Cobalt(II)porphyrin-Mediated Selective Synthesis of 1,5-Diketones via an Interrupted-Borrowing Hydrogen Strategy Using Methanol as a C1 Source

Article abstract of DOI:10.1021/acs.joc.1c00476

A novel cobalt(II)porphyrin-mediated acceptorless dehydrogenation of methanol is reported for the first time. This methodology has been applied for the coupling of a variety of ketones with methanol to produce 1,5-diketones along with H2 and H2O as the environment friendly byproducts. This paradigm was also demonstrated for a one-pot synthesis of substituted pyridines using a sequential addition protocol where the 1,5-diketones were generated in situ. From many experiments including those involving deuterium labeling, it is proposed that protonated cobalt(II)porphyrin methoxide complex acts as an intermediate to generate formaldehyde along with a metal hydride.

Full text of DOI:10.1021/acs.joc.1c00476

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Article
Cobalt(II)porphyrin-Mediated Selective Synthesis of 1,5-Diketones
via an Interrupted-Borrowing Hydrogen Strategy Using Methanol as
a C1 Source
Priyabrata Biswal, Shaikh Samser, Prakash Nayak, Vadapalli Chandrasekhar,*
and Krishnan Venkatasubbaiah*
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ABSTRACT: A novel cobalt(II)porphyrin-mediated acceptorless
dehydrogenation of methanol is reported for the first time. This
methodology has been applied for the coupling of a variety of
ketones with methanol to produce 1,5-diketones along with H2 and
H2O as the environment friendly byproducts. This paradigm was
also demonstrated for a one-pot synthesis of substituted pyridines
using a sequential addition protocol where the 1,5-diketones were
generated in situ. From many experiments including those involving
deuterium labeling, it is proposed that protonated cobalt(II)-
porphyrin methoxide complex acts as an intermediate to generate formaldehyde along with a metal hydride.
Metal complex catalysts are also used for the synthesis of
INTRODUCTION
■
1,5-diketones.8e−h For example, Trost and co-workers used a
Ru(II)-catalyst8e and Zhang and Guo utilized a Rh(I)-catalyst
for the synthesis of 1,5-diketones. However, selective synthesis
of 1,5-diketones from ketones and methanol using the
interrupted-borrowing hydrogen strategy is scarcely reported.
The Donohoe5a group reported the synthesis of one
symmetrical and two unsymmetrical 1,5-diketones (sequential
multistep) using an expensive Ir-complex (2 mol %) with
excess of base and oxygen as an external oxidant (Scheme 1c).
Later, the Das5b group reported a polymer supported
palladium nanoparticle for synthesis of α-methylation of
ketone; in the course of the reaction, they found symmetrical
1,5-diketone as a side product with less yield (20−40%), as
their protocol focused on major product α-methylation of
ketone (Scheme 1d). Recently, the Xiao5c group demonstrated
α-methoxylation of ketones using CoCl2·6H2O (10 mol %),
Cs2CO3 (2 equiv), and oxygen as an external oxidant; in the
course of the optimization, they observed 1,5-diketone as a
side product with a low yield (29%) (Scheme 1e). Lack of
selectivity (Scheme 2a) and inadequate substrate scope
attracted our attention to find a method for the selective
synthesis of 1,5-diketones.
Formation of carbon−carbon bonds using commercially
available feedstocks is a highly desirable goal in organic
synthesis.1 Over the last few decades, significant efforts have
been made to develop environmentally benign acceptorless
dehydrogenation of inexpensive substrates such as alcohols
without having to use stoichiometric quantities of the oxidant.2
Alcohols can be transformed into the corresponding carbonyl
compounds using different metal complexes; the in situ formed
carbonyl compounds can lead to successive reaction in the
same pot to generate compounds with new functionalities.2,3
Methanol is a cheap, abundant, and renewable C-1 feedstock
that has been used to make C−C and C−N bonds. During the
past decade, selective α-methylation of ketones by borrowing
hydrogen catalysis (BH) has been elegantly applied using
methanol.4 However, studies to generate α-methylenated
architectures using the interrupted-borrowing hydrogen
strategy (I-BH) are limited.4a,5
Diketones are versatile building blocks and are important in
the synthesis of a wide variety of organic molecules. Among the
different diketones, 1,5-diketones have gained attraction due to
their potential biological and pharmacological activities.6
Furthermore, 1,5-diketones have also proven to be invaluable
building blocks for the synthesis of many heterocyclic7a−d and
polyfunctional7e,f (cyclopentenes, piperidines, pyridines, hydra-
zines, ketolactones, and many other heterocyclic molecules)
compounds. Traditionally, 1,5-diketones are synthesized
through the condensation reaction between α,β-unsaturated
ketones with ketones8a (Michael addition) or silyl enolethers
(Scheme 1a)8b also via condensation between aldehydes and
aryl methyl ketones (Scheme 1b).8c,d
Received: February 26, 2021
Published: April 27, 2021
https://doi.org/10.1021/acs.joc.1c00476
© 2021 American Chemical Society
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Scheme 1. Synthesis of 1,5-Diketones Using Traditional
Methods and Selectivity in Catalytic BH and I-BH Methods
Scheme 2. Schematic Representation of Expected Products
Using Borrowing Hydrogen (BH) Methodology and
Interrupted-Borrowing Hydrogen (I-BH) Methodology
Using Methanol and Selectivity Using Co-Catalysts in This
Study
The major challenge in the selective synthesis of 1,5-
diketones from ketones and methanol is to develop a
sustainable I-BH methodology which can diminish the chances
of formation of other side products, as discussed vide supra
(Scheme 1). Herein, we report a unique, simple Co(II)-
porphyrin-mediated selective synthesis of symmetrical 1,5-
diketones directly from ketones and methanol (Scheme 2b)
without using stochiometric base and external oxidant.
RESULTS AND DISCUSSION
■
Keeping this in mind, our initial investigation started with
cobalt(II)porphyrin9 (Co-por) as a catalyst and propiophe-
none and methanol as the model system to scrutinize the
reaction conditions. Treatment of propiophenone (0.5 mmol)
with methanol (0.5 mL), Co-por (2 mol %), and base (20 mol
%) in dry toluene (0.5 mL) produced the desired product in
62% isolated yield in the form of inseparable diastereomers
(Table 1, entry 1). The formation of diastereomers was
analyzed and identified using NMR techniques (Supporting
Information, Figure S76). Bases like KOtBu, LiOtBu, Na2CO3,
KOH, and NaOH gave a low yield (Table 1, entries 2−6).
Further studies indicated that 3 mol % Co-por and 30 mol %
base gave the desired product in higher yield (78%) (Table 1,
entry 7). Changing the cobalt source to Co-salen, Co(acac)2,
CoCl2, and CoBr2 resulted in lower yields (Table 1, entries 9−
12). Use of polar solvents such as THF and dioxane resulted in
a significant reduction in yield (Table 1, entries 13 and 14).
Notably, on increasing the base load to 50 mol %, an
impressive change in the isolated yield (92%) was observed
(Table 1, entry 15). Further increase of catalyst load did not
affect the product yield (Table 1, entry 16). Reaction without
toluene also gave comparatively low yield (Table 1, entry 17).
The scope of the Co-por-mediated synthesis of 1,5-
diketones using the optimized reaction conditions was
explored. Reaction of butyrophenone and 1-phenylpentan-1-
one with methanol exclusively yielded the corresponding 1,5-
diketones in 86% yield (Table 2, entries 1b and 1c). Substrates
bearing electron-donating substituents (CH3−, C2H5−) on the
para position of aryl ketones under similar reaction conditions
yielded 1,5-diketones in good yields (Table 2, entries 2a−2c
and 4a−4c). 3,5-Dimethyl aryl ketones yielded the respective
1,5-diketones in 84, 82, and 81%, respectively (Table 2, entries
3a−3c).
Notably, thioketones were found to be active enough to
yield the desired products 5a−5c in 72, 68, and 66%,
respectively. The catalytic system also tolerated “methoxy”
substitution on the phenyl and yielded the desired product in
62, 72, 76, and 64%, respectively (Table 2, entries 8 and 6a−
6c). Meta substituted propiophenone also gave the 1,5-
diketone product in 87% yield (Table 2, entry 7). Surprisingly,
alicyclic ketone gave the desired diastereomer product in 57%
yield (Table 2, entry 9). To demonstrate the catalytic activity,
we further explored using a biphenyl system. The reaction
proceeded smoothly to yield the corresponding 1,5-diketones
in 58 and 55%, respectively (Table 2, entries 10a and 10b).
However, halo aryl ketones under the optimized conditions did
not yield the desired product. To our delight, compound 10b
crystallized in a monoclinic system (P21/c) which was
analyzed using single crystal X-ray crystallography (Figure
S1). To check the practicality of our method, a gram scale
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a
reaction was carried out with propiophenone under the
optimized conditions. The reaction produced the desired 1,5-
diketone product in 78% isolated yield (Table 2, entry 1a).
