Synthesis of (E)-3-(2-Oxo-2-arylethylidene)indolin-2-ones through Alkyne Carbonyl Metathesis and Their Stereospecific Application towards Spiro-oxindolopyrrolizidine Scaffolds

Article abstract of DOI:10.1002/ejoc.201701606

An iron-salt catalyzed, atom economic, unfamiliar type of alkyne carbonyl metathesis strategy has been developed by using isatins and acetylenes for the regioselective synthesis of (E)-3-(2-oxo-2-arylethylidene)indolin-2-one derivatives, which has been further utilized to develop a catalyst-free methodology for the synthesis of biologically active spiro-oxindolopyrrolizidine scaffolds in a highly regio- and stereospecific manner by reacting with l-proline and aldehydes. Both methods are acceptable towards various functionalities that include electron-donating and electron-accepting groups at the ortho-, meta- and para-positions. This protocol provides an environmentally friendly reaction methodology for the synthesis of a series of (1′S,2′R,3′R,7a′R)-1′,3′,5′,6′,7′,7a′-hexahydrospiro[indoline-3,2′-pyrrolizin]-2-ones.

Full text of DOI:10.1002/ejoc.201701606

A Journal of
Accepted Article
Title: Synthesis of (E)-3-(2-Oxo-2-Arylethylidene)Indolin-2-ones
Through Alkyne Carbonyl Metathesis and Their Stereospecific
Application Towards Spiro-Oxindolopyrrolizidine Scaffolds
Authors: Soumyadip Basu and Chhanda Mukhopadhyay
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701606
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
Synthesis
of
(E)-3-(2-Oxo-2-Arylethylidene)Indolin-2-ones
Through Alkyne Carbonyl Metathesis and Their Stereospecific
Application Towards Spiro-Oxindolopyrrolizidine Scaffolds
Soumyadip Basu [a] and Chhanda Mukhopadhyay [a]*
Abstract : An iron salt catalysed, atom economic, unfamiliar type of
alkyne carbonyl metathesis strategy has been developed using
isatins and acetylenes, for the regioselective synthesis of (E)-3-(2-
oxo-2-arylethylidene)indolin-2-one derivatives, which has been
further utilised to develop a catalyst-free methodology for the
synthesis of biologically active spiro-oxindolopyrrolizidine scaffolds in
a highly regio and stereospecific manner, by reacting with L- proline
and aldehydes. Both the methods are acceptable towards various
functionalities including electron donating as well as electron
accepting groups at ortho, meta and para positions. This protocol
provides an environment-friendly reaction methodology for the
Carbonyl group at the C-3 position of the isatin ring has high
reactivity[9]. Utilising this reactivity and the affinity of oxygen
towards the metal salts, we were able to involve the metathesis
strategy towards the synthesis of α, β-unsaturated carbonyl
moieties at the C-3 position of the isatin ring by reacting it with
phenyl acetylene, in presence of metal salt catalyst (Scheme-1).
R2
O
X
O
FeCl3
80 o
X
R2
+
O
N
C
R1
N
O
synthesis of
a
series of (1'S,2'R,3'R,7a'R)-1',3',5',6',7',7a'-
R1
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones.
3
1
2
Introduction
Scheme 1 : Preparation of the (E)-3-(2-oxo-2-arylethylidene)indolin-2-ones
using FeCl3 as catalyst
Nowadays, alkyne carbonyl metathesis strategy has become a
very effective approach towards the build-up of α, β-unsaturated
carbonyl frameworks. This process generally involves 1, 3
oxygen shift[1] via [2 + 2] cycloaddition followed by cycloreversion.
Thus, the migration will be favoured by those factors which
activate the carbonyl moiety. In this regard, use of transition
metal salts as catalyst can be extremely effective as oxygen has
very high affinity towards them. This fact has certainly increased
the interest in this scenario and many such reactions have been
developed involving salts of various metals such as Fe,[2]
Ag,[3] Pt,[4] Cu,[5] etc. Some other methods are also known which
involves non-metallic acids as the active catalyst[6]. We were
actually very reluctant to use such kind of reagent for this
transformation as use of strong acid or base might affect the
isatin ring[7]. On the other hand, the use of transition metal salts
allowed us to carry out the conversion under mild and enviro-
friendly condition, without disturbing the stability of the starting
materials. In addition, it also reduced the total number of steps
and the overall time of conversion and thus offered a much
better alternative towards this procedure. Among all the
transition metals, iron salts were automatically chosen as the
most priority catalyst due to its easy availability, lower price and
eco-friendly sustainable chemistry along with its high binding
probability with oxygen. This one step transformation also
results in a completely atom-economical approach compared to
the other possibilities[8].
On further turning our attention ahead, cycloaddition between
the so formed (E)-3-(2-oxo-2-arylethylidene)indolin-2-one
derivatives and the 1,3 dipolar azomethine, generated from an
aldehyde and L-proline, resulted in the formation of biologically
active spiro-oxindolopyrrolizidine scaffolds, with high stereo and
regiospecificly (Scheme - 2). Previous works were reported with
(E)-3-(2-oxo-2-arylethylidene)indolin-2-ones and azomethines of
various active carbonyls[10]. In this regard, our work increases
the diversity towards the spirooxindolopyrrolizidine derivatives.
In recent times, multicomponent reactions[11] (MCR’s) have
emerged as a dominant scenario for providing the molecular
diversity required in combinatorial approaches for the formation
of biologically active compounds and generating diverse
chemical nature of drug-like molecules for biological screening[12]
1, 3-Dipolar cycloadditions are highly effective methods for the
regio and stereoselective synthesis of different heterocyclic
.
frameworks[13]
.
R2
O
R1
N
X
DMF
90 oC
+
O
X
+
R3CHO
R2
COOH
R3
N
H
O
N
R1
4
5
6
O
N
H
3
Scheme
2:
Synthesis
of
the
(1'S,2'R,3'R,7a'R)-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones
[a]
Soumyadip Basu and Chhanda Mukhopadhyay
Department of Chemistry
Precisely, the chemistry of dipolar azomethine has achieved
significant importance in last few years as it acts as an
expedient source for the construction of nitrogen containing five
membered heterocycles, which constitute the backbone of
various natural products[14]. Amongst numerous aza heterocyclic
compounds, functionalized pyrrolizidines have significant
biological activity[15]. Again spiro heterocyclic motifs represent a
very important class of natural substances characterized by their
distinct biological properties[16], such as potent rhino virus and
University of Calcutta
92 APC Road, Kolkata-700009, India
E-mail : cmukhop@yahoo.co.in;
Official E-mail :chmchem@caluniv.ac.in
Supporting information for this article is given via a link at the end of
the document
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
polio 3C-proteinase inhibitions and aldose reductase inhibitions.
Spiro-oxindole ring systems are also central skeletons of many
important naturally occurring alkaloids such as spiro
tryprostatine A and B, horsfiline, elacomine[17] etc. This type of
spiro-heterocyclic motifs also have medicinal applications as
antibiotics, antimicrobial, antitumor agent and can be used as
inhibitors of human NK-1 receptor[18]. Again, spiropyrrolidines
have potential local anaesthetic activities[19] and can be used as
Table 1 : Optimization of Metal salt Catalyzed synthesis of (E)-3-(2-oxo-
2-phenylethylidene)indolin-2-one
O
O
+
O
N
H
1a
2a
N
O
3a
H
anticonvulsant,
Combination of these two heterocyclic rings in the spiro-
oxindolopyrrolizidine system affords the expansion in the
antiviral
and
antileukemic
agents[20]
.
Entry
1
Solvent
DCM
Catalyst
T (oC)
r.t.
Yield[a]
FeCl3 (10 mol %)
FeCl3 (10 mol %)
FeCl3 (10 mol %)
FeCl3 (15mol %)
FeCl3 (20mol %)
FeCl3 (15mol %)
FeCl3 (15mol %)
FeCl3 (15mol %)
FeBr3 (15mol %)
-
development of the diversity of biological active molecules.
2
DCM
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
25%
51%
70%
70%
15%
12%
40%
39%
-
Results and Discussion
The initial alkyne carbonyl metathesis is believed to be passed
through the formation of an oxetene intermediate. Though
intramolecular alkyne carbonyl metathesis strategy was applied
largely in organic synthesis in last few years, the formation of
oxetene ring via intermolecular alkyne carbonyl metathesis was
not extensively studied until now. In some examples, photo
3
CH3CN
CH3CN
CH3CN
Toluene
THF
4
5
irradiation was required for this purpose[21] whereas in other
,
6
cases, complex reaction conditions were entertained. One of
such example was found where indium salt was taken as the
catalyst for the alkyne-aldehyde metathesis and 1-butanol was
required for the transformation as an additive[22]. In comparison
to the above methods, our procedure involves a simpler reaction
condition with an easily available catalyst. Moreover, no further
additive is required for the conversion.
