Palladium Nanoparticle-Catalyzed Stereoselective Domino Synthesis of 3-Allylidene-2(3 H)-oxindoles and 3-Allylidene-2(3 H)-benzofuranones

Article abstract of DOI:10.1021/acs.joc.9b03397

A single-step, stereoselective protocol for the synthesis of unsymmetrically substituted (E)-3-allylideneoxindole and (E)-3-allylidenebenzofuran from readily accessible starting materials using palladium binaphthyl nanoparticles (Pd-BNPs) has been developed. Pd-BNP showing a wide range of functional group tolerance and an immense array of substrate scope have been explored with the successful synthesis of the drug molecule "tubulin polymerization inhibitor" free from trace metal impurities. The model reaction is extended to a gram-scale synthesis, and one of the products is utilized for derivatization. The Pd-BNP has been recycled up to 5 catalytic cycles without any loss in reaction yields and particle size of nanoparticles.

Full text of DOI:10.1021/acs.joc.9b03397

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Article
Palladium Nanoparticles-Catalyzed Stereoselective Domino Synthesis
of 3-Allylidene-2(3H)-oxindoles and 3-Allylidene-2(3H)-benzofuranones
Naziya Parveen, and Govindasamy Sekar
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03397 • Publication Date (Web): 11 Mar 2020
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Palladium Nanoparticles-Catalyzed Stereoselective Domino Synthesis of 3-Allylidene-
2(3H)-oxindoles and 3-Allylidene-2(3H)-benzofuranones
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Naziya Parveen and Govindasamy Sekar*
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Department of Chemistry, Indian Institute of Technology Madras, Chennai – 600 036,
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Tamil Nadu, INDIA
E-mail: gsekar@iitm.ac.in
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ABSTRACT
A single-step, stereoselective protocol for the synthesis of unsymmetrically substituted (E)-3-
allylideneoxindole and (E)-3-allylidenebenzofuran from readily accessible starting materials
using palladium binaphthyl nanoparticles (Pd-BNP) has been developed. Pd-BNP adept a wide
range of functional group tolerance and an immense array of substrate scope have been
explored with the successful synthesis of drug molecule “tubulin polymerization inhibitor” free
from trace metal impurities. The model reaction is extended to a gram-scale synthesis and one
of the product is utilized for derivatization. The Pd-BNP has been recycled up to 5 catalytic
cycles without any loss in reaction yields and particle size of nanoparticles.
---------------------------------------------------------------------------------------------------------------
INTRODUCTION
The aesthetic simplicity of multicomponent processes1 and domino reactions2 have enabled the
synthetic community to build pharmaceutically and industrially important complex
architecture such as oxindoles3 in a single step without isolating intermediates. Oxindoles
belongs to the family of monoterpene alkaloids4 with promising pharmaceutical properties.5
Especially, 3-alkylidene oxindoles reserve a particular interest due to their broad biological
spectrum, and used as key intermediates to access biologically important alkaloids,6 drug
molecules7 such as AMPK activator,8 synthesis of TMC-95A,9 anti-cancer drugs (Figure 1).10
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Importantly it is used as anti-cancer drug, especially for breast cancer due to the tamoxifen like
activity and antirheumatic etc.11
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Figure 1. Pharmaceutically important molecules containing oxindole skeleton.
The 3-allylideneoxindole exist as a pair of stereoisomers (E/Z), and the stereoselective
synthesis of 3-allylideneoxindole derivatives is a challenging task. Even with a demanding
pharmaceutical value, a through literature survey suggests; a very few reports12 (Figure 2)
available for synthesis of 3-alkylidene oxindoles while stereoselective synthesis of 3-
alkylidene oxindoles suffers from scarcity of efficient synthetic methods. However, most of
the reported synthetic methods suffer from serious drawbacks like lack of stereoselectivity,
need of high-temperature, need of toxic bulky phosphine ligands and arylboronic acids, limited
substrate scope and tedious separation of homogeneous Pd catalyst from the final product that
significantly restrict the use of 3-allylideneoxindole in pharmacological studies.13 These
shortcomings could be addressed using an efficient heterogeneous catalyst for the selective
synthesis of (E)-3-allylideneoxindole, completely free from trace metal impurities as the
catalyst can be recovered by simple filtration methods for recycling the expensive metal
catalyst.
In the recent years, metal nanocatalyst especially Pd-nanocatalyst has acquired a considerable
interest in organic synthesis due to their stability, higher reactivity and easy separation from
the final product.14 Recently, we have reported the selective synthesis of inter/intramolecular
reductive Heck products using binaphthyl backbone stabilized palladium nanocatalyst (Pd-
BNP).15
In continuation of our efforts to explore the potential application of Pd-BNP nanocatalyst,
herein we report a single step, stereoselective synthesis of (E)-3-allylideneoxindole, (E)-3-
allylidenebenzofuran and its derivatives using binaphthyl palladium nanoparticles (Pd-BNP).
The Pd-BNP shows a wide range of functional group tolerance and the validity of methodology
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has been investigated using various substituted and sterically hindered substrates, resulted good
to excellent yields.
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Figure 2. Recent approach for the synthesis of oxindoles.
To the best of our knowledge, single step, stereoselective synthesis of (E)-3-allylideneoxindole
and (E)-3-allylidenebenzofuran derivatives using Pd nanocatalyst has not been witnessed
earlier.
RESULTS AND DISCUSSION
We commenced our investigation by using N-(2-iodophenyl)-N-methyl-3-phenylpropiolamide
1a with styrene 2a in the presence of 2 mol% of Pd-BNP and 2.0 equiv of Na2CO3 as a base in
DMF at 110 °C. The reaction yielded 77% of 3a, exclusively with (E) stereochemistry. The
structure and relative configuration of (E)-stereoisomer was unequivocally confirmed by the
single-crystal XRD analysis. Having the preliminary results in hand, the reaction conditions
were further optimized with various bases, solvents, catalysts, etc. Further screening of various
bases undeniably confirmed that NaOAc gives the best output (Table 1, entry 4).16 Other bases
like NEt3, DIPEA, and DABCO gave low yields while strong bases like KOtBu and NaOH
performed very poorly and gave intramolecular coupling 4a as a side product along with
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desired product 3a. A brief screening of solvents confirmed that, DMF gives the highest yields
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whereas, toluene, CH3CN and THF were failed
Table 1. Optimization of the Reaction Conditionsa
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Yield (%)b
Temp
(oC)
Time
(h)
Entry
Base
Solvent (mL)
3a
4a
1
Na2CO3
NaOMe
DABCO
NaOAc
NEt3
DMF
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110
110
110
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110
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120
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8
77
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DMF
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3
DMF
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-
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DMF
DMF
96
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81
-
6
DIPEA
KOtBu
NaOH
DMF
75
-
7
DMF
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27
32
-
8
DMF
15
9
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
DMSO
DMA
Dioxane
CH3CN
Toluene
THF
74
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61
-
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Trace
-
-
-
Trace
77
-
DMF
-
DMF
94
-
-
DMF
12
12
88c
93d
-
DMF
aReaction conditions: 1a (0.25 mmol), 2a (0.37 mmol), Pd-BNP (2 mol%),
1
solvent (1 mL), reaction time (12-36 h). bYields were determined by H
NMR of the crude reaction mixture using 1,3,5-trimethoxy benzene as an
internal standard. 1.0 mol% of Pd-BNP is used. 3.0 mol% of Pd-BNP is
used.
c
d
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miserably to give the desired product (entries 9-14). Further, any deviation from the optimized
reaction temperature of 110 °C, resulted in a significant loss in the reaction yield (entries 15
and 16). Similarly, decreasing the catalyst loading to 1 mol% reduced the reaction yields (88%,
entry 17) while increasing the catalyst loading to 3 mol% gave nearly the same yield (entry
18). Conclusively, 2 mol% of Pd-BNP and 2 equiv of NaOAc in DMF at 110 °C gave the best
output with (E)-stereoselectivity. The catalytic efficiency of Pd-BNP was also compared with
commercial available Pd/C (heterogeneous catalyst) which resulted in poor yields.
Furthermore, few more commercially available homogeneous palladium catalysts such as
Pd(OAc)2 (88%), PdCl2 (85%) and Pd(dba)2 (90%) were also screened and they gave the poor
yield compared to our Pd-BNP (Table S1). This results indeed confirms the admirable potential
of Pd-BNP in catalysis.
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Having the best-optimized reaction conditions in hand (Table 1, entry 4), the substrate scope
was investigated with respect to styrene while keeping N-(2-iodophenyl)-N-methyl-3-
phenylpropiolamide constant, and the results are summarized in Table 2.
Table 2. Domino Synthesis of (E)-3-Allylideneoxindolea,b
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Electron-releasing substituents such as –OMe, –Me and weakly electron-withdrawing such as
–Cl, –Br present at the para and meta-position of the styrene yielded the corresponding (E)-3-
allylideneoxindole in good to excellent yield. Electron donating groups increase the electron
density of olefins to make it strong nucleophile and this may be a reason for aryl iodides have
higher reactivity with electron-donating substituted olefins. Interestingly, the electron-deficient
substrates containing a strong electron-withdrawing group like -CN also reacted to give the
desired products 3d in good yield. However, the unactivated alkenes such as cyclohexene and
cyclooctene failed to react under the optimized reaction conditions.
