Practical and Efficient Synthesis of Polyaryl(hetaryl)-Substituted Cyclohexenones and Salicylates

Article abstract of DOI:10.1055/s-0036-1588908

A new efficient method was developed for the synthesis of triaryl-substituted cyclohexenones and salicylates. The method is based on the Robinson annulation of readily available keto esters and chalcones, followed by the aromatization of the cyclohexenone moiety. The aromatization can be accomplished either by reaction with bromine in boiling chloroform or bromination with copper(II) bromide in ethanol followed by treatment with pyridine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The new synthetic method was also implemented in a one-pot protocol, which in some cases resulted in higher yields of the final product compared to those obtained in the stepwise synthesis.

Full text of DOI:10.1055/s-0036-1588908

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–I
paper
A
V. Z. Shirinian et al.
Paper
Synthesis
Practical and Efficient Synthesis of Polyaryl(hetaryl)-Substituted
Cyclohexenones and Salicylates
Valerii Z. Shirinian*a
Alexey M. Kavuna,b
Andrey G. Lvova
Igor V. Zavarzina
Michail M. Krayushkina
a N. D. Zelinsky Institute of Organic Chemistry, RAS 47, Lenin-
sky prosp., 119991 Moscow, Russian Federation
shir@ioc.ac.ru
b Higher Chemical College of the Russian Academy of Sciences,
D. I. Mendeleev University of Chemical Technology of Russia,
Miusskaya sq. 9, 125047 Moscow, Russian Federation
Received: 05.09.2016
Accepted after revision: 17.10.2016
Published online: 24.11.2016
utilizing acetoacetic ester derivatives and various Michael
acceptors as building blocks.4 Six-membered carbocycles
can also be constructed by the Claisen reaction,5 intramo-
lecular condensation of 1,5-dicarbonyl compounds,6 lac-
tone transformations,7 and metathesis reactions.8 The sub-
sequent transformation of cyclohexenones I to phenols II
can be performed by means of oxidation (the reaction with
bromine followed by the elimination of hydrogen bro-
mide,4a,d oxidation with various reagents7,9) or isoaromati-
zation of benzylidene derivatives (Scheme 1).8,10
DOI: 10.1055/s-0036-1588908; Art ID: ss-2016-z0605-op
Abstract A new efficient method was developed for the synthesis of
triaryl-substituted cyclohexenones and salicylates. The method is based
on the Robinson annulation of readily available keto esters and chal-
cones, followed by the aromatization of the cyclohexenone moiety. The
aromatization can be accomplished either by reaction with bromine in
boiling chloroform or bromination with copper(II) bromide in ethanol
followed by treatment with pyridine or 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU). The new synthetic method was also implemented in a one-
pot protocol, which in some cases resulted in higher yields of the final
product compared to those obtained in the stepwise synthesis.
R4
R3
R4
R3
oxidation
HO
O
Key words cyclohexenones, salicylates, polyaryl-substituted phenols,
Robinson annulation, chalcones, bromination
R1
R2
R1
R2
There is an ever-growing need for new chemical prod-
ucts to sustain and improve our lives, e.g. medicines, poly-
mers, dyes, food additives, etc. One approach to tackling
this problem is to develop facile and efficient methods for
the synthesis of these compounds from simple and readily
available precursor molecules. A perfect example of this
synthesis is the preparation of phenol and salicylic acid de-
rivatives from commercially available synthons.1 Phenol de-
rivatives are widely used in various applications, such as
medicine, agriculture, organic synthesis (fine chemicals),
polymers, etc.2 In particular, a very good example of the
practical application of substituted phenols is the use of sa-
licylates (aspirin and its analogues) as efficient analgesic
and anti-inflammatory drugs.3
IIa
Ia
acyclic precursors
R3
Ar
R3
Ar
isoaromatization
O
HO
R1
R2
R1
R2
Ib
IIb
Scheme 1 Synthesis of phenols II from polysubstituted cyclohexen-
ones I
The conventional method for the synthesis of cyclohex-
enones Va involves the Robinson annulation of readily
available acetoacetic ester III4a–d (or its derivatives11) and
chalcones IV followed by the oxidation of the resulting cy-
clohexenones Va to give 4,6-diaryl-substituted salicylates
VIa (Scheme 2). The use of γ-aryl-substituted derivatives
(ethyl 4-aryl-3-oxobutanoates) VII instead of acetoacetic
Numerous known synthetic protocols for the prepara-
tion of phenol derivatives include an approach based on the
Robinson annulation followed by the aromatization of the
cyclohexenone moiety. The Robinson annulation is com-
monly used for the assembly of the cyclohexenone ring by
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

B
V. Z. Shirinian et al.
Paper
Synthesis
ester could provide a route to 3,4,6-triaryl-substituted sa-
licylates VIb; however, almost no data concerning this ap-
proach are available in the scientific literature.
