Cp?Ir(III)-Catalyzed C-H/O-H Functionalization of Salicylaldehydes for the Synthesis of Chromones at Room Temperature

Article abstract of DOI:10.1021/acs.joc.9b01139

Herein, we report Cp Ir(III)-catalyzed C-H/O-H-bond functionalization of salicylaldehydes with α-diazocarbonyl compounds for the synthesis of chromones under redox-neutral conditions. The reaction proceeds at room temperature and displays excellent functi

Full text of DOI:10.1021/acs.joc.9b01139

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Article
Cp*Ir(III)-Catalyzed C-H/O-H Functionalization of Salicylaldehydes
for the Synthesis of Chromones at Room Temperature
Dhanaji M Lade, Yogesh N Aher, and Amit B. Pawar
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01139 • Publication Date (Web): 26 Jun 2019
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Cp*Ir(III)-Catalyzed C−H/O−H Functionalization of Salicylaldehydes for
the Synthesis of Chromones at Room Temperature
†
‡
†
†‡
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Dhanaji M. Lade , Yogesh N. Aher , and Amit B. Pawar*
†
Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad
00007, India.
5
‡
Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
Email: amitorgchem@gmail.com, amit@iict.res.in
O
O
R4
O
Me
H
Me
H
R3
O
O
O
H
N2
H
R4
R3
H
H
H
Ir(III)
OH
room temp

Room temperature
Redox-neutral


Functional group tolerance
Late stage functionalization

ABSTRACT: Herein we report Cp*Ir(III)-catalyzed C−H/O−H bond functionalization of
salicylaldehydes with -diazocarbonyl compounds for the synthesis of chromones under redox-
neutral conditions. The reactions proceeds at room temperature and displays excellent functional
group tolerance along with high yields of the corresponding products. The developed reaction
protocol was successfully applied for the late stage functionalization of estrone derivative.
INTRODUCTION
In recent years, the area of mild CH activation has gained significant importance; as it allows to
carry out the reactions at or below room temperature and in the absence of any oxidant or reductant.1
This results into the enhancement of the functional group tolerance of the reactions and ultimately it
leads to the application in the late stage functionalization of complex biomolecules. Salicylaldehydes
constitutes an important class of organic molecules wide range of applicability. They serve as an
2
important precursor for the synthesis of salen ligands of Jacobsen’s catalyst. In recent years,
2
3,4
aldehydic C(sp )−H bond functionalization has gained considerable attention. The synthesis of
various important organic scaffolds such as chromones, benzofurans, 3‑coumaranones, chroman-4-
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ones, homoisoflavonoids, and flavones have been reported starting from salicylaldehydes through
5
hydroxy-directed aldehydic CH functionalization. Although, there are several reports on transition
metal catalyzed CH functionalization/annulation reactions of salicylaldehydes, there is only one
report in the literature by Miura et al. using iridium catalytic system wherein, they have reported
iridium(III)/copper(III) catalyzed decarbonylative coupling of salicylaldehydes with alkynes for the
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synthesis of benzofurans (Scheme 1). The major limitations of this protocol are the requirements of
co-catalytic amounts of copper salt, oxygen as a external oxidant and very high temperature (165 C)
to perform the reaction. Therefore, we became interested to develop an Ir(III)-catalyzed CH
functionalization/annulation of salicylaldehydes under mild conditions, which can suppress the
decarbonylation and switch the product selectivity from benzofurans to chromones. Chromones are
oxygen containing heterocycles often encounters in biologically important natural products such
6
flavones and isoflavones. In order to achieve this goal, initially we envisioned that the coupling of
7
salicylaldehydes with diazo compounds would be an ideal route. However, very recently Huang et al.
reported Rh(III)-catalyzed coupling between salicylaldehydes with -diazomalonates for the synthesis
of 4-hydroxycoumarins, wherein during optimization studies they have reported that, the Ir(III)
catalytic system failed to produced the required product.8
Scheme 1. Ir(III)-Catalyzed CH Functionalization/Annulation of Salicylaldehydes
Previous report
Ir(III)-catalyzed coupling of salicylaldehyde with alkyne by Miura et al.
O
R1
[Cp*IrCl2]2 (2 mol %)
R2
Cu(OAc)2H2O (10 mol%)
H
R1
R
R
DBU (10 mol%), xylene
O
OH
O
R2

O2 (1 atm), 160 C
Benzofurans
This work
O
[Cp*IrCl2]2 (2.5 mol %)
PivOH (2.0 equiv.)
O
R4
R4
H
R3
R
R
MeOH
R3
OH
N2
O
room temp
Chromones
*
*
Switch of selectivity from benzofuran to chromone
Redox-neutral * Room temperature protocol
Therefore, the choice of the diazo compound would be crucial to in order to synthesize the chromones
from salicylaldehydes under Ir(III) catalytic system. In continuation of our interest in the area of mild
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CH bond functionalization, herein we report Cp*Ir(III)-catalyzed CH/OH functionalization of
salicylaldehydes with -diazocarbonyl compounds for the synthesis of chromones at room
temperature.10
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RESULTS AND DISCUSSION
Recently, we have successfully developed an iridium-catalyzed synthesis of 1,2-benzothaizines via
9b
C−H/N−H bond functionalization of sulfoximines with -diazocarbonyl compounds, wherein during
the optimization studies, ethyl diazoacetoacetate (2a) has been used as a coupling partner. Therefore,
we have decided to use salicylaldehyde (1a) and ethyl diazoacetoacetate (2a) as a model substrates for
optimization of the reaction parameters (Table 1).
Table 1. Optimization Studya
O
O
CO2Et
Me
O
O
CO2Et
Me
[
Cp*IrCl2]2 (2.5 mol %)
H
EtO
Me
Ag (I) salt
O
O
OH
N2
2a
additive, solvent
1
a
3aa
4aa
3
h, room temp
Ag(I) salt
(10 mol
Yield (%)b
of 3aa
Additive
(equiv.)
