O -Iodoxybenzoic acid mediated generation of aryl free radicals: Synthesis of stilbenes through C-C cross-coupling with β-nitrostyrenes

Article abstract of DOI:10.1039/c7nj04701k

The generation of an aryl free radicals in the presence of nitrostyrenes through a combination of aryl hydrazines and o-iodoxybenzoic acid led to the synthesis of stilbenes by forming a new carbon-carbon bond after subsequent elimination of a nitrosyl radical. The symmetrical and unsymmetrical stilbenes with excellent E-selectivity were synthesized in good yields, with advantages of broad substrate scope and transition metal free, mild reaction conditions, under an open atmosphere in a short reaction time. A free radical mediated mechanism was postulated and supported by radical trapping experiments. Application of the developed methodology is demonstrated through a simple, two step synthesis of resveratrol, a valuable stilbenoid for anticancer and neurological studies via its prodrug E-1,3-dimethoxy-5-(4-methoxystyryl)benzene.

Full text of DOI:10.1039/c7nj04701k

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AKAMANCHI, G. D. Wagh, S. B. Autade and P. C. Patil, New J. Chem., 2018, DOI: 10.1039/C7NJ04701K.
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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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PleNaeswe dJoounrnoatlaodfjCuhsetmmiastrrgyins
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DOI: 10.1039/C7NJ04701K
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ARTICLE
o-Iodoxybenzoic acid mediated generation of aryl free radicals:
synthesis of stilbenes through C-C cross-coupling with β-
nitrostyrenes
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Ganesh Wagha, Snehalata Autadea, Pravin C. Patilb and Krishnacharya G. Akamanchi*a
www.rsc.org/
Abstract: Generation of aryl free radical in the presence of nitrostyrenes through combination of arylhydrazine and o-
iodoxybenzoic acid led to synthesis of stilbenes by forming new carbon-carbon bond after subsequently elimination of
nitrosyl radical is developed. The symmetrical and unsymmetrical stilbenes with excellent E-selectivity were synthesized in
good yields with advantages of broad substrates scope, transition metal free, mild reaction conditions and under open
atmosphere in short duration of time. Free radical mediated mechanism was postulated and supported by radical trapping
experiments. Application of developed methodology demonstrated through simple and two step synthesis resveratrol, a
valuable stilbenoid for anticancer, neurological studies via its prodrug E-1,3-dimethoxy-5-(4-methoxystyryl)benzene
comprises hazardous, pyrophoric, moisture sensitive reagents and
demand for extremely inert atmosphere. Scope of most of these
Introduction
β-Nitrostyrenes are valuable intermediates in organic synthesis1-7
due to their chemical properties including ability as free radical
acceptors to form new carbon-carbon bond. Organometallic
reagents such as dialkylzinc, tert-BuHgX/KI, organomanganese,
trialkylgallium and organoboranes are known to generate alkyl
radical in presence of α,β-unsaturated nitro-olefins including β-
nitrostyrenes ensued to formation of new carbon-carbon bond
followed by elimination of nitrosyl radical and ultimately led to
synthesis of alkenes and β-alkylstyrenes.8-10 Trifluoromethyl radical
generated by Togni reagent/Fe (acac)3 has been trapped by β-
nitrostyrenes leading to a new method for trifluoromethylation
particularly suitable for synthesis β-trifluoromethylstyrenes.11
Recently, β-benzylstyrenes have been synthesized by using
literature methods is restricted to installment of only specific alkyl or
trifluoromethyl groups but not explored towards installation of other
group such as aryl group.
Fig 1: Synthesis of stilbenes by C-C cross-coupling reactions.
To the best of our knowledge, till date there is only one approach
reported with two variants to synthesize stilbenes by generating aryl
free radical from aryldiazonium tetrafluoroborate salt and
subsequently trapped by β-nitrostyrenes. In the first approach,
depicted by only one example, the aryl free radical was generated in
combination Cu/DTBP and Fe (acac)3/PhSiH3 for activation of benzylic
position followed by reductive coupling.12,
Aforementioned
13
the presence of visible light catalyzed by [Ru(bpy)3]2+ provided
methods require peroxides for efficient generation of free radical,
14
stilbene in poor yield of 37% ( Fig 1, Method A),
In another
improved approach, the photocatalyst, eosin Y /green LEDs was used
for synthesis of stilbene has been reported (Fig 1, Method B).15
Unfortunately, first approach suffers from drawbacks such as use of
costly transition metal catalyst (Ru(bpy)3]2+), poor yield (37%),
limited substrate scopes depicted by only one example while the
a.Department of Pharmaceutical Sciences and Technology, Institute of Chemical
Technology, Matunga, Mumbai 400019, India
b.Current address: Department of Chemistry, University of Louisville, Louisville, KY-
40217, USA
†. Electronic Supplementary Information (ESI) available: [The copies of 1H and 13C
NMR spectra for compounds 3a-3n, 5a-5k, 6 and 7]. See DOI: 10.1039/x0xx00000x
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16-18, 66-
another approach restricted to use of photo catalyst and longer Inspired by our achievements in hypervalent iodine research
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DOI: 10.1039/C7NJ04701K
reaction time of 12 h which abridged the importance of this method 70 and considering our further interest in exploring the reactivity of
by considering the direct application in synthetic methods.
β-nitrostyrenes towards aryl free radicals, gratifyingly herein we
report a successful attempt for synthesis of stilbenes by generating
aryl free radical using combination of IBX and arylhydrazine and
trapping it by β-nitrostyrenes under mild conditions at room
temperature. Use of IBX is noteworth because it offers
chemoselective oxidizing properties under mild reaction conditions
and not moisture sensitive.
Towards our continuous efforts16-18 for exploring the oxidizing
properties of hypervalent iodine reagents, recently we have
discovered a novel method for generation of aryl free radicals using
a combination of o-iodoxybenzoic acid (IBX) and arylhydrazines and
subsequently trapped it by 1,4-naphthoquinones and anilines to
established new methodologies for direct arylation which provided
17
3-aryl-1,4-napthquinones16 and N-arylated anilines, respectively.
Results and discussion
On the same lines, we have sucessfully extended this approach
towards new route development for synthesis of parvaquone
(Clexon), an antiprotozoal drug used for Theileriosis (East Coast
Fever). Parvaquone was synthesized in 60% yield in single step by
generating cyclohexyl radical through combination of
cyclohexylhydrazine with IBX in the presences of 1,4-
naphthoquinone.18
For preliminary investigations and optimization of reaction
parameters, E-(2-nitrovinyl)benzene 1a and phenylhydrazine 2a
were chosen as model substrates due to their easy availability. The
reactions were taken for work up after one hour stirring after
disappearance of phenylhydrazine from TLC. When to a stirred slurry
of 1a and IBX in acetonitrile was added 2a dropwise over a period of
30 min, it was satisfying to note that, the expected product stilbene
3a was formed in 68% yield with a 5% amount of azobenzene 4a as a
side product (Table 1, entry 1). For the selection of best oxidizing
reagent, viability of various oxidizing reagents were tested. Other
hypervalent iodine reagents such as Dess-Martin Periodinane (DMP)
and Diacetoxyiodobenzene (DIB) provided 3a in a lower yield of 35%
and 30%, respectively (Table 1, entries 2 and 3) with slight increased
amount of 4a. Optimization experiments with metal oxidants such as
K3Fe[CN]6, Mn(OAc)3, Cu(OAc)2 were provided poor yields of 3a such
as 22%, 25% and 28%, respectively (Table 1, entries 4-6).Oxone was
found better oxidizing reagent as compared to metal oxidants as it
afforded 3a in 43% yield (Table 1, entry 7). Molecular oxygen was
found unsuitable for this transformtion as it provided only 10% yield
of 3a (Table 1, entry 8). Based on the results obtained from various
oxidizing reagents, IBX was choosen as the best oxidizing reagent
(Table 1, entry 1) and hence used for further optimization for suitable
solvent. Reactions of 1a with 2a using IBX were performed in
different solvents such as dimethylsulfoxide, toluene, chloroform
and acetonitrile. Reaction in dimethylsulfoxide provided inseparable
complex mixture (Table 1, entry 9) while toluene and chloroform
were found inappropriate for this conversion as they provided 25%
and 28% yield of 3a, respectively (Table 1, entry 10 and 11).
