 might be attributed to a pathway
where Al2O3 competes with Pd/Cu in chelating the chromone
substrate.8
The utility of the present reaction was broadened by con-
ducting a series of experiments designed to explore the poten-
tial applicability of the methodology to the coumarin scaffold
4 (Table 3). Based on the proposed mechanism, we envisaged
that the selective C–H functionalization/C–O cyclization reac-
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 3413–3422 | 3415

View Article Online
Paper
Organic & Biomolecular Chemistry
Table 3 Scope of the C–H alkenylation/C–O cyclization of
coumarins
Fig. 2 Proposed mechanistic pathways underlying the present
reactions.
tions of the 4-arylcoumarins would be possible because elec-
trophilic palladation of the coumarins at the C3 position was
favorable due to the nucleophilic 3-position.3b Indeed, the
sequential reactions of 4 were very facile under slightly altered
reaction conditions in which Cu(OAc)2·H2O was employed as
an oxidant in 1,4-dioxane, thus allowing for the construction
of coumarin-annelated benzopyrans in good yields. Unlike the
flavone derivatives, the C–O bond formation of coumarin
derivatives took place at a comparable reaction rate in the
absence of Al2O3. We next surveyed the substrate scope, and
alkene substrates conjugated with the methyl ester, tert-butyl,
n-butyl, methyl ketone, phenyl ketone, or amide groups all
smoothly reacted with 4-arylcoumarin 4 to afford the cou-
marin-fused benzopyrans 5. The scope of the coumarin sub-
strates was subsequently examined, and diverse functional
groups (e.g., methyl, phenyl, fluoro, chloro, methoxy, naphthyl,
and dimethylamino) on the 4-arylcoumarin were found to be
compatible with the reaction conditions. Moreover, the one-
pot process was carried out on the N-sulfonyl substrate leading
to the corresponding cyclization product 5o in a moderate
yield.
Conclusions
In summary, we have developed an efficient method for
effecting the tandem C–H alkenylation/C–O cyclization reac-
tions via the C–H functionalization of flavone derivatives. This
synthetic process provides a concise access to a variety of
flavone-fused benzopyrans (Table 2). The synthetic utility of
3416 | Org. Biomol. Chem., 2014, 12, 3413–3422
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
the one-pot sequence was further demonstrated by its ability reaction mixture was diluted with CH2Cl2 and the residue was
to provide convenient access to coumarin-annelated benzopyr- extracted with aqueous NH4Cl (3 × 30 mL). The organic layer
ans (Table 3). This methodology allowed the swift development was dried over MgSO4. After removal of the solvent, the residue
of a wide range of flavone- or coumarin-fused benzopyran was purified by flash chromatography on silica gel to give the
derivatives, which are privileged structures in many biologi- desired product.
cally active compounds. Ongoing studies seek to broaden the
Butyl
2-(7-oxo-6,7-dihydrochromeno[4,3-b]chromen-6-yl)-
scope of the methodology to include related heterocycles and acetate (3a). Compound 3a was prepared (16.9 mg, 74% yield)
other applications.
according to GP I from the flavone derivative (15.0 mg,
0.063 mmol). mp 98–100 °C. IR: v = 1728, 1642, 1633, 1606,
1416 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.20 (dd, J =
.
7.9, 1.7 Hz, 1H), 7.83 (dd, J = 7.8, 1.7 Hz, 1H), 7.69 (ddd, J =
8.7, 7.1, 1.7 Hz, 1H), 7.54 (dd, J = 8.5, 1.1 Hz, 1H), 7.46–7.35
(m, 2H), 7.07 (td, J = 7.6, 1.1 Hz, 1H), 6.94 (dd, J = 8.3, 1.1 Hz,
Experimental
General methods and materials
Unless stated otherwise, reactions were performed in flame- 1H), 6.17 (dd, J = 9.4, 3.6 Hz, 1H), 4.10 (t, J = 6.7 Hz, 2H), 2.86
dried glassware under a positive pressure of nitrogen using (dd, J = 15.1, 9.4 Hz, 1H), 2.78 (dd, J = 15.1, 3.6 Hz, 1H),
freshly distilled solvents. Analytical thin layer chromatography 1.63–1.53 (m, 2H), 1.41–1.30 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H).
(TLC) was performed on precoated silica gel 60 F254 plates and 13C NMR (100 MHz, chloroform-d) δ 174.4, 169.8, 155.6, 155.3,
visualization on TLC was achieved by UV light (254 and 155.0, 134.0, 133.7, 125.7, 125.3, 124.0, 123.6, 121.9, 118.0,
354 nm). Flash column chromatography was undertaken on 115.4, 112.3, 70.5, 64.7, 39.2, 30.6, 19.1, 13.7. HRMS (ESI+) m/z
1
silica gel (400–630 mesh). H NMR was recorded on 600 MHz, calcd for C22H20NaO5+ [M + Na]+: 387.1203, found: 387.1188.
400 MHz or 300 MHz and chemical shifts were quoted in parts
Methyl 2-(7-oxo-6,7-dihydrochromeno[4,3-b]chromen-6-yl)-
per million (ppm) referenced to the appropriate solvent peak acetate (3b). Compound 3b was prepared (11.9 mg, 59% yield)
or 0.0 ppm for tetramethylsilane. The following abbreviations according to GP I from the flavone derivative (15.0 mg,
were used to describe peak splitting patterns when appropri- 0.063 mmol). mp 187–189 °C. IR: v = 1737, 1728, 1642, 1604,
1
ate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, 1414 cm−1. H NMR (400 MHz, chloroform-d) δ 8.20 (ddd, J =
m = multiplet, dd = doublet of doublet. Coupling constants, 8.0, 1.7, 0.5 Hz, 1H), 7.83 (dd, J = 7.8, 1.6 Hz, 1H), 7.68 (ddd,
J, were reported in hertz unit (Hz). 13C NMR was recorded on J = 8.7, 7.1, 1.7 Hz, 1H), 7.54 (ddd, J = 8.4, 1.1, 0.5 Hz, 1H),
100 MHz or 150 MHz and was fully decoupled by broad band 7.43–7.37 (m, 2H), 7.08 (td, J = 7.6, 1.1 Hz, 1H), 6.95 (dd, J =
proton decoupling. Chemical shifts were reported in ppm 8.3, 1.0 Hz, 1H), 6.17 (dd, J = 9.4, 3.6 Hz, 1H), 3.70 (s, 3H), 2.87
referenced to the center line of a triplet at 77.0 ppm of chloro- (dd, J = 15.2, 9.4 Hz, 1H), 2.79 (dd, J = 15.2, 3.6 Hz, 1H).
form-d. Mass spectral data were obtained using the EI method. 13C NMR (100 MHz, chloroform-d) δ 174.4, 170.1, 155.6, 155.2,
Commercial grade reagents and solvents were used without 155.0, 134.1, 133.8, 125.7, 125.3, 124.0, 123.6, 122.0, 118.0,
further purification except as indicated below. Dichloro- 118.0, 115.4, 112.2, 70.4, 51.9, 38.9. HRMS (ESI+) m/z calcd for
methane was distilled from calcium hydride. THF was distilled C19H14NaO5+ [M + Na]+: 345.0733, found: 345.0713.
from sodium.
