Palladium-Catalyzed Decarboxylative Synthesis of 5H-Benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-Diones using 2-Phenyl-4H-Benzo[d][1,3]oxazin-4-Ones and α-Oxo Carboxylic Acids

Article abstract of DOI:10.1002/adsc.201901142

A Pd-catalyzed novel and efficient protocol has been developed for the direct functionalization of 2-phenyl-4H-benzo[d][1,3]oxazin-4-ones with α-oxo carboxylic acids resulting in 5H-benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-diones using (NH₄

Full text of DOI:10.1002/adsc.201901142

Title: Palladium-Catalyzed Decarboxylative Synthesis of 5H-
Benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-diones using
2-Phenyl-4H-benzo[d][1,3]oxazin-4-ones and α-Oxo Carboxylic
Acids
Authors: Ram Sunil Kumar Lalji, Prashant Kumar, Mohit Gupta,
Virinder Parmar, and Brajendra Singh
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901142
Link to VoR: http://dx.doi.org/10.1002/adsc.201901142

Advanced Synthesis & Catalysis
10.1002/adsc.201901142
FULL PAPER
DOI: 10.1002/adsc.201901142
Palladium-Catalyzed Decarboxylative Synthesis of 5H-Benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-diones using 2-Phenyl-4H-benzo[d][1,3]oxazin-4-ones and -
Oxo Carboxylic Acids
Ram Sunil Kumar Lalji,a,b,# Prashant Kumar,a,c,# Mohit Gupta,a,d Virinder S. Parmar,a,e Brajendra K.
Singha*
a
b
c
d
e
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India
Department of Chemistry, Kirori Mal College, University of Delhi, Delhi 110007, India
Department of Chemistry, SRM University, Delhi-NCR Sonepat, Haryana-131029, India
Department of Chemistry, L.N.M.S. College, Birpur, B.N. Mandal University, Bihar-854340, India
Department of Chemistry and Environmental Science, Medgar Evers College, The City University of New York,
Brooklyn, NY 11225, USA
#
*
These authors contributed equally to this work
Corresponding-Author. Tel: +91-11-27666646, Ext: 136, Fax: +91-11-27667206, E-mail address:
singhbk@chemistry.du.ac.in (Dr. Brajendra Kumar Singh)
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.201901142.
Abstract. A Pd-catalyzed novel and efficient protocol has
been developed for the direct functionalization of 2-phenyl-
Keywords: Cyclized product, Control experiments, Pd-
catalyzed, Free-radical, Discreet assessment
4
H-benzo[d][1,3]oxazin-4-ones with -oxo carboxylic acids
resulting in 5H-benzo[4,5][1,3]oxazino[2,3-a]isoindole-
,11(6aH)-diones using (NH as effective oxidant and
AgNO as co-oxidant. All the explored substrates were
5
4 2 2 8
) S O
3
found to be compatible for this transformation and delivered
the corresponding desired products in moderate to excellent
yields.
catalyzed strategy for the synthesis of 2-phenyl-5H-
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-
diones from 4H-benzo[d][1,3]oxazin-4-ones using
readily available toluenes, aldehydes and benzyl
Introduction
Isoindolinones are an important class of heterocycles
in organic chemistry. This moiety forms an essential
structural motif of many biologically significant
[11]
alcohols as reaction partners [Scheme 1(i)].
molecules,[
1]
natural products
[2]
and useful
In recent years, transition metal-catalyzed
decarboxylative cross-coupling has proven to be an
attractive approach for the selective C-C and C-
intermediates in the synthesis of several drug like
molecules.[ Nevertheless, isoindolinones and their
derivatives have shown various pharmaceutical
3]
[12]
heteroatom bond formations. In this context,-oxo
[
4]
[5]
properties such as anti-ulcer, anti-fungal, anti-
carboxylic acids have been exploited to a great extent
as convenient sources for the functionalization of
numerous important organic molecules and
[2j]
[6]
[7]
hypertensive, vasodilatory, anti-psychotic, anti-
inflammatory[ and anti-leukemic activities. Broad
range applicability of isoindolinones in therapeutic
industries has drawn the attention of the organic
chemists worldwide and several elegant methods for
their synthesis have been developed.[ Recently, our
group has also developed a radical-induced, Pd(II)-
8]
[9]
[13]
remarkable success has been achieved. It has also
been established that the -oxo carboxylic acids have
a tendency to behave as aroyl surrogates in the
presence of radical inducer oxidants as that of
10]
[14]
aldehydes and toluenes.
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201901142
In continuation of our work[11] and to explore the
expedient behavior of -oxo carboxylic acids for the
synthesis of isoindolinones, reaction between 2-
Results and Discussion
After preliminary examination of the reaction
protocol and to assess the feasibility of -oxo
carboxylic acids for the synthesis of 5H-
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-
diones in better yields, reaction conditions were
optimized (Table 1). The reaction between 2-phenyl-
4H-benzo[d][1,3]oxazin-4-one (1a) and -oxo
carboxylic acid (2a) resulted in the formation of the
desired product in 55 % yield (Table 1, entry 2)
phenyl-4H-benzo[d][1,3]oxazin-4-one
(1a)
employing -oxo carboxylic acid (2a) was examined.
Initially, we performed the reaction between 2-
phenyl-4H-benzo[d][1,3]oxazin-4-one and -oxo
carboxylic acid with our previously reported
conditions in a sealed reaction vial,[11] the anticipated
product 5H-benzo[4,5][1,3]oxazino[2,3-a]isoindole-
5,11(6aH)-dione (3a) was obtained in 62 % yield
using Pd(OAc)
oxidant (NH
AgNO (1 equivalent) in 1,2-dichloroethane (DCE)
solvent at 50 C. However, replacement of
NH with other oxidants like K and
Na yielded inferior product yields (Table 1,
2
(10 mol %) in the presence of
[
Scheme 1(ii), Table 1, entry 1]. However, to our
4
)
2
S O
2 8
(2 equivalent) and co-oxidant
surprise B C Ranu and his group have reported the
3
formation of the acylated product 4 [Scheme 1(iii)]
o
[15]
with the same reaction substrates. On the contrary,
with the same substrates and under identical reaction
conditions, we obtained 3a in 55 % yield [Scheme
(
2
)
2
S
2
O
8
S
2 2
O
8
S O
2 2 8
entries 3 and 4). Inferior product yield was also
1(iv), Table 1, entry 2].
observed when the reaction was carried out at lower
This result prompted us to explore the compatibility
of 2-phenyl-4H-benzo[d][1,3]oxazin-4-ones and -
oxo carboxylic acids for this transformation. Herein,
we are reporting a Pd-catalyzed decarboxylative free
radical approach for the synthesis of 5H-
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-
diones from 2-phenyl-4H-benzo[d][1,3]oxazin-4-ones
and -oxo carboxylic acids. To the best of our
knowledge, this is the first report for the synthesis of
o
temperature of 30 C (Table 1, entry 5), whereas
improvement in product yield was observed when the
reaction was carried out at elevated temperature
(
(
Table 1, entries 6-8) and the best product yield
96 %) was observed when the reaction was
o
performed at 120 C (Table 1, entry 8). However,
o
further increase in the temperature above 120 C was
found unsuitable for this transformation (Table 1,
entry 9).
