BX 3-Mediated Intermolecular Formation of Functionalized 3-Halo-1 H-indenes via Cascade Halo-Nazarov-Type Cyclization

Article abstract of DOI:10.1055/s-0039-1690881

A BX 3-promoted, intermolecular regioselective synthesis of 3-halo-functionalized 1 H-indenes from 4-oxo-4 H-chromene-3-carb?-aldehydes and alkynes has been developed. BX 3 displays a dual role of Lewis acid catalyst and halide source for haloallyl cation formation for the intended halo-Nazarov-type cyclization. The overall transformation represents an efficient cascade annulation that employs readily available starting materials, inexpensive reagents and a convenient and mild reaction procedure to generate halo-functionalized indenes (45 examples). The reaction was also extended to 8-formylcoumarins to deliver coumarin-based 3-halo-1 H-indenes in 79-95percent yield (6 examples). The reaction involves conversion of the aldehyde into an sp 3 carbon with two new C-C bonds and additionally a C-X bond is formed (X = halide).

Full text of DOI:10.1055/s-0039-1690881

SYNTHESIS
0
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1
4
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0
X
© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–N
paper
A
en
A. Kumari, R. A. Fernandes
Paper
Synthesis
BX3-Mediated Intermolecular Formation of Functionalized
3-Halo-1H-indenes via Cascade Halo-Nazarov-Type Cyclization
R1
R1
Anupama Kumari
O
Rodney A. Fernandes*
0
0
0
0-0
0
0
1-8
8
8
8-
0
9
2
7
BX3
X
X
O
(X = F, Cl or Br)
CHO
R
R2
Department of Chemistry, Indian Institute of Technology
Bombay, Powai, Mumbai 400076, Maharashtra, India
rfernand@chem.iitb.ac.in
CH2Cl2
rt, 1–8 h
R2
R2 ≠ H
R
O
O
45 examples (48–96%)
halo-Nazarov-type cyclization
Mild reaction conditions
Two C-C and
R1
one C-X bond formation
R1
O
O
X
CHO R2
O
BCl3 or BBr3
O
CH2Cl2
rt, 4–11 h
extended to
coumarin-8-carbaldehydes
R2
R
6 examples (79–95%)
R
Received: 31.01.2020
Accepted after revision: 10.03.2020
Published online: 06.04.2020
and halocyclopentene products.6 However, most of these
reactions involved the generation of vinylhalo compounds
that were then subjected to halo-Nazarov cyclization, thus
involving two steps in the protocol.
DOI: 10.1055/s-0039-1690881; Art ID: ss-2019-n0717-op
Abstract A BX3-promoted, intermolecular regioselective synthesis of
3-halo-functionalized 1H-indenes from 4-oxo-4H-chromene-3-carb-
aldehydes and alkynes has been developed. BX3 displays a dual role of
Lewis acid catalyst and halide source for haloallyl cation formation for
the intended halo-Nazarov-type cyclization. The overall transformation
represents an efficient cascade annulation that employs readily avail-
able starting materials, inexpensive reagents and a convenient and mild
reaction procedure to generate halo-functionalized indenes (45 exam-
ples). The reaction was also extended to 8-formylcoumarins to deliver
coumarin-based 3-halo-1H-indenes in 79–95% yield (6 examples). The
reaction involves conversion of the aldehyde into an sp3 carbon with
two new C–C bonds and additionally a C–X bond is formed (X = halide).
The traditional 4-electrocyclization of an oxy- or aza-
arylallyl cation or -dienyl cation 1a (OH or NR2) would be
slower, affecting the equilibrium between 1a and 1b
(Scheme 1). This can be attributed to the electron-releasing
ability of oxygen or nitrogen to stabilize the cation, thereby
decreasing its reactivity. Frontier and co-workers6 have re-
cently demonstrated that generation of a halo cation 2a (X =
halide) would speed up the reaction delivering the useful
vinylhalo compounds. By computational studies, it has been
observed that the arylallyl cation cyclizations are thermo-
dynamically disfavoured and endothermic by >15 kcal/mol,
due to aromaticity loss.6c,7 However, the corresponding halo
cation cyclizations were thermoneutral, despite aromatici-
ty loss, and were predicted to be exothermic. Experimen-
tally, the reactions occurred efficiently at 0 °C validating the
computational data. Over the past decade, isolated exam-
ples of similar reactions have emerged, although these were
considered as intramolecular Friedel–Crafts arylations.8 The
reaction now termed as ‘halo-Nazarov cyclization’ is under-
developed,6,8 probably due to a lack of direct methods to
prepare the intermediates of type 2a from suitable precur-
sors. While the work of Frontier and co-workers6 marks an
excellent beginning, there exists immense potential for fur-
ther development in this area, as the vinylhalo compounds
are useful intermediates in various transition-metal-
catalyzed coupling reactions.6a,b,8b,d,9
Key words Lewis acids, Nazarov cyclization, hybrid structures, C–C
bond formation, electrocyclic reactions
Indenes1 and chromones2 are very promising targets
and central structural units ubiquitous in many biologically
active molecules. A hybrid displaying both these units
might hold promise for resourceful biological activities.
Combination of two different bioactive pharmacophores in
a single molecule has been shown to possess better activi-
ty.3 The Nazarov cyclization has been well explored since its
discovery in the middle of the last century.4 Traditionally,
the reaction is based on cross-conjugated divinyl ketones
undergoing ring closure to give the cyclopentenone or inda-
none products. Several natural products and valuable com-
pounds have been synthesized employing this reaction.4,5
However, it is also associated with some limitations, like the
difficulty to synthesize and handle dienone precursors, es-
pecially when terminal disubstituted vinyl groups are
needed. Recently, there have been interesting reports on
halo-Nazarov-type cyclizations to provide the haloindene
Our venture into the halo-Nazarov cyclization came ser-
endipitously. Lee and co-workers10 recently reported the
BF3·OEt2-promoted cyclization of chromenone-3-carbalde-
hydes 3 with terminal arylacetylenes 4 in CH3CN for the
construction of 2,5-disubstituted 2-arylpyridines
5
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. Kumari, R. A. Fernandes
Paper
Synthesis
O
LA
O
H
LA
O
O
classical
Nazarov cyclization
3
R2
R2
R3
BF3·OEt2
O
+
R
R
4π
R
R
R1
OH
N
CH3CN (wet)
O
R1
R1
R3
R1
5
4
3
1a
1b
Dienone
3-oxydienyl cation
O
or
O
H
Ph
other precursors
BF3·OEt2
X
O
X (halide)
3
R2
+
OH
5'
N
R2
CH3CN (wet)
R
R
O
4π
Ph
4a
halo-Nazarov cyclization
3a
R1
R3
(Not formed)
R1
R3
2a
3-halodienyl cation
2b
A: BF3·OEt2
O
O
CH3CN (wet)/CH2Cl2 (1:1)
rt, 6 h
Scheme 1 Oxy- and halo-Nazarov cyclization processes (LA = Lewis
acid)
F
B: BF3·OEt2
CH2Cl2, rt, 4 h
6aa (12% by method A)
6aa (21% by method B)
(Scheme 2). The nitrogen source for the pyridine moiety is
derived from the solvent, CH3CN. We visualized to explore
the outcome with internal alkynes, to result in the expected
2,3,5-trisubstituted pyridine 5′ that can be further subject-
ed to an intramolecular oxa-Michael addition resulting in
the fused chromenone–pyridine hybrid. The reaction of 3a
with diphenylacetylene (4a) in CH3CN failed to deliver
2,3,5-trisubstituted pyridine 5′, even with excess BF3·OEt2
or under heating conditions. A change to the solvent mix-
ture CH3CN/CH2Cl2 (1:1) furnished a new product, charac-
terized to be a chromenone–3-indene incorporating the
aryl ring, the alkyne and the aldehyde group of the chrome-
none with a further interesting incorporation of fluoride
from BF3·OEt2 leading to the functionalized five-membered-
ring compound 6aa (12%, Scheme 2). The reaction in only
CH2Cl2 provided 6aa in an improved yield of 21% and can be
visualized as an intermolecular cascade halo-Nazarov-type
cyclization with the incorporation of the vinyl halide group
and differs in the substrates used by Frontier and co-work-
ers6 for similar cyclizations. Often the aryl vinyl ketone sub-
strates for such reactions need to be synthesized with a
heavy bias toward reactivity and the intended Nazarov cy-
clization becomes an intramolecular process. The present
reaction being intermolecular and interesting in having the
indene cyclopentene ring functionalized, the added vinyl-
fluoro group, and the 4-chromenone moiety, we considered
studying the scope and limitations of this cyclization reac-
tion. It also holds the promise that a change of Lewis acid
BF3·OEt2 could incorporate other halide groups in the prod-
ucts.
Scheme 2 Strategies for 2-arylpyridines and haloindenes
Table 1 Optimization of the Halo-Nazarov Reaction Conditionsa
O
O
O
O
Ph
Lewis acid
solvent
X
H
+
rt, time (h)
Ph
O
3a
4a
6aa, X = F
6ba, X = Cl
6ca, X = Br
Entry Acid (equiv)
Solvent Temp Time (h)
X
Yield (%)b
1
2
BF3·OEt2 (1.0)
BF3·OEt2 (1.0)
BF3·OEt2 (1.0)
BF3·OEt2 (1.0)
BF3·OEt2 (1.0)
BF3·OEt2 (1.0)
BF3·OEt2 (1.0)
BF3·OEt2 (2.5)
BF3·OEt2 (3.0)
BF3·OEt2 (3.0)
BF3·THF (2.5)
CH2Cl2 rt
4
36
36
22
1
F
21
THF
rt
rt
rt
F
NR
NR
NR
CM
NR
8c
3
DMF
DMSO
F
4
F
5
CH3CN rt
DCE rt
F
6
24
16
F
7
benzene rt
CH2Cl2 rt
CH2Cl2 rt
CH2Cl2 reflux
CH2Cl2 rt
CH2Cl2 rt
CH2Cl2 rt
CH2Cl2 rt
CH2Cl2 rt
F
8
3.5
F
F
58
60
9
3.5
3.0
8
10
11
12
13
14
15
F
57
F
CM
CM
87
85
CM
HF–pyridine (2.5)
BCl3 (2.5)
6
F
5
Cl
Br
I
We screened various halide sources and available Lewis
acids containing halides for the reaction of 3a and dipheny-
lacetylene (4a) as model substrates with variation of sol-
vent and temperature, as shown in Table 1. Various solvents
were initially screened with BF3·OEt2 (1.0 equiv) at room
temperature (for full details, see the Supporting Informa-
tion). Except CH2Cl2 (entry 1), other solvents were not com-
patible for this reaction (entries 2–6). In benzene, the reac-
tion occurred with addition of a phenyl group (6, X = Ph, en-
try 7), in 8% yield. We considered raising the amount of
BBr3 (2.5)
5.5
8
BF3·OEt2
(2.5)/PhI(OAc)2 (1.0)
BCl3 (2.5)/I2 (1.0)
BCl3 (2.5)/KI (1.0)
16
17
CH2Cl2 rt
CH2Cl2 rt
24
24
I
I
NR
NR
a Reaction conditions: 3a (0.172 mmol), 4a (0.172 mmol), acid (1.0–3.0
equiv), solvent (2 mL), rt or reflux, 1–36 h.
b Isolated yield. NR = no reaction, CM = complex mixture.
c In place of halogen, solvent addition observed (X = Ph).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

