Palladium(II)-Catalyzed Direct Access to Indeno[1,2-c]isochromen-5(11H)-Ones via Intramolecular Oxypalladation-Initiated Cascade Process

Article abstract of DOI:10.1002/adsc.202000456

A palladium(II)-catalyzed cascade approach was established for the synthesis of indeno[1,2-c]isochromen-5(11H)-ones starting from 2-alkynyl tert-butyl benzoates bearing a pendant α,β-unsaturated carbonyl moiety in high yields (up to 99%) under mild condit

Full text of DOI:10.1002/adsc.202000456

Title: Palladium(II)-Catalyzed Direct Access to Indeno[1,2-
c]isochromen-5(11H)-ones via Intramolecular Oxypalladation-
Initiated Cascade Process
Authors: Muthu Karuppasamy, B.S. Vachan, Tanvi Jandial, Sesuraj
Babiola Annes, Nattamai Bhuvanesh, C. Uma Maheswari,
and Vellaisamy Sridharan
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000456
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Palladium(II)-Catalyzed Direct Access to Indeno[1,2-
c]isochromen-5(11H)-ones via Intramolecular Oxypalladation-
Initiated Cascade Process
Muthu Karuppasamy,a B. S. Vachan,a Tanvi Jandial,b Sesuraj Babiola Annes,a Nattamai
Bhuvanesh,c C. Uma Maheswari,a and Vellaisamy Sridharan*a,b
a
Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur-613401,
Tamil Nadu, India.
b
Department of Chemistry and Chemical Sciences, Central University of Jammu, Rahya-Suchani (Bagla), District-
Samba, Jammu-181143, J&K, India. Email: vesridharan@gmail.com or sridharan.che@cujammu.ac.in.
Department of Chemistry, Texas A & M University, College Station, Texas 77843, United States.
c
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. A palladium(II)-catalyzed cascade approach was of the cascade process was visualized comprising sequential
established for the synthesis of indeno[1,2-c]isochromen- intramolecular oxypalladation (6-endo-dig), intramolecular
5(11H)-ones starting from 2-alkynyl tert-butyl benzoates olefin insertion, and protonation steps.
bearing a pendant α,β-unsaturated carbonyl moiety in high
yields (up to 99%) under mild conditions. This strategy
offered high atom and step economy by delivering isobutene
as the only side product, and by generating two new bonds
and two rings in a single synthetic operation. The mechanism
Keywords: cascade reaction; oxypalladation;
nucleopalladation; olefin insertion; indeno[1,2-
c]isochromen-5(11H)-one.
hydroxyphthalide followed by intramolecular
cyclization (eq. 3).[8]
Introduction
In the recent years we have been working on the
development of nucleopalladation-initiated cascade
reactions for the synthesis of diverse complex
compounds in a single synthetic operation and
exploring their mechanistic aspects, which includes
Among the diverse oxygen heterocycles, isocoumarin
is one of the most significant structural frameworks
that is found in a large number of natural products
and synthetic compounds with potential biological
significance.[1,2] Consequently, numerous methods
have been developed for the synthesis of
isocoumarins that include the intramolecular
cyclization (6-endo-dig) of 2-alkynylbenzoates[3] and
2-alkynylbenzamides,[4] annulation of benzoic acids,
benzaldehydes or benzyl alcohols with alkynes,[5]
reaction of diazo compounds with benzoic acids,
benzaldehydes or benzamides,[6] and many others.[7]
The indene-fused isocoumarins i.e. indeno[1,2-
c]isochromen-5(11H)-ones are potential precursors
for the synthesis of topoisomerase I inhibitors 5H-
indeno[1,2-c]isoquinolin-5-ones,[8] nonetheless, only
very few strategies are available in the literature to
access these valuable compounds (Scheme 1). The
developed approaches include polyphosphoric acid-
mediated cyclization of -(o-carboxypheny1)-6-
phenylpropionic acid (eq. 1),[9] rhodium-catalyzed
syn-oxypalladation,[12]
syn-chloropalladation,[13]
internal
nucleophile-assisted
hydration,[14]
carboxypalladation,[15]
and
the
subsequent
intramolecular olefin insertion cascades. Owing to the
significance of indeno[1,2-c]isochromen-5(11H)-ones
2, and the scarcity of efficient procedures available in
the literature, we envisioned to develop a simple
palladium(II)-catalyzed
intramolecular
oxypalladation-olefin insertion cascade from readily
available starting materials 1, via the intermediacy of
the -vinylpalladium intermediate A (Scheme 1, eq.
4). It is relevant to quote here the related palladium-
catalyzed 6-endo-dig cyclization followed by
intermolecular alkenylation with electron-deficient
alkenes,[16a] oxidative olefination with acrylates and
styrenes,[16b] oxidative Heck reaction with alkenyl
alcohols,[16c] intramolecular 1,2-addition of C–PdII
cyclic carbonylation of 2-phenylethynylbenzoates (eq. bond to the carbonyl group,[16d] and reaction with
2),[10] two-step, one-pot condensation between
phthalide and 2-carboxybenzaldehydes (eq. 3),[11] and
base-mediated condensation of phthalide with 3-
methyl vinyl ketone.[16e]
1
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
Takahashi: Rh-Catalyzed cyclic carbonylation of
Wawzonek: PPA-Mediated cyclization of
a-(o-carboxypheny1)-6-phenylpropionic acid (1975)9
2-phenylethynylbenzoates (1997)10
O
O
Rh6(CO)16, Et3N
CO + H2O
O
O
CO2R
CO2H CO2H
(1)
PPA, 160 oC
(59%)
(2)
PPh3, 180 oC
(18-75%)
R = Me, Et, i-Pr, Ph
Cushman: Two-step, one-pot condensation between phthalide and 2-carboxybenzaldehydes or 3-hydroxyphthalide
(200611 and ref. 8)
O
O
O
O
HO2C
OHC
1. NaOMe
(3)
O
R
+
O
R
(or)
2. HCl
TsOH
R
O
HO
This work: Intramolecular oxypalladation-intramolecular olefin insertion cascade
O
O
R3
O
R3
t-BuO
O
O
PdII
(4)
R3
6-endo-dig
PdII
R1
R1
R1
O
R2
R2
R2
O
1
2
O
A
Scheme 1. Established methods to access indeno[1,2-c]isochromen-5(11H)-ones and the envisioned Pd(II)-catalyzed
cascade strategy
Subsequently, DMSO was selected as the solvent
for further screening of the palladium catalysts.
Results and Discussion
Switching the catalyst to PdCl2 allowed the reaction
to proceed at ambient temperature and delivered the
product 2a in 76% together with 20% of the
unreacted starting material 1a in 48 h (entry 13).