Acetonitrile was selected as the best solvent as it afforded 3a in 68%
(Tale 1, entry 1).
On the other side, stilbene scaffold has received a great deal of
attention from the synthetic chemistry and biology researchers in
the past decade because of their wide-ranging spectrum of biological
activities and broad applications in various fields of research.
Stilbene
motifs
containing
compounds
such
as
resveratrol, tamoxifen, piceatannol has shown anti-cancer, anti-
platelet anti-aggregation, anti-oxidative, anti-bacterial, anti-
inflammatory and antidyslipidemic activities.19-25 Pterostilbene
(3’,5’-dimethoxy-4-stilbenol) a natural polyphenol found in almonds,
grape leaves and blue berries possesses lipid- and glucose-lowering
effects.26 Combretastatin analogs such as combretastatin A-4 and
ombrabulin are undergoing various clinical trials for development of
anticancer drugs.27 Besides their prominence in pharmaceutical and
medicinal field, stilbenes are also considered as important building
blocks in synthetic molecule and dyes having organic light emitting
diodes and liquid crystals.28-19, 29, 30 There are several direct methods
for synthesis of stilbenes, such as wittig or Julia olefination,31-34 Heck-
type reactions,35-52 a recent unusual variant of Mizoroki-Heck-type
reaction in absence of Pd53-58 and some condensation and reduction
methods using suitable substrates.59-65 Most of these reported
methods demands for necessity of transition metal catalysts,
pyrophoric reagents, costly catalysts and ligands and need special
handling skills for hazardous reagents under inert atmosphere.
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condition reverse trend was observed with respect to formation of
Table 1: Optimization of reaction conditions.a
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4a and yield increased substantially to 60% (Table 1, entry 13). This
valuable supporting evidence was considered and explained while
postulating the mechanism. On the contrary at a higher temperature
such as 40-45 °C and 60-65 °C though the somewhat lower yield of
3a, 55% and 52%, respectively, were observed (Table 1 entries 14
and 15), but to our surprise 4a was not formed even in trace amount.
Extending reaction time in acetonitrile upto 10 h did not help to
increase the yield of 3a to more than 65% (Table 1, entry 16). Finally,
the mole ratio of IBX was optimized. Reaction with 2.0 equiv of IBX
(Table 1, entry 17) provided same results as reaction with 2.5 equiv
(Table 1, entry 1) whereas reaction with 1.5 equiv of IBX resulted into
decrease the yield from 68% to 55% (Table 1, entry 18). After
summarizing an optimization study results, reaction of 1a with 2a in
2.0 equiv of IBX in acetonitrile at room temperature (Table 1, entry
17) was chosen as the best condition for further investigation toward
substrates scope and reaction mechanistic.
With the optimized reaction condition in hand, substrates scope was
explored with a series of substituted aromatic nitrostyrenes and
arylhydrazines. Investigation was commenced with by exploring the
reactivity of differently substituted nitrostyrenes with respect to
phenylhydrazine. Nitrostyrenes 1a-1n reacted with phenylhydrazine
2a under standard conditions provided corresponding stilbenes 3a-
3n in moderate to good yields. It was observed that reactions of
nitrostyrenes bearing electron donating substituents such as 4-
methoxynitrostyrene 1c, 3-methoxynitrostyrene 1d, 3,4-
dimethoxynitrostyrene 1e provided stilbenes 3c-3e in 80%, 72% and
72% yields, respectively which were slightly better compared to
unsubstituted nitrostyrene 68% (3a). The electron donating effect of
4-methyl substituent of 1b did not have significant effect on
reactivity when compared to unsubstituted stilbene 3a and provided
3b in same as 68% yield. The reactions of nitrostyrenes 1f-1j
substituted with electronwithdrawing groups offered 3f-3j in 62-67%
yields (Table 2). However, nitrostyrene 1k bearing stronger electron
withdrawing nitro group on phenyl ring showed negative effect on
the yield by providing 54% yield of 3k.
[a]Reaction Conditions:1a (1 eq), 2a (1.2 eq), oxidant (2.5 eq), 4.5 h, solvent,
[b]isolated yields of 3a and 4a,[c]reaction time was extended to 10 h, [d] IBX:2
eq,[e] IBX:1.5 eq
Effect of temperature on the yield of 3a was studied by set of
reactions performed at wide range of temperature. At 0 to 5 °C the
yield of 3a was reduced to 60% (Table 1, entry 12), and with further
decrease in temperature to -20 to -10 °C the yield of 3a drastically
reduced to 20% (Table 1, entry 13). Surprisingly, at -20 to -10 °C
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conclude that electron donating nitrostyrene and VaierwylAhrtyicdleraOznilninee
might be the best combination to obtain hiDgOheI:r10y.i1e0ld39o/Cf7sNtiJl0b4e7n0e1sK.
Table 2: Synthesis of stilbenes using differently substituted β-nitrostyrenes and
phenylhydrazine 2a.a
3,5-dimethoxynitrostyrene 1o and 4-chloronitrostyrene 1g when
combined with
4-chlorophenylhydrazine resulted 5e
and 5f in 68% and 61%, respectively, demonstrating that electron
donating nitrostyrene favored the reaction over electron
withdrawing nitrostyrenes to obtain corresponding stilbenes.
Table 3: Synthesis of stilbenes with differently substituted β-nitrostyrenes and
arylhydrazines.[a
Reagent and conditions: 1a-1n (1.0 equiv.), 2a (1.2 equiv.), IBX (2.0 equiv.),
Acetonitrile as solvent. [a]-Isolated yield after column chromatography.
Additionally, both polyaromatic 1l and conjugated diene 1m were
screened and offered corresponding products 3l and 3m in 62% and
64% yields respectively. To our delight, heterocyclic 2-
nitrovinylthiophene 1n was found compatible to optimized reaction
conditions and product 3n was isolated in 64% yield. Overall, it was
found that unsubstituted and substituted styrenes with electron
donating and electron withdrawing groups satisfactorily reacted
under optimized reaction conditions and provided 3a-3n in
moderate to good yields.
Reagent and conditions: 1(1.0 equiv.), 2b-2e (1.2 equiv.), IBX (2.0 equiv.),
Acetonitrile as solvent. [a]-Isolated yield after column chromatography.
2-Methylphenylhydrazine was reacted with series of differently
substituted nitrostyrenes to give corresponding stilbenes 5g-5k. It is
noteworthy to mention that reactions of conjugated diene and
heteroaromatic nitrostyrene with 2-methylphenylhydrazine
proceeded well and stilbenes 5j and 5k were obtained in 63% and
65% yields, respectively.
To broaden the further substrates scope, effect of differently
substituted arylhydrazines counterpart was investigated under the
standard reaction conditions. All the reactions afforded the expected
stilbenes in moderate to good yields (Table 3). To study the effect of
After summarizing the results from Table 2 and Table 3, it was
concluded that the presence of electron donating substituents on
both the reacting substrates, nitrostyrenes and arylhydrazines could
be an advantageous factor toward high yielding synthesis of
stilbenoid polyphenols.
various substituted arylhydrazines on nitrostyrene,
methoxynitrostyrene 1c was reacted with2- methylphenylhydrazine
2b, 4-methoxyphenylhydrazine 2c, 3-chlorophenylhydrazine
4-
Considering the importance of our developed methodology, we
hypothesized synthesis of 3,4’,5-trihydroxystilbene, resveratrol.