tert-Butyl 2-(7-oxo-6,7-dihydrochromeno[4,3-b]chromen-6-yl)-
General procedure (GP I) for flavone C–H alkenylation/ C–O acetate (3c). Compound 3c was prepared (14.5 mg, 63% yield)
cyclization. The flavone derivative (0.063 mmol or according to GP I from the flavone derivative (15.0 mg,
0.095 mmol), Pd(acac)2 (0.2 equiv.), Cu(OAc)2 (3 equiv.), 0.063 mmol). mp 144–146 °C. IR: v = 1721, 1467, 1416,
1
Cs2CO3 (2 equiv.), and Al2O3 (0.2 equiv.) were combined in 1153 cm−1. H NMR (400 MHz, chloroform-d) δ 8.20 (ddd, J =
t-BuOH (0.63 mL) in a cap test tube. The alkene (2 equiv.) was 8.0, 1.7, 0.5 Hz, 1H), 7.81 (dd, J = 7.8, 1.6 Hz, 1H), 7.67 (ddd,
added and the reaction mixture was heated to 120 °C for 4 h. J = 8.7, 7.2, 1.7 Hz, 1H), 7.53 (ddd, J = 8.5, 1.1, 0.5 Hz, 1H),
The reaction mixture was monitored by TLC using ethyl 7.42–7.36 (m, 2H), 7.06 (td, J = 7.6, 1.1 Hz, 1H), 6.93 (dd, J =
acetate–hexanes (1 : 3) as the mobile phase. The reaction 8.2, 1.0 Hz, 1H), 6.12 (dd, J = 8.9, 4.1 Hz, 1H), 2.78–2.67 (m,
mixture was diluted with CH2Cl2 and the residue was extracted 2H), 1.42 (s, 9H). 13C NMR (100 MHz, chloroform-d) δ 174.4,
with aqueous NH4Cl (3 × 30 mL). The organic layer was dried 168.9, 155.6, 155.4, 155.0, 134.0, 133.7, 125.7, 125.2, 124.0,
over MgSO4. After removal of the solvent, the residue was puri- 123.6, 121.8, 118.0, 118.0, 115.5, 112.4, 80.9, 70.7, 40.4, 28.0.
fied by flash chromatography on silica gel to give the desired HRMS (ESI+) m/z calcd for C22H20NaO5 [M + Na]+: 387.1203,
+
product.
General procedure (GP II) for coumarin C–H alkenylation/
found: 387.1178.
6-(2-Oxo-2-phenylethyl)chromeno[4,3-b]chromen-7(6H)-one
C–O cyclization. The coumarin derivative (0.063 mmol), (3d). Compound 3d was prepared (26.4 mg, 77% yield) accord-
Pd(acac)2 (0.2 equiv.), Cu(OAc)2·H2O (3 equiv.), and Cs2CO3 ing to GP I from the flavone derivative (22.5 mg, 0.095 mmol).
(2 equiv.) were combined in a Schlenk tube under a N2 atmos- mp 180–182 °C. IR: v = 1677, 1644, 1631, 1606, 1414 cm−1
.
phere (balloon). The alkene (2 equiv.) and 1,4-dioxane 1H NMR (400 MHz, chloroform-d) δ 8.21 (dd, J = 8.0, 1.7 Hz,
(0.63 mL) were added and the reaction mixture was heated to 1H), 8.06–8.01 (m, 2H), 7.82 (dd, J = 7.8, 1.6 Hz, 1H), 7.71–7.66
120 °C for 8 h. The reaction mixture was monitored by TLC (m, 1H), 7.54 (td, J = 6.9, 6.3, 1.0 Hz, 2H), 7.48–7.39 (m, 3H),
using ethyl acetate–hexanes (1 : 3) as the mobile phase. The 7.38–7.33 (m, 1H), 7.06 (td, J = 7.5, 0.9 Hz, 1H), 6.87 (dd, J =
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 3413–3422 | 3417

View Article Online
Paper
Organic & Biomolecular Chemistry
8.3, 1.0 Hz, 1H), 6.34 (dd, J = 7.1, 5.3 Hz, 1H), 3.44 (d, J = 8.1 Hz, 1H), 7.75 (dd, J = 7.7, 1.6 Hz, 1H), 7.39–7.30 (m, 1H),
2.0 Hz, 1H), 3.43 (s, 1H). 13C NMR (100 MHz, chloroform-d) 7.29 (s, 1H), 7.17 (d, J = 8.2 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H),
δ 196.2, 174.6, 155.6, 155.2, 155.0, 136.3, 134.1, 133.8, 6.90 (d, J = 8.0 Hz, 1H), 6.11 (dd, J = 9.4, 3.6 Hz, 1H), 4.08 (t, J =
133.2, 128.7, 128.5, 125.6, 125.3, 124.0, 123.6, 121.9, 118.2, 6.6 Hz, 2H), 2.82 (dd, J = 15.1, 9.4 Hz, 1H), 2.75 (dd, J = 15.1,
118.1, 115.4, 112.7, 70.7, 42.7. HRMS (ESI+) m/z calcd for 3.6 Hz, 1H), 2.46 (s, 3H), 1.63–1.51 (m, 2H), 1.39–1.29 (m, 2H),
C24H16NaO4+ [M + Na]+: 391.0941, found: 391.0939.
0.89 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, chloroform-d)
6-(2-Oxopropyl)chromeno[4,3-b]chromen-7(6H)-one (3e). δ 174.2, 169.7, 155.6, 155.1, 154.6, 145.1, 133.7, 126.7, 125.3,
Compound 3e was prepared (12.1 mg, 63% yield) according to 123.4, 121.8, 121.6, 117.9, 117.7, 115.4, 112.0, 70.4, 64.6, 39.1,
GP I from the flavone derivative (15.0 mg, 0.063 mmol). mp 30.5, 21.8, 19.0, 13.6. HRMS (ESI+) m/z calcd for C23H22NaO5
+
168–170 °C. IR: v = 1710, 1598, 1463, 1414 cm−1 1H NMR [M + Na]+: 401.1359, found: 401.1343.
.
(400 MHz, chloroform-d) δ 8.20 (dd, J = 8.0, 1.7 Hz, 1H), 7.83
Butyl 2-(9-methyl-7-oxo-6,7-dihydrochromeno[4,3-b]chromen-
(dd, J = 7.8, 1.7 Hz, 1H), 7.69 (ddd, J = 8.7, 7.1, 1.7 Hz, 1H), 6-yl)acetate (3i). Compound 3i was prepared (12.2 mg, 53%
7.55 (dd, J = 8.4, 1.0 Hz, 1H), 7.44–7.37 (m, 2H), 7.08 (td, J = yield) according to GP I from the flavone derivative (15.9 mg,
7.6, 1.1 Hz, 1H), 6.93 (dd, J = 8.3, 1.0 Hz, 1H), 6.21 (dd, J = 9.9, 0.063 mmol). mp 132–134 °C. IR: v = 1730, 1638, 1602,
1
3.0 Hz, 1H), 3.02 (dd, J = 15.7, 9.9 Hz, 1H), 2.82 (dd, J = 15.7, 1043 cm−1. H NMR (400 MHz, chloroform-d) δ 7.96 (ddd, J =
3.0 Hz, 1H), 2.26 (s, 3H). 13C NMR (100 MHz, chloroform-d) 2.2, 1.4, 0.7 Hz, 1H), 7.79 (dt, J = 7.8, 1.1 Hz, 1H), 7.47 (dd, J =
δ 204.9, 174.5, 155.6, 155.2, 155.0, 134.1, 133.8, 125.7, 125.3, 8.5, 2.1 Hz, 1H), 7.41 (d, J = 8.5 Hz, 1H), 7.39–7.34 (m, 1H),
124.0, 123.7, 122.0, 118.0, 118.0, 115.5, 112.5, 70.0, 47.4, 30.0. 7.09–7.00 (m, 1H), 6.92 (d, J = 8.2 Hz, 1H), 6.14 (ddd, J = 9.3,
HRMS (ESI+) m/z calcd for C19H14NaO4 [M + Na]+: 329.0784, 3.7, 0.8 Hz, 1H), 4.09 (t, J = 6.6 Hz, 2H), 2.84 (dd, J = 15.1,
+
found: 329.0764.
9.3 Hz, 1H), 2.76 (dd, J = 15.2, 3.7 Hz, 1H), 2.43 (s, 3H),
N,N-Dimethyl-2-(7-oxo-6,7-dihydrochromeno[4,3-b]chromen- 1.62–1.54 (m, 2H), 1.41–1.30 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H).
6-yl)acetamide (3f). Compound 3f was prepared (15.1 mg, 13C NMR (100 MHz, chloroform-d) δ 174.4, 169.8, 155.2, 154.8,
47% yield) according to GP I from the flavone derivative 153.8, 135.3, 134.9, 133.8, 125.0, 123.6, 123.6, 121.8, 117.9,
(22.5 mg, 0.095 mmol). mp 159–161 °C. IR: v = 1642, 1631, 117.7, 115.5, 112.1, 70.5, 64.6, 39.1, 30.6, 20.9, 19.1, 13.7.