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Meanwhile, the effect of different protecting groups such as -ethyl, -propyl, -benzyl, -hexyl, -
octyl and acetyl groups on N-phenylpropanolamine were investigated (Table 3); interestingly
all the protected substrates reacted unconditionally under optimized reaction conditions to
yielded the corresponding product (3h-3m).
Table 3. Effect of N-Protecting Groups on Domino Synthesis of (E)-3-Allylideneoxindolea,b
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Additionally, an attempt was made to achieve the domino synthesis of (E)-4-((E)-1-methyl-2-
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oxoindolin-3-ylidene)-4-phenylbut-2-enoate/amide/nitrile
derivative
from
acrylate,
acrylamide and acrylonitrile. The 2-iodophenylpropiolamide 1a reacted without compromising
optimized reaction to give the corresponding (E)-3-allylideneoxindole derivative (3n-3r) in
acceptable yields (Table 4).
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Table 4. Domino Synthesis of (E)-3-Allylideneoxindolea,b
Along with the synthesis of ester/amide/nitrile derivative of (E)-3-allylideneoxindole, the
stereoselective synthesis of (E)-3-allylideneoxindole (5a-5e) has been attempted using
unprotected N-(2-iodophenyl)-3-phenylpropiolamide (Table 5). The reaction proceed evenly
under optimized conditions to give the corresponding substituted (E)-3-allylideneoxindole in
good yields.
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Table 5. Domino Synthesis of (E)-3-Allylideneoxindolea,b
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After the successful synthesis of (E)-3-allylideneoxindole, the stereoselective synthesis of (E)-
3-((E)-1,3-diphenylallylidene)benzofuran-2(3H)-one has been tackled using 2-iodophenyl 3-
phenylpropiolate and 2 under optimized reaction conditions.
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To our delight, the reaction proceeds equally with both electron donating as well as electron
withdrawing substituents and yielded the corresponding (E)-3-allylidenebenzofuran
derivatives (7a-7e) in good yields (Table 6). This results undeniably presents the utility of
present methodology in synthesis of a library of various heteroaromatics.
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Table 6. Domino Synthesis of (E)-3-Allylidenebenzofuransa,b
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The reaction proceeds with exquisite trans selectivity that apparently disobeys the necessity of
cis carbopalladation in alkyne insertion step. The vinyl palladium species formed in the
intermolecular cross-coupling reaction undergoes cis-trans isomerization via η2-vinyl
transition state in the absence of any other possible pathways i.e. β-hydride elimination. The
presence of extended conjugation and higher stability of E isomer also facilitates the cis-trans
isomerization of η2-vinyl palladium complex that position the palladium opposite to the
emerging double bond. Finally, the reductive elimination step results in the regeneration of Pd-
BNP catalyst and selective formation of E-isomer. This plausible explanation for E-selectivity
is in good agreement with the mechanistic hypothesis, and DFT calculation reported earlier in
the literature.17
The effect of halogen substituent (bromo, iodo, etc.) on the fate of reaction was investigated
using less reactive N-(2-bromophenyl)-3-phenylpropiolamide 1′. Gratifyingly, 1′ reacted
smoothly with 2 without any modification in the optimised reaction conditions and gave final
product 3a in 72% yield in 12 h (Table 7). The validity of reaction was also investigated with
few more electron rich and deficient styrene’s and the corresponding final products (3b, 3d and
3e) were isolated in good yields. Notably, the yields of isolated products with N-(2-
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bromophenyl)-3-phenylpropiolamide was found compromised as compared to its iodide
analogue The compromise in reaction yields might be attributed to the least polarizability of
the C-Br bond as compared to the C-I bond for oxidative insertion step of the reaction, that
considerably affects the yields of reaction.18
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Table 7. Domino Synthesis of (E)-3-((E)-1,3-Diphenylallylidene)-1-methylindolin-2-onea,b
To the point of industrial applications, the scalability of the reaction was investigated with large
scale (1.5 gram) reaction of 2-iodophenylpropiolamide and 2a under optimized reaction
conditions that gave the corresponding product (E)-3-allylideneoxindole 3a in excellent yield
(89%) without any significant loss in the optimized reaction yields (Scheme 1).
Scheme 1. Gram Scale Synthesis
Notably, the product containing halogen substituents could be further functionalized by a C-C
coupling reaction to expand the molecular skeleton19 for instance, 3f readily undergoes
Sonogshira coupling reaction to yield the corresponding product 8 in 80% yield (Scheme 2).
Scheme 2. Diversification of (E)-3-Allylideneoxindole
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Moreover, to address the utility of the present methodology, tubulin polymerization inhibitor 9
has been synthesized in 73% yield (Scheme 3). The isolated product was found absolutely free
from trace amount of palladium impurities (ca. palladium level 0.002 ppm, Figure S81)
confirmed by ICP-OES analysis, that’s far lesser than FDA approved palladium level in
drugs.20
Scheme 3. Synthesis of Tubulin Polymerization Inhibitor
This might be attributed to the heterogeneous nature of Pd-BNP that helps in achieving the
metal impurities free drug molecules, thus can be utilized directly in biomedical studies that
indeed reduces the labor and cost of production of important drug molecules. Additionally the
E stereoconformation of 9 was confirmed by X-ray analysis (Scheme 3, inset).
Finally, the recovery and recyclability of Pd-BNP were examined (Figure 3a). The catalyst was
successfully recovered by centrifugation and reused for five consequent cycles without any
appreciable loss in the catalytic efficiency which clearly indicates that catalyst is free from any
sort of agglomeration. Notably, slight decrease in the reaction yields in the subsequent catalytic
cycles from 1-5 might be attributed the minor loss of Pd-BNP catalyst (5-6%) during workup
and recovery procedures.
The hot filtration test were generally used to investigate the heterogeneity of palladium catalyst.
To understand whether the reaction is catalyzed by heterogeneous Pd-BNP catalyst or a leached
Pd-BNP catalyst, the hot filtration experiment has been used in the present manuscript. A set
of two reactions (Figure 3b) were carried out separately and the reaction mixtures were filtered
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off at 2 h for first reaction (22%, NMR yield) and at 4 h for second reaction (48%, NMR yield).
The filtrates were further allowed to react for next 12 h. However, no improvement in the yields
was observed in both the cases. This confirms that no leaching of Pd-BNP catalyst was
observed during the course of reactions.
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Figure 3. (a) Pd-BNP recovery cycle and effect on the yields (b) effect of hot filtration on the
yields of reaction.
Notably, the catalytic activity of Pd-BNP residue was similar to that of freshly prepared Pd-
BNP catalyst. That is in good agreement with HRTEM analysis of recovered and freshly
prepared Pd-BNP catalyst that shows the similar particle size without any obvious
agglomeration before and after the catalytic cycles (Figure 4).
Figure 4. HRTEM images: (a) freshly prepared Pd-BNP catalyst (b) recovered Pd-BNP
catalyst.
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CONCLUSION
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In conclusion, we have presented a one-pot, stereoselective synthesis of unsymmetrically
substituted (E)-3-allylideneoxindole and (E)-3-allylidenebenzofuran derivatives with immense
array of substrate scope using ligand-free, stable and reusable Pd-BNP catalyst. The utility of
present methodology was reflected with the synthesis of tubulin polymerization inhibitors in
good yields. The present strategy features mild reaction conditions, practical simplicity, and
high stereoselectivity to expand the portfolio of domino Heck chemistry. However, a detailed
mechanistic study are currently underway in our laboratory.
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EXPERIMENTAL SECTION
Reactions were performed in an oven-dried reaction tube under a closed atmosphere. Nano
pure water was obtained from Milli-Q Integral Water Purification System. Extra pure analytical
grade DMF and methanol were purchased from Sisco Research Laboratories Pvt. Ltd. Solvents
used for extraction and purification were technical grade and distilled before to use. K2[PdCl4]
(98%) and NaBH4 (99%) were purchased from Aldrich and used without further purification.
(±)-BINAM was purchased from Aldrich and used as such received. 1,1'-binaphthyl,-2,2'-
bis(diazoniumtetrafluoroborate) was prepared using literature procedure. All other chemicals
were obtained from Aldrich, Acros, Avra, Alfa Aesar and used as received unless otherwise
indicated. Reactions were monitored by thin-layer chromatography on pre-coated aluminum-
packed plates (0.25 mm, Merck Kieselgel 60 with fluorescent indicator UV254) and visualized
by fluorescence quenching. Column chromatography was performed with silica gel (particle
size 100-200 mesh). Infrared spectra were recorded on an FTIR 4000 Series Spectrometer using
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13
KBr pellet. The wavenumbers of recorded IR signals are quoted in cm-1. H and C NMR
spectra were recorded in CDCl3 or DMSO-D6 solvent using Bruker AV-400 MHz spectrometer.