Both, 3,4’,5-trimethoxystilbene 6 and resveratrol 7 are undergoing
various clinical trials for wide ranging spectrum of biological activities
2d and 4-chlorophenylhydrazine 2e.All the reactions proceeded
smoothly and provided 5a, 5b, 5c and 5d in 65%, 70%, 62%, and 64%
yields respectively. Among these, higher yield of 5b helped to
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and free radical scavenging properties.71-74 In literature, compound 6 In order to gain insight into the mechanistic investigation, series of
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DOI: 10.1039/C7NJ04701K
was synthesized using Wittig type reaction but the disadvantages of experiments were performed using the model substrates 1a and 2a.
this method included use of pyrophoric reagents, cryogenic reaction When a reaction was carried out using 1a and 2a under optimized
conditions, and generation of stoichiometric amount of phosphine conditions and in the presence of 2,2,6,6-tetramethylpiperidine-1-
oxide hence isolation of product could be troublesome. Other oxyl (TEMPO), a well-known radical trapping agent, the free radical
approaches for synthesis of 6 included coupling reaction and partial trapped product 1-(2,2,6,6-tetramethylpiperidinyloxy)- benzene 8
hydrogenation but it required use of transition metal catalyst and was obtained in 30% yield with no formation of 3a (Scheme 2, i). In
hence these method were not considered particularly attractive. another supportive experiment, when 2a was mixed with IBX in
Ramberg-Baklund rearrangement based synthetic routes possesses acetonitrile at room temperature resulted into formation of biphenyl
the problems of waste generation and use of hazardous benzyl (60%), azobenzene (10%) and benzene in trace amount (< 5%)
bromides.34, 75-83
(Scheme 2, ii).
Scheme 1: New route for synthesis of resveratrol 7
Scheme 2: Radical trapping and control experiments
We believe that the formation of 8 in (scheme 2, i) and isolation of
biphenyl 9 in 60% yield in (scheme 2, ii) found strongly supportive for
the radical pathway. A control experiment was also conducted to
confirm that E-selectivity is due to trans elimination of NO2 and not
because of cis-trans isomerization (Scheme 2, iii). When cis-stilbene
was treated under the standard condition and in the absence of both
the substrates 1a and 2a, the cis-stilbene remained unchanged and
was recovered completely after workup. This experiment confirmed
that during the reaction, no isomerization of cis stilbene into trans
stilbene was possible and the isolation of trans-stilbene product
must be due to the trans elimination of nitro group.
Reagents and conditions: 1o (1.0 equiv), 2c (1.2 equiv), IBX (2.0 equiv), Acetonitrile as
solvent at room temperature.
Inspired with outcome of our methodology and our interest to
develop alternate route for synthesis of 3,4’,5-trimethoxystilbene,
we applied our protocols for the synthesis of 6. When 3, 5-
dimethoxy-2-nitrostyrene
1e
reacted
with
4-
methoxyphenylhydrazine 2c under optimized reaction conditions,
compound 6 was isolated in 70% yield in 4h at room temperature,
compound 6 was subsequently converted to resvertrol 7 in 91% by
using literature procedure.78 Stoichiometric amount of hypervalent
iodine (III) compound, iodosobenzoic acid (IBA), formed as by
product during the reaction could be easily recovered after filtration
and is amenable for recycling after reoxidation. The present method
has an advantages over reported methods such as being clean, two
step transformation, mild reaction conditions at room temperature,
open to atmosphere and no special handing required for the
reagents.
Based on radical trapping experiments results and supported by the
prior literature84-87 a plausible mechanism is outlined in Scheme 3.
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combination of IBX with aryl hydrazine, and β-niVtrieowstAyrtricelenOesnlinies
Scheme 3: Plausible Mechanism
developed. The established method provideDsOacI:c1e0s.1s0t3o9s/Cym7NmJ0e4t7r0ic1aKl
and unsymmetrical stilbenes by following transition metal free, mild
protocols under open atmosphere. The synthetic potential of the
method was successfully demonstrated towards an effective, two
step and good yielded synthesis of resvertrol via 3,4’,5-trans-
trimethoxystilbene an invetsigation new drug and prodrug of
resveratrol. A free radical mediated reaction mechanism is
postulated and supported by radical trapping experiments. We
believe that the developed method could be a good alternative for
the synthesis of stilbenoid polyphenols class of natural products and
their analogs.
Experimental
General methods
Phenylhydrazine 2a gets attracted towards IBX due to the
electrophilic nature of iodine center and subsequently undergo first
oxidation, leading to the formation of phenyldiazine 11 and IBA.
Being nucleophilic in nature, 11 would react with another molecule
of IBX and undergo another oxidation through single electron
transfer (SET) to form phenyl radical C with the liberation of nitrogen
gas. Due to nucleophilic nature of phenyl radical88 it reacts with
electrophilic double bond in 1a to form adduct E to establish new C-
C bond and is followed by trans elimination of NO2. In addition to
(Scheme 2, iii), trans elimination of NO2 group is also supported by
experimental observation of formation of brown fumes of nitrogen
oxides during the reaction, to give 3a. The postulated mechanism
was further supported by the observations found during the
optimization of reaction temperature parameter. When the reaction
was performed at lower temperature, diazo product 4a was obtained
in high yield of 60% (Table 1, entry 13) whereas it was completely
absent in the reaction carried out at 40-45 °C (Table 1, entries 14)
indicating that rate of oxidation of 11 is the deciding factor for the
formation 4a. This also explains the lower yield 3a at higher
temperature where the rapid formation and utilization of phenyl
radical in concomitantly accelerated other side reactions.
All chemicals used were of reagent grade and used as received
without further purification. The FTIR spectra were recorded on a
shimadzu IR prestige-21 spectrometer and Perkin Elmer IR spectrum
1
version 10.4.2. All H NMR and 13C-NMR spectra were recorded on
Agilent FTNMR 400 or 500 MHz and 101 or 126 MHz
spectrophotometer respectively. Chemical shift values are expressed
in δ units relative to tetramethylsilane (TMS) signal as an internal
reference standard in CDCl3 or DMSO. The following abbreviations
are used for the multiplicities: s, singlet; d, doublet; dd, doublet of
doublet; ddd, doublet of doublet of doublet; t, triplet; q, quadruplet;
m, multiplet; dt, doublet of triplet; br, broad; for proton spectra,
coupling constants (J) are reported in hertz (Hz). High-resolution
mass spectra (HRMS) were recorded on a micro mass ESI -TOF mass
spectrometer. Melting points were recorded on THERMONIK-
Campbell Melting Point apparatus-Instrument having an oil heating
system with stirring and are uncorrected. Purification of compounds
was carried out by column chromatography using Silica gel #100-200
as stationary phase.
Typical Procedure for synthesis of stilbenes.
To a stirred slurry of o-iodoxybenzoic acid (2 mmol) in 10 mL of
acetonitrile was added nitrostyrenes 1 (1 mmol) and stirred for 10
min. To this solution was slowly added a solution of phenylhydrazines
2 (1.2 mmol) dissolved in 10 mL of acetonitrile over a period of 30
Conclusion:
A free radical-mediated novel method for synthesis of stilbenes by
carbon-carbon cross-coupling between aryl free radical, formed by
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min, and stirring was continued at room temperature for 3-6 h. 148.9, 137.5, 130.4, 128.6, 128.4, 127.3, 126.8, 126.2, 119.9, 111.2,
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Progress of the reaction was monitored by TLC using petroleum ether 108.7, 55.9, 55.8; FT-IR (ν) 2893, 1606, 1517, 1455, 1291, 1183, 1025,
/ ethyl acetate mobile phase. After completion of the reaction, 984 cm−1.
acetonitrile was evaporated under vacuum to obtain residue. To this (E)-1-fluoro-4-styrylbenzene 3f 90: Yield 67% (133 mg) ; White solid;
118-120 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3)
residue were added ethyl acetate (15 mL) and water (15 mL),
followed by saturated sodium bicarbonate solution (10 mL).