Entry
Solvent
%)
AgSbF6
-
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
n.d.c
n.d.d
73
1
2
3
4
5
6
7
8
9
AgSbF6
PivOH (1.0)
PivOH (1.0)
PivOH (2.0)
AcOH (2.0)
-
-
-
-
-
-
-
-
-
-
-
97
62
AdCO
PhCO
2
H (2.0)
77
2
H (2.0)
86
NaOAc (2.0)
KOAc (2.0)
PivOH (2.0)
PivOH (2.0)
PivOH (2.0)
PivOH (2.0)
60
62
1
1
1
0
1
2
1,4-Dioxane
1,2-DCE
THF
80
62
44
13
4e
MeCN
71
1
-
PivOH (2.0)
PivOH (2.0)
MeOH
70
1
5f
6g
7h
-
-
-
-
MeOH
MeOH
MeOH
MeOH
n.d.
1
1
PivOH (2.0)
PivOH (2.0)
PivOH (2.0)
13
n.d.
n.d.
1
8i
aReaction conditions: 1a (0.10 mmol), 2a (0.12 mmol), [Cp*IrCl
] (2.5 mol %), AgSbF (10 mol %) and
2 2 6
b
1
additives in solvent (0.6 mL) at room temperature for 3 h. Yields are based on crude H NMR (internal
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c
d
standard: 1,1,2,2 tetrachloroethane). Formation of 4aa was observed in 22% yield. Formation of 4aa was
e
f
. gUsing [Cp*RhCl
h
observed in 27% yield. [Cp*IrCl
2
]
2
(1.0 mol %). Without [Cp*IrCl
2
]
2
2 2
] (2.5 mol %). Using
i
[Ru(p-Cymene)Cl
2 2 2
] (2.5 mol %). Using [Cp*Co(CO)I ] (5.0 mol %). n.d. = not detected. Room temperature
refers to 25 C.
0
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At first, when salicylaldehyde 1a was reacted with ethyl diazoacetoacetate (2a) in presence of
Cp*IrCl ] /AgSbF in MeOH at room temperature, it resulted in the formation of benzofuran 4aa in
[
2
2
6
lower yield (entry 1). The addition of PivOH (1.0 equiv.) also did not change the outcome of the
reaction (entry 2). To our surprise, when the reaction was performed using 1.0 equiv of PivOH in the
absence of AgSbF , it resulted in the complete switch in the product selectivity from benzofuran (4aa)
6
to chromone (3aa), wherein 3aa was formed exclusively in 73% yield (entry 3). After screening the
effect of different additives (entries 4-9), it was observed that the 2.0 equiv. of pivalic acid furnished
the superior results giving quantitative yield of the product (entry 4). The use of other solvents such as
1,2-DCE, CH CN, 1,4-dioxane, and THF was not beneficial to further improve the yield of the
3
reaction (entries 10-13). The yield of the product was dropped to 70% when catalyst loading was
reduced to 1 mol% (entry 14). It is worth to mention that, although Lin and Yao et al. reported a
5d
similar reaction using [Cp*RhCl ] catalyst, when we used Rh(III) catalytic system under the present
2
2
condition at room temperature, it resulted in the sluggish reaction with the lower yield (13% yield) of
required chromone 3aa (entry 16). The use of other catalysts such as [(p-cymene)RuCl ] and
2
2
[
Cp*Co(CO)I ] did not furnish the required product (entries 17-18).
2
After optimizing the reaction parameters, next we investigated the scope and generality of the
developed protocol using different salicylaldehydes with ethyl diazoacetoacetate (2a) as a
representative coupling partner (Scheme 2). To our delight, salicylaldehydes having electron-donating
t
substituents such as Me, Bu, and OMe at C5 position and C4 position gave the corresponding
products in high yields (3ba−3fa).The substrate with C5 phenyl group also furnish the chromone 3ha
in 70% yield. The substrate bearing electron-withdrawing fluoro substituent (1g) at C4 position
furnished the corresponding product (3ga) in quantitative yield. The salicylaldehyde bearing free
hydroxy group also well tolerated furnishing the chromone 3ia in 71% yield. Ethyl 6-methyl-8-oxo-
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H-[1,3]dioxolo[4,5-g]chromene-7-carboxylate
(3ja)
was
obtained
starting
from
6-
hydroxybenzo[d][1,3]dioxole-5-carbaldehyde (1j) in 90% yield. The substrates having halogen
functionality such as Cl, Br and I gave the corresponding products in high yield (3ka−3ma).
1
1
1
1
1
1
1
1
1
1
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Scheme 2. Scope of Salicylaldehydesa
O
O
O
O
CO2Et
Me
[
Cp*IrCl2]2 (2.5 mol %)
H
R
R
Me
OEt
PivOH (2.0 equiv.)
MeOH, 3 h
O
OH
N2
2a
1
3
room temp
O
O
O
O
O
O
Me
CO2Et tBu
Me
CO2Et
Me
MeO
CO Et
CO Et
2
2
O
O
Me
R
Me
91% (3ba)
84% (3ca)
90% (3da)
R = Me, 91% (3ea)
R = OMe, 82% (3fa)
O
O
O
O
CO2Et
Ph
CO2Et
CO2Et
CO2Et
O
O
F
O
Me
O
Me
HO
O
Me
O
Me
8
5% (3ga)b
70% (3ha)
71% (3ia)
90% (3ja)
O
O
O
O
Cl
CO2Et
Br
CO2Et
I
CO2Et
Me
O2N
CO2Et
Me
O
Me
O
Me
O
O
75% (3ka)b
71% (3la)b
64% (3ma)b
73% (3na)b
O
O
Me
O
H
O
O
CO2Et
CO2Et
CO2Et
CO2Et
O
O
Me
O
Me
O
Me
O
Me
Me
8
2% (3qa)b,c
90% (3ra)b,c
86% (3pa)
8
9% (3oa)
aReaction conditions: 1 (0.40 mmol), 2a (1.5 equiv.), [Cp*IrCl
] (2.5 mol %) and PivOH (2.0 equiv.) in MeOH (2.5
2 2
b
c
mL) at room temperature for 3 h. t-AmOH was used as a solvent. Reaction carried out on 0.3 mmol scale. Isolated
yields are given.