+
1600, 1622, 1414 cm−1
.
1H NMR (400 MHz, chloroform-d) HRMS (ESI+) m/z calcd for C23H22NaO5 [M + Na]+: 401.1359,
δ 8.16 (dd, J = 7.9, 1.6 Hz, 1H), 7.80 (dd, J = 7.8, 1.6 Hz, 1H), found: 401.1367.
7.66 (ddd, J = 8.7, 7.2, 1.7 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H),
Butyl 2-(9-fluoro-7-oxo-6,7-dihydrochromeno[4,3-b]chromen-
7.40–7.34 (m, 2H), 7.04 (td, J = 7.7, 0.9 Hz, 1H), 6.99 (dd, J = 6-yl)acetate (3j). Compound 3j was prepared (13.8 mg, 57%
8.3, 1.0 Hz, 1H), 6.15 (dd, J = 9.5, 2.9 Hz, 1H), 3.03 (s, 3H), 2.93 yield) according to GP I from the flavone derivative (16.1 mg,
(s, 3H), 2.88 (dd, J = 15.0, 9.6 Hz, 1H), 2.76 (dd, J = 15.0, 0.063 mmol). mp 105–107 °C. IR: v = 1737, 1730, 1633, 1454,
1
2.9 Hz, 1H). 13C NMR (100 MHz, chloroform-d) δ 174.6, 168.7, 1162 cm−1. H NMR (400 MHz, chloroform-d) δ 7.84–7.77 (m,
155.6, 155.4, 154.9, 134.0, 133.7, 125.5, 125.2, 123.9, 123.5, 2H), 7.54 (dd, J = 9.1, 4.1 Hz, 1H), 7.39 (dddd, J = 9.9, 7.3, 2.0,
121.7, 118.2, 118.0, 115.4, 112.7, 70.6, 37.6, 37.5, 35.4. HRMS 1.2 Hz, 2H), 7.09–7.03 (m, 1H), 6.93 (d, J = 8.3 Hz, 1H), 6.13
+
(ESI+) m/z calcd for C20H17NNaO4 [M + Na]+: 358.1050, found: (dd, J = 9.3, 3.6 Hz, 1H), 4.09 (t, J = 6.7 Hz, 2H), 2.84 (dd, J =
391.1033.
Diethyl
15.1, 9.3 Hz, 1H), 2.75 (dd, J = 15.1, 3.6 Hz, 1H), 1.62–1.53 (m,
((7-oxo-6,7-dihydrochromeno[4,3-b]chromen-6-yl) 2H), 1.40–1.30 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13C NMR
methyl)phosphonate (3g). Compound 3g was prepared (100 MHz, chloroform-d) δ 173.6 (d, JCF = 2.3 Hz), 169.6, 159.6
(14.6 mg, 58% yield) according to GP I from the flavone deriva- (d, JCF = 247.2 Hz), 155.3, 151.7 (d, JCF = 1.6 Hz), 134.2, 125.1
tive (15.0 mg, 0.063 mmol). mp 118–120 °C. IR: v = 1644, 1606, (d, JCF = 7.3 Hz), 123.6, 122.0, 121.7, 120.1 (d, JCF = 8.0 Hz),
1463, 1421, 1208 cm−1
.
1H NMR (400 MHz, chloroform-d) 118.0, 115.1, 111.7, 110.7 (d, JCF = 23.8 Hz), 70.4, 64.7,
δ 8.20 (dd, J = 8.0, 1.7 Hz, 1H), 7.84 (dd, J = 7.8, 1.6 Hz, 1H), 39.1, 30.6, 19.1, 13.6. HRMS (ESI+) m/z calcd for C22H19FNaO5
7.68 (ddd, J = 8.7, 7.1, 1.7 Hz, 1H), 7.54 (dd, J = 8.5, 1.1 Hz, [M + Na]+: 405.1109, found: 405.1102.
+
1H), 7.47–7.36 (m, 2H), 7.09 (td, J = 7.5, 1.1 Hz, 1H), 7.03 (dd, J =
Butyl 2-(10-fluoro-7-oxo-6,7-dihydrochromeno[4,3-b]chromen-
8.3, 1.1 Hz, 1H), 6.08 (td, J = 10.2, 2.8 Hz, 1H), 4.22–4.06 (m, 6-yl)acetate (3k). Compound 3k was prepared (23.8 mg, 66%
4H), 2.42 (td, J = 15.2, 10.4 Hz, 1H), 2.24 (ddd, J = 19.2, 15.6, yield) according to GP I from the flavone derivative (24.2 mg,
2.8 Hz, 1H), 1.32 (t, J = 7.0 Hz, 6H). 13C NMR (100 MHz, chloro- 0.095 mmol). mp 136–138 °C. IR: v = 1739, 1633, 1615, 1443,
form-d) δ 174.3, 155.6, 155.1, 154.8, 134.0, 133.7, 125.7, 125.3, 1065 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.20 (dd, J =
.
124.1, 123.6, 122.0, 118.4, 118.0, 115.5, 113.1 (d, J = 14.9 Hz), 8.8, 6.3 Hz, 1H), 7.76 (dd, J = 7.8, 1.6 Hz, 1H), 7.41–7.35 (m,
69.0 (d, J = 5.8 Hz), 61.8 (dd, J = 16.8, 6.3 Hz), 30.6 (d, J = 139.6 1H), 7.21 (dd, J = 8.9, 2.4 Hz, 1H), 7.12 (td, J = 8.5, 2.4 Hz, 1H),
Hz), 16.5 (dd, J = 6.1, 2.3 Hz). HRMS (ESI+) m/z calcd for 7.06 (td, J = 7.6, 1.0 Hz, 1H), 6.92 (dd, J = 8.3, 1.1 Hz, 1H), 6.12
C21H21NaO6P+ [M + Na]+: 423.0968, found: 423.0990.
(dd, J = 9.4, 3.5 Hz, 1H), 4.09 (t, J = 6.7 Hz, 2H), 2.84 (dd, J =
Butyl 2-(10-methyl-7-oxo-6,7-dihydrochromeno[4,3-b]chromen- 14.8, 9.4 Hz, 1H), 2.75 (dd, J = 15.1, 3.6 Hz, 1H), 1.62–1.53 (m,
6-yl)acetate (3h). Compound 3h was prepared (29.8 mg, 83% 2H), 1.40–1.30 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13C NMR
yield) according to GP I from the flavone derivative (23.8 mg, (100 MHz, chloroform-d) δ 173.5, 169.6, 165.6 (d, JCF = 255.2
0.095 mmol). mp 83–85 °C. IR: v = 1728, 1638, 1602, Hz), 156.5 (d, JCF = 13.4 Hz), 155.3, 155.2, 134.2, 128.2 (d, JCF
=
1045 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.03 (d, J = 10.6 Hz), 123.5, 122.0, 120.8 (d, JCF = 2.4 Hz), 118.0, 115.1,
.
3418 | Org. Biomol. Chem., 2014, 12, 3413–3422
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
114.0 (d, JCF = 22.7 Hz), 112.2, 104.8 (d, JCF = 25.6 Hz), 70.4, 1.61–1.53 (m, 2H), 1.39–1.29 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H).
64.7, 39.1, 30.6, 19.0, 13.7. HRMS (ESI+) m/z calcd for 13C NMR (100 MHz, chloroform-d) δ 174.3, 169.5, 155.5, 153.7,
C22H19FNaO5+ [M + Na]+: 405.1109, found: 405.1095.
134.0, 133.6, 127.1, 125.7, 125.5, 123.9, 123.2, 119.3, 118.1,
Butyl 2-(9-chloro-7-oxo-6,7-dihydrochromeno[4,3-b]chromen- 116.6, 112.6, 70.8, 64.7, 39.1, 30.5, 19.0, 13.7. HRMS (ESI+) m/z
6-yl)acetate (3l). Compound 3l was prepared (21.3 mg, 56% calcd for C22H19ClNaO5+ [M + Na]+: 421.0813, found: 421.0803.
yield) according to GP I from the flavone derivative (25.8 mg,
0.095 mmol). mp 111–113 °C. IR: v = 1733, 1631, 1443, 1156, 6-yl)acetate (3p). Compound 3p was prepared (21.1 mg, 51%
1408 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.12 (d, J = yield) according to GP I from the flavone derivative (30.0 mg,
2.6 Hz, 1H), 7.84–7.71 (m, 1H), 7.65–7.56 (m, 1H), 7.48 (d, J = 0.095 mmol). mp 114–116 °C. IR: v = 1724, 1642, 1629,
8.9 Hz, 1H), 7.42–7.35 (m, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.92 1407 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.18 (dd, J =
Butyl 2-(2-bromo-7-oxo-6,7-dihydrochromeno[4,3-b]chromen-
.