7
8
CH3NO2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
Various salts of iron and some other transition metal salts were
attempted as catalyst for the conversion. Most successful result
was obtained with FeCl3 (15 mol %) (Table 1, entry 4) in dry
acetonitrile solvent, under reflux, when around 70% yield was
observed. Further increasing of catalyst load (Table 1, entry 5),
did not respond with any increment of the yield; whereas
lowering the amount of catalyst (Table 1, entry 3) resulted in the
large drop in yield percentage. The conversion was also
examined using varieties of available organic solvents, such as
DCM (Table 1, entries 1 and 2), THF (Table 1, entry 7),
Nitromethane (Table 1, entry 8) and Toluene (Table 1, entry 6),
but none of them could match with acetonitrile in terms of yield.
It was observed that the other salts of iron like Fe(OTf)3 (Table 1,
entry 11) and FeBr3 (Table 1, entry 9) also catalysed the
reaction but the yields were comparatively low, whereas
Fe(acac)3 (Table 1, entry 10) did not shown any catalytic
property in this protocol. Some other metal salts such as NiCl2
(Table 1, entry 13) and InCl3 (Table 1, entry 12) were also
investigated under the same reaction condition. In both of the
cases, not much catalytic activity was observed. The complete
studies of reaction using different metal catalyst in different
solvents are listed in Table 1.
10
11
12
13
Fe(acac)3 (15mol %)
Fe(OTf)3 (15mol %)
InCl3 (15mol %)
40%
10%
-
NiCl2 (15mol %)
[a]Yield after column chromatography.
It was found that both electron withdrawing (Table 2, entries 2, 3,
5, 6, 7, 9, 10, 12, 13, 14 and 15) and donating (Table 2, entries
16 and 18) substitution on the 5 position of isatin were well
comfortable under the reaction condition without any difficulty. It
was observed that electron withdrawing groups offered higher
and electron donating groups offered lower yields compared to
normal isatins with no substitution on the aromatic ring (Table 2,
entries 1, 4, 8, 11 and 17) (also evident from Figure 2, Case 1).
Also N-protected isatins (Table 2, entries 7, 8, 9, 10, 11, 12 and
13) were used in this condition and slightly lower yields were
observed. In addition, the aromatic as well as heterocyclic
(Table 2, entries 15 and 16) terminal alkynes produced sufficient
yield, whereas aliphatic acetylene (Table 2, entry 19) gave
extremely low conversion, due to high instability of the oxetene
intermediate B and vinylic carbocation A. Those with strong
electron donating groups on the phenyl acetylene moiety, such
as 4-OMe (Table 2, entries 4, 5, 6, 7, 9 and 10), 3,4-diOMe
(Table 2, entry 14) , 2-OMe (Table 2, entry 17) favoured higher
The feasibility of the conversion was examined with various
functionalised starting materials under the optimized reaction
condition. The complete study of the effect of substitution on the
yield of the product is summarized in Table 2.
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
yields of the products. While both weak electron withdrawing
groups such as 4-Br (Table 2, entry 11) and weak electron
donating groups such as 4-Me (Table 2, entries 12 and 13),
were well-tolerated under the present reaction condition.
O
N
Cl
Cl
OMe
O
O
9 (3i)
64
N
OMe
O
Table 2. Synthesis of Various Functionalized (E)-3-(2-oxo-2-
arylethylidene)indolin-2-ones[a]
O
N
Br
Br
O
O
R2
O
10 (3j)
63
OMe
X
N
O
OMe
FeCl3
X
O
+
O
Dry MeCN
R2
N
80 o
C
R1
N
O
O
N
R1
O
3
1
2
O
N
Br
11 (3k)
12 (3l)
55
Br
O
Entry
Isatins
Acetylenes
Products
Yield(%)[b]
O
Cl
O
Cl
O
O
N
59
O
1 (3a)
69
N
O
N
H
HN
O
O
O
N
Br
O
Cl
O
Br
2 (3b)
Cl
O
O
O
HN
13 (3m)
60
N
H
N
66
64
O
O
Br
Cl
O
O
O
Cl
OMe
Br
O
3 (3c)
4 (3d)
O
HN
O
OMe
N
H
14 (3n)
15 (3o)
16 (3p)
73
N
H
HN
OMe
O
O
MeO
O
O
Br
O
Br
O
OMe
HN
OMe
O
O
S
N
S
S
H
O
N
H
72
67
HN
74
72
O
O
Cl
Cl
O
O
O
N
H
O
5 (3e)
S
OMe
O
HN
OMe
N
HN
O
H
O
O
Br
Br
O
OMe
O
O
O
N
H
6 (3f)
7(3g)
71
66
O
HN
MeO
HN
OMe
17 (3q)
18 (3r)
N
H
72
64
MeO
O
O
O
Cl
O
OMe
Cl
MeO
O
O
OMe
O
O
N
N
OMe
OMe
N
H
HN
O
OMe
O
O
N
O
O
Cl
O
Cl
N
O
O
8 (3h)
58
N
O
19 (3s)
10
H
HN
O
[a]Reaction conditions : substrate 1 (1 mmol), substrate 2 (1 mmol), FeCl3
(15 mol %), Dry acetonitrile (5 ml), [b]Yield after column chromatography.
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
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The ultimate condensation was carried out under a simple
catalyst-free reaction condition. Various solvents such as
ethanol (Table 3, entry1), DMF (Table 3, entries 2, 7, 8 and 9),
THF (Table 3, entry 4), nitromethane (Table 3, entry 5) and
toluene (Table 3, entry 6) were used to optimize the reaction
condition as shown in Table 3. It appeared that, the conversion
in DMF produced the maximum yield among all the solvents.
The reaction temperature was then optimized using DMF as
solvent and maximum conversion was observed when the
temperature had fixed at 90 oC (Table 3, entry 8).
Among the (E)-3-(2-oxo-2-arylethylidene)indolin-2-ones (3), the
N-protected ones offered better yields
compare to the
unprotected molecules. Again, the conversion was found to be
quite general with respect to both electron accepting as well as
electron donating groups in the indoline ring of 3 and similar type
of yield was observed in each cases. Electronic nature of
substituent on the aryl ring of 3, believed to have sufficient
influence on the yield of the product. It was found that electron
donating groups produced higher yields compared to the
electron withdrawing groups on the aromatic ring.
Table
3 : Optimization of the synthesis of 1'-benzoyl-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones
Table 4. Preparation of Various Functionalized (1'S,2'R,3'R,7a'R)-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones.[a],[b]
O
NH
H
R2
CHO
R1
DMF
90 o
O
N
+
+
O
X
COOH
N
C
DMF
90 o
+
O
O
R2
4
X
+
R3CHO
H
COOH
R3
6a
N
H
C
O
N
N
H
O
4
5
6
O
N
5a
N
R1
3a
H
3
Entry
Solvent
EtOH
T ( oC)
Yield[a]
54%
82%
51%
12%
40%
15%
85%
86%
65%
1
2
3
4
5
6
7
8
9
reflux
reflux
reflux
reflux
reflux
reflux
100 oC
NH
NH
H
NH
O
Br
Cl
O
O
DMF
6c
6a
6b
O
O
N
O
H
N
N
H
CH3CN
THF
6a (86%)
6b (81%)
6c (74%)
CH3NO2
Toluene
DMF
OMe
NH
O
NH
Br
NH
H
O
O
O
Cl
O2N
Cl
6e
6f
6d
O
N
N
O
N
H
H
6d (71%)
6e (77%)
6f (71%)
DMF
90 o
C
OMe
OMe
DMF
80 oC
NH
O
NH
O
Cl
Cl
N
O
Br
MeO
MeO
O2N
6g
6h
[a]Yield after column chromatography
O
O
N
N
O
N
H
H
H
NO2
6i
6g (70%)
6h (76%)
6i (78%)
Numbers of variable products were synthesized using differently
functionalised starting materials (Table 4). Various types of
aldehydes (5) including aromatic, aliphatic and heterocyclic,
were found to participate smoothly under this reaction condition.
Higher yields were observed for aromatic aldehydes compared
to the aliphatic (Table 4, entry 14,) and heterocyclic (Table 4,
entry 15) ones. It was found that, the process was almost
unaffected by the electronic nature of the substituent on the aryl
rings of 5, and both electron donating and electron withdrawing
groups produced good yield of the products. OH- group at the
para position (Table 4, entry 10) and nitro groups at both ortho
and para positions of the aromatic aldehydes (Table 4, entry 9),
were also found to be well tolerated under this reaction condition.
N
O
6j
Cl
N
O
OMe
N
Cl
HO
MeO
O
MeO
O
N
Cl
6l
O
N
6k
H
O
N
H
MeO
H
6j (71%)
6k (67%)
6k (67%)
6l (64%)
6l (64%)
6j (71%)
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
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The result concluded that the reaction had not gone through the
Meyer–Schuster type rearrangement pathway but may be
through the only remaining possibility, that is, formation of an
oxetene intermediate B[25,11] as shown in Scheme-4. Here, the
role of the metal ion is to activate the carbonyl by co-ordinating
with the oxygen atom. The reaction was believed to pass
through the formation of vinylic carbocation A, which is
supported by the regiospecificity of the reaction. Also it can
explain the unreactivity of diester acetylene dicarboxylates
towards the reaction. The fact that, higher yield was obtained for
the strong EDG in the acetylene moiety and very poor yield was
observed for aryl terminal alkenes, due to low stability of its
oxetene intermediate B and vinylic carbocation A, also supports
the mechanism. To retain the activity of the catalyst and to
prevent the attack of external H2O (from solvent) on the
carbocation, dry solvent was chosen.