C
A. Kumari, R. A. Fernandes
Paper
Synthesis
BF3·OEt2 used (1.5–3.0 equiv), the yield of 6aa being in-
creased with 2.5–3.0 equivalents (entries 8 and 9). There
was no change in yield in carrying out the reaction at reflux
in CH2Cl2 (entry 10). Other sources of fluoride like BF3·THF
or HF–pyridine did not yield product 6aa (entries 11 and
12). We considered 2.5 equivalents of BF3·OEt2 to be opti-
mal. Further, the reaction was mimicked for chlorine incor-
poration using various chloride sources (AlCl3, FeCl3, TiCl4
and BCl3). Except BCl3 (entry 13), other chloride sources
were not successful (see the Supporting Information). The
optimum requirement was 2.5 equivalents. Similarly, the
use of BBr3 in 2.5 equivalents was optimum for bromide in-
corporation (entry 14). The reactions for iodine incorpora-
tion using various iodide sources in combination with
BF3·OEt2 or BCl3 (entries 15–17) failed to deliver the iodine-
incorporated products. This study revealed that BF3·OEt2,
BCl3 or BBr3 (each 2.5 equiv) among the various halide
sources in CH2Cl2 at room temperature are the optimum re-
quirements. Among the three, the fluoride incorporation
occurred in moderate yield in comparison to bromide and
chloride.
The scope and limitations of this method were next in-
vestigated on a series of substituted 4-oxo-4H-chromene-3-
carbaldehydes 3 with diarylacetylenes 4 (Scheme 3) using
BF3·OEt2 for fluoride incorporation. Substrates 3 with a Me,
F, NO2 or Br group reacted well with 4a giving the 3-fluo-
roindenes 6ab–6ae in moderate yields. Compound 6ae gave
suitable crystals for X-ray analysis,11 unambiguously con-
firming the structure. The naphthalene-based substrates
also reacted well to provide 6af and 6ag in 50% and 48%
yield, respectively. The use of the unsymmetrical alkyne 1-
(4-bromophenyl)-2-phenylacetylene gave 3-fluoroindene
6ah in 59% yield, with the unsubstituted benzene chemose-
lectively involved in indene formation.
We continued the scope of substrates for chloride incor-
poration using BCl3 (2.5 equiv), as shown in Scheme 4. Sub-
strates 3 with a NO2, Me, F or Br group reacted well with 4a
giving the 3-chloroindenes 6bb–6be in good yields (68–
76%). Similarly, di-p-tolylacetylene reacted with various 4-
oxo-4H-chromene-3-carbaldehydes 3 to deliver the 3-
chloroindene compounds 6bf–6bj in good to excellent
yields (61–94%). The naphthalene-based substrates also re-
acted well to provide 6bk and 6bl in 96% and 76% yield, re-
spectively. The unsymmetrical diarylalkyne 1-(4-methoxy-
phenyl)-2-phenylacetylene also worked well to regio- and
chemoselectively provide the 3-chloroindenes 6bm–6bo in
up to 95% yield, in which the electron-rich methoxyben-
zene ring is chemoselectively involved in indene formation.
Arylalkylalkynes (1-butyn-1-ylbenzene and 1-hexyn-1-yl-
benzene) also reacted to give the 3-chloroindenes 6bp–6bs
in 80–93% yield. In these cases also, the benzene ring is in-
volved in the annulation reaction. Compounds 6bb, 6bi and
6bm provided suitable crystals for X-ray analysis.11
We next examined BBr3, for bromine incorporation in
the intermolecular cascade bromo-Nazarov indene forma-
tion (Scheme 5). With 4a and with di-p-tolylacetylene, the
reaction with various 4-oxo-4H-chromene-3-carbalde-
hydes 3 in the presence of BBr3 furnished the 3-bromo-
R1
R1
O
O
O
O
BCl3
R
R
Cl
(2.5 equiv)
H
+
R2
R2
CH2Cl2
rt, 1–7 h
O
4 (0.172 mmol)
3 (0.172 mmol)
6ba–6bs
19 examples
O
O
O
R1
BF3·OEt2
(2.5 equiv)
R
R
F
R1
H
+
R1
CH2Cl2
rt, 1.5–6.5 h
Ph
O
O
O
O
Cl
O
O
R
3 (0.172 mmol) 4 (0.172 mmol)
6aa–6ah
Cl
R
Cl
8 examples
O
O
O
O
O
O
F
F
F
R
R
Br
6ba, R = H, 87% (5 h)
6bb, R = NO2, 72% (6 h) 6bg, R = Me, 92% (1 h)
6bc, R = Me, 75% (2 h)
6bd, R = F, 76% (1 h)
6be, R = Br, 68% (1.5 h)
6bf, R = H, 94% (1.5 h)
R3
6bh, R = F, 61% (2.5 h)
6bi, R = Br, 76% (1.5 h)
6bj, R = NO2, 66% (1.5 h)
6bk, R1 = R3 = H, 96% (2.5 h)
6bl, R1 = R3 = Me, 76% (1 h)
O
O
6aa, R = H, 58% (3.5 h)
6ab, R = Me, 52% (2 h)
6ac, R = F, 53% (3 h)
6ad, R = NO2, 51% (6.5 h)
6ae, 50% (1.5 h)
MeO
O
O
O
Cl
O
R
O
O
Cl
C4H9
Cl
R
R
F
F
F
O
O
O
O
O
O
6bm, R = H, 95% (7 h)
6bn, R = Me, 83% (6 h)
6bo, R = F, 95% (6 h)
6bp, R = H, 93% (4 h)
6bq, R = F, 83% (3 h)
6br, R = H, 84% (5 h)
6bs, R = F, 80% (6 h)
6af, 50% (6 h)
6ag, 48% (6 h)
6ah, 59% (2 h)
Br
Scheme 3 Substrate scope for 3-fluoro-functionalized 1H-indene syn-
thesis. Reagents and conditions: 3 (0.172 mmol), 4 (0.172 mmol),
BF3·OEt2 (2.5 equiv), CH2Cl2 (2 mL), rt, 1.5–6.5 h. Isolated yields were
recorded.
Scheme 4 Substrate scope for 3-chloro-functionalized 1H-indene syn-
thesis. Reagents and conditions: 3 (0.172 mmol), 4 (0.172 mmol), BCl3
(2.5 equiv), CH2Cl2 (2 mL), rt, 1–7 h. Isolated yields were recorded.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

D
A. Kumari, R. A. Fernandes
Paper
Synthesis
indenes 6ca–6cl in good yields (72–88%). The unsymmetrical
alkyne 1-(4-bromophenyl)-2-phenylacetylene provided 3-
bromoindene 6cm selectively, with the unsubstituted ben-
zene ring undergoing the indene ring formation. This was
further confirmed by X-ray analysis of 6cm.11 Arylalkylal-
kynes (1-butyn-1-ylbenzene, 1-heptyn-1-ylbenzene and 1-
hexyn-1-ylbenzene) also reacted to give 3-bromoindenes
6cn–6cq in 80–85% yield. In the case of 4-phenylbut-3-yn-
1-ol, reaction with 3a gave product 6cr (80% yield), with the
hydroxyl group converted into a bromide with the addi-
tional 1.0 equivalent of BBr3. A reaction with 6.1 mmol of 3a
(R = H, 1.1 g) delivered 6ca in 74% yield, indicating possible
scale-up of the reaction (Scheme 5).
good to excellent yields (79–95%). Compound 8e gave suit-
able crystals for X-ray analysis, confirming the structure.11
R1
R1
O
O
O
BX3
(2.5 equiv)
O
R
CHO
X
+
CH2Cl2
rt, 4–11 h
X = Cl or Br
R
R2
7 (0.172 mmol) 4 (0.172 mmol)
6 examples
R2
8
O
O
O
O
O
O
Br
Cl
Cl
The present method was extended to 8-formylcouma-
rins 7, as shown in Scheme 6. These, on reaction with di-
phenylacetylene (4a) or di-p-tolylacetylene, delivered the
3-chloro- or 3-bromo-functionalized 1H-indenes 8a–8f in
8a, 95% (4 h)
8b, 93% (4.5 h)
8c, 90% (10 h)
O
O
O
O
O
O
R1
Br
Cl
Br
O
O
O
O
BBr3
(2.5 equiv)
R
R
R1
Br
H
+
R3
CH2Cl2
rt, 2.5–8 h
R3
O
3 (0.172 mmol)
4 (0.172 mmol)
6ca–6cr
8d, 88% (11 h)
8e, 79% (5 h)
8f, 88% (6 h)
18 examples
R1
Scheme 6 Substrate scope for coumarin-based 3-halo-functionalized
1H-indene synthesis. Reagents and conditions: 7 (0.172 mmol), 4 (0.172
mmol), BX3 (2.5 equiv), CH2Cl2 (2 mL), rt, 4–11 h. Isolated yields were
recorded.
O
O
O
O
Br
Br
R
O
Br
O
6ca, R = H, 85% (5.5 h)
6cb, R = Me, 80% (5 h)
6cc, R = Br, 85% (5.5 h)
6cd, R = F, 82% (3.5 h)
6ce, R = NO2, 81% (3.5 h)
6ch, 88% (2.5 h)
We also considered exploring alkynes with an electron-
withdrawing group and various other aldehydes to gain in-
sight into the mechanism of the reaction (Scheme 7). The
reaction of 4-oxo-4H-chromene-3-carbaldehydes 3a, 3b or
3d with 1-(2-methoxyphenyl)-2-(4-nitrophenyl)acetylene
(4f) in the presence of BCl3 or BBr3 failed to deliver the
chloro- or bromoindene compounds. Similarly, the reaction
of aldehyde 3a with phenylacetylene (9a) (terminal alkyne)
in the presence of BF3·OEt2 did not yield the corresponding
indene product. Most of the starting materials were recov-
ered in all these cases. This indicated that the alkyne should
be nucleophilic enough for reaction with the aldehyde. The
reaction of various other aldehydes, like p-chlorobenzalde-
hyde (10a), cinnamaldehyde (10b), o-anisaldehyde (10c),
salicylaldehyde (10d) and 3-oxocyclohex-1-ene-2-carb-
aldehyde (10e), with diphenylacetylene (4a) in the pres-
ence of BF3·OEt2 or BBr3 gave either a complex mixture or
no reaction, with the substrates being recovered unreacted.
Comparison of 13C NMR and IR spectral values for the alde-
hyde carbonyl of 10e with that of chromonecarbaldehyde
3a was not conclusive for the reactivity difference. The re-
action studied is substrate specific and at this stage only the
chromone- and coumarincarbaldehydes react. It appears
clear that simple aryl aldehydes do not react probably due
to lack of a -keto group that is required for complexation
with the Lewis acid. Also, the chromone oxygen stabilizes
R2
6cf, R1 = R2 = H, 82% (8 h)
6cg, R1 = R2 = Me, 84% (6.5 h)
R1
O
Br
R
R3
O
O
Br
R
6cn, R = H, R3 = C2H5, 85% (5 h)
6co, R = Me, R3 = C2H5, 83% (6 h)
6cp, R = Br, R3 = C5H11, 80% (5.5 h)
6cq, R = F, R3 = C4H9, 84% (6 h)
O
R2
6ci, R = H, R1 = R2 = Me, 80% (5.5 h)
6cj, R = R1 = R2 = Me, 83% (6 h)
O
6ck, R = F, R1 = R2 = Me, 86% (4 h)
6cl, R = Br, R1 = R2 = Me, 72% (6 h)
6cm, R = Me, R1 = H, R2 = Br, 73% (2.5 h)
Br
O
Br
6cr, 80% (5.5 h)a
O
gram-scale reaction
Br
6ca, 74% (4 h)
(from 6.1 mmol, 1.1 g of 3a)
O
Scheme 5 Substrate scope for 3-bromo-functionalized 1H-indene
synthesis and a gram-scale reaction. Reagents and conditions: 3 (0.172
mmol), 4 (0.172 mmol), BBr3 (2.5 equiv), CH2Cl2 (2 mL), rt, 2.5–8 h. Iso-
lated yields were recorded. a BBr3 (3.5 equiv) used.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

