Thermally Induced Intramolecular Benzannulation of Diazoacetoacetate Enones Tethered with Unactivated Alkynes: Synthesis of Substituted 6 H-Benzo[ c ]chromenes

Article abstract of DOI:10.1055/s-0039-1690191

A facile and efficient intramolecular benzannulation strategy for the synthesis of substituted 6 H-benzo[ c ]chromenes from diazoaceto? acetate enones tethered with unactivated alkynes has been developed. The reaction proceeds in moderate to good yields under operationally simple conditions with thermally induced [4+2]-Annulation of intermediate vinyl ketenes as the key step.

Full text of DOI:10.1055/s-0039-1690191

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2019, 51, A–E
paper
A
en
Synthesis
Y. Chen et al.
Paper
Thermally Induced Intramolecular Benzannulation of Diazoaceto-
acetate Enones Tethered with Unactivated Alkynes: Synthesis of
Substituted 6H-Benzo[c]chromenes
O
Yangfan Chen
Di Wu
Wolff rearrangement
R1
benzannulation
CO2Me
H
Jiawen Zhou
Yun Wang
Jing Huang
Xichen Xu*
R2
O
R3
vinylketene
MeO
O
School of Chemistry and Environmental Engineering, Wuhan
Institute of Technology, Wuhan, 430205, P. R. of China
XichenXu@wit.edu.cn
O
O
H
OH
R1
xylenes, sealed tube, 190 °C, 30 min
OMe
R1
R2
N2
no catalyst
R2
O
R3
O
R3
up to 72% yield, 9 examples
Received: 13.05.2019
Accepted after revision: 06.08.2019
Published online: 28.08.2017
this end, intramolecular arylations of ortho-halo substitut-
ed aryl benzyl ethers either under transition-metal cataly-
4
5
DOI: 10.1055/s-0039-1690191; Art ID: ss-2019-h0266-op
sis or under transition-metal-free conditions have been
reported. The intramolecular Au-catalyzed biaryl coupling
of electron-rich arenes by aryltrimethylsilanes represents
Abstract A facile and efficient intramolecular benzannulation strategy
for the synthesis of substituted 6H-benzo[c]chromenes from diazoaceto-
acetate enones tethered with unactivated alkynes has been developed.
The reaction proceeds in moderate to good yields under operationally
simple conditions with thermally induced [4+2]-annulation of interme-
diate vinyl ketenes as the key step.
6
an alternative approach. The palladium-catalyzed intra-
molecular decarboxylative7 or dehydrogenative8 cross-
coupling, and, more recently, the visible-light-driven inter-
molecular radical cyclization of 2-(vinyloxy)-1,1′-biphenyls
with 2-bromo-2,2-difluoroamides/esters have also been
devised.9
Key words vinyl ketene, Wolff rearrangement, benzannulation, 6H-
benzo[c]chromene, diazoacetoacetate enone
Diazoacetate enones, which are readily prepared in a
one-pot protocol,10 belong to the class of acceptor/acceptor-
substituted diazo compounds. Diazoacetoacetate enones, as
demonstrated by Doyle et al.,11 are prone to Wolff rear-
rangement under catalysis of Rh (OAc) to afford intermedi-
ate vinyl ketenes, which react further with imines to pro-
vide lactams (Scheme 1, pathway a). Following the general
trend, ketenes have a strong propensity to participate in
[2+2]-cycloaddition. Consequently, vinyl ketenes rarely
engage in cycloadditions as [4+2] enophiles.12 Notable
exceptions include (trialkylsilyl)vinyl ketenes devised by
Danheiser et al.,13 which react as electron-rich dienes in
Diels–Alder and hetero-Diels–Alder reactions, and [4+1]-
annulations, due to the stabilization effect of trialkylsilyl
6
H-Benzo[c]chromene has recently emerged as one of
the privileged scaffolds in modern drug discovery because
of the broad range of significant biological activities and
pharmacological properties that its derivatives exhibit. In-
deed, 6H-benzo[c]chromene represents a key structural
motif that is found in many natural products (Figure 1).2
Moreover, 6H-benzo[c]chromene derived polymers have
been integrated into photovoltaic devices as functional ma-
2
4
1
3
terials. Therefore, the application of 6H-benzo[c]chromene
derivatives in pharmaceutical chemistry and material sci-
ence have spurred intense research endeavors to discover
efficient and high-yielding preparative methods. Towards
OH
O
Me
Me
OH
HO
MeO
MeO
Me
Me
Me
Me
Me
Me
Me
Me
O
Me
O
O
O
Pulchrol
Pulchral
Didehydroconicol
Cannabinol
Figure 1 Representative examples of natural products that contain the 6H-benzo[c]chromene motif
