Phosphine-Free and Reusable Palladium Nanoparticles-Catalyzed Domino Strategy: Synthesis of Indanone Derivatives

Article abstract of DOI:10.1021/acs.joc.8b00463

The carbene migratory insertion involving a domino reaction by highly stable, reusable, and binaphthyl-stabilized Pd-nanoparticles (Pd-BNP) is disclosed. The reaction was catalyzed by 2 mol % of a heterogeneous Pd-BNP catalyst under external ligand-free c

Full text of DOI:10.1021/acs.joc.8b00463

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Phosphine-Free and Reusable Palladium Nanoparticles
Catalyzed Domino Strategy: Synthesis of Indanone Derivatives
Rajib Saha, Dhanarajan Arunprasath, and Govindasamy Sekar
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00463 • Publication Date (Web): 02 Apr 2018
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Phosphine-Free and Reusable Palladium Nanoparticles Catalyzed
Domino Strategy: Synthesis of Indanone Derivatives
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Rajib Saha, Dhanarajan Arunprasath, and Govindasamy Sekar*
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Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu –
600036, India
ABSTRACT: The carbene migratory insertion involving domino reaction by highly stable,
reusable and binaphthyl stabilized Pdꢀnanoparticles (PdꢀBNP) is disclosed. The reaction was
catalyzed by 2 mol% of heterogeneous PdꢀBNP catalyst under external ligandꢀfree conditions
and afforded 3ꢀarylꢀsubstituted indanone derivatives in up to 90% yield with exclusive Eꢀ
selectivity. Furthermore, a oneꢀpot reaction and derivatization of indanone derivatives were
also successfully demonstrated.
KEYWORDS: Pd-nanoparticles; nano-catalyst; ligand-free; domino; N-tosylhydrazones;
indanones
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INTRODUCTION
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Transitionꢀmetalꢀcatalyzed CꢀC bond formation reactions are wellꢀaccepted synthetic
strategies for the synthesis of rich biologically active pharmaceuticals and natural products.1ꢀ
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Recently the use of metalꢀcarbenoid involving domino reactions holds tremendous promise
to construct cyclic architectures via multiple CꢀC bond formation in a single step.3ꢀ5 While
diazo compounds have been primarily used as carbene precursors, they lessen synthetic
strategies due to instability and explosive nature in the absence of electron withdrawing
groups.6ꢀ7 In this regard, stable and safe Nꢀtosylhydrazones have been introduced as an
alternative carbene precursors.8ꢀ15 Utilizing Nꢀtosylhydrazones, few Pdꢀcatalytic cycles have
been reported that converges carbene migratory insertion with other transformation for the
synthesis of cyclic skeletons (Scheme 1a).16ꢀ21
Recently, our group and Valdés et al. have independently reported the homogeneous Pdꢀ
catalyzed carbene insertion followed by an intramolecular Heck reaction for the formation of
indanone motifs (Scheme 1b).22ꢀ23 Despite their own merits, these protocols have few
shortcomings. For instance, the requirement of bulky and electronꢀrich external phosphine
ligands to achieve smooth conversions make them less adaptable for the sustainable synthesis
and it produces inevitable phosphine oxides which are tedious to remove. Moreover, the
difficulties in the separation of homogeneous palladium catalyst from the final product create
costꢀeffective and environmental barriers to broadening their scope.
These difficulties could be addressed by emergent palladium nanoꢀcatalysis which has
increasing attention in both academic and industry owing to their unique reactivity, stability,
recyclability and avoidance of metal residues in the products.24ꢀ27 In this context, we have
developed a binaphthyl backꢀbone stabilized Pdꢀnano catalyst (PdꢀBNP) which has shown
excellent activity, robustness, and recyclability for several times for many kinds of reactions
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without any apparent metal leaching.28ꢀ31 We intended to investigate the catalytic activity of
PdꢀBNP in domino reactions as there are very less literature reports available for nanoꢀ
particle catalyzed domino reactions32ꢀ35 and to the best of our knowledge, there is no report
available for the heterogeneous Pdꢀcatalyzed domino reaction which involves carbene
migratory insertion as a keyꢀstep.
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Scheme 1. PdꢀCatalyzed Carbene Migratory Insertion Involving Domino Reactions
To our continuous efforts toward Pdꢀnanoparticles catalyzed sustainable organic
transformations, we herein report the external phosphine ligandꢀfree and reusable PdꢀBNP
catalyzed domino carbene migratory insertion/Heckꢀtype cyclization strategy for the
synthesis of indanone derivatives in excellent yields using mild organic base (Scheme 1c). It
is noteworthy to mention that indanone containing scaffolds have been reported to show
interesting biological activities.36ꢀ42
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RESULTS AND DISCUSSION
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Our initial investigation was carried out by using 2'ꢀiodochalcone 1a and benzaldehyde
derived Nꢀtosylhydrazone 2a as model substrates in the presence of PdꢀBNP 5 (2.0 mol%)
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catalyst with Et3N (3 equiv) in 1,4ꢀdioxane as solvent at 80 C. To our delight, the
corresponding domino cyclized product 2ꢀarylideneꢀ3ꢀarylꢀ1ꢀindanones 3a was detected in
71% yield with exclusive Eꢀselectivity along with 8% of intramolecular reductive Heck
cyclized product 4a. Next, the reaction was studied with various nanoparticles as the catalytic
activity of nanoꢀcatalyst is very much dependent on the stabilizers and results were
summarized in Scheme 2.
Scheme 2. Domino Reaction with Various PdꢀNanoparticles
aYields were determined by 1H NMR using 1,3,5ꢀtrimethoxy benzene as an internal standard.
Other stabilizers such as phenyl (PdꢀPNP) 6, nꢀdecylꢀphenyl (PdꢀDPNP) 7, nꢀdecyloxyꢀ
phenyl (PdꢀDOPNP) 8 and commercially available PdꢀNP have been used to improve the
yield of the process. However, these stabilizers showed only low to moderate activities
compared with binaphthyl stabilizer (PdꢀBNP). Notably, Pd supported on carbon (10 wt% of
Pd) gave 3a in 33% yield. Additional investigation on Pd:stabilizer ratio manifested that
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stabilizer quantity tunes the catalytic activity of nanoparticles. PdꢀBNP (Pd:binaphthyl=1:2)
gave less yield presumably due to decrease in active sites with excess stabilizer.
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Additional investigations on catalyst loading showed that, use of 2.0 mol% was found to be
optimal as 3.0 mol% and 1.0 mol% loading led to slightly decreased yield of 68% and 59%
respectively (Table 1, entries 1 and 2). Except Et3N and Hünig’s base (N,Nꢀ
diisopropylethylamine), both organic and inorganic bases failed to provide the desired
product 3a (entries 3ꢀ7). Modification in the equiv of Et3N did not improve the yield (entries
8 and 9). Further screening of solvents to improve efficacy of the reaction were ineffective as
1,4ꢀdioxane was found to be the best solvent (entries 10ꢀ12). Lowering the reaction
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temperature to 70 C, decreased the yield dramatically to 36% (entry 13). It can be observed
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that raising the temperature to 90 C also led to slight decrease in yield (entry 14).
Delightfully, we obtained the product 3a in the best yield (94%) while adding 2a in two
portions (entry 15). However, addition of 2a using syringe pump over 3 h resulted in slightly
decreased yield (entry 16). No product 3a was observed in the absence of the PdꢀBNP
catalyst. It must be noted that, domino reaction was found to be very selective towards Eꢀ
isomer as we did not observe other isomer in the 1H NMR analysis of crude mixture.
Having optimized reaction conditions (Table 1, entry 15), we then explored the scope of
substrates and the results were summarized in Scheme 3. At first, various substituted Nꢀ
tosylhydrazones 2 were employed with 2'ꢀiodochalcone 1a. It was observed that electronꢀ
donating group containing Nꢀtosylhydrazones gave good yields of the corresponding cyclized
products (3b-3e). Bromoꢀsubstituted hydrazones also gave the desired product 3f in 90%
yield. Electron withdrawing group such as 4ꢀNO2 and 4ꢀCN bearing Nꢀtosylhydrazones were
unable to furnish the desired cyclized products (3ah and 3ai) as hydrazones decomposed
rapidly to give the corresponding carbonyl compounds. This may be due to unfavorable
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increment in the electron deficiency of Pdꢀcarbenoids.43 In case of orthoꢀsubstituted
hydrazones 2aj, the reaction did not occur presumably due to the increased steric hindrance
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which may suppress the carbene migratory insertion as it situated near to η3ꢀbenzylpalladium
intermediate.