E
A. Kumari, R. A. Fernandes
Paper
Synthesis
the benzylic carbocation, as shown by intermediate 14′ in
Scheme 8. This oxygen is absent in 10e. The reaction of ben-
zoylacetone (11) and 4a with BF3·OEt2 delivered the BF2
complex 12 in 60% yield, the structure of which was estab-
lished by X-ray analysis.11 Thus, the -keto group in 4-oxo-
4H-chromene-3-carbaldehydes 3 is necessary for the reac-
tion apart from the chromone oxygen. It has also been ob-
served in this work that chloride and bromide incorpora-
tion gave superior yields in comparison to fluoride
(Schemes 4 and 5 vs Scheme 3).
BF2·OEt2
BF3·OEt2
O
O
O
O
O
O
Ph
BF3·OEt2
H
3a
Ph
4a
Ph
F
3a'
13
Ph
–
F
O
O
+
F
F
6aa
+
O
Ph
Ph
O
14'
14
BCl3 (2.5 equiv)
CH2Cl2, rt, 24 h
O
O
O
Scheme 8 Plausible mechanism (F incorporation in 6aa is representa-
tive)
R
+
No
Reaction
OMe
or
H
or
BBr3 (2.5 equiv)
CH2Cl2, rt, 24 h
or
BF3·OEt2/BBr3
(2.5 equiv)
Ph
3a, R = H
3b, R = Me
3d, R = NO2
In summary, we have developed an efficient intermolec-
ular halo-Nazarov-type cyclization of 4-oxo-4H-chromene-
3-carbaldehydes and 1,2-disubstituted acetylenes in the
presence of a halide source, BF3·OEt2, BCl3 or BBr3, which
also acts as a Lewis acid to mediate the reaction, giving vi-
nylhaloindenes (45 examples).13 The aldehyde carbon of 4-
oxo-4H-chromene-3-carbaldehydes is converted from sp2
into the sp3 carbon in the product by formation of two new
C–C bonds. An additional C–X bond formed by incorpora-
tion of a halide into the cyclopentene ring is remarkable,
generating the functionalized indene moiety. The reaction
was also extended to 8-formylcoumarins to deliver couma-
rin-based 3-halo-1H-indenes in good to excellent yields (6
examples). The overall transformation represents an effi-
cient intermolecular cascade halo-Nazarov-type cyclization
strategy that employs readily available starting materials,
inexpensive reagents and a convenient and mild reaction
procedure to generate halo-functionalized indenes.
4f
9a
O2N
CH2Cl2, rt, 3 h
O
O
or
4a, BF3·OEt2
Cl
or BBr3 (2.5 equiv)
10a
10b
Complex mixture
CH2Cl2, rt, 2 h
O
O
or
OH
OMe
10c
10d
O
O
Ph
BF3·OEt2/BBr3
(2.5 equiv)
H
+
No reaction
–
CH2Cl2, rt, 12 h
Ph
4a
10e
F
F
+
B
BF3·OEt2
(2.5 equiv)
Ph
O
O
O
O
+
CH2Cl2, rt, 7 h
Ph
4a
11
12, 60%
Scheme 7 Reactivity of alkyne with an electron-withdrawing group on
the aryl ring and scope of other aldehydes
Considering the selective reactivity of 4-oxo-4H-
chromene-3-carbaldehydes and not other aldehydes in this
reaction, we considered the plausible mechanism as shown
in Scheme 8, with probable involvement of the chromone
oxygen. Suitably placed neighbouring groups accelerating
the reaction has been developed earlier.12 Thus, coordina-
tion of Lewis acid BF3·OEt2 (or BCl3 or BBr3) with the alde-
hyde carbonyl initiates alkyne attack on the boron-com-
plexed aldehyde 3a′, with fluoride attack on the alkyne, giv-
ing intermediate 13. Further generation of the fluoroallylic
cation 14 triggers the halo-Nazarov-type cyclization. The
chromone oxygen probably stabilizes the carbocation, gen-
erating the extended oxocarbenium ion 14′. Intramolecular
aryl ring closure produces the vinylfluoroindene product
6aa. Terminal arylacetylenes may not be reactive as the in-
termediate cation before halide attack may not be stable or
formed. This substrate bias is evident in the Nazarov cy-
clization being mostly explored with substituted vinyl
bonds.
TLC was performed on EM 250 Kieselgel 60 F254 silica gel plates. The
spots were visualized by staining with KMnO4 or by using a UV lamp.
1H and 13C NMR spectra were recorded with spectrometers operating
at 400 or 500 and at 100 or 125 MHz for proton and carbon nuclei,
respectively. The chemical shifts are based on the TMS peak at  =
0.00 pm for proton NMR and the CDCl3 peak at  = 77.00 ppm (t) for
carbon NMR. IR spectra were obtained on a FT-IR spectrophotometer.
HRMS (ESI-TOF) spectra were recorded using positive electrospray
ionization by the TOF method. CH2Cl2 was dried by refluxing over
P2O5 and distillation on calcium hydride. THF and benzene were dried
over sodium. All chromenone-3-carbaldehydes (except 3-formylben-
zo[h]chromone that was prepared14) were obtained from Aldrich
Chemical Co. All Lewis acids, phenylacetylene and 1-butyn-1-ylben-
zene are commercial reagents and were used as such without further
purification. Other alkynes were prepared using established litera-
ture protocols.15 Room temperature = 32–35 °C.
3-(2-Aryl-3-fluoro-1H-inden-1-yl)-4H-chromen-4-ones 6aa–6ah;
General Procedure
To a mixture of carbaldehyde 3 (0.172 mmol, 1.0 equiv) and alkyne 4
(0.172 mmol, 1.0 equiv) in CH2Cl2 (2 mL) was added BF3·OEt2 (0.43
mmol, 2.5 equiv) at room temperature. The mixture was stirred for
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

F
A. Kumari, R. A. Fernandes
Paper
Synthesis
the required time (monitored by TLC). After completion of the reac-
tion, it was quenched with a few drops of sat. Na2S2O3 solution. The
solvent was removed through vacuum and the residue was purified
by silica gel column chromatography (petroleum ether/EtOAc, 4:1) to
afford 6aa–6ah.
3-(3-Fluoro-2-phenyl-1H-inden-1-yl)-6-nitro-4H-chromen-4-one
(6ad)
Yield: 35 mg (51%, reaction time = 6.5 h); white solid; mp 189–191 °C.
IR (CHCl3): 1652, 1632, 1531, 1467, 1345, 826, 695 cm–1
.
1H NMR (500 MHz, CDCl3):  = 9.23 (d, J = 2.4 Hz, 1 H), 8.46 (dd, J = 9.2,
2.3 Hz, 1 H), 7.58 (d, J = 8.3 Hz, 2 H), 7.50–7.45 (m, 4 H), 7.39–7.34 (m,
3 H), 7.26–7.23 (m, 2 H), 5.58 (d, J = 5.3 Hz, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 176.5, 159.0, 157.3 (d, 1JC-F = 280.4
Hz), 153.3, 144.8, 143.7, 135.4 (d, 2JC-F = 24.8 Hz), 131.1, 128.9, 128.0,
127.8, 127.7, 127.6, 127.5, 124.0, 123.9, 123.8, 122.8, 120.0, 119.3,
118.2, 40.6.
3-(3-Fluoro-2-phenyl-1H-inden-1-yl)-4H-chromen-4-one (6aa)
Yield: 35.4 mg (58%, reaction time = 3.5 h); white solid; mp 182–
184 °C.
IR (CHCl3): 3058, 2850, 1648, 1617, 1465, 1350, 1220, 1176, 696, 594
cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.38 (t, J = 6.1 Hz, 1 H), 7.66–7.61 (m, 3
H), 7.53 (t, J = 5.7 Hz, 1 H), 7.47–7.43 (m, 2 H), 7.39–7.32 (m, 5 H),
7.27–7.21 (m, 2 H), 5.63 (s, 1 H).
19F NMR (470 MHz, CDCl3):  = –127.9.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H14FNNaO4: 422.0799;
found: 422.0788.
1
13C{1H} NMR (125 MHz, CDCl3):  = 177.8, 157.3 (d, JC-F = 248.4 Hz),
156.0, 153.0, 144.5, 135.5, 135.3, 133.7, 131.3 (d, 4JC-F = 4.1 Hz), 128.8,
128.6, 127.7 (d, 3JC-F = 6.2 Hz), 127.4, 127.2, 125.9, 125.2, 124.0, 123.8,
122.7, 119.8, 118.1 (d, 2JC-F = 18.9 Hz), 40.7.
6-Bromo-3-(3-fluoro-2-phenyl-1H-inden-1-yl)-4H-chromen-4-
one (6ae)
Yield: 37.2 mg (50%, reaction time = 1.5 h); white solid; mp 156–
158 °C.
19F NMR (470 MHz, CDCl3):  = –128.5.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H16FO2: 355.1129; found:
IR (CHCl3): 2923, 2857, 1676, 1641, 1605, 1461, 1376, 910, 815, 734,
355.1130.
693 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.48 (d, J = 2.3 Hz, 1 H), 7.71 (dd, J = 8.8,
2.5 Hz, 1 H), 7.58 (d, J = 7.3 Hz, 2 H), 7.49–7.45 (m, 2 H), 7.38–7.33 (m,
4 H), 7.24–7.21 (m, 3 H), 5.58 (d, J = 5.7 Hz, 1 H).
3-(3-Fluoro-2-phenyl-1H-inden-1-yl)-6-methyl-4H-chromen-4-
one (6ab)
Yield: 33 mg (52%, reaction time = 2 h); white solid; mp 162–164 °C.
1
13C{1H} NMR (125 MHz, CDCl3):  = 176.5, 157.2 (d, JC-F = 279.2 Hz),
IR (CHCl3): 3056, 2924, 1642, 1618, 1484, 1376, 1319, 1161, 911, 812,
155.1, 153.1, 144.3 (d, 3JC-F = 7.2 Hz), 136.7, 135.5, 135.3, 131.3 (d, 4JC-F
693, 544 cm–1
.
3
= 4.9 Hz), 128.8, 128.6, 127.7 (d, JC-F = 6.4 Hz), 127.6, 127.4, 125.2,
1H NMR (400 MHz, CDCl3):  = 8.14 (s, 1 H), 7.60 (d, J = 8.1 Hz, 2 H),
7.51 (d, J = 7.3 Hz, 1 H), 7.45 (d, J = 7.5 Hz, 2 H), 7.36–7.32 (m, 4 H),
7.24–7.19 (m, 3 H), 5.63 (d, J = 5.4 Hz, 1 H), 2.49 (s, 3 H).
124.0, 123.1, 120.1, 119.7, 118.7, 118.1, 40.7.
19F NMR (470 MHz, CDCl3):  = –128.3.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H14BrFNaO2: 457.0036;
found: 457.0035.
1
13C{1H} NMR (100 MHz, CDCl3):  = 177.8, 157.1 (d, JC-F = 280.2 Hz),
3
154.6, 152.9, 144.6 (d, JC-F = 6.9 Hz), 135.5, 135.3, 134.9, 131.4,
3
131.38, 128.8, 127.5 (d, JC-F = 6.5 Hz), 127.4, 127.2, 125.2, 124.1,
2-(3-Fluoro-2-phenyl-1H-inden-1-yl)-1H-benzo[f]chromen-1-one
(6af)
123.6, 122.4, 119.9, 117.98 (d, 4JC-F = 2.5 Hz), 117.9, 40.7, 21.0.
19F NMR (470 MHz, CDCl3):  = –128.7.
Yield: 34.8 mg (50%, reaction time = 6 h); white solid; mp 185–187 °C.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H17FNaO2: 391.1105;
found: 391.1106.
IR (CHCl3): 2926, 2855, 1642, 1609, 1516, 1441, 1375, 910, 820, 732,
693, 607 cm–1
.
1H NMR (400 MHz, CDCl3):  = 10.26 (d, J = 8.4 Hz, 1 H), 8.04 (d, J = 8.9
Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.85 (t, J = 7.8 Hz, 1 H), 7.69–7.60 (m,
4 H), 7.48–7.44 (m, 2 H), 7.38–7.33 (m, 4 H), 7.21 (t, J = 7.5 Hz, 2 H),
5.78 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 179.2, 157.5, 157.2 (d, 1JC-F = 279.3
Hz), 150.4, 144.6, 135.5, 135.3, 131.4, 130.6, 130.5, 129.3, 128.8,
128.3, 127.7 (d, 3JC-F = 6.3 Hz), 127.4, 127.2, 127.1, 126.7, 125.3, 124.1,
119.9, 118.0, 117.5, 117.1, 40.8.
6-Fluoro-3-(3-fluoro-2-phenyl-1H-inden-1-yl)-4H-chromen-4-
one (6ac)
Yield: 34 mg (53%, reaction time = 3 h); white solid; mp 220–222 °C.
IR (CHCl3): 2932, 2857, 1637, 1625, 1476, 1457, 1049, 910, 610 cm–1
1H NMR (400 MHz, CDCl3):  = 7.98 (dd, J = 7.9, 2.6 Hz, 1 H), 7.60–7.58
(m, 2 H), 7.51–7.45 (m, 2 H), 7.39 (s, 1 H), 7.38–7.33 (m, 5 H), 7.23 (t,
J = 7.3 Hz, 2 H), 5.58 (d, J = 5.5 Hz, 1 H).
.
1
13C{1H} NMR (100 MHz, CDCl3):  = 177.1, 159.7 (d, JC-F = 248.6 Hz),
19F NMR (470 MHz, CDCl3):  = –128.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C28H17FNaO2: 427.1105;
155.8, 153.2, 152.6, 144.4 (d, 3JC-F = 7.3 Hz), 135.5, 135.3, 131.3 (d, 4JC-F
= 4.9 Hz), 128.8, 127.7 (d, 3JC-F = 6.4 Hz), 127.6, 127.3, 124.9 (d, 3JC-F
=
found: 427.1098.
4
4
7.5 Hz), 124.0 (d, JC-F = 2.5 Hz), 122.2 (d, JC-F = 4.6 Hz), 121.9, 120.3
(d, JC-F = 8.1 Hz), 119.7, 118.1 (d, JC-F = 2.3 Hz), 110.8 (d, JC-F = 23.9
3
4
2
3-(3-Fluoro-2-phenyl-1H-inden-1-yl)-4H-benzo[h]chromen-4-
one (6ag)
Hz), 40.7.
19F NMR (470 MHz, CDCl3):  = –114.8, –128.5.
Yield: 33.4 mg (48%, reaction time = 6 h); white solid; mp 138–140 °C.
IR (CHCl3): 1683, 1642, 1601, 1445, 1380, 910, 694, 668 cm–1
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H15F2O2: 373.1035; found:
.
373.1042.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