Data are expressed as a chemical shift in parts per million (ppm) relative to residual chloroform
and CDCl3 (1H: δ = 7.26 ppm, 13C: δ = 77.16 ppm, respectively; likewise other solvents where
1
applicable) and TMS as internal standard on the δ scale. H coupling constants J are given in
Hz and rounded to the nearest 0.1 Hz. High-resolution mass spectra (HRMS) were recorded on
Q-Tof Micro mass spectrometer and GC-MS was recorded with JEOL GCMATE II.
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X-ray photoelectron spectroscopic analysis was performed by using an ESCA probe/TPD of
Omicron Nanotechnology. Sample was spotted on a Mo plate and allowed to dry in vacuum.
In view of the sensitivity of the sample, surface cleaning was not attempted. Al Kα radiation
was used for excitation; a 180° hemispherical analyzer and a seven-channel detector were
employed. The spectrometer was operated in the constant analyzer energy mode. Survey and
high-resolution spectra were collected using pass energies of 50 and 20 eV, respectively. The
pressure in the analyzer chamber was in the low 10-10 mbar range during spectrum collection.
Binding energies of the core levels were calibrated with C 1s BE set at 284.7 eV. HRTEM
analysis was performed using a JEOL 3010 microscope. Samples for TEM analysis were
prepared in carbon coated copper grids (nanoparticles in dichloromethane solutions). The
instrument was operated at 200 kV. Inductively coupled plasma-optical emission spectrometer
(ICP-OES) from Perkin Elmer Optima 5300 DV was used to identify the Pd content of the
nanoparticles. Samples were prepared by digesting 10 mg of nanoparticles in 2.0 mL of H2SO4
using domestic microwave oven for 30 min. and the solutions was made up to 25 mL in
standard flask. Pd emissions were detected at 340.458 nm under the flow condition.
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Typical
procedure
for
synthesis
of
1,1'-binaphthyl,-2,2'
bis(diazoniumtetrafluoroborate)14a,14e
Sodium nitrite (1.2 g, 18.0 mmol) in 3 mL of water was added slowly to a stirred solution of
(±)-BINAM (1.2 g, 4.0 mmol) and HBF4 (45% in H2O, 10 mL) at 0 oC. Then the reaction was
o
stirred at 0 C for 30 min and further stirred at room temperature for 30 min. The resulting
yellow solid was filtered using a Buchner funnel and washed with cold HBF4 (2 × 5 mL), H2O
(2 × 10 mL) and EtOH (10 mL). The diazonium salt crystalline yellow solid (1.75 g, 91%) was
dried under a vacuum desiccator and store at 0 °C. 1H NMR (400 MHz, DMSO-D6): δ7.55 (d,
J=8.4 Hz, 2H), 7.88 (t, J=7.6 Hz, 2H), 8.17 (t, J = 7.2 Hz, 2H), 8.54 (d, J=8.4 Hz, 2H), 8.84-
8.99 (m, 4H); 13C{1H} NMR (100 MHz, DMSO-D6): δ 125.2, 127.5, 130.1, 130.6, 132.1,
133.6, 132.0, 133.4, 135.0, 135.1, 137.8.
Synthesis of Pd-binapthyl nanoparticles (Pd-BNP)14a, 14e
To a To a 250 mL round bottomed flask potassium tetrachloropalladate (326.5 mg, 1.0 mmol)
in nanopure water (50 mL) was added. 1,1'-binaphthyl,-2,2'-bis(diazoniumtetrafluoroborate) 1
(482.1 mg, 1.0 mmol) and toluene (50 ml) was added and vigorously stirred in magnetic stirrer
for 1 hour. The orange-brown colour formation shows the complexation of palladium with
diazonium salt. NaBH4 (226.9 mg, 6.0 mmol) in water (2 mL) was added drop wise at room
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temperature to the solution and the immediate colour change to dark greenish black signifies
the Pd NPs formation. The reaction mixture was stirred at room temperature for 2 hours. The
toluene layer was separated and washed with 0.5 M aq. H2SO4 (3 × 50 mL) and 0.5 M aq.
NaHCO3 (3 × 50 mL) to remove unreacted metal complexes. Then the solvent was completely
evaporated under rotary evaporator. The solid particles were suspended in ethanol (2 × 10 mL)
and sonicated for half an hour at room temperature. The suspension was centrifuged (4500 rpm,
approx. 30 mins). The ethanol was removed and dried in vacuo to furnish the Pd-binapthyl
nanoparticles (400 mg, 10 wt% Pd, ICP-OES analysis) crystalline black solid.
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General General experimental procedure for (E)-3-((E)-1,3-diphenylallylidene)-1-
methylindolin-2-one:
To a solution of N-(2-iodophenyl)-N-methyl-3-phenylpropiolamide 1a (0.25 mmol) in DMF
were added Pd-BNP (2 mol%), styrene 2a (0.37 mmol), NaOAc (0.5 mmol), The reaction
mixture was kept in a pre-heated oil bath at 110 °C and the resulting solution was stirred for
12 h. Upon completion (monitored by TLC), the reaction mixture was cooled down to room
temperature, extracted with EtOAc and dried over Na2SO4. The residue was purified by column
chromatography on silica gel (hexane/EtOAc) to give (E)-1,3-diphenylallylidene)-1-
methylindolin-2-one 3a.
(E)-3-((E)-1,3-Diphenylallylidene)-1-methylindolin-2-one (3a): 78.3 mg, 93% yield; orenge
solid; mp 98-100 oC; Rf 0.45 (10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  =
3.30 (s, 3H), 5.72 (d, J = 7.6 Hz, 1H), 6.47 (d, J = 16.4 Hz, 1H), 6.60 (t, J = 8.0 Hz, 1H ), 6.74
(d, J = 8.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H) 7.23-7.37 (m, 5H), 7.49-7.60 (m, 5H), 9.38 (d, J =
16.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):  = 25.8, 107.6, 121.6, 122.6, 123.4, 123.7,
127.7, 128.0, 128.3, 128.6, 128.6, 128.8, 129.2, 129.3, 137.0, 137.7, 141.6, 142.9, 151.2, and
168.1; FTIR (KBr): ν = 3062, 2980, 1730, 1436, 1251, 734 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C24H20NO: 338.1545; found: 338.1528.
(E)-1-Methyl-3-((E)-1-phenyl-3-(p-tolyl)allylidene)indolin-2-one (3b): 78.9 mg, 90% yield;
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orenge solid; mp 110-112 C; Rf 0.5 (10% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  2.33 (s, 3H), 3.29 (s, 3H), 5.71 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 16.0 Hz, 1H), 6.59
(t, J = 7.6 Hz, 1H ), 6.73 (d, J = 7.6 Hz, 1H), 7.05-7.15 (m, 3H), 7.22-7.32 (m, 2H), 7.42 (d, J
= 7.6 Hz, 2H ), 7.48-7.60 (m, 3H), 9.34 (d, J = 16.0 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):
 21.5, 25.8, 107.5, 121.5, 122.1, 123.5, 123.6, 126.8, 128.0, 128.1, 128.5, 128.7, 129.3, 129.5,
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134.3, 137.8, 139.4, 141.7, 142.8, 151.6, 168.1; FTIR (KBr): 3047, 2980, 1734, 1683, 1600,
717 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H22NO: 352.1701; found: 352.1698.
(E)-3-((E)-3-(4-Methoxyphenyl)-1-phenylallylidene)-1-methylindolin-2-one (3c): 78.9 mg,
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87% yield; orenge solid; mp 96-98 C; Rf 0.3 (10% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  3.29 (s, 3H), 3.80 (s, 3H), 5.69 (d, J = 7.6 Hz, 1H), 6.43 (d, J = 16.0 Hz, 1H),
6.59 (t, J = 8.0 Hz, 1H ), 6.74 (d, J = 7.6 Hz, 1H), 6.84 (d, J = 8.8 Hz, 2H), 7.08 (t, J = 8.0 Hz,
1H ), 7.23-7.31 (m, 2H), 7.48 (d, J = 8.4 Hz, 2H ), 7.50-7.57 (m, 3H), 9.27 (d, J = 16.0 Hz,
1H); 13C{1H} NMR(100 MHz, CDCl3):  25.8, 55.4, 107.5, 114.3, 121.5, 123.4, 123.6, 125.7,
127.9, 128.4, 128.7, 129.2, 129.5, 129.9, 137.9, 141.5, 142.6, 151.8, 160.6, 168.2; FTIR (KBr):
3055, 2992, 1671, 1600, 1416, 1165, 1087, 890 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd
for C25H22NO2: 368.1651; found: 368.1673.
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4-((E)-3-((E)-1-Methyl-2-oxoindolin-3-ylidene)-3-phenylprop-1-en-1-yl)benzonitrile
(3d):
81.4 mg, 90% yield; orenge solid; mp 160-162 oC; Rf 0.24 (10% ethyl acetate in hexanes); 1H
NMR (400 MHz, CDCl3):  3.28 (s, 3H), 5.75 (d, J = 7.6 Hz, 1H), 6.41 (d, J = 16.0 Hz, 1H),
6.61 (t, J = 8.0 Hz, 1H ), 6.75 (d, J = 7.6 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 7.23-7.31 (m, 2H),
7.52-7.61 (m, 7H), 9.47 (d, J = 16.0 Hz, 1H);13C{1H} NMR(100 MHz, CDCl3):  25.9, 107.8,
111.7, 118.9, 121.8, 121.8, 123.0, 124.1, 124.5, 128.1, 128.5, 128.8, 129.1, 129.5, 131.0, 132.5,
137.1, 138.4, 141.4, 143.2, 149.6, 167.9; FTIR (KBr): 3051, 2980, 1679, 1604, 1419, 1259,
734 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H19N2O: 363.1497; found: 363.1484.
