Synthesis of 2,4,6-Trisubstituted Pyridines by Oxidative Eosin y Photoredox Catalysis

Article abstract of DOI:10.1021/acs.joc.6b00979

Eosin Y, an organic dye, was activated as a photoredox catalyst in the presence of molecular oxygen using visible light and, when it was used in the reaction of aryl ketones and benzyl amines, afforded good yields (52-87%) of 2,4,6-triarylpyridines (21 examples) at ambient temperature. The aryl groups at the 2- and 6-positions are derived from ketones, while benzyl amine plays the dual role of providing an aryl functionality at the 4-position of pyridine as well as being a nitrogen donor.

Full text of DOI:10.1021/acs.joc.6b00979

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Article
Synthesis of 2,4,6-Trisubstiuted Pyridines
by Oxidative Eosin Y Photoredox Catalysis
Rajendra Shankar Rohokale, Burkhard König, and Dilip D. Dhavale
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00979 • Publication Date (Web): 30 Jun 2016
Downloaded from http://pubs.acs.org on July 3, 2016
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Synthesis of 2,4,6-Trisubstiuted Pyridines by Oxidative Eosin Y
Photoredox Catalysis
Rajendra S. Rohokale,# Burkhard Koenig*† and Dilip D. Dhavale*
#
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#Garware Research Centre, Department of Chemistry, Savitribai Phule Pune University
(formerly University of Pune), Puneꢀ411007.
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†Institute fuer Organische Chemie, Universitaet Regensburg, Universitatstrasse 31, 93053,
Regensburg, Germany.
E-mail: ddd@chem.unipune.ac.in, Burkhard.Koenig@chemie.uni-regensburg.de
Abstract: Eosin Yꢀan organic dye was activated as photoredox catalyst in the presence of
molecular oxygen using visible light and when used in the reaction of aryl ketones and benzyl
amines afforded good yields of 2,4,6ꢀtriarylpyridines (21 examples) at ambient temperature.
The aryl groups at two and six positions are derived from ketones while; benzyl amine plays
duel role of providing aryl functionality at the four position of pyridine as well as a nitrogen
donor.
Graphical abstract:
Introduction:
Redox active organic dyes such as eosin Y, rose bengal, fluorescein, xanthenes,
riboflavin, with strong absorption in the visible part of the spectrum, have been widely used
in photochemical organic transformations.1 These organic photoredox catalysts are less toxic
and cheaper compared to organometallic and inorganic catalysts.2 Amongst these, eosin Y
has found wide utility in cell staining, as a pH indicator3 and in continues flow technology.4
In addition, synthetic applications of eosin Y involves formation of reactive intermediates
such as aryl radicals, αꢀcarbonyl radicals, iminium ions, trifluromethyl radicals, enone
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radicals in organic transformations as well as in decarboxylation and cycloaddition
reactions.5,6 Our group has demonstrated the use of eosin Y for (a) formation of CꢀC and CꢀP
bonds by activation of tetrahydroisoquinoline,7 (b) enantioselective transformations in
combination with organocatalysts7c,d and (c) synthesis of substituted aromatic heterocycles by
intermolecular C−H arylation.7a,b As part of our continuous efforts in this area, we herewith
report the use of eosin YꢀO2 as a photoredox catalyst, in combination with BF3 . Et2O, in the
reaction of aryl ketones and benzyl amines to get 2,4,6ꢀtriarylpyridines.
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Functionalised 2,4,6ꢀtriarylpyridines (Krohnke pyridine)8 have been extensively
exploited as chemoꢀsensors,9 as catalysts,10as photo sensitizers11 and as intermediates in the
synthesis of therapeutic drugs, insecticides, herbicides and surfactants.12 Classic methods13
for the synthesis of 2,4,6ꢀtriarylpyridines include (a) modified multicomponent Chichibabin
pyiridine reaction employing an aldehyde, an enolizable ketone and an ammonium salt as a
nitrogen source using various catalysts at higher temperature,14 (b) condensation of ketoꢀ
oximes with aryl aldehydes15a or oxiranes15b at high temperature and (c) reaction of amino
allenes with aldehydes followed by palladium catalyzed cyclization.16 Guan and coꢀworkers
reported a copper mediated coupling of aryl aldehydes with aromatic ketoꢀoxime acetates
(Scheme 1, eq. 1)17 for the synthesis of 2,4,6ꢀtriarylpyridines. Recently, Jiang and coꢀworkers
have reported the copper catalyzed oxidative cleavage of CꢀN bonds of benzyl amines that
couple with aromatic ketones giving triarylpyridines at elevated temperature (Scheme 1, eq.
2).18 Our results for the synthesis of 2,4,6ꢀtriarylpyridines from aromatic ketones and benzyl
amines using eosin YꢀO2 in the presence of visible light are reported herein.
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Scheme 1. Synthesis of 2,4,6ꢀtriarylpyridines
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Results and Discussion:
Initially, a reaction mixture of acetophenone 1a (1.0 mmol), benzyl amine 2a (3.0
mmol) and eosin Y (5 mol %) in the presence of BF3 Et2O (0.2 mmol) and molecular oxygen
in DMSO was irradiated with green LEDs (530 nm) for 30 h at room temperature.
Purification of the crude product gave the symmetrically substituted 2,4,6ꢀtriphenyl pyridine
3a in 45% yield (Scheme 2).