5
5
H-benzo[4,5][1,3]oxazino[2,3-a]isoindole-
,11(6aH)-diones through selective functionalization
Table 1. Optimization of reaction conditions.[a]
of 2-phenyl-4H-benzo[d][1,3]oxazin-4-ones with -
oxo carboxylic acids.
Entry
Catalyst
Oxidant
Co-
Oxidant
Solvent
Temp.
[ C]
Yield
[%]
o
[b]
1
Pd(OAc)
2
TBHP
-
1,4-
120
62c
dioxane
2
3
4
5
6
7
8
9
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
-
2
2
2
2
2
2
2
2
2
2
(NH
4
)
2
S
2
O
8
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
AgNO
-
3
3
3
3
3
3
3
3
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
50
50
55
50
K S O
2 2 8
Na
2
S
2
O
8
50
26
(NH
(NH
(NH
(NH
(NH
(NH
4
4
4
4
4
4
)
2
)
2
)
2
)
2
)
2
)
2
S
2
S
2
S
2
S
2
S
2
S
2
O
O
O
O
O
O
8
8
8
8
8
8
30
39
80
62
100
120
130
120
120
120
120
120
120
71
96
87
10
11
12
13
14
15
63
-
AgNO
AgNO
AgNO
AgNO
AgNO
3
3
3
3
3
64
(NH
(NH
(NH
(NH
4
4
4
4
)
2
)
2
)
2
)
2
S
2
S
2
S
2
S
2
O
O
O
O
8
8
8
8
ND
81d
26e
94f
Scheme 1. Preliminary studies and functionalization of 2-
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
phenyl-4H-benzo[d][1,3]oxazin-4-one
oxocarboxylic acid.
with
-
[a]Reaction
conditions:
a
mixture
of
2-phenyl-4H-
benzo[d][1,3]oxazin-4-one (1a) (0.5 mmol), -oxo carboxylic
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201901142
acid 2a (1.5 mmol), catalyst Pd(OAc)
2
(10 mol%), oxidant
(1 equivalent )
was treated in DCE solvent (2 mL) at the given temperature for
Moreover, when this isolated product 4 was treated
separately under these conditions, it got fully
converted into the cyclized product 3a (Scheme 2b).
4 2 2 8 3
(NH ) S O (2 equivalent) and co-oxidant AgNO
[
b]
[c]
[d]
1
8h; isolated yields; 5 mmol of TBHP was used; 7 mol% of
[
e]
[f]
Pd(OAc)
equivalent of AgNO
2
was used; 5 mol% of Pd(OAc)
was used.
2
was used;
2
These observations suggested that the first step of the
reaction involves the acylation of 2-phenyl-4H-
benzo[d][1,3]oxazin-4-one providing the intermediate
4 and the second step entails the cyclization of
intermediate 4 into the product 3a.
3
Absence of either of the oxidant (NH
co-oxidant AgNO deterred the product yield (Table
, entries 10 and 11). In a blank experiment, without
the catalyst Pd(OAc) , no product formation was
4
)
S
2 2
O
8
or the
3
1
2
Furthermore, when compound 4 was allowed to react
observed (Table 1, entry 12). Additionally, different
catalyst concentrations were screened and it was
perceived that the lower catalyst loading yielded
inferior product yields, and merely 26 % yield could
in the absence of the catalyst Pd(OAc) , the
2
compound 3a was obtained (Scheme 2c). The
conversion of compound 4 into the desired product
3
a in the absence of Pd(OAc) ruled out any possible
2
be obtained with 5 mol % of Pd(OAc)
entries 13 and 14). However, higher AgNO
concentration did not improve the product yield
Table 1, entry 15).
2
(Table 1,
role of this catalyst in the cyclization of compound 4
into product 3a. Additionally, the role of both the
oxidants for the conversion of compound 4 into the
product 3a was examined. It was observed that the
oxidant (NH ) S O yielded the desired product 3a in
3
(
The success of this strategy was subsequently applied
towards the reactions of various substituted 2-phenyl-
4
2
2
8
absence of AgNO , whereas, oxidant AgNO solely
3
3
4
H-benzo[d][1,3]oxazin-4-ones
1
with -oxo
was unable to deliver the product in the absence of
(NH (Scheme 2d). In absence of both the
oxidants, no product formation was observed and
carboxylic acids 2 as shown in Table 2. All the tried
substrates yielded the desired products in moderate to
good yields (Table 2). Both the electron releasing
and electron withdrawing substituents on the 2-
phenyl-4H-benzo[d][1,3]oxazin-4-ones 1, as well as
on the -oxo carboxylic acids 2 were well tolerated
and resulted in formation of the targeted products in
good yields (Table 2). Unsubstituted substrates
provided the highest product yield of 96 % (Table 2,
entry 3a). -Oxo carboxylic acids bearing electron
4
)
2
S
2
O
8
compound 4 was left unreacted (Scheme 2g).
Table 2. Evaluation of substrate scope.[a],[b]
releasing substituents (-CH
3
, -OCH ) delivered better
3
product yields as compared to those containing the
electron withdrawing substituents (-Cl, -Br) (Table 2,
entries 3b-3e).
Nitro-substituted 2-phenyl-4H-benzo[d][1,3]oxazin-
4-ones delivered the products in moderate yields and
that could be attributed to the strong electron
withdrawing nature of the nitro group (Table 2,
entries 3n and 3o). Furthermore, treatment of the
substituted 2-phenyl-4H-benzo[d][1,3]oxazin-4-ones
with substituted -oxo carboxylic acids provided the
desired products in good yields, irrespective of the
position and electronic nature of the substituents;
however, relatively longer time was required in some
cases (Table 2).
Control experiments
Furthermore, to get an insight into the reaction
pathway, controlled experiments were performed and
examined (Scheme 2). A careful assessment of the
reaction condition ascertained the formation of the
intermediate 4 after 60 minutes along with the
unreacted reactants, which on continuation, were
converted into the product 3a (Scheme 2a).
[a]Reaction
benzo[d][1,3]oxazin-4-one (0.5 mmol), phenylglyoxylic acid (1.5
mmol), catalyst Pd(OAc) (10 mol%), oxidant (NH (2
equivalent ) and co-oxidant AgNO
conditions:
a
mixture
of
2-phenyl-4H-
2
4 2 2 8
) S O
3
(1 equivalent ) was treated in
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201901142
o
the DCE (1,2-dichloroethane; 2 mL) at 120 C for different time
interval as indicated in parenthesis; [b]isolated yields are given in
parentheses.
Finally, the plausible reaction pathway for this
reaction was examined. For this purpose, the reaction
was run in the presence of the free radical scavenger
(
(
2,2,6,6-tertamethylpiperidin-1-yl)oxidanyl
TEMPO) between the reactants 1 and 2 under
optimized reaction conditions (Scheme 2e) when
only the TEMPO-trapped intermediate 5 could be
isolated and no desired product formation was
observed. This indicated the formation of acyl radical
at the outset, which suggests that the first acylation
step follows a radical pathway.
Further, isolated intermediate 4 was reacted with
radical scavengers TEMPO and BHT (2,6-di-tert-
butyl-4-methylphenol) independently (Scheme 2f).
To our surprise, no TEMPO-trapped intermediate was
observed in the reaction under these conditions,
rather a complete conversion of the intermediate into
the product 3a was observed. The absence of any
TEMPO-trapped intermediate suggested that the
cyclization step is independent of radical mechanism.
Scheme 2. Monitoring of the reaction and controlled
experiments.