(E)-3-((E)-3-(4-Chlorophenyl)-1-phenylallylidene)-1-methylindolin-2-one (3e): 87.1 mg, 94%
o
1
yield; orenge solid; mp 118-120 C; Rf 0.45 (10% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  3.28 (s, 3H), 5.72 (d, J = 7.6 Hz, 1H), 6.39 (d, J = 16.0 Hz, 1H), 6.60 (t, J =
7.6 Hz, 1H ), 6.73 (d, J = 7.6 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 7.23-7.31 (m, 4H), 7.44 (d, J =
8.4 Hz, 2H), 7.50-7.53 (m, 3H), 9.35 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):
 25.8, 107.7, 121.7, 123.0, 123.3, 123.8, 128.2, 128.5, 128.6, 129.0, 129.0, 129.4, 134.8,
135.5, 137.5, 139.8, 143.0, 150.7, 168.1; FTIR (KBr): 3055, 2980, 1734, 1671, 1607, 1427,
1259, 882, 717 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H19NOCl: 372.1155; found:
372.1166.
(E)-3-((E)-3-(4-Bromophenyl)-1-phenylallylidene)-1-methylindolin-2-one (3f): 93.3 mg, 90%
yield; orenge solid; mp 136-138 oC; Rf 0.5 (10% ethyl acetate in hexanes); 1H NMR (400 MHz,
CDCl3):  3.30 (s, 3H), 5.73 (d, J = 8.0 Hz, 1H), 6.38 (d, J = 16.4 Hz, 1H), 6.61 (t, J = 7.6 Hz,
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1H ), 6.75 (d, J = 7.6 Hz, 1H), 7.12 (t, J = 8.0 Hz, 1H ), 7.23-7.30 (m, 2H), 7.38 (d, J = 8.4 Hz,
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2H), 7.43 (d, J = 8.8 Hz, 2H), 7.51-7.65 (m, 3H), 9.37 (d, J = 16.0 Hz, 1H); C{1H} NMR
(100 MHz, CDCl3):  25.9, 107.7, 121.7, 123.1, 123.1, 123.3, 123.8, 128.1, 128.5, 128.6, 129.3,
129.4, 131.9, 135.9, 137.5, 139.9, 142.9, 150.7, 168.1; FTIR (KBr): 3059, 2929, 1686, 1604,
1573, 1471, 1341, 1251, 1078, 729 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C24H19NOBr: 416.0650; found: 416.0672.
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(E)-3-((E)-3-(3-Bromophenyl)-1-phenylallylidene)-1-methylindolin-2-one (3g): 89.2 mg, 86%
yield; orenge solid; mp 78-80 oC; Rf 0.45 (10% ethyl acetate in hexanes); 1H NMR (400 MHz,
CDCl3):  3.28 (s, 3H), 5.73 (d, J = 8.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 6.60 (t, J = 7.6 Hz,
1H ), 6.74 (d, J = 8.0 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H ), 7.17 (t, J = 7.6 Hz, 1H ), 7.22-7.23 (m,
2H), 7.35-7.40 (m, 1H), 7.46 (d, J = 7.6 Hz, 1H ), 7.50-7.53 (m, 3H), 7.61 (s, 1H), 9.34 (d, J =
13
16.0 Hz, 1H); C{1H} NMR (100 MHz, CDCl3):  25.9, 107.7, 121.7, 123.0, 123.2, 123.4,
123.8, 126.2, 128.6, 128.7, 128.9, 129.4, 130.2, 130.8, 131.8, 137.4, 139.1, 139.6, 143.0, 150.5,
168.0; FTIR (KBr): 3051, 2988, 1632, 1431, 1263, 894, 738 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C24H19NOBr: 416.0650; found: 416.0625.
(E)-3-((E)-1,3-Diphenylallylidene)-1-ethylindolin-2-one (3h): 72.8 mg, 83% yield; orenge
liquid; Rf 0.56 (10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  1.31 (t, J = 7.2
Hz, 3H), 3.86 (q, J = 7.2 Hz, 2H), 5.74 (d, J = 8.0 Hz, 1H), 6.47 (d, J = 16.0 Hz, 1H), 6.58 (t,
J = 7.6 Hz, 1H ), 6.75 (d, J = 8.0 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H) 7.20-7.35 (m, 5H), 7.48-
7.60 (m, 5H), 9.40 (d, J = 16.0 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):  12.9, 34.4, 107.6,
121.4, 122.7, 123.6, 123.9, 127.7, 127.9, 128.9, 128.5, 128.6, 128.8, 129.1, 129.3, 137.0, 137.7,
141.5, 141.9, 151.2, 167.7; FTIR (KBr): 3055, 2969, 2929, 1675, 1569, 1463, 1357, 1114, 738
cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H22NO: 352.1701; found: 352.1719.
(E)-3-((E)-1,3-Diphenylallylidene)-1-propylindolin-2-one (3i): 80.3 mg, 88% yield; orenge
liquid; Rf 0.65 (10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  1.02 (t, J = 7.6
Hz, 3H), 1.77 (q, J = 7.6 Hz, 2H), 3.76 (t, J = 7.2 Hz, 2H), 5.73 (t, J = 8.0 Hz, 1H), (6.47 (d, J
= 16.0 Hz, 1H), 6.58 (t, J = 7.6 Hz, 1H ), 6.75 (d, J = 7.6 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H) 7.20-
7.35 (m, 5H), 7.49-7.61 (m, 5H), 9.40 (d, J = 16.4 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):
 11.7, 21.2, 41.4, 107.8, 121.4, 122.6, 123.5, 123.8, 127.8, 128.0, 128.2, 128.5, 128.7, 128.8,
129.1, 129.3, 136.9, 137.8, 141.5, 142.4, 151.2, 168.0; FTIR (KBr): 3059, 2984, 1730, 1600,
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1444, 1259, 1043, 894, 734 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C26H24NO:
366.1858; found: 366.1828.
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(E)-1-Benzyl-3-((E)-1,3-diphenylallylidene)indolin-2-one (3j): 92.9 mg, 98% yield; orenge
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solid; mp 98-100 C; Rf 0.59 (10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3): 
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5.02 (s, 2H), 5.74 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 16.0 Hz, 1H), 6.57 (t, J = 7.6 Hz, 1H ), 6.66
(d, J = 7.6 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H) 7.20-7.40 (m, 10H), 7.50-7.60 (m, 5H), 9.40 (d, J
= 16.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):  43.5, 108.5, 121.7, 122.4, 123.5, 123.8,
127.4, 127.6, 127.8, 128.1, 128.3, 128.6, 128.7, 128.8, 128.9, 129.2, 129.4, 136.4, 137.4, 141.9,
142.1, 151.9, 168.1; FTIR (KBr): 3059, 2984, 1734, 1683, 1368, 1259, 1051, 717 cm-1; HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C30H24NO: 414.1858; found: 414.1872.
(E)-1-Acetyl-3-((E)-1,3-diphenylallylidene)indolin-2-one (3k): 92.9 mg, 60% yield; orenge
solid; mp 220-222 oC; Rf 0.61(10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3): 
2.81 (s, 3H), 5.78 (d, J = 7.5 Hz, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.75 (td, J = 7.5, 1.0 Hz, 1H ),
7.16 (td, J = 8.0, 1.0 Hz, 1H), 7.26-7.30 (m, 2H), 7.30-7.39 (m, 3H), 7.51-7.55 (m, 2H), 7.55-
7.59 (m, 3H), 8.25 (d, J = 8.0 Hz, 1H), 9.18 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3):  27.4, 116.1, 121.0, 123.3, 124.3, 124.4, 127.5, 128.2, 128.6, 128.7, 129.0, 129.6,
129.7, 136.6, 137.5, 139.0, 143.6, 153.0, 168.2, 171.0; FTIR (KBr): 3054, 2984, 1705, 1560,
1419, 901, 752 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C25H20NO2: 366.1494; found:
366.1517.