Motivated by these results, we next examined the reactivity of
3-phenylpropiophenones; the C-alkylated products that were
synthesized using the hydrogen borrowing methodology.1d
Under the optimized conditions, the reaction of 3-phenyl
propiophenones gave the conjugate addition products in
moderate yields (Table 2, entries 11a−11d). Reaction of
ethanol with propiophenone instead of methanol did not
produce the desired 1,5-diketone product under the optimized
reaction conditions. A trace amount of conversion was
observed when acetophenone was used as a substrate;
however, the reaction produced a complex mixture without
any product formation.
Table 1. Optimization Table
d
b
catalyst
(mol %)
T
yield
c
entry
base (mol %)
(°C)
solvent
(%)
1
2
3
4
5
6
7
8
Co-por (2)
Co-por (2)
Co-por (2)
Co-por (2)
Co-por (2)
Co-por (2)
Co-por (3)
Co-por (3)
Co-salen (3)
Co(acac)2 (3)
CoCl2 (3)
NaOtBu (20)
KOtBu (20)
LiOtBu (20)
NaOH (20)
KOH (20)
Na2CO3 (20)
NaOtBu (30)
NaOtBu (30)
NaOtBu (30)
NaOtBu (30)
NaOtBu (30)
NaOtBu (30)
NaOtBu (30)
NaOtBu (30)
NaOtBu (50)
NaOtBu (50)
NaOtBu (50)
135
135
135
135
135
135
135
100
135
135
135
135
135
135
135
135
135
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
62
45
40
ND
ND
ND
78
trace
62
Controlled experiments were performed to gain insights into
the reaction mechanism. When propiophenone was reacted
with deuterated methanol (CD3OD), selectively deuterated
1,5-diketone product 12 was obtained in 72% yield. This
observation indicates that the proton at the α-carbon has its
origin from methanol during the course of the reaction
(Scheme 3a). The in situ generated formaldehyde after
condensing with propiophenone yields the interrupted-
borrowing hydrogen product or the enone (C*). This transient
α-methenylated unsaturated ketone subsequently reacts with
propiophenone via Michael addition to yield the 1,5-diketone
product (1a) exclusively.5 We believe that this step proceeds in
the presence of a base. The reaction of propiophenone with
paraformaldehyde instead of methanol gave the desired 1,5-
diketone product in 86% isolated yield, which further supports
that formaldehyde is formed during the course of the reaction
(Scheme 3c). To confirm our hypothesis, we reacted the
intermediate (C*) and propiophenone in the presence of
NaOtBu (50 mol %), which resulted in the 1,5-diketone (1a)
as the major product in 94% yield (Scheme 3b). As expected,
no conversion was observed, when we reacted 13a in our
standard experimental conditions, which indicates that C* is
the intermediate formed during the course of the reaction
(Scheme 3d). In the latter reaction, the α-position of the
carbonyl moiety is occupied; hence, it hinders the formation of
the α-methenylated unsaturated ketone (C*) intermediate. In
addition, presence of TEMPO (1.5 equiv) under the standard
conditions used for the synthesis of 1,5-diketones yielded 78%
(1a) of the product, clarifying that the reaction did not adopt
any free radical pathway (Scheme 3e). We reacted 4-
nitroacetophenone under similar conditions; surprisingly, the
nitro group reduced to an amino group,4g,h producing 4-
aminoacetophenone 13b in a yield of 62% (Scheme 3f). This
justifies that methanol is converting to formaldehyde with
evolution of H2 gas. Based on the controlled experiments and
from the literature reports,5,2a,10 a plausible mechanism for the
reaction of propiophenone and methanol in the presence of
Co-por is proposed (Scheme 3g). We believe that the catalytic
cycle is initiated by the formation of a complex (A*) generated
by MeOH in the presence of Co-por and base. Based on our
controlled experiments and the literature suggested method-
s,2a,10 we speculate that the complex (A*) is liberating
formaldehyde and metal hydride (B*) species during the
reaction. Then, the metal hydride (B*) species regenerates the
complex (A*) with the liberation of H2 gas on reaction with
methanol. The ephemeral formaldehyde generates the α-
methylenated intermediate (C*) on reaction with propiophe-
none. The resultant α-methylenated intermediate (C*) and
9
10
11
12
13
14
15
16
17
32
28
31
35
30
92
93
76
CoBr2 (3)
Co-por (3)
Co-por (3)
Co-por (3)
Co-por (5)
Co-por (3)
1,4-dioxane
toluene
toluene
a
Reaction conditions: propiophenone 5 × 10−1 mmol, 0.5 mL of
CH3OH, 24 h. All yields are isolated yields. 0.5 mL of solvent. Oil
bath temperature.
b
c
d
a b
,
Table 2. Substrate Scope
a
Reaction conditions: ketone 0.5 mmol, catalyst 1.5 × 10−2 mmol,
b
and base 2.5 × 10−1 mmol. All yields are isolated yields. 1a gram
scale yield 78%.
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Scheme 3. Mechanistic Studies
Scheme 4. Synthetic Application
60:40 (H2O: THF) composition. Afterward, the intensity of
the emission increased rapidly (Figure 1 and Supporting
Information). This phenomenon is called aggregation induced
enhanced emission (AIEE) or aggregation induced emission
(AIE). Molecules with AIEE properties are of interest due to
their diverse applications as bioprobes, chemosensor stimuli-
responsive nanomaterials, and active layers in the construction
of efficient organic light-emitting diodes.11 We believe that our
protocol will help to make a wide variety of substituted
pyridines that will show AIEE properties and also may have
other potential applications, as mentioned vide supra.
CONCLUSIONS
■
In summary, a novel interrupted-borrowing hydrogen strategy
for coupling of methanol and ketones using a bench stable
Co(II)porphyrin complex is disclosed. Our environmentally
benign method was employed on a variety of ketones for the
direct and selective synthesis of 1,5-diketones having H2O and
H2 as the eco-friendly byproducts. Control experiments and
deuterium-labeling study showed that the reaction proceeds
through an α-methylenated intermediate. The synthetic utility
of this protocol was extended for the preparation of AIEE
active pyridines which may have potential application in
making organic light-emitting diodes.
EXPERIMENTAL SECTION
propiophenone condense via Michael addition to give the
desired 1,5-diketone (1a).
■
General Procedure for the 1,5-Diketone Reaction. An oven-
dried sealed tube (50 mL) was charged with Co-por (1.5 × 10−2
mmol, 0.03 equiv) and NaOtBu (2.5 × 10−1 mmol, 0.50 equiv).
Under an inert atmosphere, ketone (0.50 mmol, 1 equiv), methanol
(0.5 mL), and toluene (0.5 mL) were added to the reaction mixture
and the system was purged with nitrogen gas. Then, the sealed tube
was closed with a PTFE stopper and the reaction mixture was stirred
at 135 °C (oil bath temperature) for 24 h. The reaction mixture was
transferred to a round-bottom flask after cooling it to room
temperature, the sealed tube was rinsed with methanol (2 × 5 mL),
and the combined organic mixture was concentrated under a vacuum.
The crude mixture was subjected to column chromatography on silica
gel using n-hexane and ethyl acetate mixtures to afford the desired 1,5-
diketone product in high purity. All of the crude mixture was purified
by column chromatography using n-hexane:EtOAc (20:1 to 10:1).
(Note: All reactions were carried out in a 50 mL sealed tube made up
of a material that can withstand the internal pressure.)
As alluded to in the Introduction, 1,5-diketones act as
intermediates for the synthesis of heterocycles. We investigated
the transformation of diketones to pyridines (Scheme 4). For
example, treatment of 1,5-diketones 1a, 1b, and 10b with
NH2OH·HCl resulted in the substituted pyridines 14a, 14b,
and 14c, respectively, in good yields. Compounds 14a, 14b,
and 14c were also synthesized in one pot using sequential
addition of reagents, as shown in Scheme 4. The formation of
1
pyridines was confirmed using H and 13C NMR and HRMS.
The molecular structure of 14c was further confirmed by X-ray
crystal structure analysis (Figure S2a). All three pyridines
showed interesting photophysical properties which exhibit
absorption maxima (λmax) at around 300 nm (Figure S2b). We
analyzed the photoluminescence (PL) behavior of the
pyridines in solution and aggregate states.
Procedure for the Gram Scale Reaction. An oven-dried sealed
tube was charged with Co-por (3 × 10−1 mmol, 0.03 equiv) and
NaOtBu (5.00 mmol, 0.50 equiv). Under an inert atmosphere, ketone
The emission of pyridines is weak in tetrahydrofuran (THF)
solution and increases slowly (or) remains unchanged up to
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17.7. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C19H20O2 +
Na]+, 303.1356; found, 303.1369.