OMe
OMe
N
N
N
Cl
Br
O
O
O
O
O
Br
N
6m
O
N
6o
6n
N
H
N
H
H
6m (66%)
6n (64%)
6o (69%)
NH
OMe
S
NH
Br
S
NH
O
Cl
O
O
OMe
Cl
Br
6r
O
N
H
O
N
O
H
6q
N
H
6p
NO2
6p (61%)
6q (67%)
6r (71%)
NH
H
O
Cl
OMe
O
N
6s
FeCl3
FeCl3
O
6s (73%)
substrate (0.5 mmol), substrate 4 (0.5mmol),
substrate 5 (0.5 mmol), DMF (4ml),[b]Yield after column chromatography
C-3
O
O
R2
X
FeCl3
X
X
R2
2
O
[a]Reaction conditions
:
3
O
O
N
N
N
A
R1
R1
R1
1
1
- FeCl3
To examine the reaction mechanism, we initially used CuI along
with FeCl3, in the first transformation (Scheme - 1), expecting
the formation Cu(I)-acetylene complex, followed by its attack on
the C-3 carbon of the isatin and finally the 1,3 shift of the oxygen
atom, alike Meyer–Schuster type rearrangement[23]. In this
method, some amount of diphenyldiacetylene was also obtained
as by-product due to the self-coupling of Cu(I)-acetylene
complex[24]. To further investigate the mechanism, when we
carried out the same reaction without CuI, we obtained only the
expected product without diphenyldiacetylene. That result
demolished the possibility that the reaction is passed through
the formation of Cu(I)-acetylene complex, and increased our
interest to study the mechanism more precisely. Next, we used
1-(prop-1-ynyl)benzene in place of phenyl acetylene with FeCl3
as the only catalyst and it was found to achieve the α, β-
unsaturated carbonyl moiety in good yield (65 %) (Scheme -3).
Again we used diester acetylene dicarboxylate moieties in place
of phenylacetylene under the same reaction condition, but no
product was obtained in this case.
R2
O
R2
X
X
5
6
O
O
4
9
B
3
3
8
N
7
N
O
1
2
R1
R1
Scheme 4 : Plausible Mechanism for the FeCl3 Catalyzed Alkyne Carbonyl
Metathesis Reaction
1, 3 Dipolar cycloadditions generally produce high regio and
stereo selective products[26],[27]. In our case initially azomethine
ylide was formed insitu by decarboxylative condensation
between aldehyde and L-proline. Both E- and Z- isomers can be
possible, but for sterically hindered aldehydes, E-azomithine
being more exposed towards cycloaddtion, exclusively involved
in further reaction[28]. In this (3+2) cycloaddition with the (E)-3-(2-
oxo-2-phenylethylidene)indolin-2-one under thermal condition
predominately endo product was obtained because of higher
stability of its T.S. due to secondary orbaital interaction[30]. This
phenomenon also dictates the stereo nature of C2 centre. Again
the stereocentre of L- proline guides the stereochemistry of
centre C7a and the stereochemistry of centre C3 is directed by
the geometry of the ylide. Thus this cycloaddition
O
O
FeCl3
+
O
Dry MeCN
80 o
Yieldb - 65%
N
H
C
N
H
O
stereospecificly
produced
(1'S,2'R,3'R,7a'R)-1'-benzoyl-
8
1
6
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones,
Which again confirmed by the crude NMR (Figure - 1) of 6i and
by single crystal X-ray diffraction study. In the 1H NMR of the
Crude product, there is no corresponding isomeric peak for the
product’s peak at δ 5.06, which is expected peak for proton at 3
position, which is a characteristic peak in this reaction. This
result confirm that no diastereomer is formed in this reaction, as
Scheme-3
ynyl)benzene and Isatin[a]
: alkyne carbonyl metathesis reaction between 1-(prop-1-
:
[a]Reaction conditions : substrate 1 (1 mmol), substrate 2 (1 mmol), FeCl3
(15 mol %), Dry acetonitrile (5 ml), [b]Yield after column chromatography,
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
if it is formed there should be corresponding isomeric peak near
δ 5.06. Again in the 13C NMR there are additional peaks of the
starting materials only, with the major peaks of the product as
expected. This result also supports the formation of only one
stereo or regioisomer in this reaction.
The Previous reports support the undesired regiospecificity of
the cycloaddition[29]. It can be explained by considering the
stability of the carbanion produced, after the initial nucleophilic
attack of the 1,3 dipolar azomethine from its carbon centre
(Figure - 2). This carbanion can be generated on two positions,
one on the carbon of the isatin ring and the other on the β-
carbon to the –COAr group. In the first case the anion can be
stabilised in two ways, one by the conjugation with the phenyl
ring of the isatin moiety and the other with the conjugation with
the amide carbonyl part of isatin. In second case, it can be
stabilised in only one way, by the conjugation with the keto
carbonyl group (the bond formed in case 2, is not observed in
the final compound). This explanation is also supported by the
fact that higher yield has observed for electron withdrawing
group at the 5-possition of isatin moiety. So, the stability of the
carbanion may be the reason for the formation of the
regiospecific product.
NO2
O
N
Br
DMF
90 o
+
Br
+
O
COOH
N
H
C
NO2
O
4
6
O
N
CHO
5
N
O2N
H
NO2
3
R1
N
O
X
R1
O
N
X
O
R3
R3
O
R2
N
NO2
N
R2
O
N
Br
DMF
90 o
+
H
Br
+
O
COOH
H
N
C
NO2
O
4
H
6
O
N
CHO
5
N
O2N
H
Case - 1
X
NO2
3
R1
O
R1
N
N
X
R3
O
O
R3
N
O
R2
H
N
R2
H
Case - 2
Figure 2. Explanation of the regiospecificity of the reaction.
Figure 1. Crude NMR (1H and 13C) of Compound 6i.
The structures of the all synthesized compounds were fully
characterized by H ,13C NMR and Mass spectra. The structure
1
The probable mechanism is shown in Scheme 5.
H
N
of compounds 3a (CCDC 1575100) and 6m (CCDC 1575153)
(Figure 3) were further confirmed by single crystal X-ray
diffraction. The ORTEP diagram of product 3a and 6m are given
below.
L-Proline
COOH
H
+
R3
R3 CHO
R3
N
COOH
N
COOH
H
H
R3
R3
Decarboxylation
-CO2
Decarboxylation
-CO2
N
N
H
H
R1
N
R1
N
X
X
O
N
R3
O
O
3a
R3
azomethine ylide is more
exposed towards cycloaddition
O
R2
N
Highly hindered
reaction zone
R2
H
H
No
Cycloaddition
R1
R1
X
N
X
N
2
O
R3
R2
O
R2
3
R3
1
N
O
O
N
H
7
7a
6
H
5
6
Scheme 5 : Plausible Mechanism for the synthesis of (1'S,2'R,3'R,7a'R)-
6m
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones. :
Figure 3. ORTEP drawing of product 3a (CCDC 1575100)and 6m (CCDC
1575100).
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10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
135.8, 134.2, 132.4, 129.2, 128.7, 127.2, 126.4, 125.6, 121.4, 111.9;
HRMS : calcd for C16H11ClNO2 [M +H] 284.0478, found 284.0477.
Conclusions
In short, our main target was the formation of α,β-unsaturated
carbonyl framework involving isatin moiety in an enviro-friendly
metal salt catalysis procedure, giving priority to the atom
economy, simpler reaction condition, availability of starting
materials, and utilised this scaffold to synthesize biologically
active heterocyclic compounds stereospecificly in a catalyst-free
reaction condition. This protocol is an interesting combination of
metal salt catalysis and multicomponent strategy. Various
functional groups, both electron donating and accepting, nicely
participated in both the reactions without any difficulties.
(E)-5-Bromo-3-(2-oxo-2-phenylethylidene)indolin-2-one (3c) (entry 3,
Table-2)
: Yield 61 %; Orange solid; Mp : 165 °C; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.37; 1H NMR (300 MHz, DMSO-
d6) δH : 10.98 (s, 1H), 8.27 (s,1H), 8.10 (d, J = 7.8 Hz, 2H), 7.81 (s, 1H),
7.73 (t, J = 7.5 Hz, 1H), 7.65-7.53 (m, 3H), 6.87 (d, J = 8.4 Hz. 1H); 13C
NMR (75 MHz, DMSO-d6) δC : 190.9, 167.8, 144.2, 137.0, 135.8, 135.3,
134.2, 129.2, 128.7, 127.3, 127.1, 121.9, 113.2, 112.3; HRMS : calcd for
C
16H11BrNO2 [M +H] 327.9973, found 327.9971.