(E)-3-((E)-1,3-Diphenylallylidene)-1-hexylindolin-2-one (3l): 75.7 mg, 75% yield; orenge
liquid; Rf 0.5 (10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  0.89 (t, J = 6.4
Hz, 3H), 1.28-1.50 (m, 6H), 1.64-1.76 (m, 2H), 3.78 (t, J = 7.6 Hz, 2H), 5.73 (d, J = 7.6 Hz,
1H), 6.47 (d, J = 16.0 Hz, 1H), 6.58 (t, J = 7.6 Hz, 1H ), 6.75 (d, J = 7.6 Hz, 1H), 7.09 (t, J =
7.6 Hz, 1H) 7.20-7.35 (m, 5H), 7.47-7.60 (m, 5H), 9.40 (dd, J = 16.4, 1.2 Hz, 1H); 13C{1H}
NMR(100 MHz, CDCl3):  14.2, 22.7, 26.9, 27.8, 31.7, 39.9, 107.8, 121.4, 122.6, 123.5, 123.8,
127.8, 128.0, 128.3, 128.5, 128.7, 128.8, 129.1, 137.0, 137.8, 141.5, 142.4, 151.1, 168.0; FTIR
(KBr): 3059, 2988, 1730, 1679, 1427, 1251, 1039, 738 cm-1; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C29H30NO: 408.2327; found: 408.2333.
(E)-3-((E)-1,3-Diphenylallylidene)-1-octylindolin-2-one (3m): 87.0 mg, 80% yield; orenge
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liquid; Rf 0.5 (10% ethyl acetate in hexanes); H NMR (400 MHz, CDCl3):  0.70-0.90 (m,
4H), 1.10-1.20 (m, 9H), 1.50-1.80 (m, 2H), 3.70 (t, J = 7.6 Hz, 2H), 5.64 (t, J = 8.0 Hz, 1H),
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6.39 (d, J = 16.0 Hz, 1H), 6.50 (t, J = 8.0 Hz, 1H ), 6.67 (d, J = 7.6 Hz, 1H), 7.00 (t, J = 8.0
Hz, 1H) 7.14-7.27 (m, 5H), 7.39-7.52 (m, 5H), 9.32 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3):  14.2, 22.8, 27.3, 27.9, 29.3, 29.5, 31.9, 39.9, 107.8, 121.3, 122.6, 123.5, 123.8,
127.7, 128.0, 128.2, 128.5, 128.6, 128.8, 129.1, 129.3, 137.0, 137.8, 141.5, 142.4, 151.2, 168.0;
FTIR (KBr): 3051, 2984, 1726, 1423, 1267, 898, 734 cm-1; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C31H34NO: 436.2640; found: 436.2629.
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Methyl(E)-4-((E)-1-methyl-2-oxoindolin-3-ylidene)-4-phenylbut-2-enoate (3n): 70.2 mg, 88%
yield; red orenge solid; mp 124-126 oC; Rf 0.40 (20% ethyl acetate in hexanes); 1H NMR (400
MHz, CDCl3):  3.26 (s, 3H), 3.77 (s, 3H), 5.71 (d, J = 15.6 Hz, 1H), 5.81 (d, J = 7.6 Hz, 1H),
6.61 (t, J = 7.6 Hz, 1H ), 6.73 (d, J = 7.6 Hz, 1H), 7.12-7.24 (m, 3H), 7.46-7.58 (m, 3H), 9.55
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(d, J = 15.6 Hz, 1H); C{1H} NMR (100 MHz, CDCl3):  26.0, 52.0, 108.0, 122.0, 122.5,
124.8, 127.8, 128.4, 128.7, 129.0, 129.6, 130.1, 136.5, 141.5, 144.1, 147.1, 167.1, 167.3; FTIR
(KBr): 3062, 2977, 1710, 1604, 1427, 1267, 894, 753 cm-1; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C20H18NO3: 320.1286; found: 320.1299.
Ethyl(E)-4-((E)-1-methyl-2-oxoindolin-3-ylidene)-4-phenylbut-2-enoate (3o): 69.7 mg, 84%
yield; red orenge solid; mp 136-138 oC; Rf 0.39 (20% ethyl acetate in hexanes); 1H NMR (400
MHz, CDCl3):  1.30 (t, J = 7.2 Hz, 1H), 3.25 (s, 3H), 4.23 (q, J = 7.2 Hz, 2H) 5.71 (d, J =
15.6 Hz, 1H), 5.79 (d, J = 8.0 Hz, 1H), 6.60 (t, J = 7.6 Hz, 1H ), 6.73 (d, J = 7.6 Hz, 1H), 7.10-
7.24 (m, 3H), 7.46-7.57 (m, 3H), 9.54 (d, J = 16.0 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):
 14.4, 25.9, 60.8, 107.9, 121.9, 122.5, 124.8, 127.6, 128.3, 128.4, 128.9, 129.2, 129.5, 129.5,
129.6, 130.0, 136.6, 141.3, 144.1, 147.2, 166.7, 167.3; FTIR (KBr): 3059, 2988, 1698, 1596,
1471, 1282, 738 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H20NO3: 334.1443; found:
334.1469.
Butyl (E)-4-((E)-1-methyl-2-oxoindolin-3-ylidene)-4-phenylbut-2-enoate (3p): 73.1 mg, 81%
1
yield; orenge solid; Rf 0.30 (10% ethyl acetate in hexanes); H NMR (400 MHz, CDCl3): 
0.94 (t, J = 7.6 Hz, 3H), 1.35-1.47 (m, 2H), 1.61-1.72 (m, 2H), 3.26 (s, 3H), 4.17 (t, J = 6.8 Hz,
2H ), 5.71 (d, J = 16.0 Hz, 1H), 5.79 (d, J = 7.6 Hz, 1H), 6.01 (t, J = 7.6 Hz, 1H), 6.73 (d, J =
8.0 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H), 7.18-7.24 (m, 2H), 7.45-7.55 (m, 3H), 9.54 (d, J = 16.0
Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):  13.9, 19.3, 26.0, 30.8, 64.8, 107.9, 122.0, 122.6,
124.8, 128.4, 128.9, 129.2, 129.6, 130.0, 136.6, 141.3, 144.1, 147.2, 166.8, 167.3; FTIR (KBr):
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3054, 2954, 2928, 2871, 2212, 1700, 1640, 1468, 1365 cm-1; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C23H24NO3: 362.1688; found: 362.1678.
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(E)-4-((E)-1-Methyl-2-oxoindolin-3-ylidene)-4-phenylbut-2-enamide (3q): 53.9 mg, 71%
yield; red orenge solid; mp 240-242 oC; Rf 0.3(70% ethyl acetate in hexanes); 1H NMR (400
MHz, CDCl3):  3.26 (s, 3H), 5.69-5.87 (m, 3H), 6.61 (t, J = 8.0 Hz, 1H), 6.74 (d, J = 8.0 Hz,
1H), 7.16 (t, J = 8.0 Hz, 1H), 7.19-7.25 (m, 2H), 7.48-7.58 (m, 3H), 9.36 (d, J = 16.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3):  26.0, 106.1, 108.2, 118.1, 122.0, 125.1, 128.2, 128.5,
129.4, 129.8, 130.8, 135.0, 139.7, 144.4, 145.0, 147.2, 166.9; FTIR (KBr): 3059, 2988, 1683,
1431, 1267, 894, 725 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C19H17N2O2: 305.1290;
found: 305.1303.
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(E)-4-((E)-1-Methyl-2-oxoindolin-3-ylidene)-4-phenylbut-2-enenitrile (3r): 55.0 mg, 77%
yield; red orenge solid; mp 178-180 oC; Rf 0.30 (10% ethyl acetate in hexanes); 1H NMR (400
MHz, CDCl3):  3.25 (s, 3H), 5.18 (d, J = 16.4 Hz, 1H), 5.78 (d, J = 7.6 Hz, 1H), 6.62 (d, J =
7.6 Hz, 1H), 6.74 (t, J = 8.0 Hz, 1H ), 7.15-7.22 (m, 3H), 7.51-7.59 (m, 3H), 9.42 (d, J = 16.4
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):  26.0, 106.1, 108.2, 118.1, 122.0, 125.1, 128.2,
128.5, 129.4, 129.8, 130.8, 135.0, 139.7, 144.4, 145.0, 147.2, 166.9; FTIR (KBr): ν = 3059,
2984, 1694, 1604, 1472, 1419, 1266, 1090, 891, 738 cm-1; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C19H15N2O: 287.1184; found: 287.1195.
(E)-3-((E)-1,3-Diphenylallylidene)indolin-2-one (5a): 54.9 mg, 68% yield; orenge solid; Rf 0.5
(20% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  5.72 (d, J = 7.6 Hz, 1H), 6.50
(d, J = 16.0 Hz, 1H), 6.59 (t, J = 7.6 Hz, 1H ), 6.81 (d, J = 8.0 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H),
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7.27-7.38 (m, 5H), 7.-7.62 (m, 5H), 8.43 (s, 1H), 9.29 (d, J = 16.0 Hz, 1H); C{1H} NMR
(100 MHz, CDCl3):  109.4, 121.6, 122.9, 124.0, 124.3, 127.6, 128.1, 128.4, 128.6, 128.7,
128.8, 129.2, 129.4, 136.9, 137.7, 140.3, 142.0, 151.8, 169.9; FTIR (KBr): 3426, 3197, 3061,
1675, 1607, 1574, 1263, 735 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H18NO:
324.1388; found: 324.1419.