Scheme 2: Synthesis of 2,4,6ꢀtriphenylpyridine
To identify which aryl group is derived from which substrate, we performed the same
reaction using 1ꢀ(pꢀtolyl) ethanone (1.0 eq.) and benzyl amine (3.0 eq.) yielding 2,4,6ꢀtriarylꢀ
pyridine 3b in 50% yield wherein; the pꢀmethyl phenyl group of the aryl ketone was found to
be at the two and six positions and the phenyl group of benzyl amine was found to be at the
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four position of the pyridine. The benzyl amine played dual role of phenyl group as well as a
nitrogen atom donor in the pyridine ring.
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Next, the reaction conditions were optimized by variation of the photocatalyst,
additives and solvent to increase product yield. The results are summarized in Table 1.
Reactions of equal amounts of pꢀmethyl phenyl ethanone (1.0 eq.) and benzyl amine (1.0 eq.)
as well as reactions of pꢀmethyl phenyl ethanone (2.0 eq.) and benzylamine (1.0 eq.) afforded
low product yields (<20%; Table 1, entry 1 and 2). Therefore, we maintained a 1:3 ratio of
aryl ketone and benzyl amine. Other photocatalysts, such as rose bengal (with green light) or
the metal complex Ru(bpy)3.6H2O (with blue light), under the identical condition, afforded
3b in 30% and 12% yields, respectively (entry 3 and 4). The use of Bronsted acids such as pꢀ
TSA and acetic acid gave 3b in 22% and 40% yields, respectively (entry 5, 6). The use of
iodine (2.0 mol %) as an additive afforded a complex product of mixture (entry 7).
Decreasing the mol% of BF3ꢁEt2O to 10% in DMSO reduced the yield of product (entry 9).
Increase in the molar ratio of the BF3ꢁEt2O to 50 mol% gave 3b in 79% (entry 10). The use of
acetonitrile (entry 11, 60%), DMF (entry 12, 50%) and dichloromethane (entry 13, 48%) as
solvents gave lower yields. The better results were obtained using BF3ꢁEt2O (50 mol %) in
MeOH providing 3b in 87% yield (entry 14).
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With the optimized conditions, the scope of the reaction was studied for the synthesis
of substituted 2,4,6ꢀtriarylpyridines (Scheme 3). The reaction of pꢀmethoxy phenyl ethanone
(1.0 eq.) with benzyl amine (3.0 eq.), under the optimized conditions, gave corresponding
2,4,6ꢀtriarylpyridine 3c in 72% yield. Reactions of electron withdrawing substituted
acetophenones such as pꢀfluoroꢀ, pꢀchloroꢀ, pꢀbromoꢀphenyl ethanone and benzyl amine
afforded good yields of products 3d (68%), 3e (68%), 3f (64%). However, pꢀnitroꢀphenyl
ethanone was found to be unreactive under the reaction conditions. The effect of electron
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donating orthoꢀ group was demonstrated by using sterically hindered oꢀmethoxy phenyl
ethanone as a substrate that also provided 3m in 66% yield.
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Table 1. Optimization of reaction conditions.a
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No.
1c
2d
3
catalyst
Eosin Y
additive (%)
BF3.Et2O (20%)
BF3.Et2O (20%)
BF3.Et2O (20%)
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CN
DMF
Yields(%)b
<20
<20
30
Eosin Y
Rose Bengal
4
Ru(bpy)3.6H2O BF3.Et2O (20%)
12
5
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
No catalyst
Eosin Y
pꢀTSA (20%)
AcOH (20%)
22
6
40
7
Iodine (20%)
00
8e
9
BF3.Et2O (20%)
BF3.Et2O (10%)
BF3.Et2O (50%)
BF3.Et2O (50%)
BF3.Et2O (50%)
BF3.Et2O (50%)
BF3.Et2O (50%)
BF3.Et2O (50%)
none
50
32
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12
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18
79
60
50
DCM
48
MeOH
neat
87
40
MeOH
MeOH
MeOH
Trace
trace
trace
BF3.Et2O (50%)
BF3.Et2O (50%)
aConditions: aryl ketone 1b (1.0 mmol), benzyl amine 2a (3.0 mmol), catalyst (5 mol%), additive,
solvent, O2, green light, 30 oC, 30ꢀ40 h. bisolated yields. caryl ketone 1b (1.0 mmol), benzyl amine 2a
(1.0 mmol),daryl ketone 1b (1.0 mmol), benzyl amine 2a (2.0 mmol), e2 mol% catalyst was used.
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Next, we studied the effect of substituents in the benzyl amine. Thus, reaction of 4ꢀ
methoxybenzyl amine with pꢀchloroꢀ, pꢀfluoroꢀ, pꢀmethylꢀ, pꢀmethoxyꢀphenyl ethanone,
under the optimized reaction conditions, gave corresponding 2,4,6ꢀtriarylpyridines 3h-i in
good yields (62ꢀ80%). The reaction of 4ꢀmethoxybenzyl amine with 1ꢀ(naphthaleneꢀ2ꢀyl)
ethanone yielded 3o in 60% and the reaction of 3,4ꢀdichlorobenzyl amine and 4ꢀfluorobenzyl
amine with 1ꢀ(pꢀtolyl) ethanone provided corresponding products 3p and 3q in 76 and 72%
yields, respectively. The scope of the reaction was further studied with aliphatic as well as
cyclic ketones. Thus, reaction of pentanꢀ2ꢀone with benzyl amine afforded product 3t in 54%
yield while; the reaction with cyclohexanone led to complex mixture of products. Further, the
reaction was also studied with secondary amine namely dibenzylamine. Thus, reaction of
dibenzylamine (3 eq.) with pꢀmethyl acetophenone (1 eq.) under standard conditions gave 3b
in 49% yield. Treatment of 3ꢀpicolylamine with pꢀmethylꢀphenyl ethanone gave the desired
product 3r in 61% yield. Interestingly, when 2ꢀpicolyl amine was employed with 1ꢀ(pꢀtolyl)
ethanone, the desired product 3s was obtained in 22% yield with deamination cross coupled
product 4 (48%).18The formation of product 4 was noticed only in the case of 2ꢀpicolyl
amine. A possible mechanism is shown in Scheme 4. We believe that, under the reaction
conditions, complexation of BF3.Et2O with acetophenone gives alkenyloxy boron complex A
with the formation of HF that reacts with 2ꢀpicolyl amine to give ammonium ion species B.