.
(d, J = 8.3 Hz, 1H), 6.12 (dd, J = 9.3, 3.6 Hz, 1H), 4.08 (t, J = 7.9, 1.7 Hz, 1H), 7.90 (dd, J = 2.4, 0.8 Hz, 1H), 7.72–7.67 (m,
6.7 Hz, 2H), 2.84 (dd, J = 15.1, 9.3 Hz, 1H), 2.75 (dd, J = 15.0, 1H), 7.54 (d, J = 8.6 Hz, 1H), 7.45 (ddd, J = 8.7, 2.4, 0.7 Hz, 1H),
3.6 Hz, 1H), 1.61–1.53 (m, 2H), 1.39–1.29 (m, 2H), 0.90 (t, J = 7.46–7.36 (m, 1H), 6.82 (dd, J = 8.8, 0.8 Hz, 1H), 6.13 (dd, J =
7.4 Hz, 3H). 13C NMR (100 MHz, chloroform-d) δ 173.2, 169.6, 8.9, 3.9 Hz, 1H), 4.09 (t, J = 6.7 Hz, 2H), 2.84 (dd, J = 15.2,
155.3, 155.3, 153.8, 134.3, 133.9, 131.3, 125.1, 124.9, 123.6, 9.0 Hz, 1H), 2.77 (dd, J = 15.3, 3.9 Hz, 1H), 1.61–1.52 (m, 2H),
122.0, 119.7, 118.0, 115.0, 112.2, 70.4, 64.7, 39.0, 30.6, 19.0, 1.39–1.29 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
13.7. HRMS (ESI+) m/z calcd for C22H19ClNaO5 [M + Na]+: chloroform-d) δ 174.3, 169.5, 155.5, 154.2, 153.5, 136.5, 134.0,
+
421.0813, found: 421.0802.
126.1, 125.7, 125.5, 123.9, 119.7, 118.0, 117.0, 114.1, 112.6,
Butyl 2-(4-chloro-7-oxo-6,7-dihydrochromeno[4,3-b]chromen- 70.8, 64.7, 39.1, 30.5, 19.0, 13.7. HRMS (ESI+) m/z calcd for
6-yl)acetate (3m). Compound 3m was prepared (17.5 mg, 70% C22H19BrNaO5+ [M + Na]+: 465.0308, found: 465.0312.
yield) according to GP I from the flavone derivative (17.2 mg,
0.063 mmol). mp 131–133 °C. IR: v = 1743, 1620, 1611, 1410, 6-yl)acetate (3q). Compound 3q was prepared (20.2 mg, 52%
1067 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.17 (dt, J = yield) according to GP I from the flavone derivative (27.3 mg,
Butyl 2-(7-oxo-6,7-dihydrobenzo[h]chromeno[4,3-b]chromen-
.
8.0, 1.1 Hz, 1H), 7.75–7.63 (m, 2H), 7.52 (d, J = 8.5 Hz, 1H), 0.095 mmol). mp 104–106 °C. IR: v = 1739, 1640, 1631, 1410,
1
7.46–7.35 (m, 2H), 6.99 (td, J = 7.9, 0.7 Hz, 1H), 6.24 (t, J = 6.5 1054 cm−1. H NMR (400 MHz, chloroform-d) δ 8.53–8.45 (m,
Hz, 1H), 4.15–4.04 (m, 2H), 2.81 (d, 2H), 1.63–1.54 (m, 2H), 1H), 8.08 (dd, J = 8.7, 1.5 Hz, 1H), 7.90 (dt, J = 7.8, 1.8 Hz, 1H),
1.40–1.30 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, 7.86 (ddd, J = 6.0, 3.8, 1.9 Hz, 1H), 7.70 (dd, J = 8.8, 1.7 Hz,
chloroform-d) δ 174.3, 169.3, 155.5, 154.1, 150.9, 134.1, 133.9, 1H), 7.69–7.61 (m, 2H), 7.45–7.35 (m, 1H), 7.15–7.06 (m, 1H),
125.7, 125.4, 123.8, 123.1, 122.0, 121.9, 118.0, 116.9, 112.5, 6.95 (d, J = 8.2 Hz, 1H), 6.17 (ddd, J = 9.1, 3.7, 1.2 Hz, 1H), 4.11
71.4, 64.9, 39.4, 30.5, 19.1, 13.7. HRMS (ESI+) m/z calcd for (t, J = 6.7 Hz, 2H), 2.89 (dd, J = 15.3, 9.2 Hz, 1H), 2.82 (dd, J =
C22H19ClNaO5+ [M + Na]+: 421.0813, found: 421.0802.
15.0, 4.0 Hz, 1H), 1.63–1.55 (m, 2H), 1.40–1.31 (m, 2H), 0.90 (t,
Butyl 2-(3-chloro-7-oxo-6,7-dihydrochromeno[4,3-b]chromen- J = 7.4 Hz, 3H). 13C NMR (100 MHz, chloroform-d) δ 174.1,
6-yl)acetate (3n). Compound 3n was prepared (20.1 mg, 53% 169.8, 155.1, 154.2, 152.7, 135.8, 133.9, 129.3, 128.2, 127.2,
yield) according to GP I from the flavone derivative (25.8 mg, 125.3, 123.9, 123.3, 122.0, 121.9, 120.6, 120.2, 118.0, 115.5,
0.095 mmol). mp 80–82 °C. IR: v = 1728, 1642, 1633, 113.3, 70.6, 64.7, 39.1, 30.6, 19.1, 13.7. HRMS (ESI+) m/z calcd
1598 cm−1
.
1H NMR (400 MHz, chloroform-d) δ 8.15 (dd, J = for C26H22NaO5+ [M + Na]+: 437.1359, found: 437.1368.
Butyl 2-(7-oxo-5-tosyl-6,7-dihydro-5H-chromeno[3,2-c]quino-
7.9, 1.7 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.69–7.64 (m, 1H),
7.50 (dd, J = 8.3, 0.9 Hz, 1H), 7.41–7.36 (m, 1H), 7.02 (dd, J = lin-6-yl)acetate (3r). Compound 3r was prepared (30.3 mg,
8.4, 2.0 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 6.12 (dd, J = 8.7, 62% yield) according to GP I from the flavone derivative
4.1 Hz, 1H), 4.09 (t, J = 6.7 Hz, 2H), 2.87–2.75 (m, 2H), (37.1 mg, 0.095 mmol). mp 131–133 °C. IR: v = 1744, 1726,
1.61–1.53 (m, 2H), 1.40–1.29 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H). 1626, 1410 cm−1. 1H NMR (400 MHz, chloroform-d) δ 8.12 (dd,
13C NMR (100 MHz, chloroform-d) δ 174.2, 169.5, 155.8, 155.4, J = 8.1, 1.7 Hz, 1H), 7.82–7.78 (m, 2H), 7.65–7.57 (m, 2H), 7.44
154.1, 139.6, 133.9, 125.7, 125.4, 124.5, 123.8, 122.4, 118.2, (td, J = 7.6, 1.2 Hz, 1H), 7.40–7.36 (m, 2H), 7.17–7.13 (m, 2H),
117.9, 113.9, 111.9, 71.1, 64.7, 39.2, 30.5, 19.1, 13.6. HRMS 6.77–6.72 (m, 2H), 6.04 (dd, J = 10.0, 4.6 Hz, 1H), 4.09 (td, J =
(ESI+) m/z calcd for C22H19ClNaO5+ [M + Na]+: 421.0813, found: 6.8, 1.4 Hz, 2H), 2.55 (dd, J = 14.2, 4.6 Hz, 1H), 2.34 (dd, J =
421.0800.