δ 7.49 (dd, J = 12.5, 7.5 Hz, 4H), 7.36 (t, J = 7.2 Hz, 2H), 7.30 – 7.24
Separated organic layer was dried over anhydrous sodium sulfate
(m, 1H), 7.11 – 6.98 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 162.3(d, J
and evaporated under vacuum to obtain residue. The residue was
= 248.06 Hz), 137.1, 133.5, 128.7, 128.5 (d, J =2.02 Hz), 128.0 (d, J =
purified by column chromatography on silica gel (#100-200) with
8.08 Hz), 127.7, 127.5, 126.4, 115.6 (d, J = 21.21 Hz); FT-IR (ν) 2946,
(petroleum ether: ethyl acetate = 9:1) as eluent to afford the
1893, 1592, 1509, 1448, 1238, 1097, 967, 825 cm−1.
corresponding pure stilbenes.
(E)-1-chloro-4-styrylbenzene 3g90: Yield 64% (137 mg); Yellow solid;
(E)-1,2-diphenylethene 3a89: Yield 68% (122 mg); White solid; mp
100-102 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3)
120-122 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3
δ 7.49 (d, J = 7.3 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 7.38 – 7.28 (m, 4H),
) δ 7.41 (d, J = 7.9 Hz, 4H), 7.30 (t, J = 7.8 Hz, 4H), 7.19 – 7.17 (m, 2H),
7.28 – 7.23 (m, 1H), 7.07 (d, J = 16.4 Hz, 1H), 7.03 (d, J = 16.4 Hz, 1H);
7.03 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 137.30, 128.7, 127.6, 126.5;
13C NMR (101 MHz, CDCl3) δ 136.9, 135.8, 133.1, 129.3, 128.8, 128.7,
FT-IR (ν) 3019, 1589, 1514, 1445, 956, 814, 756, 696 cm−1.
127.8, 127.6, 127.3, 126.5. FT-IR (ν) 3021, 2780, 1583, 1448, 1217,
(E)-1-methyl-4-styrylbenzene 3b53: Yield 68% (131 mg); White solid;
1180, 817, 783, 691,cm−1.
1
(E)-1-bromo-4-styrylbenzene 3h92: Yield 65% (167 mg); White solid;
mp 110-112 °C (recrystallized with n-pentane); H NMR (400 MHz,
127-129 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3)
CDCl3) δ 7.51 (d, J = 7.5 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.36 (t, J = 7.6
Hz, 2H), 7.28 – 7.24 (m, 1H), 7.18 (d, J = 7.8 Hz, 2H), 7.09 (d, J = 2.3
Hz, 2H), 2.37 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 137.5, 137.5, 134.5,
129.4, 128.6, 128.6, 127.7, 127.4, 126.4, 126.4, 21.3; FT-IR (ν) 3023,
1594, 1509, 1447, 967, 808, 748 cm−1.
δ 7.52 – 7.45 (m, 4H), 7.36 (m, 4H), 7.26 (dd, J = 9.9, 4.3 Hz, 1H), 7.09
(d, J = 16.2 Hz, 1H), 7.02 (d, J = 16.3 Hz, 1H); 13C NMR (101 MHz, CDCl3)
δ 136.9, 136.2, 131.7, 129.9, 128.7, 127.9, 127.9, 127.4, 126.5, 121.3;
FT-IR (ν) 3014, 2956, 1446, 1410, 1350, 1045, 1010, 698, 537 cm−1.
(E)-1-bromo-3-styrylbenzene 3i78: Yield 63% (163 mg); White solid;
(E)-1-methoxy-4-styrylbenzene 3c89: Yield 80% (168 mg); White
1
solid; mp 133-135 °C (recrystallized with n-pentane); H NMR (400
88-89 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3) δ
MHz, CDCl3) δ 7.47 (m, 4H), 7.34 (d, J = 7.2 Hz, 2H), 7.24 (d, J = 7.7 Hz,
1H), 7.07 (d, J = 16.3 Hz, 1H), 6.97 (d, J = 16.3 Hz, 1H), 6.90 (d, J = 8.0
Hz, 2H), 3.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 159.3, 137.6, 130.1,
128.6, 128.9, 127.7, 127.2, 126.6, 126.2, 114.1, 55.3; FT-IR (ν) 2836,
1606, 1508, 1449, 1289, 1180, 900, 840cm−1.
7.67 (s, 1H), 7.51 (d, J = 7.2 Hz, 2H), 7.39 (dd, J = 16.8, 9.1 Hz, 4H),
7.30 (d, J = 7.0 Hz, 1H), 7.22 (d, J = 7.7 Hz, 1H), 7.11 (d, J = 16.3 Hz,
1H), 7.02 (d, J = 16.2 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 139.5,
136.8, 130.9, 130.1, 129.2, 128.7, 128.0, 127.1, 126.6, 125.2, 122.9;
FT-IR (ν) 3024, 2958, 1585, 1425, 1356, 1073, 967, 781, 706 cm−1.
(E)-2,4-dichloro-1-styrylbenzene 3j93: Yield 62% (154 mg); White
(E)-1-methoxy-3-styrylbenzene 3d90: Yield 72% (151 mg); Colourless
oil; 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 2H), 7.41 (t, J = 7.0
Hz, 2H), 7.36 – 7.29 (m, 2H), 7.15 (m, 4H), 6.88 (m, 1H), 3.88 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 159.9, 138.8, 137.3, 129.7, 129.0, 128.7,
128.6, 127.7, 126.6, 119.3, 113.3, 111.8, 55.3; FT-IR (ν) 2903, 1609,
1
solid; 79-81 °C (recrystallized with n-pentane); H NMR (400 MHz,
CDCl3) δ 7.60 (d, J = 8.5 Hz, 1H), 7.53 (d, J = 7.4 Hz, 2H), 7.45 – 7.33
(m, 4H), 7.29 (t, J = 7.3 Hz, 1H), 7.25 – 7.21 (m, 1H), 7.04 (d, J = 16.3
Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 136.7, 134.02, 133.8, 133.4,
131.7, 129.5, 128.7, 128.3, 127.3, 127.1, 126.8, 123.6; FT-IR (ν) 3101,
2789, 1596, 1563, 1454, 1213, 1198, 869, 785cm−1.
1515, 1413, 1289, 1180, 1114, 900, 846 cm−1
.