The salicylaldehyde containing electron-withdrawing NO group at C5 position also participated in
2
the reaction to furnish 3na in 73% yield. The reaction was further employed to the substrate having
ortho-methyl group which resulted in the 89% yield of 3oa.Furthermore, when the reaction was
performed on 1-hydroxy-2-naphthaldehyde (1p), it resulted in formation of required product (3pa) in
good yield. The functional group tolerance of the current protocol was further demonstrated by using
salicylaldehydes possessing keto and aldehyde functionalities which furnished the required
chromones in excellent yields (3qa−3ra). It is quite interesting to note that, in case of 5-formyl
salicylaldehyde (1r) the reaction selectively occurs at aldehydic CH bond next to the hydroxy group,
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and thus keep other formyl group intact and provides an opportunity for further manipulation of C5
formyl group.
Next, the scope and reactivity pattern of -diazocarbonyl compounds was investigated using
salicylaldehyde 1a as a representative coupling partner (Scheme 3). The reaction worked well with
diazo compounds having ethyl ester (2a), methyl ester (2b), and tert-butyl ester (2c) to give the
chromones in excellent yields (3aa−3ac). The reaction worked well with -diazocarbonyls having
various substituents such as ethyl (2d), propyl (2e), isopropyl (2f), cyclopropyl (2g), and chloromethyl
0
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9
0
(2h), to furnish corresponding chromones in excellent yields (3ad−3ah). Diazo precursor obtained
from pentane-2,4-dione also underwent coupling with salicylaldehyde to furnish the required product
in moderate yield (3ai). The practicality of the current protocol was demonstrated by gram scale
synthesis of the chromone 3aa; wherein when 1.0 gm of 1a was reacted under standard conditions, it
furnished 3aa in 83% yield (1.58 gm).
Scheme 3. Scope of -diazocarbonyl compoundsa
O
O
O
O
R4
[Cp*IrCl2]2 (2.5 mol %)
H
R4
R3
PivOH (2.0 equiv.)
MeOH, 3 h
R3
OH
N2
2
1a
3
room temp
O
O
O
O
CO2Et
Me
CO2Me
CO2tBu
Me
O
Me
O
94% (3aa)
94% (3ab)
92% (3ac)
Gram scale reaction
83% (1.58 gm)
O
O
O
CO2Et
CO2Et
CO2Et
O
O
O
90% (3ad)
93% (3ae)
90% (3af)
O
O
O
O
CO2Me
CO2Et
Cl
O
O
O
44% (3ag)
92% (3ah)
64% (3ai)
aReaction conditions: 1a (0.40 mmol), 2 (1.5 equiv.), [Cp*IrCl
] (2.5 mol %) and PivOH (2.0 equiv.) in MeOH (2.5
2 2
mL) at room temperature for 3 h. Isolated yields are given.
Late stage functionalization has gain considerable attention in recent years, as it utilizes CH bond
of drug-like molecules for further diversification in order to generate new functionalized analogues.11
Hence, we were interested check the applicability of the current protocol for the late stage
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functionalization (Scheme 4). To our delight, estrone derivative 5 underwent CH/OH
functionalization to furnish the required chromones in good yields (6a, 6f and 6c).
Scheme 4. Late Stage Functionalization of Estrone Derivativea
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
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4
5
6
7
8
9
0
1
2
3
4
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1
2
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1
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1
2
3
4
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9
0
O
R4
O
R3
O
Me
Me
O
N2
O
O
H
H
2
R4
R3
H
H
H
[Cp*IrCl2]2 (2.5 mol %)
PivOH (2.0 equiv.)
H
H
OH
5
MeOH, 3 h, room temp
6
O
O
O
Me
Me
Me
H
O
O
O
O
O
H
H
H
t
CO2Et
Me
CO2Et
CO2 Bu
H
H
H
H
H
O
Me
91% (6a)
93% (6f)
87% (6c)
aReaction conditions: 5 (0.20 mmol), 2 (1.5 equiv.), [Cp*IrCl
] (2.5 mol %) and PivOH (2.0 equiv.) in MeOH (1.2
2 2
mL) at room temperature for 3 h. Isolated yields are given.
In order to elucidate the reaction mechanism, some preliminary experiments were conducted
1
2
(
Scheme 5). At first, H/D exchange experiments of salicylaldehyde 1a was carried out to check the
reversibility of the C−H activation step. When 1a was treated with 2.5 mol% of [Cp*IrCl ] along
2
2
with CD COOD (2.0 equiv.) in the absence of ethyl diazoacetoacetate (2a) in CD OD, it did not show
3
3
any D incorporation at the aldehydic CH bond (Scheme 5a), which indicates the irreversible nature
of the C−H activation step.
Scheme 5. Mechanistic Findings
(a) H/D Exchange Study
O
O
[Cp*IrCl2]2 (2.5 mol %)
H/D
0% D
H
CD3COOD (2.0 equiv.)
CD3OD, rt, 3 h
OH
OH
[
D]n-1a
1
a
(b) Intermolecular Competitive Experiment
O
O
O
O
CO2Et
Me
H
H
2a (1.5 equiv.)
MeO
OH
F
OH
[Cp*IrCl2]2 (2.5 mol %)
X
PivOH (2.0 equiv.)
MeOH, rt, 3 h
1f
(0.1 mmol)
1g (0.1 mmol)
X = OMe, 3fa
X = F, 3ga
1
3
fa/3ga = 1/2.2 ( H NMR)
(c) Kinetic Isotope Effect
O
O
O
H
D
2a (1.5 equiv.)
H/D
3
aa
standard conditions
OH
OH
1a-D
OH
1
9%
1a
1.34 (1H NMR)
1a + 1a-D
kH/kD =
(1:1.3)
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The intermolecular competition experiment between salicylaldehydes having OMe and F substituents
at C4 position revealed that substrate having F functionality reacts preferentially (Scheme 5b). In
order to determine the kinetic isotope effect (KIE), the intermolecular competition experiment was
1
carried out between equimolar quantities of 1a and 1a-D. The H NMR analysis of the mixture of
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
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8
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0
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0
unreacted 1a and 1a-D gave k /k = 1.34 (Scheme 5c). Furthermore, parallel experiments were
H
D
conducted using 1a and 1a-D which resulted in KIE of value k /k = 1.5 (see supporting information
H
D
for details). These moderate values of KIE indicates that the C−H bond cleavage may be the turnover-
determining step.