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Table 1. Optimization of the Reaction Conditionsa
base
(equiv)
temp
(oC)
80
yield (%)b
3a/4a
entry
solvent
1c
2d
3
Et3N (3.0)
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
THF
68/16
Et3N (3.0)
DIPEA (3.0)
DBU (3.0)
DABCO (3.0)
K2CO3 (3.0)
LiOtBu (3.0)
Et3N (2.5)
Et3N (4.0)
Et3N (3.0)
Et3N (3.0)
Et3N (3.0)
Et3N (3.0)
Et3N (3.0)
Et3N (3.0)
Et3N (3.0)
80
80
80
80
80
80
80
80
80
80
80
70
90
80
80
59/6
40/48
0/0
4
5
0/0
6
7e
0/0
trace/0
57/0
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9
60/15
55/12
30/0
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14
15f,g
16h
Diphenyl ether
Toluene
49/0
1,4ꢀDioxane
1,4ꢀDioxane
1,4-Dioxane
1,4ꢀDioxane
36/10
65/15
94 (90)/0
91/0
aReaction conditions: 1a (0.5 mmol), 2a (1.25 mmol), 9.6 mg of PdꢀBNP (2 mol %, 11 wt%
Pd by ICPꢀOES analysis) in 2 mL solvent for 12ꢀ15 h. Yields were determined by 1H NMR
b
c
d
using 1,3,5ꢀtrimethoxy benzene as an internal standard. 3.0mol% PdꢀBNP. 1.0mol% Pdꢀ
e
f
BNP. 10.0 equiv of H2O was additionally used. 2a was added in two portions with 3 h time
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interval. gValue in parentheses represents isolated yield. h2a was added using a syringe pump
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over 3 h.
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Scheme 3. Substrate Scope of PdꢀBNP Catalyzed Domino Reactiona,b
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O
O
R
Pd-BNP (2 mol %)
Et3N (3 equiv)
R
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NNHTs
H
Ar
Ar
1,4-dioxane, 80 o
C
Ar
I
Ar
1
2
3
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
3a, 90%
O
Me
3b, 85%
Me
tBu
3c, 88%
3d, 81%
SMe
3e, 82%
O
O
O
O
Ph
Ph
Ph
Me
OMe
Ph
Ph
OMe
3j, 86%
O
3f, 90%
3g, 84%
3h, 86%
3i, 82%
Me
O
Br
O
O
O
Cl
Br
F
Cl
Ph
Ph
Ph
3m, 83%
O
Br
iPr
Cl
3k, 81%
3l, 79%
3o, 90%
3n, 78%
OMe
O
O
O
O
Br
F
OMe
CF3
tBu
OMe
OMe
3q, 80%
OMe
3r, 89%
OMe
3s, 82%
Me
3p, 85%
3t, 83%
O
O
O
O
O
O
Cl
F
Me
Me
MeO
Me
Et
3v, 84%
SMe
3w, 86%
OMe
3u, 86%
3x, 83%
3y, 84%
O
O
O
O
O
O
O
Br
S
Ph
Ph
3ag, 56%
O
Ph
CN
3ab, 81%
3z, 83%
Me
3aa, 86%
iPr
3ah, 0%
NO2
O
O
O
Ph
Ph
Ph
Ph
Me
N
3al, 0%
3ai, 0%
3ak, 0%
3aj, 0%
CN
aReaction conditions: 1 (0.5 mmol), 2 (1.25 mmol), 9.6 mg of PdꢀBNP (2 mol %, 11 wt% by
ICPꢀOES analysis) in 2 mL of 1,4ꢀdioxane at 80 oC for 12ꢀ15 h. b2 was added in two portions
with 3 h time interval.
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Next, a series of substituted 2'ꢀiodochalcones 1 were subjected to react with benzaldehyde
derived Nꢀtosylhydrazones 2a and the products were isolated in 79ꢀ86% yields (3g-3l). Diꢀ
haloꢀsubstituted 2'ꢀiodochalcones also furnished corresponding products 3m and 3p in 83%
and 85% yields respectively without affecting the halogen groups. This implies that the
protocol is highly selective and the unaffected halogen groups of the resulting products can
be used for further transformations. In addition, the structure of 3m was confirmed by single
crystal XRD analysis (See SI). Importantly, sterically demanding diꢀorthoꢀsubstituted system
offered the product 3n in 78% yield. This result suggests that diꢀortho substitution did not
affect the βꢀH elimination as substituents present away from the reaction taking place.
Heterocyclic systems such as 2ꢀfuryl and 2ꢀthienyl containing chalcones also offered the
products in good yields (3y and 3z). Further, we investigated the effect of substitution on the
iodoꢀattached ring of the 2'ꢀiodochalcone and the products were isolated in admirable yields
(3aa and 3ab). Electronꢀwithdrawing group was also well tolerated as 4ꢀCN containing
chalcone gave the desired product in 3ag in 56% yield. However, 4ꢀpyridine containing
tosylhydrazone did not deliver the product 3ak. Less reactive 2'ꢀbromochalcones, alkyl
aldehyde 2al and acetophenone derived tosylhydrazones also did not furnish the desired
products. It must be noted that the current PdꢀBNP heterogeneous catalyst displayed higher
yields of many substrates than our previous homogenous Pd(OAc)2 catalytic system. This is
presumably due to Pd2+ complex has to get reduced to active Pd0 species to initiate the
domino process via oxidative addition onto the ArꢀI bond of 1 while PdꢀBNP catalyst possess
native Pd0 form.
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To check the scalability of our optimized reaction conditions, a gramꢀscale reaction was
carried out by using of 1.0 g of 2'ꢀiodochalcone 1a and Nꢀtosylhydrazones 2a. Scaleꢀup
reaction afforded the cyclic product 3a in 82% yield in 12 h (Scheme 4).
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Scheme 4. GramꢀScale Synthesis using PdꢀBNP Catalyst
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Next, the newly developed catalytic system was tested in a oneꢀpot condition by promoting in
situ generation of Nꢀtosylhydrazones from the corresponding carbonyl partner and Nꢀ
tosylhydrazide. Pleasantly, 78% yield of 3a was obtained in the oneꢀpot reaction where the 2'ꢀ
iodochalcone and catalyst were added after reacting the Nꢀtosylhydrazide with benzaldehyde
in 1,4ꢀdioxane for 1 h (Scheme 5). 4ꢀEt and 4ꢀCl substituted arylaldehydes were good
substrates, giving 76% and 75% yields respectively (3ac and 3ad). A thienylchalcone
produced 3af in 68% yield. However, 4ꢀCN bearing benzaldehyde did not produce the
desired product under our oneꢀpot reaction conditions.43
Scheme 5. A Oneꢀpot Reaction from Aldehyde
We suggest a possible reaction pathway based on the literature precedent (Scheme 6).20ꢀ22 Pdꢀ
BNP nanoꢀcatalyst first reacts with the 2'ꢀiodochalcone 1 to yield an intermediate A which
then advances to Pdꢀcarbenoid B by reacting with in situ generated diazo spices. The
electrophilic carbenoid B subsequently undergoes migratory insertion and furnishes
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benzylpalladium intermediate C44 which further undergoes intramolecular 5ꢀexo-trig mode of
carbopalladation giving rise to D. Upon synꢀβꢀH elimination, D delivers the desired product 3
with Eꢀselectivity.
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Scheme 6. Plausible Reaction Mechanism
1ꢀIndanone 3a was further derivatized into useful heterocyclic compounds (Scheme 7).
Densely functionalized pyridineꢀcontaining heteroꢀtricyclic core 10 and 11 were synthesized
while treating 3a with malononitrile in 82% and 74% yield respectively. Upon reacting with
pyridinium salt, 3a furnished 5Hꢀindeno[1,2ꢀb]pyridine derivative 12 in 80% yield after 24 h.