(E)-3-(2-(4-Methoxyphenyl)-2-oxoethylidene)indolin-2-one (3d) (entry
4, Table-2) : Yield 70 %; Orange solid; Mp : 232 °C; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.31; 1H NMR (300 MHz, DMSO-
d6) δH : 10.80 (s, 1H), 8.05(d, J = 7.2 Hz, 2H), 7. 94 (d, J = 6.6 Hz, 1H),
7.69 (s, 1H) 7.32 (t, J = 7.2 Hz, 1H), 7.11 (d, J = 8.1 Hz. 2H), 6.94 (d, J =
7.2 Hz, 1H), 6.87 (d, J = 7.5 Hz, 1H), 3.86 (s, 3H); 13C NMR (75 MHz,
Experimental Section
General Methods :
Synthesis of (E)-3-(2-Oxo-2-Arylethylidene)Indolin-2-ones derivatives
were achieved and further utilised in the catalyst free methodology for the
preparation of various 1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-
pyrrolizin]-2-ones under the reflux condition and the progress of the
reaction was checked by TLC using silica gel. All reagents were
purchased from commercial sources and used without further purification.
DMSO-d6) δC
129.0, 125.9, 123.7, 121.2, 114.0, 109.5, 55.7; HRMS : calcd for
17H14NO3 [M +H] 280.0974, found 280.0969.
: 190.1, 169.1, 163.4, 143.1, 137.9, 132.0, 130.4, 129.3,
C
(E)-5-Chloro-3-(2-(4-methoxyphenyl)-2-oxoethylidene)indolin-2-one
(3e) (entry 5, Table-2) : Yield 68 %; Orange solid; Mp : 190 °C; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.40; 1H NMR (300 MHz, DMSO-
d6) δH : 10.96 (s, 1H), 8.10–8.07(m, 3H), 7.80 (s, 1H) 7.41 (d, J = 8.1
Hz, 1H), 7.13 (d, J = 8.1 Hz. 2H), 6.90 (d, J = 8.4 Hz, 1H), 3.89 (s,
3H); 13C NMR (75 MHz, DMSO-d6) δC : 189.2, 168.0, 164.1, 143.7,
135.2, 132.2, 131.3, 130.1, 127.7, 126.4, 125.6, 121.6, 114.5, 111.8,
55.8; HRMS : calcd for C17H13ClNO3 [M +H] 314.0584, found 314.0582.
Melting points were determined in open capillary tubes. 1H NMR and 13
C
NMR spectra were recorded on Bruker 300 MHz instrument using CDCl3
and DMSO-d6. Chemical shifts are given in δ values referenced to the
solvent. X-Ray crystallographic analysis was performed with a Bruker
SMART diffractometer.
General Procedure for FeCl3-Catalyzed Synthesis of (E)-3-(2-Oxo-2-
Arylethylidene)Indolin-2-ones (3a–3m):
(E)-5-Bromo-3-(2-(4-methoxyphenyl)-2-oxoethylidene)indolin-2-one
(3f) (entry 6, Table-2) : Yield 62 %; Orange solid; Mp : 192 °C; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.39; 1H NMR (300 MHz, DMSO-
d6) δH : 10.97 (s, 1H), 8.23(s, 1H), 8.08 (d, J = 8.7 Hz, 2H), 7.78 (s, 1H),
7.52 (d, J = 8.4 Hz, 1H), 7.12 (d, J = 9 Hz, 2H), 6.86 (d, J = 8.1 Hz, 1H),
3.88 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δC : 189.2, 167.9, 164.1,
144.1,135.1, 135.0, 131.3, 130.0, 129.1, 127.7, 122.0, 114.5, 113.2,
112.3, 55.8; HRMS : calcd for C17H13BrNO3 [M +H] 358.0079, found
358.0076.
A mixture of Isatins (1) (1mmol) and Phenyl Acetylenes (2) (1 mmol),
was taken in a 10 mL round-bottom flask containing 5 mL of dry
acetonitrile solvent. Anhydrous FeCl3 (0.15 mmol) was added, and the
reaction mixture was heated to reflux for 6 h maintaining anhydrous
condition. After complete conversion of the starting materials (TLC),
acetonitrile was distilled out under reduced pressure and the residue was
purified by silica gel (mess 60-120) column chromatography.
General
Procedure
for
Synthesis
of
(1'S,2'R,3'R,7a'R)-
(E)-1-Benzyl-5-chloro-3-(2-(4-methoxyphenyl)-2-
1',3',5',6',7',7a'hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones (6a–
6o) :
oxoethylidene)indolin-2-one (3g) (entry 7, Table-2) : Yield 74 %; Red
solid; 133 °C; Rf [15 % EtOAc/Petroleum ether (60–80 °C)] : 0.48; 1H
NMR (300 MHz, CDCl3) δH : 8.35 (s, 1H), 8.14 (d, J =8.1 Hz, 2H), 8.02
(s, 1H), 7.33-7.22 (m, 6H), 7.03 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 7.8 Hz,
1H), 4.99 (s, 2H), 3.93 (s, 3H); 13C NMR (75 MHz, CDCl3) δC : 189.1,
167.8, 164.4, 143.3, 135.1, 134.8, 131.8, 131.4, 130.5, 128.9, 128.6,
128.3, 127.9, 127.7, 127.2, 121.5, 114.2, 110.1, 55.6, 44.0; HRMS :
calcd for C24H19ClNO3 [M +H] 404.1053, found 404.1049.
A mixture of compound 3 (0.5 mmol), Aldehyde (0.5 mmol) and L-proline
(0.5 mmol), was taken in a 10 mL round-bottom flask containing 4 ml
DMF solvent. The reaction mixture was heated at 90 oC for 8 h. After
complete conversion of the starting materials (TLC), the crude product
was extracted with ethyl acetate and the solvent was distilled out under
reduced pressure and the residue was purified by silica gel (mess 60-
120) column chromatography.
(E)-1-Allyl-3-(2-oxo-2-phenylethylidene)indolin-2-one (3h) (entry 8,
Table-2) : Yield 69 %; Red solid; Mp : 84 °C; Rf [15 % EtOAc/Petroleum
ether (60–80 °C)] : 0.33; 1H NMR (300 MHz, CDCl3) δH : 8.09 (d, J = 7.5
Hz, 1H), 7.86 (d, J = 7.5 Hz, 2H), 7.39 (s, 1H), 7.37 (t, J = 6.9 Hz, 1H),
7.27 (t,J = 7.5 Hz, 2H), 7.07 (t, J = 7.5 Hz, 1H), 6.76 (t, J = 7.5 Hz, 1H),
6.55 (d, J = 7.8 Hz, 1H), 5.67–5.55 (m, 1H), 5.04–4.98 (m, 2H), 4.12 (s,
1H); 13C NMR (75 MHz, CDCl3) δC : 190.9, 167.4, 145.0, 137.4, 136.2,
133.6, 132.4, 130.9, 128.7, 128.6, 127.5, 126.2, 122.6, 120.0, 117.5,
108.9, 42.2; HRMS : calcd for C19H16NO2 [M +H] 290.1181, found
290.1175.
(E)-3-(2-Oxo-2-phenylethylidene)indolin-2-one (3a) (entry 1, Table-
2) : Yield 69 %; Orange solid; Mp : 192 °C; Rf [40 % EtOAc/Petroleum
ether (60–80 °C)] : 0.45; 1H NMR (300 MHz, DMSO-d6) δH : 10.86 (s,
1H), 8.11 (d, J = 7.5 Hz, 2H), 8.06 (d, J = 7.8 Hz, 1H), 7.77-7.63 (m, 4H),
7.39 (t, J = 7.5 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H), 6.94 (t, J = 7.5 Hz,
1H); 13C NMR (75 MHz, DMSO-d6) δC : 191.4, 168.2, 145.0, 137.1, 136.4,
134.1, 133.0, 129.2, 128.6, 126.7, 126.0, 121.8, 120.0, 110.4; HRMS :
calcd for C16H12NO2 [M +H] 250.0868, found 250.0862.
(E)-5-Chloro-3-(2-oxo-2-phenylethylidene)indolin-2-one (3b) (entry 2,
(E)-1-Allyl-5-chloro-3-(2-(4-methoxyphenyl)-2-oxoethylidene)indolin-
2-one (3i) (entry 9, Table-2) : Yield 67 %; Red solid; Mp : 91 °C; Rf
[40 % EtOAc/Petroleum ether (60–80 °C)] : 0.35; 1H NMR (300 MHz,
CDCl3) δH : 8.26 (s, 1H),8.01 (d, J = 7.2 Hz,, 2H), 7.84 (s, 1H), 7.21–
7.18 (m, 1H), 6.91 (d, J = 7.5 Hz, 2H), 6.63 (d, J = 8.4 Hz,, 1H), 5.79–
Table-2)
: Yield 65 %; Orange solid; Mp : 160 °C; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.39; 1H NMR (300 MHz, DMSO-
d6) δH : 11.03 (s, 1H), 8.18–8.14 (m, 3H), 7.86 (s, 1H), 7.79 (t, J = 6.8 Hz,
1H), 7.68 (t, J = 7.5 Hz, 1H), 7.47 (d, J = 7.5 Hz, 1H), 6.97 (d, J = 7.5 Hz,
1H); 13C NMR (75 MHz, DMSO-d6) δC : 191.0, 167.9, 143.9, 137.0,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
5.70 (m, 1H), 5.18–5.13 (m, 2H), 4.30 (s, 2H), 3.81 (s, 3H); 13C NMR (75
MHz, CDCl3) δC : 188.9, 167.2, 164.2, 143.3, 134.7, 131.7, 131.2, 130.7,
130.4, 128.1, 128.0, 127.6, 121.3, 117.8, 114.1, 109.8, 55.5, 42.4;
HRMS : calcd for C20H17ClNO3 [M +H] 354.0897, found 354.0896.