10
Based on our preliminary mechanistic studies and precedent literature, the plausible mechanistic
cycle is proposed in Scheme 6. At first [Cp*IrCl ] reacts with PivOH to form catalytically active
2
2
Ir(III) species A, which undergoes irreversible cyclometallation with 1 through hydroxy-directed
aldehydic CH bond activation to generate five-membered iridacycle B. Later on, diazo precursor 2
7
c
coordinates with B in order to generate diazonium species C, which undergoes loss of nitrogen to
generates Ir(III)-carbene species D. Migratory insertion of the Ir-carbene D into the iridium−carbon
bond provides the six membered iridacyclic intermediate E which on protonolysis with pivalic acid
leads to the formation F and regenerates Ir(III) species A. Finally, the alkylated product F undergoes
acid promoted cyclization followed by dehydration to generate required chromone 3.
Scheme 6. Plausible Mechanism
[Cp*IrCl2]2 + PivOH
O
H2O
R4
R3
O
Me
3
Me
Me
Me
Me
PivOH
H
OH
O
Ir
A
O
OH
PivOH
PivCO2
F
1
O
Piv
2PivOH
2
R3
O
O
O
O
R4
Ir Cp*
O
Ir
Cp*
Ir(III)
B
O
E
R4
R3
N2
2
O
O
Cp*
Cp*
Ir
Ir
O
R4
O
R3
R4
R3
N
O
O
N
D
N2
C
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CONCLUSION
In conclusion, we have developed Ir(III)-catalyzed CH/OH functionalization of salicylaldehyde
with -diazocarbonyl compounds for the synthesis of chromones. The salient features of the present
protocol includes mild reaction conditions (room temperature), high yields of the products with
excellent functional group tolerance. The reaction works under air atmosphere and doesn't require any
special precaution to maintain the inert atmosphere, thus makes it very operationally simple and
practical method. The mechanistic studies revealed that C−H activation step is irreversible and may be
the rate-determining step. The synthetic utility of this protocol was demonstrated via late stage
functionalization.
1
1
1
1
1
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0
EXPERIMENTAL SECTION
General Remarks
Unless otherwise stated, all commercial reagents and solvents were used without additional
purification. Analytical thin layer chromatography (TLC) was performed on pre-coated silica gel 60
F254 plates. Visualization on TLC was achieved by the use of UV light (254 nm). Column
chromatography was undertaken on silica gel (100‒200 mesh) using a proper eluent system. NMR
1
spectra were recorded in chloroform-d at 300 or 400 MHz for H NMR spectra and 75 MHz or 100
1
3
MHz for C NMR spectra. Chemical shifts were quoted in parts per million (ppm) referenced to the
appropriate solvent peak or 0.0 ppm for tetramethylsilane. The following abbreviations were used to
describe peak splitting patterns when appropriate: br = broad, s = singlet, d = doublet, t = triplet, q =
quartet, dd = doublet of doublet, td = triplet of doublet, m = multiplet. Coupling constants, J, were
reported in hertz unit (Hz). For 13C NMR chemical shifts were reported in ppm referenced to the
center of a triplet at 77.0 ppm of chloroform-d. HRMS were recorded using ESI-TOF techniques. The
substituted salicylaldehyde derivatives were prepared according to literature procedure.13 The -
diazocarbonyl compounds were prepared according to the procedure described in the literature.14
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6
General Procedure for Ir-Catalyzed CH/OH Functionalization of Salicylaldehydes for the
Synthesis of Chromones.
To a screw capped seal tube vial with a Teflon stirbar were added salicylaldehyde 1 (0.40 mmol),
diazo compound 2 (0.60 mmol, 1.2 equiv), [Cp*IrCl ] (8.0 mg, 2.5 mol %), PivOH (81.6 mg, 2.0
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
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8
9
0
1
2
3
4
5
6
7
8
9
0
2 2
equiv.), and MeOH (2.5 mL) under air atmosphere. The reaction mixture was stirred at room
temperature for 3 h. Then the reaction mixture was diluted with CH Cl (10 mL). The solvents were
2
2
removed under reduced pressure and the residue was purified by column chromatography on silica gel
n-hexane/EtOAc) to give the desired chromone derivatives.
(
1
0
1
Ethyl 2-methyl-4-oxo-4H-chromene-3-carboxylate (3aa). White solid (87.0 mg, 94%); H NMR
(500 MHz, CDCl ) δ 8.20 (dd, J = 7.9, 1.0 Hz, 1H), 7.69 – 7.64 (m, 1H), 7.45 – 7.36 (m, 2H), 4.42
3
1
3
1
(q, J = 7.1 Hz, 2H), 2.52 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.3,
3
1
66.6, 165.1, 155.5, 133.9, 126.1, 125.5, 123.3, 118.1, 117.7, 61.7, 19.5, 14.2.
Gram Scale Synthesis of 3aa: To a screw capped seal tube vial with a Teflon stirbar were added
salicylaldehyde 1a (1.0 gm, 8.20 mmol), ethyl diazoacetoacetate 2a (1.92 gm, 12.3 mmol, 1.5 equiv),
[
Cp*IrCl ] (163 mg, 2.5 mol %), PivOH (1.67 gm, 2.0 equiv.), and MeOH (50 mL) under air
2 2
atmosphere. The reaction mixture was stirred at room temperature for 3 h. Then solvent was removed
under reduced pressure and the residue was purified by column chromatography on silica gel (n-
hexane/EtOAc) to give the desired chromone 3aa (1.58 gm, 83%).