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synthesis
Y. Chen et al.
Paper
Ph
CO2Me
OMe
N
OMe
[2+2]-cycloaddition
O
N
E
Ph
(a)
CO2Me
O
O
Rh2(OAc)4, -N2
Wolff rearrangement
C
Doyle et al.11
E
E
N2
E
N
OH
(b)
[4+2]-annulation
Doutheau et al.14
this work:
O
E
O
C
OH
E
(c)
E
intramolecular [4+2]-annulation
aromatization
N2
O
O
O
E = CO2Me, CO2Et
Scheme 1 (a) The intermolecular [2+2]-cycloaddition of vinyl ketene with imines. (b) The intermolecular [4+2]-annulation of vinyl ketene with enam-
ine. (c) Reaction hypothesis for the intramolecular [4+2]-benzannulation of the vinyl ketene with an unactivated alkyne functionality.
substituents.13 We are particularly interested in expanding
the synthetic utility of diazoacetoacetate enones because of
their diverse reactivity profiles. Inspired by an intermolecu-
lar vinyl ketene-enamine cyclocondensation (pathway b),14
we hypothesize that the judicious placement of a pendant
alkyne functionality on the aryl fragment of the diazoaceto-
acetate enone would render the intramolecular [4+2]-
benzannulation and the subsequent aromatization feasible
lation of 1a may require a higher temperature to initiate.
Accordingly, we decided to substitute 1,2-dichloroethane
with xylenes, which could provide a broader temperature
range for probing the optimal reaction conditions. In addi-
tion, we speculated that the slow addition of 1a to the reac-
tion system may not be required because free carbenes
generated from acceptor/acceptor-substituted diazo com-
pounds under thermal induction tend to be resistant to di-
merization. To our delight, when the xylenes solution of 1a
was heated without a metal catalyst in a sealed Schlenk
tube at 100 °C for 12 hours, the formation of a product,
which was highly fluorescent under UV irradiation by TLC
analysis, was observed (entry 7). Elevation in the reaction
temperature to 140 °C effectively improved the reaction
yield to 41% (entry 8). The identity of the product 2a was
assigned according to the H and C NMR spectra and the
ortho positions for the phenolic hydroxy and the carbome-
thoxy were consolidated by the phenolic proton signal res-
onating at 10.86 ppm, which supported the [4+2]-annula-
tion pathway in preference to the Danheiser benzannula-
tion. After a thorough search for the combinations of
temperature and reaction time, we discovered that heating
the reaction mixture at 190 °C for 30 minutes enhanced the
reaction yield to 66% (entry 9). Finally, a decrease in the re-
actant concentration resulted in the formation of the 6H-
benzo[c]chromene 2a in 72% yield under otherwise identi-
cal conditions (entry 10).
(pathway c). In principle, this benzannulation strategy
would provide a convergent route to densely functionalized
6
H-benzo[c]chromenes that complements the Danheiser
15
benzannulation
products.
by offering orthogonally substituted
In an effort to validate our hypothesis, we evaluated the
dinitrogen extrusion and subsequent benzannulation of di-
azoacetoacetate enone 1a; the results are summarized in
Table 1. First, we surveyed a series of transition-metal cata-
lysts that have been conventionally used to catalyze the di-
nitrogen extrusion of diazo compounds to afford metal car-
1
13
benes (entries 1–6). Although Rh (OAc)4 (entry 1) and
2
Pd(OAc) (entry 2) actively catalyzed the decomposition of
2
1a, the formation of complex mixtures were indicated by
TLC analysis. Unexpectedly, Cu(hfacac) , Cu(OTf) , AgOTf,
2
2
and AgSbF failed to promote the denitrogenation of diazo-
6
acetoacetate enone 1a (entries 3–6). The reaction outcomes
implied that diazoacetoacetate enone 1a might coordinate
to the copper and silver catalysts, leading to catalyst deacti-
vation. At this stage, we reasoned that the [4+2]-benzannu-
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