Reduction of 3a with molecular hydrogen in the presence of Pd/C gave compound 13 in 92%
yield with a dr 1:1.
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Scheme 7. Synthetic Application of the Indanones
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Further efforts were made to examine the reusability and recoverability of the PdꢀBNP
catalyst from the viewpoint of industrial applications. The model reaction was conducted at 1
mmol scale under the standard conditions. The catalyst was recovered and reused up to five
catalytic cycles and desired product 3a was isolated in the yields of 89%, 87%, 87%, 86%
and 85% in successive runs which proves the preserved activity of the catalyst (Figure 1).
Figure 1. Recyclability of PdꢀBNP catalyst
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Moreover, HRꢀTEM analysis of recovered PdꢀBNP catalyst after five runs showed that there
was no major change in the size distribution and dispersion of the nanoparticles compared
with the fresh catalyst. The average size of PdꢀBNP was found to be 5ꢀ6 nm (Figure 2).
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Figure 2. HRꢀTEM pictures of PdꢀBNP catalyst: Fresh catalyst (left) and recycled catalyst
after five runs (right)
Stability of the nanoꢀcatalyst in the solution phase is also crucial for an outstanding
heterogeneous catalyst as leaching of the metal could make the catalyst to lose its activity. As
our nano particles size is < 6 nm, it can pass through membrane filters. So, instead of hot
filtration test, hot centrifugation test has been carried out to prove that reaction was catalyzed
by the heterogeneous palladium. PdꢀBNP catalyst was removed from the reaction by simple
centrifugation in the middle of the reaction at two different time intervals. After
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centrifugation, both liquid portions were allowed to continue the reaction at 80 C. The
reaction did not proceed in both the cases which clearly prove that no catalytically active
palladium had been present in the liquid phase of the reaction (Figure 3).
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Figure 3. Hot centrifugation test. Black line: X = 3 h; Red line: X = 6 h.
Additionally, centrifuged residue has shown almost similar catalytic activity as compared
with the fresh PdꢀBNP. ICPꢀOES analysis of the reaction solution revealed that Pd
concentration is 0.021 wt% indicating that leaching of Pd into the solution is very negligible.
Mercury poisoning test also confirmed that the main catalyst to accelerate the domino
reaction was the heterogeneous PdꢀBNP (See SI for details). These results illustrate that Pdꢀ
BNP behaves as a sole heterogeneous catalyst for the domino process rather than leached
palladium.
CONCLUSIONS
In conclusion, an efficient and robust heterogeneous PdꢀBNP catalyzed domino synthesis of
indanone derivatives was developed through carbene migratory insertion strategy. This
ligandꢀfree protocol showed a broad substrate scope with respect to both the coupling
partners with good to excellent yields and Eꢀselectivity. PdꢀBNP was easily recovered and
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reused up to five times without any apparent agglomeration. However, a detailed mechanistic
study and further application of PdꢀBNP are under progress.
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Experimental Section
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General remarks: All reactions were carried out in ovenꢀdried reaction tubes. Reactions
were monitored by thinꢀlayer chromatography (TLC) using Merck silica gel 60 F254 precoated
plates (0.25 mm) and visualized by UV fluorescence quenching using appropriate mixture of
ethyl acetate and hexanes. Silica gel (particle size: 100ꢀ200 mesh) was purchased from Avra
Synthesis Pvt. Ltd. and used for column chromatography using hexanes and ethyl acetate
mixture as eluent. Solvents used for extraction and column chromatography were laboratory
grade and used as received. Reaction solvents used were obtained from Fischer Scientific,
India Pvt. Ltd. K2PdCl4 (98%), various aldehydes and Nꢀtosylhydrazide were purchased from
SigmaꢀAldrich, AlfaꢀAesar, TCI and Spectrochem Pvt. Ltd. India. Other chemicals like
NaBH4, DIPEA, DBU, DABCO and triethylamine were purchased from Avra and
Spectrochem Pvt. Ltd., India. (±)ꢀBINAM was purchased from Gerchem Pvt. Ltd.
Hyderabad, India. 1,1'ꢀBinaphthyl,ꢀ2,2'ꢀbis(diazoniumtetrafluoroborate) was prepared using
literature reported procedure.1 Nano pure water was obtained from MilliꢀQ Integral Water
Purification System. All the reactions were carried out in temperature controlled IKA
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magnetic stirrers. H and C NMR spectra were recorded on a Bruker 400 MHz (100 MHz
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for C) instrument. H NMR spectra were reported relative to residual CDCl3 (δ 7.26 ppm).
Chemical shifts were reported in parts per million and multiplicities are as indicated: s
(singlet,) d (doublet,) t (triplet,) q (quartet,) and m (multiplet). Coupling constants J, are
reported in Hertz. Melting points were recorded on a Guna capillary melting point apparatus
and are corrected. Infrared spectra were recorded on a FTIR 4000 Series Spectrometer. The
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wave numbers of recorded IR signals are quoted in cmꢀ1. High resolution mass spectra
(HRMS) were recorded on QꢀTof Micro mass spectrometer.
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Inductively coupled plasmaꢀoptical emission spectrometer (ICPꢀOES) from Perkin Elmer
Optima 5300 DV was used to find the Pdꢀcontent of the nanoparticles. Samples were
prepared by digesting 5 mg of nanoparticles in 1.0 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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HRꢀTEM analysis of samples was performed using a JEM 2010 electron microscope. TEM
analysis of the samples was done using carbon coated copper grids (nanoparticles in
dichloromethane solutions). The instrument was operated at 200 kV.
Diazotization of (1,1'-binaphthalene)-2,2'-diamine (BINAM)28
The binaphthyldiazonium salt 2 was synthesized by the diazotization of (1,1'ꢀbinaphthalene)ꢀ
2,2'ꢀdiamine (BINAM ) 1. The stable binaphthyldiazonium salt was prepared by the slow
addition of aqueous solution of sodium nitrite (NaNO2) to a stirred solution of BINAM in
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HBF4 at 0 C and the reaction mixture was stirred further at 0 C for 30 min. The colour
change from pale brown to yellow colour indicates the formation of diazonium salt. The
resulting yellow solid was filtered and washed with cold HBF4, H2O and EtOH. The
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diazonium salt 2 was dried under a vaccum desiccator and stored at 0 C. The reaction
yielded 95% of the diazonium salt.
General procedure for the preparation of Pd-BNP catalyst28
To a 250 mL round bottom flask potassium tetrachloropalladate (K2PdCl4) (653 mg,
2.0 mmol, 1 equiv) was dissolved in nanopure water (30 mL). 1,1'ꢀbinaphthyl,ꢀ2,2'ꢀ
bis(diazoniumtetrafluoroborate) 2 (964.2 mg, 2.0 mmol, 1 equiv) and toluene (30 mL) was
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added to this solution and stirred vigorously for 1 h at room temperature. The orangeꢀbrown
colour formation shows the complexation of Pd with diazonium salt 2. After that a solution of
NaBH4 (453.8 mg, 12.0 mmol) in nanopure water (1.5 mL) was added slowly dropwise at rt
and the immediate colour change to dark greenish black indicates the formation of palladium
nanoparticles. The reaction mixture was further stirred at room temperature for another 2 h.
The toluene layer was then separated and washed with 0.5 M aq. H2SO4 (3 × 40 mL) and 0.5
M aq. NaHCO3 (3 × 40 mL) to remove unreacted metal complexes. Then the solvent was
completely evaporated under rotary evaporator and the resultant solid residues were
suspended in ethanol (2 × 10 mL) and sonicated for 30 minutes at room temperature. The
suspension was further centrifuged (5000 rpm) for 30 min. The ethanol was decanted and
dried in vacuum to obtain the Pdꢀbinapthyl NPs (PdꢀBNP) 3 (789 mg, 11 wt% Pd, ICPꢀOES
analysis).