2,4-Diethyl-1,5-diphenylpentane-1,5-dione (Table 1, Entry 1b).5b
Prepared from butyrophenone (0.074 g, 0.50 mmol). After
purification by column chromatography (n-hexane/EtOAc, 20/1),
an inseparable mixture of two diastereomers anti-1b and syn-1b in
1
1:1.1 ratio was isolated as a yellow liquid (0.066 g, 86%). H NMR
(400 MHz, CDCl3) δ 8.00 (d, J = 7.9 Hz, 4H), 7.70 (d, J = 7.9 Hz,
4H), 7.57 (t, J = 7.3 Hz, 2H), 7.49 (t, J = 7.6 Hz, 4H), 7.42 (t, J = 7.4
Hz, 2H), 7.27 (t, J = 7.6 Hz, 4H), 3.45 (p, J = 7.9 Hz, 2H), 3.31 (p, J
= 7.9 Hz, 2H), 2.31 (dt, J = 14.0, 7.1 Hz, 1H), 2.06 (t, J = 7.9 Hz,
2H), 1.81−1.66 (m, 5H), 1.57−1.46 (m, 4H), 0.86 (t, J = 7.4 Hz,
6H), 0.80 (t, J = 7.4 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ
204.8, 203.9, 137.6, 137.3, 133.2, 133.0, 128.8, 128.6, 128.44, 128.1,
45.5, 45.1, 33.5, 33.2, 27.2, 25.4, 11.85, 11.7. HRMS (ESI-TOF) m/z
[M + Na]+ Calcd for [C21H24O2 + Na]+, 331.1669; found, 331.1679.
1,5-Diphenyl-2,4-dipropylpentane-1,5-dione (Table 1, Entry 1c).
Prepared from 1-phenylpentan-1-one (0.081 g, 0.50 mmol). After
purification by column chromatography (n-hexane/EtOAc, 20/1), an
inseparable mixture of two diastereomers anti-1c and syn-1c in 1.1:1
1
ratio was isolated as a yellow liquid (0.072 g, 86%). H NMR (400
MHz, CDCl3) δ 8.00 (d, J = 7.1 Hz, 4H), 7.68 (d, J = 7.1 Hz, 4H),
7.58 (t, J = 7.3 Hz, 2H), 7.49 (t, J = 7.5 Hz, 4H), 7.42 (t, J = 7.4 Hz,
2H), 7.29−7.23 (m, 4H), 3.52 (p, J = 8.0 Hz, 2H), 3.36 (p, J = 8.0
Hz, 2H), 2.29 (dt, J = 14.0, 7.2 Hz, 1H), 2.08−2.04 (m, 2H), 1.79−
1.72 (m, 1H), 1.70−1.60 (m, 4H), 1.48−1.39 (m, 4H), 1.34−1.27
(m, 4H), 1.23−1.09 (m, 4H), 0.84 (t, J = 7.3 Hz, 6H), 0.78 (t, J = 7.3
Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.9, 204.0, 137.5,
137.3, 133.2, 133.0, 128.8, 128.6, 128.4, 128.1, 43.9, 43.5, 36.3, 34.5,
34.2, 20.7, 20.6, 14.3, 14.2. HRMS (ESI-TOF) m/z [M + Na]+ Calcd
for [C23H28O2 + Na]+, 359.1982; found, 359.1999. FT-IR (ATR,
neat): 2957, 2871, 1677, 1595, 1001, 701 cm−1.
2,4-Dimethyl-1,5-di-p-tolylpentane-1,5-dione (Table 1, Entry
2a). Prepared from 1-(p-tolyl)propan-1-one (0.074 g, 0.50 mmol).
After purification by column chromatography (n-hexane/EtOAc, 20/
1), an inseparable mixture of two diastereomers anti-2a and syn-2a in
1
1.16:1 ratio was isolated as a yellow liquid (0.071 g, 92%). H NMR
(400 MHz, CDCl3) δ 7.95 (d, J = 8.3 Hz, 4H), 7.67 (d, J = 8.3 Hz,
4H), 7.30 (d, J = 7.9 Hz, 4H), 7.11 (d, J = 7.9 Hz, 4H), 3.58 (sextet, J
= 8.0 Hz, 2H), 3.46 (sextet, J = 8.0 Hz, 2H), 2.42 (s, 6H), 2.42−2.37
(m, 1H), 2.33 (s, 6H), 1.98 (t, J = 8.0 Hz, 2H), 1.46 (dt, J = 14.0, 7.2
Hz, 1H), 1.19 (d, J = 6.9 Hz, 6H), 1.15 (d, J = 6.9 Hz, 6H). 13C{1H}
NMR (101 MHz, CDCl3) δ 204.2, 203.7, 144.0, 143.8, 134.1, 133.8,
129.5, 129.3, 128.7, 128.4, 38.5, 38.1, 37.5, 37.3, 21.8, 21.7, 18.9, 17.7.
HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C21H24O2 + Na]+,
331.1669; found, 331.1654. FT-IR (ATR, neat): 2979, 1676, 1606,
1377, 1181, 742 cm−1.
Figure 1. (top) Emission spectra of 14c in THF/water mixtures with
different fractions of water (fw) (concentration = 20 μM). (bottom)
Relative intensity vs water fraction (vol %) in THF/water mixtures;
[14c] = 20 μM.
2,4-Diethyl-1,5-di-p-tolylpentane-1,5-dione (Table 1, Entry 2b).
Prepared from 1-(p-tolyl)butan-1-one (0.081 g, 0.50 mmol). After
purification by column chromatography (n-hexane/EtOAc, 20/1), an
inseparable mixture of two diastereomers anti-2b and syn-2b in 1:1.4
(10 mmol, 1 equiv), methanol (5 mL), and toluene (5 mL) were
added to the reaction mixture and the system was purged with
nitrogen gas. Then, the sealed tube was closed with a PTFE stopper
and the reaction mixture was stirred at 135 °C (oil bath temperature)
for 24 h. The reaction mixture was transferred to a round-bottom flask
after cooling it to room temperature. After purification by column
chromatography, an inseparable mixture of two diastereomers anti-1a
and syn-1a in 1:1 ratio was isolated as a yellow liquid (1.092 g, 78%).
Analytical Data for Diketone Compounds. 2,4-Dimethyl-1,5-
diphenylpentane-1,5-dione (Table 1, Entry 1a).5b Prepared from
propiophenone (0.067 g, 0.50 mmol). After purification by column
chromatography (n-hexane/EtOAc, 20/1), an inseparable mixture of
two diastereomers anti-1a and syn-1a in 1:1 ratio was isolated as a
yellow liquid (0.063 g, 92%). 1H NMR (400 MHz, CDCl3) δ 8.05 (d,
J = 7.5 Hz, 4H), 7.78 (d, J = 7.5 Hz, 4H), 7.58 (t, J = 7.3 Hz, 2H),
7.50 (t, J = 7.5 Hz, 4H), 7.50 (t, J = 7.5 Hz, 2H), 7.33 (t, J = 7.6 Hz,
4H), 3.62 (sextet, J = 7.6 Hz, 2H), 3.51 (sextet, J = 7.6 Hz, 2H), 2.44
(dt, J = 14.0, 7.1 Hz, 1H), 2.01 (t, J = 7.6 Hz, 2H), 1.49 (dt, J = J =
14.0, 7.1 Hz, 1H), 1.22 (d, J = 6.9 Hz, 6H), 1.17 (d, J = 6.9 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 204.5, 203.9, 136.6, 136.4,
1
ratio was isolated as a yellow liquid (0.071 g, 85%). H NMR (400
MHz, CDCl3) δ 7.90 (d, J = 8.3 Hz, 4H), 7.59 (d, J = 8.2 Hz, 4H),
7.28 (d, J = 8.0 Hz, 4H), 7.05 (d, J = 8.0 Hz, 4H), 3.48−3.35 (m,
2H), 3.30−3.23 (m, 2H), 2.41 (s, 6H), 2.31 (s, 6H), 2.30−2.19 (m,
1H), 2.03−2.01 (m, 2H), 1.80−1.67 (m, 4H), 1.65−1.57 (m, 1H),
1.55−1.44 (m, 4H), 0.84 (t, J = 7.5 Hz, 6H), 0.78 (t, J = 7.4 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 204.4, 143.9, 143.6, 135.1,
134.8, 129.5, 129.2, 128.6, 128.3, 45.3, 45.0, 33.8, 33.5, 27.2, 25.4,
21.7, 21.6, 11.8, 11.7. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for
[C23H28O2 + Na]+, 359.1982; found, 359.1990. FT-IR (ATR, neat):
2969, 2871, 1673, 1602, 1264, 1118, 732 cm−1.
2,4-Dipropyl-1,5-di-p-tolylpentane-1,5-dione (Table 1, Entry 2c).
Prepared from 1-(p-tolyl)pentan-1-one (0.088 g, 0.50 mmol). After
purification by column chromatography (n-hexane/EtOAc, 20/1), an
inseparable mixture of two diastereomers anti-2c and syn-2c in 1:1.4
1
ratio was isolated as a yellow liquid (0.076 g, 84%). H NMR (400
MHz, CDCl3) δ 7.90 (d, J = 8.2 Hz, 4H), 7.57 (d, J = 8.2 Hz, 4H),
7.36−7.16 (d, J = 8.2 Hz, 4H), 7.04 (d, J = 8.1 Hz, 4H), 3.55−3.43
(m, 2H), 3.35−3.28 (m, 2H), 2.41 (s, 6H), 2.31 (s, 6H), 2.28−2.21
133.2, 133.0, 128.9, 128.7, 128.6, 128.3, 38.7, 38.2, 37.4, 37.1, 18.8,
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Article
(m, 1H), 2.08−1.96 (m, 2H), 1.78−1.54 (m, 5H), 1.44−1.37 (m,
4H), 1.35−1.26 (m, 4H), 1.23−1.07 (m, 4H), 0.82 (t, J = 7.3 Hz,
6H), 0.77 (t, J = 7.3 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ
204.60, 203.69, 143.94, 143.64, 135.05, 134.78, 129.51, 129.20,
128.56, 128.29, 43.69, 43.33, 36.42, 34.57, 34.46, 21.76, 21.63, 20.70,
20.60, 14.28, 14.26. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for
[C25H32O2 + Na]+, 387.2295; found, 387.2276. FT-IR (ATR, neat):
2957, 2872, 1672, 1606, 1180, 736 cm−1.