G
A. Kumari, R. A. Fernandes
Paper
Synthesis
1H NMR (500 MHz, CDCl3):  = 8.30–8.26 (m, 2 H), 7.90 (d, J = 8.1 Hz, 1
H), 7.80 (d, J = 8.7 Hz, 1 H), 7.68–7.64 (m, 3 H), 7.60–7.57 (m, 3 H),
7.47 (d, J = 7.4 Hz, 1 H), 7.37–7.34 (m, 3 H), 7.24–7.20 (m, 2 H), 5.70
(d, J = 5.3 Hz, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 176.1, 158.9, 153.5, 144.8, 144.1,
141.5, 139.3, 132.5, 129.5, 128.7, 128.5, 128.2, 127.93, 127.9, 127.2,
123.8, 123.7, 123.4, 122.8, 120.0, 119.9, 45.1.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H14ClNNaO4: 438.0504;
found: 438.0501.
1
13C{1H} NMR (125 MHz, CDCl3):  = 177.5, 157.3 (d, JC-F = 279.9 Hz),
2
153.9, 152.1, 144.5, 135.7, 135.4 (d, JC-F = 25.7 Hz), 131.4, 129.4,
128.8, 128.7, 128.0, 127.7 (d, 3JC-F = 6.2 Hz), 127.5, 127.3, 127.2, 126.7,
3-(3-Chloro-2-phenyl-1H-inden-1-yl)-6-methyl-4H-chromen-4-
one (6bc)
2
125.5, 124.2 (d, JC-F = 13.5 Hz), 123.9, 122.1, 120.8, 120.2, 119.8,
118.0, 40.8.
19F NMR (470 MHz, CDCl3):  = –128.0.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C28H17FNaO2: 427.1105;
Yield: 49.6 mg (75%, reaction time = 2 h); white solid; mp 140–142 °C.
IR (CHCl3): 3057, 2924, 2853, 1641, 1622, 1483, 1319, 1160, 910, 748,
695 cm–1
.
found: 427.1100.
1H NMR (500 MHz, CDCl3):  = 8.10 (s, 1 H), 7.76 (d, J = 6.9 Hz, 2 H),
7.54 (d, J = 7.5 Hz, 1 H), 7.49–7.48 (m, 1 H), 7.42–7.35 (m, 4 H), 7.29 (s,
1 H), 7.27–7.23 (m, 2 H), 7.22–7.19 (m, 1 H), 5.81 (s, 1 H), 2.46 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.5, 154.5, 153.1, 145.1, 141.4,
140.0, 135.2, 134.9, 132.8, 128.9, 128.61, 128.6, 128.0, 127.5, 127.0,
125.2, 123.52, 123.5, 122.4, 119.6, 117.9, 45.3, 20.9.
3-(2-(4-Bromophenyl)-3-fluoro-1H-inden-1-yl)-4H-chromen-4-
one (6ah)
Yield: 44 mg (59%, reaction time = 2 h); white solid; mp 103–105 °C.
IR (CHCl3): 2945, 2833, 1686, 1640, 1608, 1465, 1395, 1028, 824, 690
cm–1
.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H17ClNaO2: 407.0809;
found: 407.0811.
1H NMR (500 MHz, CDCl3):  = 8.15 (d, J = 7.1 Hz, 1 H), 7.45 (dt, J = 7.7,
1.7 Hz, 1 H), 7.29–7.24 (m, 6 H), 7.16–7.13 (m, 3 H), 7.06 (s, 1 H), 7.03
(dt, J = 7.5, 1.0 Hz, 1 H), 5.38 (s, 1 H).
3-(3-Chloro-2-phenyl-1H-inden-1-yl)-6-fluoro-4H-chromen-4-
one (6bd)
13C{1H} NMR (100 MHz, CDCl3):  = 177.7, 157.6 (d, JC-F = 262.5 Hz),
1
156.2, 153.0, 144.5, 135.3, 135.0, 133.8, 132.0, 131.6, 130.3, 129.2 (d,
3JC-F = 6.3 Hz), 127.6, 126.0, 125.4, 124.1, 123.8, 122.4, 121.2, 119.0,
118.2, 40.6.
19F NMR (470 MHz, CDCl3):  = –127.5.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H14BrFNaO2: 455.0053;
found: 455.0056.
Yield: 50.7 mg (76%, reaction time = 1 h); white solid; mp 183–186 °C.
IR (CHCl3): 3057, 2922, 2850, 1635, 1617, 1476, 1265, 1129, 817, 725,
509 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.94 (dd, J = 7.9, 2.4 Hz, 1 H), 7.74 (d, J =
7.4 Hz, 2 H), 7.55 (d, J = 7.6 Hz, 1 H), 7.47 (d, J = 7.4 Hz, 1 H), 7.41–7.35
(m, 3 H), 7.34–7.31 (m, 3 H), 7.28–7.22 (m, 2 H), 5.76 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 176.8, 159.6 (d, JC-F = 247.3 Hz),
1
153.4, 152.5, 144.8, 141.4, 139.7, 132.7, 129.1, 128.6 (d, 3JC-F = 6.3 Hz),
3-(2-Aryl-3-chloro-1H-inden-1-yl)-4H-chromen-4-ones 6ba–6bs;
General Procedure
3
128.1, 127.7, 127.1, 124.91, 124.9, 123.5, 122.1 (d, JC-F = 5.5 Hz),
Compounds 6ba–6bs were prepared by following a similar procedure
as described for compounds 6aa–6ah, using BCl3 (2.5 equiv) instead of
BF3·OEt2 and 0.172 mmol each of 3 and 4.
121.9, 120.3 (d, 3JC-F = 8.1 Hz), 119.7, 110.7 (d, 2JC-F = 23.6 Hz), 45.2.
19F NMR (470 MHz, CDCl3):  = –114.8.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H14ClFNaO2: 411.0559;
found: 411.0551.
3-(3-Chloro-2-phenyl-1H-inden-1-yl)-4H-chromen-4-one (6ba)
Yield: 55.5 mg (87%, reaction time = 5 h); white semisolid.
6-Bromo-3-(3-chloro-2-phenyl-1H-inden-1-yl)-4H-chromen-4-
IR (CHCl3): 3057, 2923, 2850, 1650, 1617, 1465, 1349, 1220, 912, 736,
one (6be)
701, 592 cm–1
.
Yield: 52.6 mg (68%, reaction time = 1.5 h); white solid; mp 88–90 °C.
1H NMR (500 MHz, CDCl3):  = 8.32 (d, J = 7.7 Hz, 1 H), 7.78 (d, J = 7.5
Hz, 2 H), 7.60 (dt, J = 6.9, 1.6 Hz, 1 H), 7.55 (d, J = 7.6 Hz, 1 H), 7.50 (d,
J = 7.4 Hz, 1 H), 7.40–7.34 (m, 4 H), 7.32 (s, 1 H), 7.30–7.27 (m, 2 H),
7.24–7.22 (m, 1 H), 5.80 (s, 1 H).
13C{1H} NMR (100 MHz, CDCl3):  = 177.4, 156.2, 153.2, 144.9, 141.4,
139.9, 133.6, 132.7, 128.9, 128.6, 128.0, 127.6, 127.0, 125.9, 125.2,
123.8, 123.5, 122.6, 119.6, 118.1, 45.2.
IR (CHCl3): 3066, 2925, 1641, 1604, 1461, 1312, 1266, 1146, 908, 732,
697, 595 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.43 (s, 1 H), 7.75 (d, J = 7.7 Hz, 2 H),
7.67 (dd, J = 8.7, 1.7 Hz, 1 H), 7.55 (d, J = 7.5 Hz, 1 H), 7.47 (d, J = 7.4 Hz,
1 H), 7.41–7.36 (m, 3 H), 7.31–7.28 (m, 2 H), 7.24–7.23 (m, 1 H), 7.18
(d, J = 8.8 Hz, 1 H), 5.76 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 176.1, 154.9, 153.3, 144.6, 141.4,
139.6, 136.6, 132.6, 129.1, 128.6, 128.5, 128.1, 127.7, 127.1, 125.0,
123.4, 122.9, 120.0, 119.7, 118.6, 45.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H15ClNaO2: 393.0653;
found: 393.0650.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H15BrClO2: 448.9938;
found: 448.9936.
3-(3-Chloro-2-phenyl-1H-inden-1-yl)-6-nitro-4H-chromen-4-one
(6bb)
Yield: 51.5 mg (72%, reaction time = 6 h); white solid; mp 73–74 °C.
3-(3-Chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-4H-chromen-4-
one (6bf)
IR (CHCl3): 2923, 2853, 1651, 1629, 1465, 1345, 911, 746, 593 cm–1
.
1H NMR (500 MHz, CDCl3):  = 9.18 (d, J = 2.5 Hz, 1 H), 8.44 (dd, J = 9.2,
2.7 Hz, 1 H), 7.74 (d, J = 7.6 Hz, 2 H), 7.56 (d, J = 7.6 Hz, 1 H), 7.46 (d, J =
8.9 Hz, 2 H), 7.42–7.37 (m, 4 H), 7.30–7.22 (m, 2 H), 5.74 (s, 1 H).
Yield: 64.5 mg (94%, reaction time = 1.5 h); white solid; mp 221–
224 °C.
IR (CHCl3): 2921, 2856, 1633, 1610, 1466, 1354, 1164, 817, 601 cm–1
.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