5d
1
Ethyl 2,6-dimethyl-4-oxo-4H-chromene-3-carboxylate (3ba). White solid (90.0 mg, 91%); H
NMR (400 MHz, CDCl ) δ 7.97 (d, J = 0.9 Hz, 1H), 7.46 (dd, J = 8.5, 2.1 Hz, 1H), 7.31 (d, J = 8.5
3
13
1
Hz, 1H), 4.46 – 4.37 (m, 2H), 2.50 (s, 3H), 2.44 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C{ H} NMR (100
MHz, CDCl ) δ 174.4, 166.4, 165.2, 153.8, 135.5, 135.1, 125.4, 123.0, 118.0, 117.4, 61.7, 20.9, 19.5,
3
1
4.2.
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Ethyl 6-(tert-butyl)-2-methyl-4-oxo-4H-chromene-3-carboxylate (3ca).10 Pale yellow solid (97.0
1
mg, 84%); H NMR (500 MHz, CDCl ) δ 8.19 (d, J = 2.4 Hz, 1H), 7.71 (dd, J = 8.8, 2.5 Hz, 1H),
3
7
.35 (d, J = 8.8 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 2.50 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H), 1.36 (s, 9H);
1
3
1
C{ H} NMR (100 MHz, CDCl ) δ 174.6, 166.4, 165.3, 153.7, 148.8, 131.7, 122.6, 121.8, 117.9,
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
17.2, 61.6, 34.8, 31.2, 19.4, 14.2.
Ethyl 6-methoxy-2-methyl-4-oxo-4H-chromene-3-carboxylate (3da).10 White solid (94.0 mg,
1
9
0%); H NMR (400 MHz, CDCl ) δ 7.56 (d, J = 3.1 Hz, 1H), 7.35 (d, J = 9.1 Hz, 1H), 7.24 (dd, J =
3
1
3
1
9
.1, 3.1 Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 2.51 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C{ H}
NMR (100 MHz, CDCl ) δ 174.2, 166.3, 165.3, 157.1, 150.3, 123.9, 123.8, 119.1, 105.2, 61.6, 55.9,
3
1
9.4, 14.2.
Ethyl 2,7-dimethyl-4-oxo-4H-chromene-3-carboxylate (3ea).5d White solid (90.0 mg, 91%); H
1
NMR (500 MHz, CDCl ) δ 8.07 (d, J = 8.4 Hz, 1H), 7.24 – 7.12 (m, 2H), 4.41 (q, J = 7.1 Hz, 2H),
3
1
3
1
2
.49 (s, 3H), 2.47 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.3, 166.3,
3
165.23, 155.7, 145.3, 126.9, 125.8, 121.1, 118.0, 117.4, 61.7, 21.8, 19.4, 14.2.
1
0
Ethyl 7-methoxy-2-methyl-4-oxo-4H-chromene-3-carboxylate (3fa). White solid (86.0 mg, 82%);
1
H NMR (400 MHz, CDCl ) δ 8.10 (d, J = 8.9 Hz, 1H), 6.96 (dd, J = 8.9, 2.4 Hz, 1H), 6.81 (d, J =
3
1
2
.4 Hz, 1H), 4.41 (d, J = 7.1 Hz, 2H), 3.90 (s, 3H), 2.48 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); 13C{ H}
NMR (100 MHz, CDCl ) δ 173.7, 166.0, 165.2, 164.2, 157.3, 127.5, 118.0, 117.1, 114.5, 100.1, 61.7,
3
55.8, 19.3, 14.2.
Ethyl 7-fluoro-2-methyl-4-oxo-4H-chromene-3-carboxylate (3ga). White solid (64.0 mg, 85%);
1
m.p. 89– 91 °C; H NMR (400 MHz, CDCl ) δ 8.21 (dd, J = 8.7, 6.3 Hz, 1H), 7.19 – 7.06 (m, 2H),
3
1
3
1
4.42 (q, J = 7.1 Hz, 2H), 2.51 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ
3
173.3, 166.8, 165.62 (d, J = 255.7 Hz), 164.7, 156.38 (d, J = 13.3 Hz), 128.55 (d, J = 10.7 Hz), 120.1,
1
18.2, 114.19 (d, J = 22.7 Hz), 104.44 (d, J = 25.5 Hz), 61.8, 19.3, 14.1; HRMS (ESI) m/z calcd. for
+
C H FO Na [M+H] : 273.0539, found: 273.0542.
1
3
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5d
Ethyl 2-methyl-4-oxo-6-phenyl-4H-chromene-3-carboxylate (3ha). White solid (86.0 mg, 70%);
1
H NMR (400 MHz, CDCl ) δ 8.40 (d, J = 2.2 Hz, 1H), 7.89 (dd, J = 8.7, 2.3 Hz, 1H), 7.63 (d, J =
3
7
.2 Hz, 2H), 7.54 – 7.42 (m, 3H), 7.41 – 7.31 (m, 1H), 4.43 (q, J = 7.1 Hz, 2H), 2.52 (s, 3H), 1.41 (t, J
1
3
1
=
7.1 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.3, 166.6, 165.0, 154.9, 139.0, 138.6, 132.7,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
28.9, 127.9, 127.1, 123.8, 123.4, 118.2, 118.1, 61.7, 19.5, 14.2.
Ethyl 7-hydroxy-2-methyl-4-oxo-4H-chromene-3-carboxylate (3ia). Light brown solid (70.0 mg,
1
7
7
1%); m.p. 184– 186 °C; H NMR (500 MHz, CDCl ) δ 8.47 (brs, 1H), 8.04 (d, J = 8.8 Hz, 1H),
3
.01 (dd, J = 8.8, 2.2 Hz, 1H), 6.89 (d, J = 2.2 Hz, 1H), 4.40 (q, J = 7.1 Hz, 2H), 2.50 (s, 3H), 1.37 (t,
1
3
1
J = 7.1 Hz, 3H); C{ H} NMR (125 MHz, CDCl ) δ 174.7, 167.1, 165.3, 162.6, 157.5, 127.7, 117.5,
3
+
1
16.3, 115.8, 102.9, 61.9, 19.5, 14.1; HRMS (ESI) m/z calcd. for C H O [M+H] : 249.0763,
13 13
5
found: 249.0759.