128.4, 128.1, 38.5, 38.1, 37.6, 37.3, 29.1, 28.9, 18.9, 17.7, 15.3, 15.2.
HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C23H28O2 + Na]+,
359.1982; found, 359.1980. FT-IR (ATR, neat): 2965, 2931, 1676,
1605, 1225, 1181, 737 cm−1.
2,4-Diethyl-1,5-bis(4-ethylphenyl)pentane-1,5-dione (Table 1,
Entry 4b). Prepared from 1-(4-ethylphenyl) butan-1-one (0.088 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-4b
and syn-4b in 1:1.4 ratio was isolated as a yellow liquid (0.076 g,
84%). 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 4H), 7.62
(d, J = 8.3 Hz, 4H), 7.31 (d, J = 8.2 Hz, 4H), 7.07 (d, J = 8.2 Hz, 4H),
3.46−3.39 (m, 2H), 3.31−3.25 (m, 2H), 2.70 (q, J = 7.6 Hz, 4H),
2.61 (q, J = 7.6 Hz, 4H), 2.32−2.25 (m, 1H), 2.05−2.02 (m, 2H),
1.80−1.67 (m, 4H), 1.63−1.58 (m, 1H), 1.56−1.47 (m, 4H), 1.27 (t,
J = 7.6 Hz, 6H), 1.19 (t, J = 7.6 Hz, 6H), 0.85 (t, J = 7.5 Hz, 6H),
0.79 (t, J = 7.4 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.5,
203.5, 150.0, 149.8, 135.3, 135.0, 128.7, 128.4, 128.34, 128.0, 45.3,
45.0, 33.8, 29.0, 28.9, 27.2, 25.4, 15.3, 15.2, 11.9, 11.7. HRMS (ESI-
TOF) m/z [M + H]+ Calcd for [C25H32O2 + H]+, 365.2475; found,
365.2460. FT-IR (ATR, neat): 2964, 2928, 1674, 1604, 1264, 1171,
734 cm−1.
1,5-Bis(4-ethylphenyl)-2,4-dipropylpentane-1,5-dione (Table 1,
Entry 4c). Prepared from 1-(4-ethylphenyl) pentan-1-one (0.095 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-4c
and syn-4c in 1.25:1 ratio was isolated as a yellow liquid (0.082g,
84%). 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.3 Hz, 4H), 7.60
(d, J = 8.3 Hz, 4H), 7.30 (d, J = 8.2 Hz, 4H), 7.06 (d, J = 8.2 Hz, 4H),
3.53−3.46 (m, 2H), 3.37−3.30 (m, 2H), 2.71 (q, J = 7.6 Hz, 4H),
2.60 (q, J = 7.6 Hz, 4H), 2.29−2.22 (m, 1H), 2.05−2.01 (m, 2H),
1.86−1.83 (m, 1H), 1.77−1.68 (m, 2H), 1.66−1.56 (m, 3H), 1.46−
1.36 (m, 4H), 1.34−1.16 (m, 19H), 0.83 (t, J = 7.3 Hz, 6H), 0.78 (t, J
= 7.3 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.6, 149.7,
135.2, 135.0, 128.7, 128.4, 128.3, 128.0, 43.7, 43.4, 36.4, 34.5, 34.4,
29.0, 28.9, 20.7, 20.6, 15.2, 15.2, 14.2, 14.2. HRMS (ESI-TOF) m/z
[M + H]+ Calcd for [C27H36O2 + H]+, 393.2788; found, 393.2772.
FT-IR (ATR, neat): 2962, 2927, 1672, 1605, 1248, 1180, 735 cm−1.
2,4-Dimethyl-1,5-di(thiophen-2-yl)pentane-1,5-dione (Table 1,
Entry 5a). Prepared from 1-(thiophen-2-yl)propan-1-one (0.070 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-5a
and syn-5a in 1.15:1 ratio was isolated as a yellow liquid (0.053 g,
72%). 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 3.0 Hz, 2H), 7.66
(d, J = 4.9 Hz, 2H), 7.54 (d, J = 5.6 Hz, 2H), 7.44 (d, J = 3.0 Hz, 2H),
7.18−7.15 (m, 2H), 6.93−6.91 (m, 2H), 3.43 (sextet, J = 8.0 Hz,
2H), 3.31 (sextet, J = 8.0 Hz, 2H), 2.44 (dt, J = 14.0, 7.1 Hz, 1H),
2.00 (t, J = 8.0 Hz, 2H), 1.53 (dt, J = 14.0, 7.2 Hz, 1H), 1.24−1.21
(m, 12H). 13C{1H} NMR (101 MHz, CDCl3) δ 197.3, 196.7, 144.1,
143.9, 134.1, 134.1, 132.4, 132.0, 128.50, 128.1, 40.6, 40.1, 37.9, 37.8,
19.3, 17.8. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C15H16O2S2
+ Na]+, 315.0484; found, 315.0463. FT-IR (ATR, neat): 3646, 2969,
2861, 1653, 1516, 1264, 1059, 727 cm−1.
1,5-Bis(3,4-dimethylphenyl)-2,4-dimethylpentane-1,5-dione
(Table 1, Entry 3a). Prepared from 1-(3,4-dimethylphenyl) propan-1-
one (0.081 g, 0.50 mmol). After purification by column chromatog-
raphy (n-hexane/EtOAc, 20/1), an inseparable mixture of two
diastereomers anti-3a and syn-3a in 1:1.05 ratio was isolated as a
1
yellow liquid (0.071 g, 84%). H NMR (400 MHz, CDCl3) δ 7.81−
7.78 (m, 4H), 7.51−7.49 (m, 4H), 7.25 (d, J = 8.9 Hz, 2H), 7.06 (d, J
= 8.4 Hz, 2H), 3.57 (sextet, J = 8.0 Hz, 2H), 3.45 (sextet, J = 8.0 Hz,
2H), 2.55−2.50 (m, 1H), 2.34 (s, 6H), 2.33 (s, 6H), 2.23 (s, 6H),
2.16 (s, 6H), 1.97 (t, J = 8.0 Hz, 2H), 1.50−1.43 (m, 1H), 1.18 (d, J =
6.9 Hz, 6H), 1.15 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 204.6, 203.9, 142.7, 142.4, 137.2, 136.9, 134.6, 134.3, 130.1,
129.8, 129.7, 129.5, 126.3, 126.0, 38.5, 38.1, 37.9, 37.3, 20.1, 20.0,
19.9, 19.7, 19.0, 17.8. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for
[C23H28O2 + Na]+, 359.1982; found, 359.1963. FT-IR (ATR, neat):
2979, 2872, 1673, 1605, 1250, 1117, 735 cm−1.
1,5-Bis(3,4-dimethylphenyl)-2,4-diethylpentane-1,5-dione (Table
1, Entry 3b). Prepared from 1-(3,4-dimethylphenyl) butan-1-one
(0.088 g, 0.50 mmol). After purification by column chromatography
(n-hexane/EtOAc, 20/1), an inseparable mixture of two diaster-
eomers anti-3b and syn-3b in 1:1.4 ratio was isolated as a yellow liquid
1
(0.074 g, 82%). H NMR (400 MHz, CDCl3) δ 7.77−7.73 (m, 4H),
7.44−7.42 (m, 4H), 7.23 (d, J = 7.7 Hz, 2H), 7.00 (d, J = 7.7 Hz,
2H), 3.41 (p, J = 8.0 Hz, 2H), 3.26 (p, J = 8.0 Hz, 2H), 2.33 (s, 6H),
2.32 (s, 6H), 2.30−2.33 (m, 1H), 2.21 (s, 6H), 2.10 (s, 6H), 2.03−
2.00 (m, 2H), 1.80−1.66 (m, 4H), 1.64−1.61 (m, 1H), 1.56−1.43
(m, 4H), 0.84 (t, J = 7.5 Hz, 6H), 0.79 (t, J = 7.4 Hz, 6H). 13C{1H}
NMR (101 MHz, CDCl3) δ 204.8, 203.7, 142.6, 142.3, 137.1, 136.7,
135.6, 135.3, 130.0, 129.7, 129.5, 129.4, 126.2, 125.9, 45.16, 44.9,
34.2, 33.6, 27.3, 25.4, 20.1, 19.9, 19.9, 19.7, 11.9, 11.7. HRMS (ESI-
TOF) m/z [M + H]+ Calcd for [C25H32O2 + H]+, 365.2475; found,
365.2461. FT-IR (ATR, neat): 2969, 2871, 1672, 1605, 1264, 1118,
737 cm−1.