Remarkably, slight increase of the reaction
temperature to 40 oC allowed the complete
conversion of the reaction and furnished the product
in an excellent yield of 94% in 10 h (entry 14).
In order to test the viability of the proposed cascade
process, 2-alkynyl tert-butyl benzoate tethered with
α,β-unsaturated carbonyl moiety 1a, derived from
tert-butyl 2-ethynylbenzoate and 2-iodochalcone via
Sonogashira reaction, was elected as the model
substrate. At the outset, alkyne 1a was treated with 10
mol% of Pd(OAc)2 in various common organic
solvents including MeCN, THF, dioxane, DCM, DCE,
toluene, and DMF at ambient temperature as well as
at elevated temperatures. The results were
disappointing and no product formation was observed
in all the cases even after prolonging the reaction
time to 24 h (Table 1, entries 1-7). However,
encouragingly, the anticipated cascade process
o
Further increase of the reaction temperature to 60 C
enabled the reaction to afford the expected product in
a maximum yield of 96% in 6 h (entry 15). Among
the other tested palladium catalysts, PdCl2(MeCN)2
and Pd(OTf)2 furnished the product in comparable
yields to that of PdCl2 albeit in longer reaction times
(16-24 h, entries 16 and 17). In the case of
PdCl2(PPh3)2, 88% of the product was observed at 60
oC after prolonged reaction time (30 h, entry 18).
Finally, the reaction was tested using 5 mol% of
o
proceeded in DME at 80 C to deliver the product
indeno[1,2-c]isochromen-5(11H)-one 2a in a good
yield of 75% (entry 8). The polar aprotic solvent
DMSO was also effective to furnish the product 2a in
o
o
PdCl2 at 60 C, where the rate of the reaction was
moderate yield (57%) at 60 C. The reaction was
decreased significantly, and only 68% of the product
was isolated after 24 h (entry 19). The use of 2,2’-
bipyridyl ligand did not affect the outcome of the
reaction considerably (entry 20). Consequently, the
reaction condition given in entry 15 was selected to
further investigate the scope and limitations of the
cascade process (10 mol % of PdCl2, DMSO, 60 °C).
found to be sluggish and the reaction was not
completed even after 48 h, and the starting material
1a was recovered in 32% (entry 9). In order to
achieve complete conversion and to improve the yield,
the effect of reaction temperature in DMSO was
studied (entries 10-12). Although a similar result was
o
observed at 80 C (62%, 48 h), the yield was
o
significantly improved at 100 C to furnish the
desired product in 84% yield in 10 h. The highest
yield (87%), to this point, was isolated with
Pd(OAc)2 as the catalyst in DMSO at 120 oC in 6 h.
2
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
Table 1. Optimization of reaction conditions[a]
Br (2f, 88%) on the R2 aryl group, and near
quantitative yield was obtained in the case of 2b.
Furthermore, introduction of a methoxy substituent at
R1 position did not affect the outcome of the reaction
significantly, and a range of 72-97% yield was
observed for 2g-2j.
O
t-BuO
O
O
Catalyst
In a further set of experiments, indeno[1,2-
c]isochromen-5(11H)-ones 2k-2m bearing heteroaryl
substituents such as 2-furyl and 2-thienyl groups were
synthesized in 85-92% yields, and the 2-pyridyl
derivative 2n was also obtained from the
corresponding alkyne in 72% yield under the standard
reaction conditions. A near quantitative yield was
obtained for the alkyne bearing a 2-naphthyl
substituent (2o, 99%). In addition, three examples of
indeno[1,2-c]isochromen-5(11H)-ones 2p-2r bearing
a methyl substituent on the isocoumarin ring was also
synthesized in high yields (79-98%). Finally, alkyl
groups including methyl (2s, 91%) and cyclopropyl
(2t, 82%) substituents were also introduced at R2
position to access the corresponding products in high
yields. However, the reactivity of the α-tetralone
substituted analog was not appreciable, and the
reaction delivered the product 2u in 51% yield as a
single diasteroisomer after a prolonged reaction time
of 12 h. The stereochemistry of the compound 2u
could not be established by NMR analysis since,
surprisingly, the benzylic hydrogen of the indene ring
and the α-hydrogen of the tetralone moiety failed to
couple with each other. The cascade reaction was also
tested using the corresponding methyl ester 4a (see
SI) under the optimized reaction conditions, and the
desired product 2a was obtained in 87% yield. With
regard to the product yield, the tert-butyl ester is
superior to the corresponding methyl ester
presumably due to the more facile removal of the tert-
butyl cation and subsequent release of isobutene in
comparison to the elimination of a methyl cation after
the initial oxypalladation (vide infra). The structures
of the synthesized compounds were established
combining spectral studies and single crystal x-ray
analysis of a representative compound 2a (Scheme
2).[17]
Solvent
O
Ph
Ph
O
2a
1a
Catalyst
Entry
Solvent Temp Time 2a
[oC]
[h]
[%][b]
[10 mol%]
[c]
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
MeCN
THF
Dioxane 100
DCM
DCE
Toluene 120
80
60
24
24
24
48
24
24
24
24
48
48
10
6
48
10
6
24
16
30
24
10
-
-
-
-
-
-
-
[c]
[c]
[c]
40
80
[c]
[c]
[c]
DMF
DME
120
80
60
75
9
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
57[d]
62[e]
84
10
11
12
13
14
15
16
17
18
19
20
80
100
120
25
40
60
60
60
60
60
87
76[f]
94
PdCl2
PdCl2
96[g]
95
PdCl2(MeCN)2 DMSO
Pd(OTf)2
PdCl2(PPh3)2
PdCl2
DMSO
DMSO
DMSO
DMSO
94
88
68[h]
92[i]
PdCl2
60
[a]Unless otherwise noted, all reactions were carried out
with 1a (0.5 mmol) and catalyst (10 mol%) in 4 mL
solvent. [b]Isolated yield. [c]No reaction (these reactions
were also tested at room temperature). [d]32% of 1a was
recovered. [e]28% of 1a was recovered. [f]20% of 1a was
recovered. [g]Optimized reaction condition. [h]5 mol % of
catalyst was used. [i]10 mol % of 2,2’-bipyridyl was used as
ligand.
Having established the optimal reaction conditions,
the generality and scope of the cascade reaction were
examined involving various 2-alkynyl tert-butyl
benzoates 1 having a pendant olefin coupling partner.