δH : 8.93 (s, 1H), 8.32 (s, 1H), 7.87–7.86 (m, 1H),7.69–7.63 (m, 2H), 7.12
(t, J = 4.2 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H), 6.67 (d, J = 7.8 Hz, 1H), 2.24
(s, 3H). 13CNMR (75MHz, CDCl3) δC : 182.6, 170.0, 146.1, 141.5, 137.7,
135.3, 133.6, 133.2, 132.4, 129.4, 128.7, 124.6, 120.7, 110.0, 21.1.
HRMS : calcd for C15H11NO2S [M + H] 270.0583, found 270.0589.
(E)-1-Allyl-5-bromo-3-(2-(4-methoxyphenyl)-2-oxoethylidene)indolin-
2-one (3j) (entry 10, Table-2) : Yield 63 %; Red solid; Mp : 94 °C ; Rf
[40 % EtOAc/Petroleum ether (60–80 °C)] : 0.36; 1H NMR (300 MHz,
CDCl3) δH : 8.49 (s, 1H),8.11 (d, J = 8.4 Hz, 2H), 7.95 (s, 1H), 7.45 (d, J
= 8.4 Hz, 1H), 7.01 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 8.1 Hz, 1H), 5.87–
5.80 (m, 1H), 5.28–5.22 (m, 2H), 4.41 (s, 2H), 3.92 (s, 3H); 13C NMR (75
MHz, CDCl3) δC : 188.9, 167.1, 164.3, 143.8, 134.6, 131.2, 130.7, 130.5,
130.3, 128.2, 121.7, 117.8, 115.3, 114.1, 110.3, 55.5, 42.4; HRMS :
calcd for C20H17BrNO3 [M +H] 398.0392, found 398.0386.
(E)-3-(2-(2-methoxyphenyl)-2-oxoethylidene)indolin-2-one (3q) (entry
17, Table - 2) : Yield 72 % ; Red solid; Mp : 226 °C ; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.36; 1H NMR (300 MHz, DMSO-
d6) δH : 10.70 (s, 1H), 7.98 (s, 1H),7.46–7.45 (m, 3H), 7.08–6.85 (m, 3H),
6.73–6.66 (m, 2H), 3.63 (s, 3H). 13C NMR (75 MHz, CDCl3) δC : 191.9,
170.5, 159.1, 143.4, 134.5, 134.4, 132.2, 130.9, 130.8, 128.5, 127.5,
122.5, 120.9, 111.8, 110.2, 55.8. HRMS : calcd for C17H13NO3 [M + H]
280.0974, found 280.0968.
(E)-3-(2-(4-Bromophenyl)-2-oxoethylidene)-1-ethylindolin-2-one (3k)
(entry 11, Table-2) : Yield 55 %; Red solid; Mp : 98 °C; Rf [10 %
EtOAc/Petroleum ether (60–80 °C)] : 0.38; 1H NMR (300 MHz, CDCl3)
δH : 8.35 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.83 (s, 1H), 7.68
(d, J = 8.1 Hz, 2H), 7.39 (t, J = 7.5 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 6.84
(E)-5-methoxy-3-(2-(4-methoxyphenyl)-2-oxoethylidene)indolin-2-
one (3r) (entry 18, Table - 2) : Yield 64 % ; Red solid; Mp : 206 °C ; Rf
[40 % EtOAc/Petroleum ether (60–80 °C)] : 0.35; 1H NMR (300 MHz,
DMSO-d6) δH : 10.07 (s, 1H), 7.87 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7
Hz, 2H), 6.94 (s, 1H), 6.71 (s, 2H), 6.03 (s, 1H), 3.83 (s, 3H), 3.64 (s,
3H). 13C NMR (75 MHz, CDCl3) δC : 194.8, 178.4, 163.3, 154.6, 139.1,
136.2, 133.2, 130.3, 129.4, 121.2, 113.9, 113.3, 111.0, 109.7, 55.6, 55.5.
HRMS : calcd for C18H15NO4 [M + H] 310.1079, found 310.1072.
(d, J = 7.8 Hz, 1H), 3.83 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) δC : 190.0, 167.4, 145.3, 137.2, 136.4, 132.8,
132.2, 130.2, 129.1, 128.0, 125.2, 122.6, 120.2, 108.4, 34.8, 12.6;
HRMS : calcd for C18H15BrNO2 [M +H] 356.0286, found 356.0278.
(E)-5-chloro-3-(4-methyl-2-oxopentylidene)indolin-2-one(3s) (entry
19, Table - 2) : Yield 10 % ; Red solid; Mp : 156 °C ; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.30; 1H NMR (300 MHz, DMSO-
d6) δH : 10.90 (s, 1H), 7.45 (d, J = 8.1 Hz, 2H),7.26 (s, 1H), 7.05 (d, J =
8.7 Hz, 1H), 6.06 (s, 1H), 1.80 (m, 2H), 1.03 (m, 1H), 0.58 (d, J = 6.9 Hz,
6H). 13C NMR (75 MHz, DMSO-d6) δC : 202.9, 173.2, 142.2, 135.3,
132.7, 130.7, 128.4, 128.0, 123.6, 111.5, 53.5, 29.7, 23.4.HRMS : calcd
for C14H14ClNO2 [M + H] 264.0791, found 264.0788.
(E)-5-Chloro-1-ethyl-3-(2-oxo-2-p-tolylethylidene)indolin-2-one
(3l)
(entry 12, Table-2) : Yield 59 %; Red solid; Mp : 94 °C; Rf [5 %
EtOAc/Petroleum ether (60–80 °C)] : 0.33; 1H NMR (300 MHz, CDCl3)
δH : 8.27 (s, 1H), 7.91 (d, J = 8.1 Hz, 2H), 7.83 (s, 1H), 7.23 (d, J = 7.5
Hz, 3H), 6.66 (d, J = 8.1 Hz, 1H), 3.71 (q, J = 6.9 Hz, 2H), 2.35 (s, 3H),
1.19 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δC : 190.2, 167.1,
145.0, 143.4, 135.4, 134.9, 131.9, 129.5, 128.9, 127.8, 127.6, 127.5,
121.4, 109.0, 34.9, 21.7, 12.5; HRMS : calcd for C19H17ClNO2 [M +H]
326.0948, found 326.0943.
(1'S,2'R,3'R,7a'R)-1'-benzoyl-3'-phenyl-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one (6a, Table-4) : Yield
86 % ; Yellow solid; Mp : 186 °C ; Rf [25 % EtOAc/Petroleum ether (60–
80 °C)] : 0.42; 1H NMR (300 MHz, DMSO-d6) δH : 10.37 (s, 1H), 7.57-
7.49 (m, 4H), 7.34-7.24 (m, 7H), 7.13 (t, J = 7.5 Hz, 1H), 7.05 (d, J = 6.6
Hz, 1H), 6.59 (d, J = 7.2 Hz, 1H), 4.95 (m, 1H),4.69 (m, 1H), 4.31 (m, 1H),
2.91 (m, 2H), 1.91–1.81 (m, 2H), 1.53–1.29 (m, 2H); 13C NMR (75 MHz,
CDCl3) δC : 196.9, 178.7, 143.1, 140.1, 137.0, 132.7, 128.4, 128.2,
128.0, 127.8, 127.6, 127.3, 126.8, 122.3, 109.5, 74.5, 71.1, 65.9, 61.6,
53.9, 27.8, 27.1; HRMS : calcd for C27H25N2O2 [M +H] 409.1916, found
409.1911.
(E)-5-Bromo-1-ethyl-3-(2-oxo-2-p-tolylethylidene)indolin-2-one (3m)
(entry 13, Table-2) : Yield 60%; Red solid; Mp : 96 °C; Rf [5 %
EtOAc/Petroleum ether (60-80 °C)] : 0.31; 1H NMR (300 MHz, CDCl3)
δH : 8.27 (s, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.68 (s, 1H), 7.24 (d, J = 8.4
Hz, 1H), 7.09 (d, J = 7.8 Hz, 2H), 6.47 (d, J = 8.4 Hz, 1H), 3.57 (q, J = 6.9
Hz, 2H), 2.21 (s, 3H), 1.05 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δC : 190.3, 167.0, 145.1, 143.9, 135.4, 135.0, 134.8, 130.6, 129.6, 129.0,
127.8, 122.0, 115.2, 109.6, 34.9, 21.8, 12.6; HRMS
19H17BrNO2 [M +H] 370.0443, found 370.0438.