(E)-1,2-dimethoxy-4-styrylbenzene 3e91: Yield 72% (172 mg); White
1
solid; mp 109-111 °C (recrystallized with n-pentane) ; H NMR (400
(E)-1-nitro-4-styrylbenzene 3k90: Yield 54% (121 mg); Yellow solid;
MHz, CDCl3) δ 7.48 (d, J = 7.5 Hz, 2H), 7.33 (t, J = 7.6 Hz, 2H), 7.23 (d,
J = 5.9 Hz, 1H), 7.04 (m, 3H), 6.96 (d, J = 16.3 Hz, 1H), 6.85 (d, J = 8.1
Hz, 1H), 3.93 (s, 3H), 3.89 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 149.1,
151-153 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3)
δ 8.21 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 7.6 Hz,
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2H), 7.39 (t, J = 7.5 Hz, 2H), 7.35 – 7.32 (m, 1H), 7.26 (d, J = 16.2 Hz, NMR (400 MHz, CDCl3) δ 7.46 (s, 1H), 7.43 (d, J = 8.6 HVzi,e2wHA)rt,ic7le.3O2nl(inde,
1H), 7.13 (d, J = 16.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 146.7, J = 7.6 Hz, 1H), 7.24 (dd, J = 9.1, 6.4 Hz, 1H),D7O.1I:810(d.1,0J3=9/7C.78NHJ0z4, 710H1)K,
143.8, 136.1, 133.3, 128.9, 128.8, 127.0 , 126.8, 126.3, 124.1; FT-IR 7.04 (d, J = 16.3 Hz, 1H), 6.93 – 6.84 (m, 3H); 13C NMR (101 MHz,
(ν): 3077, 1633, 1595, 1454, 1523, 1344, 971, 833 cm-1.
CDCl3) δ 159.6, 139.5, 134.6, 129.8, 129.6, 129.6, 127.9, 127.0, 125.9,
125.1, 124.4, 114.2, 55.3; FT-IR (ν): 2910, 1645, 1564, 1196, 856, 661
cm-1.
(E)-2-styrylnaphthalene 3l94: Yield 62% (143 mg); White solid; mp
147-148 °C (recrystallized with n-pentane); 1H NMR (500 MHz,
(E)-1-chloro-4-(4-methoxystyryl)benzene 5d20 : Yield 64% (156 mg);
CDCl3) δ 7.85 – 7.78 (m, 4H), 7.75 – 7.70 (m, 1H), 7.55 (d, J = 7.5 Hz,
2H), 7.48 – 7.41 (m, 2H), 7.37 (t, J = 7.6 Hz, 2H), 7.24 (td, J = 16.1,
7.8 Hz, 3H).13C NMR (126 MHz, CDCl3) δ 137.4, 134.8, 129.1, 128.8,
128.8, 128.0, 127.9, 127.7, 126.6, 126.6, 126.5, 126.4, 125.2, 123.5;
FT-IR (ν): 3014, 1589, 1523, 1454, 994, 824, 765, 695 cm-1.
Yellow solid; mp 166-168 °C (recrystallized with n-pentane); 1H NMR
(400 MHz, CDCl3) δ 7.42 (d, J = 8.7 Hz, 2H), 7.39 (d, J = 8.5 Hz, 2H),
7.29 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 16.3 Hz, 1H), 6.93 – 6.85 (m, 3H),
3.81 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 159.4, 136.1, 132.6, 129.7,
128.8, 128.7, 127.7, 127.3, 125.2, 55.3; FT-IR (ν): 2960, 1604, 1574,
1176, 874, 689 cm-1.
(1E,3E)-1,4-diphenylbuta-1,3-diene 3m95: Yield 64% (131 mg); White
1
solid; mp 151-153 °C (recrystallized with n-pentane); H NMR (400
(E)-1-(4-chlorostyryl)-3,5-dimethoxybenzene 5e98: Yield 68% (186
MHz, CDCl3) δ 7.44 (d, J = 7.6 Hz, 4H), 7.33 (t, J = 7.3 Hz, 4H), 7.24 (d,
J = 7.0 Hz, 2H), 6.96 (q, J = 8.1 Hz, 2H), 6.74 – 6.61 (m, 2H). 13C NMR
(101 MHz, CDCl3) δ 137.3, 132.8, 129.2, 128.6, 127.6, 126.4; FT-IR (ν)
3016, 1491, 1443, 991, 740, 690,596 cm−1.
1
mg); White solid; 72-74 °C (recrystallized with n-pentane); H NMR
(400 MHz, CDCl3) δ 7.41 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H),
6.99 (d, J = 1.5 Hz, 2H), 6.64 (d, J = 2.1 Hz, 2H), 6.39 (t, J = 2.1 Hz, 1H),
3.81 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 160.9, 138.9, 135.6, 133.2,
129.2, 128.8, 127.8, 127.7, 104.6, 100.1, 55.3; FT-IR (ν) 2936, 2836,
1592, 1456, 1205, 1151, 822, 673 cm-1.
(E)-2-styrylthiophene 3n27: Yield 64% (120 mg); Pale yellow solid; mp
112-114 °C (recrystallized with n-pentane); 1H NMR (400 MHz, CDCl3)
δ 7.45 (d, J = 7.5 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.25 – 7.16 (m, 3H),
7.05 (d, J = 3.0 Hz, 1H), 7.01 – 6.97 (m, 1H), 6.91 (d, J = 16.1 Hz, 1H);
13C NMR (101 MHz, CDCl3) δ 142.8, 136.9, 128.7, 128.3, 127.6, 126.2,
126.1, 124.3, 121.7; FT-IR (ν): 3102, 1594, 1428, 1273, 1202, 753,
692 cm-1.
(E)-1,2-bis(4-chlorophenyl)ethane 5f5b: Yield 61% (151 mg); White
1
solid; mp 159-160 °C (recrystallized with n-pentane); H NMR (400
MHz, CDCl3) δ 7.40 (d, J = 8.4 Hz, 4H), 7.31 (d, J = 8.4 Hz, 4H), 6.99 (s,
2H); 13C NMR (101 MHz, CDCl3) δ 135.4, 133.4, 128.9, 127.9, 127.7;
FT-IR (ν) 2923, 1588, 1487, 1406, 1090, 828 cm-1.
(E)-1-(4-methoxystyryl)-2-methylbenzene 5a96: Yield 65% (145 mg);
(E)-1-methyl-2-(4-methylstyryl)benzene 5g96: Yield 63% (131 mg);
Off-white solid; mp 75-76 °C (recrystallized with n-pentane); 1H NMR
1
Colourless oil; H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 7.4 Hz, 1H),
(400 MHz, CDCl3) δ 7.59 (d, J = 7.3 Hz, 1H), 7.47 (d, J = 8.7 Hz, 2H),
7.25 – 7.12 (m, 4H), 6.97 (d, J = 16.2 Hz, 1H), 6.92 (d, J = 8.7 Hz, 2H),
3.83 (s, 3H), 2.43 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 159.3, 136.6,
135.5, 130.5, 130.4, 129.5, 127.8, 127.2, 126.2, 125.1, 124.4, 114.1,
55.3, 19.9; FT-IR (ν): 2837, 1598, 1428, 1375, 1245, 1168, 983, 714
cm-1.
7.42 (d, J = 7.5 Hz, 2H), 7.32 (d, J = 16.0 Hz, 1H), 7.25 (d, J = 5.6 Hz,
1H), 7.20 – 7.15 (m, 4H), 6.97 (d, J = 16.0 Hz, 1H), 2.42 (s, 3H), 2.36 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 137.5, 136.5, 135.7, 134.9, 130.3,
129.9, 129.4, 127.3, 126.4, 126.1, 125.5, 125.2, 21.2, 19.9; FT-IR (ν)
3029, 1589, 1574, 1445, 945, 821cm-1.
(E)-1,3-dimethoxy-5-(2-methylstyryl)benzene 5h99: Yield 62% (157
(E)-1,2-bis(4-methoxyphenyl)ethene 5b90: Yield 70% (168 mg); Pale
1
mg); Yellow oil; H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 6.6 Hz, 1H),
yellow solid; mp 207-209 °C (recrystallized with n-pentane); 1H NMR
7.30 (d, J = 16.1 Hz, 1H), 7.23 – 7.15 (m, 3H), 6.92 (d, J = 16.1 Hz, 1H),
6.67 (d, J = 2.0 Hz, 2H), 6.40 (t, J = 2.0 Hz, 1H), 3.83 (s, 6H), 2.42 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 160.9, 139.7, 136.2, 135.8, 130.4,
129.9, 127.6, 127.1, 126.2, 125.4, 104.7, 99.7, 55.4, 19.9; FT-IR (ν):
2937, 1594, 1459, 1425, 1276, 1202, 1154, 961, 828 cm-1.