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Procedure for the synthesis of other diazoniumtetrafluoroborate salt28
To a 100 mL round bottom flask, a solution of nanopure water (2.0 mL) and conc. HCl (2.0
mL) (1:1) was added to a mixture of aryl amine (16.0 mmol, 1.0 equiv) and conc. HCl (3.0
mL) at 0 oC. To this reaction mixture, a solution of NaNO2 (17.6 mmol, 1.1 equiv) in 1.5 mL
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of nanopure water was added slowly drop by drop and stirred for 30 min. at 0 C. After that
ice cold solution of 45% aq HBF4 (10 mL) was added slowly to the reaction mixture and
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stirred for 15 min at 0 C. The resulting solid precipitate was filtered and washed with ice
cold nanopure water and dried under vacuum desiccator and stored at 0 oC.
Procedure for the preparation of Pd-nanoparticles (6, 7 and 8)
To a stirred solution of K2PdCl4 (326.5 mg, 1.0 mmol, 1 equiv) in nanopure water (50 mL) in
250 mL round bottom flask, diazoniumtetrafluoroborate (2.0 mmol) and toluene (50 mL) was
added and stirred vigorously in magnetic stirrer for 4 h. After that the toluene layer was
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separated and washed twice with nanopure water. To this washed toluene layer NaBH4 (226.9
mg, 6.0 mmol) in water (3.0 mL) was added dropwise at room temperature and the immediate
colour change to dark greenish black indicates the formation of palladium nanoparticles. The
reaction mixture was further stirred for 2 h at room temperature. The toluene layer was
separated and washed with 0.5 M aq. sulphuric acid (3 × 50 mL) and 0.5 M aq. sodium
bicarbonate (3 × 50 mL). The solvent was completely evaporated under rotary evaporator.
The solid particles were suspended in ethanol (2 × 10 mL) and sonicated for 30 min. at room
temperature and further the suspension was centrifuged. The ethanol was decanted and dried
under vacuum to furnish the Pdꢀnanoparticles. See the SI for TEM images.
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General procedure for palladium nanoparticles catalyzed domino strategy to synthesis
of indanone derivatives
Under open atmosphere, (E)ꢀ2′ꢀiodochalcone 1 (167 mg, 0.5 mmol), Nꢀtosylhydrazone 2 (171
mg, 0.625 mmol), PdꢀBNP (11 wt% Pd by ICPꢀOES analysis) (9.64 mg, 0.01 mmol), and
triethylamine (0.2 mL, 1.5 mmol) were successively added to oven dried reaction tube. 1,4ꢀ
Dioxane (2.5 mL) were added and closed with a glassꢀstopper. The reaction tube was then
immersed in an 80 ºC preꢀheated oil bath. After 3 h, another portion of Nꢀtosylhydrazone 2
(171 mg, 0.625 mmol) was added. The reaction was heated with stirring till complete
consumption of 2′ꢀiodochalcone. Upon cooling down to room temperature, the solvent was
removed under reduced pressure. Water was added to reaction mixture and extracted with
ethyl acetate (3×5 mL). Brine wash (1×10 mL) was given to the combined organic
extractions and dried over anhydrous Na2SO4. Removal of solvent and silica gel column
separation of crude using hexanes and ethyl acetate mixture (19:1) afforded the
corresponding 2ꢀarylideneꢀ3ꢀarylꢀ1ꢀindanone 3.
(E)-2-Benzylidene-3-phenyl-2,3-dihydro-1H-inden-1-one (3a)
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133 mg, 90% yield; white solid; mp 143ꢀ145 C (lit. 143ꢀ145 C)22; Rf 0.37 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 5.33 (s, 1H), 7.09ꢀ7.15 (m, 1H), 7.16ꢀ7.26
(m, 7H), 7.33ꢀ7.41 (m, 2H), 7.42ꢀ7.55 (m, 3H), 7.85 (d, J = 1.6 Hz, 1H), 7.92 (d, J = 7.6 Hz,
1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.8, 124.3, 126.0, 127.0, 127.7, 128.0, 128.5,
129.0, 129.7, 131.4, 134.1, 135.2, 135.7, 136.1, 138.5, 141.4, 154.5, 194.7; FTIR (film) 3026,
1688, 1620, 1465, 1449, 749 cmꢀ1; HRMS (m/z): [M+K]+ calcd for C22H16OK: 335.0833;
found: 335.0829.
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(E)-2-Benzylidene-3-(p-tolyl)-2,3-dihydro-1H-inden-1-one (3b)
132 mg, 85% yield; pale yellow solid; mp 149ꢀ151 C (lit. 148ꢀ150 oC)22; Rf 0.62 (15% ethyl
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acetate in hexanes); H NMR (CDCl3, 400 MHz) 2.22 (s, 3H), 5.31 (s, 1H), 7.00 (d, J = 7.6
Hz, 2H), 7.10 (d, J = 7.6 Hz, 2H), 7.20ꢀ7.28 (m, 3H), 7.33ꢀ7.42 (m, 2H), 7.43ꢀ7.53 (m, 3H),
7.81 (s, 1H), 7.91 (d, J = 7.2 Hz, 1H); 13C{1H}NMR (CDCl3, 100 MHz) δ 21.1, 48.5, 124.3,
126.0, 127.5, 127.9, 128.5, 129.7, 129.8, 131.6, 134.2, 135.2, 135.6, 136.1, 136.6, 138.6,
138.7, 154.8, 194.9; FTIR (film) 3025, 2917, 1698, 1623, 1292, 1093, 746 cmꢀ1; HRMS
(m/z): [M+K]+ calcd for C23H18OK: 349.0989; found: 349.0982.
(E)-2-Benzylidene-3-(4-(tert-butyl)phenyl)-2,3-dihydro-1H-inden-1-one (3c)
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155 mg, 88% yield; white solid; mp 177ꢀ179 C (lit. 176ꢀ178 C)22; Rf 0.42 (10% ethyl
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acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 1.22 (s, 9H), 5.31 (s, 1H), 7.11ꢀ7.29 (m,
7H), 7.36ꢀ7.55 (m, 5H), 7.83 (s, 1H), 7.92 (d, J = 7.6 Hz, 1H); C{1H}NMR (CDCl3, 100
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MHz) δ 31.4, 34.5, 48.4, 124.3, 126.0, 126.1, 127.2, 127.9, 128.5, 129.6, 131.6, 134.3, 135.1,
135.5, 136.1, 138.4, 138.8, 149.8, 154.8, 195.0; FTIR (KBr) 2961, 2870, 1690, 1619, 1601,
1292, 1093 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C26H24ONa: 375.1719; found: 375.1709.
(E)-2-Benzylidene-3-(4-(methylthio)phenyl)-2,3-dihydro-1H-inden-1-one (3d)
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139 mg, 81% yield; pale yellow solid; mp 140ꢀ142 C (lit. 138ꢀ140 oC)22; Rf 0.58 (15% ethyl
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acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 2.34 (s, 3H), 5.31 (s, 1H), 7.05ꢀ7.19 (m,
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4H), 7.22ꢀ7.30 (m, 3H), 7.32ꢀ7.43 (m, 2H), 7.43ꢀ7.60 (m, 3H), 7.84 (s, 1H), 7.92 (d, J = 7.2
Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 15.8, 48.3, 124.4, 126.0, 127.1, 128.1, 128.2,
128.6, 129.8, 131.5, 134.1, 135.2, 135.8, 136.1, 137.1, 138.3, 138.4, 154.4, 194.7; FTIR
(film) 3029, 1698, 1622, 1491, 1292, 1092, 752 cmꢀ1; HRMS (m/z): [M+K]+ calcd for
C23H18OSK: 381.0710; found: 381.0704.
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(E)-2-Benzylidene-3-(m-tolyl)-2,3-dihydro-1H-inden-1-one (3e)
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127 mg, 82% yield; pale yellow solid; mp 130ꢀ132 C (lit. 127ꢀ129 oC)22; Rf 0.41 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.21 (s, 3H), 5.29 (s, 1H), 6.93 (d, J = 7.2
Hz, 1H), 6.98 (s, 1H), 7.09ꢀ7.16 (m, 2H), 7.20ꢀ7.29 (m, 3H), 7.33ꢀ7.42 (m, 2H), 7.43ꢀ7.52
(m, 3H), 7.83 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H); 13C{1H}NMR (CDCl3, 100 MHz) δ 21.5,
48.8, 124.3, 124.9, 126.1, 127.8, 128.0, 128.2, 128.5, 128.9, 129.7, 130.5, 134.3, 135.2,
135.7, 136.1, 138.7 (2C), 141.5, 154.7, 194.9; FTIR (film) 3025, 1698, 1624, 1464, 1292,
1093, 742 cmꢀ1; HRMS (m/z): [M+K]+ calcd for C23H18OK: 349.0989; found: 349.0978.