H
A. Kumari, R. A. Fernandes
Paper
Synthesis
1H NMR (500 MHz, CDCl3):  = 8.34 (d, J = 7.8 Hz, 1 H), 7.66–7.60 (m, 3
H), 7.44–7.39 (m, 2 H), 7.32–7.29 (m, 3 H), 7.19–7.16 (m, 3 H), 5.74 (s,
1 H), 2.34 (s, 3 H), 2.32 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.6, 156.2, 153.3, 145.1, 139.0,
138.8, 137.8, 137.0, 133.6, 130.0, 129.3, 128.4, 128.3, 126.0, 125.2,
124.3, 123.8, 123.0, 119.2, 118.1, 44.9, 21.5, 21.2.
3-(3-Chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-6-nitro-4H-
chromen-4-one (6bj)
Yield: 50.4 mg (66%, reaction time = 1.5 h); white solid; mp 230–
232 °C.
IR (CHCl3): 2925, 2857, 1641, 1629, 1529, 1464, 1341, 1263, 814, 690,
593 cm–1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H20ClO2: 399.1146; found:
399.1145.
1H NMR (400 MHz, CDCl3):  = 9.19 (d, J = 2.6 Hz, 1 H), 8.43 (dd, J = 6.5,
2.9 Hz, 1 H), 7.62 (d, J = 8.1 Hz, 2 H), 7.46 (d, J = 9.2 Hz, 1 H), 7.40 (d, J =
7.7 Hz, 1 H), 7.37 (s, 1 H), 7.27 (s, 1 H), 7.21–7.17 (m, 3 H), 5.68 (s, 1
H), 2.35 (s, 3 H), 2.33 (s, 3 H).
3-(3-Chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-6-methyl-4H-
chromen-4-one (6bg)
13C{1H} NMR (100 MHz, CDCl3):  = 176.3, 159.0, 153.5, 144.7, 144.3,
140.0, 138.12, 138.1, 137.3, 129.7, 129.4, 128.8, 128.6, 128.3, 127.9,
124.2, 123.8, 122.9, 119.9, 119.4, 44.8, 21.5, 21.3.
Yield: 65.3 mg (92%, reaction time = 1 h); white solid; mp 233–236 °C.
IR (CHCl3): 2920, 2881, 1642, 1624, 1509, 1483, 1320, 1167, 818, 726,
508 cm–1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H19ClNO4: 444.0997;
1H NMR (500 MHz, CDCl3):  = 8.12 (s, 1 H), 7.66 (d, J = 8.2 Hz, 2 H),
7.43–7.39 (m, 2 H), 7.31–7.29 (m, 2 H), 7.18 (dd, J = 14.9, 8.4 Hz, 4 H),
5.75 (s, 1 H), 2.47 (s, 3 H), 2.34 (s, 3 H), 2.32 (s, 3 H).
found: 444.0995.
3-(3-Chloro-2-phenyl-1H-inden-1-yl)-4H-benzo[h]chromen-4-
one (6bk)
13C{1H} NMR (125 MHz, CDCl3):  = 177.6, 154.5, 153.1, 145.2, 138.9,
138.8, 137.7, 136.9, 135.1, 134.8, 130.0, 129.2, 128.4, 128.2, 128.1,
125.2, 124.2, 123.5, 122.7, 119.1, 117.8, 44.9, 21.5, 21.2, 20.9.
Yield: 69.5 mg (96%, reaction time = 2.5 h); white solid; mp 80–84 °C.
IR (CHCl3): 3061, 2925, 2850, 1642, 1462, 1400, 1265, 1156, 698, 583
cm–1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H22ClO2: 413.1303; found:
1H NMR (500 MHz, CDCl3):  = 8.25 (dd, J = 8.5, 4.5 Hz, 2 H), 7.88 (d, J =
8.1 Hz, 1 H), 7.81 (d, J = 7.6 Hz, 2 H), 7.77 (d, J = 8.7 Hz, 1 H), 7.65 (t, J =
7.6 Hz, 1 H), 7.58–7.52 (m, 4 H), 7.41–7.36 (m, 3 H), 7.27–7.26 (m, 1
H), 7.24–7.22 (m, 1 H), 5.87 (s, 1 H).
413.1308.
3-(3-Chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-6-fluoro-4H-
chromen-4-one (6bh)
13C{1H} NMR (125 MHz, CDCl3):  = 177.2, 153.8, 152.3, 144.9, 141.5,
139.9, 135.7, 134.9, 132.8, 129.4, 129.0, 128.6, 128.03, 128.0, 127.6,
127.13, 127.1, 125.4, 124.2, 123.9, 123.6, 122.1, 120.8, 120.1, 119.7,
45.3.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H18ClO2: 421.0990; found:
421.0985.
Yield: 43.7 mg (61%, reaction time = 2.5 h); white solid; mp 155–
158 °C.
IR (CHCl3): 2912, 1636, 1626, 1613, 1478, 1326, 964, 816, 725, 603,
508 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.95 (dd, J = 8.1, 2.6 Hz, 1 H), 7.63 (d, J =
7.1 Hz, 2 H), 7.40 (d, J = 7.3 Hz, 1 H), 7.37–7.29 (m, 3 H), 7.28 (s, 1 H),
7.19–7.16 (m, 3 H), 5.70 (s, 1 H), 2.34 (s, 3 H), 2.32 (s, 3 H).
3-(3-Chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-4H-benzo[h]-
chromen-4-one (6bl)
1
13C{1H} NMR (100 MHz, CDCl3):  = 176.9, 159.5 (d, JC-F = 247.5 Hz),
153.5, 152.5, 144.9, 139.0, 138.6, 137.9, 137.1, 129.9, 129.3, 128.4,
128.36, 124.9 (d, 3JC-F = 7.6 Hz), 124.2, 122.5, 122.0, 121.8, 120.3 (d,
3JC-F = 8.1 Hz), 119.3, 110.8 (d, 2JC-F = 23.8 Hz), 44.9, 21.5, 21.2.
Yield: 58.7 mg (76%, reaction time = 1 h); white solid; mp 223–226 °C.
IR (CHCl3): 2983, 2928, 2850, 1637, 1625, 1444, 1415, 1374, 1241,
1047, 814, 639 cm–1
.
19F NMR (470 MHz, CDCl3):  = –114.9.
1H NMR (400 MHz, CDCl3):  = 8.25 (t, J = 8.5 Hz, 2 H), 7.88 (d, J = 8.1
Hz, 1 H), 7.77 (d, J = 78.8 Hz, 1 H), 7.69 (d, J = 8.2 Hz, 2 H), 7.67–7.62
(m, 1 H), 7.56 (dt, J = 7.1, 0.9 Hz, 1 H), 7.50 (s, 1 H), 7.42 (d, J = 7.7 Hz,
1 H), 7.35 (s, 1 H), 7.20–7.17 (m, 3 H), 5.81 (s, 1 H), 2.34 (s, 3 H), 2.30
(s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H19ClFO2: 417.1052; found:
417.1054.
6-Bromo-3-(3-chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-4H-
chromen-4-one (6bi)
13C{1H} NMR (100 MHz, CDCl3):  = 177.3, 153.8, 152.4, 145.1, 139.0,
138.7, 137.8, 137.0, 135.7, 130.0, 129.33, 129.3, 128.4, 128.3, 128.0,
127.1, 125.4, 124.5, 124.3, 123.9, 122.1, 120.9, 120.1, 119.2, 45.0, 21.5,
21.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C30H22ClO2: 449.1303; found:
449.1297.
Yield: 62.5 mg (76%, reaction time = 1.5 h); white solid; mp 218–
220 °C.
IR (CHCl3): 2920, 1642, 1604, 1462, 1437, 1335, 1313, 1267, 819, 733,
598 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.45 (d, J = 2.5 Hz, 1 H), 7.69 (dd, J = 8.9,
2.4 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 2 H), 7.40 (d, J = 7.7 Hz, 1 H), 7.31 (s, 1
H), 7.26 (s, 1 H), 7.22–7.16 (m, 4 H), 5.69 (s, 1 H), 2.34 (s, 3 H), 2.32 (s,
3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 176.3, 155.0, 153.4, 144.8, 139.0,
138.5, 137.9, 137.1, 136.6, 129.9, 129.4, 128.6, 128.43, 128.4, 125.1,
124.2, 123.3, 120.1, 119.3, 118.6, 44.9, 21.5, 21.2.
3-(3-Chloro-6-methoxy-2-phenyl-1H-inden-1-yl)-4H-chromen-4-
one (6bm)
Yield: 65.5 mg (95%, reaction time = 7 h); white solid; mp 83–86 °C.
IR (CHCl3): 3003, 2955, 2833, 1638, 1622, 1484, 1320, 1285, 1031,
817, 695, 609 cm–1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H19BrClO2: 477.0251;
found: 477.0251.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

I
A. Kumari, R. A. Fernandes
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 8.32 (d, J = 6.7 Hz, 1 H), 7.74 (d, J = 7.3
Hz, 2 H), 7.61 (dt, J = 7.7, 1.6 Hz, 1 H), 7.44–7.41 (m, 2 H), 7.39–7.34
(m, 3 H), 7.30 (d, J = 8.4 Hz, 1 H), 7.25–7.22 (m, 1 H), 7.08 (d, J = 1.6 Hz,
1 H), 6.93 (dd, J = 8.4, 2.2 Hz, 1 H), 5.76 (s, 1 H), 3.78 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 177.7, 159.8, 156.4, 153.6, 147.0,
137.8, 134.6, 133.8, 133.2, 128.8, 127.8, 126.1, 125.4, 124.0, 123.0,
120.5, 118.3, 113.7, 109.8, 55.8, 45.3.
3-(3-Chloro-2-ethyl-1H-inden-1-yl)-6-fluoro-4H-chromen-4-one
(6bq)
Yield: 48.7 mg (83%, reaction time = 3 h); white solid; mp 121–123 °C.
IR (CHCl3): 3071, 2970, 2934, 1646, 1479, 1319, 1264, 1175, 960, 824,
722, 600, 555 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 6.0 Hz, 1 H), 7.45–7.37 (m, 3
H), 7.36–7.31 (m, 3 H), 7.18 (dt, J = 7.5, 1.0 Hz, 1 H), 5.15 (s, 1 H), 2.74
(sextet, J = 7.1 Hz, 1 H), 2.19 (sextet, J = 7.4 Hz, 1 H), 1.14 (t, J = 7.6 Hz,
3 H).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H17ClNaO3: 423.0758;
found: 423.0754.
13C{1H} NMR (100 MHz, CDCl3):  = 176.6, 159.7 (d, JC-F = 247.2 Hz),
1
3-(3-Chloro-6-methoxy-2-phenyl-1H-inden-1-yl)-6-methyl-4H-
chromen-4-one (6bn)
3
153.1, 152.6, 145.5, 144.5, 141.6, 128.0, 127.4, 126.0, 124.9 (d, JC-F
7.3 Hz), 123.2, 122.1, 121.8 (d, JC-F = 6.9 Hz), 120.3 (d, JC-F = 8.1 Hz),
=
3
3
118.8, 110.8 (d, 2JC-F = 23.7 Hz), 44.6, 20.0, 13.2.
Yield: 59.2 mg (83%, reaction time = 6 h); white solid; mp 93–95 °C.
19F NMR (470 MHz, CDCl3):  = –114.7.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H14ClFNaO2: 363.0559;
IR (CHCl3): 3006, 2925, 2833, 1639, 1618, 1444, 1285, 1032, 817, 695,
543 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.09 (s, 1 H), 7.73 (d, J = 7.5 Hz, 2 H),
7.42 (d, J = 8.4 Hz, 2 H), 7.35 (t, J = 7.9 Hz, 2 H), 7.32 (s, 1 H), 7.24 (d, J =
7.4 Hz, 1 H), 7.21 (d, J = 8.5 Hz, 1 H), 7.07 (d, J = 1.6 Hz, 1 H), 6.92 (dd,
J = 8.4, 2.3 Hz, 1 H), 5.76 (s, 1 H), 3.78 (s, 3 H), 2.46 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.5, 159.6, 154.5, 153.3, 147.0,
137.7, 135.2, 134.9, 134.4, 133.0, 128.5, 128.3, 127.6, 125.2, 123.5,
122.6, 120.3, 117.9, 113.6, 109.5, 55.6, 45.1, 20.9.
found: 363.0556.
3-(2-Butyl-3-chloro-1H-inden-1-yl)-4H-chromen-4-one (6br)
Yield: 50.7 mg (84%, reaction time = 5 h); pale yellow oil.
IR (CHCl3): 3068, 2929, 2858, 1647, 1480, 1318, 1157, 822, 723, 600
cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.31 (d, J = 7.5 Hz, 1 H), 7.69–7.66 (m, 1
H), 7.46–7.39 (m, 4 H), 7.35–7.33 (m, 2 H), 7.17 (t, J = 7.5 Hz, 1 H), 5.16
(s, 1 H), 2.71 (sextet, J = 7.9 Hz, 1 H), 2.17 (septet, J = 5.5 Hz, 1 H),
1.56–1.46 (m, 2 H), 1.37–1.28 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.3, 156.4, 152.9, 145.0, 144.5,
141.6, 133.7, 128.5, 127.3, 126.1, 126.0, 125.3, 123.9, 123.3, 122.4,
118.8, 118.2, 44.9, 30.8, 26.4, 22.5, 13.8.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C26H19ClNaO3: 437.0915;
found: 437.0902.
3-(3-Chloro-6-methoxy-2-phenyl-1H-inden-1-yl)-6-fluoro-4H-
chromen-4-one (6bo)
Yield: 68.4 mg (95%, reaction time = 6 h); white solid; mp 165–168 °C.
IR (CHCl3): 3067, 2925, 2844, 1634, 1612, 1479, 1454, 1286, 1029,
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H19ClNaO2: 373.0966;
found: 373.0970.
829, 688, 558 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.94 (dd, J = 8.4, 2.2 Hz, 1 H), 7.72 (d, J =
7.5 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 1 H), 7.38–7.32 (m, 5 H), 7.24–7.22 (m,
1 H), 7.06 (s, 1 H), 6.93 (dd, J = 8.4, 2.0 Hz, 1 H), 5.72 (s, 1 H), 3.78 (s, 3
H).
3-(2-Butyl-3-chloro-1H-inden-1-yl)-6-fluoro-4H-chromen-4-one
(6bs)
Yield: 50.8 mg (80%, reaction time = 6 h); pale yellow oil.
13C{1H} NMR (100 MHz, CDCl3):  = 176.8, 159.6, 159.5 (d, 1JC-F = 247.3
IR (CHCl3): 3067, 2932, 2857, 1645, 1481, 1459, 1315, 1159, 817, 722,
2
Hz), 153.6, 152.5, 146.6, 137.4, 134.4, 132.9, 128.8, 128.5 (d, JC-F
=
600 cm–1
.
3
27.8 Hz), 127.7, 124.9, 122.3, 122.1, 121.8, 120.4, 120.3 (d, JC-F = 8.3
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 7.2 Hz, 1 H), 7.44–7.38 (m, 3
H), 7.36–7.31 (m, 3 H), 7.17 (t, J = 7.2 Hz, 1 H), 5.12 (s, 1 H), 2.71
(quint, J = 7.9 Hz, 1 H), 2.15 (septet, J = 5.6 Hz, 1 H), 1.58–1.45 (m, 2
H), 1.39–1.29 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H).
Hz), 113.6, 110.7 (d, 2JC-F = 23.9 Hz), 109.6, 55.6, 45.0.
19F NMR (470 MHz, CDCl3):  = –114.8.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H16ClFNaO3: 441.0664;
found: 441.0657.
1
13C{1H} NMR (100 MHz, CDCl3):  = 176.6, 159.7 (d, JC-F = 247.0 Hz),
3
153.1, 152.6, 144.7, 144.3, 141.6, 128.7, 127.4, 126.1, 124.9 (d, JC-F
=
3-(3-Chloro-2-ethyl-1H-inden-1-yl)-4H-chromen-4-one (6bp)
Yield: 51.6 mg (93%, reaction time = 4 h); white semisolid.
IR (CHCl3): 2964, 2927, 2856, 1643, 1611, 1466, 1349, 1143, 724, 670
4
3
7.6 Hz), 123.3, 122.1, 121.8 (d, JC-F = 4.6 Hz), 120.3 (d, JC-F = 8.1 Hz),
118.8, 110.8 (d, 2JC-F = 23.7 Hz), 44.9, 30.8, 26.4, 22.5, 13.8.
19F NMR (470 MHz, CDCl3):  = –114.7.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H18ClFNaO2: 391.0872;
cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.32 (d, J = 7.8 Hz, 1 H), 7.67 (dt, J = 7.7,
1.7 Hz, 1 H), 7.47–7.39 (m, 3 H), 7.36–7.31 (m, 3 H), 7.18 (dt, J = 6.9,
1.2 Hz, 1 H), 5.18 (s, 1 H), 2.74 (sextet, J = 7.5 Hz, 1 H), 2.20 (sextet, J =
7.4 Hz, 1 H), 1.14 (t, J = 7.5 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 177.3, 156.4, 152.9, 145.8, 144.8,
141.7, 133.7, 127.8, 127.3, 126.0, 126.0, 125.3, 123.8, 123.3, 122.3,
118.8, 118.1, 44.5, 20.0, 13.2.
found: 391.0868.
3-(2-Aryl-3-bromo-1H-inden-1-yl)-4H-chromen-4-ones 6ca–6cr;
General Procedure
Compounds 6ca–6cr were prepared by following a similar procedure
as described for compounds 6aa–6ah, using BBr3 (2.5 equiv) instead
of BF3·OEt2 and 0.172 mmol each of 3 and 4. In the case of 6cr, 3.5
equivalents of BBr3 were used.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H15ClNaO2: 345.0653;
found: 345.0655.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