Nevertheless, the radical initiator (NH
4
)
2
S
2
8
O did not
generate any persulphate radicals that could have
been trapped with radical scavengers, TEMPO and
BHT. The complete conversion of intermediate 4 into
the desired product 3a, and the absence of any by
product indicates that (NH
4
)
S
2 2
8
O does not act as a
radical initiator rather as an oxidant for this
cyclization step.
On the basis of the results of the control experiments
[
12], [14b], [14g], [14h]
and literature information,
a plausible
reaction pathway has been proposed (Scheme 3). We
believe that initially complex 6 is formed by the
ortho-palladation of compound 1a with Pd(OAc)
2
[
14e]
with the liberation of AcOH.
At the same time,
persulphate oxidizes Ag(I) to Ag(II), which then
provides the carboxyl radical 2ʹ by the abstraction of
single electron from the -oxo carboxylic acid 2.
Carboxyl
radical
2ʹ
rapidly
undergoes
[
14b],
decarboxylation and generates the acyl radical 7.
[
14g], [14h]
Subsequently, complex 6 reacts with the acyl
[
14i], [16]
radical 7 and forms complex 8.
complex 8 undergoes a reductive elimination process
to give compound
Thereafter,
Scheme 3. Plausible reaction mechanism.
4
which on subsequent Conclusion
intramolecular cyclization results in compound 9. The
compound 9 thus produced undergoes 1,2-hydride
shift which leads to the formation of the intermediate
In conclusion, we have developed
methodology for the selective functionalization of 2-
phenyl-4H-benzo[d][1,3]oxazin-4-ones with -oxo
a
new
10, which on aromatization affords the final
carboxylic acids using Pd(OAc)
NH as an oxidant and AgNO
2
as a catalyst,
as co-oxidant.
compound 3a.
(
4
)
2
S
2
O
8
3
In this transformation, the cyclized products 5H-
4
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Advanced Synthesis & Catalysis
10.1002/adsc.201901142
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-
diones could be obtained in good yields. In total, 23
products have been successfully synthesized and fully
characterized by different spectroscopic techniques;
the formation of the acylated product 4 and one of the
final product 3l was also confirmed by X-ray
6a-Phenyl-5H-benzo[4,5][1,3]oxazino[2,3-a]isoindole-
o
5
,11(6aH)-dione (3a): White solid; mp: 182-184 C. 96 %
-
1
yield. IR (KBr) νmax (cm ): 3058, 2926, 1752, 1735, 1702,
1
1
607, 1486, 1361, 1068, 1024, 753. H NMR (400 MHz,
3
CDCl ): δ 8.16 (1H, d, J = 8.2 Hz), 8.00-7.97 (2H, m),
7
7
.71-7.67 (1H, m), 7.64-7.56 (2H, m), 7.54-7.51 (3H, m),
.34-7.28 (3H, m), 7.23 (1H, dd, J = 7.7, 1.0 Hz).
13
C
[17]
crystallographic analysis (Figure 1).
3
NMR (100 MHz, CDCl ): δ 165.83, 162.53, 145.01,
1
1
9
37.47, 136.65, 135.95, 134.23, 130.84, 130.81, 129.68,
29.39, 125.71, 125.65, 124.90, 123.68, 121.24, 116.27,
+
+
4.54. HRMS (ESI ): m/z [M+H]
: 328.0968; found: 328.0974.
calculated for
21 3
C H13NO
6
5
a-(p-Tolyl)-5H-benzo[4,5][1,3]oxazino[2,3-a]isoindole-
o
,11(6aH)-dione (3b): White solid, mp: 208-210 C, 57%
-
1
yield. IR (KBr) νmax (cm ): 3026, 2925, 1734, 1723, 1604,
1
1
487, 1375, 1251, 1069, 750. H NMR (400 MHz, CDCl
3
):
δ 8.15 (1H, d, J = 8.0 Hz), 7.99 (2H, t, J = 6.4 Hz), 7.71-
7
7
.67 (1H, m), 7.63-7.56 ( 2H, m), 7.51 (1H, d, J = 7.0 Hz),
.40 (2H , d, J = 7.4 Hz), 7.23 (1H , d, J = 7.4 Hz), 7.11
3
l
4
13
(
2H, d, J = 7.5 Hz), 2.26 (3H, s). C NMR (100 MHz,
CDCl
1
1
3
), 165.86, 162.65, 145.20, 139.77, 136.68, 135.90,
34.46, 134.21, 130.79, 130.76, 130.08, 129.36, 125.65,
25.60, 124.86, 123.62, 121.23, 116.36, 94.64, 21.21
Figure 1. Single crystal X-ray structure of final compound
l and acylated product 4.
3
+
+
3
HRMS (ESI ): m/z [M+H] calculated for C22H15NO :
3
42.1125; found: 342.1131.
Experimental Section
6
a-(4-Methoxyphenyl)-5H-benzo[4,5][1,3]oxazino[2,3-
All the experiments were performed in a reaction tube
under conventional heating conditions. Analytical TLCs
were performed on Merck silica gel 60F254 plates. IR
a]isoindole-5,11(6aH)-dione (3c): White solid; mp: 205-
2
1
MHz, CDCl
7
o
-1
07 C; 45% yield. IR (KBr) νmax (cm ): 1728, 1608, 1477,
1
365, 1313, 1249, 1166, 1022, 763, 678. H NMR (400
3
): δ 8.15 (1H, d, J = 8.4 Hz), 7.99 (2H, t, J =
.9 Hz), 7.69 (1H, t, J = 7.6 Hz), 7.64-7.55 (2H, m), 7.51
1
spectra were recorded using KBr film method. The H and
13
3
C NMR spectra (in DMSO or CDCl ) were recorded on a
JEOL ECX-400P NMR at 400 MHz and 100 MHz,
respectively using TMS as internal standard. The high-
resolution mass spectral data was obtained using an
Agilent Technology-6530, Accurate mass, Q-TOF LCMS
spectrometer. Melting points were recorded on a Buchi M-
(
(
1H, d, J = 7.2 Hz), 7.43 (2H, dd, J = 9.0, 1.9 Hz), 7.23
1H, d J=7.6Hz), 6.81 (dd, J = 8.9, 1.8 Hz, 2H), 3.72 (3H,
13
s). C NMR (100 MHz, CDCl
3
): δ 165.82, 162.66, 160.48,
1
1
1
45.30, 136.62, 135.88, 134.20, 130.74, 130.71, 129.26,
29.19, 127.15, 125.59, 124.84, 123.55, 121.25, 116.40,
14.70, 94.58, 55.39. HRMS (ESI ): m/z [M+H]
: 358.1074; found: 358.1047.
5
60 melting point apparatus and are uncorrected. All the
+
+
chemicals and reagents were purchased from commercial
sources and used as received unless otherwise indicated.
calculated for C22H15NO
4
4
8 % Pd(OAc)
2
was used as a source of Pd-catalyst.