(E)-2-Benzylidene-3-(4-bromophenyl)-2,3-dihydro-1H-inden-1-one (3f)
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169 mg, 90% yield; pale brown solid, mp 146ꢀ148 C (lit. 144ꢀ147 oC)22; Rf 0.37 (10% ethyl
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acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 5.34 (s, 1H), 7.10 (d, J = 8.4 Hz, 2H),
7.23ꢀ7.30 (m, 3H), 7.33 (d, J = 8.0 Hz, 3H),7.40ꢀ7.48 (m, 3H), 7.52ꢀ7.59 (m, 1H), 7.86 (s,
1H), 7.94 (d, J = 7.2 H , 1H); 13C{1H}NMR (CDCl3, 100 MHz) δ 48.2, 121.0, 124.5, 126.0,
128.3, 128.6, 129.4, 130.0, 131.4, 132.2, 134.0, 135.3, 136.1, 136.2, 138.1, 140.6, 153.9,
194.4; FTIR (film) 3029, 1698, 1624, 1292, 1092, 750 cmꢀ1; HRMS (m/z): [M+Na]+calcd for
C22H15OBrNa: 397.0198; found: 397.0183.
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(E)-2-(3-Methylbenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3g)
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130 mg, 84% yield; white solid; mp 144ꢀ146 C (lit. 141ꢀ143 C)22; Rf 0.36 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.16 (s, 3H), 5.26 (s, 1H), 6.97 (d, J = 7.6
Hz, 1H), 7.02ꢀ7.10 (m, 2H), 7.12ꢀ7.23 (m, 6H), 7.26ꢀ7.35 (m, 2H), 7.45 (t, J = 7.2 Hz, 1H),
7.75 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 21.3, 49.0, 124.4,
126.1, 127.0, 127.8, 128.0, 128.4, 128.8, 129.0, 130.1, 132.2, 134.1, 135.1, 136.0, 136.2,
138.0, 138.4, 141.7, 154.6, 194.8; FTIR (film) 3024, 2917, 1697, 1618, 1490, 1292, 1088,
747 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C23H18ONa: 333.1250; found: 333.1247.
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(E)-2-(4-Methylbenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3h)
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133 mg, 86% yield; white solid; mp 205ꢀ206 C (lit. 202ꢀ204 C)22; Rf 0.42 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 2.29 (s, 3H), 5.34 (s, 1H), 7.05 (d, J = 7.6
Hz, 2H), 7.12ꢀ7.17 (m, 1H), 7.20ꢀ7.28 (m, 4H), 7.34ꢀ7.43 (m, 4H), 7.49ꢀ7.56 (m, 1H), 7.83
(d, J = 1.6 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 21.6, 48.9,
124.4, 126.0, 127.1, 127.7, 128.0, 129.1, 129.4, 131.4, 131.7, 135.1, 135.9, 136.3, 137.4,
140.4, 141.7, 154.5, 194.9; FTIR (film) 3019, 1690, 1601, 1582, 1292, 1093, 737 cmꢀ1;
HRMS (m/z): [M+K]+ calcd for C23H18OK: 349.0989; found: 349.0976.
(E)-2-(3-Methoxybenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3i)
134 mg, 82% yield; pale yellow solid, mp 136ꢀ138 oC (lit. 137ꢀ1390 oC)22; Rf 0.31 (10% ethyl
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acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 3.62 (s, 3H), 5.35 (s, 1H), 6.81(dd, J =
8.0, 1.6 Hz, 1H), 6.94 (s, 1H), 7.04ꢀ7.13 (m, 1H), 7.13ꢀ7.20 (m, 2H), 7.21ꢀ7.30 (m, 4H), 7.35ꢀ
7.43 (m, 2H), 7.49ꢀ7.57 (m, 1H), 7.83 (d, J = 1.6 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H); 13C{1H}
NMR (CDCl3, 100 MHz) δ 48.8, 55.4, 115.3, 116.7, 124.4, 124.8, 126.0, 127.2, 127.6, 128.1,
129.2, 129.5, 135.2, 135.5, 135.9, 136.1, 138.4, 141.7, 154.5, 159.6, 194.7; FTIR (film) 3029,
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365.0938; found: 365.0932.
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(E)-2-(4-Methoxybenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3j)
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140 mg, 86% yield; pale yellow solid; mp 166ꢀ168 C (lit. 163ꢀ165 oC)22; Rf 0.28 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz,) δ 3.76 (s, 3H), 5.30 (s, 1H), 6.76 (d, J = 8.8
Hz, 2H), 7.10ꢀ7.19 (m, 1H), 7.20ꢀ7.29 (m, 4H), 7.34ꢀ7.41 (m, 2H), 7.44 (d, J = 7.6 Hz, 2H),
7.48ꢀ7.56 (m, 1H), 7.82 (d, J = 1.6 Hz ,1H), 7.92 (d, J = 7.6 Hz, 1H); 13C{1H} NMR (CDCl3,
100 MHz) δ 48.9, 55.4, 114.1, 124.3, 126.0, 126.9, 127.1, 127.7, 127.9, 129.1, 133.6, 134.9,
135.6, 135.9, 136.4, 141.6, 154.4, 161.0, 194.8; FTIR (film) 3029, 1693, 1599, 1510, 1253,
1174, 743 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C23H18O2Na: 349.1199; found: 349.1193.
(E)-2-(Naphthalen-2-ylmethylene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3k)
o
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140 mg, 81% yield; pale white solid; mp 200 C; Rf 0.34 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 5.46 (s, 1H), 7.14 (t, J = 7.2 Hz, 1H), 7.20ꢀ7.28 (m, 2H), 7.32 (d,
J = 7.6 Hz, 2H), 7.40ꢀ7.51 (m, 4H), 7.52ꢀ7.60 (m, 2H), 7.65ꢀ7.78 (m, 3H), 7.93ꢀ8.00 (m, 2H),
8.02 (d, J = 1.6 Hz, 1H);13C{1H} NMR (CDCl3, 100 MHz) δ 49.1, 124.4, 126.1, 126.6,
127.2, 127.5, 127.7, 127.8, 127.9, 128.0 (2C), 128.7, 129.2, 131.8, 132.5, 133.1, 133.6, 135.2,
135.9 ,136.3, 138.7, 141.8, 154.5, 194.7; FTIR (film) 3019, 1684, 1605, 1581, 1294, 1091,
749 cmꢀ1; HRMS (m/z): [M+H]+ calcd for C26H19O: 347.1436; found: 347.1447.
(E)-2-(4-Chlorobenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3l)
130 mg, 79% yield; white solid; mp 196ꢀ199 C (lit. 198ꢀ200 C)22; Rf 0.42 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 5.31 (s, 1H), 7.10ꢀ7.25 (m, 7H), 7.34ꢀ7.45
(m, 4H), 7.54 (td, J = 1.2, 7.2 Hz, 1H), 7.78 (d, J = 2.0 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H);
13C{1H} NMR (CDCl3, 100 MHz) δ 48.8, 124.4, 126.1, 127.3, 127.7, 128.2, 128.8, 129.2,
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132.6, 132.7, 134.3, 135.4, 135.8, 136.1, 139.1, 141.2, 154.4, 194.5; FTIR (film) 3025, 1686,
1614, 1291, 1090, 736 cmꢀ1; HRMS (m/z): [M+K]+ calcd for C22H15OClK: 369.0443; found:
369.0438.