Ethyl 6-methyl-8-oxo-8H-[1,3]dioxolo[4,5-g]chromene-7-carboxylate (3ja).5d White solid (99.0
1
mg, 90%); H NMR (400 MHz, CDCl ) δ 7.49 (s, 1H), 6.81 (s, 1H), 6.10 (s, 2H), 4.41 (q, J = 7.1 Hz,
3
1
3
1
2H), 2.47 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 173.3, 165.6, 165.2,
3
152.9, 152.8, 146.3, 118.3, 117.5, 102.6, 102.5, 97.7, 61.7, 19.2, 14.2.
1
0
Ethyl 6-chloro-2-methyl-4-oxo-4H-chromene-3-carboxylate (3ka). Light yellow solid (77.0 mg,
1
7
5%); H NMR (400 MHz, CDCl ) δ 8.15 (d, J = 2.6 Hz, 1H), 7.61 (dd, J = 8.9, 2.6 Hz, 1H), 7.39 (d,
3
1
3
1
J = 8.9 Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 2.52 (s, 3H), 1.39 (d, J = 7.1 Hz, 3H); C{ H} NMR (100
MHz, CDCl ) δ 173.1, 166.9, 164.7, 153.8, 134.2, 131.5, 125.5, 124.3, 119.5, 118.1, 61.9, 19.5, 14.2.
3
5
d
Ethyl 6-bromo-2-methyl-4-oxo-4H-chromene-3-carboxylate (3la). White solid (88.0 mg, 71%);
1
H NMR (400 MHz, CDCl ) δ 8.31 (d, J = 2.4 Hz, 1H), 7.75 (dd, J = 8.9, 2.4 Hz, 1H), 7.32 (d, J =
3
8.9 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 4.41 (q, J = 7.1 Hz, 2H), 2.51 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H);
1
3
1
C{ H} NMR (100 MHz, CDCl ) δ 173.0, 166.9, 164.7, 154.3, 136.9, 128.7, 124.7, 119.7, 119.0,
3
1
18.2, 61.9, 19.5, 14.2.
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Ethyl 6-iodo-2-methyl-4-oxo-4H-chromene-3-carboxylate (3ma).10 White solid (92.0 mg, 64%);
1
H NMR (500 MHz, CDCl ) δ 8.50 (d, J = 2.1 Hz, 1H), 7.92 (dd, J = 8.8, 2.2 Hz, 1H), 7.19 (d, J =
3
1
8
.8 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 2.51 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); 13C{ H} NMR (125
MHz, CDCl ) δ 172.8, 166.9, 164.6, 155.0, 142.5, 134.9, 124.9, 119.8, 118.3, 89.4, 61.9, 19.5, 14.2.
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Ethyl 2-methyl-6-nitro-4-oxo-4H-chromene-3-carboxylate (3na).5d White solid (81.0 mg, 73%);
1
H NMR (400 MHz, CDCl ) δ 9.04 (d, J = 2.8 Hz, 1H), 8.51 (dd, J = 9.2, 2.8 Hz, 1H), 7.61 (d, J =
3
1
9
.2 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 2.57 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H); 13C{ H} NMR (100
MHz, CDCl ) 172.7, 167.4, 164.0, 158.2, 144.9, 128.3, 123.5, 122.7, 119.6, 118.6, 62.1, 19.4, 14.1.
3
,
Ethyl 2,8-dimethyl-4-oxo-4H-chromene-3-carboxylate (3oa).5d White solid (88.0 mg, 89%); H
1
NMR (500 MHz, CDCl ) δ 8.03 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 7.3 Hz, 1H), 7.28 (t, J = 7.6 Hz,
3
1
3
1
1
H), 4.42 (q, J = 7.1 Hz, 2H), 2.54 (s, 3H), 2.46 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); C{ H} NMR (125
MHz, CDCl ) δ 174.6, 166.2, 165.2, 154.0, 134.8, 127.0, 124.9, 123.6, 123.2, 117.9, 61.6, 19.4, 15.4,
3
1
4.2.
1
0
Ethyl 2-methyl-4-oxo-4H-benzo[h]chromene-3-carboxylate (3pa). White solid (97.0 mg, 86%);
1
H NMR (500 MHz, CDCl ) δ 8.38 (d, J = 8.1 Hz, 1H), 8.08 (d, J = 8.7 Hz, 1H), 7.88 (d, J = 8.1 Hz,
3
1
1
H), 7.73 – 7.60 (m, 3H), 4.45 (q, J = 7.1 Hz, 2H), 2.62 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H); 13C{ H}
NMR (100 MHz, CDCl ) δ 174.1, 165.5, 165.0, 152.8, 135.8, 129.3, 128.0, 127.1, 125.4, 123.3,
3
121.9, 120.7, 119.6, 119.7, 61.71, 19.3, 14.2.
Ethyl 6-acetyl-2-methyl-4-oxo-4H-chromene-3-carboxylate (3qa). White solid (68.0 mg, 82%);
1
m.p. 134– 136 °C; H NMR (400 MHz, CDCl ) δ 8.73 (d, J = 2.2 Hz, 1H), 8.30 (dd, J = 8.8, 2.2 Hz,
3
1
H), 7.50 (d, J = 8.8 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 2.69 (s, 3H), 2.55 (s, 3H), 1.41 (t, J = 7.1 Hz,
3H); 13C{ H} NMR (100 MHz, CDCl ) δ 196.2, 173.8, 167.0, 164.5, 158.0, 134.2, 133.0, 127.4,
1
3
122.8, 118.5, 61.9, 26.6, 19.4, 14.1 (one carbon is missing because of overlap); HRMS (ESI) m/z
+
calcd. for C H O [M+H] : 275.0919, found 275.0919.
1
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Ethyl 6-formyl-2-methyl-4-oxo-4H-chromene-3-carboxylate (3ra). White solid (70.0 mg, 90%);
1
m.p. 126– 128 °C; H NMR (400 MHz, CDCl ) δ 10.10 (s, 1H), 8.67 (d, J = 2.0 Hz, 1H), 8.22 (dd, J
3
=
8.7, 2.1 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 2.56 (s, 3H), 1.41 (t, J = 7.1 Hz,
1
3
H); 13C{ H} NMR (100 MHz, CDCl ) δ 190.2, 173.4, 167.1, 164.3, 158.7, 133.5, 132.2, 130.7,
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1
23.5, 119.2, 118.7, 62.0, 19.4, 14.1; HRMS (ESI) m/z calcd. for C H O [M+H] : 261.0763,
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4
14
5
found: 261.0765.