1,5-Bis(3,4-dimethylphenyl)-2,4-dipropylpentane-1,5-dione
(Table 1, Entry 3c). Prepared from 1-(3,4-dimethylphenyl) pentan-1-
one (0.095 g, 0.50 mmol). After purification by column chromatog-
raphy (n-hexane/EtOAc, 20/1), an inseparable mixture of two
diastereomers anti-3c and syn-3c in 1:1.6 ratio was isolated as a
1
yellow liquid (0.079 g, 81%). H NMR (400 MHz, CDCl3) δ 7.76−
7.72 (m, 4H), 7.43−7.41 (m, 4H), 7.23 (d, J = 7.6 Hz, 2H), 6.99 (d, J
= 7.6 Hz, 2H), 3.51−3.44 (m, 2H), 3.35−3.28 (m, 2H), 2.33 (s, 6H),
2.29−2.23 (m. 1H), 2.31 (s, 6H), 2.21 (s, 6H), 2.10 (s, 6H), 2.04−
2.00 (m, 2H), 1.74−1.57 (m, 5H), 1.47−1.36 (m, 4H), 1.35−1.26
(m, 4H), 1.24−1.12 (m, 4H), 0.82 (t, J = 7.3 Hz, 6H), 0.78 (t, J = 7.3
Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.9, 204.0, 142.7,
142.3, 137.1, 136.7, 135.5, 135.2, 130.0, 129.7, 129.6, 129.4, 126.2,
125.9, 43.6, 43.4, 36.5, 34.8, 34.6, 20.7, 20.6, 20.1, 19.9, 19.9, 19.7,
14.3, 14.3. HRMS (ESI-TOF) m/z [M + H]+ Calcd for [C27H36O2 +
H]+, 393.2788; found, 393.2776. FT-IR (ATR, neat): 2926, 1670,
1605, 1264, 1122, 736 cm−1.
2,4-Diethyl-1,5-di(thiophen-2-yl)pentane-1,5-dione (Table 1,
Entry 5b). Prepared from 1-(thiophen-2-yl)butan-1-one (0.077 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-5b
and syn-5b in 1:1.3 ratio was isolated as a yellow liquid (0.054 g,
68%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 3.6 Hz, 2H), 7.65
(d, J = 4.9 Hz, 2H), 7.50 (d, J = 4.9 Hz, 2H), 7.33 (d, J = 3.7 Hz, 2H),
7.16−7.13 (m, 2H), 6.86−6.84 (m, 2H), 3.27−3.21 (m, 2H), 3.15−
3.08 (m, 2H), 2.33−2.26 (m, 1H), 2.04−2.01 (m, 2H), 1.82−1.65
(m, 5H), 1.61−1.50 (m, 4H), 0.84 (t, J = 7.4 Hz, 12H). 13C{1H}
NMR (101 MHz, CDCl3) δ 197.4, 196.5, 145.4, 144.9, 134.1, 134.1,
132.2, 132.0, 128.46, 128.1, 47.5, 47.3, 34.4, 34.4, 27.6, 25.6, 12.0,
11.9. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C17H20O2S2 +
Na]+, 343.0797; found, 343.0777. FT-IR (ATR, neat): 3647, 2971,
2862, 1653, 1516, 1247, 1064, 726 cm−1.
1,5-Bis(4-ethylphenyl)-2,4-dimethylpentane-1,5-dione (Table 1,
Entry 4a). Prepared from 1-(4-ethylphenyl) propan-1-one (0.081 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-4a
and syn-4a in 1.3:1 ratio was isolated as a yellow liquid (0.072 g,
86%). 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.3 Hz, 4H), 7.70
(d, J = 8.3 Hz, 4H), 7.32 (d, J = 8.3 Hz, 4H), 7.14 (d, J = 8.3 Hz, 4H),
3.59 (sextet, J = 8.0 Hz, 2H), 3.48 (sextet, J = 8.0 Hz, 2H), 2.72 (q, J
= 7.6 Hz, 4H), 2.63 (q, J = 7.6 Hz, 4H), 2.46−2.39 (m, 1H), 1.99 (t, J
= 8.0 Hz, 2H), 1.50−1.43 (m, 1H), 1.27 (t, J = 7.6 Hz, 6H), 1.22−
1.18 (m,12H), 1.16 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 204.2, 203.6, 150.1, 149.9, 134.3, 134.1, 128.82, 128.5,
2,4-Dipropyl-1,5-di(thiophen-2-yl)pentane-1,5-dione (Table 1,
Entry 5c). Prepared from 1-(thiophen-2-yl)pentan-1-one (0.084 g,
0.50 mmol). After purification by column chromatography (n-hexane/
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J. Org. Chem. 2021, 86, 6744−6754

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Article
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-5c
and syn-5c in 1:1.3 ratio was isolated as a yellow liquid (0.057 g,
66%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 3.2 Hz, 2H), 7.65
(d, J = 4.9 Hz, 2H), 7.50 (d, J = 4.9 Hz, 2H), 7.32 (d, J = 3.7 Hz, 2H),
7.16−7.13 (m, 2H), 6.85−6.83 (m, 2H), 3.34−3.28 (m, 2H), 3.21−
3.14 (m, 2H), 2.30−2.23 (m, 1H), 2.04−2.00 (m, 2H), 1.79−1.74
(m, 1H), 1.73−1.61 (m, 4H), 1.50−1.41 (m, 4H), 1.37−1.28 (m,
4H), 1.24−1.14 (m, 4H), 0.84 (t, J = 7.3 Hz, 6H), 0.80 (t, J = 7.3 Hz,
12H). 13C{1H} NMR (101 MHz, CDCl3) δ 197.5, 196.7, 145.3,
144.9, 134.1, 134.1, 132.2, 132.0, 128.5, 128.1, 46.0, 45.7, 36.8, 35.2,
35.0, 34.7, 20.8, 20.7, 14.2. HRMS (ESI-TOF) m/z [M + Na]+ Calcd
for [C19H24O2S2 + Na]+, 371.1110; found, 371.1094. FT-IR (ATR,
neat): 3647, 2979, 2872, 1653, 1517, 1247, 1059, 723 cm−1.
6H), 1.89 (t, J = 7.2, 2H), 1.38 (dt, J = 13.9, 7.0, 1H), 1.08 (dd, J =
11.5, 6.9, 12H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.84, 204.19,
138.44, 136.69, 133.98, 133.80, 129.06, 128.83, 128.72, 128.55,
125.77, 125.45, 38.65, 38.25, 37.71, 37.11, 21.53, 21.34, 18.96, 17.78.
HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C21H24O2 + Na]+,
303.1356; found, 303.1369. FT-IR (ATR, neat): 2979, 1678, 1601,
1584, 1261, 1160, 737 cm−1.
1,5-Bis(4-methoxyphenyl)-2,4-dimethylpentane-1,5-dione
(Table 1, Entry 8). Prepared from 4-methoxy propiophenone (0.082 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-8 and
syn-8 in 1:1.3 ratio was isolated as a yellow liquid (0.053 g, 62%). 1H
NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.8 Hz, 4H), 7.73 (d, J = 8.8
Hz, 4H), 6.95 (d, J = 8.8 Hz, 4H), 6.75 (d, J = 8.8 Hz, 4H), 3.85 (s,
6H), 3.77 (s, 6H), 3.54 (sextet, J = 8.0 Hz, 2H), 3.48−3.37 (m, 2H),
2.38 (dt, J = 14.0, 7.2 Hz, 1H), 1.96 (t, J = 8.0 Hz 2H), 1.43 (dt, J =
14.0, 7.2 Hz, 1H), 1.16 (d, J = 6.9 Hz, 6H), 1.13 (d, J = 6.8 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 203.1, 202.5, 163.6, 163.4,
1,5-Bis(2,5-dimethoxyphenyl)-2,4-dimethylpentane-1,5-dione
(Table 1, Entry 6a). Prepared from 1-(2,5-dimethoxyphenyl) propan-
1-one (0.097 g, 0.50 mmol). After purification by column
chromatography (n-hexane/EtOAc, 20/1), an inseparable mixture of
two diastereomers anti-6a and syn-6a in 1:1.3 ratio was isolated as a
1
yellow liquid (0.072 g, 72%). H NMR (400 MHz, CDCl3) δ 7.06
130.8, 130.5, 129.6, 129.3, 113.95, 113.7, 55.5, 55.4, 38.1, 37.9, 37.8,
37.5, 18.9, 17.7. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for
[C21H24O4 + Na]+, 363.1567; found, 363.1572. FT-IR (ATR, neat):
2931, 1669, 1598, 1574, 1246, 1142, 735 cm−1.
(dd, J = 7.1, 3.2, 4H), 6.97 (dd, J = 9.0, 3.2, 1H), 6.92−6.86 (m, 3H),
6.77 (d, J = 9.0, 4H), 3.82 (s, 6H), 3.77 (s, 12H), 3.74 (s, 12H), 3.69
(s, 6H), 3.62−3.51 (m, 4H), 2.31 (m, 1H), 1.82 (m, 2H), 1.40 (m,
1H), 1.13 (d, J = 6.9, 6H), 1.10 (d, J = 6.9, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 207.38, 207.28, 154.06, 153.58, 153.47, 153.45,
152.47, 152.36, 151.86, 151.52, 131.06, 129.64, 129.15, 119.12,
118.79, 117.05, 116.99, 114.50, 114.43, 113.04, 112.84, 77.48, 77.16,
76.84, 56.21, 55.86, 43.15, 42.82, 36.78, 36.14, 18.62, 17.27. HRMS
(ESI-TOF) m/z [M + H]+ Calcd for [C23H28O6 + H]+, 401.1959;
found, 401.1938. FT-IR (ATR, neat): 2979, 2834, 1671, 1582, 1492,
1222, 1046, 730 cm−1.