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(E)-2-(2-Bromo-4-fluorobenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3m)
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163 mg, 83% yield; white solid; mp 142ꢀ144 C; Rf 0.36 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 5.23 (s, 1H), 6.80ꢀ6.90 (m, 1H), 7.02 (d, J = 8.0 Hz, 2H), 7.08ꢀ
7.19 (m, 3H), 7.20ꢀ7.29 (m, 2H), 7.31 (s, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.57 (td, J = 1.2, 7.6
Hz, 1H), 7.91ꢀ8.02 (m, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.3, 114.2 (d, 2J = 21 Hz),
120.1 (d, 2J = 24 Hz), 124.4, 125.7 (d, 3J = 9 Hz), 126.3, 127.1, 128.0, 128.3, 128.9, 131.2 (d,
3
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4J = 4 Hz), 131.8 (d, J = 9 Hz), 133.4, 135.5, 136.5, 141.0, 142.0, 154.4, 162.3 (d, J = 253
Hz), 193.8; FTIR (film) 3076, 3029, 2884, 1700, 1594, 1481, 1226 cmꢀ1; HRMS (m/z):
[M+H]+ calcd for C22H15OFBr: 393.0290; found: 393.0289.
(E)-2-(2,6-Dichlorobenzylidene)-3-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (3n)
142 mg, 78% yield; white solid; mp 126 oC; Rf 0.36 (10% ethyl acetate in hexanes); 1H NMR
(CDCl3, 400 MHz) δ 3.67 (s, 3H), 5.08 (s, 1H), 6.50 (d, J = 8.8 Hz, 2H), 6.66 (d, J = 8.8 Hz,
2H), 6.99ꢀ7.06 (m, 1H), 7.10 (d, J = 7.6 Hz, 2H), 7.19 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 7.2 Hz,
1H), 7.56 (td, J = 7.6 Hz, 1H), 7.61 (s, 1H), 7.95 (d, J = 7.6 Hz, 1H); 13C{1H} NMR (CDCl3,
100 MHz) δ 48.2, 55.4, 113.5, 124.2, 126.5, 127.6, 128.1, 129.1, 129.5, 130.1, 132.9, 133.6,
134.2, 135.7, 137.2, 145.7, 154.5, 158.3, 193.4; FTIR (film) 3004, 2957, 2903, 2834, 1705,
1509,1249 cmꢀ1; HRMS (m/z): [M+H]+ calcd for C23H17O2Cl2: 395.0606; found: 395.0605.
(E)-2-(4-Bromobenzylidene)-3-(4-isopropylphenyl)-2,3-dihydro-1H-inden-1-one (3o)
o
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188 mg, 90% yield; white solid; mp 203ꢀ205 C; Rf 0.46 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 1.16 (d, J = 6.8 Hz, 6H), 2.80 (h, J = 6.8 Hz, 1H), 5.25 (s, 1H),
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7.07 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H), 7.33ꢀ7.43 (m,
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4H), 7.50ꢀ7.59 (m, 1H), 7.74 (s, 1H), 7.91 (d, J = 7.6 Hz, 1H); C{1H} NMR (CDCl3, 100
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MHz) δ 24.0, 33.7, 48.5, 124.1, 124.4, 126.1, 127.2, 127.5, 128.0, 131.7, 132.8, 134.1, 135.3,
136.0, 138.4, 139.5, 147.8, 154.6, 194.7; FTIR (film) 2961, 2928, 2867, 1689, 1617, 1582,
1290 cmꢀ1; HRMS (m/z): [M+H]+ calcd for C25H22OBr: 417.0854; found: 417.0845.
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(E)-2-(2-Bromo-4-fluorobenzylidene)-3-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one
(3p)
178 mg, 85% yield; white solid; mp 114 oC; Rf 0.28 (10% ethyl acetate in hexanes); 1H NMR
(CDCl3, 400 MHz) δ 3.73 (s, 3H), 5.19 (d, J = 1.6 Hz, 1H), 6.79 (d, J = 8.8 Hz, 2H), 6.86 (dt,
J = 8.4, 2.8 Hz, 1H), 6.94 (d, J = 8.8 Hz, 2H), 7.24 (dd, J = 8.4, 2.8 Hz, 1H), 7.28ꢀ7.32 (m,
2H), 7.44 (d, J = 7.2 Hz, 1H), 7.56 (dt, J = 7.6, 1.2 Hz, 1H), 7.80ꢀ7.92 (m, 2H); 13C{1H}
2
2
NMR (CDCl3, 100 MHz) δ 47.5, 55.3, 114.1, 114.2 (d, J = 21 Hz), 120.2 (d, J = 24 Hz),
124.4, 125.8 (d, 3J = 10 Hz), 126.2, 128.2, 128.9, 131.2 (d, 4J = 4 Hz), 131.9, 132.0 (d, 3J = 9
1
Hz), 133.2, 133.3, 135.5, 136.4, 142.1, 154.7, 158.5, 162.5 (d, J = 253 Hz), 194.0; FTIR
(film) 3074, 2937, 2839, 1701, 1594, 1481, 1324, 744 cmꢀ1; HRMS (m/z): [M+H]+ calcd for
C23H17O2FBr: 423.0396; found: 423.0380.
(E)-3-(4-Methoxyphenyl)-2-(4-(trifluoromethyl)benzylidene)-2,3-dihydro-1H-inden-1-
one (3q)
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158 mg, 80% yield; white solid; mp 143ꢀ145 C; Rf 0.31 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 3.72 (s, 3H), 5.29 (s, 1H), 6.75 (d, J = 8.8 Hz, 2H), 7.11 (d, J =
7.8 Hz, 2H), 7.36 (dd, J = 7.6, 0.8 Hz, 1H), 7.41 (t, J = 7.2 Hz, 1H), 7.47ꢀ7.59 (m, 5H), 7.81
(d, J = 2.0 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.0, 55.3,
114.9, 122.6, 124.5, 125.4 (q, J = 4 Hz), 126.1, 128.2, 128.7, 130.8 (q, J = 27 Hz), 131.3,
133.2, 133.6, 135.6, 135.9, 137.7, 141.3, 154.8, 158.7, 194.5 ; FTIR (film) 2936, 1700, 1626,
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1509, 1323, 1068 cm ; HRMS (m/z): [M+Na]+ calcd for C24H17O2F3Na: 417.1078; found:
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417.1053.
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(E)-2-(4-(tert-butyl)benzylidene)-3-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (3r)
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170 mg, 89% yield; pale semi solid; Rf 0.37 (15% ethyl acetate in hexanes); H NMR
(CDCl3, 400 MHz) δ 1.27 (s, 9H), 3.72 (s, 3H), 5.27 (s, 1H), 6.78 (d, J = 8.8 Hz, 2H), 7.18 (d,
J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.34ꢀ7.41 (m, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.49ꢀ
7.55 (m, 1H), 7.82 (d, J = 1.6 Hz, 1H), 7.89ꢀ7.94 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz)
δ 31.2, 35.0, 48.1, 55.3, 114.6, 124.3, 125.6, 126.0, 127.9, 128.7, 131.5, 131.7, 134.0, 135.1,
135.6, 136.1, 137.9, 153.3, 154.9, 158.5, 195.0; FTIR (film) 3033, 2961, 2933, 1697, 1605,
1509, 1463 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C27H26O2Na: 405.1825; found: 405.1815.
(E)-3-(4-Methoxyphenyl)-2-(naphthalen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one
(3s)
o
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154 mg, 82% yield; white solid; mp 150ꢀ152 C; Rf 0.23 (10% ethyl acetate in hexanes); H
NMR CDCl3, 400 MHz) δ 3.68 (s, 3H), 5.42 (s, 1H), 6.76 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.8
Hz, 2H), 7.37ꢀ7.51 (m, 4H), 7.52ꢀ7.62 (m, 2H), 7.66ꢀ7.78 (m, 3H), 7.45 (d, J = 7.6 Hz, 1H),
7.98ꢀ8.03 (m, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.2, 55.2, 114.5, 124.3, 126.0,
126.5, 127.5, 127.7, 127.9, 128.0, 128.1, 128.7, 128.8, 131.8, 132.6, 133.1, 133.6, 133.9,
135.2, 135.7, 136.1, 139.0, 154.9, 158.6, 194.8.; FTIR (film) 3054, 3004, 2932, 1696, 1614,
1509, 1464 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C27H20O2Na: 399.1361; found: 399.1391.