Methyl 2-methyl-4-oxo-4H-chromene-3-carboxylate (3ab).10 Yellow solid (82.0 mg, 94%); H
1
NMR (500 MHz, CDCl ) δ 8.19 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.46 – 7.37 (m, 2H),
3
1
3
1
.94 (s, 3H), 2.52 (s, 3H); 13C{ H} NMR (125 MHz, CDCl ) δ 174.2, 167.2, 165.5, 155.4, 133.9,
3
26.0, 125.5, 123.2, 117.6, 52.6, 19.6.
tert-Butyl 2-methyl-4-oxo-4H-chromene-3-carboxylate (3ac).5d White solid (96.0 mg, 92%); H
1
NMR (500 MHz, CDCl ) δ 8.18 (dd, J = 7.9, 1.4 Hz, 1H), 7.68 – 7.60 (m, 1H), 7.43 – 7.33 (m, 2H),
3
1
2
.48 (s, 3H), 1.61 (s, 9H); 13C{ H} NMR (125 MHz, CDCl ) δ 174.4, 165.1, 164.2, 155.6, 133.7,
3
125.9, 125.2, 123.4, 119.6, 117.6, 82.7, 28.1, 19.1.
5
d
1
Ethyl 2-ethyl-4-oxo-4H-chromene-3-carboxylate (3ad). Yellow gummy solid; (88.0 mg, 90%); H
NMR (500 MHz, CDCl ) δ 8.20 (dd, J = 8.0, 1.5 Hz, 1H), 7.67 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 7.44
3
(d, J = 8.4 Hz, 1H), 7.42 – 7.36 (m, 1H), 4.42 (q, J = 7.1 Hz, 2H), 2.78 (q, J = 7.6 Hz, 2H), 1.40 (t, J =
7.1 Hz, 3H), 1.37 (t, J = 7.6 Hz, 3H); 13C{ H} NMR (125 MHz, CDCl ) δ 174.6, 170.2, 165.0,
1
3
155.6, 133.9, 126.0, 125.4, 123.3, 117.9, 117.5, 61.67, 26.63, 14.1, 11.6.
5
d
1
Ethyl 4-oxo-2-propyl-4H-chromene-3-carboxylate (3ae). White solid (97.0 mg, 93%); H NMR
(
400 MHz, CDCl ) δ 8.20 (dd, J = 7.9, 1.5 Hz, 1H), 7.67 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 7.49 – 7.34
3
(m, 2H), 4.42 (q, J = 7.1 Hz, 2H), 2.73 (t, J = 7.5 Hz, 2H), 1.96 – 1.72 (m, 2H), 1.40 (t, J = 7.1 Hz,
1
3
1
3H), 1.04 (t, J = 7.4 Hz, 3H); C{ H} NMR (100 MHz, CDCl ) δ 174.5, 169.1, 165.0, 155.6, 133.9,
3
1
25.9, 125.3, 123.2, 118.2, 117.7, 61.6, 34.8, 20.8, 14.1, 13.6.
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Ethyl 2-isopropyl-4-oxo-4H-chromene-3-carboxylate (3af). Pale yellow solid (94.0 mg, 90%);
1
m.p.58– 60 °C; H NMR (400 MHz, CDCl ) δ 8.20 (dd, J = 7.9, 0.9 Hz, 1H), 7.71 – 7.63 (m, 1H),
3
7
1
1
2
.46 (d, J = 8.4 Hz, 1H), 7.43 – 7.36 (m, 1H), 4.41 (q, J = 7.1 Hz, 2H), 3.14 (hept, J = 6.8 Hz, 1H),
1
3
1
.42 – 1.35 (m, 9H); C{ H} NMR (125 MHz, CDCl ) δ 174.8, 172.0, 165.0, 155.6, 133.8, 125.9,
3
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+
25.3, 123.3, 117.7, 116.9, 61.7, 32.2, 19.8, 14.1; HRMS (ESI) m/z calcd. for C H O [M+H] :
1
5
17
4
61.1127, found: 261.1124.
Methyl 2-cyclopropyl-4-oxo-4H-chromene-3-carboxylate (3ag). White solid (43.0 mg, 44%); m.p.
1
1
1
1
51– 153 °C; H NMR (500 MHz, CDCl ) δ 8.19 (dd, J = 7.9, 1.6 Hz, 1H), 7.63 (ddd, J = 8.7, 7.2,
3
.7 Hz, 1H), 7.41 – 7.35 (m, 1H), 7.31 (d, J = 8.4 Hz, 1H), 3.97 (s, 3H), 2.35 – 2.26 (m, 1H), 1.39 –
1
3
1
.33 (m, 2H), 1.21 – 1.13 (m, 2H); C{ H} NMR (100 MHz, CDCl ) δ 173.9, 170.0, 166.0, 154.9,
3
133.8, 126.2, 125.4, 123.4, 117.3, 117.0, 52.7, 13.1, 9.7; HRMS (ESI) m/z calcd. for C H O
4
1
4
13
+
[M+H] : 245.0814, found: 245.0813.
5
d
Ethyl 2-(chloromethyl)-4-oxo-4H-chromene-3-carboxylate (3ah). Yellow solid (98.0 mg, 92%);
1
H NMR (400 MHz, CDCl ) δ 8.20 (d, J = 8.0 Hz, 1H), 7.77 – 7.67 (m, 1H), 7.50 (d, J = 8.4 Hz,
3
1
3
1
1H), 7.44 (t, J = 7.6 Hz, 1H), 4.63 (s, 2H), 4.45 (q, J = 7.1 Hz, 2H), 1.42 (t, J = 7.1 Hz, 3H); C{ H}
NMR (100 MHz, CDCl ) δ 174.2, 163.8, 162.5, 155.4, 134.6, 126.1, 126.0, 123.4, 118.5, 118.0, 62.2,
3
3
9.8, 14.1.