14.2, 10.0 Hz, 1H), 1.78 (s, 3H), 1.69–1.61 (m, 2H), 1.44–1.34
Butyl 2-(2-chloro-7-oxo-6,7-dihydrochromeno[4,3-b]chromen- (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, chloro-
6-yl)acetate (3o). Compound 3o was prepared (13.8 mg, 55% form-d) δ 174.0, 169.2, 155.2, 154.5, 144.0, 135.8, 134.7, 133.7,
yield) according to GP I from the flavone derivative (17.2 mg, 132.5, 129.8, 128.9, 127.6, 126.8, 125.6, 125.2, 123.6, 123.4,
0.063 mmol). mp 107–109 °C. IR: v = 1724, 1631, 1461, 1408, 123.1, 117.6, 115.3, 65.0, 49.8, 38.2, 30.5, 20.8, 19.1, 13.7.
1065, 1056 cm−1. 1H NMR (400 MHz, chloroform-d) δ 8.18 (dd, HRMS (ESI+) m/z calcd for C29H27NNaO6S+ [M
J = 8.0, 1.7 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.69 (ddd, J = 8.7, 540.1451, found: 540.1414.
+
Na]+:
7.2, 1.7 Hz, 1H), 7.57–7.52 (m, 1H), 7.41 (ddd, J = 8.0, 7.2,
Butyl
2-(7-oxo-6,7-dihydrochromeno[3,4-c]chromen-6-yl)-
1.1 Hz, 1H), 7.31 (dd, J = 8.8, 2.6 Hz, 1H), 6.87 (d, J = 8.8 Hz, acetate (5a). Compound 5a was prepared (17.7 mg, 77% yield)
1H), 6.13 (dd, J = 9.0, 3.8 Hz, 1H), 4.09 (t, J = 6.6 Hz, 2H), 2.84 according to GP II from the coumarin derivative (15.0 mg,
(dd, J = 15.2, 9.1 Hz, 1H), 2.77 (dd, J = 15.2, 3.8 Hz, 1H), 0.063 mmol). mp 96–98 °C. IR: v = 1713, 1604, 1173,
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 3413–3422 | 3419

View Article Online
Paper
Organic & Biomolecular Chemistry
1107 cm−1. 1H NMR (400 MHz, chloroform-d) δ 8.10 (d, J = 8.1 0.10 mmol). mp 202–204 °C. IR: v = 1701, 1679, 1445, 1197,
Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.58–7.52 (m, 1H), 7.45–7.38 1109 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.13 (dd, J =
.
(m, 2H), 7.37–7.27 (m, 1H), 7.18–7.12 (m, 1H), 7.08 (d, J = 8.2, 1.5 Hz, 1H), 7.98–7.94 (m, 2H), 7.91 (dd, J = 7.9, 1.6 Hz,
8.2 Hz, 1H), 5.86 (ddd, J = 7.5, 6.2, 1.1 Hz, 1H), 4.11 (t, J = 6.7 1H), 7.60–7.52 (m, 2H), 7.47–7.42 (m, 3H), 7.41–7.39 (m, 1H),
Hz, 2H), 2.68 (s, 1H), 2.66 (d, J = 0.9 Hz, 1H), 1.67–1.54 (m, 7.37–7.32 (m, 1H), 7.18–7.13 (m, 1H), 7.02 (dd, J = 8.2, 1.3 Hz,
2H), 1.44–1.29 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H). 13C NMR 1H), 6.07 (dd, J = 8.6, 4.4 Hz, 1H), 3.31 (d, J = 5.2 Hz, 1H), 3.29
(100 MHz, chloroform-d) δ 169.4, 158.7, 154.6, 153.8, 140.4, (s, 1H). 13C NMR (100 MHz, chloroform-d) δ 195.9, 158.9,
132.8, 131.5, 127.6, 126.4, 124.3, 122.3, 119.8, 119.7, 154.7, 153.8, 140.5, 136.3, 133.3, 132.9, 131.6, 128.7, 128.4,
119.0, 117.8, 116.3, 70.0, 64.8, 35.9, 30.6, 19.1, 13.7. HRMS 127.6, 126.4, 124.4, 122.3, 120.3, 120.1, 119.0, 117.9, 116.4,
+
+
(ESI+) m/z calcd for C22H20NaO5 [M + Na]+: 387.1203, found: 70.1, 39.0. HRMS (ESI+) m/z calcd for C24H16NaO4 [M + Na]+:
387.1198.
391.0941, found: 391.0942.
tert-Butyl 2-(7-oxo-6,7-dihydrochromeno[3,4-c]chromen-6-yl)-
N,N-Dimethyl-2-(7-oxo-6,7-dihydrochromeno[3,4-c]chromen-
acetate (5b). Compound 5b was prepared (24.5 mg, 67% yield) 6-yl)acetamide (5f). Compound 5f was prepared (15.5 mg,
according to GP II from the coumarin derivative (23.8 mg, 46% yield) according to GP II from the coumarin derivative
0.10 mmol). mp 134–136 °C. IR: v = 1724, 1693, 1606, 1251, (23.8 mg, 0.10 mmol). mp 201–203 °C. IR: v = 1693, 1640,
1149 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.09 (dd, J = 1111 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.09 (dd, J =
. .
8.1, 1.6 Hz, 1H), 7.86 (dd, J = 8.0, 1.6 Hz, 1H), 7.54 (ddd, J = 8.2, 1.6 Hz, 1H), 7.87 (d, J = 7.6 Hz, 1H), 7.54 (ddd, J = 8.4, 7.2,
8.4, 7.2, 1.4 Hz, 1H), 7.41 (dddd, J = 9.7, 8.4, 7.2, 1.4 Hz, 2H), 1.4 Hz, 1H), 7.46–7.35 (m, 2H), 7.34–7.29 (m, 1H), 7.14 (t, J =
7.35–7.27 (m, 1H), 7.19–7.09 (m, 1H), 7.07 (dd, J = 8.1, 1.2 Hz, 7.9 Hz, 2H), 5.88 (dd, J = 9.7, 3.2 Hz, 1H), 2.94 (s, 3H), 2.93 (s,
1H), 5.81 (dd, J = 9.7, 4.2 Hz, 1H), 2.65–2.49 (m, 2H), 1.46 3H), 2.75 (dd, J = 14.9, 9.8 Hz, 1H), 2.64 (dd, J = 14.9, 3.2 Hz,
(s, 9H). 13C NMR (100 MHz, chloroform-d) δ 168.5, 158.6, 1H). 13C NMR (100 MHz, chloroform-d) δ 168.5, 158.9, 154.9,
154.7, 153.8, 140.3, 132.8, 131.5, 127.6, 126.4, 124.3, 122.2, 153.8, 140.3, 132.8, 131.4, 127.6, 126.4, 124.3, 122.1, 120.4,
120.0, 119.7, 119.0, 117.8, 116.3, 81.2, 70.1, 36.9, 28.0. HRMS 119.9, 119.1, 117.8, 116.4, 70.1, 37.5, 35.5, 34.1. HRMS (ESI+)
(ESI+) m/z calcd for C22H20NaO5 [M + Na]+: 387.1203, found: m/z calcd for C20H17NNaO4 [M + Na]+: 358.1050, found:
+
+
387.1197.
358.1035.
Methyl 2-(7-oxo-6,7-dihydrochromeno[3,4-c]chromen-6-yl)-
Butyl 2-(2-fluoro-7-oxo-6,7-dihydrochromeno[3,4-c]chromen-
acetate (5c). Compound 5c was prepared (15.0 mg, 74% yield) 6-yl)acetate (5g). Compound 5g was prepared (15.2 mg, 63%
according to GP II from the coumarin derivative (15.0 mg, yield) according to GP II from the coumarin derivative
0.063 mmol). mp 176–178 °C. IR: v = 1733, 1693, 1604, (16.1 mg, 0.063 mmol). mp 102–104 °C. IR: v = 1719, 1480,
1175 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.11 (d, J = 1273, 1175 cm−1. 1H NMR (400 MHz, chloroform-d) δ 8.06 (dd,
.