1,5-Bis(2,5-dimethoxyphenyl)-2,4-diethylpentane-1,5-dione
(Table 1, Entry 6b). Prepared from 1-(2,5-dimethoxyphenyl) butan-1-
one (0.104 g, 0.50 mmol). After purification by column chromatog-
raphy (n-hexane/EtOAc, 20/1), an inseparable mixture of two
diastereomers anti-6b and syn-6b in 1:1.6 ratio was isolated as a
yellow liquid (0.081 g, 76%). 1H NMR (400 MHz, CDCl3) δ 7.07 (d,
J = 3.2, 4H), 6.96 (d, J = 9.0, 3.2, 2H), 6.91−6.85 (m, 4H), 6.73 (s,
1H), 6.71 (s, 1H), 3.84−3.68 (m, 14H), 3.74 (s, 6H), 3.58 (s, 6H),
3.51−3.44 (m, 2H), 2.21 (m, 1H), 1.94−1.90 (m, 2H), 1.69 (m, 4H),
1.56 (m, 1H), 1.43 (m, 4H), 0.88 (t, J = 7.4, 6H), 0.81 (t, J = 7.4,
6H). 13C{1H} NMR (101 MHz, CDCl3) δ 206.9, 206.7, 153.3, 152.6,
152.4, 130.2, 129.7, 119.0, 118.7, 114.50, 114.3, 113.1, 112.9, 56.1,
55.9, 55.8, 55.7, 49.8, 49.4, 32.2, 26.1, 24.9, 11.7, 11.7. HRMS (ESI-
TOF) m/z [M + Na]+ Calcd for [C25H32O6 + Na]+, 451.2091; found,
451.2072. FT-IR (ATR, neat): 2969, 2834, 1670, 1607, 1491, 1222,
1165, 729 cm−1.
1,5-Bis(2,5-dimethoxyphenyl)-2,4-dipropylpentane-1,5-dione
(Table 1, Entry 6c). Prepared from 1-(2,5-dimethoxyphenyl) pentan-
1-one (0.111 g, 0.50 mmol). After purification by column
chromatography (n-hexane/EtOAc, 20/1), an inseparable mixture of
two diastereomers anti-6c and syn-6c in 1:2 ratio was isolated as a
yellow liquid (0.073 g, 64%). 1H NMR (400 MHz, CDCl3) δ 7.07 (d,
J = 3.0, 4H), 6.96 (dd, J = 9.0, 3.2, 2H), 6.91−6.85 (m, 2H), 6.72 (s,
1H), 6.70 (s, 1H), 3.83−3.70 (m, 14H), 3.74 (s, 6H), 3.56 (s, 6H),
3.62−3.51 (m, 2H), 2.24−2.13 (m, 1H), 1.91 (m, 2H), 1.74−1.56
(m, 4H), 1.53 (m, 1H), 1.43−1.09 (m, 12H), 0.84 (t, J = 7.1, 6H),
0.78 (t, J = 7.2, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 207.0,
206.9, 153.5, 153.3, 152.6, 129.6, 119.1, 118.8, 114.5, 114.4, 113.0,
112.8, 56.1, 55.90, 55.83, 55.6, 48.2, 47.8, 35.4, 34.3, 33.0, 20.5, 20.50,
14.3, 14.3. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C27H36O6 +
Na]+, 479.2404; found, 479.2397. FT-IR (ATR, neat): 2980, 2831,
1669, 1494, 1263, 1163, 731 cm−1.
2,2′-Methylenebis(3,4-dihydronaphthalen-1(2H)-one) (Table 1,
Entry 9).5e Prepared from 1-tetralone (0.073 g, 0.50 mmol). After
purification by column chromatography (n-hexane/EtOAc, 20/1), an
inseparable mixture of two diastereomers anti-9 and syn-9 in 1.05:1
1
ratio was isolated as a yellow liquid liquid (0.051 g, 57%). H NMR
(400 MHz, CDCl3) δ 8.00 (d, J = 7.9 Hz, 4H), 7.46 (t, J = 7.5 Hz,
4H), 7.29 (t, J = 8.4 Hz, 4H), 7.24 (d, J = 7.7 Hz, 4H), 3.05 (dq, J =
5.2, 3.3, 2.1 Hz, 8H), 2.87−2.76 (m, 4H), 2.72 (q, J = 6.7 Hz, 1H),
2.33 (ddq, J = 22.6, 13.7, 4.7 Hz, 4H), 2.03 (t, J = 6.6 Hz, 2H), 2.00−
1.85 (m, 4H), 1.59 (dt, J = 13.6, 5.9 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 201.03, 200.51, 144.07, 144.03, 133.36, 132.67,
128.85, 127.55, 127.48, 126.70, 45.98, 44.97, 30.95, 30.10, 29.45,
29.26, 28.69, 28.53. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for
[C21H20O2 + Na]+, 327.1356; found, 327.1352.
1,5-Di([1,1′-biphenyl]-4-yl)-2,4-dimethylpentane-1,5-dione
(Table 1, Entry 10a). Prepared from 4′-phenyl propiophenone (0.105
g, 0.50 mmol). After purification by column chromatography (n-
hexane/EtOAc, 20/1), an inseparable mixture of two diastereomers
anti-10a and syn-10a in 1.5:1 ratio was isolated as a yellowish solid
1
(0.063 g, 58%). H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 8.4 Hz,
4H), 7.83 (d, J = 8.5 Hz, 4H), 7.74 (d, J = 8.0 Hz, 4H), 7.65 (d, J =
7.1 Hz, 4H), 7.54−7.44 (m, 12H), 7.44−7.32 (m, 8H), 3.67 (h, J =
7.0 Hz, 2H), 3.59−3.50 (m, 2H), 2.51 (dt, J = 14.1, 7.2 Hz, 1H), 2.06
(t, J = 7.2 Hz, 2H), 1.54 (dt, J = 13.9, 7.1 Hz, 1H), 1.25 (d, J = 6.8
Hz, 6H), 1.23 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3)
δ 204.28, 203.57, 145.93, 145.76, 140.04, 139.81, 135.32, 135.02,
129.23, 129.10, 129.01, 128.89, 128.36, 128.28, 127.55, 127.43,
127.32, 38.58, 38.35, 38.09, 19.04, 17.82. HRMS (ESI-TOF) m/z [M
+ H]+ Calcd for [C31H28O2 + H]+, 433.2162; found, 433.2172. FT-IR
(ATR, neat): 2969, 2931, 1672, 1604, 1255, 1178, 732 cm−1.
1,5-Di([1,1′-biphenyl]-4-yl)-2,4-diethylpentane-1,5-dione (Table
1, Entry 10b). Prepared from 4′-phenyl butyrophenone (0.112 g,
0.50 mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-10b
and syn-10b in 1:1.5 ratio was isolated as a yellowish solid (0.063 g,
55%). Single crystals were grown by slow evaporation of a solution of
the product 10b in methanol. 1H NMR (400 MHz, CDCl3) δ 8.10 (d,
J = 8.4 Hz, 4H), 7.73 (dd, J = 15.8, 8.4 Hz, 8H), 7.64 (d, J = 7.1 Hz,
4H), 7.50−7.43 (m, 6H), 7.43−7.38 (m, 8H), 7.37−7.32 (m, 6H),
3.58−3.46 (m, 2H), 3.41−3.30 (m, 2H), 2.38 (dt, J = 14.4, 7.5 Hz,
1H), 2.15−2.05 (m, 2H), 1.79 (m, 4H), 1.72−1.67 (m, 1H), 1.61−
1.48 (m, 4H), 0.90 (t, J = 7.4 Hz, 6H), 0.85 (t, J = 7.4 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 204.56, 203.43, 145.80, 145.61,
2,4-Dimethyl-1,5-di-m-tolylpentane-1,5-dione (Table 1, Entry 7).
Prepared from 3′-methyl propiophenone (0.074 g, 0.50 mmol). After
purification by column chromatography (n-hexane/EtOAc, 20/1), an
inseparable mixture of two diastereomers anti-7 and syn-7 in 1:1.17
139.96, 139.67, 136.21, 135.90, 129.05, 128.94, 128.76, 128.30,
128.20, 127.40, 127.36, 127.24, 127.14, 45.24, 34.50, 34.41, 27.31,
25.49, 11.91, 11.82. HRMS (ESI-TOF) m/z [M + H]+ Calcd for
[C33H32O2 + H]+, 461.2475; found, 461.2478. FT-IR (ATR, neat):
2962, 2926, 1671, 1602, 1264, 1186, 741 cm−1.