: calcd for
C
(E)-5-chloro-3-(2-(3,4-dimethoxyphenyl)-2-oxoethylidene)indolin-2-
one( 3n ) (entry 14, Table-2) : Yield 73 %; Red solid; Mp : 240 °C; Rf
[40 % EtOAc/Petroleum ether (60-80 °C)] : 0.41; 1H NMR (300 MHz,
DMSO-d6) δH : 10.95 (s, 1H), 8.16 (s, 1H), 7.81–7.76 (m, 2H),7.59 (s,
1H), 7.41 (d, J = 8.1 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 6.90 (d, J = 8.4 Hz,
1H), 3.89 (s, 3H), 3.88 (s, 3H). 13C NMR (75MHz, DMSO-d6) δC : 188.9,
168.1, 154.2, 149.2, 143.7, 135.3, 132.2, 130.1, 127.4, 126.5, 125.6,
(1'S,2'R,3'R,7a'R)-1'-benzoyl-5-chloro-3'-phenyl-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one (6b, Table-4) : Yield
81 % ; White solid; Mp : 180 °C ; Rf [25 % EtOAc/Petroleum ether (60–
80 °C)] : 0.38; 1H NMR (300 MHz, DMSO-d6) δH : 10.23 (s, 1H), 7.54–
7.49 (m, 3H), 7.38–7.33 (m, 4H), 7.09 (m, 4H), 6.94 (d, J = 7.8 Hz, 1H),
6.24 (d, J = 7.8 Hz, 1H), 4.53–4.49 (m, 3H), 2.91 (m, 1H), 2.51 (m, 1H),
2.11 – 1.99 (m, 4H); 13C NMR (75 MHz, CDCl3) δC : 197.5, 176.8, 137.8,
137.4, 137.0, 132.8, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5,
109.5, 77.7, 66.1, 64.4, 59.4, 52.9, 32.8, 26.8; HRMS : calcd for
124.3, 121.6, 111.8, 111.1, 110.3, 56.0, 55.7. HRMS
18H14ClNO4 [M + H] 344.0690, found 344.06388.
: calcd for
C
C
27H24ClN2O2[M +H] 443.1526, found 443.1522.
(E)-5-bromo-3-(2-oxo-2-(thiophen-2-yl)ethylidene)indolin-2-one (3o)
(entry 15, Table-2) : Yield 72 %; Red solid; Mp : 196 °C ; Rf [40 %
EtOAc/Petroleum ether (60–80 °C)] : 0.31; 1H NMR (300 MHz, DMSO-
d6) δH : 10.99 (s, 1H), 8.57 (s, 1H), 8.20–8.18 (m, 2H),7.69 (s, 1H), 7.54
(d, J = 8.1 Hz, 1H), 7.35–7.34 (m, 2H), 6.85 (d, J = 8.1 Hz, 1H). 13C NMR
(75MHz, DMSO-d6) δC : 182.7, 168.3, 145.6, 144.9, 137.7, 136.8, 135.9,
135.2, 130.6, 129.9, 125.9, 122.4, 113.8, 112.7. HRMS : calcd for
(1'S,2'R,3'R,7a'R)-1'-benzoyl-5-bromo-3'-phenyl-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one (6c, Table-4) : Yield
74 % ; Off White solid; Mp : 192 °C ; Rf [25 % EtOAc/Petroleum ether
(60–80 °C)] : 0.39; 1H NMR (300 MHz, DMSO-d6) δH : 10.22 (s, 1H),
7.52–7.44 (m, 4H), 7.34 (t, J = 7.5 Hz, 3H), 7.07–7.03 (m, 5H), 6.18 (d, J
= 8.1Hz, 1H), 4.51–4.47 (m, 3H), 2.89–2.87 (m, 1H), 2.49 (m, 1H), 2.09–
1.90 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δC : 197.8, 176.4, 140.9,
137.8, 137.3, 133.5, 131.0, 129.9, 129.1, 128.7, 128.3, 128.1, 127.8,
127.4, 112.9, 111.0, 77.0, 66.0, 64.5, 58.9, 53.0, 32.3, 26.8; HRMS :
calcd for C27H24BrN2O2 [M +H] 487.1021, found 487.1018.
C
14H8BrNO2S [M + H] 333.9537, found 333.9528.
E)-5-methyl-3-(2-oxo-2-(thiophen-2-yl)ethylidene)indolin-2-one (3p)
(entry 16,Table-2) : Yield 67 % ; Red solid; Mp : 186 °C ; Rf [40 %
EtOAc/Petroleum ether (60-80 °C)] : 0.34; 1H NMR (300 MHz, CDCl3)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
(1'S,2'R,3'R,7a'R)-1'-benzoyl-5-bromo-3'-(4-nitrophenyl)-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 7.03 (d, J = 8.1 Hz, 2H), 6.16 (d, J = 7.8
Hz, 1H), 5. 51 (s, 1H), 4.79–4.77 (m, 1H), 4.43 (d, J = 8.7 Hz, 1H), 3.29–
3.24 (m, 2H), 3.11–2.99 (m, 2H), 2.29 (s, 3H), 2.26–2.22 (m, 2H), 2.18–
2.09 (m, 1H), 2.08–1.89 (m, 1H), 0.74(t, J = 7.2 Hz, 3H); 13C NMR (75
MHz, CDCl3) δC : 196.5, 174.6, 149.1, 146.8, 143.9, 140.9, 139.9, 134.5,
132.5, 131.6, 130.4, 128.8, 128.1, 126.7, 125.5, 119.0, 114.4, 109.2,
71.7, 65.9, 65.4, 60.3, 53.3, 34.9, 31.8, 26.2, 21.5, 11.4; HRMS : calcd
for C30H28BrN4O6 [M + H] 619.1192, found 619.1190.
(6d,
Table-4) : Yield 71 % ; Yellow solid; Mp : 250 °C ; Rf [25 %
EtOAc/Petroleum ether (60–80 °C)] : 0.46; 1H NMR (300 MHz, DMSO-
d6) δH : 10.38 (s, 1H), 7.99 (d, J = 7.8 Hz, 2H), 7.57–7.50 (m, 3H), 7.45
(s, 1H), 7.39–7.35 (m, 4H), 7.10 (d, J = 7.5 Hz, 1H), 6.23 (d, J = 8.4 Hz,
1H), 4.61–4.60 (m, 3H), 2.96–2.92 (m, 1H), 2.51(m, 1H), 2.13–1.95 (m,
4H); 13C NMR (75 MHz, DMSO-d6) δC : 197.2, 175.5, 146.8, 145.6,
140.4, 136.8, 133.3, 131.1, 129.3, 128.3, 128.2, 128.0, 127.9, 122.9,
112.7, 110.9, 75.9, 65.5, 64.4, 58.5, 52.7, 31.8, 26.5; HRMS : calcd for
(1'S,2'R,3'R,7a'R)-5-chloro-1-ethyl-3'-(4-hydroxy-3-methoxyphenyl)-
1'-(4-methylbenzoyl)-1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-
pyrrolizin]-2-one (6j, Table-4) : Yield 71 % ; White solid; Mp :
222 °C ;Rf [20 % EtOAc/Petroleum ether (60–80 °C)] : 0.39; 1H NMR
(300 MHz, CDCl3) δH : 7.44 (s, 1H), 7.23 (d, J = 7.8 Hz, 2H), 6.91 (d, J =
7.8 Hz, 2H), 6.80 (d, J = 7.5 Hz, 1H), 6.64 (s, 1H), 6.41–6.35 (m, 2H),
6.00(d, J = 8.4 Hz, 1H), 5.29 (s, 1H), 4.57 ((d, J = 7.2 Hz, 1H), 4.35 (s,
1H), 4.25 (d, J = 7.8 Hz, 1H), 3.55 (s, 3H), 3.14–2.90 (m, 2H), 2.82–2.76
(m, 1H), 2.51–2.48 (m, 1H), 2.15 (s, 3H), 2.04–2.02 (m, 2H), 1.85–1.68
(m, 2H), 0.51(t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δC : 197.1,
174.7, 145.8, 144.8, 143.3, 140.2, 134.8, 128.9, 128.7, 128.1, 127.8,
126.8, 120.3, 113.1, 110.2, 108.1, 77.2, 65.6, 64.1, 58.8, 55.9, 52.7, 34.4,
32.8, 26.6, 21.4, 11.7; HRMS : calcd for C31H32ClN2O4 [M + H]
531.2051, found 531.2046.
C
27H23BrN3O4 [M +H] 532.0872, found 532.0870.
(1'S,2'R,3'R,7a'R)-1'-benzoyl-3'-(4-chlorophenyl)-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one(6e, Table-4)
:
Yield
77 % ; Off White solid; Mp : 186 °C ; Rf [25 % EtOAc/Petroleum ether
(60–80 °C)] : 0.36; 1H NMR (300 MHz, DMSO-d6) δH : 9.99 (s, 1H), 7.49
(d, J = 7.2 Hz, 1H), 7.41 (d, J = 6.9 Hz, 2H), 7.24 (d, J = 6.6 Hz, 3H), 6.87
(d, J = 8.1Hz, 4H), 6.38 (d, J = 7.8 Hz, 2H), 6.22 (d, J = 7.5 Hz, 1H), 4.59
(s, 1H), 4.41 (d, J = 8.1 Hz, 1H), 4.35 (s, 1H), 2.83 (m, 1H), 1.99–1.88 (m,
5H); 13C NMR (75 MHz, DMSO-d6) δC : 196.2, 177.9, 141.7, 136.4,
133.3, 131.8, 129.3, 128.4, 127.9,127.7, 127.5, 126.3, 121.3, 109.6, 73.9,
70.0, 64.8, 61.0, 53.2, 27.5, 26.7; HRMS : calcd for C27H24ClN2O2 [M
+H] 443.1526, found 443.1524.