3-Acetyl-2-methyl-4H-chromen-4-one (3ai).10 White solid (52.0 mg, 64%); H NMR (400 MHz,
1
CDCl ) δ 8.21 (dd, J = 8.4, 1.6 Hz, 1H), 7.73 – 7.61 (m, 1H), 7.47 – 7.38 (m, 2H), 2.65 (s, 3H), 2.53
3
1
3
1
(
s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 200.5, 175.9, 168.7, 155.4, 134.1, 125.9, 125.6, 123.8,
3
1
23.7, 117.7, 32.2, 19.9.
Ethyl (3aS,3bR,11bS,13aS)-8,13a-dimethyl-1,10-dioxo-1,2,3,3a,3b,4,5,10,11b,12,13,13a-dodeca-
5
d
hydrocyclopenta[5,6]naphtho[1,2-g]chromene-9-carboxylate (6a). White solid (74.0 mg, 91%);
1
H NMR (400 MHz, CDCl ) δ 8.06 (s, 1H), 7.14 (s, 1H), 4.41 (q, J = 7.1 Hz, 2H), 3.18 – 2.93 (m,
3
2
H), 2.60 – 2.49 (m, 2H), 2.48 (s, 3H), 2.39 – 2.26 (m, 1H), 2.23 – 1.95 (m, 4H), 1.71 – 1.45 (m, 6H),
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.40 (t, J = 7.1 Hz, 3H), 0.92 (s, 3H); 13C{ H} NMR (100 MHz, CDCl ) δ 220.3, 174.3, 166.2,
3
65.3, 153.7, 144.4, 138.2, 122.2, 120.9, 117.7, 116.8, 61.6, 50.4, 47.8, 43.9, 37.7, 35.7, 31.3, 29.6,
5.9, 25.6, 21.5, 19.4, 14.1, 13.7.
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Ethyl (3aS,3bR,11bS,13aS)-8-isopropyl-13a-methyl-1,10-dioxo-1,2,3,3a,3b,4,5,10,11b,12,13, 13a-
dodecahydrocyclopenta[5,6]naphtho[1,2-g]chromene-9-carboxylate (6f). White solid (81.0 mg,
1
9
3%); m.p. 176– 178 °C; H NMR (400 MHz, CDCl ) δ 8.07 (s, 1H), 7.19 (s, 1H), 4.40 (q, J = 7.1
3
Hz, 2H), 3.24 – 2.95 (m, 3H), 2.63 – 2.43 (m, 2H), 2.40 – 2.26 (m, 1H), 2.22 – 1.93 (m, 4H), 1.74 –
1
1
.43 (m, 6H), 1.39 (t, J = 7.1 Hz, 3H), 1.35 (d, J = 3.2 Hz, 3H), 1.33 (d, J = 3.2 Hz, 3H); 13C{ H}
NMR (125 MHz, CDCl ) δ 220.3, 174.8, 171.6, 165.3, 153.9, 144.3, 138.1, 122.1, 121.0, 116.9,
3
1
16.6, 61.6, 50.4, 47.8, 44.0, 37.8, 35.7, 32.1, 31.3, 29.6, 25.9, 25.6, 21.5, 19.8, 14.1, 13.7; HRMS
+
(ESI) m/z calcd. for C H O [M+H] : 437.2328, found: 437.2335.
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tert-Butyl
(3aS,3bR,11bS,13aS)-8,13a-dimethyl-1,10-dioxo-1,2,3,3a,3b,4,5,10,11b,12,13,13a-
dodecahydrocyclopenta[5,6]naphtho[1,2-g]chromene-9-carboxylate (6c). White solid (76.0 mg,
1
87%); m.p. 163– 165 °C; H NMR (400 MHz, CDCl ) δ 8.05 (s, 1H), 7.12 (s, 1H), 3.11 – 2.91 (m,
3
2H), 2.61 – 2.47 (m, 2H), 2.45 (s, 3H), 2.37 – 2.26 (m, 1H), 2.23 – 1.95 (m, 4H), 1.69 – 1.43 (m,
1
3
1
6H),1.62 (s, 9H) 0.91 (s, 3H); C{ H} NMR (100 MHz, CDCl ) δ 220.3, 174.4, 164.8, 164.5, 153.8,
3
1
2
44.1, 138.0, 122.1, 121.1, 119.2, 116.8, 82.5, 50.4, 47.8, 43.9, 37.7, 35.7, 31.3, 29.6, 28.1, 26.0, 25.6,
+
1.5, 19.1, 13.7; HRMS (ESI) m/z calcd. for C H O Na [M+Na] : 459.2147, found: 459.2158.
2
7
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge at http://pubs.acs.org.
Details of mechanistic studies including the isotope labeling experiments (H/D exchange and KIE),
competitive experiment and characterization data for all synthesized chromone derivatives including
1
13
H and C NMR spectra
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AUTHOR INFORMATION
Corresponding Author
*
E-mail: amitorgchem@gmail.com, amit@iict.res.in
Author Contributions
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
D.M.L. and Y.N.A. contributed equally.
NOTES
The authors declare no competing financial interest.
ACKNOWLEDGMENT
A.B.P thanks DST, New Delhi for the INSPIRE Faculty Award (IFA 14, CH-157, GAP-0520).
Y.N.A thanks DST, New Delhi for research fellowship. D.M.L. thanks CSIR for a senior
research fellowship. We thank Dr. S. Chandrasekhar (Director, CSIR-IICT) for his support
and encouragement. IICT Communication No. for this manuscript is IICT/Pubs./2019/159.
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von Delius, M.; Le, C. M.; Dong, V. M. Rhodium-Phosphoramidite Catalyzed Alkene
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5022-15032. (c) Wang, H.; Xie, F.; Qi, Z.; Li, X. Iridium- and Rhodium-Catalyzed C–H Activation
and Formyl Alkynylation of Benzaldehydes under Chelation-Assistance. Org. Lett. 2015, 17, 920-
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3791-13794. (e) Grenet, E.; Waser, J. Iridium- and Rhodium-Catalyzed Directed C–H
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(
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