Delightfully, all the tested starting compounds
proceeded this intramolecular oxypalladation-olefin
insertion cascade smoothly to deliver the
corresponding indeno[1,2-c]isochromen-5(11H)-ones
2 in high yields (Scheme 2). The alkynes 1 have three
diversity points including both the aryl rings and the
α,β-unsaturated carbonyl moiety (R2). A variety of
aryl, naphthyl, heteroaryl, methyl, cyclopropyl, and
α-tetralone moieties were introduced in the R2
diversity point. For instance, the reaction well
tolerated both electron donating and -withdrawing
substituents including p-Me (2b, 99%), p-OMe (2c,
94%), 3,4-(OMe)2 (2d, 92%), p-Cl (2e, 81%), and p-
Next, 2-alkynyl tert-butyl benzoate bearing an α,β-
unsaturated ester 1v was synthesized, and subjected
to the standard reaction conditions. Interestingly,
compound 3v was obtained in 58% yield via
intramolecular oxypalladation-olefin insertion-β-
hydride elimination cascade (Scheme 3). The final β-
hydride elimination step could not be avoided by
using two or four equivalents of LiBr,[18] and in both
the reactions, only compound 3v was obtained in
49% and 53% yields respectively.
The plausible mechanism of the cascade process
was
visualized
involving
intramolecular
oxypalladation, intramolecular olefin insertion, and
protonation steps (Scheme 4). The catalytic cycle
starts with the coordination of the internal alkyne 1
with palladium catalyst to generate the reactive
species A. Subsequently, tert-butyl benzoate
3
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
O
R3
O
t-BuO
O
PdCl2 (10 mol%)
R3
DMSO, 60 oC, 6 h
(up to 99%)
R1
O
R1
R2
R2
2a-u
1
O
2a (CCDC: 1993673)
O
O
O
O
O
O
R1
MeO
O
O
O
R4
R5
R4
R5
X
R6
R6
2g: R4 = R5 = R6 = H (95%)
2h: R4 = H, R5 = R6 = OMe (72%)
2i: R4 = R5 = H, R6 = OMe (91%)
2j: R4 = R6 = Cl, R5 = H (97%)
2k: X = S, R1 = H (85%)
2l: X = O, R1 = H (86%)
2m: X = O, R1 = OMe (92%)
2a: R4 = R5 = R6 = H (96%, 87%[b]
2b: R4 = R5 = H, R6 = Me (99%)
2c: R4 = R5 = H, R6 = OMe (94%)
2d: R4 = H, R5 = R6 = OMe (92%)
2e: R4 = R5 = H, R6 = Cl (81%)
2f: R4 = R5 = H, R6 = Br (88%)
)
O
O
O
O
O
O
Me
R1
O
MeO
O
N
O
R4
R6
2p: R1 = R6 = H, R4 = Cl (98%)
2n (72%)
2o (99%)
2q: R1 = R6 = OMe, R4 = H (88%)
O
O
O
O
O
O
O
O
Me
O
H
O
H
O
O
Me
2s (91%)
2t (82%)
O
O
2u (12 h, 51%)
2r (79%)
[a] Reaction conditions: 1 (0.5 mmol), PdCl2 (10 mol%), DMSO (4 mL), 60 oC, 6 h. [b] Yield was obtained from the corresponding methyl ester 4a
Scheme 2. Scope and limitations of the synthesis of indeno[1,2-c]isochromen-5(11H)-ones[a]
O
undergoes intramolecular oxypalladation followed by
O
elimination of a molecule of 2-methylprop-1-ene and
O
a proton to afford σ-vinyl palladium intermediate C
through the intermediacy of species B.[16b,19] Next, the
t-BuO
O
highly reactive σ-vinyl palladium species
C
OMe
O
PdCl2 (10 mol%)
undergoes intramolecular olefin insertion with the
tethered α,β-unsaturated carbonyl moiety followed by
protonation of intermediate D furnishes indeno[1,2-
c]isochromen-5(11H)-ones 2. In the case of ester 1v,
β-hydride elimination of intermediate D takes place
to deliver compound 3v bearing an α,β-unsaturated
ester moiety. The regeneration of the active Pd(II)
species from Pd(0) obtained after β-hydride
elimination could have been effected under air
3v (58%)
+
DMSO
60 oC, 20 h
O
OMe
1v
O
O
OMe
2v (0%)
Scheme 3. Reactivity of 2-alkynyl tert-butyl benzoate
bearing a pendant α,β-unsaturated ester moiety
4
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
oxidation facilitated by DMSO.[20a,b] It has also been
shown in a recent report that DMSO itself was found
to oxidize Pd(0) to Pd(II) under the experimental
conditions.[20c]
1.0 equiv) in DMSO (4 mL) was added PdCl2 (0.05 mmol,
o
10 mol%), and stirring was continued at 60 C for 6 h.
After completion of the reaction, as indicated by TLC, the
reaction mixture was diluted with water and the aqueous
suspension was extracted with ethyl acetate EtOAc (2 x 15
mL), washed with water and brine. The organic layer was
dried over anhydrous Na2SO4 and concentrated under
reduced pressure. The crude product was purified by flash
column chromatography using petroleum ether and ethyl
acetate mixture as eluent (80:20, v/v) to obtain the desired
product 2 or 3. In the case of compound 1a, the reaction
was performed in 1 mmol scale.
Ot-Bu
R3
O
O
O
R3
R1
O
(±)
11-(2-Oxo-2-phenylethyl)indeno[1,2-c]isochromen-
o
R1
5(11H)-one (2a). Yellow solid; mp: 147-148 C; yield:
R2
R2
2
1
0.338 g, 96%; IR (neat): 3067.2, 2907.2, 1734.6, 1676.8,
1609.3, 1493.6, 1384.6, 1227.5, 1040.4 cm-1; H NMR
1
O
O
PdIICl2
(300 MHz, CDCl3): δ 3.16-3.23 (m, 1H), 3.74 (dd, J = 18.0,
2.7 Hz, 1H) 4.87 (dd, J = 9.6, 2.4 Hz, 1H), 7.30 (dd, J =
7.5, 1.2 Hz, 1H), 7.40 (t, J = 7.5 Hz, 1H), 7.44-7.53 (m,
5H), 7.57-7.62 (m, 1H), 7.68-7.77 (m, 2H), 7.96-8.00 (m,
2H), 8.41 (dd, J = 8.4, 1.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): δ 38.7, 41.2, 118.2, 119.2, 120.2, 122.1, 124.8,
127.3, 127.8, 128.1, 128.2, 128.8, 131.5, 133.7, 134.9,
135.1, 135.2, 136.6, 147.2, 153.6, 162.7; Anal Calcd for
C24H16O3: C, 81.80; H, 4.58. Found: C, 81.40; H, 4.61.