Further complexation of A and B leads to the formation of intermediate C that undergoes
intramolecular displacement of ammonium ion to give product 4.
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Scheme 3. Substrate scope for the synthesis of 2,4,6ꢀtrisubstituted pyridine.
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In support of mechanistic hypothesis a few control experiments were performed.
Thus, reaction of acetophenone (1.0 eq.) and benzyl amine (3.0 eq.) in the absence of either
.
(a) BF3 Et2O (Table 1, entry 16), (b) eosin Y (entry 17), (c) LEDs light (entry 18) or (d)
molecular oxygen (reaction mixture was purged with and kept under N2 atmosphere) failed to
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give 2,4,6ꢀtriarylpyridine. In order to validate the intermediacy of benzaldehyde, as reported
by Jiang and coworkers,18 we performed the reaction of acetophenone (1.0 eq.) and benzyl
amine (1.0 eq.) in the presence of pꢀmethyl benzaldehyde (1.0 eq.) under the optimized
reaction conditions as reported for 3a. This reaction failed to give either 3a or 3ab (Scheme
5, eq. a). Increasing the molar ratio of benzylamine (3.0 eq.), gave 3a in 35% yield while, no
trace amount of triarylpyridine 3ab was detected by LCꢀMSꢀMS.19 This experiment excludes
the formation of benzaldehyde in the present protocol by using eosin Y as photoredox
catalyst. Next, we explored imine 5 as a possible intermediate.18 Thus, reaction of
acetophenone (1.0 eq.) with of imine 5 (2.0 eq.), separately prepared and isolated from benzyl
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amine and O2 at 100 C in DMSO,20 gave 3a in 43 % yield (Scheme 5, eq. b) under the
optimized reaction conditions. This indicates imine 5 as a likely intermediate in the formation
of triarylpyridine. The same reaction in the absence of eosin Y failed to give 3a. To confirm
the formation of imine 5 in the reaction, the benzyl amine was irradiated under the green light
in the presence of eosin Y and O2 in dry acetonitrile that afforded imine 5 (1H, 13C NMR and
HRMS is given in SI) in quantitative yield (Scheme 5, eq. c).
Scheme 4. Plausible mechanism for crossꢀcoupled product 4.
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Scheme 5. Control experiments.
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Based on these observations, we propose the following plausible mechanism for the
formation of triarylpyridines (Scheme 6). Under the reaction conditions, the photocatalytic
oxidative coupling of benzyl amine is induced by eosin Y generating the iminium ion
intermediate A and ammonia.21 Subsequently the addition of enol I, facilitated by the
BF3.Et2O as an additive, to the iminium ion A results in the formation of II that upon
photocatalytic oxidation gives III. A second addition of enol I to III leads to the formation
IV. The condensation of IV with ammonia gives V that on aromatization provides triaryl
pyridine 3.
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Scheme 6. Plausible reaction mechanism.
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In conclusion, we have demonstrated the use of eosin YꢀO2 as a photoredox catalyst
in combination with aryl ketones and benzyl amines, using visible light for the synthesis of
triarylpyridines. We presume that the role of BF3ꢁEt2O is to catalyses the formation of imine
and enamine intermediates and the additionꢀelimination sequence. The reaction proceeds at
ambient temperature in high yields and has a wide scope in substituted 2,4,6ꢀtriarylpyridines
as the aryl groups at the two and four position are derived from the aryl ketones and the aryl
functionality at four positions is provided by the benzyl amines. In addition, to its role as
nitrogen atom donor. The method is a mild, ecoꢀfriendly and reliable alternative to the
established procedures for the selective synthesis of triarylpyridines. Further applications of
eosin Y as photoredox catalyst in the synthesis of heteroaromatic compounds is in progress.
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Experimental Section:
1
General Methods. H and 13C NMR spectra were recorded using a 500 MHz NMR
spectrometer. The chemical shifts are expressed in d with reference to TMS as the internal
standard. Highꢀresolution mass spectra were obtained with a HRMS TOF mass spectrometer
ESI. Melting points were recorded with Thomas Hoover Capillary melting point apparatus.
TLC was performed using commercially available 100−400 mesh silica gel plates (GF254).
Eosin Y (spirit soluble, 99% dye content) was purchased from Sigma Aldrich. The green light
irradiation was performed using highꢀpower LEDs (3W, λ = 530±10 nm).
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General Procedure for the Synthesis of 2,4,6-Trisubstituted Pyridines. In a round bottom
flask (10 mL) equipped with magnetic stirring bar, eosinꢀY (5 mol %), aromatic ketone 1 (1 eq.)
and benzylamine 2 (3 eq.) were dissolved in MeOH (2 mL) and BF3·Et2O (50 mol %). The
round bottom flask was evacuated and then refilled with oxygen using an oxygen balloon.