cones 3 followed by the bromination and aromatization of
the resulting six-membered ring (Scheme 3). Readily avail-
able aryl- or hetarylethanones 1, aryl- or hetarylcarbalde-
hydes 2, as well as acetic acids of various carbo- and het-
eroaromatic derivatives 4, were used as the starting com-
pounds. In the cases where the aryl- or hetarylacetic acids
were commercially unavailable, they were synthesized
from appropriate aryl- or hetarylethanones by the
Willgerodt−Kindler reaction.14 To develop an efficient prac-
tical method for the synthesis of polyaryl(hetaryl)-substi-
tuted cyclohexenones 6 and salicylates 8, we performed a
step-by-step optimization of this synthetic protocol. The
optimized conditions were used for the synthesis of a wide
range of salicylates based on benzene, naphthalene, thio-
phene, oxazole, and thiazole derivatives (Table 1).
Our studies demonstrated that potassium hydroxide
(1.0 equiv) in aqueous ethanol (water–ethanol, 1:1) is the
reagent of choice for the step giving the chalcones 3. The
use of alternative conditions (sodium ethoxide in anhy-
drous ethanol, potassium carbonate in anhydrous DMF, so-
dium hydroxide in ethanol, piperidine in ethanol, etc.)
proved to be less efficient and, in some cases, resulted in
the formation of byproducts and a decrease in the yields of
the final chalcones (the examination of these conditions
was important for the development also of the one-pot pro-
tocol). The reaction time depends on the nature of the aryl
substituents and the solubility of the starting compounds
in an aqueous ethanol solution and varies from 15 minutes
to 2 hours.
Previous work
EtO2C
HO
Ar2
Ar1
Ar2
Ar1
EtO2C
O
Ar2
Ar1
EtO2C
O
[O]
base
+
O
CH3
IV
Va
III
VIa
This work
EtO2C
EtO2C
O
Ar3
Ar2
Ar3
Ar2
EtO2C
HO
Ar3
Ar2
CuBr2
base
KOH
O
+
O
Ar1
Ar1
Ar1
VII
IV
Vb
VIb
Scheme 2 Synthesis of cyclohexenones and phenols from keto esters
and chalcones
In the present study, we describe an efficient method
for the synthesis of triaryl(hetaryl)-substituted cyclohexen-
one and salicylic acid derivatives involving the Robinson
annulation as a key step. This method includes preparative
steps based on commercially available starting compounds,
primarily acetyl and formyl derivatives of aromatic and het-
eroaromatic compounds. Aryl (or hetaryl) substituents in
the cyclohexenone and phenol moieties were chosen be-
cause of the interest in studying photochemical transfor-
mations of these compounds12 and their biological activity.
The development of this synthetic protocol was made pos-
sible because the starting keto esters (4-aryl-3-oxobuta-
noates) became available and can be prepared from appro-
priate arylacetic acids by the proposed method.13
The second step of this synthetic procedure is based on
the Robinson annulation of keto esters 5 with chalcones 3
in ethanol in the presence of an alkali (Scheme 3). This step
is the most intricate and unpredictable. Due to the presence
of acidic protons in the resulting cyclohexenone system,
these compounds are very sensitive to various transforma-
tions under basic conditions and, depending on the struc-
ture of the resulting cyclohexenone, the reaction can afford
the enol form as potassium enolate, which adds complexity
to the workup of the reaction mixture.