1
ratio was isolated as a yellowish solid (0.067 g, 87%). H NMR (400
MHz, CDCl3) δ 7.75 (s, 4H), 7.51−7.40 (m, 4H), 7.29 (dd, J = 4.5,
1.5, 4H), 7.18−7.14 (m, 2H), 7.11 (t, J = 7.5, 2H), 3.49 (h, J = 7.0,
2H), 3.37 (h, J = 7.0, 2H), 2.34 (s, 6H), 2.31−2.25 (m, 1H), 2.16 (s,
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2,4-Dibenzyl-1,5-diphenylpentane-1,5-dione (Table 1, Entry
11a).5b Prepared from 1,3-diphenylpropan-1-one (0.105 g, 0.50
mmol). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-11a
and syn-11a in 1:1.3 ratio was isolated as a yellow liquid (0.067 g,
Analytical Data of Mechanistic Study. 2,4-Dimethyl-1,5-
diphenylpentane-1,5-dione-2,3,3,4-d4 (Scheme 3, Entry 12).
Prepared from propiophenone (0.067 g, 0.5 mmol) and CD3OD
(0.5 mL). After purification by column chromatography (n-hexane/
EtOAc, 20/1), an inseparable mixture of two diastereomers anti-12a
and syn-12a in 1:1.15 ratio was isolated as a yellow liquid (0.051 g,
72%). 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 7.2 Hz, 4H), 7.77
(d, J = 8.1 Hz, 4H), 7.58 (t, J = 7.3 Hz, 2H), 7.54−7.42 (m, 6H), 7.32
(t, J = 7.7 Hz, 4H), 1.20 (s, 6H), 1.16 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 204.5, 204.0, 136.6, 136.3, 133.2, 133.0, 128.8, 128.7,
128.5, 128.3, 38.49, 38.34, 38.27, 38.07, 38.05, 37.88, 37.84, 37.64,
37.50, 37.47, 18.64, 17.53. HRMS (ESI-TOF) m/z [M + Na]+ Calcd
for [C19H16D4O2 + Na]+, 307.1607; found, 307.1597. FT-IR (ATR,
neat): 2979, 2928, 1676, 1595, 1578, 1273, 1168, 702 cm−1.
1
62%). H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.1, 4H), 7.56−
7.52 (m, 6H), 7.43 (t, J = 7.6, 4H), 7.35 (t, J = 6.8, 2H), 7.21−7.06
(m, 20H), 6.97 (d, J = 6.5, 4H), 3.78 (p, J = 8.0, 2H), 3.71 (p, J = 8.0,
2H), 3.03 (dd, J = 12, 8.0 Hz, 2H), 3.00 (dd, J = 12, 8.0 Hz, 2H), 2.70
(dd, J = 12, 8.0 Hz, 2H), 2.63 (dd, J = 12, 8.0 Hz, 2H), 2.40 (dt, J =
14.0, 7.1 Hz, 1H), 2.12 (t, J = 8.0 Hz, 2H), 1.74 (dt, J = 14.0, 7.1 Hz,
1H). 13C{1H} NMR (101 MHz, CDCl3) δ 203.9, 203.2, 139.3, 138.9,
137.3, 136.9, 133.2, 132.9, 129.0, 129.0, 128.8, 128.5, 128.5, 128.5,
128.4, 128.1, 126.4, 126.4, 46.0, 45.7, 39.9, 38.4, 34.6, 34.4. HRMS
(ESI-TOF) m/z [M + Na]+ Calcd for [C31H28O2 + Na]+, 455.1982;
found, 455.1962.
2-Methyl-1-phenylprop-2-en-1-one (Scheme 3, Entry C*).12a
Prepared from propiophenone (0.067 g, 0.5 mmol). After purification
by column chromatography (n-hexane/EtOAc, 100/1), the com-
2,4-Dibenzyl-1,5-di-p-tolylpentane-1,5-dione (Table 1, Entry
11b). Prepared from 3-phenyl-1-(p-tolyl)propan-1-one (0.112 g,
0.50 mmol). After purification by column chromatography (n-
hexane/EtOAc, 20/1), an inseparable mixture of two diastereomers
anti-11b and syn-11b in 1:1.1 ratio was isolated as a yellow liquid
(0.064 g, 56%). 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.3, 4H),
7.41 (d, J = 8.3, 4H), 7.23−7.05 (m, 20H), 6.95 (d, J = 8.7, 8H), 3.73
(p, J = 8.0, 2H), 3.65 (p, J = 8.0, 2H), 3.01 (dd, J = 12, 8.0 Hz, 2H),
2.98 (dd, J = 12, 8.0 Hz, 2H), 2.67 (dd, J = 12, 8.0 Hz, 2H), 2.61 (dd,
J = 12, 8.0 Hz, 2H), 2.40 (s, 6H), 2.37−2.33 (m, 1H), 2.27 (s, 6H),
2.11−2.04 (m, 2H), 1.73−1.66 (m, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 203.55, 202.79, 144.06, 143.60, 139.53, 139.12, 134.88,
134.48, 129.50, 129.12, 129.04, 128.63, 128.52, 128.49, 128.27,
126.40, 126.33, 45.94, 45.60, 39.91, 38.43, 34.58, 21.77, 21.62. HRMS
(ESI-TOF) m/z [M + H]+ Calcd for [C33H32O2 + H]+, 461.2475;
found, 461.2469. FT-IR (ATR, neat): 2980, 1674, 1606, 1249, 1180,
744 cm−1.
2,4-Dibenzyl-1,5-bis(4-ethylphenyl)pentane-1,5-dione (Table 1,
Entry 11c). Prepared from 1-(4-ethylphenyl)-3-phenylpropan-1-one
(0.120 g, 0.50 mmol). After purification by column chromatography
(n-hexane/EtOAc, 20/1), an inseparable mixture of two diaster-
eomers anti-11c and syn-11c in 1:1.05 ratio was isolated as a yellow
liquid (0.068g, 56%). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0
Hz, 4H), 7.46 (d, J = 8.0 Hz, 4H), 7.26−7.06 (m, 20H), 7.00−6.95
(m, 8H), 3.74 (p, J = 8.0 Hz, 2H), 3.67 (p, J = 8.0 Hz, 2H), 3.02 (dd,
J = 12, 8.0 Hz, 2H), 2.99 (dd, J = 12, 8.0 Hz, 2H), 2.73−2.53 (m,
12H), 2.36 (dt, J = 14.0, 7.1 Hz, 1H), 2.08 (t, J = 8.0 Hz, 2H), 1.73−
1.66 (m, 1H), 1.26 (t, J = 7.6 Hz, 6H), 1.16 (t, J = 7.6 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 203.5, 202.8, 150.2, 149.7,
1
pound was isolated as a yellow liquid (0.067 g, 92%). H NMR (400
MHz, CDCl3) δ 7.73 (d, J = 7.0, 2H), 7.53 (t, J = 7.4, 1H), 7.43 (t, J =
7.5, 2H), 5.91 (s, 1H), 5.62 (s, 1H), 2.07 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 198.5, 143.9, 137.8, 132.1, 129.5, 128.3, 127.2,
18.7. HRMS (ESI-TOF) m/z [M + H]+ Calcd for [C10H10O + H]+,
147.0804; found, 147.0809. FT-IR (ATR, neat): 2979, 1681, 1596,
1448, 1232, 1175, 974, 701 cm−1.
2-Methyl-1-phenylpropan-1-one (Scheme 3, Entry 13a).4e
Prepared from propiophenone (0.067 g, 0.50 mmol) and MeOH (1
mL). After purification by column chromatography (n-hexane/
EtOAc, 100/1), the compound was isolated as a yellow liquid
(0.068 g, 92%). 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.1, 2H),
7.55 (t, J = 7.3, 1H), 7.46 (t, J = 7.5, 2H), 3.56 (h, J = 6.9, 1H), 1.22
(d, J = 6.9, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 204.71, 136.31,
132.94, 128.74, 128.45, 35.48, 19.28.
1-(4-Aminophenyl)ethan-1-one (Scheme 3, Entry 13b).12b
Prepared from 1-(4-nitrophenyl)ethan-1-one (0.0825 g, 0.50 mmol)
and MeOH (1 mL) under optimized conditions. After purification by
column chromatography (n-hexane/EtOAc, 20/1), the compound
1
was isolated as a yellow liquid (0.042 g, 62%). H NMR (400 MHz,
CDCl3) δ 7.81 (d, J = 8.1 Hz, 2H), 6.65 (d, J = 8.1 Hz, 2H), 4.12 (s,
2H), 2.50 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 196.59,
151.20, 130.94, 128.07, 113.86, 26.23.
SYNTHETIC APPLICATION OF 1,5-DIKETONE
■
General Procedure for Pyridine Synthesis. General
Procedure A. An oven-dried sealed tube was charged with Co-
por (1.5 × 10−2 mmol, 0.03 equiv) and NaOtBu (2.5 × 10−1
mmol, 0.5 equiv). Under an inert atmosphere, ketone (0.5
mmol, 1 equiv), methanol (0.5 mL), and toluene (0.5 mL)
were added to the reaction mixture and the system was purged
with nitrogen gas. Then, the sealed tube was closed with a
PTFE stopper and the reaction mixture was stirred at 135 °C
for 24 h. The reaction mixture was cooled to room
temperature followed by the addition of NH4OAc (1 mmol)
along with acetic acid (0.5 mL) and again heated at 90 °C for 6
h. The reaction mixture was cooled to room temperature and
concentrated under a vacuum. The crude mixture was
subjected to column chromatography on silica gel using n-
hexane and ethyl acetate mixtures to afford the substituted
pyridine products 14a, 14b, and 14c in 85% (0.055 g, 78%
(0.056 g) and 78% (0.086 g) yields.