7.7 Hz, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.59–7.54 (m, 1H), J = 8.2, 1.5 Hz, 1H), 7.62–7.56 (m, 2H), 7.42 (dd, J = 8.3, 1.3 Hz,
7.46–7.40 (m, 2H), 7.33 (ddd, J = 8.4, 7.3, 1.2 Hz, 1H), 7.16 (td, 1H), 7.36 (ddd, J = 8.4, 7.3, 1.3 Hz, 1H), 7.15 (ddd, J = 8.9, 7.8,
J = 7.5, 1.1 Hz, 1H), 7.11 (dd, J = 8.2, 1.2 Hz, 1H), 5.87 (dd, J = 2.9 Hz, 1H), 7.06 (dd, J = 8.9, 4.9 Hz, 1H), 5.85 (dd, J = 7.3, 6.4
8.2, 5.4 Hz, 1H), 3.71 (s, 3H), 2.70 (d, J = 3.2 Hz, 1H), 2.69 (s, Hz, 1H), 4.11 (t, J = 6.7 Hz, 2H), 2.68 (s, 1H), 2.67 (d, J = 0.9 Hz,
1H). 13C NMR (100 MHz, chloroform-d) δ 169.9, 158.7, 1H), 1.65–1.57 (m, 2H), 1.42–1.32 (m, 2H), 0.92 (t, J = 7.4 Hz,
154.5, 153.8, 140.5, 132.9, 131.6, 127.7, 126.4, 124.4, 122.4, 3H). 13C NMR (100 MHz, chloroform-d) δ 169.3, 158.6 (d, JCF
=
119.8, 119.7, 119.0, 117.9, 116.3, 69.9, 52.0, 35.7. HRMS (ESI+) 28.5 Hz), 155.0 (d, JCF = 259.5 Hz), 150.5, 139.6, 131.8, 125.9,
m/z calcd for C19H14NaO5 [M + Na]+: 345.0733, found: 124.6, 120.9 (d, JCF = 8.1 Hz), 120.8, 119.8 (d, JCF = 8.3 Hz),
+
345.0724.
119.5 (d, JCF = 23.1 Hz), 118.0, 115.9, 114.0 (d, JCF = 25.5 Hz),
7-(2-Oxopropyl)chromeno[3,4-c]chromen-6(7H)-one (5d). 70.2, 64.9, 35.8, 30.6, 19.1, 13.7. HRMS (ESI+) m/z calcd for
Compound 5d was prepared (13.9 mg, 72% yield) according to C22H19FNaO5+ [M + Na]+: 405.1109, found: 405.1099.
GP II from the coumarin derivative (15.0 mg, 0.063 mmol). mp
Butyl 2-(2-chloro-7-oxo-6,7-dihydrochromeno[3,4-c]chromen-
148–150 °C. IR: v = 1702, 1691, 1587 cm−1. 1H NMR (400 MHz, 6-yl)acetate (5h). Compound 5h was prepared (22.6 mg, 78%
DMSO-d6) δ 8.20 (dd, J = 8.2, 1.5 Hz, 1H), 8.05 (dd, J = 7.9, yield) according to GP II from the coumarin derivative
1.5 Hz, 1H), 7.71 (ddd, J = 8.5, 7.3, 1.5 Hz, 1H), 7.54 (td, J = 8.0, (17.2 mg, 0.063 mmol). mp 102–104 °C. IR: v = 1722, 1265,
1.4 Hz, 2H), 7.47 (ddd, J = 8.4, 7.3, 1.3 Hz, 1H), 7.27 (td, J = 7.6, 1246, 1182 cm−1. 1H NMR (400 MHz, chloroform-d) δ 8.03 (dd,
1.3 Hz, 1H), 7.11 (dd, J = 8.1, 1.2 Hz, 1H), 5.78 (dd, J = 10.1, J = 8.2, 1.5 Hz, 1H), 7.85 (d, J = 2.5 Hz, 1H), 7.58 (ddd, J = 8.5,
2.9 Hz, 1H), 2.86 (dd, J = 16.1, 10.2 Hz, 1H), 2.61 (dd, J = 16.1, 7.3, 1.5 Hz, 1H), 7.41 (dd, J = 8.4, 1.2 Hz, 1H), 7.39–7.34 (m,
3.0 Hz, 1H), 2.14 (s, 3H). 13C NMR (100 MHz, DMSO-d6) 2H), 7.03 (d, J = 8.7 Hz, 1H), 5.85 (dd, J = 7.7, 6.0 Hz, 1H), 4.11
δ 204.6, 157.8, 153.9, 153.1, 139.0, 133.0, 131.8, 128.2, 126.4, (t, J = 6.7 Hz, 2H), 2.68 (s, 1H), 2.66 (d, J = 1.7 Hz, 1H),
124.8, 122.7, 120.1, 119.1, 118.6, 117.4, 115.7, 68.9, 42.9, 30.2. 1.64–1.56 (m, 2H), 1.41–1.31 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H).
+
HRMS (ESI+) m/z calcd for C19H14NaO4 [M + Na]+: 329.0784, 13C NMR (100 MHz, chloroform-d) δ 169.2, 158.4, 153.7, 153.1,
found: 329.0778.
139.3, 132.5, 131.9, 127.4, 127.2, 125.9, 124.7, 121.1, 120.5,
7-(2-Oxo-2-phenylethyl)chromeno[3,4-c]chromen-6(7H)-one 120.2, 117.9, 115.8, 70.3, 64.9, 35.9, 30.6, 19.0, 13.7. HRMS
(5e). Compound 5e was prepared (18.6 mg, 51% yield) accord- (ESI+) m/z calcd for C22H19ClNaO5+ [M + Na]+: 421.0813, found:
ing to GP II from the coumarin derivative (23.8 mg, 421.0807.
3420 | Org. Biomol. Chem., 2014, 12, 3413–3422
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
Butyl 2-(11-methyl-7-oxo-6,7-dihydrochromeno[3,4-c]chromen- 154.5, 152.2, 139.5, 133.1, 131.5, 129.9, 127.2, 125.9, 122.6,
6-yl)acetate (5i). Compound 5i was prepared (27.6 mg, 74% 120.7, 119.8, 119.2, 118.5, 117.4, 69.9, 64.8, 35.8, 30.6, 19.0,
yield) according to GP II from the coumarin derivative 13.6. HRMS (ESI+) m/z calcd for C22H19ClNaO5 [M + Na]+:
+
(25.2 mg, 0.10 mmol). IR: v = 1702, 1387, 1257, 1166 cm−1
.
421.0813, found: 421.0808.
Butyl 2-(10-methoxy-7-oxo-6,7-dihydrochromeno[3,4-c]chromen-
1H NMR (400 MHz, chloroform-d) δ 7.91–7.82 (m, 2H), 7.41
(ddd, J = 8.1, 7.4, 1.5 Hz, 1H), 7.34 (dd, J = 8.4, 1.5 Hz, 1H), 6-yl)acetate (5m). Compound 5m was prepared (49.8 mg, 84%
7.27 (d, J = 8.4 Hz, 1H), 7.16 (td, J = 7.6, 1.2 Hz, 1H), 7.07 (dd, yield) according to GP II from the coumarin derivative
J = 8.2, 1.2 Hz, 1H), 5.83 (t, J = 6.9 Hz, 1H), 4.10 (t, J = 6.7 Hz, (40.2 mg, 0.15 mmol). mp 135–137 °C. IR: v = 1701, 1609,
1
2H), 2.65 (d, J = 6.9 Hz, 2H), 2.41 (s, 3H), 1.60 (m, 2H), 1280, 1167 cm−1. H NMR (400 MHz, chloroform-d) δ 7.98 (d,
1.43–1.29 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, J = 9.8 Hz, 1H), 7.83 (d, J = 7.8 Hz, 1H), 7.43–7.38 (m, 1H), 7.13
chloroform-d) δ 169.5, 158.8, 154.5, 151.9, 140.3, 134.0, 132.7, (t, J = 7.6 Hz, 1H), 7.06 (d, J = 8.2 Hz, 1H), 6.91–6.83 (m, 2H),
132.5, 127.6, 126.1, 122.2, 119.7, 119.7, 119.0, 117.4, 115.9, 5.82 (t, J = 6.8 Hz, 1H), 4.10 (t, J = 6.6 Hz, 2H), 3.86 (s, 3H),
70.0, 64.7, 35.8, 30.6, 21.1, 19.0, 13.6. HRMS (ESI+) m/z calcd 2.65 (d, J = 7.0 Hz, 2H), 1.64–1.56 (m, 2H), 1.43–1.30 (m, 2H),
for C23H22NaO5+ [M + Na]+: 401.1359, found: 401.1351.