The reaction mixture was irradiated using 530 nm LEDs at room temperature for 30 h. After the
completion of reaction, the methanol was removed on vacuum the residue was purified by
flash column chromatography by using ethyl acetate and petroleum ether as eluent to afford
pure product 3.
o
1
2,4,6-Triphenylpyridine (3a).18 In 72% yield (184 mg), white solid, (mp. 136ꢀ137 C): H
NMR (500 MHz, CDCl3) δ 8.22 (d, J = 7.1 Hz, 4H), 7.91 (s, 2H), 7.77 (d, J = 7.0 Hz, 2H),
13
7.57−7.43 (m, 9H); C NMR (125 MHz, CDCl3) δ 157.5, 150.3, 139.5, 139.0, 129.1, 129.1,
129.0, 128.7, 127.2, 127.2, 117.2; HRMS (ESI) calc. C23H18N [M + H]+ 308.1434, found
308.1438.
4-Phenyl-2,6-di-p-tolylpyridine (3b).18 In 87% yield (217 mg), white solid, (mp. 158ꢀ159
oC): 1H NMR (500 MHz, CDCl3) δ 8.08 (d, J = 7.9 Hz, 4H), 7.79 (s, 2H), 7.68 (d, J = 7.8 Hz,
2H), 7.49−7.38 (m, 3H), 7.28 (d, J = 7.9 Hz, 4H), 2.39 (s, 6H); 13C NMR (125 MHz, CDCl3)
δ 157.3, 149.9, 139.2, 138.9, 136.8, 129.3, 129.0, 128.8, 127.1, 126.9, 116.4, 21.3; HRMS
(ESI) calc. C25H22N [M + H]+ 336.1747, found 336.1753.
2,6-Bis(4-methoxyphenyl)-4-phenylpyridine (3c).18 In 77% yield (188 mg), white solid,
(mp. 98ꢀ99 oC): 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J = 8.7 Hz, 4H), 7.79 (s, 2H), 7.75 (d,
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J = 7.2 Hz, 2H), 7.56−7.45 (m, 3H), 7.06 (d, J = 8.7 Hz, 4H), 3.89 (s, 6H); 13C NMR (125
MHz, CDCl3) δ 160.5, 156.9, 149.9, 139.3, 132.3, 129.0, 128.8, 128.3, 127.1, 115.6, 114.0,
55.3; HRMS (ESI) calc. C25H21NNaO2 [M + Na]+ 390.1470, found 390.1467.
2,6-Bis(4-fluorophenyl)-4-phenylpyridine (3d).18 In 68% yield (168 mg), white solid, (mp.
100ꢀ101 oC): 1H NMR (500 MHz, CDCl3) δ 8.18 (dd, J = 8.2, 5.6 Hz, 4H), 7.82 (s, 2H), 7.73
(d, J = 7.6 Hz, 2H), 7.58−7.46 (m, 3H), 7.20 (t, J = 8.5 Hz, 4H); 13C NMR (125 MHz,
CDCl3) δ 163.6 (d, J C-F = 248.6 Hz), 156.4, 150.4, 138.8, 135.5, 129.1, 129.1, 128.9, 127.1,
116.7, 115.5; HRMS (ESI) calc. C23H16 F2N [M + H]+ 344.1245, found 344.1252.
2,6-Bis(4-chlorophenyl)-4-phenylpyridine (3e).18 In 68% yield (165 mg), white solid, (mp.
183ꢀ184 oC): 1H NMR (500 MHz, CDCl3) δ 8.13 (d, J = 7.9 Hz, 4H), 7.85 (s, 2H), 7.72 (d, J
= 7.7 Hz, 2H), 7.57−7.46 (m, 7H); 13C NMR (125 MHz, CDCl3) δ 156.3, 150.6, 138.6, 137.7,
135.3, 129.2, 129.1, 128.9, 128.3, 127.1, 117.1; HRMS (ESI) calc. C23H16Cl2N [M + H]+
376.0654, found 376.0658.
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2,6-Bis(4-bromophenyl)-4-phenylpyridine (3f).13d In 64% yield (149 mg), white solid, (mp.
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195ꢀ197 oC): H NMR (500 MHz, CDCl3) δ 8.09 (d, J = 8.6 Hz, 4H), 7.89 (s, 2H), 7.75 (d, J
= 7.0 Hz, 2H), 7.67 (d, J = 8.6 Hz, 4H), 7.58ꢀ7.50 (m, 3H); 13C NMR (125 MHz, CDCl3) δ
156.4, 150.6, 138.6, 138.2, 131.9, 129.2, 129.2, 128.6, 127.1, 123.6, 117.1. HRMS (ESI)
calc. C23H16Br2N [M + H]+ 463.9644, found 463.9645.
4-(4-Methoxyphenyl)-2,6-diphenylpyridine (3h).15a In 62% yield (173 mg), white solid,
(mp. 100ꢀ101 oC): 1H NMR (500 MHz, CDCl3) δ 8.25 (d, J = 7.2 Hz, 4H), 7.88 (s, 2H), 7.72
(d, J = 8.8 Hz, 2H), 7.58−7.46 (m, 6H), 7.07 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 160.4, 157.3, 149.5, 139.6, 131.1, 128.9, 128.6, 128.2, 127.1, 116.5, 114.4,
55.3; HRMS (ESI) calc. C24H20NO [M + H]+ 338.1539, found 338.1544.