(E)-3-((E)-3-(4-Methoxyphenyl)-1-phenylallylidene)indolin-2-one (5b): 53.8 mg, 61% yield;
orenge solid; Rf 0.35 (20% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  3.81 (s,
3H), 5.69 (d, J = 7.6 Hz, 1H), 6.46 (d, J = 16.0 Hz, 1H), 6.58 (t, J = 7.6 Hz, 1H ), 6.81 (d, J =
7.6 Hz, 1H), 6.86 (d, J = 8.8 Hz, 1H), 7.03 (t, J = 7.6 Hz, 1H),7.26-7.34 (m, 2H), 7.48 (d, J =
8.4 Hz, 2H), 7.51-7.60 (m, 3H), 8.66 (s, 1H), 9.19 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (100
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MHz, CDCl3):  55.5, 109.4, 114.3, 121.4, 121.8, 123.7, 124.4, 125.6, 128.0, 128.5, 128.7,
129.3, 129.6, 129.8, 137.9, 140.1, 152.4, 160.7, 170.1; FTIR (KBr): 3424, 3194, 3062, 1672,
1605, 1571, 1266, 734 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H20NO2: 354.1494;
found: 354.1530.
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(E)-3-((E)-3-(4-Chlorophenyl)-1-phenylallylidene)indolin-2-one (5c): 62.4 mg, 70% yield;
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orenge solid; mp 156-158 C; Rf 0.52 (20% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  5.71 (d, J = 7.6 Hz, 1H), 6.42 (d, J = 16.0 Hz, 1H), 6.58 (t, J = 7.6 Hz, 1H ), 6.80
(d, J = 8.0 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H), 7.23-7.33 (m, 5H), 7.43 (d, J = 8.4 Hz, 2H), 7.51-
7.60 (m, 3H), 8.50-8.64 (m, 1H), 9.25 (d, J = 16.0 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):
 109.5, 121.6, 123.3, 124.1, 126.9, 128.1, 128.6, 128.6, 128.7, 128.9, 129.0, 129.0, 129.1,
129.2, 129.2, 129.4, 129.5, 134.9, 135.5, 137.5, 140.2, 140.4, 151.3, 169.9; FTIR (KBr): 3428,
3196, 3062, 1675, 1607, 1573, 1263, 734 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C23H17NOCl: 358.0998; found: 358.1029.
(E)-3-((E)-3-(4-Bromophenyl)-1-phenylallylidene)indolin-2-one (5d): 67.1 mg, 67% yield;
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orenge solid; mp 198-200 C; Rf 0.52 (20% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  5.72 (d, J = 8.0 Hz, 1H), 6.40 (d, J = 16.0 Hz, 1H), 6.59 (t, J = 7.6 Hz, 1H ), 6.80
(d, J = 7.6 Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 7.24-7.32 (m, 3H), 7.37 (d, J = 8.4 Hz, 2H), 7.44
(d, J = 8.0 Hz, 2H), 7.52-7.61 (m, 3H), 8.45 (s, 1H), 9.27 (d, J = 16.0 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3):  109.5, 121.7, 123.2, 123.3, 124.1, 128.2, 128.6, 129.4, 129.4, 132.0,
135.9, 137.5, 140.2, 140.3, 151.3, 169.8; FTIR (KBr): 3062, 2980, 1690, 1423, 1259, 902, 753
cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H17NOBr: 402.0493; found: 402.0525.
4-((E)-3-((E)-2-Oxoindolin-3-ylidene)-3-phenylprop-1-en-1-yl)benzonitrile (5e): 62.6 mg,
o
72% yield; red solid; mp 164-166 C; Rf 0.38 (20% ethyl acetate in hexanes); 1H NMR (400
MHz, CDCl3):  5.74 (d, J = 8.0 Hz, 1H), 6.43 (d, J = 16.0 Hz, 1H), 6.59 (t, J = 7.6 Hz, 1H ),
6.81 (d, J = 7.6 Hz, 1H), 7.07 (t, J = 7.6 Hz, 1H), 7.24-7.32 (m, 2H), 7.53-7.62 (m, 7H), 8.57
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(s, 1H), 9.37 (d, J = 16.0 Hz, 1H); C{1H} NMR (100 MHz, CDCl3):  109.6, 117.8,118.9,
121.8, 123.8, 124.3, 124.7, 128.2, 128.5, 128.9, 129.1, 129.5, 130.8, 132.5, 137.0, 138.7, 140.7,
141.3, 150.2, 169.7; FTIR (KBr): 3429, 2977, 2929, 1734, 1734, 1604, 1436, 1267, 734 cm-1;
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H17N2O: 349.1340; found: 349.1359.
(E)-3-((E)-1,3-Diphenylallylidene)benzofuran-2(3H)-one (7a): 52.6 mg, 65% yield; orenge
solid; Rf 0.67 (10% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  5.76 (d, J = 8.0
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Hz, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.73 (t, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 7.16 (t, J
= 8.0 Hz, 1H), 1.35-1.47 (m, 2H), 7.27-7.32 (m, 2H), 7.32-7.38 (m, 3H), 7.53 (d, J = 6.8 Hz,
2H ), 7.56-7.61 (m, 3H), 8.98 (d, J = 15.6 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):  110.5,
117.8, 123.5, 124.7, 126.7, 128.3, 128.4, 129.0, 129.1, 129.3, 129.6, 129.7, 136.4, 136.9, 143.6,
153.3, 154.2, 167.4; FTIR (KBr): 3054, 2984, 1753, 1564, 1424, 1261, 1046, 896, 738 cm-1;
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H17O2: 325.1252; found: 325.1252.
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(E)-3-((E)-1-phenyl-3-(p-tolyl)allylidene)benzofuran-2(3H)-one (7b): 57.4 mg, 68% yield;
orenge semi solid; Rf 0.63 (20% ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  2.36
(s, 3H), 5.74 (d, J = 8.0 Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.73 (t, J = 8.0 Hz, 1H), 7.04 (d, J
= 8.0 Hz, 1H), 7.10-7.18 (m, 3H), 7.27-7.32 (m, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.55-7.63 (m,
3H), 8.94 (d, J = 16.0 Hz, 1H), 8.95 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):
 29.8, 110.4, 125.9, 128.3, 128.4, 129.0, 129.1, 129.5, 129.7, 133.7, 137.0, 140.4, 143.8,
154.6; FTIR (KBr): 3051, 2982, 1748, 1563, 1428, 1257, 1142, 1067, 895, 717 cm-1; HRMS
(ESI-TOF) m/z: [M+H]+ calcd for C24H18O2: 339.1385; found: 339.1369.
(E)-3-((E)-3-(4-Chlorophenyl)-1-phenylallylidene)benzofuran-2(3H)-one (7c): 59.1 mg, 66%
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yield; orenge solid; mp 176-178 C; Rf 0.67 (10% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  5.76 (dd, J = 6.4, 0.8 Hz, 1H), 6.51 (d, J = 12.8 Hz, 1H), 6.74 (td, J = 6.4, 0.8
Hz, 1H), 7.04 (d, J = 6.0 Hz, 1H), 7.17 (td, J = 6.4, 0.8 Hz, 1H), 7.26-7.30 (m, 2H), 7.31 (d, J
= 6.8 Hz, 2H), 7.46 (d, J = 6.8 Hz, 2H),7.56-7.62 (m, 3H), 8.95 (d, J = 12.8 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3):  110.5, 118.2, 123.5, 124.5, 127.3, 128.3, 129.2, 129.2, 129.4,
129.5, 129.6, 134.9, 135.6, 136.7, 141.8, 153.4, 153.7, 167.4; FTIR (KBr): 3059, 2984, 1757,
1564, 1424, 1261, 1054, 896, 733 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H16ClO2:
359.0838; found: 359.0862.
(E)-3-((E)-3-(3-Bromophenyl)-1-phenylallylidene)benzofuran-2(3H)-one (7d): 64.3 mg, 64%
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yield; orenge solid; mp 196-198 C; Rf 0.51 (20% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  5.77 (d, J = 8.0 Hz, 1H), 6.48 (d, J = 16.0 Hz, 1H), 6.74 (td, J = 8.0, 1.0 Hz,
1H), 7.05 (d, J = 7.5 Hz, 1H), 7.18 (td, J = 7.7, 1.5 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 7.26-2.29
(m, 2H), 7.43 (dd, J = 8.0, 1.0 Hz, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.57-7.60 (m, 3H), 7.61 (t, J
= 2.0 Hz, 1H), 8.95 (d, J = 16.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):  110.6, 118.7,
123.1, 123.6, 123.6, 124.4, 126.4, 128.0, 128.3, 129.2, 129.6, 130.4, 131.2, 132.5, 136.6, 138.5,
141.7, 153.4, 153.5, 167.3; FTIR (KBr): 3054, 2984, 1749, 1560, 1427, 1257, 1142, 1063, 896,
716 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C23H16BrO2: 403.0336; found: 403.0354.