Protonation
HCl
Ot-Bu
R3
3v
b-Hydride
Elimination
O
O
PdIICl2
R3
R1
R2
R1
O
A
ClPdII
(±) 11-(2-Oxo-2-(p-tolyl)ethyl)indeno[1,2-c]isochromen-
O
R2
o
D
5(11H)-one (2b). Yellow solid; mp: 152-153 C; yield:
Intramolecular
Oxypalladation
0.181 g, 99%; IR (neat): 3058.3, 2921.4, 1731.3, 1668.2,
Cl–
R3
1
1610.3, 1510.7, 1420.3, 1248.3, 1140.4, 1014.1 cm-1; H
Olefin
Insertion
O
Ot-Bu
NMR (300 MHz, CDCl3): δ 2.41 (s, 3H), 3.13-3.22 (m,
1H), 3.70 (dd, J = 18.0, 2.7 Hz, 1H), 4.86 (dd, J = 9.6, 2.7
Hz, 1H), 7.25-7.30 (m, 3H), 7.39 (t, J = 7.5 Hz, 1H), 7.46-
7.52 (m, 3H), 7.68 (d, J = 7.5 Hz, 1H), 7.74 (td, J = 7.8,
1.2 Hz, 1H), 7.87 (d, J = 8.1 Hz, 2H), 8.41 (dd, J = 8.4, 1.2
Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 21.7, 38.8, 41.0,
118.3, 119.1, 120.2, 122.2, 124.8, 127.3, 127.8, 128.19,
128.3, 129.5, 131.5, 134.2, 134.9, 135.2, 144.6, 147.2,
153.5, 162.7, 197.9; Anal Calcd for C25H18O3: C, 81.95; H,
4.95. Found: C, 81.58; H, 5.08.
R3
O
O
PdIICl
R2
PdIICl
R2
R1
R1
O
C
B
Cl–
– Me2C=CH2,
O
HCl
Scheme 4. Proposed mechanism for the intramolecular
oxypalladation-initiated cascade
(±)
11-(2-(4-Methoxyphenyl)-2-oxoethyl)indeno[1,2-
c]isochromen-5(11H)-one (2c). Yellow solid; mp: 131-132
oC; yield: 0.185 g, 97%; IR (neat): 3049.4, 2928.4, 1731.4,
1668.3, 1611.4, 1516.3, 1421.3, 1240.7, 1145.4, 1010.4
cm-1; H NMR (300 MHz, CDCl3): δ 3.10-3.20 (m, 1H),
1
Conclusion
3.67 (dd, J = 18.0, 2.7 Hz, 1H), 3.87 (s, 3H), 4.86 (dd, J =
9.6, 2.7 Hz, 1H), 6.93 (d, J = 9.0 Hz, 2H), 7.26-7.30 (m,
1H), 7.39 (t, J = 7.5 Hz, 1H), 7.48-7.51 (m, 3H), 7.67-7.74
(m, 2H), 7.95 (d, J = 8.7 Hz, 2H), 8.40 (d, J = 7.5 Hz, 1H);
13C NMR (75 MHz, CDCl3): δ* 38.9, 40.7, 55.6, 113.9,
118.4, 119.1, 120.2, 122.2, 124.8, 127.3, 127.7, 128.1,
129.7, 130.5, 131.5, 134.9, 135.2, 147.3, 153.5, 162.7,
163.9, 196.8; Anal Calcd for C25H18O4: C, 78.52; H, 4.74.
Found: C, 78.14; H, 4.81. *One aromatic carbon is merged
with others.
In conclusion, we have developed a simple
palladium(II)-catalyzed cascade strategy for the
synthesis of indeno[1,2-c]isochromen-5(11H)-ones in
excellent yields (up to 99%) under mild conditions.
The 2-alkynyl tert-butyl benzoates tethered with α,β-
unsaturated carbonyl moiety, readily accessible from
tert-butyl 2-ethynylbenzoates and 2-iodochalcones
via Sonogashira reaction, allow access to the title
compounds by generating two new bonds and two
rings in a single synthetic operation. The reaction
addresses several important aspects of green
chemistry and ideal synthesis including atom
economy by allowing a molecule of isobutene as the
only side product, and step economy by generating
the tetracyclic scaffold in a one-pot. The mechanistic
rationale of the cascade reaction involves a sequential
intramolecular oxypalladation, intramolecular olefin
insertion, and protonation steps.
(±) 11-(2-(3,4-Dimethoxyphenyl)-2-oxoethyl)indeno[1,2-
c]isochromen-5(11H)-one (2d). Yellow solid; mp: 178-179
oC; yield: 0.190 g, 92%; IR (neat): 3067.2, 2927.4, 1738.5,
1667.2, 1605.5, 1516.7, 1422.2, 1258.3, 1145.5, 1016.3
cm-1; H NMR (300 MHz, CDCl3): δ 3.13-3.22 (m, 1H),
1
3.68 (dd, J = 18.0, 3.0 Hz, 1H), 3.94 (s, 3H), 3.96 (s, 3H),
4.87 (dd, J = 9.9, 2.7 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H),
7.30 (dd, J = 7.5, 0.9 Hz, 1H), 7.40 (t, J = 7.2 Hz, 1H),
7.47-7.62 (m, 5H), 7.67-7.77 (m, 2H), 8.41 (d, J = 7.8 Hz,
1H); 13C NMR (75 MHz, CDCl3): δ 39.0, 40.5, 56.0, 56.1,
110.0, 110.1, 118.3, 119.1, 120.2, 122.2, 123.0, 124.8,
127.3, 127.7, 128.1, 129.9, 131.5, 134.9, 135.2, 147.2,
149.1, 153.5, 153.7, 162.7, 196.8; Anal Calcd for
C26H20O5: C, 75.72; H, 4.89. Found: C, 75.33; H, 4.91.
(±)
11-(2-(4-Chlorophenyl)-2-oxoethyl)indeno[1,2-
c]isochromen-5(11H)-one (2e). Yellow solid; mp: 175-176
Experimental Section
oC; yield: 0.157 g, 81%; IR (neat): 3090.4, 2910.0, 1731.8,
1687.4, 1589.1, 1489.7, 1387.0, 1224.6, 1094.4 cm-1; H
1
General Procedure for the Synthesis of Compounds 2a-
u and 3. To a stirred solution of compound 1 (0.5 mmol,
NMR (300 MHz, CDCl3): δ 3.11-3.21 (m, 1H), 3.70 (dd,
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000456
Advanced Synthesis & Catalysis
18.3, 2.7 Hz, 1H), 4.85 (dd, J = 9.6, 2.4 Hz, 1H), 7.30 (d, J
= 7.5 Hz, 1H), 7.38-7.52 (m, 6H), 7.69 (d, J = 7.5 Hz, 1H),
7.75 (t, J = 7.5 Hz, 1H), 7.91 (d, J = 8.7 Hz, 2H), 8.42 (d, J
= 7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 38.7, 41.2,
118.0, 119.2, 120.2, 122.0, 124.7, 127.4, 127.9, 128.2,
129.1, 129.6, 131.6, 134.9, 135.0, 135.1, 135.2, 140.2,
147.0, 153.6, 162.6, 197.2; Anal Calcd for C24H15ClO3: C,
74.52; H, 3.91. Found: C, 74.65; H, 4.02.