6a-(4-Chlorophenyl)-5H-benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-dione (3d): Pale yellow solid; mp:
Experimental procedure for the synthesis of
compounds of series 3
o
-1
2
1
09-211 C; 55% yield. IR (KBr) νmax (cm ): 3059, 2924,
731, 1702, 1606, 1485, 1363, 1252, 1067, 1007, 762. H
1
An oven dried reaction tube (10 mL) with a small stir bar
was charged with a mixture of 4H-benzo[d][1,3]oxazin-4-
ones (1, 0.5 mmol), the corresponding phenylglyoxylic
3
NMR (400 MHz, CDCl ): δ 8.14 (1H, d, J = 8.1 Hz), 8.02-
7.99 (2H, m), 7.71 (1H, dd, J = 11.0, 4.4 Hz), 7.66-
7.59(2H, m), 7.48 (3H, dd, J = 11.1, 8.3 Hz), 7.28 (3H, dd,
J = 7.6, 6.3 Hz). 13C NMR (100 MHz, CDCl
): δ 165.71,
acid (1.5 mmol), Pd(OAc)
2
(10 mol %), (NH
4
)
2
S
2
O
8
(2
3
equivalent) and AgNO (1 equivalent). The tube was
3
162.25, 144.67, 136.51, 136.21, 136.13, 135.93, 134.38,
131.07, 130.92, 129.73, 129.34, 127.23, 125.87, 125.07,
o
capped tightly and heated at 120 C for appropriate time.
The progress of the reaction was monitored by TLC. After
completion of the reaction, mixture was cooled to ambient
temperature and passed through a short plug of celite and
washed with EtOAc (3x10 mL). The combined organic
filtrate was further diluted with 30 mL EtOAc and washed
+
+
123.60, 121.30, 116.16, 94.15. HRMS (ESI ): m/z [M+H]
calculated for C21 : 362.0578; found: 362.0566.
H
12ClNO
3
6a-(4-Bromophenyl)-5H-benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-dione (3e): White solid; mp: 226-
o
-1
with 20 mL saturated NaHCO
by distilled water (2x15 mL). The organic layer was
separated, dried over solid anhydrous Na SO and
3
solution 2 times, followed
228 C. 52% yield. IR (KBr) νmax (cm ): 3086, 3058, 2925,
1729, 1702, 1606, 1485, 1363, 1252, 1148, 1068, 1016,
1
761. H NMR (400 MHz, CDCl
3
): δ 8.13 (1H , d, J = 8.1
2
4
concentrated on a rotary evaporator to obtain the crude
product which was purified on a silica gel column using
hexane/ethyl acetate as eluent to give the pure targeted
product.
Hz), 7.99 (2H, t, J = 6.2 Hz), 7.70 (1H, t, J = 7.6 Hz), 7.65-
7.58 (m, 2H),7.48 (1H, d, J = 7.2 Hz) 7.42 (4H, dd, J =
20.2, 8.4 Hz), 7.26 (1H, t, J = 7.5 Hz,). 13C NMR (100
MHz, CDCl
3
): δ 165.67, 162.21, 144.52, 136.71, 136.44,
5
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901142
1
1
36.12, 134.37, 132.65, 131.06, 130.89, 129.28, 127.46,
25.86, 125.05, 124.12, 123.57, 121.27, 116.08, 94.14.
Hz, 1H), 7.65-7.57 (m, 5H), 7.47 (t, J = 7.6 Hz, 2H), 7.35
(d, J = 6.8 Hz, 3H). C NMR (100 MHz, CDCl ): δ 165.60,
3
13
+
+
HRMS (ESI ): m/z [M+H] calculated for C21
4
H
12BrNO
3
:
161.31, 156.37, 153.82, 145.19, 136.42, 134.25, 131.04,
129.98, 129.50, 127.54, 126.13, 125.81, 125.14, 123.99,
06.0073; found: 406.0081.
+
+
1
23.37, 123.18, 119.15, 95.38. HRMS (ESI ): m/z [M+H]
6
a-(3,4-Dichlorophenyl)-5H-benzo[4,5][1,3]oxazino[2,3-
calculated for C21 : 346.0874; found: 346.0801.
H
12 FNO
3
a]isoindole-5,11(6aH)-dione (3f): White solid; mp: 167-
1
1
o
-1
69 C; 69% yield. IR (KBr) νmax (cm ): 3067, 2925, 1774,
3
-Iodo-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
1
736, 1604, 1484, 1466, 1363, 1247, 1064, 1015, 748. H
a]isoindole-5,11(6aH)-dione (3k): Yellow solid; mp: 223-
NMR (400 MHz, CDCl
3
): δ 8.14 (d, J = 7.8 Hz, 1H), 8.01
o
-1
2
1
25 C; 47% yield. IR (KBr) νmax (cm ): 1728, 1593, 1477,
(
t, J = 7.5 Hz, 2H), 7.73 (t, J = 7.1 Hz, 1H), 7.66-7.62 (m,
1
409, 1361, 1222, 1064, 754, 692, 513. H NMR (400
2
1
1
1
1
H), 7.50 (d, J = 6.7 Hz, 1H), 7.40 (s, 2H), 7.31-7.27 (m,
H). 13C NMR (100 MHz, CDCl
): δ 165.60, 161.88,
MHz, CDCl
m), 7.66-7.58 (2H, m), 7.50 (3H, t, J = 8.3 Hz), 7.36-7.31
3H, m). 13C NMR (100 MHz, CDCl
) δ 165.63, 161.13, ,
44.88, 144.52, 139.30, 137.13, 136.17, 134.44, 131.00,
29.90, 129.53, 129.10, 125.66, 125.01, 123.71, 122.91,
3
): δ 8.31 (1H, d, J = 1.7 Hz), 8.00-7.93 (3H,
3
44.21, 137.98, 136.32, 134.52, 134.37, 134.02, 131.53,
31.28, 131.03, 129.23, 127.81, 126.05, 125.21, 125.14,
(
3
1
1
1
+
+
23.56, 121.37, 115.91, 93.49. HRMS (ESI ): m/z [M+H]
NO : 396.0189; found: 396.0182.
calculated for C21
H
11Cl
2
3
+
+
17.81, 94.55,88.96. HRMS (ESI ): m/z [M+H]
: 453.9935; found: 453.9861.
9
-Methyl-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
calculated for C21
H
12INO
3
a]isoindole-5,11(6aH)-dione (3g): White solid; mp: 189-
3
-Bromo-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
o
-1
1
1
91 C. 70% yield. IR (KBr) νmax (cm ): 3059, 2922, 1746,
718, 1604, 1486, 1361, 1238, 1041, 759. H NMR (400
a]isoindole-5,11(6aH)-dione (3l): White solid; mp: 185-
1
1
1
o
-1
87 C. 64% yield. IR (KBr) νmax (cm ): 3056, 2925, 1753,
MHz, CDCl
7
7
3
): δ 8.14 (1H, d, J = 7.8 Hz), 7.98 (1H, d, J =
.3 Hz), 7.86 (1H, d, J = 7.4 Hz), 7.67 (1H, t, J = 7.1 Hz),
.53 (2H, d, J = 6.2 Hz), 7.37 (1H, d, J = 7.4 Hz), 7.30 (4H,
1
731, 1690, 1603, 1482, 1364, 1224, 1066, 1016, 756. H
NMR (400 MHz, CDCl
1H, d, J = 8.6 Hz), 7.99 (1H, d, J = 7.2 Hz), 7.79 (1H, dd,
J = 8.8, 2.2 Hz), 7.66-7.58 (2H, m), 7.52-7.48 (3H, m),
3
): δ 8.12 (1H, d, J = 2.1 Hz), 8.07
(
1
3
s), 7.24-7.20 (1H, m), 2.42 (3H, s). C NMR (100 MHz,
CDCl ): δ 165.93, 162.59, 145.56, 145.42, 137.70, 136.84,
35.89, 131.79, 130.77, 129.60, 129.37, 126.79, 125.75,
25.47, 124.74, 124.10, 121.22, 116.27, 94.43, 22.21.