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4-((E)-3-((E)-2-Oxobenzofuran-3(2H)-ylidene)-3-phenylprop-1-en-1-yl)benzonitrile
(7e):
60.2 mg, 69% yield; orenge solid; mp 226-228 oC; Rf 0.60 (20% ethyl acetate in hexanes); 1H
NMR (400 MHz, CDCl3):  5.79 (dd, J = 8.0, 1.0 Hz, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.75 (td,
J = 8.5, 1.0 Hz, 1H), 7.05 (d, J = 6.0 Hz, 1H), 7.21 (td, J = 7.7, 1.5 Hz, 1H), 7.27-7.31 (m, 2H),
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7.58-7.65 (m, 7H), 9.06 (d, J = 16.0 Hz, 1H); C{1H} NMR (100 MHz, CDCl3):  110.7,
112.4, 118.8, 119.8, 123.7, 123.9, 124.2, 128.3, 128.4, 129.4, 129.7, 129.9, 130.1, 132.6, 136.3,
140.4, 140.7, 152.5, 153.6, 167.2; FTIR (KBr): 3054, 2984, 2254, 1757, 1564, 1266, 1054,
729, 702 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C24H16NO2: 350.1181; found:
350.1199.
Experimental procedure to synthesize of olefins from corresponding aldehydes by Wittig
reaction (styrene 2 was synthesized using reported literature procedure with modification.)21
Benzaldehyde derivative (5 mmol) was added to potassium carbonate (1.03 g, 7.5 mmol) and
methyltriphenylphosphonium bromide (2.1 g, 6 mmol) in anhydrous 1,4-dioxane (10 mL) and
heated at reflux for 16 h. The reaction mixture was then cooled, filtered and washed with
hexane and then concentrated in vaccuo and purified by column chromatography (10% ethyl
acetate in hexanes).
styrene (2a): colourless liquid; 477 mg, 90% yield; 1H NMR (400 MHz, CDCl3):  5.24 (d, J
= 10.8 Hz, 1H), 5.74 (d, J = 17.6 Hz, 1H), 6.72 (dd, J = 11.2, 6.4 Hz, 1H), 7.24 (t, J = 7.2 Hz,
1H), 7.32 (t, J = 7.2 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): 
113.9, 126.3, 127.9, 128.6, 137.0, 137.7.
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1-methyl-4-vinylbenzene (2b): light brown liduid; 552 mg, 92% yield; H NMR (400 MHz,
CDCl3):  3.26 (s, 3H), 5.19 (d, J = 10.8 Hz, 1H), 5.71 (d, J = 17.6 Hz, 1H), 6.71 (dd, J = 17.6,
10.8 Hz, 1H), 7.15 (d, J = 7.6 Hz, 2H ), 7.32 (d, 7.6 Hz , 2H), 13C{1H} NMR (100 MHz,
CDCl3):  137.7, 136.8, 135.0, 129.3, 126.2, 112.9 and 21.3; FTIR (KBr): ν = 3094, 3015,
2939, 1630, 1503, 1268, 990, 907, 754 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C9H11:
119.0860; found: 119.0861.
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1-bromo-3-vinylbenzene (2g): light brown liduid; 863 mg, 87% yield; H NMR (400 MHz,
CDCl3):  5.30 (d, J = 10.8 Hz, 1H), 5.76 (d, J = 17.6 Hz, 1H), 6.64 (dd, J = 17.6, 10.8 Hz,
1H), 7.19 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H ), 7.38 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H);
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13C{1H} NMR(100 MHz, CDCl3):  139.8, 135.6, 130.8, 130.2, 129.3, 125.0, 122.8 and 115.5;
FTIR (KBr): ν = 3085, 3060, 1593, 1560, 1468, 1273, 912 cm-1.
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75% yield; H NMR (400 MHz, CDCl3):  3.85 (s, 3H), 3.88 (s, 6H), 5.21 (d, J = 10.8 Hz,
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1H), 5.65 (d, J = 17.2 Hz, 1H), 6.59-6.69 (m, 3H);13C{1H} NMR (100 MHz, CDCl3):  153.4,
138.1, 136.9, 133.4, 113.4, 103.4, 61.0 and 56.2; FTIR (KBr): ν = 3081, 2993, 2936, 1581,
1502, 1455, 1406 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C11H15O3: 195.1021; found:
195.1021.
Experimental procedure to synthesize of acrylate from corresponding acid (acrylate was
synthesized using reported literature procedure with modification.)
A solution of a mixture containing acrylic acid (5 mmol) in methanol and 98% sulfuric acid
was heated to an oil bath at reflux temperature for 12 h and the mixture was left to cool. The
resulting light yellow solution was purified by column chromatography.
methyl acrylate (2n): light brown liduid; 344 mg, 80% yield; 1H NMR (400 MHz, CDCl3): 
3.75 (s, 3H), 5.81 (d, J = 10.4 Hz, 1H), 6.11 (dd, J = 17.6, 10.4 Hz, 1H), 6.39 (d, J = 17.6 Hz,
1H); 13C{1H} NMR(100 MHz, CDCl3):  166.8, 130.9, 128.3 and 51.8; FTIR (KBr): ν = 2939,
2885, 2831, 1718, 1268, 912, 741 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C4H6O2:
104.0675; found: 104.0677.
ethyl acrylate (2o): light brown liduid; 410 mg, 82% yield; 1H NMR (400 MHz, CDCl3):  1.28
(t, J = 7.2 Hz, 3H), 4.19 (q, J = 7.2 Hz, 2H), 5.79 (d, J = 10.0 Hz, 1H), 6.09 (dd, J = 17.6, 10.4
Hz, 1H ), 6.38 (d, J = 17.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3):  166.4, 130.5, 128.7,
60.6 and 14.3; FTIR (KBr): ν = 2986, 2894, 2828, 1718, 1265, 1194, 912, 749 cm-1.
Experimental procedure to synthesize N-(2-iodophenyl)-3-phenylpropiolamide
(N-(2-iodophenyl)-3-phenylpropiolamide was synthesized using reported literature procedure
with modification).21
A suspension of phenylpropiolic acid (2.50 g, 17.1 mmol) and SOCl2 (1.49 mL, 20.5 mmol) in
anhydrous benzene (20 mL) was stirred for 3 h at 70 °C. After 30 min., a clear solution was
resulted. Excess SOCl2 and benzene were removed in vaccuo. The oily residue was dissolved
in anhydrous benzene (20 mL) and cooled to 0 °C. A solution of 2-Iodoaniline (3.4 g, 15.6
mmol) in anhydrous benzene (9 mL) was added over 10 min. The ice bath was removed and
the mixture was stirred for 80 min at r.t. The beige and turbid mixture was poured into ice-cold
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water (40 mL), the organic layer was separated, and the aqueous layer was extracted with
EtOAc (3 × 20 mL). The combined organic layers were washed with 5% HCl, H2O, 5% aq
Na2CO3, and again with H2O (30 mL each). After drying (Na2SO4), the solvent was removed
in vaccuo and the crude product was purified by column chromatography (hexane/EtOAc 9:1
to 8:2 v/v) to give crystalline white solid product. 1H NMR (400 MHz, CDCl3):  6.89 (t, J =
7.2 Hz, 1H), 7.34-7.50 (m, 4H), 7.62 (d, J = 6.8 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 8.26 (d, J =
8.0 Hz, 1H); 13C{1H} NMR(100 MHz, CDCl3):  83.3, 86.6, 89.7, 119.9, 122.5, 126.7, 128.7,
129.5, 130.6, 132.7, 137.9, 139.0, 151.0.
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Experimental procedure to synthesize N-(2-iodophenyl)-N-methyl-3-phenylpropiolamide
(N-(2-iodophenyl)-N-methyl-3-phenylpropiolamide 1 was synthesized using reported
literature procedure with modification.)21
The same procedure was followed for synthesis of other starting materials of Table 3.
A mixture of N-(2-iodophenyl)-3-phenylpropiolamide (10.0 mmol, 3.46 g), methyl iodide
(13.0 mmol, 1.83 g) and anhydrous K2CO3 (15 mmol, 2.07 g) in DMF (10 mL) was stirred
vigorously for 12 h at room temperature and complete reaction was detected by TLC
analysis.The reaction mixture was poured into water (100 mL) and the precipitate was
concentrated to give the crude product was purified by column chromatography
(hexane/EtOAc 9:1 to 8:2 v/v) to give the crystalline white solid product. 1H NMR (400 MHz,
CDCl3):  3.29 (s, 3H), 6.57 (d, J = 7.6 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz,
2H), 7.31 (t, J = 7.6 Hz, 1H ), 7.39 (d, J = 6.8 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H ), 7.96 (d, J =
7.6 Hz, 1H ); 13C{1H} NMR (100 MHz, CDCl3):  35.4, 82.5, 90.7, 99.8, 120.4, 128.4, 129.6,
129.6, 129.9, 130.1, 130.2, 132.6, 139.9, 145.7, 154.5.