C
Synthesis
Y. Chen et al.
Paper
Table 1 Optimization of the Reaction Conditionsa
Having accomplished the optimization of the reaction
conditions, we sought to investigate the scope and generali-
ty of this novel [4+2]-benzannulation. As illustrated in
Scheme 2, good compatibility with methyl, fluoro, chloro
and bromo substituents on the aromatic rings of diazoace-
toacetate enones was evident. Although the 3,5-dichloro-
substituted substrate 1f performed reasonably well, the
MeO
O
O
O
OH
1,2-DCE or xylenes
OMe
N2
O
O
6H-benzo[c]chromene 2a
diazoacetoacetate enone 1a
3,5-dibromo analogue 1g afforded 2g in a lower yield. We
only observed the formation of 2h in a trace amount, which
may be attributed to the geometric alternation of the corre-
sponding intermediate vinyl ketene by introducing the in-
ternal alkyne functionality. Diazoacetate enones incorpo-
rating strong electron-donating (1i) or electron-withdraw-
ing (1j) substituents were tolerated, affording the
corresponding 6H-benzo[c]chromene 2i and 2j, respective-
ly, in moderate to low yields. Nonetheless, the synthetic
methodology exemplified a practical synthesis of substitut-
ed 6H-benzo[c]chromenes since the reaction was highly
operable and dinitrogen was released as the only byprod-
uct.
To conclude, the development of the intramolecular
benzannulation of diazoacetoacetate enones with pendant
alkynes to produce 6H-benzo[c]chromenes under thermal
induction has been achieved. Noteworthy features include
the relative ease of operation, good functional group toler-
ance, and the circumvention of using a catalyst. Further ap-
plications of this methodology towards the total synthesis
of related natural products and mechanistic studies are un-
der way.
Entry
Catalyst (mol%)
Temp (°C) Time (h) Yield (%)b
1c
Rh
Pd(OAc)
Cu(hfacac)
Cu(OTf) (5.0)
AgOTf (5.0)
(OAc)
(2.5)
(5.0)
(5.0)
60
60
12
12
12
12
12
12
12
12
complex mixture
complex mixture
no conversion
no conversion
no conversion
no conversion
trace
2
4
2c
2
3c
2
60
4c
5c
6c
7d
60
2
60
AgSbF
none
none
none
none
6
(5.0)
60
100
140
190
190
8d
41
9d
0.5
0.5
66
1
0d,e
72
a
The reactions were carried out with 1a (0.50 mmol) in a pressure-
resistant Schlenk tube under a nitrogen atmosphere at a concentration of
0
.20 M unless otherwise noted.
Isolated reaction yield.
b
c
Compound 1a (0.50 mmol) was dissolved in 1,2-DCE (1.5 mL) and the
solution was added via a syringe pump over 30 min to the Schlenk tube
heated at 60 °C, where the corresponding catalysts were either dissolved
or suspended in 1,2-DCE (1.0 mL).
d
Xylenes (a mixture of isomers) was used as the solvent.
The reaction was performed at a concentration of 0.10 M.
e
MeO
O
O
O
OH
R4
R1
R2
xylenes, sealed tube, 190 °C, 30 min
OMe
R1
R2
N2
O
R3
R4
O
R3
1
2
MeO
O
MeO
O
MeO
O
MeO
O
MeO
O
OH
OH
OH
OH
OH
Br
Me
F
Cl
O
O
a, 72% yield
O
2b, 69% yield
O
2c, 70% yield
O
2d, 59% yield
2
2e, 58% yield
MeO
O
MeO
O
MeO
O
MeO
O
MeO
O
OH
OH
OH
Me
OH
OH
Cl
Br
O2N
O
O
O
Cl
Br
MeO
O
O
2j, 21% yield
2f, 62% yield
2g, 23% yield
2h, trace
2i, 48% yield
Scheme 2 Synthesis of functionalized 6H-benzo[c]chromenes
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