(400 MHz, CDCl3) δ 7.41 (d, J = 8.8 Hz, 4H), 6.92 (s, 2H), 6.87 (d, J =
8.8 Hz, 4H), 3.81 (s, 6H); 13C NMR (101 MHz, CDCl3) δ: 156.9, 128.4,
125.4, 124.1, 112.1, 53.3; FT-IR (ν): 3015, 2838, 1608, 1515, 1441,
1250, 956 cm-1.
(E)-1-chloro-3-(4-methoxystyryl)benzene 5c97: Yield 62% (151mg);
(E)-1-(4-bromostyryl)-2-methylbenzene 5i: Yield 64% (174 mg); Pale
1
Pale yellow solid; mp 94-96 °C (recrystallized with n-pentane); H
1
yellow solid; mp 91-94 °C (recrystallized with n-pentane); H NMR
8 | J. Name., 2012, 00, 1-3
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NJC
(400 MHz, CDCl3) δ 7.63 – 7.58 (m, 1H), 7.50 (d, J = 8.5 Hz, 2H), 7.39 crude residue. Which was further purified by column
View Article Online
(d, J = 8.4 Hz, 2H), 7.34 (d, J = 16.2 Hz, 1H), 7.23 (ddd, J = 6.3, 5.2, 3.0 chromatography on silica gel (#100-200) withD(pOeI:t1ro0.l1e0u3m9/Cet7hNeJr0:4e7t0h1yKl
Hz, 3H), 6.94 (d, J = 16.2 Hz, 1H), 2.45 (s, 3H); 13C NMR (101 MHz, acetate = 9:1) as eluent to afford the (E)-1,3-dimethoxy-5-(4-
CDCl3) δ 136.6, 136.0, 135.9, 131.8, 130.5, 128.7, 128.1, 127.8, 127.2, methoxystyryl)benzene (6)100 with Yield 70% (378 mg) ; White solid;
mp 54-56 °C (recrystallized with n-pentane); 1H NMR (400 MHz,
126.3, 125.4, 121.3, 20.3; FT-IR (ν) 3078, 2954, 1464, 1390, 1247,
1078, 989, 704, 686 cm-1; HRMS (ESI-TOF) m/z (M+Na)+ calcd. For
CDCl3) δ 7.43 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 16.4 Hz, 1H), 6.93 – 6.86
C15H13BrNa: 295.0093; found: 295.0044.
(m, 3H), 6.64 (d, J = 2.0 Hz, 2H), 6.36 (s, 1H), 3.81 (s, 9H); 13C NMR
1-methyl-2-((1E,3E)-4-phenylbuta-1,3-dien-1-yl)benzene 5j: Yield
(101 MHz, CDCl3) δ 160.9, 159.3, 139.6, 129.9, 128.7, 127.8, 126.5,
63% (138 mg); White solid; mp 112-113 °C (recrystallized with n-
114.1, 104.3, 99.6, 55.3; FT-IR (ν): 2989, 1696, 1452, 1320,1145,
1061, 972, 695 cm-1.
1
pentane); H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.3 Hz, 1H), 7.46
(d, J = 7.4 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.25 (d, J = 7.3 Hz, 1H), 7.23
– 7.13 (m, 3H), 7.01 (ddd, J = 15.5, 7.7, 2.1 Hz, 1H), 6.89 (d, J = 7.7 Hz,
2H), 6.68 (d, J = 15.4 Hz, 1H), 2.40 (s, 3H); 13C NMR (101 MHz, CDCl3)
δ 137.4, 136.1, 135.6, 132.7, 130.5, 130.4, 130.3, 129.6, 128.7, 127.5,
127.5, 126.4, 126.2, 125.0, 19.9; FT-IR (ν) 3089, 1489, 1445, 981, 754,
676,584 cm-1; HRMS (ESI-TOF) m/z (M+H)+ calcd. For C17H17
221.1325; found 221.0936.
Step 2: (E)-5-(4-hydroxystyryl)benzene-1,3-diol 7: Compound 7 was
obtained by using procedure as follows: In 6 mL of anhydrous
methylene chloride, 200 mg of (E)-1,3-dimethoxy-5-(4-
methoxystyryl)benzene 6 (0.74 mmol) was dissolved and cooled to -
10 °C under argon. BBr3 (0.6 mL, 6.3 mmol, 17 percent in
dichloromethane) in anhydrous methylene chloride (5 mL) was
added slowly, and the mixture was allowed to reach to room
temperature and stirred overnight. 10 mL water was added to
quench the excess BBr3, and the mixture was extracted twice with 20
mL dichloromethane. The organic extracts were combined and
washed with 10 mL water and 10 mL brine. Organic layer was
separated and dried over anhydrous sodium sulfate and evaporated
under vacuum to obtain crude residue. The residue was purified by
column chromatography on silica gel (#100-200) with (petroleum
ether: ethyl acetate = 8:2) as eluent to afford the (E)-5-(4-
hydroxystyryl)benzene-1,3-diol ( Resveratrol ) 7 with 91% yield
(E)-2-(2-methylstyryl)thiophene 5k: Yield 65% (130 mg) ; Yellow
liquid; 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 6.8 Hz, 1H), 7.42 – 7.23
(m, 2H), 7.23 – 7.16 (m, 4H), 7.11 (d, J = 2.7 Hz, 1H), 7.05 (dd, J = 5.0,
3.6 Hz, 1H), 2.46 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 143.3, 135.9,
135.7, 130.5, 127.7, 127.6, 126.3, 126.1, 125.1, 124.3, 123.0, 19.97;
FT-IR (ν) 3102, 3059, 1583, 1489, 1438, 1264, 961, 843, 822, 724 cm-
1; HRMS (ESI-TOF) m/z (M+H)+ calcd. For C13H13S: 201.0732; found
201.0752.
Procedure for synthesis of resveratrol 7.
(0.154 mg) ; White solid; mp 252-254 °C (recrystallized with
1
Step 1: Synthesis of (E)-1,3-dimethoxy-5-(4-methoxystyryl)benzene
6 : To a stirred slurry of o-iodoxybenzoic acid (4 mmol) in 20 mL of
acetonitrile was added (E)-1,3-dimethoxy-5-(2-nitrovinyl)benzene
1o (2 mmol) and stirred for 10 min. To this solution was slowly added
a solution of (4-methoxyphenyl)hydrazine 2c (2.4 mmol) dissolved in
15 mL of acetonitrile over a period of 45 min, and stirring was
continued at room temperature for 4 h. Progress of the reaction was
monitored by TLC using Petroleum ether / Ethyl acetate as a mobile
phase. After completion of the reaction, acetonitrile was evaporated
under vacuum to obtain residue. To this residue were added ethyl
acetate (25 mL) and water (25 mL), followed by saturated sodium
bicarbonate solution (15 mL). Separated organic layer was dried over
anhydrous sodium sulfate and evaporated under vacuum to obtain
methanol); H NMR (500 MHz, DMSO-d6) δ 9.55 (s, 1H), 9.20 (s, 2H),
7.40 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 16.3 Hz, 1H), 6.82 (d, J = 16.3 Hz,
1H), 6.79 – 6.73 (m, 2H), 6.40 (d, J = 2.0 Hz, 2H), 6.18 – 6.10 (m, 1H);
13C NMR (126 MHz, DMSO-d6) δ 158.9, 157.7, 139.7, 128.5, 128.3,
126.1, 115.9, 104.8, 102.2.; FT-IR (ν): 3203, 1604, 1583, 1511, 1264,
1174, 1105, 964, 814 cm-1.