0.91 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, chloroform-d)
Butyl 2-(14-oxo-1,14-dihydrobenzo[h]chromeno[3,4-c]chromen- δ 169.5, 162.3, 158.9, 155.7, 154.6, 140.6, 132.7, 127.6, 127.4,
1-yl)acetate (5j). Compound 5j was prepared (36.9 mg, 60% 122.2, 119.7, 119.1, 116.6, 112.5, 109.6, 101.5, 69.9, 64.7, 55.7,
yield) according to GP II from the coumarin derivative 36.1, 30.6, 19.0, 13.7. HRMS (ESI+) m/z calcd for C23H22NaO6
+
(43.2 mg, 0.15 mmol). mp 106–108 °C. IR: v = 1737, 1711, [M + Na]+: 417.1309, found: 417.1294.
1604, 1357, 1098 cm−1
.
1H NMR (400 MHz, chloroform-d)
Butyl 2-(10-(dimethylamino)-7-oxo-6,7-dihydrochromeno[3,4-c]-
δ 8.58–8.50 (m, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.92 (dd, J = 7.9, chromen-6-yl)acetate (5n). Compound 5n was prepared
1.5 Hz, 1H), 7.89–7.81 (m, 1H), 7.69 (d, J = 8.9 Hz, 1H), (15.5 mg, 61% yield) according to GP II from the coumarin
7.68–7.56 (m, 2H), 7.49–7.40 (m, 1H), 7.18 (td, J = 7.7, 1.3 Hz, derivative (17.7 mg, 0.063 mmol). mp 95–97 °C. IR: v = 1728,
1
1H), 7.11 (dd, J = 8.2, 1.2 Hz, 1H), 5.91 (dd, J = 7.9, 5.8 Hz, 1H), 1691, 1596 cm−1. H NMR (400 MHz, chloroform-d) δ 7.89 (d,
4.13 (t, J = 6.7 Hz, 2H), 2.73 (s, 1H), 2.71 (d, J = 2.0 Hz, 1H), J = 9.1 Hz, 1H), 7.85 (dd, J = 7.9, 1.6 Hz, 1H), 7.39 (ddd, J = 8.1,
1.69–1.57 (m, 2H), 1.44–1.34 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 7.4, 1.5 Hz, 1H), 7.11 (td, J = 7.6, 1.2 Hz, 1H), 7.06 (dd, J = 8.2,
13C NMR (100 MHz, chloroform-d) δ 169.5, 158.6, 154.7, 151.1, 1.2 Hz, 1H), 6.63 (dd, J = 9.1, 2.7 Hz, 1H), 6.56 (d, J = 2.6 Hz,
141.3, 134.3, 132.8, 128.9, 127.9, 127.5, 127.2, 124.1, 123.5, 1H), 5.82 (dd, J = 8.2, 5.6 Hz, 1H), 4.11 (t, J = 6.7 Hz, 2H), 3.05
122.6, 122.3, 121.8, 119.8, 119.3, 119.2, 111.6, 70.1, 64.8, 35.9, (s, 6H), 2.66 (s, 1H), 2.64 (d, J = 2.7 Hz, 1H), 1.65–1.57 (m, 2H),
+
30.6, 19.1, 13.7. HRMS (ESI+) m/z calcd for C26H22NaO5
1.42–1.33 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
chloroform-d) δ 169.8, 159.6, 156.1, 154.7, 152.4, 140.9, 132.3,
[M + Na]+: 437.1359, found: 437.1372.
Butyl 2-(10-fluoro-7-oxo-6,7-dihydrochromeno[3,4-c]chromen- 127.7, 127.2, 122.0, 119.6, 119.6, 113.8, 109.1, 105.5, 98.8, 70.1,
6-yl)acetate (5k). Compound 5k was prepared (17.2 mg, 71% 64.7, 40.0, 36.4, 30.6, 19.1, 13.7. HRMS (ESI+) m/z calcd for
yield) according to GP II from the coumarin derivative C24H25NNaO5+ [M + Na]+: 430.1625, found: 430.1628.
(16.1 mg, 0.063 mmol). mp 101–103 °C. IR: v = 1724, 1611,
Butyl 2-(6-oxo-8-tosyl-7,8-dihydro-6H-chromeno[3,4-c]quino-
1272, 1151 cm−1. 1H NMR (400 MHz, chloroform-d) δ 8.10 (dd, lin-7-yl)acetate (5o). Compound 5o was prepared (26.5 mg,
J = 9.0, 5.9 Hz, 1H), 7.82 (dd, J = 7.9, 1.5 Hz, 1H), 7.46–7.41 (m, 51% yield) according to GP II from the coumarin derivative
1H), 7.18–7.04 (m, 4H), 5.84 (dd, J = 8.1, 5.5 Hz, 1H), 4.11 (t, (39.2 mg, 0.10 mmol). mp 97–99 °C. IR: v = 1724, 1701, 1354,
J = 6.7 Hz, 2H), 2.67 (d, J = 2.8 Hz, 1H), 2.65 (s, 1H), 1.66–1.54 1155 cm−1 1H NMR (400 MHz, chloroform-d) δ 7.83 (dd, J =
.
(m, 2H), 1.42–1.31 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C NMR 8.1, 1.4 Hz, 1H), 7.73 (dd, J = 8.0, 1.6 Hz, 1H), 7.65 (dd, J = 8.1,
(100 MHz, chloroform-d) δ 169.4, 164.0 (d, JCF = 254.8 Hz), 1.6 Hz, 1H), 7.61 (td, J = 7.8, 1.5 Hz, 1H), 7.51–7.41 (m, 2H),
158.4, 155.1 (d, JCF = 12.5 Hz), 154.7, 140.2, 133.1, 128.2 (d, JCF
9.9 Hz), 127.4, 122.4, 119.9, 118.8, 118.6 (d, JCF = 2.5 Hz), 113.0 8.3 Hz, 2H), 6.64 (d, J = 8.1 Hz, 2H), 5.88 (dd, J = 10.3, 4.6 Hz,
(d, JCF = 3.1 Hz), 112.4 (d, JCF = 22.4 Hz), 105.2 (d, JCF 1H), 4.11 (td, J = 6.8, 1.8 Hz, 2H), 2.51 (dd, J = 14.3, 4.6 Hz,
25.3 Hz), 69.9, 64.8, 35.9, 30.6, 19.1, 13.7. HRMS (ESI+) m/z 1H), 2.13 (dd, J = 14.3, 10.4 Hz, 1H), 1.71–1.62 (m, 5H),
calcd for C22H19FNaO5+ [M + Na]+: 405.1109, found: 405.1099. 1.46–1.34 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
=
7.27 (dd, J = 8.3, 1.3 Hz, 1H), 7.27–7.18 (m, 1H), 7.11 (d, J =
=
Butyl 2-(11-chloro-7-oxo-6,7-dihydrochromeno[3,4-c]chromen- chloroform-d) δ 168.8, 158.5, 153.3, 143.9, 140.3, 135.7, 134.3,
6-yl)acetate (5l). Compound 5l was prepared (24.8 mg, 63% 131.7, 131.3, 131.3, 129.2, 127.6, 127.4, 126.7, 126.3, 125.8,
yield) according to GP II from the coumarin derivative 123.9, 121.5, 117.4, 115.6, 65.1, 50.8, 36.1, 30.5, 20.8, 19.1,
(27.3 mg, 0.10 mmol). mp 93–95 °C. IR: v = 1719, 1270, 13.7. HRMS (ESI+) m/z calcd for C29H27NNaO6S+ [M + Na]+:
1166 cm−1 1H NMR (400 MHz, chloroform-d) δ 8.05 (t, J = 540.1451, found: 540.1471.
.