(300 MHz, CDCl3): δ 3.14-3.23 (m, 1H), 3.79 (dd, J = 18.0,
3.0 Hz, 1H), 3.86 (s, 3H), 4.69 (dd, J = 9.3, 2.7 Hz, 1H),
6.93 (dd, J = 8.4, 2.1 Hz, 1H ), 7.10 (d, J = 2.1 Hz, 1H),
7.25-7.29 (m, 1H), 7.38-7.42 (m, 2H), 7.46 (d, J = 7.5 Hz,
2H), 7.56 (d, J = 8.4 Hz, 1H), 7.75 (t, J = 7.5 Hz, 1H), 8.36
(dd, J = 7.2, 1.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
39.0, 45.2, 55.6, 111.1, 113.6, 115.7, 119.5, 120.1, 121.6,
126.8, 127.4, 127.8, 130.3, 130.6, 131.5, 132.3, 135.2,
135.3, 136.7, 138.0, 148.5, 153.8, 160.4, 162.7, 199.8;
Anal Calcd for C25H16Cl2O4: C, 66.54; H, 3.57. Found: C,
66.21; H, 3.76.
(±)
11-(2-(4-Bromophenyl)-2-oxoethyl)indeno[1,2-
c]isochromen-5(11H)-one (2f). Off-white solid; mp: 190-
o
191 C; yield: 0.190 g, 88%; IR (neat): 3090.1, 2910.0,
1728.4, 1684.4, 1584.1, 1486.2, 1381.3, 1220.8, 1089.3
(±)
11-(2-Oxo-2-(thiophen-2-yl)ethyl)indeno[1,2-
cm-1; H NMR (300 MHz, CDCl3): δ 3.11-3.20 (m, 1H),
c]isochromen-5(11H)-one (2k). Yellow solid; mp: 168-169
1
3.70 (dd, J = 18.0, 2.7 Hz, 1H), 4.84 (dd, J = 9.9, 2.7 Hz,
1H), 7.27- 7.31 (m, 1H), 7.41 (t, J = 7.2 Hz, 1H), 7.46-7.52
(m, 3H), 7.61 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 7.5 Hz, 1H),
7.75 (td, J = 7.8, 1.2 Hz, 1H), 7.83 (d, J = 8.7 Hz, 2H),
8.41 (d, J = 7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
38.7, 41.1, 118.0, 119.2, 120.2, 122.0, 124.7, 127.4, 127.9,
128.2, 128.9, 129.7, 131.6, 132.1, 134.9, 135.1, 135.2,
135.3, 146.9, 153.6, 162.6, 197.4; Anal Calcd for
C24H15BrO3: C, 66.84; H, 3.51. Found: C, 66.64; H, 3.56.
oC; yield: 0.152 g, 85%; IR (neat): 2920.6, 1738.5, 1656.6,
1609.3, 1414.5, 1380.8, 1231.3, 1115.6, 1013.4 cm-1; H
1
NMR (300 MHz, CDCl3): δ 3.06-3.15 (m, 1H), 3.68 (dd, J
= 17.4, 3.0 Hz, 1H), 4.82 (dd, J = 9.9, 3.0 Hz, 1H), 7.11 (t,
J = 4.5 Hz, 1H), 7.31 (d, J = 7.5 Hz, 1H), 7.41 (t, J = 7.2
Hz, 1H), 7.47-7.54 (m, 3H), 7.62 (d, J = 3.9 Hz, 1H), 7.67-
7.71 (m, 2H), 7.76 (td, J = 8.1, 0.9 Hz, 1H), 8.40 (d, J =
7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 38.9, 41.6,
118.0, 119.2, 120.2, 122.1, 124.8, 127.4, 127.9, 128.2,
128.4, 131.5, 132.6, 134.5, 134.9, 135.1, 135.3, 143.8,
146.8, 153.6, 162.7, 191.2; Anal Calcd for C22H14O3S: C,
73.73; H, 3.94. Found: C, 73.57; H, 4.03.
(±)
9-Methoxy-11-(2-oxo-2-phenylethyl)indeno[1,2-
c]isochromen-5(11H)-one (2g). Pale brown solid; mp: 159-
o
160 C; yield: 0.182g, 95%; IR (neat): 2960.2, 2930.1,
1738.4, 1671.4, 1600.4, 1391.4, 1300.8, 1231.4, 1171.6,
(±)
11-(2-(Furan-2-yl)-2-oxoethyl)indeno[1,2-
1128.6, 1025.7 cm-1; H NMR (300 MHz, CDCl3): δ 3.15-
c]isochromen-5(11H)-one (2l). Yellow solid; mp: 160-161
1
3.24 (m, 1H), 3.74 (dd, J = 18.0, 2.7 Hz, 1H), 3.78 (s, 3H),
4.81 (dd, J = 9.9, 2.4 Hz, 1H), 6.92 (dd, J = 8.1, 2.1 Hz,
1H), 7.09 (d, 1.8 Hz, 1H), 7.42 (d, J = 7.8 Hz, 2H), 7.48 (d,
J = 7.8 Hz, 2H), 7.57-7.62 (m, 2H), 7.71 (t, J = 7.5 Hz,
oC; yield: 0.147 g, 86%; IR (neat): 3090.4, 2916.8, 1734.6,
1683.5, 1585.2, 1489.7, 1231.3, 1091.5 cm-1; H NMR
1
(300 MHz, CDCl3): δ 3.00-3.09 (m, 1H), 3.62 (dd, J = 17.7,
3.0 Hz, 1H), 4.77 (dd, J = 9.9, 3.0 Hz, 1H), 6.54-6.56 (m,
1H), 7.22 (d, J = 3.3 Hz, 1H), 7.30 (dd, J = 7.5, 1.2 Hz,
1H), 7.40 (t, J = 7.5 Hz, 1H), 7.47-7.59 (m, 4H), 7.68 (d, J
= 7.5 Hz, 1H), 7.73-7.79 (m, 1H), 8.41 (d, J = 8.1 Hz, 1H);
13C NMR (75 MHz, CDCl3): δ 38.6, 40.8, 112.6, 117.9,
118.0, 119.2, 120.1, 122.2, 124.7, 127.3, 127.8, 128.1,
131.5, 134.9, 135.1, 135.2, 146.7, 146.9, 152.5, 153.6,
162.7, 187.3; Anal Calcd for C22H14O4: C, 77.18; H, 4.12.