(1'S,2'R,3'R,7a'R)-3'-(4-chlorophenyl)-1'-(4-methoxybenzoyl)-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(1'S,2'R,3'R,7a'R)-1-benzyl-5-chloro-3'-(4-chlorophenyl)-1'-(4-
methoxybenzoyl)-1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-
pyrrolizin]-2-one (6k, Table-4) :Yield 67 % ; Off White solid; Mp :
190 °C ; Rf [12 % EtOAc/Petroleum ether (60–80 °C)] : 0.33; 1H NMR
(300 MHz, CDCl3) δH : 7.65 (d, J = 7.5 Hz, 3H), 7.16–7.00 (m, 7H), 6.89–
6.84 (m, 3H), 6.54 (d, J = 7.2 Hz, 2H), 6.00(d, J = 8.4 Hz, 1H), 4.79 (s,
1H), 4.63 (s, 1H), 4.58–4.49 (m, 2H), 4.33–4.26 (m, 1H), 3.89 (s, 3H),
2.99 (m, 1H), 2.61 (m, 1H), 2.20 (m, 2H), 1.70 (m, 2H); 13C NMR (75
MHz, CDCl3) δC : 194.9, 175.1, 163.5, 140.1, 135.6, 134.4, 133.2, 130.7,
129.9, 129.0, 128.5, 128.1, 127.8, 127.6, 127.4, 127.2, 126.4, 113.5,
109.4, 77.9, 65.9, 64.5, 58.5, 55.4, 52.8, 43.5, 36.1, 26.9; HRMS : calcd
for C35H31Cl2N2O3 [M +H] 597.1712, found 597.1708.
(6f,
Table-4) : Yield 75 % ; Yellow solid; Mp : 188 °C ; Rf [25 %
EtOAc/Petroleum ether (60–80 °C)] : 0.35; 1H NMR (300 MHz, DMSO-
d6) δH : 10.17 (s, 1H), 7.54 (d, J = 8.7Hz, 2H), 7.35 (d, J = 7.2 Hz, 1H),
7.11 (s,4H), 6.90–6.83 (m, 4H), 6.29 (d, J = 7.5 Hz, 1H), 4.63 (d, J = 6.3
Hz, 1H), 4.47 (s, 1H), 4.42 (d, J = 8.1 Hz, 1H), 3.79(s, 3H), 2.89–2.86 (m,
1H), 2.10–1.87 (m, 5H); 13C NMR (75 MHz, DMSO-d6) δC : 195.0, 176.4,
163.1, 141.0, 137.1, 131.6, 130.3, 129.7, 128.9, 128.0, 127.5, 127.2,
125.8, 120.9, 113.5, 108.8, 76.5, 65.6, 64.4, 58.1, 55.6, 52.9, 31.9, 26.3;
HRMS : calcd for C28H26ClN2O3 [M +H] 473.1632, found 473.1629.
(1'S,2'R,3'R,7a'R)-5-chloro-3'-(3,4-dimethoxyphenyl)-1'-(4-
methoxybenzoyl)-1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-
pyrrolizin]-2-one (6g, Table-4) :Yield 70 % ; Light Brown solid; Mp :
204 °C ; Rf [25 % EtOAc/Petroleum ether (60–80 °C)] : 0.36; 1H NMR
(300 MHz, DMSO-d6) δH : 10.25 (s, 1H), 7.62 (d, J = 8.7Hz, 2H), 7.44 (s,
1H), 6.98 (d, J = 8.1 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 6.75 (s,1H), 6.66(d,
J = 8.1 Hz, 1H), 6.56 (d, J = 7.8 Hz, 1H), 6.32 (d, J = 8.4 Hz, 1H), 4.56 (d,
J = 6.6 Hz, 1H), 4.46(d, J = 8.1 Hz, 1H), 4.41 (s, 1H), 3.79 (s, 3H), 3.60
(s, 3H), 3.55 (s, 3H), 2.91–2.89 (m, 1H), 2.56–2.54 (m, 1H), 2.10–1.89 (m,
4H); 13C NMR (75 MHz, DMSO-d6) δC : 195.0, 176.1, 163.3, 148.0,
147.8, 140.1, 130.5, 129.5, 128.5, 127.7, 127.3, 124.7, 119.5, 113.6,
110.8, 110.6, 110.1, 76.8, 65.9, 64.2, 57.6, 55.6, 55.3, 55.0, 52.5, 31.9,
26.2; HRMS : calcd for C30H30ClN2O5 [M +H] 533.1843, found 533.1840.
(1'S,2'R,3'R,7a'R)-1-Allyl-1'-benzoyl-3'-(3,4-dimethoxyphenyl)-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(6l,
Table-4) : Yield 64 % ; Brown solid; Mp : 212 °C ; Rf [12 %
EtOAc/Petroleum ether (60–80 °C)] : 0.35; 1H NMR (300 MHz, CDCl3)
δH : 7.49 (s, 2H), 7.29–7.28 (m, 4H), 7.00 (s, 2H), 6.62 (s, 3H), 6.32 (s,
1H), 5.24–5.17 (m, 1H), 4.71 (d, J = 9.9 Hz, 2H), 4.52 (s, 2H), 4.28 (s,1H),
3.86 (d, J = 10.5 Hz, 2H), 3.57(s, 3H), 3.45 (s, 3H), 2.92 (m, 1H), 2.60 (m,
1H), 2.11–1.97 (m, 4H); 13C NMR (75 MHz, CDCl3) δC : 197.9, 175.1,
148.1, 147.9, 141.7, 137.4, 132.1, 130.7, 130.3, 128.7, 127.9, 127.7,
127.1, 121.7., 120.0, 116.4, 110.7, 109.8, 108.1, 77.3, 65.2, 63.7, 59.5,
55.5, 52.7, 41.6, 32.7, 26.3; HRMS : calcd for C32H33N2O4 [M +H]
509.2440, found 509.2438.
(1'S,2'R,3'R,7a'R)-5-chloro-1'-(4-methoxybenzoyl)-3'-p-tolyl-
(1'S,2'R,3'R,7a'R)-1-allyl-1'-benzoyl-3'-(4-bromophenyl)-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(6h,
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(6m,
Table-4) : Yield 76 % ; Golden Yellow solid; Mp : 192 °C ; Rf [25 %
EtOAc/Petroleum ether (60–80 °C)] : 0.38; 1H NMR (300 MHz, DMSO-
d6) δH : 10.27 (s, 1H), 7.59 (d, J = 8.7Hz, 2H), 7.37 (s, 1H), 7.00-6.87 (m,
7H), 6.29 (d, J = 8.1 Hz, 1H), 4.54–4.45 (m, 3H), 3.79 (s, 3H), 2.89–2.86
(m, 1H), 2.29 (m, 1H), 2.11 (s, 3H), 2.00–1.87 (m, 4H); 13C NMR (75 MHz,
CDCl3) δC : 195.0, 176.2, 163.3, 140.0, 136.4, 134.5, 130.4, 129.6,
128.4, 128.3, 127.7, 127.1, 127.0, 124.7, 113.6, 110.1, 76.5, 65.9, 64.2,
57.9, 55.6, 52.6, 31.9, 26.4, 20.6; HRMS : calcd for C29H28ClN2O3 [M
+H] 487.1788, found 487.1780.
Table-4) : Yield 66 % ; Off White solid; Mp : 210 °C ; Rf [12 %
EtOAc/Petroleum ether (60–80 °C)] : 0.38; 1H NMR (300 MHz, CDCl3)
δH : 7.54–7.52 (m, 1H), 7.43–7.34 (m, 3H), 7.25 (t, J = 8.4 Hz, 3H), 7.13
(d, J = 8.1 Hz, 2H), 7.05 (d, J = 7.8 Hz, 2H), 6.98–6.97 (m, 1H), 6.20–
6.18 (m, 1H), 5.26–5.16 (m, 1H), 4.88–4.80 (m, 2H), 4.60–4.48 (m, 2H),
4.41 (d, J = 7.8 Hz, 1H), 4.01–3.96 (m, 1H), 3.49–3.43 (m,1H), 3.01–2.97
(m,1H), 2.65–2.63 (m, 1H), 2.22 (m, 2H), 2.04–2.00 (m, 1H), 1.87 (m,
1H); 13C NMR (75 MHz, CDCl3) δC : 198.0, 175.2, 141.7, 137.5, 136.7,
132.4, 130.5, 129.3, 128.2, 128.0, 127.9, 127.2, 125.3, 122.1, 121.2,
117.0, 108.3, 76.8, 65.3, 64.1, 59.8, 53.1, 42.0, 32.9, 26.8; HRMS : calcd
for C30H28BrN2O2 [M +H] 527.1334, found 527.1331.