J
A. Kumari, R. A. Fernandes
Paper
Synthesis
1
3-(3-Bromo-2-phenyl-1H-inden-1-yl)-4H-chromen-4-one (6ca)
13C{1H} NMR (125 MHz, CDCl3):  = 176.6, 159.5 (d, JC-F = 247.3 Hz),
2
153.4, 152.4, 144.9, 143.5, 142.7, 133.4, 128.6 (d, JC-F = 15.4 Hz),
Yield: 60.7 mg (85%, reaction time = 5.5 h); white solid; mp 150–
153 °C.
3
128.2, 127.7, 127.1, 124.9 (d, JC-F = 7.1 Hz), 123.4, 122.1, 121.9,
121.85, 121.0, 120.3 (d, 3JC-F = 8.0 Hz), 119.0, 110.7 (d, 2JC-F = 23.8 Hz),
IR (CHCl3): 2915, 2857, 1631, 1613, 1465, 1395, 1351, 909, 816, 592,
46.5.
534 cm–1
.
19F NMR (470 MHz, CDCl3):  = –114.8.
1H NMR (500 MHz, CDCl3):  = 8.29 (dd, J = 8.5, 1.9 Hz, 1 H), 7.77–7.75
(m, 2 H), 7.61 (ddd, J = 7.0, 5.1, 1.8 Hz, 1 H), 7.54 (d, J = 7.6 Hz, 1 H),
7.47 (d, J = 7.5 Hz, 1 H), 7.42–7.36 (m, 4 H), 7.33 (s, 1 H), 7.31–7.28 (m,
2 H), 7.23 (dt, J = 7.4, 1.1 Hz, 1 H), 5.76 (s, 1 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H15BrFO2: 435.0216;
found: 435.0218.
3-(3-Bromo-2-phenyl-1H-inden-1-yl)-6-nitro-4H-chromen-4-one
(6ce)
13C{1H} NMR (125 MHz, CDCl3):  = 177.3, 156.2, 153.2, 145.2, 143.7,
142.7, 133.6, 133.5, 128.7, 128.5, 128.1, 127.6, 127.0, 125.9, 125.2,
123.8, 123.4, 122.4, 120.9, 118.8, 118.1, 46.6.
Yield: 64.1 mg (81%, reaction time = 3.5 h); white solid; mp 180–
184 °C.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H15BrNaO2: 437.0148;
IR (CHCl3): 3080, 2924, 2857, 1649, 1628, 1529, 1465, 1345, 1321,
found: 437.0152.
1262, 746, 696, 592 cm–1
.
3-(3-Bromo-2-phenyl-1H-inden-1-yl)-6-methyl-4H-chromen-4-
one (6cb)
1H NMR (400 MHz, CDCl3):  = 9.16 (d, J = 2.6 Hz, 1 H), 8.44 (dd, J = 9.2,
2.7 Hz, 1 H), 7.74 (d, J = 7.5 Hz, 2 H), 7.54 (d, J = 7.5 Hz, 1 H), 7.48–7.44
(m, 2 H), 7.42–7.37 (m, 4 H), 7.32–7.27 (d, J = 7.4 Hz, 1 H), 7.25–7.23
(m, 1 H), 5.71 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 176.0, 158.9, 153.5, 144.8, 144.4,
143.0, 142.7, 133.2, 128.7, 128.6, 128.3, 128.0, 127.9, 127.2, 123.74,
123.7, 123.3, 122.8, 121.2, 119.9, 119.4, 46.4.
Yield: 59 mg (80%, reaction time = 5 h); white solid; mp 172–175 °C.
IR (CHCl3): 3057, 2926, 1641, 1622, 1574, 1483, 1243, 1046, 807, 696,
604 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.08 (s, 1 H), 7.76 (d, J = 7.4 Hz, 2 H),
7.53 (d, J = 7.6 Hz, 1 H), 7.46 (d, J = 7.5 Hz, 1 H), 7.42–7.35 (m, 4 H),
7.30–7.27 (m, 2 H), 7.24–7.18 (m, 2 H), 5.77 (s, 1 H), 2.45 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.4, 154.5, 153.1, 145.2, 143.7,
142.6, 135.2, 134.9, 133.5, 128.7, 128.5, 128.1, 127.6, 127.0, 125.2,
123.44, 123.4, 122.2, 120.9, 118.7, 117.8, 46.6, 20.9.
HRMS (ESI-TOF): m/z [M + K]+ calcd for C24H14BrKNO4: 497.9738;
found: 497.9740.
3-(3-Bromo-2-phenyl-1H-inden-1-yl)-4H-benzo[h]chromen-4-
one (6cf)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H17BrNaO2: 451.0304;
found: 451.0304.
Yield: 65.6 mg (82%, reaction time = 8 h); white solid; mp 68–70 °C.
IR (CHCl3): 3065, 2979, 2928, 1642, 1462, 1442, 1379, 1254, 1046,
914, 698, 570 cm–1
.
6-Bromo-3-(3-bromo-2-phenyl-1H-inden-1-yl)-4H-chromen-4-
one (6cc)
1H NMR (400 MHz, CDCl3):  = 8.23 (t, J = 8.8 Hz, 2 H), 7.87 (d, J = 8.2
Hz, 1 H), 7.81 (d, J = 7.7 Hz, 2 H), 7.75 (d, J = 8.8 Hz, 1 H), 7.64 (t, J = 7.8
Hz, 1 H), 7.57–7.52 (m, 4 H), 7.42–7.36 (m, 3 H), 7.29–7.27 (m, 1 H),
7.23–7.22 (m, 1 H), 5.84 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.1, 153.7, 152.3, 145.1, 143.6,
142.7, 135.7, 133.5, 129.3, 128.7, 128.6, 128.2, 128.0, 127.7, 127.1,
127.0, 125.4, 124.0, 123.8, 123.5, 122.1, 121.0, 120.8, 120.1, 118.9,
46.7.
Yield: 72.2 mg (85%, reaction time = 5.5 h); white solid; mp 110–
112 °C.
IR (CHCl3): 3064, 2925, 1641, 1620, 1483, 1320, 1160, 935, 746, 696,
604 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.41 (d, J = 2.3 Hz, 1 H), 7.75 (s, 1 H),
7.73 (s, 1 H), 7.69 (dd, J = 8.9, 2.4 Hz, 1 H), 7.53 (d, J = 7.6 Hz, 1 H),
7.44–7.42 (m, 1 H), 7.40–7.36 (m, 3 H), 7.33–7.29 (m, 2 H), 7.23–7.19
(m, 2 H), 5.72 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 176.0, 154.9, 153.3, 144.8, 143.4,
142.6, 136.6, 133.3, 128.7, 128.5, 128.2, 127.7, 127.0, 125.0, 123.3,
122.7, 120.9, 120.0, 119.0, 118.6, 46.5.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C28H17BrNaO2: 489.0287;
found: 489.0286.
3-(3-Bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-4H-benzo[h]-
chromen-4-one (6cg)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H14Br2NaO2: 514.9253;
found: 514.9248.
Yield: 71.3 mg (84%, reaction time = 6.5 h); white solid; mp 172–
174 °C.
IR (CHCl3): 2985, 2938, 1642, 1447, 1374, 1243, 1048, 914, 738, 609
3-(3-Bromo-2-phenyl-1H-inden-1-yl)-6-fluoro-4H-chromen-4-
one (6cd)
cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.24 (dd, J = 8.1, 2.3 Hz, 2 H), 7.87 (d, J =
8.1 Hz, 1 H), 7.76 (d, J = 8.8 Hz, 1 H), 7.69 (d, J = 8.3 Hz, 2 H), 7.64 (dt,
J = 7.3, 1.3 Hz, 1 H), 7.56 (dt, J = 7.6, 1.1 Hz, 1 H), 7.51 (s, 1 H), 7.40 (d,
J = 7.7 Hz, 1 H), 7.32 (s, 1 H), 7.20–7.16 (m, 3 H), 5.79 (s, 1 H), 2.35 (s, 3
H), 2.29 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.3, 153.8, 152.4, 145.3, 142.4,
140.2, 138.0, 137.0, 135.7, 130.7, 129.3, 129.27, 128.6, 128.3, 128.0,
127.1, 125.4, 124.3, 124.2, 123.9, 122.1, 120.9, 120.5, 120.1, 118.1,
46.3, 21.4, 21.2.
Yield: 61.1 mg (82%, reaction time = 3.5 h); white solid; mp 190–
193 °C.
IR (CHCl3): 3064, 2923, 2850, 1637, 1580, 1478, 1458, 1264, 1129,
939, 828, 731, 693, 594 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.92 (dd, J = 7.9, 2.5 Hz, 1 H), 7.75 (d, J =
7.6 Hz, 2 H), 7.53 (d, J = 7.6 Hz, 1 H), 7.46–7.42 (m, 1 H), 7.40–7.36 (m,
3 H), 7.34–7.29 (m, 4 H), 7.26–7.22 (m, 1 H), 5.73 (s, 1 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