3
7
1
1
1
.35-7.31 (3H, m). 13C NMR (100 MHz, CDCl
3
): δ 165.69,
1
1
61.37, 144.85, 138.82, 137.11, 135.59, 134.47, 133.42,
31.02, 129.93, 129.54, 129.11, 125.68, 125.03, 123.75,
+
+
3
HRMS (ESI ): m/z [M+H] calculated for C22H15NO :
+
+
22.86, 118.66, 117.76, 94.64. HRMS (ESI ): m/z [M+H]
: 406.0073; found: 406.0088.
3
42.1125; found: 342.1127.
calculated for C21H12BrNO
3
9
-Chloro-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
2
-Bromo-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-dione (3h): White solid; mp: 245-
2
1
a]isoindole-5,11(6aH)-dione (3m): Pale yellow solid; mp:
1
1
o
-1
47 C. 67% yield. IR (KBr) νmax (cm ): 3050, 2925, 1748,
o
-1
82-184 C; 67% yield IR (KBr) νmax (cm ): 3062, 2924,
1
736, 1719, 1602, 1485, 1363, 1248, 1065, 1024, 756. H
1
730, 1593, 1433, 1346, 759, 694. H NMR (400 MHz,
NMR (400 MHz, CDCl
3
): δ 8.12 (d, J = 8.1 Hz, 1H), 7.98
CDCl
3
): δ 8.37 (1H, s), 8.00 (1H, d J = 7.0 Hz), 7.84 (1H,
(
d, J = 7.7 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.69 (t, J =
d, J = 8.4 Hz), 7.66-7.58 (2H, m), 7.52-7.49 (3H, m), 7.37
7
7
1
1
.6 Hz, 2H), 7.55-7.48 (m, 4H), 7.32 (d, J = 6.6 Hz, 3H),
13
(
1H, d J = 8.7 Hz ), 7.32 (3H, t, J = 6.7 Hz). C NMR (100
MHz, CDCl ): δ 165.62, 161.99, 144.95, 137.40, 137.20,
34.50, 131.99, 130.99, 130.95, 129.87, 129.54, 129.10,
29.01, 125.67, 125.10, 124.17, 123.73, 115.01 94.65,
1
3
3
.25-7.22 (m, 1H). C NMR (100 MHz, CDCl ): δ 164.77,
3
62.04, 146.47, 140.68, 136.82, 136.41, 136.06, 131.47,
30.90, 130.00, 129.60, 127.77, 126.14, 125.88, 125.69,
1
1
2
+
1
24.25, 121.21, 116.21, 93.94. HRMS (ESI ): m/z [M+H]
+
+
1.22. HRMS (ESI ): m/z [M+H]
: 406.0073; found: 406.0091.
calculated for
+
calculated for C21
3
H12ClNO : 362.0578; found: 362.0579.
21 3
C H12BrNO
2
-Fluoro-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
9-Nitro-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-dione (3i): Light grey solid; mp:
a]isoindole-5,11(6aH)-dione (3n): Yellow solid; mp: 205-
o
-1
o
-1
2
1
7
05-207 C; 72% yield. IR (KBr) νmax (cm ): 1724, 1608,
593, 1492, 1456, 1355, 1315, 1257, 1055, 1012, 810, 790,
207 C; 44% yield. IR (KBr) νmax (cm ): 2924, 2854, 1734,
1
1600, 1529, 1487, 1346, 1253, 1014,765, 696. H NMR
1
58, 742, 698, 686, 640, 611. H NMR (400 MHz, CDCl
3
):
(400 MHz, CDCl
13.5 Hz), 8.29-8.15 (2H, m), 8.02 (1H, d, J = 7.5 Hz),
.58 (2H, m), 7.52 (3H, dd, J = 7.1, 5.1 Hz), 7.36-7.30 (3H, 7.91-7.72 (2H, m), 7.62-7.53 (2H, m), 7.37-7.29 (3H, m).
3
): δ 8.51-8.46 (1H, m), 8.36 (1H, d, J =
δ 8.03-7.99 (2H, m), 7.91 (1H, dd, J = 9.4, 2.4 Hz), 7.66-
7
1
3
13
m), 6.93 (1H, td, J = 8.5, 2.4 Hz). C NMR (100 MHz,
CDCl ): δ 168.43, 165.87, 165.68, 161.72, 144.98, 138.67,
38.54, 137.35, 134.52, 133.60, 133.49, 130.98, 129.84,
3
C NMR (100 MHz, CDCl ): δ 163.44, 161.47, 151.59,
3
146.10, 137.06, 136.24, 135.99, 134.50, 131.09, 130.41,
129.87, 129.40, 127.81, 126.42, 126.18, 125.68, 124.04,
1
1
+
+
29.51, 129.04, 125.62, 125.07, 123.74, 113.60, 113.38,
121.21, 119.42, 116.28, 94.18 HRMS (ESI ): m/z [M+H]
calculated for C21 : 373.0819; found: 373.0748.
+
1
12.53, 108.71, 108.44, 94.70, . HRMS (ESI ): m/z [M+H]
12 2 5
H N O
+
calculated for C21
3
H12FNO : 346.0874; found: 346.0802.
2
-Nitro-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
1
-Fluoro-6a-phenyl-5H-benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-dione (3o): White solid; mp: 256-
o
-1
a]isoindole-5,11(6aH)-dione(3j): Pale yellow solid; mp:
2
1
258 C; 46% yield. IR (KBr) νmax (cm ): 2924, 1737, 1612,
o
-1
1
24-226 C; IR (KBr) νmax (cm ): 2924, 1737, 1612, 1494,
1494, 1467, 1346, 1278, 1124, 754, 696. H NMR (400
1
467, 1346, 1278, 1124, 950, 754, 696. H NMR (400
3
MHz, CDCl ): δ 9.01 (1H, d, J = 2.0 Hz), 8.19 (1H, d, J =
MHz, CDCl
3
): δ 8.00 (d, J = 7.1 Hz, 1H), 7.82 (d, J = 7.7
8.6 Hz), 8.06-8.03 (2H, m), 7.71-7.63 (2H, m), 7.56-7.50
6
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901142
(
3H, m), 7.38-7.31(3H, m). 13C NMR (100 MHz, CDCl
δ 165.56, 160.94, 152.14, 144.69, 137.50, 136.67, 134.86,
3
):
6a-(4-Methoxyphenyl)-9-methyl-5H-
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-dione
o
1
1
[
32.28, 131.29, 130.17, 129.71, 128.63, 125.73, 125.35,
(3t): White solid; mp: 157-159 C; 45% yield. IR (KBr)
+
-1
23.85, 120.68, 119.90, 116.59, 94.94. HRMS (ESI ): m/z
ν
max (cm ): 1728, 1608, 1477, 1365, 1249, 1166, 1022, 763.
+
1
M+H] calculated for C21
H
12
N
2
O
5
: 373.0819; found:
H NMR (400 MHz, CDCl
7.99 (1H, dd, J = 7.8, 1.1 Hz), 7.85 (1H, d, J = 7.8 Hz),
.70-7.66 (1H, m), 7.44-7.42 (2H, m), 7.37 (1H, d, J = 7.8
3
): δ 8.14 (1H, d, J = 8.1 Hz),
3
73.0745.