139.5, 139.1, 135.0, 134.7, 129.0, 129.0, 128.7, 128.5, 128.5, 128.4,
128.3, 127.9, 126.4, 126.3, 45.9, 45.6, 39.8, 38.3, 34.8, 34.6, 29.0, 28.9,
15.3, 15.1. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for [C35H36O2 +
Na]+, 511.2608; found, 511.2587. FT-IR (ATR, neat): 2925, 1674,
1605, 1264, 1180, 735 cm−1.
2,4-Bis(4-fluorobenzyl)-1,5-di-p-tolylpentane-1,5-dione (Table 1,
Entry 11d). Prepared from 3-(4-fluorophenyl)-1-(p-tolyl)propan-1-
one (0.121 g, 0.50 mmol). After purification by column chromatog-
raphy (n-hexane/EtOAc, 20/1), an inseparable mixture of two
diastereomers anti-11d and syn-11d in 1:1 ratio was isolated as a
yellow liquid (0.064 g, 52%). 1H NMR (400 MHz, CDCl3) δ 7.74 (d,
J = 8.2 Hz, 4H), 7.39 (d, J = 8.3 Hz, 4H), 7.23 (d, J = 7.7 Hz, 4H),
7.01−6.78 (m, 20H), 3.69 (p, J = 8.0 Hz, 2H), 3.59 (p, J = 8.0 Hz,
2H), 2.96 (dd, J = 12, 8.0 Hz, 2H), 2.93 (dd, J = 12, 8.0 Hz, 2H), 2.66
(dd, J = 12, 8.0 Hz, 2H), 2.59 (dd, J = 12, 8.0 Hz, 2H), 2.66−2.59 (m,
4H), 2.41 (s, 6H), 2.38−2.30 (m, 1H), 2.27 (s, 6H), 2.04 (t, J = 8.0
Hz 2H), 1.70−1.63 (m, 1H). 19F NMR (377 MHz, CDCl3) δ −116.9,
−116.8. Fluorine-decoupled 13C{1H, 19F} NMR (101 MHz, CDCl3)
δ 203.44, 202.56, 144.33, 143.87, 135.11, 134.83, 134.66, 134.42,
130.46, 130.42, 129.60, 129.20, 129.04, 128.57, 128.25, 115.30, 45.99,
45.64, 39.25, 37.54, 34.92, 34.54, 21.78, 21.63. HRMS (ESI-TOF) m/
z [M + Na]+ Calcd for [C33H30F2O2 + Na]+, 519.2106; found,
519.2092. FT-IR (ATR, neat): 2979, 1680, 1606, 1491, 1454, 1228,
1179, 972, 813, 755 cm−1.
General Procedure B. An oven-dried sealed tube was
charged with 1,5-diketone (0.25 mmol, 1 equiv) at room
temperature; then, hydroxylamine hydrochloride (0.75 mmol,
3 equiv) and ethanol (1 mL) were added. The resulting
mixture was refluxed at 90 °C for 4 h. The resulting reaction
mixture was purified by column chromatography on silica gel
with ethyl acetate/petroleum ether as eluent without any
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workup to give the desired products 14a, 14b, and 14c in 95%
(0.0615 g), 95% (0.068 g), and 92% (0.101 g) yields.
NMR spectra for all compounds and photophysical data,
crystal data, and molecular structure of compounds 10b
and 14c (PDF)
General Procedure C. An oven-dried sealed tube was
charged with Co-por (1.5 × 10−2 mmol, 0.03 equiv) and
NaOtBu (2.5 × 10−1 mmol, 0.5 equiv). Under an inert
atmosphere, ketone (0.5 mmol, 1 equiv), methanol (0.5 mL),
and toluene (0.5 mL) were added to the reaction mixture and
the system was purged with nitrogen gas. Then, the sealed tube
was closed with a PTFE stopper and the reaction mixture was
stirred at 135 °C for 24 h. The reaction mixture was cooled to
room temperature followed by the addition of NH2NH2·H2O
(1.5 mmol) along with acetic acid (0.5 mL) and heated at 90
°C for 6 h. The reaction mixture was cooled to room
temperature, diluted with dichloromethane (2 × 5 mL), and
concentrated under a vacuum. The crude mixture was
subjected to column chromatography on silica gel using n-
hexane and ethyl acetate mixtures to afford the substituted
pyridine products 14a, 14b, and 14c in 82% (0.053 g), 78%
(0.056 g), and 73% (0.080 g) yields, respectively.
3,5-Dimethyl-2,6-diphenylpyridine (Scheme 4, Entry
14a).12c Prepared from propiophenone (0.067 g, 0.50
mmol), after purification by column chromatography (n-
hexane/EtOAc, 98/2), the compound was isolated as a white
solid (method C, 0.053 g, 82%). 1H NMR (400 MHz, CDCl3)
δ 7.59 (d, J = 6.9, 4H), 7.50 (s, 1H), 7.44 (t, J = 7.3, 4H), 7.37
(t, J = 7.3, 2H), 2.38 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 141.53, 140.31, 129.45, 129.36, 128.19, 127.92,
19.71. HRMS (ESI-TOF) m/z [M + H]+ Calcd for [C19H17N
+ H]+, 260.1434; found, 260.1418.
Accession Codes
CCDC 2046746−2046747 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Vadapalli Chandrasekhar − Tata Institute of Fundamental
Research Hyderabad, Hyderabad 500046, Telangana, India;
Department of Chemistry, Indian Institute of Technology
Kanpur, Kanpur 208016, Uttar Pradesh, India;
orcid.org/0000-0003-1968-2980; Email: vc@iitk.ac.in
Krishnan Venkatasubbaiah − School of Chemical Sciences,
National Institute of Science Education and Research
(NISER), Bhubaneswar 752050, Odisha, India;
orcid.org/0000-0002-4858-8590; Email: krishv@
niser.ac.in
Authors
Priyabrata Biswal − School of Chemical Sciences, National
Institute of Science Education and Research (NISER),
Bhubaneswar 752050, Odisha, India
Shaikh Samser − School of Chemical Sciences, National
Institute of Science Education and Research (NISER),
Bhubaneswar 752050, Odisha, India; orcid.org/0000-
0002-2669-2020
Prakash Nayak − School of Chemical Sciences, National
Institute of Science Education and Research (NISER),
Bhubaneswar 752050, Odisha, India
3,5-Diethyl-2,6-diphenylpyridine (Scheme 4, Entry
14b).12c Prepared from butyrophenone (0.074 g, 0.5 mmol)
and MeOH followed by addition of NH4OAc and AcOH. After
purification by column chromatography (n-hexane/EtOAc,
98/2), the compound was isolated as a white solid (method C,
0.056 g, 78%). Single crystals were grown by slow evaporation
1
of a solution of the product 14b in methanol. H NMR (400
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00476
MHz, CDCl3) δ 7.59 (s, 1H), 7.53 (d, J = 7.0, 4H), 7.39 (dt, J
= 23.0, 7.1, 6H), 2.71 (q, J = 7.5, 4H), 1.20 (t, J = 7.5, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 155.48, 138.03, 135.91,
129.30, 128.23, 127.91, 25.41, 15.41. HRMS (ESI-TOF) m/z
[M + H]+ Calcd for [C21H21N + H]+, 288.1747; found,
288.1725.
2,6-Di([1,1′-biphenyl]-4-yl)-3,5-diethylpyridine (Scheme 4,
Entry 14c). Prepared from 4′-phenyl butyrophenone (0.112 g,
0.50 mmol) and MeOH followed by addition of NH4OAc and
AcOH. After purification by column chromatography (n-
hexane/EtOAc, 20/1), the compound was isolated as a white
solid (method C, 0.080 g, 73%). 1H NMR (400 MHz, CDCl3)
δ 7.63 (dd, J = 8.2, 3.8, 12H), 7.60 (s, 1H), 7.45 (t, J = 7.6,
4H), 7.35 (t, J = 7.3, 2H), 2.79 (q, J = 7.5, 4H), 1.25 (t, J = 7.5,
6H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.43, 141.14,
139.87, 137.73, 135.72, 129.73, 128.91, 127.41, 127.29, 127.02,
25.49, 15.54. HRMS (ESI-TOF) m/z [M + H]+ Calcd for
[C33H30N + H]+, 440.2373; found, 440.2361. FT-IR (ATR,
neat): 2979, 2883, 2283, 2067, 1487, 1435, 1385, 1263, 1155,
760, 736 cm−1.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
K.V. thanks Science & Engineering Research Board (SERB)
(EMR/2017/000620), New Delhi, and Department of Atomic
Energy (DAE) for financial support; P.B. thanks CSIR for a
research fellowship; and S.S. thanks DST for an INSPIRE
fellowship.
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ASSOCIATED CONTENT
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