Found: C, 76.86; H, 4.34.
1H), 7.97 (d, J = 7.5 Hz, 2H), 8.38 (d, J = 8.4 Hz, 1H); 13
C
NMR (75 MHz, CDCl3): δ 38.7, 41.4, 55.6, 111.4, 113.4,
116.3, 119.5, 119.9, 121.7, 126.7, 127.8, 128.2, 128.8,
131.5, 133.6, 135.2, 135.4, 136.7, 149.4, 153.7, 160.4,
162.8, 198.5; Anal Calcd for C25H18O4: C, 78.52; H, 4.74.
Found: C, 78.29; H, 4.79.
(±)
11-(2-(3,4-Dimethoxyphenyl)-2-oxoethyl)-9-
methoxyindeno[1,2-c]isochromen-5(11H)-one
(2h).
o
Yellow solid; mp: 166-167 C; yield: 0.159 g, 72%; IR
(neat): 2968.2, 2928.4, 1731.6, 1671.8, 1605.5, 1390.6,
(±) 11-(2-(Furan-2-yl)-2-oxoethyl)-9-methoxyindeno[1,2-
c]isochromen-5(11H)-one (2m). Pale brown solid; mp:
153-154 oC; yield: 0.171 g, 92%; IR (neat): 3000.6, 1744.3,
1300.6, 1238.8, 1170.2, 1123.5, 1029.1 cm-1; H NMR
1
(300 MHz, CDCl3): δ 3.12-3.21 (m, 1H), 3.68 (dd, J = 18.0, 1681.8, 1621.4, 1480.8, 1378.2, 1301.4, 1230.2, 1158.7,
2.7 Hz, 1H), 3.78 (s, 3H), 3.94 (s, 3H), 3.96 (s, 3H), 4.81
(dd, 9.6, 2.4 Hz, 1H), 6.85 (d, J = 8.4 Hz, 1H), 6.93 (dd, J
= 8.4, 2.1 Hz, 1H), 7.09 (d, J = 1.8 Hz, 1H), 7.41-7.61 (m,
1121.6 cm-1; 1H NMR (300 MHz, CDCl3): δ 2.99-3.01 (m,
1H), 3.61 (dd, J = 17.7, 3.0 Hz, 1H), 3.79 (s, 3H), 4.71 (dd,
J = 9.9, 2.7 Hz, 1H), 6.54-6.56 (m, 1H), 6.93 (dd, J = 8.4,
2.1 Hz, 1H), 7.07 (d, J = 2.1 Hz, 1H), 7.22 (d, J = 3.3 Hz,
1H), 7.41-7.48 (m, 2H), 7.56-7.59 (m, 2H), 7.72 (td, J =
8.4, 1.2 Hz, 1H), 8.37 (d, J = 8.1 Hz, 1H); 13C NMR (75
MHz, CDCl3): δ 38.5, 41.0, 55.6, 111.2, 112.6, 113.5,
116.2, 117.9, 119.5, 120.0, 121.7, 126.7, 127.8, 131.4,
135.2, 135.4, 146.9, 149.0, 152.5, 153.7, 160.4, 162.8,
187.4; Anal Calcd for C23H16O5: C, 74.19; H, 4.33. Found:
C, 73.88; H, 4.28.
5H), 7.71 (t, J = 7.8 Hz, 1H), 8.38 (d, J = 8.1 Hz, 1H); 13
C
NMR (75 MHz, CDCl3): δ 38.9, 40.8, 55.6, 56.0, 56.1,
110.1, 110.2, 111.4, 113.2, 116.5, 119.5, 119.9, 121.7,
123.0, 126.6, 127.8, 129.9, 131.4, 135.1, 135.5, 149.1,
149.5, 153.6, 153.7, 160.3, 162.9, 196.9; Anal Calcd for
C27H22O6: C, 73.29; H, 5.01. Found: C, 73.02; H, 5.20.
(±)
9-Methoxy-11-(2-(4-methoxyphenyl)-2-
oxoethyl)indeno[1,2-c]isochromen-5(11H)-one (2i). Pale
o
brown solid; mp: 151-152 C; yield: 0.188 g, 91%; IR
(±)
11-(2-Oxo-2-(pyridin-2-yl)ethyl)indeno[1,2-
(neat): 2961.1, 2930.3, 1738.5, 1673.9, 1605.5, 1391.4,
c]isochromen-5(11H)-one (2n). Yellow solid; mp: 141-142
1302.7, 1238.1, 1173.5, 1129.1, 1026.9 cm-1; H NMR
oC; yield: 0.127 g, 72%; IR (neat): 3154.9, 2903.3, 1733.7,
1
(300 MHz, CDCl3): δ 3.09-3.19 (m, 1H), 3.67 (dd, J = 18.0, 1670.0, 1465.6, 1387.5, 1292.1, 1159.9, 1029.8 cm-1; H
1
2.7 Hz, 1H), 3.78 (s, 3H), 3.87 (s, 3H), 4.81 (dd, J = 9.6,
2.4 Hz, 1H), 6.91-6.95 (m, 3H), 7.09 (d, J = 2.1 Hz, 1H),
NMR (300 MHz, CDCl3): δ 3.40-3.49 (m, 1H), 4.07 (dd, J
= 18.3, 3.0 Hz, 1H), 4.76 (dd, J = 10.2, 2.7 Hz, 1H), 7.26-
7.41-7.46 (m, 2H), 7.58 (d, J = 8.4, 1H), 7.71 (t, J = 7.5 Hz, 7.31 (m, 1H), 7.39 (t, J = 7.2 Hz, 1H), 7.46-7.50 (m, 3H),
1H), 7.95 (d, J = 9.0 Hz, 2H), 8.38 (dd, J = 8.4, 1.2 Hz,
1H); 13C NMR (75 MHz, CDCl3): δ* 38.8, 40.9, 55.5,
111.3, 113.4, 113.9, 116.5, 119.5, 119.9, 121.7, 126.6,
127.8, 129.8, 130.5, 131.4, 135.1, 135.5, 149.5, 153.6,
160.3, 162.9, 163.9, 196.9; Anal Calcd for C26H20O5: C,
75.72; H, 4.89. Found: C, 75.43; H, 4.98. *One aromatic
carbon is merged with others.