The synthetic protocol for the preparation of the cyclo-
hexenone and salicylic acid derivatives is based on the
Robinson annulation of 4-aryl-3-oxobutanoates 5 and chal-
O
Ar3
H
O
O
2
Ar3
Ar2
Ar2
CH3
Br
EtO2C
HO
Ar3
Ar2
Ar3
base
EtO2C
O
Ar3
CuBr2
base
EtO2C
O
KOH
3
1
EtOH
EtOH
Ar1
Ar1
Ar2
1. Meldrum's acid
CDI, CH2Cl2
Ar1
Ar2
O
O
Ar1
6
7
8
Ar1
CO2Et
OH
2. EtOH
5
4
Scheme 3 Synthetic method to triaryl(hetaryl)-substituted cyclohexenones and phenols
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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V. Z. Shirinian et al.
Paper
Synthesis
The Robinson annulation is also catalyzed by bases, but,
as opposed to the synthesis of chalcones, the best results
were obtained when using 0.2–0.5 equivalents potassium
hydroxide in an aqueous ethanol solution. An increase in
the amount of potassium hydroxide (more than 0.5 equiv)
led to a decrease in the yields of the target cyclohexenones.
The conditions of choice for the Robinson annulation in-
clude running the reaction at room temperature, at which
the reaction is complete in approximately 25−30 hours. In
reactions using azole derivatives as Ar1 or Ar2 (entries 5, 6,
and 10; in Table 1), a temperature rise results in an increase
in the yields of the target products. Therefore, the reaction
Table 1 Synthesis of Triarylcyclohexenones 6 and Phenols 8
Entry
6/8
Ar1
Ar2
Ar3
Yield of 6 (%)a
Yield of 8 (%)b,c
One-pot yield of 8
(%)d
1
a
70
74 (A)
25
30
2
3
4
5
6
7
b
c
34
39
34
40
63
45
55 (A)
60 (B)
49 (B)
49 (C)
64 (B)
61 (C)
29
30
37
30
22
S
O
S
d
e
f
S
N
Ph
N
Ph
O
S
S
g
8
h
60
50 (C)
28
F
9
i
j
63
68
35 (C)
71 (C)
23
30
Cl
S
10
Ph
N
a Yield of cyclohexenone 6 from chalcone 3.
b Yield of phenol 8 from cyclohexenone 6.
c Method given in parentheses: A: Br2, CHCl3; B: 1. CuBr2, EtOH; 2. pyridine; C: 1. CuBr2, EtOH; 2. DBU, CH2Cl2.
d Overall yield from ketone 1.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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V. Z. Shirinian et al.
Paper
Synthesis
for these compounds was performed under reflux. The re-
action with sodium ethoxide as a base in anhydrous ethanol
is also efficient for the azole derivatives; however, this
method can be implemented only in a stepwise protocol.
We have also revealed some trends in the effects of sub-
stituents on aryl moieties on the reactions of chalcones
with keto esters. It was found that the nature of the aryl
moiety (Ar3) of the aldehyde component 2 substantially in-
fluences the formation of the cyclohexenone ring (Robinson
cyclization). In the case of compounds containing a 4-halo-
gen-substituted phenyl moiety (F, Cl), the cyclization occurs
in low yields, apparently due to the electron-withdrawing
inductive effect of the halogen atom that has an effect on
the reactivity of chalcone 3 in the conjugate addition, al-
though the starting chalcones 3 containing these substitu-
ents are produced in high yields. It was also found that chal-
cones 3 containing a heterocyclic moiety at the first posi-
tion (Ar2) react more readily with keto esters compared to
compounds containing phenyl substituents. This can be at-
tributed to the difference in solubility.
The third step in this synthesis involves the oxidation of
the cyclohexenone ring giving phenol derivatives. The con-
ventional method for this transformation is based on bro-
mination with molecular bromine in chloroform under re-
flux.15 The reaction results in the dehydrobromination of
the primary halogen derivative and gives the phenol deriva-
tive in good yield. We tested this method for model com-
pound 6a, the bromination of which afforded phenol 8a in
74% yield (Scheme 4). However, the drawback of this meth-
od is the sensitivity of aromatic substituents on the cyclo-
hexenone ring to molecular bromine. In particular, we
found that the aromatization of thiophene-containing com-
pounds is accompanied by the bromination of the aromatic
ring, which results in a decrease in the yield and interferes
with purification of the target products. For this reason, we
examined different aromatization methods for the cyclo-
hexenone system.