(E)-2-(3-Methoxybenzylidene)-3-(p-tolyl)-2,3-dihydro-1H-inden-1-one (3t)
141 mg, 83% yield; light yellow solid; mp 96ꢀ98 oC; Rf 0.29 (10% ethyl acetate in hexanes);
1H NMR (CDCl3, 400 MHz) 2.25 (s, 3H), 3.64 (s, 3H), 5.32 (s, 1H), 6.82 (d, J = 8.0 Hz, 1H),
6.97 (s, 1H), 7.05 (d, J = 7.6 Hz, 2H), 7.11 (d, J = 7.6 Hz, 1H), 7.14ꢀ7.22 (m, 3H), 7.35ꢀ7.43
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(m, 2H), 7.53 (d, J = 8.6 Hz, 1H), 7.82 (s, 1H), 7.91 (d, J= 7.2 Hz, 1H); C{1H} NMR
(CDCl3, 100 MHz) δ 21.2, 48.5, 55.4, 115.3, 116.7, 124.4, 124.9, 126.0, 127.5, 128.0, 129.5,
129.9, 135.2, 135.6, 135.7, 136.0, 136.8, 138.5, 138.7, 154.7, 159.6, 194.9; FTIR (film) 3049,
3003, 2957, 2921, 1697, 1622, 1464 cmꢀ1; HRMS (m/z): [M+Na]+calcd for C24H20O2Na:
363.1361; found: 363.1331
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(E)-2-(4-Fluorobenzylidene)-3-(p-tolyl)-2,3-dihydro-1H-inden-1-one (3u)
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141 mg, 86% yield; white solid; mp 155ꢀ157 C; Rf 0.36 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 2.25 (s, 3H), 5.27 (s, 1H), 6.87ꢀ7.19 (m, 2H), 7.03 (d, J = 7.6 Hz,
2H), 7.11 (d, J = 8.0 Hz, 2H), 7.33ꢀ7.42 (m, 2H), 7.43ꢀ7.57 (m, 3H), 7.79 (d, J = 1.2 Hz, 1H),
7.92 (d, J = 7.6 Hz, 1H); C{1H} NMR (CDCl3, 100 MHz) δ 21.2, 48.4, 115.7 (d, J = 21
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Hz), 124.4, 126.0, 127.5, 128.0, 129.9, 130.5 (d, J = 3 Hz), 133.5 (d, J = 9 Hz), 134.3,
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135.3, 136.1, 136.9, 138.3, 154.7, 163.3 (d, J = 250 Hz), 194.7; FTIR (film) 3015, 2971,
2921, 1690, 1597, 1509 cmꢀ1; HRMS (m/z): [M+H]+ calcd for C23H18OF: 329.1342; found:
329.1350.
(E)-3-(4-Ethylphenyl)-2-(4-methylbenzylidene)-2,3-dihydro-1H-inden-1-one (3v)
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142 mg, 84% yield; white solid; mp 205ꢀ207 C ; Rf 0.42 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 1.15 (t, J = 7.6 Hz, 3H), 2.29 (s, 3H), 2.55 (q, J = 7.6 Hz, 2H),
5.30 (s, 1H), 7.02ꢀ7.10 (m, 4H), 7.16 (d, J = 8.0 Hz, 2H), 7.34ꢀ7.44 (m, 4H), 7.48ꢀ7.55 (m,
1H), 7.81 (d, J = 1.6 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ
15.4, 21.6, 28.5, 48.6, 124.3, 126.0, 127.5, 127.9, 128.6, 129.4, 131.5, 131.8, 135.1, 135.7,
136.2, 137.6, 1389, 140.3, 142.9, 154.8, 195.0; FTIR (film) 3050, 2965, 2874, 1687, 1600,
1581 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C25H22ONa: 361.1568; found: 361.1545.
(E)-2-(4-Methylbenzylidene)-3-(4-(methylthio)phenyl)-2,3-dihydro-1H-inden-1-one (3w)
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153 mg, 86% yield; light yellow solid; mp 194ꢀ196 C; Rf 0.30 (10% ethyl acetate in
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hexanes); H NMR (CDCl3, 400 MHz) δ 2.30 (s, 3H), 2.40 (s, 3H), 5.30 (s, 1H), 7.05ꢀ7.13
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(m, 4H), 7.17 (dd, J = 6.8, 2.0 Hz, 2H), 7.34ꢀ7.43 (m, 4H), 7.52 (td, J = 7.6, 0.8 Hz, 1H), 7.82
(d, J = 1.6 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H) ; 13C{1H} NMR (CDCl3, 100 MHz) δ 15.8, 21.6,
48.4, 124.4, 126.0, 127.1, 128.0, 128.2, 129.4, 131.3, 131.7, 135.1, 135.9, 136.3, 137.0,
137.3, 138.5, 140.4, 154.4, 194.8; FTIR (film) 3055, 3024, 2919, 1695, 1621, 1604 cmꢀ1;
HRMS (m/z): [M+H]+ calcd for C24H21OS: 357.1343; found: 357.1313.
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(E)-2-(3-Chlorobenzylidene)-3-(3-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (3x)
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149 mg, 83% yield; white solid; mp 140ꢀ142 C; Rf 0.27 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 3.70 (s, 3H), 5.29 (s, 1H), 6.64ꢀ6.76 (m, 2H), 6.84 (d, J = 7.6 Hz,
1H), 7.13ꢀ7.25 (m, 3H), 7.33 (dt, J = 6.8, 1.6 Hz, 1H), 7.36ꢀ7.45 (m, 2H), 7.48 (s, 1H), 7.55
13
(td, J = 8.4, 1.2 Hz, 1H), 7.75 (d, J = 2.0 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H); C{1H} NMR
(CDCl3, 100 MHz) δ 48.8, 55.3, 112.6, 113.4, 120.4, 124.5, 126.1, 128.2, 129.5, 129.6, 129.7,
130.2, 130.8, 134.1, 134.4, 135.5, 135.9, 136.0, 139.9, 142.7, 154.3, 160.1, 194.4; FTIR
(film) 3000, 2835, 1698, 1465, 1264, 743 cmꢀ1; HRMS (m/z): [M+K]+ calcd for
C23H17O2ClK: 399.0549; found: 399.0539.
(E)-2-(Furan-2-ylmethylene)-3-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (3y)
o
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133 mg, 84% yield; white solid; mp 144ꢀ146 C; Rf 0.18 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 3.72 (s, 3H), 5.27 (s, 1H), 6.39 (s, 1H), 6.57 (s, 1H), 6.77 (d, J =
8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.29ꢀ7.41 (m, 2H), 7.44 (s, 1H), 7.52 (t, J = 7.2 Hz,
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1H), 7.58 (s, 1H), 7.89 (d, J = 7.6 Hz, 1H); C{1H} NMR (CDCl3, 100 MHz) δ 48.2, 55.3,
112.8, 114.1, 117.8, 121.3, 124.3, 126.1, 127.8, 128.8, 134.8, 135.1, 136.5, 136.7, 145.6,
151.3, 154.8, 158.4, 194.5; FTIR (KBr) 3062, 3004, 2957, 1693, 1622, 1509 cmꢀ1; HRMS
(m/z): [M+H]+calcd for C21H17O3: 317.1178; found: 317.1167.
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131 mg, 83% yield; white solid; mp 196ꢀ198 C; Rf 0.36 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 2.27 (s, 3H), 5.18 (s, 1H), 7.01 (t, J = 4.0 Hz, 1H), 7.08 (d, J =
7.6 Hz, 2H), 7.20 (d, J = 7.6 Hz, 2H), 7.32 (d, J = 2.8 Hz, 1H), 7.35ꢀ7.45 (m, 3H), 7.52 (t, J =
7.6 Hz, 1H), 7.90 (t, J = 7.2 Hz, 1H), 8.04 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 21.2,
48.4, 124.3, 125.9, 127.7, 127.8, 127.9, 128.0, 129.8, 132.0, 134.2, 135.1, 136.2, 136.4,
136.8, 138.1, 138.6, 154.5, 194.5; FTIR (film) 3029, 2979, 2921, 1691, 1613, 1418 cmꢀ1;
HRMS (m/z): [M+Na]+calcd for C21H16ONaS: 339.0820; found: 339.0797.