2,6-Bis(4-methylphenyl)-4-(4-methoxyphenyl)pyridine (3i).18 In yield (217 mg), white
solid, (mp. 156ꢀ157 oC): 1H NMR (500 MHz, CDCl3) δ 8.12 (d, J = 8.1 Hz, 4H), 7.83 (s, 2H),
7.73 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.1 Hz, 4H), 7.07 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H), 2.46
(s, 6H).13C NMR (125 MHz, CDCl3) δ 160.3, 157.3, 149.4, 138.8, 137.0, 131.5, 129.3, 128.3,
126.9, 116.04, 114.4, 55.4, 21.3. HRMS (ESI) calc. C26H24NO [M + H]+ 366.1852, found
366.1855.
2,6-Bis(4-methoxyphenyl)-4-(4-methoxyphenyl)pyridine (3j).15a In 68% yield (179 mg),
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white solid, (mp. 133ꢀ134 C): H NMR (500 MHz, CDCl3) δ 8.18 (d, J = 8.8 Hz, 4H), 7.76
(s, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.12 – 7.01 (m, 6H), 3.91 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 160.4, 160.3, 156.9, 149.4, 132.4, 131.6, 128.3, 128.3, 115.2, 114.4, 114.0, 55.4,
55.3. HRMS (ESI) calc. C26H24NO3 [M + H]+ 398.1751, found 398.1759.
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2,6-Bis(4-fluorophenyl)-4-(4-methoxyphenyl)pyridine (3k). In 62% yield (167 mg), white
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solid, (mp. 124ꢀ125 C): H NMR (500 MHz, CDCl3) δ 8.19 (dd, J = 8.8, 5.4 Hz, 4H), 7.82
(s, 2H), 7.72 (d, J = 8.7 Hz, 2H), 7.22 (t, J = 8.7 Hz, 4H), 7.08 (d, J = 8.7 Hz, 2H), 3.92 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 163.6 (d, JC-F = 248.4 Hz), 160.5, 156.4, 149.9, 135.7,
135.7, 131.0, 128.9, 128.8, 128.3, 116.20, 115.6, 115.5, 114.5, 55.4. HRMS (ESI) calc.
C24H18F2NO [M + H]+ 374.1351, found 374.1360.
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2,6-Bis(4-chlorophenyl)-4-(4-methoxyphenyl)pyridine (3l). In 62% yield (162 mg), white
solid, (mp. 180ꢀ181 oC): 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J = 8.6 Hz, 4H), 7.84 (s,2H),
7.71 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.6 Hz, 4H), 7.08 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 160.6, 156.3, 150.0, 137.9, 135.2, 130.8, 128.9, 128.3, 128.3,
116.5, 114.6, 55.4. HRMS (ESI) calc. C24H18Cl2NO [M + H]+ 406.0760, found 406.0766.
2,6-Bis(2-methoxyphenyl)-4-phenylpyridine (3m).18 In 66% yield (161 mg), white solid,
(mp. 153ꢀ154 oC): 1H NMR (500 MHz, CDCl3) δ 8.05 (s, 2H), 8.02 (d, J = 7.6 Hz, 2H), 7.78
(d, J = 7.3 Hz, 2H), 7.58−7.37 (m, 5H), 7.15 (t, J = 7.4 Hz, 2H), 7.06 (d, J = 8.2 Hz, 2H),
3.92 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 157.0, 155.9, 147.6, 139.4, 131.5, 129.7, 129.6,
128.9, 128.5, 127.3, 121.3, 121.0, 111.4, 55.7; HRMS (ESI) calc. C25H21NNaO2 [M + Na]+
390.1470, found 390.1464.
2,6-Bis(2-methoxyphenyl)-4-(4-methoxyphenyl)pyridine (3n). In 62% yield (164 mg),
white solid, (mp. 183ꢀ184 oC): 1H NMR (500 MHz, CDCl3) δ 7.98 (dd, J = 7.7, 2.0 Hz, 4H),
7.72 (dd, J = 6.8, 1.9 Hz, 2H), 7.50 – 7.35 (m, 2H), 7.14 (t, J = 7.0 Hz, 2H), 7.06 (d, J = 8.3
Hz, 4H), 3.93 (s, 6H), 3.90 (s,3H); 13C NMR (125 MHz, CDCl3) δ 160.1, 157.1, 155.9, 147.1,
131.7, 131.5, 129.7, 129.6, 128.4, 121.0, 120.9, 114.3, 111.4, 55.7, 55.3. HRMS (ESI) calc.
C26H24NO3 [M + H]+ 398.1751, found 398.1755.
2,6-Di(naphthalene-2-yl)-4-(4-methoxyphenyl)pyridine (3o). In 60% yield (154 mg), white
solid, (mp. 157ꢀ158 oC): 1H NMR (500 MHz, CDCl3) δ 8.36 – 8.26 (m, 2H), 7.95 (d, J = 7.5
Hz, 4H), 7.86 (s, 2H), 7.81 (d, J = 7.0 Hz, 2H), 7.77 (d, J = 8.7 Hz, 2H).7.67 – 7.58 (m, 2H),
7.54 (dd, J = 6.2, 3.3 Hz, 4H), 7.06 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 160.6, 159.5, 148.5, 138.9, 133.99, 131.4, 130.5, 128.8, 128.4, 128.4, 127.6, 126.4,
125.8, 125.8, 125.4, 120.9, 114.6, 55.4. HRMS (ESI) calc. C32H24NO [M + H]+ 438.1852,
found 438.1856.