1.9 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.54–7.45 (m, 1H),
7.49–7.40 (m, 1H), 7.34 (dd, J = 8.8, 1.6 Hz, 1H), 7.21–7.16 (m,
1H), 7.09 (d, J = 8.2 Hz, 1H), 5.84 (ddd, J = 8.3, 5.2, 1.4 Hz, 1H),
4.10 (t, J = 6.7 Hz, 2H), 2.67 (dd, J = 4.0, 1.2 Hz, 1H), 2.65 (d, J =
Acknowledgements
1.0 Hz, 1H), 1.66–1.54 (m, 2H), 1.41–1.31 (m, 2H), 0.91 (t, J = This research was supported by the National Research Foun-
7.4 Hz, 3H). 13C NMR (100 MHz, chloroform-d) δ 169.3, 158.1, dation of Korea (NRF) funded by the Ministry of Education,
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 3413–3422 | 3421

View Article Online
Paper
Organic & Biomolecular Chemistry
Science and Technology (NRF-2010-0022179 and 2011-
0016436) and the Institute for Basic Science (IBS).
2011, 111, 1170; (f) J. Le Bras and J. Muzart, Chem. Rev.,
2011, 111, 1170.
5 (a) S. A. Achmad, E. H. Hakim, L. D. Juliawaty, L. Makmur,
A. N. Suyatno and E. L. Ghisalberti, J. Nat. Prod., 1996, 59,
878; (b) Z.-P. Zheng, K.-W. Cheng, J. T.-K. To, H. Li and
M. Wang, Mol. Nutr. Food Res., 2008, 52, 1530; (c) B.-L. Wei,
J.-R. Weng, P.-H. Chiu, C.-F. Hung, J.-P. Wang and
C.-N. Lin, J. Agric. Food Chem., 2005, 53, 3867;
(d) K. Likhitwitayawuid, B. Supudompol, B. Sritularak,
V. Lipipun, K. Rapp and R. F. Schinazi, Pharm. Biol., 2005,
43, 651.
6 (a) M. Miura, T. Tsuda, T. Satoh and M. Nomura, Chem.
Lett., 1997, 1103; (b) H. P. Kahn and J. Cossy, Tetrahedron
Lett., 1999, 40, 8113; (c) J. Y. Goujon, F. Zammattio and
B. Kirschleger, Tetrahedron: Asymmetry, 2000, 11, 2409;
(d) C. A. James, A. Coelho, M. Gevaert, P. Forgione and
V. Snieckus, J. Org. Chem., 2009, 74, 4094; (e) Y. Lu,
D.-H. Wang, K. M. Engle and J.-Q. Yu, J. Am. Chem. Soc.,
2010, 132, 5916; (f) S. R. Chidipudi, M. D. Wieczysty,
I. Khan and H. W. Lam, Org. Lett., 2013, 15, 570.
Notes and references
1 For selected reviews on C–H activation, see:
(a) P. B. Arockiam, C. Bruneau and P. H. Dixneuf, Chem.
Rev., 2012, 112, 5879; (b) G. Song, F. Wang and X. Li, Chem.
Soc. Rev., 2012, 41, 3651; (c) J. Wencel-Delord, T. Dröge,
F. Liu and F. Glorius, Chem. Soc. Rev., 2011, 40, 4740;
(d) W. Shi, C. Liu and A. Lei, Chem. Soc. Rev., 2011, 40,
2761; (e) C. Liu, H. Zhang, W. Shi and A. Lei, Chem. Rev.,
2011, 111, 1780; (f) T. W. Lyons and M. S. Sanford, Chem.
Rev., 2010, 110, 1147; (g) D. A. Colby, R. G. Bergman and
J. A. Ellman, Chem. Rev., 2010, 110, 624; (h) L.-M. Xu,
B.-J. Li, Z. Yang and Z.-J. Shi, Chem. Soc. Rev., 2010, 39, 712;
(i) C.-J. Li, Acc. Chem. Res., 2009, 42, 335; ( j) X. Chen,
K. M. Engle, D.-H. Wang and J.-Q. Yu, Angew. Chem., Int.
Ed., 2009, 48, 5094; (k) R. Giri, B.-F. Shi, K. M. Engle,
N. Maugel and J.-Q. Yu, Chem. Soc. Rev., 2009, 38, 3242;
(l) C. S. Yeung and V. M. Dong, Chem. Rev., 2011, 111,
1215; (m) S.-H. Cho, J. Y. Kim, J. Kwak and S. Chang, Chem.
Soc. Rev., 2011, 40, 5068; (n) L. Ackermann, R. Vicente and
A. R. Kapdi, Angew. Chem., Int. Ed., 2009, 48, 9792;
(o) J. A. Ashenhurst, Chem. Soc. Rev., 2010, 39, 540;
(p) P. Tansandote and M. Lautens, Chem. – Eur. J., 2009,
15, 5874; (q) B. J. Stokes and T. G. Driver, Eur. J. Org. Chem.,
2011, 4071; (r) M. Zhang, Adv. Synth. Catal., 2009, 351,
2243.
2 (a) I. Moritani and Y. Fujiwara, Tetrahedron Lett., 1967, 8,
1119; (b) Y. Fujiwara, I. Noritani, S. Danno, R. Asano and
S. Teranishi, J. Am. Chem. Soc., 1969, 91, 7166.
3 For C–H alkenylation of chromones and coumarins:
(a) D. Kim and S. Hong, Org. Lett., 2011, 13, 4466;
(b) M. Min, Y. Kim and S. Hong, Chem. Commun., 2013, 49,
196.
4 For selected recent examples of oxidative Heck coupling:
(a) Y.-Y. Yu, M. J. Niphakis and G. I. Georg, Org. Lett., 2011,
13, 5932; (b) D. Cheng and T. Gallagher, Org. Lett., 2009,
11, 2639; (c) Y.-H. Xu, Y. K. Chok and T.-P. Loh, Chem. Sci.,
2011, 2, 1822; (d) N. P. Grimster, C. Gauntlett,
C. R. A. Godfrey and M. J. Gaunt, Angew. Chem., Int. Ed.,
2005, 44, 3125; (e) J. Le Bras and J. Muzart, Chem. Rev.,
7 (a) I. T. Horvath and P. T. Anastas, Chem. Rev., 2007, 107,
2167; (b) P. A. Clarke, S. Santos and W. H. C. Martin, Green
Chem., 2007, 9, 438; (c) C. Vaxelaire, P. Winter and
M. Christmann, Angew. Chem., Int. Ed., 2011, 50, 3605;
(d) E. P. Kündig, Science, 2006, 314, 430.
8 Y. Moon, Y. Kim, H. Hong and S. Hong, Chem. Commun.,
2013, 49, 8323.
9 For selected reports: (a) L. Klier, T. Bresser, T. A. Nigst,
K. Karaghioso and P. Knochel, J. Am. Chem. Soc., 2012, 134,
13584; (b) H. Geo, M. J. Niphakis and G. I. Georg, J. Am.
Chem. Soc., 2008, 130, 3708; (c) Y. Moon, D. Kwon and
S. Hong, Angew. Chem., Int. Ed., 2012, 51, 11333;
(d) F. Chen, Z. Feng, C.-Y. He, H.-Y. Wang, Y.-L. Guo and
X. Zhang, Org. Lett., 2012, 14, 1176; (e) Y. Moon and
S. Hong, Chem. Commun., 2012, 48, 7191; (f) M. Min,
H. Choe and S. Hong, Asian J. Org. Chem., 2012, 1, 47.
10 (a) J. R. Zimmerman, M. Manpadi and R. Spatney, Green
Chem., 2011, 13, 3103; (b) M. Min, H. Choe and S. Hong,
Asian J. Org. Chem., 2012, 1, 47; (c) D. Kim, K. Ham and
S. Hong, Org. Biomol. Chem., 2012, 10, 7305; (d) M. Min
and S. Hong, Chem. Commun., 2012, 48, 9613;
(e) M. Khoobi, M. Alipour, S. Zarei, F. Jafarpour and
A. Shafiee, Chem. Commun., 2012, 48, 2985; (f) Y. Li, Z. Qi,
H. Wang, X. Fu and C. Duan, J. Org. Chem., 2012, 77, 2053.
3422 | Org. Biomol. Chem., 2014, 12, 3413–3422
This journal is © The Royal Society of Chemistry 2014