Scheme 4 displays the results of the investigation of the
aromatization of the model compound, cyclohexenone 6a
containing three phenyl substituents. We studied various
brominating and oxidizing systems, in particular, iodine in
ethanol, DDQ, copper acetate, etc. The best results were ob-
tained with the use of copper(II) bromide16 for the bromi-
nation, followed by treatment with pyridine or DBU. The
bromination was found to be the most efficient with the
use of 2.2 equivalents of CuBr2 in ethanol at 60–80 °C. In
this case, product 7a was isolated in 80% yield.
After the usual workup of the reaction mixture, one of
two procedures for the aromatization of 7a can be applied
(Scheme 4). In the one method, the solvent is removed by
distillation and the residue is heated in pyridine at 80 °C
until the starting bromine derivative is completely con-
sumed. An alternative method involves the use of DBU as
the dehydrobrominating agent and dichloromethane as the
solvent. A twofold excess of DBU is added to a dichloro-
methane solution of 7a obtained in the previous step, the
reaction mixture is stirred for 30 minutes and then succes-
sively washed with hydrochloric acid and water, then the
solvent is removed by distillation, and the residue is puri-
fied by flash chromatography. It is an alternative method
that is less laborious and more efficient than the approach
using pyridine (pyridine as solvent, reflux, 20–24 h), but it
requires a more expensive reactant (DBU) as the dehydro-
brominating agent. The bromination in ethanol and subse-
quent dehydrobromination and aromatization using DBU
(method C) is an operationally simple and efficient workup
method that leads to high yields of the target phenols, and
excludes the possibility of bromination of a heteroaromatic
system.
We applied these procedures to synthesize a number of
previously unknown triaryl-substituted salicylates 8 (Table
1). The structures of the resulting compounds were estab-
lished by 1H and 13C NMR spectroscopy and high-resolution
mass spectrometry. The structure of compound 8e was also
confirmed by X-ray crystal structure analysis17 (Figure 1).
This synthetic route to salicylates 8 was also accom-
plished in a one-pot protocol starting from 1-aryl- or 1-het-
arylethanones 1. The first two steps are performed in an
aqueous ethanol solution in the presence of potassium hy-
droxide. We found that 0.8–1.0 equivalents of KOH is the
optimum quantity of the base for the first two steps. An in-
crease in the amount of the hydroxide has a very positive
impact on the yields in the first step, but negatively affects
the cyclization. In contrast, a decrease in the amount of the
base results in lower yields of chalcones 3, but has a posi-
tive effect on the formation of the cyclohexenone deriva-
tives 6 (for this stage, catalytic amounts of base are re-
quired). Then, in order to neutralize the base, an equimolar
amount of NH4Cl (with respect to the amount of potassium
hydroxide used) and CuBr2 (2.1 equiv) as the brominating
agent are added. The bromination proceeds under reflux in
ethanol for 4–6 hours. After extraction and drying of the
DBU, CH2Cl2 (72% from 6a)
C
A
Br
EtO2C
HO
Ph
Ph
EtO2C
O
Ph
Ph
Ph
Ph
EtO2C
O
Br2
CuBr2
CHCl3
74%
EtOH
80%
Ph
Ph
Ph
8a
6a
7a
pyridine (63% from 6a)
B
Scheme 4 Different approaches for the aromatization of 6a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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V. Z. Shirinian et al.
Paper
Synthesis
To summarize, we have developed a new efficient meth-
od for the synthesis of polyaryl(hetaryl)substituted cyclo-
hexenones and salicylates from readily available starting
compounds. It was shown that polyaromatic derivatives of
phenol and salicylic acid can be synthesized in good yields
from simple and readily available acyclic starting com-
pounds – aromatic (heteroaromatic) aldehydes, ketones,
and acetic acid derivatives. This synthetic protocol involves
the Robinson annulation of keto esters with chalcones as a
key step. Various benzene, naphthalene, thiophene, oxaz-
ole, and thiazole derivatives were used as aryl moieties. The
aromatization can be accomplished either by reaction with
bromine in refluxing chloroform or bromination with cop-
per(II) bromide in ethanol followed by treatment with pyri-
dine or DBU. The new method was also implemented in a
one-pot protocol, which in some cases resulted in the for-
mation of the final products in higher yields compared to
those obtained in the stepwise procedure. This method can
be applied to synthesize desired polyaryl(hetaryl)-substi-
tuted salicylates containing different predetermined aro-
matic substituents.