2,6-Bis(4-methylphenyl)-4-(3,4-dichlorophenyl)pyridine (3p). In 76% yield (228 mg),
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white solid, (mp. 185ꢀ186 C): H NMR (500 MHz, CDCl3) δ 8.12 (d, J = 8.2 Hz, 4H), 7.84
(d, J = 2.0 Hz, 1H), 7.78 (s, 2H), 7.59 (dt, J = 8.3, 5.2 Hz, 2H), 7.35 (d, J = 7.9 Hz, 4H), 2.47
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(s, 6H); 13C NMR (125 MHz, CDCl3) δ 157.7, 147.5, 139.2, 139.2, 136.4, 133.3, 133.1,
131.0, 129.4, 129.0, 126.9, 126.4, 116.0, 21.3. HRMS (ESI) calc. C25H20Cl2N [M + H]+
404.0973, found 404.0971.
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2,6-Bis(4-methylphenyl)-4-(4-flurophenyl)pyridine (3q). In 72% yield (189 mg), white
solid, (mp. 173ꢀ174 oC): 1H NMR (500 MHz, CDCl3) δ 8.13 (d, J = 8.2 Hz, 4H), 7.81 (s, 2H),
7.79 – 7.69 (m, 2H), 7.35 (d, J = 7.9 Hz, 4H), 7.24 (t, J = 8.7 Hz, 2H), 2.47 (s, 6H); 13C NMR
(125 MHz, CDCl3) δ 164.3, 162.3, 157.4, 148.9, 139.0, 136.7, 135.3, 135.3, 129.4, 128.9,
128.8, 126.99, 116.3, 116.1, 115.9, 21.3. HRMS (ESI) calc. C25H20FN [M + H]+ 354.1658,
found 354.1663.
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2,6-Di(4-methylphenyl)-3,4-bipyridine (3r). In 61% yield (152 mg), yellow solid, (mp. 145ꢀ
146 oC): 1H NMR (500 MHz, CDCl3) δ 9.02 (s, 1H), 8.74 (d, J = 4.1 Hz, 1H), 8.13 (d, J = 7.5
Hz, 4H), 8.05 (d, J = 7.7 Hz, 1H), 7.84 (s, 2H), 7.56 – 7.44 (m, 1H), 7.35 (d, J = 7.6 Hz, 4H),
2.46 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 157.7, 149.9, 148.3, 146.8, 139.3, 136.5, 134.9,
134.5, 129.5, 127.0, 123.8, 116.2, 21.3. HRMS (ESI) calc. C24H21N2 [M + H]+ 337.1705,
found 337.1703.
2,6-Di(4-methylphenyl)-2,4-bipyridine (3s). In 22% yield (55 mg), yellow solid, (mp. 138ꢀ
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139 C): H NMR (500 MHz, CDCl3) δ 8.82 (ddd, J = 4.8, 1.7, 0.9 Hz, 1H), 8.27 (s, 2H),
8.18 (d, J = 8.2 Hz, 4H), 7.99 – 7.90 (m, 1H), 7.88 (td, J = 7.7, 1.8 Hz, 1H), 7.39 (ddd, J =
7.4, 4.8, 1.1 Hz, 1H), 7.35 (d, J = 7.9 Hz, 4H), 2.46 (s, 6H); 13C NMR (125 MHz, CDCl3) δ
157.5, 155.5, 150.0, 147.9, 139.01, 137.0, 136.8, 129.8, 129.5, 129.4, 129.1, 127.0, 126.9,
125.9, 123.6, 121.1, 115.7, 21.3. HRMS (ESI) calc. C24H21N2 [M + H]+ 337.1698, found
337.1699.
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2,6-Bis(propyl)-4-phenylpyridine (3t). In 54% yield (151 mg), yellowish thick liquid: H
NMR (500 MHz, CDCl3) δ 7.65 (dd, J = 5.2, 3.3 Hz, 2H), 7.52 – 7.41 (m, 4H), 7.20 (s, 2H),
2.85 – 2.80 (t, J = 7.7 Hz, 4H), 1.87 – 1.72 (m, 4H), 1.02 (t, J = 7.4 Hz, 6H).13C NMR (125
MHz, CDCl3) δ 162.2, 148.8, 139.1, 128.9, 128.6, 127.1, 118.0, 40.6, 23.5, 13.9. HRMS
(ESI) calc. C17H21NNa [M + Na]+ 262.1572, found 262.1571.
1-(4-Methylphenyl)-3-(pyridin-2-yl)-propan-1-one (4).18 In 48% yield (81 mg), yellowish
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thick liquid: H NMR (500 MHz, CDCl3) δ 8.66 – 8.42 (m, 1H), 7.91 (d, J = 8.2 Hz, 2H),
7.61 (td, J = 7.7, 1.8 Hz, 1H), 7.27 (dd, J = 12.2, 5.5 Hz, 3H), 7.13 (dd, J = 7.0, 5.4 Hz, 1H),
3.50 (t, J = 7.3 Hz, 2H), 3.25 (t, J = 7.3 Hz, 2H), 2.42 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
198.9, 160.8, 149.2, 143.8, 136.4, 134.4, 129.2, 128.2, 123.4, 121.2, 37.7, 32.1, 21.6. HRMS
(ESI) calc. C15H16NO [M + H]+ 226.1232, found 226.1231.
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Supporting Information: Characterization of products and copies of 1H, 13C NMR spectra
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and HRMS data.
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Acknowledgement: R.S.R. is thankful to the CSIR, New Delhi and the DAAD/BASF
(INDIGO programme, Germany) for the fellowships. We are thankful to the Department of
Science and Technology, New Delhi (Project File No. EMR/2014/000873) and the Deutsche
Forschungsgemeinschaft (GRK 1626) for financial support.
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References and Note:
1. (a) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle, A. G.; MacMillan, D. W. C.