K
A. Kumari, R. A. Fernandes
Paper
Synthesis
1
HRMS (ESI-TOF): m/z [M + K]+ calcd for C30H21BrKO2: 531.0357;
13C{1H} NMR (125 MHz, CDCl3):  = 176.8, 159.6 (d, JC-F = 248.6 Hz),
found: 531.0353.
153.5, 152.5, 145.1, 142.3, 140.2, 138.0, 137.0, 130.6, 129.3, 128.5,
3
3
128.4, 124.9 (d, JC-F = 7.3 Hz), 124.1, 122.3, 121.9 (d, JC-F = 10.2 Hz),
3
2
120.6, 120.3 (d, JC-F = 8.1 Hz), 118.2, 110.7 (d, JC-F = 23.7 Hz), 46.2,
2-(3-Bromo-2-phenyl-1H-inden-1-yl)-1H-benzo[f]chromen-1-one
(6ch)
21.5, 21.3.
19F NMR (470 MHz, CDCl3):  = –114.9.
Yield: 70.4 mg (88%, reaction time = 2.5 h); white solid; mp 88–90 °C.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H19BrFO2: 461.0547;
found: 461.0552.
IR (CHCl3): 3064, 2981, 2925, 1642, 1461, 1442, 1400, 1244, 1046,
792, 698, 575 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.21 (dd, J = 8.1, 2.5 Hz, 2 H), 7.85–7.81
(m, 3 H), 7.72 (d, J = 8.8 Hz, 1 H), 7.61 (dt, J = 7.5, 1.0 Hz, 1 H), 7.56–
7.50 (m, 4 H), 7.42–7.37 (m, 3 H), 7.28–7.27 (m, 1 H), 7.23 (dt, J = 7.5,
0.8 Hz, 1 H), 5.84 (s, 1 H).
6-Bromo-3-(3-bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-4H-
chromen-4-one (6cl)
Yield: 64.7 mg (72%, reaction time = 6 h); white solid; mp 184–186 °C.
13C{1H} NMR (125 MHz, CDCl3):  = 177.1, 153.7, 152.3, 145.1, 143.6,
142.6, 135.6, 133.5, 129.3, 128.7, 128.5, 128.1, 127.9, 127.6, 127.1,
127.0, 125.4, 123.9, 123.8, 123.4, 122.0, 120.9, 120.7, 120.0, 118.9,
46.6.
HRMS (ESI-TOF): m/z [M + K]+ calcd for C28H17BrKO2: 503.0043;
found: 503.0038.
IR (CHCl3): 2921, 2854, 1641, 1621, 1483, 1432, 1320, 1166, 909, 817,
787, 594 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.43 (d, J = 2.2 Hz, 1 H), 7.68 (dd, J = 8.9,
2.4 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 7.9 Hz, 1 H), 7.31 (s, 1
H), 7.24 (s, 1 H), 7.21–7.16 (m, 4 H), 5.66 (s, 1 H), 2.35 (s, 3 H), 2.32 (s,
3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 176.2, 155.0, 153.4, 145.0, 142.2,
140.2, 138.0, 137.1, 136.6, 130.6, 129.3, 128.6, 128.5, 128.4, 125.1,
124.1, 123.1, 120.6, 120.1, 118.6, 118.3, 46.2, 21.5, 21.3.
3-(3-Bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-4H-chromen-4-
one (6ci)
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H19Br2O2: 520.9746; found:
Yield: 61 mg (80%, reaction time = 5.5 h); white solid; mp 184–186 °C.
520.9739.
IR (CHCl3): 3054, 2918, 2854, 1631, 1465, 1393, 1351, 907, 816, 710,
590 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.31 (d, J = 7.0 Hz, 1 H), 7.65–7.62 (m, 3
H), 7.43–7.38 (m, 2 H), 7.32–7.27 (m, 3 H), 7.19–7.16 (m, 3 H), 5.70 (s,
1 H), 2.34 (s, 3 H), 2.31 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 177.5, 156.2, 153.3, 145.3, 142.5,
140.2, 137.9, 137.0, 133.6, 130.7, 129.2, 128.6, 128.3, 126.0, 125.2,
124.1, 123.9, 122.8, 120.5, 118.12, 118.1, 46.3, 21.5, 21.3.
3-(3-Bromo-2-(4-bromophenyl)-1H-inden-1-yl)-6-methyl-4H-
chromen-4-one (6cm)
Yield: 63.8 mg (73%, reaction time = 2.5 h); white solid; mp 160–
164 °C.
IR (CHCl3): 1640, 1622, 1483, 1458, 1319, 1158, 910, 819, 732, 606
cm–1
.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C26H19BrNaO2: 467.0443;
found: 467.0444.
1H NMR (500 MHz, CDCl3):  = 8.07 (s, 1 H), 7.73 (d, J = 7.7 Hz, 1 H),
7.64–7.61 (m, 1 H), 7.53–7.50 (m, 2 H), 7.48 (d, J = 8.5 Hz, 1 H), 7.44–
7.41 (m, 2 H), 7.39–7.35 (m, 2 H), 7.31–7.28 (m, 1 H), 7.25–7.19 (m, 1
H), 5.72 (s, 1 H), 2.46 (s, 3 H).
3-(3-Bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-6-methyl-4H-
13C{1H} NMR (125 MHz, CDCl3):  = 177.2, 154.5, 153.2, 142.8, 142.6,
135.4, 135.0, 132.4, 131.7, 130.7, 130.2, 128.7, 127.7, 127.2, 125.2,
123.4, 122.3, 121.9, 121.0, 119.3, 117.9, 46.6, 20.9.
chromen-4-one (6cj)
Yield: 65.3 mg (83%, reaction time = 6 h); white solid; mp 228–230 °C.
IR (CHCl3): 3027, 2921, 2854, 1641, 1621, 1484, 1320, 1166, 909, 816,
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H16Br2NaO2: 528.9409;
787, 594 cm–1
.
found: 528.9401.
1H NMR (500 MHz, CDCl3):  = 8.10 (s, 1 H), 7.64 (d, J = 8.2 Hz, 2 H),
7.43–7.37 (m, 2 H), 7.29–7.27 (m, 2 H), 7.21–7.15 (m, 4 H), 5.71 (s, 1
H), 2.46 (s, 3 H), 2.34 (s, 3 H), 2.31 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 177.5, 154.5, 153.2, 145.4, 142.5,
140.2, 137.9, 136.9, 135.1, 134.8, 130.7, 129.2, 128.5, 128.2, 125.2,
124.1, 123.5, 122.5, 120.4, 118.0, 117.9, 46.3, 21.4, 21.2, 20.9.
3-(3-Bromo-2-ethyl-1H-inden-1-yl)-4H-chromen-4-one (6cn)
Yield: 53.7 mg (85%, reaction time = 5 h); pale yellow oil.
IR (CHCl3): 2966, 2923, 1644, 1621, 1483, 1459, 1339, 1318, 1160,
1139, 935, 817, 727, 597 cm–1
.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H22BrO2: 457.0798; found:
457.0799.
1H NMR (400 MHz, CDCl3):  = 8.32 (d, J = 7.1 Hz, 1 H), 7.68 (t, J = 7.6
Hz, 1 H), 7.47–7.41 (m, 2 H), 7.39–7.31 (m, 4 H), 7.17 (t, J = 7.1 Hz, 1
H), 5.18 (s, 1 H), 2.72 (sextet, J = 7.4 Hz, 1 H), 2.21 (sextet, J = 6.9 Hz, 1
H), 1.14 (t, J = 7.5 Hz, 3 H).
3-(3-Bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-6-fluoro-4H-
13C{1H} NMR (100 MHz, CDCl3):  = 177.3, 156.3, 153.0, 149.3, 145.0,
142.8, 133.7, 128.0, 127.4, 126.0, 125.3, 123.8, 123.2, 122.2, 119.9,
118.2, 118.0, 45.5, 21.7, 13.3.
chromen-4-one (6ck)
Yield: 68.2 mg (86%, reaction time = 4 h); white solid; mp 250–252 °C.
IR (CHCl3): 3061, 2921, 2854, 1635, 1613, 1476, 1454, 1390, 1265,
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H15BrNaO2: 389.0147;
1129, 817, 593 cm–1
.
found: 389.0143.
1H NMR (400 MHz, CDCl3):  = 7.95 (t, J = 7.5 Hz, 1 H), 7.64 (t, J = 7.7
Hz, 2 H), 7.42–7.33 (m, 4 H), 7.27–7.26 (m, 1 H), 7.22–7.16 (m, 3 H),
5.68 (s, 1 H), 2.36–2.31 (m, 6 H).
3-(3-Bromo-2-ethyl-1H-inden-1-yl)-6-methyl-4H-chromen-4-one
(6co)
Yield: 54.4 mg (83%, reaction time = 6 h); pale yellow oil.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

L
A. Kumari, R. A. Fernandes
Paper
Synthesis
IR (CHCl3): 2965, 2927, 2871, 1644, 1621, 1483, 1459, 1318, 1160,
1045, 816, 727, 542 cm–1
1H NMR (400 MHz, CDCl3):  = 8.09 (s, 1 H), 7.48 (d, J = 7.7 Hz, 1 H),
7.38–7.30 (m, 5 H), 7.16 (t, J = 7.2 Hz, 1 H), 5.18 (s, 1 H), 2.71 (sextet,
J = 7.3 Hz, 1 H), 2.48 (s, 3 H), 2.21 (sextet, J = 6.8 Hz, 1 H), 1.13 (t, J =
7.5 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 177.1, 156.3, 153.4, 144.6, 144.3,
142.5, 133.9, 127.7, 126.7, 126.1, 125.5, 123.7, 123.3, 121.7, 121.3,
120.5, 118.2, 46.1, 31.7, 30.1.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H14Br2NaO2: 468.9233;
found: 468.9238.
.
13C{1H} NMR (100 MHz, CDCl3):  = 177.4, 154.7, 152.9, 149.5, 145.1,
142.8, 135.3, 135.0, 127.4, 126.0, 125.3, 123.5, 123.2, 121.9, 119.9,
117.9, 117.87, 45.5, 21.7, 21.0, 13.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H17BrNaO2: 403.0304;
found: 403.0305.
8-(2-Aryl-3-halo-1H-inden-1-yl)-2H-chromen-2-ones 8a–8f; Gen-
eral Procedure
Compounds 8a–8f were prepared by following a similar procedure as
described for compounds 6aa–6ah, using BBr3 or BCl3 (2.5 equiv) in-
stead of BF3·OEt2 and 0.172 mmol each of 7 and 4.
8-(3-Chloro-2-phenyl-1H-inden-1-yl)-2H-chromen-2-one (8a)
Yield: 60.5 mg (95%, reaction time = 4 h); white solid; mp 126–130 °C.
IR (CHCl3): 2923, 2850, 1735, 1602, 1490, 1400, 1267, 1076, 918, 868,
6-Bromo-3-(3-bromo-2-pentyl-1H-inden-1-yl)-4H-chromen-4-
one (6cp)
Yield: 67.2 mg (80%, reaction time = 5.5 h); pale yellow oil.
665, 534 cm–1
.
IR (CHCl3): 2959, 2928, 2856, 1647, 1622, 1605, 1461, 1435, 1335,
1149, 933, 818, 725, 600 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.72–7.70 (m, 3 H), 7.56 (d, J = 7.5 Hz, 1
H), 7.39 (t, J = 7.5 Hz, 1 H), 7.32–7.29 (m, 2 H), 7.27–7.25 (m, 2 H),
7.22–7.19 (m, 2 H), 6.96 (t, J = 7.0 Hz, 1 H), 6.84 (s, 1 H), 6.50 (d, J = 8.9
Hz, 1 H), 6.04 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 160.5, 152.1, 144.0, 141.9, 141.5,
133.0, 130.4, 129.1, 128.5, 128.4, 127.8, 127.6, 127.3, 127.0, 126.8,
124.6, 123.6, 119.7, 119.1, 116.5, 47.8.
1H NMR (500 MHz, CDCl3):  = 8.44 (s, 1 H), 7.75 (dd, J = 8.9, 2.5 Hz, 1
H), 7.39–7.29 (m, 5 H), 7.17 (dt, J = 7.2, 1.2 Hz, 1 H), 5.12 (s, 1 H), 2.70–
2.64 (m, 1 H), 2.16 (septet, J = 5.2 Hz, 1 H), 1.58–1.48 (m, 2 H), 1.34–
1.27 (m, 4 H), 0.85 (t, J = 6.7 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 176.0, 155.1, 153.1, 147.8, 144.8,
142.7, 136.7, 128.7, 127.5, 126.1, 125.1, 123.2, 122.6, 120.13, 120.0,
119.0, 118.8, 45.7, 31.5, 28.4, 28.2, 22.4, 13.9.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H15ClNaO2: 393.0653;
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H21Br2O2: 488.9883; found:
found: 393.0647.
488.9883.
8-(3-Chloro-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-2H-chromen-2-
one (8b)
3-(3-Bromo-2-butyl-1H-inden-1-yl)-6-fluoro-4H-chromen-4-one
(6cq)
Yield: 63.8 mg (93%, reaction time = 4.5 h); white solid; mp 139–
142 °C.
Yield: 59.7 mg (84%, reaction time = 6 h); pale yellow oil.
IR (CHCl3): 2854, 1734, 1602, 1490, 1400, 1266, 1076, 914, 699, 578,
IR (CHCl3): 2959, 2928, 2856, 1647, 1622, 1606, 1461, 1435, 1335,
538 cm–1
.
1149, 933, 725, 600 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.69 (d, J = 8.8 Hz, 1 H), 7.62 (d, J = 7.8
Hz, 2 H), 7.43 (d, J = 7.7 Hz, 1 H), 7.24 (d, J = 7.5 Hz, 1 H), 7.18 (d, J = 7.7
Hz, 1 H), 7.11 (d, J = 8 Hz, 2 H), 7.06 (s, 1 H), 6.95 (t, J = 6.8 Hz, 1 H),
6.86 (s, 1 H), 6.50 (d, J = 8.7 Hz, 1 H), 5.99 (s, 1 H), 2.32 (s, 3 H), 2.27 (s,
3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 160.5, 152.0, 145.2, 143.9, 140.4,
139.4, 137.5, 136.8, 130.4, 130.2, 129.0, 128.3, 128.27, 128.25, 127.7,
126.7, 124.6, 124.3, 119.2, 119.1, 116.3, 47.3, 21.4, 21.1.
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 6.7 Hz, 1 H), 7.44–7.42 (m, 1
H), 7.41–7.39 (m, 1 H), 7.37–7.29 (m, 4 H), 7.17 (dt, J = 7.3, 1.4 Hz, 1
H), 5.12 (s, 1 H), 2.73–2.65 (m, 1 H), 2.16 (septet, J = 5.2 Hz, 1 H), 1.54–
1.45 (m, 2 H), 1.39–1.30 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H).
1
13C{1H} NMR (125 MHz, CDCl3):  = 176.6, 159.7 (d, JC-F = 248.1 Hz),
153.1, 152.6, 147.8, 145.0, 142.7, 127.5, 126.1, 124.9 (d, 3JC-F = 7.4 Hz),
2
3
123.2, 122.0 (d, JC-F = 25.8 Hz), 121.7, 120.3 (d, JC-F = 8.0 Hz), 120.0,
118.9, 110.8 (d, 2JC-F = 23.7 Hz), 45.7, 30.9, 27.9, 22.5, 13.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H20ClO2: 399.1146; found:
399.1138.
19F NMR (470 MHz, CDCl3):  = –114.7.
HRMS (ESI-TOF): m/z [M + K]+ calcd for C22H18BrFKO2: 451.0106;
found: 451.0106.
8-(3-Bromo-2-phenyl-1H-inden-1-yl)-2H-chromen-2-one (8c)
Yield: 64.3 mg (90%, reaction time = 10 h); white solid; mp 110–
112 °C.
3-(3-Bromo-2-(2-bromoethyl)-1H-inden-1-yl)-4H-chromen-4-one
(6cr)
IR (CHCl3): 3067, 1734, 1602, 1574, 1488, 1402, 1175, 918, 621, 578
Yield: 61.3 mg (80%, reaction time = 5.5 h); white semisolid.
cm–1
.
IR (CHCl3): 3077, 2925, 2857, 1639, 1610, 1479, 1463, 1317, 909, 824,
1H NMR (500 MHz, CDCl3):  = 7.70–7.69 (m, 3 H), 7.55 (d, J = 7.6 Hz, 1
H), 7.40 (t, J = 7.0 Hz, 1 H), 7.32–7.29 (m, 2 H), 7.25–7.19 (m, 4 H), 6.95
(t, J = 6.8 Hz, 1 H), 6.82 (s, 1 H), 6.47 (d, J = 10.4 Hz, 1 H), 6.01 (s, 1 H).
13C{1H} NMR (125 MHz, CDCl3):  = 160.4, 152.1, 145.3, 143.9, 143.1,
133.7, 129.3, 128.7, 128.2, 127.9, 127.7, 127.0, 126.9, 126.8, 124.6,
123.5, 120.9, 119.1, 118.9, 117.0, 116.4, 49.0.
668 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.30 (d, J = 7.9 Hz, 1 H), 7.72–7.67 (m, 1
H), 7.48–7.43 (m, 3 H), 7.40–7.36 (m, 2 H), 7.31 (d, J = 7.2 Hz, 1 H),
7.23 (dt, J = 7.4, 0.9 Hz, 1 H), 5.17 (s, 1 H), 3.65–3.55 (m, 2 H), 3.25
(quint, J = 6.7 Hz, 1 H), 2.76 (septet, J = 7.3 Hz, 1 H).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H15BrNaO2: 437.0148;
found: 437.0140.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