D
Synthesis
Y. Chen et al.
Paper
1
3
C NMR (100 MHz, CDCl ):  = 170.31, 161.11, 151.73, 139.91,
All chemicals and catalysts were purchased from commercial sources
and were used as received unless otherwise noted. 1,2-Dichlo-
roethane (1,2-DCE) was distilled over calcium hydride under a nitro-
gen atmosphere. Xylenes (a mixture of isomers) and toluene were pu-
rified by distillation from metallic sodium under a nitrogen atmo-
sphere. Tetrahydrofuran was distilled under a nitrogen atmosphere
from sodium in the presence of benzophenone. All reactions were
performed under a nitrogen atmosphere using standard Schlenk tech-
niques. Analytical thin-layer chromatography (TLC) was conducted
with silica gel 60F254 precoated plates (0.25 mm) and visualized by
exposure to UV light (254 or 365 nm) or stained with anisaldehyde,
ceric ammonium molybdate, or potassium permanganate followed by
heating. Column chromatography was performed on silica gel
3
1
1
31.56, 129.45, 123.18, 123.00, 121.94, 121.67, 117.06, 113.49,
12.13, 67.99, 52.40, 20.89.
HRMS (ESI–): m/z [M – H]– calcd for C16H13O : 269.0814; found:
269.0817.
4
Methyl 2-Fluoro-8-hydroxy-6H-benzo[c]chromene-9-carboxylate
(2c)
Yield: 96.5 mg (70%); white solid.
1
H NMR (400 MHz, CDCl ):  = 10.92 (s, 1 H), 8.09 (s, 1 H), 7.36 (dd, J =
3
9
3
.2, 2.8 Hz, 1 H), 6.97–6.85 (m, 2 H), 6.79 (s, 1 H), 5.04 (s, 2 H), 4.01 (s,
H).
13
(500−800 mesh) eluting with a mixture of petroleum ether (PE) and
C NMR (100 MHz, CDCl ):  = 170.11, 161.62, 158.22 (d, J =
3
ethyl acetate (EtOAc). Nuclear magnetic resonance spectra were re-
239.2 Hz), 149.80 (d, J = 2.0 Hz), 139.66, 123.63, 123.16 (d, J = 8.3 Hz),
121.03 (d, J = 2.2 Hz), 118.41 (d, J = 8.3 Hz), 115.14 (d, J = 23.5 Hz),
113.57, 112.24, 108.97 (d, J = 24.4 Hz), 68.01, 52.50.
1
corded in CDCl with a 400 MHz spectrometer. Data for H NMR spec-
3
tra are reported as: chemical shift (, ppm), multiplicity, coupling
1
constant (Hz), and integration. The H chemical shift was referenced
HRMS (ESI–): m/z [M – H]– calcd for C15H10FO : 273.0563; found:
4
to the residual solvent signal (H = 7.26 ppm for CDCl ). Multiplicity
3
273.0567.
was reported as s (singlet), d (doublet), t (triplet), dd (doublet of dou-
1
3
blet), dt (doublet of triplet), m (multiplet), brs (broad singlet), etc.
C
13
Methyl 2-Chloro-8-hydroxy-6H-benzo[c]chromene-9-carboxylate
(2d)
NMR spectra were recorded at 100 MHz. Data for C NMR spectra are
reported in terms of chemical shift. The C chemical shift was refer-
13
Yield: 86.2 mg (59%); white solid.
enced to the solvent signal ( = 77.0 ppm for CDCl ). High-resolution
C
3
1
mass spectra were obtained with
a
conventional instrument
H NMR (400 MHz, CDCl ):  = 10.92 (s, 1 H), 8.11 (s, 1 H), 7.63 (d, J =
3
equipped a TOF analyzer.
2.5 Hz, 1 H), 7.14 (dd, J = 8.6, 2.5 Hz, 1 H), 6.91 (d, J = 8.6 Hz, 1 H), 6.78
(
1
s, 1 H), 5.05 (s, 2 H), 4.01 (s, 3 H).