Science 2014, 345, 437. (b) Prier, C. K.; Rankic, D. A.; Macmillan, D. W. C. Chem. Rev.
2013, 113, 5322 and references cited therein. (c) Narayanam J. M. R.; Stephenson C. R. J.,
Chem. Soc. Rev. 2011, 40, 102 and references cited therein. (d) Zeitler K. Angew. Chem., Int.
Ed. 2009, 48, 9785. (e) Shi, L.; Xia,W. Chem. Soc. Rev. 2012, 41, 7687. (f) Rueping, M.;
Vila, C.; Bootwicha, T. ACS Catal. 2013, 3, 1676.
2. (a) Liu, H.; Feng, W.; Kee, C. W.; Zhao, Y.; Leow, D.; Pan, Y.; Tan, C.ꢀH. Green Chem.
2010, 12, 953. (b) Vila, C.; Rueping, M. Green Chem. 2013, 15, 2056. (c) Chen, K.; Zhang,
P.; Wanga, Y.; Li, H. Green Chem., 2014, 16, 2344. (d) Gu, L.; Jinb, C.; Liu, J. Green Chem.
2015, 17, 3733. (e) Rackl, D.; Kreitmeier, P.; Reiser, O. Green Chem. 2016, 18, 214.
3. (a) Selsted, M. E.; Becker Iii, H. W.; Anal. Biochem. 1986, 155, 270. (b) Sabnis, R. W.
Handbook of Acid-Base Indicators, Taylor & Francis, 2007. (c) Ahluwalia,V. K.; Dhingra, S.
D.; S. College Practical Chemistry, Universities Press, 2005. (d) Brennecke, E. Furman, N.
H.; Stamm, H.; Lang, R.; Fajans, K.; Bottger, C. W; Oesper, R. E.; Newer Methods of
Volumetric Chemical Analysis, D. Van Nostrand Company, Incorporated, 1938.
4. (a) Cantillo, D.; de Frutos, O.; Rincon, J. A.; Mateos, C.; Kappe, C. O.; Org. Lett. 2014,
16, 896. (b) Neumann, M.; Zeitler, K.; Org. Lett. 2012, 14, 2658.
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5. (a) Hari, D. P.; Koenig, B. Angew. Chem., Int. Ed. 2013, 52, 4734. (b) Sun, C.ꢀL.; Shi, Z.ꢀJ.
Chem. Rev. 2014, 114, 9219 and references cited therein. (c) Schultz, D. M.; Yoon, T. P.
Science 2014, 343, 1239176. (d) Beatty, J. W.; Stephenson, C. R. J. Acc. Chem. Res. 2015,
48, 1474 and references cited therein. (e) Zhang, G.; Liu, C.; Yi, H.; Meng, Q.; Bian, C.;
Chen, H.; Jian, J.ꢀX.; Wu, L.ꢀZ.; Lei, A. J. Am. Chem. Soc. 2015, 137, 9273 and references
cited therein.
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6. (a) Li, X.; Gu, X.; Li, P. ACS Catal. 2014, 4, 1897. (b) Fan, W.; Yang, Q.; Xu, F.; Li, P. J.
Org. Chem. 2014, 79, 10588. (c) Xiao, T.; Li, L.; Lin, G.; Mao, Z.; Zhou, L. Org. Lett. 2014,
16, 4232. (d) Yang, W.; Yang, S.; Li, P.; Wang, L. Chem. Commun. 2015, 51, 7520. (e) Li,
J.; Zhang, J.; Tan, H.; Wang, D. Z. Org. Lett. 2015, 17, 2522.
7. (a) Hari, D. P.; Schroll, P.; Koenig, B.; J. Am. Chem. Soc. 2012, 134, 2958. (b) Hari, D. P.;
Hering, T. Koenig, B.; Org. Lett. 2012, 14, 5334. (c) Neumann, M.; Fueldner, S.; Koenig, B.;
Zeitler, K.; Angew. Chem., Int. Ed. 2011, 50, 951. (d) Hari, D. P.; Koenig, B.; Org. Lett.
2011, 13, 3852.
8. (a) Progress in Heterocyclic Chemistry; Gribble, G. W.; Joule, J. A.; Eds.; Elsevier:
Oxford, 2008; Vol. 20 and others in this series. (b) Comprehensive Heterocyclic Chemistry
III; Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K.; Eds.; Pergamon:
Oxford, 2008. (c) Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. A.,
Scriven, E. F. V., Taylor, R. J. K., Eds.; Pergamon: Oxford, 2008. (d) Comprehensive
Heterocyclic Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.; McKillop, A.;
Eds.; Pergamon: Oxford, 1996 and references therein. (e) Eicher, T.; Hauptmann, S. The
Chemistry of Heterocycles; WileyꢀVCH: Weinheim, 2003. (f) The Chemistry of Heterocyclic
Compounds; Coppola, G. M.; Schuster, H. F.; Eds.: WileyꢀVCH: New York, 1981. (g)
Michael, J. P. Nat. Prod. Rep. 2005, 22, 627. (h) Plunkett, A. O. Nat. Prod. Rep. 1994, 11,
581. (i) Daly, J. W.; Pinder, A. R. Nat. Prod. Rep. 1992, 9, 491.
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9. Fang, A. G.; Mello, J. V.; Finney, N. S. Tetrahedron 2004, 60, 11075.