Acknowledgement:
The author Ganesh Wagh is thankful to UGC-CSIR and author
Snehalata Autade is thankful to UGC-SAP for financial support.
Conflict of Interest: The author declares no financial conflict of
interest.
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28. A. Kraft, A. C. Grimsdale and A. B. Holmes, Angew. ChemV.iIenwt.AErtnicdleEOnnglli,ne
1998, 37, 402-428.
References and Notes:
1. M. Gao, J. Tian and A. Lei, Chem. Asian J, 2014, 9, 2068-2071.
DOI: 10.1039/C7NJ04701K
29. R. E. Martin and F. Diederich, Angew. Chem., Int. Ed, 1999, 38, 1350-
1377.
2. C. M. R. Volla, I. Atodiresei and M. Rueping, Chem. Rev, 2014, 114,
2390-2431.
30. P. Waffo-Teguo, D. Lee, M. Cuendet, J.-M. Mérillon, J. M. Pezzuto and A.
D. Kinghorn, J. Nat. Prod., 2001, 64, 136-138.
3. S. Lancianesi, A. Palmieri and M. Petrini, Chem. Rev, 2014, 114, 7108-
7149.
31. J. Boutagy and R. Thomas, Chem. Rev, 1974, 74, 87-99.
4. P. Talalay, M. J. De Long and H. J. Prochaska, Proc. Natl. Acad. Sci, 1988,
85, 8261-8265.
32. J. B. Baudin, G. Hareau, S. A. Julia and O. Ruel, Tetrahedron Lett., 1991,
32, 1175-1178.
5. J. C. Lo, J. Gui, Y. Yabe, C.-M. Pan and P. S. Baran, Nature, 2014, 516,
343-348.
33. R. Robiette and J. Pospíšil, Eur. J. Org. Chem., 2013, 2013, 836-840.
6. J. H. Kim, J. H. Kim, G. E. Lee, J. E. Lee and I. K. Chung, Mol. Pharmacol,
2003, 63, 1117-1124.
34. D. A. Alonso, M. Fuensanta, C. Nájera and M. Varea, J. Org. Chem., 2005,
70, 6404-6416.
7. G. Yan, A. J. Borah and L. Wang, Org. Biomol. Chem, 2014, 12, 6049-
6058.
35. M. Chalal, D. Vervandier-Fasseur, P. Meunier, H. Cattey and J.-C. Hierso,
Tetrahedron, 2012, 68, 3899-3907.
8. Y.-J. Jang, Y.-K. Shih, J.-Y. Liu, W.-Y. Kuo and C.-F. Yao, Chem. Eur. J.,
2003, 9, 2123-2128.
36. J.-B. Liu, F.-J. Chen, N. Liu and J. Hu, RSC Advances, 2015, 5, 45843-
45846.
9. C.-F. Yao, C.-M. Chu and J.-T. Liu, J. Org. Chem., 1998, 63, 719-722.
10. J.-Y. Liu, J.-T. Liu and C.-F. Yao, Tetrahedron Lett., 2001, 42, 3613-3615.
37. M. E. Weiss, L. M. Kreis, A. Lauber and E. M. Carreira, Angew. Chem.,
2011, 123, 11321-11324.
38. Y. Ikeda, H. Yorimitsu, H. Shinokubo and K. Oshima, Adv. Synth. Catal.,
2004, 346, 1631-1634.
11. J.-j. Ma, W.-b. Yi, G.-p. Lu and C. Cai, Adv. Synth. Catal., 2015, 357, 3447-
3452.
39. R. Loska, C. M. R. Volla and P. Vogel, Adv. Synth. Catal., 2008, 350, 2859-
2864.
12. J. Zheng, D. Wang and S. Cui, Org. Lett., 2015, 17, 4572-4575.
13. S. Guo, Y. Yuan and J. Xiang, New J. Chem, 2015, 39, 3093-3097.
14. P. Schroll, D. P. Hari and B. König, ChemistryOpen, 2012, 1, 130-133.
40. R. Matsubara, A. C. Gutierrez and T. F. Jamison, J. Am. Chem. Soc, 2011,
133, 19020-19023.
15. N. Zhang, Z.-J. Quan, Z. Zhang, Y.-X. Da and X.-C. Wang, Chem. Comm,
2016, 52, 14234-14237.
41. J. G. Taylor, A. V. Moro and C. R. D. Correia, Eur. J. Org. Chem., 2011,
2011, 1403-1428.
16. P. Patil, A. Nimonkar and K. G. Akamanchi, J. Org. Chem., 2014, 79,
2331-2336.
42. J. Iqbal, B. Bhatia and N. K. Nayyar, Chem. Rev, 1994, 94, 519-564.
43. X. Qu, P. Sun, T. Li and J. Mao, Adv. Synth. Catal., 2011, 353, 1061-1066.
17. R. R. Jadhav, S. N. Huddar and K. G. Akamanchi, Eur. J. Org. Chem., 2013,
2013, 6779-6783.
44. T. Nishikata, Y. Noda, R. Fujimoto and T. Sakashita, J. Am. Chem. Soc,
2013, 135, 16372-16375.
18. P. C. Patil and K. G. Akamanchi, Tetrahedron Lett., 2017, 58, 1883-1886.
45. A. F. Littke and G. C. Fu, J. Am. Chem. Soc, 2001, 123, 6989-7000.
19. M. Jang, L. Cai, G. O. Udeani, K. V. Slowing, C. F. Thomas, C. W. Beecher,
H. H. Fong, N. R. Farnsworth, A. D. Kinghorn and R. G. Mehta, Science, 1997,
275, 218-220.
46. S. J. Sabounchei and M. Hosseinzadeh, J. Chem. Sci., 2015, 127, 1919-
1926.
47. A. R. Hajipour and G. Azizi, Green Chem, 2013, 15, 1030-1034.
48. T. W. Liwosz and S. R. Chemler, Org. Lett, 2013, 15, 3034-3037.
20. T. Shen, X.-N. Wang and H.-X. Lou, Nat. Prod. Rep., 2009, 26, 916-935.
21. S. Albert, R. Horbach, H. B. Deising, B. Siewert and R. Csuk, Biorg. Med.
Chem., 2011, 19, 5155-5166.
49. K.-J. Shi, C.-H. Shu, C.-X. Wang, X.-Y. Wu, H. Tian and P.-N. Liu, Org. Lett.,
2017.
22. M. H. Keylor, B. S. Matsuura and C. R. Stephenson, Chem. Rev, 2015,
115, 8976-9027.
50. A. R. Ehle, Q. Zhou and M. P. Watson, Org. Lett., 2012, 14, 1202-1205.
23. J. M. Estrela, S. Mena, E. Obrador, M. Benlloch, G. Castellano, R.
Salvador and R. W. Dellinger, J. Med. Chem., 2017, DOI:
10.1021/acs.jmedchem.6b01026.
51. A. Skhiri, R. B. Salem, J.-F. Soulé and H. Doucet, Synthesis, 2016, 48,
3097-3106.
52. Y.-B. Zhou, Y.-Q. Wang, L.-C. Ning, Z.-C. Ding, W.-L. Wang, C.-K. Ding, R.-
H. Li, J.-J. Chen, X. Lu and Y.-J. Ding, J. Am. Chem. Soc, 2017, 139, 3966-3969.
24. B.-B. Yu, X.-Z. Han and H.-X. Lou, J. Agric. Food Chem., 2007, 55, 7753-
7757.
53. E. Shirakawa, X. Zhang and T. Hayashi, Angew. Chem., 2011, 123, 4767-
4770.