Caution: Although we have not experienced any problems handling
the diazo compounds prepared and used in this publication, appro-
priate care should be exercised.
3
C NMR (100 MHz, CDCl ):  = 170.08, 161.61, 152.30, 139.37,
3
128.40, 127.27, 123.53, 123.38, 122.42, 120.59, 118.72, 113.59,
12.30, 67.94, 52.52.
1
Preparation of 6H-Benzo[c]chromene 2; General Procedure
HRMS (ESI–): m/z [M – H]– calcd for C15H10ClO : 289.0268; found:
4
In a 25 mL pressure-resistant Schlenk tube charged with a magnetic
stirring bar, diazoacetoacetate enone 1 (0.50 mmol) was dissolved in
xylenes (5.0 mL) under a nitrogen atmosphere to provide a colorless
solution. The Schlenk tube was sealed and then heated in an oil bath
at 190 °C for 30 min. The evolution of nitrogen was observed and the
reaction mixture became light-yellow. The reaction mixture was
cooled to r.t. and concentrated under reduced pressure to afford a res-
idue, which was purified by silica gel column chromatography to af-
ford 6H-benzo[c]chromenes 2.
298.0273.
Methyl 2-Bromo-8-hydroxy-6H-benzo[c]chromene-9-carboxylate
(2e)
Yield: 97.9 mg (58%); white solid.
1
H NMR (400 MHz, CDCl ):  = 10.92 (s, 1 H), 8.10 (s, 1 H), 7.78 (d, J =
3
2.4 Hz, 1 H), 7.28 (dd, J = 8.6, 2.4 Hz, 1 H), 6.86 (d, J = 8.6 Hz, 1 H), 6.78
(s, 1 H), 5.06 (s, 2 H), 4.01 (s, 3 H).
13
C NMR (100 MHz, CDCl ):  = 170.07, 161.60, 152.79, 139.31,
3
1
1
31.30, 125.33, 123.90, 123.52, 120.44, 119.15, 114.69, 113.60,
12.31, 67.90, 52.53.
Methyl 8-Hydroxy-6H-benzo[c]chromene-9-carboxylate (2a)
Yield: 91.7 mg (72%); white solid.
HRMS (ESI–): m/z [M – H]– calcd for C15
32.9770.
H10BrO : 332.9762; found:
4
1
H NMR (400 MHz, CDCl ):  = 10.86 (s, 1 H), 8.15 (s, 1 H), 7.69 (dd, J =
3
3
7
1
3
.8, 1.6 Hz, 1 H), 7.21 (td, J = 7.8, 1.6 Hz, 1 H), 7.05 (td, J = 7.5, 1.3 Hz,
H), 6.98 (dd, J = 8.1, 1.3 Hz, 1 H), 6.77 (s, 1 H), 5.06 (s, 2 H), 3.99 (s,
H).
Methyl 2,4-Dichloro-8-hydroxy-6H-benzo[c]chromene-9-carbox-
ylate (2f)
13
C NMR (100 MHz, CDCl ):  = 170.22, 161.14, 153.83, 139.62,
3
Yield: 100.2 mg (62%); white solid.
1
1
28.78, 123.23, 122.66, 122.25, 121.94, 121.64, 117.34, 113.40,
12.12, 67.86, 52.36.
1
H NMR (400 MHz, CDCl ):  = 10.96 (s, 1 H), 8.11 (s, 1 H), 7.55 (d, J =
3
HRMS (ESI–): m/z [M – H]– calcd for C15H11O : 255.0657; found:
2.4 Hz, 1 H), 6.81 (s, 1 H), 5.16 (s, 2 H), 4.02 (s, 3 H) (one aromatic pro-
ton signal is missing due to overlapping with the chloroform signal).
4
255.0659.
13
C NMR (100 MHz, CDCl ):  = 169.81, 161.89, 148.18, 138.82,
3
1
1
28.43, 126.92, 124.38, 123.98, 123.19, 120.88, 119.82, 113.65,
12.42, 68.26, 52.47.
Methyl 8-Hydroxy-2-methyl-6H-benzo[c]chromene-9-carboxyl-
ate (2b)
HRMS (ESI–): m/z [M – H]– calcd for C15
322.9882.