7.63-7.78 (m, 3H), 7.90 (td, J = 7.8, 1.5 Hz, 1H), 8.18 (d, J
= 7.8 Hz, 1H), 8.40 (d, J = 8.1 Hz, 1H), 8.61-8.62 (m, 1H);
13C NMR (75 MHz, CDCl3): δ 39.0, 40.6, 118.4, 119.1,
120.2, 122.0, 122.4, 124.7, 127.2, 127.6, 127.7, 128.0,
131.4, 135.0, 135.2, 135.3, 137.1, 147.0, 149.1, 152.9,
153.5, 162.8, 200.2; Anal Calcd for C23H15NO3: C, 78.18;
H, 4.28; N, 3.96. Found: C, 77.85; H, 4.46; N, 3.83.
(±)
11-(2-(2,4-Dichlorophenyl)-2-oxoethyl)-9-
(±)
9-Methoxy-11-(2-(naphthalen-2-yl)-2-
methoxyindeno[1,2-c]isochromen-5(11H)-one (2j). Yellow
oxoethyl)indeno[1,2-c]isochromen-5(11H)-one (2o). Pale
o
o
solid; mp: 159-160 C; yield: 0.219 g, 97%; IR (neat):
brown solid; mp: 170-171 C; yield: 0.214 g, 99%; IR
2967.2, 2921.3, 1736.6, 1671.7, 1600.3, 1466.7, 1390.3,
(neat): 2994.9, 1745.3, 1680.7, 1629.6, 1489.7, 1384.6,
1306.4, 1233.3, 1177.8, 1129.3, 1026.7 cm-1; H NMR
1302.7, 1231.3, 1122.3, 1029.8 cm-1; H NMR (300 MHz,
1
1
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000456
Advanced Synthesis & Catalysis
CDCl3): δ 3.31-3.40 (m, 1H), 3.77 (s, 3H), 3.86 (dd, J =
18.0, 2.7 Hz, 1H), 4.87 (dd, J = 9.9, 2.4 Hz, 1H), 6.92 (dd,
= 18.0, 3.0 Hz, 1H), 4.62 (dd, J = 9.6, 3.0 Hz, 1H), 7.33 (td,
J = 7.5, 1.2 Hz, 1H), 7.40 (dd, J = 7.5, 1.2 Hz, 1H), 7.44-
J = 8.4, 2.1 Hz, 1H), 7.13 (d, J = 2.1 Hz, 1H), 7.42-7.64 (m, 7.52 (m, 3H), 7.67 (d, J = 7.5 Hz, 1H), 7.77 (td, J = 7.8,
5H), 7.72 (t, J = 7.8 Hz, 1H), 7.87-7.94 (m, 3H), 8.10 (dd,
J = 8.4, 1.5 Hz, 1H), 8.38-8.43 (m, 2H); 13C NMR (75
MHz, CDCl3): δ* 38.8, 41.4, 55.6, 111.4, 113.4, 116.4,
119.6, 120.0, 121.7, 123.7, 126.7, 127.0, 127.8, 128.7,
128.8, 129.6, 130.1, 131.5, 132.4, 134.0, 135.2, 135.5,
135.8, 149.5, 153.8, 160.4, 162.9, 198.4; Anal Calcd for
C29H20O4: C, 80.54; H, 4.66. Found: C, 80.25; H, 4.82.
*One aromatic carbon is merged with others.
1.5 Hz, 1H), 8.40 (dd, J = 7.8, 1.5 Hz, 1H); 13C NMR (75
MHz, CDCl3): δ 11.4, 11.5, 21.3, 38.8, 45.5, 118.1, 119.1,
120.1, 122.2, 124.5, 127.3, 127.8, 128.1, 131.4, 134.9,
135.2, 146.9, 153.5, 162.6, 209.1; Anal Calcd for
C21H16O3: C, 79.73; H, 5.10. Found: C, 79.47; H, 5.14.
(±)
11-(1-Oxo-1,2,3,4-tetrahydronaphthalen-2-
yl)indeno[1,2-c]isochromen-5(11H)-one (2u). Colourless
o
solid; mp: 202-203 C; yield: 0.096 g, 51%; IR (neat):
(±)
11-(2-(2-Chlorophenyl)-2-oxoethyl)-3-
3063.4, 2914.8, 1738.5, 1667.2, 1612.2, 1489.7, 1384.6,
1
methylindeno[1,2-c]isochromen-5(11H)-one (2p). Pale
1278.6, 1227.5, 1162.9, 1009.6 cm-1; H NMR (300 MHz,
o
brown solid; mp: 184-185 C; yield: 0.196 g, 98%; IR
CDCl3): δ 1.38-1.56 (m, 2H), 2.70-2.90 (m, 2H), 3.29 (dd,
J = 12.6, 5.4 Hz, 1H), 5.28 (s, 1H), 7.16 (d, J = 7.5 Hz,
1H), 7.34-7.70 (m, 8H), 7.71-7.72 (m, 1H), 8.30 (t, J = 9.0
Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 23.7, 29.5, 42.9,
52.0, 117.4, 119.1, 119.7, 123.3, 124.1, 126.9, 127.2, 127.8,
127.9, 128.3, 128.9, 131.1, 132.3, 134.0, 135.4, 135.8,
136.0, 144.2, 147.0, 154.8, 162.7, 199.1; Anal Calcd for
C26H18O3: C, 82.52; H, 4.79. Found: C, 82.58; H, 4.85.
(neat): 3091.4, 2916.5, 1726.4, 1681.2, 1588.5, 1489.1,
1380.6, 1228.3, 1091.3 cm-1; 1H NMR (300 MHz, CDCl3):
δ 2.50 (s, 3H), 3.15-3.24 (m, 1H), 3.79 (dd, J = 18.0, 3.0
Hz, 1H), 4.75 (dd, J = 9.9, 3.0 Hz, 1H), 7.28-7.47 (m, 7H),
7.55-7.67 (m, 3H), 8.21 (s, 1H); 13C NMR (75 MHz,
CDCl3): δ* 21.4, 39.1, 45.2, 117.9, 119.0, 120.1, 122.1,
124.6, 127.8, 127.9, 129.1, 130.7, 131.1, 131.3, 132.2,
132.6, 135.2, 136.4, 137.7, 138.7, 146.3, 152.8, 162.8,
201.2; Anal Calcd for C25H17ClO3: C, 74.91; H, 4.27.
Found: C, 74.63; H, 4.34. *One aromatic carbon is merged
with others.