7
6
a-(4-Bromophenyl)-9-Chloro-5H-
Hz), 7.30 (1H, s), 7.23 (1H, t, J = 7.6 Hz), 6.82 (2H, d, J =
8.9 Hz), 3.73 (3H, s), 2.42 (3H, s). 13C NMR (100 MHz,
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-dione
o
(
3p): White solid; mp: 131-133 C; 48% yield. IR (KBr)
3
CDCl ): δ 165.93, 162.73, 160.48, 145.73, 145.52, 136.83,
-
1
ν
max (cm ): 2926, 1730, 1604, 1487, 1363, 1249, 1066,
135.84, 131.68, 130.73, 129.45, 127.19, 126.71, 125.43,
124.69, 123.99, 121.25, 116.41, 114.71, 94.48, 55.40,
1
1
8
014, 966, 769, 752, 677. H NMR (400 MHz, CDCl
3
): δ
+
+
.11 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.92 (d,
22.24. HRMS (ESI ): m/z [M+H]
23 4
C H17NO : 372.1230; found: 372.1154.
calculated for
J = 8.1 Hz, 1H), 7.71 (t, J = 8.1 Hz, 1H), 7.58 (d, J = 8.2
Hz, 1H), 7.48 (d, J = 8.4 Hz, 3H), 7.38 (d, J = 8.7 Hz, 2H),
7
1
1
1
3
.29 (d, J = 7.6 Hz, 1H). C NMR (100 MHz, CDCl
3
): δ
9-Nitro-6a-(p-tolyl)-5H-benzo[4,5][1,3]oxazino[2,3-
a]isoindole-5,11(6aH)-dione (3u): Pale yellow solid; mp:
65.57, 148.40, 138.90, 136.50, 135.28, 134.70, 131.95,
28.91, 128.11, 127.57, 127.41, 121.80, 116.66, 94.48
o
-1
185-187 C; 52% yield. IR (KBr) νmax (cm ): 2924, 2852,
+
+
HRMS (ESI ): m/z [M+H]
C
calculated for
1732, 1604, 1537, 1487, 1367, 1344, 1244, 1064, 1020,
1
21
H
11BrClNO : 439.9684; found: 439.9612.
3
854, 767, 671. H NMR (400 MHz, CDCl
3
): δ 8.46 (1H, dd,
J = 8.3, 1.9 Hz), 8.33 (1H, d, J = 1.7 Hz), 8.16 ( 2H, d, J =
8.2 Hz), 8.03 (1H, d, J = 7.8 Hz), 7.73 (1H, t, J = 7.1 Hz),
9
-Chloro-6a-(4-chlorophenyl)-5H-
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-dione
7.41 (2H, d, J = 8.3 Hz), 7.30 (1H, t, J = 7.6 Hz), 7.16 (2H,
o
13
(
ν
6
3q): White solid; mp: 179-181 C; 59% yield. IR (KBr)
d, J = 8.1 Hz), 2.28 (3H, s). C NMR (100 MHz, CDCl
3
):
-
1
max (cm ): 1734, 1606, 1481, 1365, 1311, 1244, 1016, 759,
δ 163.45, 161.56, 151.63, 146.34, 142.00, 140.67, 136.15,
135.05, 134.49, 133.00, 131.07, 130.55, 126.41, 126.31,
126.12, 125.63, 121.21, 119.39, 116.41, 94.04, 27.06,
1
71, 601. H NMR (400 MHz, CDCl
3
): δ 8.11 (d, J = 8.1
Hz, 1H), 8.00 (dd, J = 7.8, 0.8 Hz, 1H), 7.92 (d, J = 8.1 Hz,
+
+
1
7
H), 7.73-7.69 (m, 1H), 7.57 (dd, J = 8.1, 1.5 Hz, 1H),
.47 (d, J = 8.8 Hz, 3H), 7.38 (d, J = 8.6 Hz, 2H), 7.29 (d,
HRMS (ESI ): m/z [M+H] calculated for C22
387.0975; found: 387.0901.
14 2 5
H N O :
1
3
J = 7.6 Hz, 1H). C NMR (100 MHz, CDCl
3
):`1 δ 164.60,
2
-Fluoro-6a-(p-tolyl)-5H-benzo[4,5][1,3]oxazino[2,3-
1
1
1
61.71, 146.02, 140.88, 136.23, 136.07, 132.87, 131.69,
31.00, 127.69, 127.43, 126.27, 126.06, 124.51, 124.14,
21.25, 116.04, 93.55.HRMS (ESI+): m/z [M+H]
a]isoindole-5,11(6aH)-dione (3v): White solid; mp: 193-
o
-1
1
1
95 C; 54% yield. IR (KBr) νmax (cm ): 1728, 1608, 1492,
+
1
458, 1357, 1315, 1257, 1184, 1056, 748, 680, 642. H
2 3
calculated for C21H11Cl NO : 396.0189; found: 396.0117.
NMR (400 MHz, CDCl
1H, m), 7.66-7.58 (2H, m), 7.53-7.51 (1H, m), 7.38 (2H, d,
J = 7.4 Hz), 7.13 (2H, d, J = 8.1 Hz), 6.96-6.91 (1H, m),
3
): δ 8.04-7.98 (2H, m), 7.91-7.88
(
9
-Chloro-6a-(3,4-dichlorophenyl)-5H-
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-dione
13
2
1
1
1
3
.27 (3H, s). C NMR (100 MHz, CDCl ): δ 168.49,
(
(
1
8
3r): Pale yellow solid; mp: 216-218oC; 37% yield. IR
66.04, 162.30, 145.06, 140.09, 138.47, 134.67, 134.04,
33.66, 130.99, 130.23, 128.82, 125.50, 125.09, 123.71,
-
1
KBr) νmax (cm ): 3076, 2924, 2854, 1732, 1602, 1485,
1
361, 1246, 1022,763, 677. H NMR (400 MHz, CDCl
3
): δ
+
13.73, 112.51, 108.77, 94.96, 21.22. HRMS (ESI ): m/z
.12 (1H, d, J = 8.2 Hz), 8.03 (1H, d, J = 7.1 Hz), 7.93
[
M+H] + calculated for C22
H14FNO : 360.1030; found:
3
(
1H, d, J = 8.1 Hz), 7.73 (1H, t, J = 7.2 Hz), 7.60-7.56 (2H,
3
60.0954.
-Bromo-6a-(4-methoxyphenyl)-5H-
13
m), 7.46-7.37 (3H, m), 7.30 (1H, t, J = 7.6 Hz). C NMR
100 MHz, CDCl ): δ 164.52, 161.38, 145.68, 141.05,
37.29, 136.42, 136.08, 134.78, 134.25, 131.90, 131.73,
(
3
2
1
1
1
benzo[4,5][1,3]oxazino[2,3-a]isoindole-5,11(6aH)-dione
31.12, 127.72, 127.60, 126.41, 125.12, 124.16, 121.34,
o
(
ν
1
3w): White solid; mp: 132-134 C; 48 % yield. IR (KBr)
+
15.84, 92.89. HRMS (ESI+): m/z [M+H] calculated for
-
1
max (cm ): 3072, 2922, 2852, 1726, 1591, 1514, 1467,
431, 1342, 1242, 1033, 883, 754, 675, 599, 555. H NMR
C
21
H
3
11Cl NO
3
: 429.9799; found: 429.9722.