H Cl O : 322.9878; found:
9 2 4
Yield: 93.0 mg (69%); white solid.
1
H NMR (400 MHz, CDCl ):  = 10.85 (s, 1 H), 8.13 (s, 1 H), 7.48 (d, J =
3
2.0 Hz, 1 H), 7.01 (dd, J = 8.2, 2.0 Hz, 1 H), 6.88 (d, J = 8.2 Hz, 1 H), 6.77
(s, 1 H), 5.02 (s, 2 H), 4.00 (s, 3 H), 2.36 (s, 3 H).
©
2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

E
Synthesis
Y. Chen et al.
Paper
Methyl 2,4-Dibromo-8-hydroxy-6H-benzo[c]chromene-9-carbox-
ylate (2g)
References
(
1) (a) Sun, W.; Cama, L. D.; Birzin, E. T.; Warrier, S.; Locco, L.;
Mosley, R.; Hammond, M. L.; Rohrer, S. P. Bioorg. Med. Chem.
Lett. 2006, 16, 1468. (b) Rahn, E. J.; Zvonok, A. M.; Thakur, G. A.;
Khanolkar, A. D.; Makriyannis, A.; Hohmann, A. G. J. Pharmacol.
Exp. Ther. 2008, 327, 584. (c) Pratap, R.; Ram, V. J. Chem. Rev.
2014, 114, 10476.
Yield: 47.0 mg (23%); white solid.
1
H NMR (400 MHz, CDCl ):  = 10.96 (s, 1 H), 8.10 (s, 1 H), 7.72 (d, J =
.2 Hz, 1 H), 7.56 (d, J = 2.2 Hz, 1 H), 6.80 (s, 1 H), 5.15 (s, 2 H), 4.02 (s,
H).
3
2
3
13
C NMR (100 MHz, CDCl ):  = 169.99, 162.10, 149.85, 138.98,
3
1
1
34.08, 124.99, 124.65, 124.18, 119.94, 114.63, 113.83, 112.63,
12.44, 68.51, 52.66.
(2) Killander, D.; Sterner, O. Eur. J. Org. Chem. 2014, 1594.
(3) Lee, J. W.; Bae, S.; Jo, W. H. J. Mater. Chem. A 2014, 2, 14146.
(4) (a) Campeau, L.-C.; Parisien, M.; Leblanc, M.; Fagnou, K. J. Am.
Chem. Soc. 2004, 126, 9186. (b) Campeau, L.-C.; Parisien, M.;
Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581. (c) Lafrance,
M.; Lapointe, D.; Fagnou, K. Tetrahedron 2008, 64, 6015. (d) Liu,
W.; Cao, H.; Xin, J.; Jin, L.; Lei, A. Chem. Eur. J. 2011, 17, 3588.
HRMS (ESI–): m/z [M – H]– calcd for C15H Br O : 412.8847; found:
9
2
4
412.8850.
Methyl 8-Hydroxy-3-methoxy-6H-benzo[c]chromene-9-carboxyl-
ate (2i)
(e) Ortiz Villamizar, M. C.; Zubkov, F. I.; Puerto Galvis, C. E.;
Yield: 68.0 mg (48%); white solid.
Vargas Méndez, L. Y.; Kouznetsov, V. V. Org. Chem. Front. 2017,
4, 1736.
1
H NMR (400 MHz, CDCl ):  = 10.79 (s, 1 H), 8.05 (s, 1 H), 7.59 (d, J =
3
8
.6 Hz, 1 H), 6.75 (s, 1 H), 6.63 (dd, J = 8.6, 2.6 Hz, 1 H), 6.54 (d, J =
(5) Sun, C. L.; Gu, Y. F.; Huang, W. P.; Shi, Z. J. Chem. Commun. 2011,
47, 9813.
2.6 Hz, 1 H), 5.05 (s, 2 H), 3.98 (s, 3 H), 3.81 (s, 3 H).
1
3
(6) Corrie, T. J. A.; Ball, L. T.; Russell, C. A.; Lloyd-Jones, G. C. J. Am.
Chem. Soc. 2017, 139, 245.