M
A. Kumari, R. A. Fernandes
Paper
Synthesis
8-(3-Bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-2H-chromen-2-
IR (CHCl3): 2929, 2869, 1670, 1391, 1173, 1068, 910, 543 cm–1
.
one (8d)
1H NMR (400 MHz, CDCl3):  = 6.92 (t, J = 3.8 Hz, 1 H), 4.21 (s, 2 H),
2.59 (s, 1 H), 2.44–2.36 (m, 4 H), 1.99 (quint, J = 6.6 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 200.6, 146.9, 138.2, 61.8, 38.1,
Yield: 67.1 mg (88%, reaction time = 11 h); white solid; mp 145–
148 °C.
IR (CHCl3): 2922, 1735, 1602, 1491, 1258, 1075, 733, 618 cm–1
.
25.6, 22.6.
1H NMR (500 MHz, CDCl3):  = 7.68 (d, J = 6.7 Hz, 1 H), 7.60 (d, J = 8 Hz,
2 H), 7.41 (d, J = 7.7 Hz, 1 H), 7.24 (d, J = 7.5 Hz, 1 H), 7.19 (d, J = 7.7 Hz,
1 H), 7.10 (d, J = 7.9 Hz, 2 H), 7.03 (s, 1 H), 6.96 (t, J = 7.0 Hz, 1 H), 6.84
(s, 1 H), 6.49 (d, J = 8.8 Hz, 1 H), 5.96 (s, 1 H), 2.32 (s, 3 H), 2.27 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 160.5, 152.0, 144.2, 143.9, 143.2,
140.6, 137.6, 136.8, 130.9, 130.5, 129.0, 128.4, 128.3, 127.5, 126.7,
124.6, 124.2, 120.5, 119.0, 118.2, 116.3, 48.7, 21.4, 21.2.
6-Oxocyclohex-1-ene-1-carbaldehyde (10e)17
To a stirred solution of 2-(hydroxymethyl)cyclohex-2-en-1-one (15;
50 mg, 0.396 mmol, 1.0 equiv) in EtOAc (3 mL) was added IBX (166
mg, 0.594 mmol, 1.5 equiv) under N2 atmosphere. The resulting sus-
pension was refluxed for 5 h (TLC monitoring). The reaction mixture
was cooled to room temperature and filtered through a sintered glass
funnel. The filter cake was washed with EtOAc (3 × 2 mL). The com-
bined filtrate was concentrated and the residue was purified by silica
gel column chromatography (petroleum ether/EtOAc, 7:3) to afford
10e (39.3 mg, 80%) as a green oil.
IR (CHCl3): 2924, 2854, 1714, 1460, 1267, 1068, 822, 669 cm–1
1H NMR (400 MHz, CDCl3):  = 10.07 (s, 1 H), 7.81 (t, J = 4.1 Hz, 1 H),
2.63–2.58 (m, 2 H), 2.55–2.51 (m, 2 H), 2.07 (quint, J = 7.1 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3):  = 197.9, 189.2, 157.8, 135.0, 38.0,
26.4, 21.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H20BrO2: 443.0641; found:
443.0634.
8-(3-Chloro-2-phenyl-1H-inden-1-yl)-6-methyl-2H-chromen-2-
one (8e)
.
Yield: 53.1 mg (79%, reaction time = 5 h); yellow solid; mp 105–
108 °C.
IR (CHCl3): 2924, 1732, 1625, 1606, 1583, 1429, 1295, 1110, 878, 655,
593 cm–1
.
LRMS (ESI-TOF): m/z [M + K]+ calcd for C7H8KO2: 163.0155; found:
163.0735.
1H NMR (500 MHz, CDCl3):  = 7.96 (d, J = 7.6 Hz, 2 H), 7.87 (d, J = 8.8
Hz, 1 H), 7.81 (d, J = 7.6 Hz, 1 H), 7.63 (t, J = 7.3 Hz, 1 H), 7.57–7.54 (m,
2 H), 7.50–7.44 (m, 4 H), 6.86 (s, 1 H), 6.70 (d, J = 8.1 Hz, 1 H), 6.26 (s,
1 H), 2.34 (s, 3 H).
2,2-Difluoro-6-methyl-4-phenyl-2H-1,3,2-dioxaborinin-1-ium-2-
uide (12)
13C{1H} NMR (125 MHz, CDCl3):  = 160.7, 150.2, 145.2, 143.9, 141.8,
141.6, 134.3, 133.1, 131.0, 128.9, 128.5, 128.3, 127.7, 127.5, 126.9,
126.8, 123.6, 119.6, 118.9, 116.3, 47.7, 20.5.
To a mixture of benzoylacetone (11; 50 mg, 0.308 mmol, 1.0 equiv)
and alkyne 4a (55 mg, 0.308 mmol, 1.0 equiv) in CH2Cl2 (2 mL) was
added BF3·OEt2 (0.215 mL, 0.77 mmol, 2.5 equiv) at room tempera-
ture. The mixture was stirred for 7 h at which time TLC indicated con-
sumption of 11. The reaction was then quenched with a few drops of
sat. aq Na2S2O3 solution. The solvent was removed through vacuum
and the residue was purified by silica gel column chromatography
(petroleum ether/EtOAc, 4:1) to afford 12 (38.4 mg, 60%) as a cream-
coloured solid; mp 120–123 °C.11
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H17ClNaO2: 407.0809;
found: 407.0802.
8-(3-Bromo-6-methyl-2-(p-tolyl)-1H-inden-1-yl)-6-methyl-2H-
chromen-2-one (8f)
Yield: 69.1 mg (88%, reaction time = 6 h); yellow solid; mp 78–80 °C.
IR (CHCl3): 1542, 1440, 1357, 1116, 1069, 707, 680, 575 cm–1
1H NMR (400 MHz, CDCl3):  = 8.05 (d, J = 7.6 Hz, 2 H), 7.68 (t, J = 7.4
Hz, 1 H), 7.52 (t, J = 7.7 Hz, 2 H), 6.60 (s, 1 H), 2.41 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 192.6, 182.8, 135.4, 131.1, 129.1,
129.0, 97.5, 24.7.
19F NMR (470 MHz, CDCl3):  = –138.6.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C10H9BF2NaO2: 233.0558;
.
IR (CHCl3): 2922, 1732, 1623, 1606, 1459, 1395, 1286, 1156, 1106,
914, 790, 666, 614 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.59 (d, J = 8.1 Hz, 2 H), 7.40 (d, J = 7.7
Hz, 1 H), 7.30–7.25 (m, 1 H), 7.18 (d, J = 7.7 Hz, 1 H), 7.09 (d, J = 7.9 Hz,
2 H), 7.01 (d, J = 5.5 Hz, 2 H), 6.60 (s, 1 H), 6.48–6.42 (m, 1 H), 5.91 (s,
1 H), 2.32 (s, 3 H), 2.27 (s, 3 H), 2.11 (s, 3 H).
13C{1H} NMR (125 MHz, CDCl3):  = 160.9, 150.3, 144.4, 143.9, 140.7,
137.6, 136.8, 134.3, 131.2, 131.1, 129.0, 128.5, 128.3, 127.1, 126.9,
124.3, 120.5, 118.9, 118.2, 116.4, 48.7, 21.5, 21.2, 20.6.
found: 233.0554.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C27H21BrNaO2: 479.0617;
found: 479.0609.
Funding Information
2-(Hydroxymethyl)cyclohex-2-en-1-one (15)16
This work was supported by the Science and Engineering Research
To a stirred mixture of 36% aq HCHO (0.45 mL, 5.20 mmol, 5.0 equiv)
and cyclohex-2-enone (100 mg, 1.040 mmol, 1.0 equiv) was added
DMAP (38 mg, 0.312 mmol, 0.3 equiv). The resulting mixture was
stirred at room temperature. After consumption of the starting mate-
rial (2 d), the reaction was quenched with 1.5 N HCl until pH 4. The
mixture was extracted with CH2Cl2 (3 × 3 mL) and the combined or-
ganic layers were washed successively with sat. aq NaHCO3 solution
and brine. Solvents were removed through vacuum and the residue
was purified by silica gel column chromatography (petroleum
ether/EtOAc, 3:2) to afford 15 (92 mg, 70%) as a pale yellow oil.
Board (SERB) New Delhi, Grant No. EMR/2017/000499.
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Acknowledgment
A.K. thanks the Indian Institute of Technology Bombay for a research
fellowship.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N

N
A. Kumari, R. A. Fernandes
Paper
Synthesis
Supporting Information
(i) Carlsen, P. N.; Mann, T. J.; Hoveyda, A. H.; Frontier, A. J.
Angew. Chem. Int. Ed. 2014, 53, 9334. (j) Grant, T. N.; Rieder, C. J.;
West, F. G. Chem. Commun. 2009, 5676. (k) Malona, J. A.; Cariou,
K.; Frontier, A. J. J. Am. Chem. Soc. 2009, 131, 7560. (l) Churruca,
F.; Fousteris, M.; Ishikawa, Y.; von Wantoch Rekowski, M.;
Hounsou, C.; Surrey, T.; Giannis, A. Org. Lett. 2010, 12, 2096.
(m) Vaidya, T.; Eisenberg, R.; Frontier, A. J. ChemCatChem 2011,
3, 1531. (n) Magnus, P.; Freund, W. A.; Moorhead, E. J.; Rainey,
T. J. Am. Chem. Soc. 2012, 134, 6140. (o) Zhou, Z.; Tius, M. A.
Angew. Chem. Int. Ed. 2015, 54, 6037.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690881.
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–N