Methyl
(Z)-2-(5-oxoindeno[1,2-c]isochromen-11(5H)-
o
ylidene)acetate (3). Yellow solid; mp: 161-162 C; yield:
0.088 g, 58%; IR (neat): 2967.9, 2927.4, 1755.9, 1725.0,
1605.4, 1489.7, 1401.0, 1302.7, 1200.5, 1020.1 cm-1; H
1
(±)
9-Methoxy-11-(2-(4-methoxyphenyl)-2-oxoethyl)-3-
NMR (300 MHz, CDCl3): δ 3.91 (s, 3H), 7.08 (s, 1H),
7.35-7.43 (m, 2H), 7.48-7.57 (m, 2H), 7.79 (td, J = 8.4, 1.2
Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 8.41 (d, J = 8.1 Hz, 1H),
8.60-8.63 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 52.1,
110.4, 118.7, 118.9, 120.0, 121.9, 127.3, 127.7, 129.9,
130.2, 131.9, 133.6, 134.1, 134.4, 135.4, 145.2, 158.9,
161.2, 165.9; Anal Calcd for C19H12O4: C, 74.99; H, 3.98.
Found: C, 74.68; H, 4.08.
methylindeno[1,2-c]isochromen-5(11H)-one (2q). Pale
o
brown solid; mp: 152-153 C; yield: 0.188 g, 88%; IR
(neat): 3071.1, 2930.3, 1734.6, 1670.0, 1629.6, 1595.8,
1512.8, 1435.7, 1234.2, 1180.2, 1125.3, 1057.7 cm-1; H
1
NMR (300 MHz, CDCl3): δ 2.47 (s, 3H), 3.08-3.17 (m,
1H), 3.65 (dd, J = 18.0, 3.0 Hz, 1H), 3.77 (s, 3H), 3.87 (s,
3H), 4.78 (dd, J = 9.9, 2.7 Hz, 1H), 6.90-6.94 (m, 3H),
7.07 (d, J = 2.1 Hz, 1H), 7.35 (d, J = 7.8 Hz, 1H), 7.51-
7.57 (m, 2H), 7.93-7.96 (m, 2H), 8.20 (s, 1H); 13C NMR
(75 MHz, CDCl3): δ* 21.3, 38.8, 41.0, 55.5, 111.4, 113.3,
113.9, 116.6, 119.3, 119.6, 121.7, 128.0, 129.8, 130.5,
131.2, 133.1, 136.4, 136.9, 149.3, 152.8, 160.1, 163.1,
163.9, 196.9; Anal Calcd for C27H22O5: C, 76.04; H, 5.20.
Found: C, 75.90; H, 5.25. *One carbon is merged with
others.
Acknowledgements
Financial support from the Department of Science and
Technology–Science and Engineering Research Board, DST-
SERB (No. EMR/2016/001619) is gratefully acknowledged.
(±)
11-(2-(Benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-3-
methylindeno[1,2-c]isochromen-5(11H)-one (2r). Yellow
o
References
solid; mp: 220-221 C; yield: 0.162 g, 79%; IR (neat):
2913.9, 1721.2, 1670.0, 1503.2, 1445.4, 1380.8, 1251.6,
1115.6, 1036.6 cm-1; H NMR (300 MHz, CDCl3): δ 2.49
1
[1] For a monograph, see: S. Pal, M. Pal, Isocoumarin,
(s, 3H), 3.05-3.14 (m, 1H), 3.63 (dd, J = 18.0, 3.0 Hz, 1H),
4.82 (dd, J = 9.9, 3.0 Hz, 1H), 6.06 (s, 2H), 6.81 (d, J = 8.7
Hz, 1H), 7.24-7.29 (m, 1H), 7.36-7.41 (m, 2H), 7.46-7.58
(m, 4H), 7.65 (d, J = 7.5 Hz, 1H), 8.23 (s, 1H); 13C NMR
(75 MHz, CDCl3): δ 21.4, 39.0, 40.9, 102.0, 107.9, 108.0,
118.4, 118.9, 120.2, 122.1, 124.6, 124.7, 127.8, 127.9,
131.4, 131.6, 132.7, 135.1, 136.4, 137.6, 147.0, 148.4,
152.2, 152.7, 163.0, 196.4; Anal Calcd for C26H18O5: C,
76.09; H, 4.42. Found: C, 75.86; H, 4.48.
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Occurrences,
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(±) 11-(2-Oxopropyl)indeno[1,2-c]isochromen-5(11H)-one
(2s). Off-white solid; mp: 131-132 oC; yield: 0.132 g, 91%;
IR (neat): 3067.2, 2994.9, 2896.6, 1738.5, 1711.5, 1605.5,
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1
1493.6, 1394.2, 1322.9, 1203.4, 1047.2, 1006.7 cm-1; H
NMR (300 MHz, CDCl3): δ 2.24 (s, 3H), 2.57-2.66 (m,
1H), 3.28 (dd, 18.0, 2.7 Hz, 1H), 4.60 (dd, J = 9.6, 2.7 Hz,
1H), 7.31-7.52 (m, 5H), 7.67 (d, J = 7.5 Hz, 1H), 7.77 (t, J
= 7.5 Hz, 1H), 8.40 (d, J = 7.8 Hz, 1H); 13C NMR (75
MHz, CDCl3): δ 30.7, 38.6, 45.7, 117.9, 119.1, 120.1,
122.0, 124.4, 127.3, 127.8, 128.2, 131.5, 134.9, 135.0,
135.2, 146.9, 153.4, 162.6, 206.9; Anal Calcd for
C19H14O3: C, 78.61; H, 4.86. Found: C, 78.30; H, 4.91.
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(±)
11-(2-Cyclopropyl-2-oxoethyl)indeno[1,2-
c]isochromen-5(11H)-one (2t). Yellow solid; mp: 146-147
oC; yield: 0.130 g, 82%; IR (neat): 3070.1, 2920.6, 1725.0,
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1704.8, 1609.3, 1496.5, 1384.6, 1193.7, 1080.9 cm-1; H
1
NMR (300 MHz, CDCl3): δ 0.93-0.98 (m, 2H), 1.15-1.19
(m, 2H), 1.87-1.95 (m, 1H), 2.70-2.80 (m, 1H), 3.41 (dd, J
7
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
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8
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10.1002/adsc.202000456
Advanced Synthesis & Catalysis
FULL PAPER
O
R3
PdCl2 (10 mol%)
O
Palladium(II)-Catalyzed Direct Access to
Indeno[1,2-c]isochromen-5(11H)-ones via
Intramolecular Oxypalladation-Initiated Cascade
Process
t-BuO
O
R3
DMSO, 60 o
6-12 h
C
R1
O
R1
(up to 99%)
R2
R2
O
Adv. Synth. Catal. Year, Volume, Page – Page
R3
(22 examples)
O
O
Muthu Karuppasamy, B. S. Vachan, Tanvi Jandial,
Sesuraj Babiola Annes, Nattamai Bhuvanesh, C.
Uma Maheswari, and Vellaisamy Sridharan*
PdII
R1
R2
O
Sequential intramolecular oxypalladation (6-endo-dig)-
intramolecular olefin insertion-protonation cascade
9
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