C NMR (100 MHz, CDCl ):  = 170.38, 160.56, 160.44, 155.07,
3
1
1
38.64, 123.57, 122.33, 122.03, 114.95, 113.41, 112.21, 109.02,
02.29, 68.23, 55.40, 52.39.
(
(
(
7) Shen, Z.; Ni, Z.; Mo, S.; Wang, J.; Zhu, Y. Chem. Eur. J. 2012, 18,
4859.
HRMS (ESI+): m/z [M + Na]+ calcd for C16H14NaO : 309.0733; found:
3
5
8) Guo, D. D.; Li, B.; Wang, D. Y.; Gao, Y. R.; Guo, S. H.; Pan, G. F.;
Wang, Y. Q. Org. Lett. 2017, 19, 798.
9) Deng, Q.; Tan, L.; Xu, Y.; Liu, P.; Sun, P. J. Org. Chem. 2018, 83,
09.0733.
Methyl 8-Hydroxy-2-nitro-6H-benzo[c]chromene-9-carboxylate
2j)
6151.
(
(
10) Shanahan, C. S.; Truong, P.; Mason, S. M.; Leszczynski, J. S.;
Yield: 32.2 mg (21%); yellow solid.
Doyle, M. P. Org. Lett. 2013, 15, 3642.
1
(11) (a) Xu, X.; Xu, X.; Zavalij, P. Y.; Doyle, M. P. Chem. Commun.
013, 49, 2762. (b) Mandler, M. D.; Truong, P. M.; Zavalij, P. Y.;
H NMR (400 MHz, CDCl ):  = 11.00 (s, 1 H), 8.59 (d, J = 2.7 Hz, 1 H),
.23 (s, 1 H), 8.09 (dd, J = 9.0, 2.7 Hz, 1 H), 7.04 (d, J = 9.0 Hz, 1 H), 6.80
3
2
8
Doyle, M. P. Org. Lett. 2014, 16, 740.
(s, 1 H), 5.20 (s, 2 H), 4.05 (s, 3 H).
(
(
12) Tidwell, T. T. Ketenes, 2nd ed; Wiley: Hoboken, 2006.
13) (a) Davie, C. P.; Danheiser, R. L. Angew. Chem. Int. Ed. 2005, 44,
13
C NMR (100 MHz, CDCl ):  = 170.01, 162.24, 158.90, 142.85,
3
1
1
38.41, 124.42, 124.26, 122.28, 119.56, 118.65, 118.11, 113.81,
12.91, 68.32, 52.73.
5867. (b) Austin, W. F.; Zhang, Y.; Danheiser, R. L. Org. Lett.
2005, 7, 3905.
+
HRMS (ESI+): m/z [M + Na] calcd for C15H11NNaO : 324.0479; found:
3
(14) Collomb, D.; Doutheau, A. Tetrahedron Lett. 1997, 38, 1397.
(15) (a) Danheiser, R. L.; Gee, S. K. J. Org. Chem. 1984, 49, 1672.
6
24.0478.
(b) Danheiser, R. L.; Brisbois, R. G.; Kowalczyk, J. J.; Miller, R. F.
J. Am. Chem. Soc. 1990, 112, 3093. (c) Mak, X. Y.; Crombie, A. L.;
Danheiser, R. L. J. Org. Chem. 2011, 76, 1852. (d) Lam, T. Y.;
Wang, Y. P.; Danheiser, R. L. J. Org. Chem. 2013, 78, 9396.
(e) Willumstad, T. P.; Haze, O.; Mak, X. Y.; Lam, T. Y.; Wang, Y.
P.; Danheiser, R. L. J. Org. Chem. 2013, 78, 11450. (f) Willumstad,
T. P.; Boudreau, P. D.; Danheiser, R. L. J. Org. Chem. 2015, 80,
Funding Information
This work was supported by the National Natural Science Foundation
of China (21801198) and by the Wuhan Institute of Technology
(17QD05).
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11794. (g) Forneris, C. C.; Wang, Y. P.; Mamaliga, G.;
Willumstad, T. P.; Danheiser, R. L. Org. Lett. 2018, 20, 6318.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690191.
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