Experimental procedure to synthesize 2-iodophenyl 3-phenylpropiolate (6):
(N-(2-iodophenyl)-3-phenylpropiolamide was synthesized using reported literature procedure
with modification);21
A suspension of phenylpropiolic acid (2.50 g, 17.1 mmol) and SOCl2 (1.49 mL, 20.5 mmol) in
anhydrous benzene (20 mL) was stirred for 3 h at 70 °C. After 30 min., a clear solution was
resulted. Excess SOCl2 and benzene were removed in vaccuo. The oily residue was dissolved
in anhydrous benzene (20 mL) and cooled to 0 °C. A solution of 2-Iodophenol (3.41 g, 15.6
mmol) in anhydrous benzene (9 mL) was added over 10 min. The ice bath was removed and
the mixture was stirred for 80 min at r.t. The beige and turbid mixture was poured into ice-cold
water (40 mL), the organic layer was separated, and the aqueous layer was extracted with
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EtOAc (3 × 20 mL). The combined organic layers were washed with 5% HCl, H2O, 5% aq
Na2CO3, and again with H2O (30 mL each). After drying (Na2SO4), the solvent was removed
in vaccuo and the crude product was purified by column chromatography (hexane/EtOAc 9:1
to 8:2 v/v) to give oily liquid product.
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Experimental procedure to synthesize of (E)-1-methyl-3-((E)-1-phenyl-3-(4-(phenylethy
nyl)phenyl)allylidene)indolin-2-one (8):
To a solution of (E)-3-((E)-3-(4-bromophenyl)-1-phenylallylidene)-1-methylindolin-2-one 3f
(0.25 mmol, 103 mg) in THF solvent under inert atmosphere, CuI (4.7 mg, 0.1 equiv) PdCl2
(PPh3)2, (8.7 mg, 0.05 equiv), phenylacetylene (30 mg, 0.3 mmol) and NEt3 (50 mg, 0.5 mmol)
were simultaneously added, the solution was stirred for 12 h at 60 °C. Upon completion
(monitored by TLC), the reaction mixture was cooled down to room temperature and extracted
with EtOAc and dried over Na2SO4. The residue was purified by column chromatography on
silica gel (hexane/EtOAc) to give desired product 8. 87.2 mg, 80% yield; orenge solid; Rf 0.24
(20% ethyl acetate in hexanes).1H NMR (400 MHz, CDCl3):  3.31 (s, 3H), 5.73 (dd, J = 7.6
Hz, 1H), 6.45 (d, J = 16.0 Hz, 1H), 6.61 (t, J = 7.6 Hz, 1H), 6.76 (d, J =8.0 Hz, 1H), 7.12 (t, J
= 7.6 Hz, 1H), 7.21-7.30 (m, 2H), 7.31-7.36 (m, 3H), 7.46-7.57 (m, 9H), 9.41 (d, J =16.0 Hz,
1H), 13C{1H} NMR (100 MHz, CDCl3):  25.9, 89.7, 91.3, 107.7, 121.7, 123.0, 123.3, 123.4,
123.8, 127.9, 128.5, 128.5, 128.7, 129.4, 131.8, 132.0, 136.9, 137.6, 140.6, 143.0, 150.9, 168.1;
HRMS (ESI-TOF) m/z: [M+H]+ calcd for C32H24NO: 438.1857; found: 438.1857.
Experimental procedure to synthesize of (E)-1-methyl-3-((E)-1-phenyl-3-(3,4,5-
trimethoxyphenyl)allylidene) indolin-2-one (9):
To a solution of N-(2-iodophenyl)-N-methyl-3-phenylpropiolamide 1a (0.25 mmol, 90 mg) in
DMF were added Pd-BNP (2 mol%), 1,2,3-trimethoxy-5-vinylbenzene (0.37 mmol, 71.8 mg),
and NaOAc (0.5 mmol, 41 mg), and the solution was stirred for 14 h at 110 °C. Upon
completion (monitored by TLC), the reaction mixture was cooled down to room temperature
and extracted with EtOAc and dried over Na2SO4. The residue was purified by column
chromatography on silica gel (hexane/EtOAc) to give (E)-1,3-diphenylallylidene)-1-
methylindolin-2-one 9, 77.9 mg, 73% yield; orenge solid; Rf 0.24 (20% ethyl acetate in
hexanes). 1H NMR (400 MHz, CDCl3):  3.28 (s, 3H), 3.85 (s, 3H), 3.88 (s, 6H), 5.68 (d, J =
7.6 Hz, 1H), 6.39 (d, J = 15.6 Hz, 1H), 6.59 (t, J = 7.6 Hz, 1H), 6.68-6.79 (m, 3H), 7.09 (t, J
=8.0 Hz, 1H), 7.23-7.33 (m, 2H), 7.51-7.61 (m, 7H), 9.28 (d, J = 15.6 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3):  25.8, 56.2, 61.0, 105.0, 107.5, 121.6, 122.3, 123.4, 123.6, 127.1, 128.2,
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128.5, 128.6, 129.3, 132.6, 137.9, 139.3, 141.6, 142.7, 151.1, 153.4, 168.1; FTIR (KBr): 3067,
2940, 2838, 1684, 1607, 1574, 1459, 1341, 1242, 1124, 1001, 744 cm-1; HRMS (ESI-TOF)
m/z: [M+H]+ calcd for C27H26NO4: 428.1861; found: 428.1849.
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Experimental procedure for recovery of the Pd-BNP catalyst14a,14e
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For recyclability of Pd-BNP, the reaction was carried out with 1.0 mmol scale using the
optimized reaction condition such as N-methyl-3-phenylpropiolamide 1a (1 equiv), styrene 2a
o
(1.5 equiv), NaOAc (2 equiv), Pd-BNP (2 mol%) and DMF as a solvent at 110 C, After
completion of the reaction, the reaction mixture was allowed to cool to room temperature.
EtOH (5 mL) was added to the reaction mixture and centrifuged. The liquid was decanted to a
50 mL conical flask. Again EtOH (5 mL) was added and centrifuged and decanted to the same
conical flask, this procedure was repeated up to three to four times. After that, the catalyst was
washed with nano-pure water and ethanol three to four times. Finally, the resulting solid black
colored particles (Pd-BNP) dried under vacuum. The dried catalyst was reused for further
catalytic cycle. The collected liquid was extracted with ethyl acetate (3 × 10 mL), followed by
brine solution. Then the organic phase was dried over Na2SO4 and concentrated in vacuum.
The resulting reaction mixture was purified by column chromatography.
Experimental procedure for hot filtration test14a,14e
The reaction was catalyzed by a heterogeneous catalyst, not by the leached homogeneous
catalyst a hot centrifugation test was performed under the standard reaction condition. In which
two separate reactions were carried out by using 1a (1.0 mmol, 1.0 equiv), 2a (1.5 equiv),
NaOAc (2 equiv.), Pd-BNP catalyst (2 mol%), in 4 mL DMF were taken in oven-dried reaction
o
tube equipped with magnetic pellet and stirred at 110 C. After 2 h of reaction, one set of the
reaction was removed cool down at rt added EtOH, reaction mixture was centrifuged, and Pd-
BNP catalyst was removed from the reaction mixture. This process was repeated multiple time
sequentially and mother liquid (which is completely free from the catalyst), 0.1 mL was taken
from the mother liquid, extracted with ethyl acetate and submitted for NMR. 1H NMR showed
that 22% yield of 3a was obtained. From the remaining mother liquid i.e., Pd-BNP free-
reaction mixture, under similar conditions further continued for 12 h. After 12 h, the reaction
was stoped and the reaction mixture was submitted for NMR, no improvement of yield was
observed indicating no active catalyst was present to catalyzed further reaction. The yield was
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determined by H NMR using 1,3,5-Trimethoxybenzene as an internal standard. The same
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procedure was followed to another set of reactions.
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Mercury poisoning experiment14a,14e
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Mercury poisoning experiment was performed to support that the domino reaction was
accelerated by heterogeneous Pd-BNP catalyst, not by the leached homogeneous Pd.
 In this experiment, Hg (30 equiv) and Pd-BNP (2 mol%) were stirred at room
temperature for 2 h, then other reagents: 1a (0.25 mmol), 2a (1.5 equiv), NaOAc (2
equiv) in DMF 1,3,5 trimethoxy benzene (1.0 equiv) was added and stirred at 110 °C.
Even trace amount of product 3a was not detected in the reaction even continue the
reaction for 12 h.
 In the second set of reaction, Hg (30 equiv) was added at a time with all other reagents
1a (0.25 mmol), 2a (1.5 equiv), NaOAc (2 equiv), Pd-BNP (2 mol%), and 1,3,5
o
trimethoxy benzene as internal standard (1.0 equiv) were added and stirred at 110 C
up to12 h. Complete inhibition in the product 3a formation was observed.
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at
DOI:
1H and 13C{1H} NMR spectra for all compounds, X-ray structure and brief crystal data of
compounds
X-ray data for compound 3a (CIF)
X-ray data for compound 3o (CIF)
X-ray data for compound 5b (CIF)
X-ray data for compound 7c (CIF)
X-ray data for compound 9 (CIF)
■ AUTHOR INFORMATION
Corresponding Author
*E-mail: gsekar@iitm.ac.in
ORCID
Govindasamy Sekar: 0000-0003-2294-0485
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Naziya Parveen: 0000-0002-0038-2403
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Notes
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The authors declare no competing financial interest.
9
ACKNOWLEDGMENTS
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G.S. thank IIT Madras for financial support (No. CHY/17-18/847/RFIR/GSEK). N.P. thanks
CSIR-UGC, New Delhi for senior research fellowship. We thank department of chemistry, IIT
Madras for infrastructure and instrumentation facilities.
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