1
9
-Methyl-6a-(p-tolyl)-5H-benzo[4,5][1,3]oxazino[2,3-
(400 MHz, CDCl ): δ 8.36 (1H, d, J = 1.8 Hz), 7.99 (1H, d
3
a]isoindole-5,11(6aH)-dione (3s): White solid; mp: 181-
J = 6.9 Hz ), 7.85 (1H, d, J = 8.4 Hz), 7.66-7.57 (2H, m ),
o
-1
1
1
83 C. 62% yield. IR (KBr) νmax (cm ): 1722, 1606, 1487,
465, 1363, 1064, 1022, 767, 754. H NMR (400 MHz,
7.51 (1H , d, J = 7.4 Hz), 7.44-7.33 (3H, m), 6.83 (2H, d, J
1
13
= 8.9 Hz), 3.74 (3H, s). C NMR (100 MHz, CDCl
3
): δ
CDCl
3
): δ 8.14 (1H, d, J = 8.5 Hz), 7.98 (1H, d, J = 7.9
164.62, 161.14, 159.68, 144.26, 136.38, 133.48, 130.93,
129.87, 128.06, 127.90, 126.13, 124.04, 123.20, 122.62,
Hz), 7.85 (1H, d, J = 7.8 Hz), 7.69-7.65 (1H, m), 7.38 (3H,
dd, J = 14.2, 7.9 Hz), 7.30 (1H, s), 7.22 (1H, t, J = 7.7 Hz),
+
+
114.15 113.87, 93.71, 55.44, HRMS (ESI ): m/z [M+H]
calculated for C22 : 436.0179; found: 436.0107.
7
.12 (2H, d, J = 8.3 Hz), 2.41 (3H, s), 2.26 ( 3H, s). 13
C
H14BrNO
4
3
NMR (100 MHz, CDCl ): δ 165.94, 162.70, 145.58,
2
-Bromo-6a-(p-tolyl)-5H-benzo[4,5][1,3]oxazino[2,3-
1
1
1
45.52, 139.69, 136.86, 135.84, 134.68, 131.71, 130.75,
30.07, 126.76, 125.68, 125.42, 124.70, 124.03, 121.20,
16.33, 94.51, 22.22, 21.22. HRMS (ESI ): m/z [M+H]
: 356.1281; found: 356.1268.
a]isoindole-5,11(6aH)-dione (3x): Light pink solid; mp
2
1
o
-1
21-223 C; 49 % yield. IR (KBr) νmax (cm ): 1732, 1602,
+
+
1
3
473, 1435, 1350, 756, 671, H NMR (400 MHz, CDCl ):
calculated for C23H17NO
3
δ 8.36 (1H, d, J = 1.8 Hz), 7.99 (1H, dd J = 7.3, 0.9 Hz ),
7
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Advanced Synthesis & Catalysis
10.1002/adsc.201901142
7
.84 (1H, d, J = 8.4 Hz), 7.65-7.57 (2H, m ), 7.51 (1H , d,
Ferland, C. A. Demerson, L. G. Humber, Can. J. Chem.
1985, 63, 361-365.
J = 7.4 Hz), 7.38-7.35 (3H, m), 7.13 (2H, d, J = 8.01 Hz),
1
3
3
1
1
1
3
.74 (3H, s). C NMR (100 MHz, CDCl ): δ 165.64,
[
3] a) D. L. Boger, J. K. Lee, J. Goldberg, Q. Jin, J. Org.
Chem. 2000, 65, 1467-1474; b) M. S. Egbertson, G. D.
Hartman, R. J. Gould, R. A. Bednar, J. J. Cook, S. L.
Gaul, M. A. Holahan, L. A. Libby, J. J. Lynch, G. R.
Sitko, M. T. Stranieri, L. M. Vassallo, Bioorg. Med.
Chem. Lett. 1996, 6, 2519-2524.
62.11, 145.10, 140.02, 137.40, 134.48, 134.16, 131.96,
30.91, 130.21, 129.05, 128.97, 125.60, 125.04, 124.16,
+
+
23.66 115.07, 94.74, 21.22, HRMS (ESI ): m/z [M+H]
: 420.0230; found: 420.0217
calculated for C22H12BrNO
3
[
[
4] W. Lippmann, U.S. Patent 4,267,189, 1981. Chem.
Acknowledgements
Abstr. 1981, 95, 61988m.
The authors acknowledge financial assistance from the
Science Engineering Research Board (SERB,
5] a) N. Slavov, J. Cvengroꢁ, J. Neudꢂerfl, H. Schmalz,
Angew. Chem., Int. Ed. 2010, 49, 7588-7591; b) E. Li,
L. Jiang, L. Guo, H. Zhang, Y. Che, Bioorg. Med.
Chem. 2008, 16, 7894-7899.
&
SB/SO/BB-0092/2013). P.K. thanks the University Grants
Commission (UGC, New Delhi, India) for providing Senior
Research Fellowship. M. G. thanks the CSIR (New Delhi,
India) for providing Senior Research Fellowship. Authors
are thankful to (USIC) University Science Instrumentation
Centre, University of Delhi, Delhi, India. The authors also
[6] K. Achinami, N. Ashizawa, F. Kobayasui, Japanese
Patent 03,133,955, 1991; Chem. Abstr. 1991, 115,
255977j.
acknowledge
AIRF
and
DBT
grant
(no.
[
7] a) Z. Zhuang, M. Kung, M. Mu, H. F. Kung, J. Med.
Chem. 1998, 41, 157-166; b) M. H. Norman, D. J.
Minick, G. C. Rigdon, J. Med. Chem. 1996, 39, 149-
BT/PR3130/INF/22/139/2011 for providing EPR facility.
1
57.
References
[
[
8] A. Buttinoni, M. Ferrari, M. Colombo, R. J. Ceserani,
[
1] a) E. Y. Moon, J. M. Oh, Y. H. Kim, I. J. Ryoo, I. D.
Yoo, Biol. Pharm. Bull. 2009, 32, 1689-1694; b) C.
Maugeri, M. A. Alisi, C. Apicella, L. Cellai, P.
Dragone, E. Fioravanzo, S. Florio, G. Furlotti, G.
Mangano, R. Ombrato, R. Luisi, R. Pompei, V.
Rincicotti, V. Russo, M. Vitiello, N. Cazzolla, Bioorg.
Med. Chem. 2008, 16, 3091-3107; c) E. C. Lawson, D.
K. Luci, S. Ghosh, W. A. Kinney, C. H. Reynolds, J.
Qi, C. E. Smith, Y. Wang, L. K. Minor, B. J.
Haertlein, T. J. Parry, B. P. Damiano, B. E. Maryanoff,
J. Med. Chem. 2009, 52, 7432-7445; d) H. M. B. Cid, C.
Tränkle, K. Baumann, R. Pick, E. Mies-Klomfass, E.
Kostenis, K. Mohr, U. Holzgrabe, J. Med. Chem. 2000,
Pharm. Pharmacol. 1983, 35, 603-604.
9] a) C. Riedinger, J. A. Endicott, S. J. Kemp, L. A.
Smyth, A. Watson, E. Valeur, B. T. Golding, R. J.
Griffin, I. R. Hardcastle, M. E. Noble, J. M. McDonnell,
J. Am. Chem. Soc. 2008, 130, 16038-16044; b) E. C.
Taylor, P. Zhou, L. D. Jennings, Z. Mao, B. Hu, J. G.