(1'S,2'R,3'R,7a'R)-5-bromo-3'-(2,4-dinitrophenyl)-1-ethyl-1'-(4-
methylbenzoyl)-1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-
pyrrolizin]-2-one (6i, Table-4) : Yield 78 % ; Greenish Yellow solid;
Mp : 230 °C ;Rf [10 % EtOAc/Petroleum ether (60–80 °C)] : 0.32; 1H
NMR (300 MHz, CDCl3) δH : 8.30–8.20 (m, 3H), 7.32–7.28 (m, 2H), 7.23
(1'S,2'R,3'R,7a'R)-1-allyl-5-bromo-1'-(4-methoxybenzoyl)-3'-propyl-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(6n,
Table-4) : Yield 64 % ; Light Brown solid; Mp : 216 °C ; Rf [10 %
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
EtOAc/Petroleum ether (60–80 °C)] : 0.34; 1H NMR (300 MHz, CDCl3)
δH : 7.81(s, 1H), 7.53 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.4 Hz, 1H), 6.80 (d,
J = 8.9 Hz, 2H), 6.45 (d, J = 8.4 Hz, 1H), 5.28–5.19 (m, 1H), 4.96 (d, J =
9.9 Hz, 1H), 4.86 (s, 1H), 4.19 (d, J = 9.6 Hz, 1H), 3.96–3.83 (m, 5H),
3.56 (m, 1H), 3.32 (m, 1H), 2.93 (m, 1H), 2.32–2.12 (m, 4H), 1.72–1.70
(m, 1H), 1.05–0.82 (m, 4H), 0.73 (t, J = 6.9 Hz, 3H); 13C NMR (75MHz,
EtOAc/Petroleum ether (60–80 °C)] : 0.39; 1H NMR (300 MHz, CDCl3)
δH : 9.61 (s, 1H), 7.49 (d, J= 6.6 Hz, 1H), 7.33–7.21 (m, 2H), 7.11 (d, J=
7.8 Hz, 2H), 6.97 (d, J= 7.8 Hz, 3H), 6.74 (d, J= 8.1 Hz, 1H), 6.58 (t, J=
7.2 Hz, 1H),6.31 (d, J= 6.6 Hz, 1H), 6.18 (d, J= 7.2 Hz, 1H), 4.67 (d, J =
6.9 Hz, 1H), 4.57 (d, J = 8.1 Hz, 1H), 4.46 (s, 1H), 3.79 (s, 3H), 2.96-2.94
(m, 1H), 2.60-2.58 (m, 1H), 2.24–2.14 (m, 2H), 2.01-1.88 (m, 2H). 13C
NMR (75 MHz, CDCl3) δC : 200.8, 177.0, 157.0, 140.1, 136.1, 132.9,
132.1, 128.9, 128.5, 128.1, 127.6, 127.0, 126.5, 122.1, 119.9, 110.2,
109.1, 76.5, 65.1, 63.4, 63.2, 55.3, 53.0, 33.0, 26.8. HRMS : calcd for
CDCl3) δC
: 193.3, 175.1, 163.7, 140.9, 131.5, 130.5, 130.4,
130.1,130.0, 117.8, 115.8, 113.5, 110.1, 74.6, 66.3, 63.9, 58.8, 55.6,
55.5, 42.4, 31.6, 29.7, 26.5, 19.8, 14.1; HRMS : calcd for C28H32BrN2O3
[M + H] 523.1596, found 523.1591.
C
28H25ClN2O3 [M + H] 473.1632, found 473.1629.
(1'S,2'R,3'R,7a'R)-1-allyl-5-chloro-1'-(4-methoxybenzoyl)-3'-(pyridin-
4-yl)-1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one
(6o, Table-4) : Yield 69%; Deep Brown solid; Mp : 208 °C ; Rf [10 %
EtOAc/Petroleum ether (60–80 °C)] : 0.35; 1H NMR (300 MHz, DMSO-
d6) δH : 8.28–8.26 (m, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.39–7.38 (m, 1H),
7.08–7.03 (m, 3H), 6.89 (d, J = 8.7 Hz, 2H), 6.45 (d, J = 8.4 Hz, 1H),
5.27–5.21 (m, 1H), 4.83 (d, J = 10.2 Hz, 1H), 4.58–4.50 (m, 4H), 3.93–
3.79 (m, 5H), 2.98–2.94 (m, 1H), 2.59–2.54 (m, 1H), 2.15–1.92 (m,
4H); 13C NMR (75 MHz, DMSO-d6) δC : 194.7, 173.8, 163.3, 149.1,
146.5, 140.4, 130.8, 130.3, 129.4, 128.1, 126.9, 126.6, 125.8, 121.9,
116.8, 113.4, 109.9, 75.3, 64.9, 64.3, 58.1, 55.6, 52.7, 41.6, 31.7, 26.5;
HRMS : calcd for C30H29ClN3O3 [M + H] 514.1897, found 514.1893.
(E)-3-(1-Oxo-1-phenylpropan-2-ylidene)indolin-2-one (Scheme 3, 8) :
Yield 73 % ; Red solid; Mp : 120 °C ; Rf [40 % EtOAc/Petroleum ether
(60–80 °C)] : 0.42; 1H NMR (300 MHz, DMSO-d6) δH : 10.52 (s, 1H),
7.86 (t, J = 7.8 Hz, 3H), 7.72–7.62 (m, 2H), 7.59–7.49 (m, 2H), 7.13 (t, J
= 7.5 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 2.40 (s, 3H); 13C NMR (75 MHz,
DMSO-d6) δC : 198.2, 166.6, 146.5, 137.8, 134.6, 129.7, 128.9, 128.4,
125.9, 124.4, 122.9, 121.8, 118.7, 111.7, 18.4; HRMS : calcd for
C
17H14NO2 [M +H] 264.1025, found 264.1018.
Acknowledgements
One of the authors (SB) thanks the University Grants
Commission (UGC), New Delhi, for his fellowship (JRF). We also
are grateful to CAS-V (UGC), DST-FIST and DST-PURSE,
Department of Chemistry, University of Calcutta, for funding as
departmental projects.
5-chloro-1'-(3,4-dimethoxybenzoyl)-3'-(2-nitrophenyl)-1',3',5',6',7',7a'-
hexahydrospiro[indoline-3,2'-pyrrolizin]-2-one (6p, Table-4) : Yield
61 % ; Light Brown solid; Mp : 236 °C ; Rf [20 % EtOAc/Petroleum ether
(60–80 °C)] : 0.31; 1H NMR (300 MHz, DMSO-d6) δH : 10.39 (s, 1H),
7.78 (d, J = 7.2 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.2 Hz, 1H),
7.30 (t, J = 7.5 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.07–7.05 (m, 2H),
6.96–6.87 (m, 2H), 6.29 (d, J = 7.8 Hz, 1H), 5.23 (s, 1H), 4.63 (s, 1H),
4.43 (d, J = 8.4 Hz, 1H), 3.77 (s, 3H), 3.73 (s, 3H), 2.93–2.88 (m, 2H),
2.11–1.91 (m, 4H). 13C NMR (75 MHz, DMSO-d6) δC : 195.3, 176.9,
153.0, 149.5, 148.0, 140.4, 131.6, 131.5, 130.3, 129.5, 128.9, 128.1,
127.6, 127.3, 124.7, 123.7, 122.3, 110.8, 110.2, 71.1, 65.8, 65.5, 59.2,
55.7, 55.4, 52.7, 31.2, 25.5. HRMS : calcd for C29H26ClN3O6 [M + H]
548.1510, found 548.1504.
Keywords : Alkyne carbonyl metathesis • Metal salt catalysis •
stereo and regiospecific protocol • Spiro-Oxindolopyrrolizidine
Scaffolds • Multicomponent strategy.
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701606
European Journal of Organic Chemistry
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701606
European Journal of Organic Chemistry
FULL PAPER
Soumyadip Basu[a], and Chhanda
Mukhopadhyay[a]*
R2= Aliphatic, Heterocyclic, Aromatic
R2
Page No. – Page No.
R2
2
R1
COOH
FeCl3
Dry MeCN
N
X= H, Cl, Br,
Me, OMe
N
O
X
4
H
DMF
90 oC
O
O
R2
80 oC
X
R3
Synthesis of (E)-3-(2-Oxo-2-
Arylethylidene)Indolin-2-ones
Through Alkyne Carbonyl Metathesis
and Their Stereospecific Application
Towards Spiro-Oxindolopyrrolizidine
Scaffolds
X
R3CHO
5
O
6
O
O
N
N
H
N
R3= Aliphatic, Heterocyclic, Aromatic
R1= H, Allyl, Benzyl, Ethyl
1
R1
3
R1
A Transition metal salt catalysed alkyne carbonyl metathesis followed by a
multicomponent protocol to synthesize highly substituted new (1'S,2'R,3'R,7a'R)-
1',3',5',6',7',7a'-hexahydrospiro[indoline-3,2'-pyrrolizin]-2-ones. A total of 39
compounds have been synthesized by an interesting combination of metal salt
catalysis and multicomponent strategy.
Keywords : Alkyne carbonyl metathesis • Metal salt catalysis • Stereo and regioselective protocol • Spiro-
Oxindolopyrrolizidine Scaffolds • Multicomponent strategy.
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