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10. For examples, see: (a) Chelucci, G.; Thummel, R. P. Chem. Rev. 2002, 102, 3129. (b)
Durola, F.; Sauvage, J. P.; Wenger, O. S. Chem. Commun. 2006, 171. (c) Sweetman, B. A.;
MullerꢀBunz, H.; Guiry, P. J. Tetrahedron Lett. 2005, 46, 4643. (d) Kozhevnikov, V. N.;
Kozhevnikov, D. N.; Nikitina, T. V.; Rusinov, V. L.; Chupakhin, O. N.; Zabel, M.; Koenig,
B. J. Org. Chem. 2003, 68, 2882. (e) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T.
Org. Biomol. Chem. 2006, 4, 2337. (f) Roughley, S. D.; Jordan, A. M. J. Med. Chem. 2011,
54, 3451. (g) Knip, M.; Douek, I. F.; Moore, W. P. T.; Gillmor, H. A.; McLean, A. E. M.;
Bingley, P. J. E.; Gale, A. M. Diabetologia 2000, 43, 1337.
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11. Islam, A.; Sugihara, H.; Arakawa, H. J. Photochem. Photobiol. 2003, 158, 131.
12. (a) Peter, S.; Gerhard, H.; Elisabeth, H.; Ralf, K.; Hartmann, K.; Albercht, H.; Norbert,
G.; Helmut, W.; KarlꢀOtto, W.; Uif, M. U.S. Patent 5733850, 1998; Chem. Abstr. 1996, 125,
167792w. (b) Pharmaceutical Chemistry, Drug Synthesis Vol-I; Roth, H. J.; Kleemann, A.,
Eds.; Prentice Hall Europe: London, 1988; 407. (c) Kletsas, D.; Li, W.; Han, Z.;
Papadopoulos, V. Biochem. Pharmacol. 2004, 67, 1927. (d) Basnet, A.; Thapa, P.; Karki, R.;
Na, Y.; Jahng, Y.; Jeong, B. S.; Jeong, T. C.; Lee, C. S.; Lee, E. S. Bioorg. Med. Chem. 2007,
15, 4351. (e) Kim, B. Y.; Ahn, J. B.; Lee, H. W.; Kang, S. K.; Lee, J. H.; Shin, J. S.; Ahn, S.
K.; Hong, C. I.; Yoon, S. S. Eur. J. Med. Chem. 2004, 39, 433. (f) Enyedy, I. J.; Sakamuri,
S.; Zaman, W. A.; Johnson, K. M.; Wang, S. Bioorg. Med. Chem. Lett. 2003, 13, 513. (g)
Christelle, D.; Patrick, W.; Frédéric, B.; Nicolas, H.; Cyril, A. K.; Yves, M.; JeanꢀJacques,
B.; Martine, S. J. Org. Chem. 2014, 79, 908. (h) In Comprehensive Heterocyclic Chemistry
II; Vol. 5, M. Balasubramanian, J. G Keay, A. R. Katritzky, C. W. Rees and E. V. F. Scriven,
Eds.; Chapter 6; Pergamon Press: London, 1996, 245–300; and references cited therein.
13. (a) Gulevich, A.V.; Dudnik,A. S.; Chernyak,N.; Gevorgyan,V.; Chem. Rev. 2013, 113,
3084. (b) Allais, C.; Grassot, JꢀM.; Rodriguez, J.; Constantieux, T. Chem. Rev. 2014, 114,
17
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The Journal of Organic Chemistry
Page 18 of 18
1
2
3
4
5
6
7
8
9
10829 and references cited therein. (c) Zhang, DꢀH.; Zhang, Z.; Shi, M.; Chem. Commun.
2012, 48, 10271. (d) Ren, Z.ꢀH.; Zhang, Z.ꢀY.; Yang, B.ꢀQ.; Wang, Y.ꢀY.; Guan, Z.ꢀH. Org.
Lett. 2011, 13, 5394. (e) Krohnke, F. Synthesis 1976, 1. (f) Wang, P.; Hua, R; Li, C.ꢀJ.
Current Organic Synthesis 2013, 10, 655. (g) Bai,Y.; Tang, L.; Huanga, H.; Deng, G.ꢀJ. Org.
Biomol. Chem. 2015, 13, 4404.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
14. (a) Frank, R. L.; Seven, R. P. J. Am. Chem. Soc. 1949, 71, 2629. (b) Shinde, P. V.;
Labade, V. B.; Gujar, J. B.; Shingate, B. B.; Shingare, M. S. Tetrahedron Lett. 2012, 53,
1523. (c) References cited in 13a and 13b.
15. (a) Mahernia, S.;r Mahdavi, M.; Adib, M. Synlett 2014, 25, 1299. (b) Mahernia, S.;
Adib, M. Mahdavi, M.; Nosrati, M. Tetrahedron Lett. 2014, 55, 3844.
16. He, Z.; Dobrovolsky, D.; Trinchera, P.; Yudin, A. K. Org. Lett. 2013, 15, 334.
17. Ren, Z.ꢀH.; Zhang, Z.ꢀY.; Yang, B.ꢀQ.; Wang, YꢀY.; Guan, Z.ꢀH. Org. Lett. 2011, 13,
5394.
18. Huang, H.; Ji, X.; Wu, W.; Huang, L.; Jiang, H. J. Org. Chem. 2013, 78, 3774.
19. We isolated benzaldehyde by column chromatography in nearly quantitative amount.
20. Nguyen, T. B.; Ermolenko, L.; AlꢀMourabit, A.; Green Chem. 2013, 15, 2713.
21. Park, J. H.; Ko K. C.; Kim, E.; Park, N.; Ko, J. H.; Ryu, D. H.; Ahn, T. K.; Lee, J. Y.;
Son, S. U. Org. Lett. 2012, 14, 5502.
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