Jun, Tetrahedron Lett. 1997, 38, 521-524.
[
10] a) X. Wu, B. Wang, Y. Zhou, H. Liu, Org. Lett. 2017,
1
9, 1294-1297; b) S. Dhanasekaran, A. Suneja, V. Bisai,
V. K. Singh, Org. Lett. 2016, 18, 634-637; c) S.
Dhanasekaran, A. Kayet, A. Suneja, V. Bisai, V. K.
Singh, Org. Lett. 2015, 17, 2780-2783; d) Y. Zhang, D.
Wang, S. Cui, Org. Lett. 2015, 17, 2494-2497; e) V.
Bisai, R. A. Unhale, A. Suneja, S. Dhanasekaran, V. K.
Singh, Org. Lett. 2015, 17, 2102-2105; f) H. S. P. Rao,
A. V. B. Rao, J. Org. Chem. 2015, 80, 1506-1516; g) D.
M. Shacklady-McAtee, S. Dasgupta, M. P. Watson,
Organometallics 2015, 34, 1802-1805; h) H. J. Li, Y. Q.
Zhang, L. F. Tang, Tetrahedron 2015, 71, 7681-7686. i)
S. Adachi, M. Onozuka, Y. Yoshida, M. Ide, Y.
Saikawa, M. Nakata, Org. Lett. 2014, 16, 358-361; j) S.
Dhanasekaran, V. Bisai, R. A. Unhale, A. Suneja, V. K.
Singh, Org. Lett. 2014, 16, 6068-6071; k) D. M.
Shacklady-McAtee, S. Dasgupta, M. P. Watson, Org.
Lett. 2011, 13, 3490-3493.
4
3, 2155-2164; e) Z. P. Zhuang, M. P. Kung, H. F.
Kung J. Med. Chem. 1998, 41, 157-166; f) E. D. Clercq,
J. Med. Chem. 1995, 38, 2491-2517;
[
2] a) Q. Xiao, K. Young, A. Zakarian, Org. Lett. 2013, 15,
3
314-3317; b) M. V. Tejesvi, A. M. Pirttilꢀ, In
Endophytes of Forest Trees: Biology and Applications.
Forestry Sciences; Pirttilꢀ, A. M., Frank, A. C., Eds.;
Springer: Berlin, 2011, 80, 302; c) N. J. Lawrence, J.
Liddle, S. M. Bushell, D. A. Jackson, J. Org. Chem.
2
002, 67, 457-464; d) A. Couture, E. Deniau, P.
Grandclaudon, C. Hoarau, V. Rys, Tetrahedron Lett.
002, 43, 2207-2210; e) K. W. Bentley, In The
2
Isoquinoline Alkaloids; Ravindranath, B., Ed.;
Harwood Academic: Amsterdam, 1998, 361-375; f) J.
L. Wood, B. M. Stoltz, S. N. Goodman, J. Am. Chem.
Soc. 1996, 118, 10656-10657; g) F. G.Fang, S. J.
Danishefsky, Tetrahedron Lett. 1989, 30, 2747-2750;
h) Z. L. Chen, D. Y. Zhu, In The Alkaloids: Chemistry
and Pharmacology; Brossi, A., Ed.; Academic Press:
New York, 1987, 31, 29-62; i) E. Valencia, A. J. Freyer,
M. Shamma, V. Fajardo, Tetrahedron Lett. 1984, 25,
[
[
11] P. Kumar, M. Gupta, V. Bahadur, V. S. Parmar, B. K.
Singh, Eur. J. Org. Chem. 2018, 1552-1558.
12] a) Y. Wei, P. Hu, M. Zhang, W. Su, Chem. Rev. 2017,
1
17, 8864-8907; b) K. Bharathimohan, T. Ponpandian,
A. A. Jafar, Eur. J. Org. Chem. 2017, 2806-2813.
[
13] a) J. K. Laha, K. V. Patel, S. Sharma, ACS Omega
2
017, 2, 3806-3815; b) Y. Wu, L. Sun, Y. Chen, Q.
Zhou, J. W. Huang, H. Miao, H. B. Luo, J. Org. Chem.
016, 81, 1244-1250; c) X. Chen, X. Cui, Y. Wu, Org.
5
99-602; j) V. Fajardo, V. Elango, B. K. Cassels, M.
Shamma, Tetrahedron Lett. 1982, 23, 39-42; k) J. M.
2
Lett. 2016, 18, 3722-3725; d) K. Yang, X. Chen, Y.
8
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901142
Wang, W. Li, A. A. Kadi, H. K. Fun, H. Sun, Y. Zhang,
G. Li, H. Lu, J. Org. Chem. 2015, 80, 11065-11072; e)
Z. Y. Li, D. D. Li, G. W. Wang, J. Org. Chem. 2013,
8094-8102; h) H. Wang, L. N. Guo, X. H. Duan, Adv.
Synth. Catal. 2013, 355, 2222-2226; i) Z. Yin, P. Sun, J.
Org. Chem. 2012, 77, 11339-11344.
7
3
2
8, 10414-10420; f) M. Li, H. Ge, Org. Lett. 2010, 12,
464-3467; g) P. Fang, M. Li, H. Ge, J. Am. Chem. Soc.
010, 132, 11898-11899.
[
[
15] B. Majhi, D. Kundu, T. Ghosh, B. C. Ranu, Adv.
Synth. Catal. 2016, 358, 283-295.
16] H. Song, D. Chen, C. Pi, X. Cui, Y. Wu, J. Org.
Chem. 2014, 79, 2955-2962.
[
14] a) J. T. Yu, C. Pan, Chem. Commun. 2016, 52, 2220-
236; b) S. S. Wang, H. Fu, Y. Shen, M. Sun, Y. M. Li,
2
J. Org. Chem. 2016, 81, 2920-2929; c) Q. Jiang, J. Jia,
B. Xu, A. Zhao, C. C. Guo, J. Org. Chem. 2015, 80,
[17]CCDC-1875673 (3l) and CCDC-1811270 (4) contain
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
3
586-3596; d) Z. Chen, B. Wang, J. Zhang, W. Yu, Z.
Liu, Y. Zhang, Org. Chem. Front. 2015, 2, 1107-1295;
e) F. Luo, J. Yang, Z. Li, H. Xiang, X. Zhou, Eur. J.
Org. Chem. 2015, 2463-2469; f) J. Liu, C. Fan, H. Yin,
C. Qin, G. Zhang, X. Zhang, H. Yi, A. Lei, Chem.
Commun. 2014, 50, 2145-2147; g) W. P. Mai, G. C.
Sun, J. T. Wang, G. Song, P. Mao, L. R. Yang, J. W.
Yuan, Y. M. Xiao, L. B. Qu, J. Org. Chem. 2014, 79,
9
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FULL PAPER
Palladium-Catalyzed Decarboxylative Synthesis
of
5H-Benzo[4,5][1,3]oxazino[2,3-a]isoindole-
5
,11(6aH)-diones
using
2-Phenyl-4H-
and -Oxo
benzo[d][1,3]oxazin-4-ones
Carboxylic Acids
Adv. Synth. Catal. Year, Volume, Page – Page
Ram Sunil Kumar Lalji, Prashant Kumar, Mohit
Gupta, Virinder S. Parmar, Brajendra K. Singh*
1
0
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