25. A. J. Gescher, Planta medica, 2008, 74, 1651-1655.
26. H. Hamada, K. Shimoda, Y. Horio, T. Ono, R. Hosoda, N. Nakayama and
K. Urano, Nat Prod Commun, 2017, 12, 85-86.
54. C. L. Sun, Y. F. Gu, B. Wang and Z. J. Shi, Chem. Eur. J., 2011, 17, 10844-
10847.
27. P. O Patil, A. G Patil, R. A Rane, P. C Patil, P. K Deshmukh, S. B Bari, D. A
Patil and S. S Naphade, Anticancer Agents Med Chem, 2015, 15, 955-969.
55. E. Shirakawa and T. Hayashi, Chem. Lett., 2012, 41, 130-134.
10 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 11 of 12
New Journal of Chemistry
NJC
56. J. P. Barham, G. Coulthard, K. J. Emery, E. Doni, F. Cumine, G. Nocera, M. 82. B. Schmidt, N. Elizarov, R. Berger and F. Hölter, Org. Biomol. Chem,
View Article Online
DOI: 10.1039/C7NJ04701K
P. John, L. E. Berlouis, T. McGuire and T. Tuttle, J. Am. Chem. Soc, 2016, 138,
2013, 11, 3674-3691.
7402-7410.
83. F. Lara-Ochoa, L. C. Sandoval-Minero and G. Espinosa-Perez,
57. E. Doni, S. Zhou and J. A. Murphy, Molecules, 2015, 20, 1755-1774.
Tetrahedron Lett., 2015, 56, 5977-5979.
58. J. F. Guastavino, M. E. Buden and R. A. Rossi, J. Org. Chem, 2014, 79,
9104-9111.
84. K. Nicolaou, C. J. Mathison and T. Montagnon, J. Am. Chem. Soc, 2004,
126, 5192-5201.
59. M. Zhang, T. Jia, I. K. Sagamanova, M. A. Perica
Lett., 2015, 17, 1164-1167.
́
85. K. Nicolaou, T. Montagnon, P. Baran and Y.-L. Zhong, J. Am. Chem. Soc,
2002, 124, 2245-2258.
60. F. Zhao, J. Luo, Q. Tan, Y. Liao, S. Peng and G. J. Deng, Adv. Synth. Catal.,
2012, 354, 1914-1918.
86. K. Nicolaou, P. Baran, Y.-L. Zhong, S. Barluenga, K. Hunt, R. Kranich and
J. Vega, J. Am. Chem. Soc, 2002, 124, 2233-2244.
61. S. A. Jagtap, T. Sasaki and B. M. Bhanage, J. Mol. Catal. A: Chem., 2016,
414, 78-86.
87. K. Nicolaou, P. S. Baran, R. Kranich, Y. L. Zhong, K. Sugita and N. Zou,
Angew. Chem., 2001, 113, 208-212.
62. M. W. van Laren and C. J. Elsevier, Angew. Chem., Int. Ed, 1999, 38,
3715-3717.
88. F. De Vleeschouwer, V. Van Speybroeck, M. Waroquier, P. Geerlings and
F. De Proft, Org. Lett., 2007, 9, 2721-2724.
63. J. G. Ulan, W. F. Maier and D. A. Smith, J. Org. Chem., 1987, 52, 3132-
3142.
89. R. Najman, J. K. Cho, A. F. Coffey, J. W. Davies and M. Bradley, Chem.
Comm, 2007, DOI: 10.1039/B711978J, 5031-5033.
64. A. M. Kluwer, T. S. Koblenz, T. Jonischkeit, K. Woelk and C. J. Elsevier, J.
Am. Chem. Soc, 2005, 127, 15470-15480.
90. P. Puthiaraj and K. Pitchumani, Green Chem, 2014, 16, 4223-4233.
91. R. Kusy and K. Grela, Org. Lett., 2016, 18, 6196-6199.
65. D. Srimani, Y. Diskin‐Posner, Y. Ben‐David and D. Milstein, Angew.
Chem., Int. Ed, 2013, 52, 14131-14134.
92. L. Yu, Y. Huang, Z. Wei, Y. Ding, C. Su and Q. Xu, J. Org. Chem., 2015, 80,
8677-8683.
66. V. G. Shukla, P. D. Salgaonkar and K. G. Akamanchi, J. Org. Chem., 2003,
68, 5422-5425.
93. O. H. Wheeler and H. N. B. d. Pabon, J. Org. Chem., 1965, 30, 1473-
1477.
67. D. S. Bhalerao, U. S. Mahajan, K. H. Chaudhari and K. G. Akamanchi, J.
Org. Chem., 2007, 72, 662-665.
94. M. A. Brooks and L. T. Scott, J. Am. Chem. Soc, 1999, 121, 5444-5449.
95. D.-J. Dong, H.-H. Li and S.-K. Tian, J. Am. Chem. Soc, 2010, 132, 5018-
5020.
68. E. V. Bellale, D. S. Bhalerao and K. G. Akamanchi, J. Org. Chem., 2008,
73, 9473-9475.
96. J. Y. Yu, R. Shimizu and R. Kuwano, Angew. Chem., Int. Ed, 2010, 49,
6396-6399.
69. P. C. Patil, D. S. Bhalerao, P. S. Dangate and K. G. Akamanchi,
Tetrahedron Lett., 2009, 50, 5820-5822.
97. J. E. Dubois and M. F. Ruasse, J. Org. Chem., 1973, 38, 493-499.
70. P. S. Chaudhari, S. P. Pathare and K. G. Akamanchi, J. Org. Chem., 2012,
77, 3716-3723.
98. S. Mochida, K. Hirano, T. Satoh and M. Miura, J. Org. Chem., 2011, 76,
3024-3033.
71. S. Fulda, Drug Discov. Today, 2010, 15, 757-765.
99. G.-G. Chen, J.-Q. Wei, X. Yang and Z.-J. Yao, Org. Lett., 2016, 18, 1502-
1505.
72. S. Kim, H. Ko, J. E. Park, S. Jung, S. K. Lee and Y.-J. Chun, J. Med. Chem.,
2002, 45, 160-164.
100.Y.-P. Qian, Y.-J. Cai, G.-J. Fan, Q.-Y. Wei, J. Yang, L.-F. Zheng, X.-Z. Li, J.-G.
Fang and B. Zhou, J. Med. Chem., 2009, 52, 1963-1974.
73. P. L. Liu, J. R. Tsai, A. L. Charles, J. J. Hwang, S. H. Chou, Y. H. Ping, F. Y.
Lin, Y. L. Chen, C. Y. Hung and W. C. Chen, Mol Nutr Food Res, 2010, 54.
74. Y. T. Yang, C. J. Weng, C. T. Ho and G. C. Yen, Mol Nutr Food Res, 2009,
53, 407-416.
75. J. Xiao, J. Yang, T. Chen and L.-B. Han, Chem. Comm, 2016, 52, 2157-
2160.
76. H. Lebel, C. Ladjel and L. Bréthous, J. Am. Chem. Soc, 2007, 129, 13321-
13326.
77. V. K. Aggarwal, J. R. Fulton, C. G. Sheldon and J. de Vicente, J. Am. Chem.
Soc, 2003, 125, 6034-6035.
78. S. C. Söderman and A. L. Schwan, J. Org. Chem., 2012, 77, 10978-10984.
79. I. Y. El-Deeb, T. Funakoshi, Y. Shimomoto, R. Matsubara and M. Hayashi,
J. Org. Chem., 2017, 82, 2630-2640.
80. E. Alonso, D. J. Ramón and M. Yus, J. Org. Chem., 1997, 62, 417-421.
81. T. Chen, J. Xiao, Y. Zhou, S. Yin and L.-B. Han, J. Organomet. Chem.,
2014, 749, 51-54.
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