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(E)-6-Benzylidene-7-(4-isopropylphenyl)-6,7-dihydro-5H-indeno[5,6-d][1,3]dioxol-5-one
(3aa)
o
1
146 mg, 86% yield; white solid; mp 240ꢀ242 C; Rf 0.28 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 1.18 (d, J = 7.2 Hz, 6H), 2.82 (h, J = 7.2 Hz, 2H), 5.19 (d, J = 12
Hz, 1H), 6.04 (dd, J = 1.2, 17.2 Hz, 2H), 6.76 (s, 1H), 7.09 (d, J = 8.4 Hz, 2H), 7.14 (d, J =
8.4 Hz, 2H), 7.21ꢀ7.28 (m, 3H), 7.29 (s, 1H), 7.41ꢀ7.50 (m, 2H), 7.73 (d, J = 1.6 Hz, 1H);
13C{1H} NMR (CDCl3, 100 MHz) δ 24.0, 33.7, 48.4, 102.3, 102.8, 105.4, 127.2, 127.5,
128.5, 129.4, 131.4, 134.0, 134.4, 138.7, 139.3, 147.7, 148.6, 152.5, 154.3, 193.1; FTIR
(film) 3058, 2936, 2820, 1667, 1594, 1596, 1442 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for
C26H22O3Na: 405.1461; found: 405.1445.
(E)-2-Benzylidene-6-bromo-3-phenyl-2,3-dihydro-1H-inden-1-one (3ab)
152 mg, 81% yield; white solid; mp 195ꢀ197 C (lit. 194ꢀ196 C)22; Rf 0.42 (10% ethyl
o
o
1
acetate in hexanes); H NMR (CDCl3, 400 MHz) δ 5.32 (s, 1H), 7.18 (d, J = 6.8 Hz, 1H),
7.21ꢀ7.30 (m, 8H), 7.42ꢀ7.55 (m, 2H), 7.65 (d, J = 8.4 Hz, 1H), 7.88 (s, 1H), 8.08 (s, 1H);
13C{1H} NMR (CDCl3, 100 MHz) δ 48.6, 122.4, 127.3, 127.4, 127.7, 127.8, 128.6, 129.2,
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130.0, 131.6, 133.9, 136.7, 137.9, 138.0, 138.1, 140.9, 153.1, 193.3; FTIR (film) 3022, 2913,
1687, 1615. 1582, 1559, 1071 cmꢀ1; HRMS (m/z): [M+K]+ calcd for C22H15OBrK: 412.9938;
found: 412.9929.
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(E)-2-Benzylidene-3-(4-ethylphenyl)-2,3-dihydro-1H-inden-1-one (3ac)
o
o
123 mg, 76% yield; white solid; mp 145ꢀ147 C (lit. 147ꢀ149 C)22; Rf 0.48 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 1.14 (t, J = 7.6 Hz, 3H), 2.54 (q, J = 7.6
Hz, 2H), 5.32 (s, 1H), 7.04 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.22ꢀ7.27 (m, 3H),
7.35ꢀ7.42 (m, 2H), 7.45ꢀ7.56 (m, 3H), 7.83 (d, J = 2.0 Hz, 1H), 7.89ꢀ7.95 (m, 1H); C{1H}
13
NMR (CDCl3, 100 MHz) δ 15.4, 28.3, 48.5, 124.3, 126.1, 127.6, 127.9, 128.5, 128.6, 129.7,
131.6, 134.3, 135.2, 135.6, 136.1, 138.7, 138.8, 142.9, 154.8, 195.0; FTIR (film) 3022, 2965,
2870, 1698, 1624, 1292 cmꢀ1; HRMS (m/z): [M+Na]+ calcd for C24H20ONa: 347.1406; found:
347.1396.
(E)-2-Benzylidene-3-(4-chlorophenyl)-2,3-dihydro-1H-inden-1-one (3ad)
o
o
124 mg, 75% yield; brown solid; mp 136ꢀ138 C (lit. 136ꢀ138 C)22; Rf 0.40 (10% ethyl
1
acetate in hexanes); H NMR (CDCl3, 400 MHz) 5.35 (s, 1H), 7.13ꢀ7.21 (m, 4H), 7.24ꢀ7.30
(m, 3H), 7.34 (d, J = 7.6 Hz, 1H), 7.39ꢀ7.48 (m, 3H), 7.55 (t, J = 7.6 Hz, 1H), 7.86 (s, 1H),
7.94 (d, J = 7.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.1, 124.5, 126.0, 128.3,
128.6, 129.1, 129.2, 129.9, 131.4, 132.9, 134.0, 135.3, 136.1, 136.2, 138.2, 140.1, 154.0,
194.4; FTIR (film) 3025, 1698, 1624, 1489, 1292, 1092 cmꢀ1; HRMS (m/z): [M+Na]+ calcd
for C22H15ONaCl: 353.0709; found: 353.0714.
(E)-2-(4-Bromobenzylidene)-3-phenyl-2,3-dihydro-1H-inden-1-one (3ae)
133 mg, 71% yield; light yellow solid; mp 206ꢀ208 oC (lit. 204ꢀ206 oC)22; Rf 0.43 (10% ethyl
acetate in hexanes); 1H NMR (CDCl3, 400 MHz) δ 5.23 (s, 1H), 7.05ꢀ7.12 (m, 1H), 7.13ꢀ7.20
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(m, 4H), 7.21ꢀ7.26 (m, 2H), 7.27ꢀ7.36 (m, 4H), 7.47 (td, J = 1.2, 7.6 Hz, 1H), 7.69 (d, J = 2.0
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13
Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H); C{1H} NMR (CDCl3, 100 MHz) δ 48.8, 124.3, 124.5,
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126.1, 127.3, 127.7, 128.2, 129.2, 131.8, 132.8, 133.1, 134.3, 135.4, 136.1, 139.2, 141.2,
154.4, 194.5; FTIR (film) 3025, 2917, 1690, 1612, 1253, 743 cmꢀ1; HRMS (m/z): [M+H]+
calcd for C22H16OBr: 375.0385; found: 375.0404.
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(E)-3-Phenyl-2-(thiophen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one (3af)
o
103 mg, 68% yield; light brown solid; mp 184ꢀ186 C; Rf 0.30 (10% ethyl acetate in
1
hexanes); H NMR (CDCl3, 400 MHz) δ 5.21 (s, 1H), 7.00 (dd, J = 5.2, 3.6 Hz, 1H), 7.16ꢀ
7.22 (m, 1H), 7.25ꢀ7.30 (m, 2H), 7.30ꢀ7.34 (m, 3H), 7.37ꢀ7.46 (m, 3H), 7.49ꢀ7.56 (m, 1H),
7.89 (d, J = 7.6 Hz, 1H), 8.05 (t, J = 0.8 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.7,
124.3, 126.0, 127.2, 127.8, 128.0, 128.1, 129.1, 132.0, 134.2, 135.1, 135.9, 136.5, 138.5,
141.1, 154.2, 194.4; FTIR (film) 3029, 2967, 1692, 1613, 1290, 1093 cmꢀ1; HRMS (m/z):
[M+Na]+ calcd for C20H14ONaS: 325.0663; found: 325.0661.
(E)-4-((1-Oxo-3-phenyl-1,3-dihydro-2H-inden-2-ylidene)methyl)benzonitrile (3ag)
o
1
91 mg, 56% yield; white solid; mp 217ꢀ219 C; Rf 0.34 (10% ethyl acetate in hexanes); H
NMR (CDCl3, 400 MHz) δ 5.33 (s, 1H), 7.11ꢀ7.18 (m, 3H), 7.19ꢀ7.25 (m, 2H), 7.35ꢀ7.40 (m,
1H), 7.43 (t, J = 7.6 Hz, 1H), 7.46ꢀ7.55 (m, 4H); 7.56 (td, J = 7.6, 0.8 Hz, 1H), 7.79 (d, J =
2.0 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 48.8, 112.6, 118.5,
124.6, 126.2, 127.5, 127.8, 128.4, 129.3, 131.3, 132.1, 133.1, 135.8, 135.9, 138.7, 140.8.
142.1, 154.4, 194.1; FTIR (film) 3024, 2220, 1684, 1625, 1292, 737 cmꢀ1; HRMS (m/z):
[M+H]+ calcd for C23H16NO: 322.1232; found: 322.1240.
Experimental procedure for the preparation of 10 and 11
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