Figure 1 Structure of compound 8e as determined by X-ray crystallo-
graphic analysis
bromine derivative 7, an excess of DBU in dichloromethane
is added to a dichloromethane solution of 7 as in the step-
wise procedure.
1H and 13C NMR spectra of samples in deuterated solvents were re-
corded at 293 K (300 MHz for 1H, 75 MHz for 13C). Melting points were
recorded by using an apparatus and are not corrected. Mass spectra
were obtained on a mass spectrometer (70 eV) with direct sample in-
jection into the ion source. High resolution mass spectra were ob-
tained on a TOF mass spectrometer with an ESI source. All chemicals
and anhydrous solvents were purchased from commercial sources
and used without further purification. Column chromatography was
performed by using silica gel 60 (70−230 mesh); TLC analysis was
conducted on silica gel 60 F254 plates. Keto esters 5 were described
previously.13,19
A comparative analysis of the yields obtained in the
stepwise method and in the one-pot protocol shows that in
some cases (entries 2–5 in the Table 1) the one-pot method
is more efficient, which can probably be attributed to losses
during the workup of the reaction mixture and purification
of the final products in these steps. Molecular bromine can
also be used as the brominating agent. However, it should
be taken into account that this method is not suitable for
the synthesis of compounds sensitive to this reactant. The
bromination with CuBr2 is a versatile and efficient method
and can be applied to any substrate. It was also shown that
DBU is an operationally convenient and efficient reagent in
the steps of elimination of HBr and aromatization.
We have also applied an alternative method to synthe-
size a phenol derivative from decarboxylated cyclohexen-
one 9 (Scheme 5). The condensation of 9 with benzalde-
hyde in an aqueous ethanol solution of an alkali afforded
phenol 10 in 35% yield via a 1,3-sigmatropic shift, resulting
in the aromatization of the cyclohexenone system.8,10,18
Cyclohexenones 6; General Procedure
KOH (0.6 mmol) was added to a solution of the keto ester 5 (1.23
mmol) and the chalcone 3 (1.23 mmol) in EtOH (4 mL). The resulting
suspension was stirred for 24 h at r.t. After the completion of the reac-
tion (TLC control) the precipitated product formed was collected by
filtration, washed with H2O (50 mL) and cold EtOH (5 mL), and dried
under vacuum. Additional quantities of the product were obtained as
following: filtrate was poured into H2O (50 mL), extracted with EtOAc
(3 × 30 mL), washed with brine (70 mL), dried (MgSO4), and evaporat-
ed under vacuum. The residue was purified by column chromatogra-
phy (silica gel, PE–EtOAc, 6:1).
Ph
O
Ethyl 3′-Oxo-5′-phenyl-3′,4′,5′,6′-tetrahydro-[1,1′:2′,1′′-terphenyl]-
4′-carboxylate (6a)
Ph
Ph
Ph
EtO2C
O
Ph
Ph
H
KOH
Colorless crystals; yield: 341 mg (70%); mp 160–161 °C.
O
HO
IR (KBr): 3024, 2993, 1741, 1664, 1256, 1032, 697 cm–1
.
EtOH/H2O
KOH
EtOH/H2O
Ph
Ph
Ph
10 35%
1H NMR (300 MHz, CDCl3): δ = 1.10 (t, J = 7.1 Hz, 3 H, CH3), 3.05–3.19
(m, 2 H, CH2), 3.92–4.16 (m, 4 H, CH+CH+CH2), 6.91–7.43 (m, 15 H,
Harom).
Ph
Ph
6a
9 73%
Scheme 5 Alternative aromatization route
13C NMR (75 MHz, CDCl3): δ = 14.0, 40.4, 43.4, 60.1, 61.0, 127.1, 127.2
(2 C), 127.4, 127.6 (2 C), 128.0 (2 C), 128.2 (3 C), 128.8 (2 C), 131.0 (2
C), 134.7, 136.8, 139.9, 141.1, 156.6, 169.3, 193.2.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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V. Z. Shirinian et al.
Paper
Synthesis
MS (EI, 70 eV): m/z (%) = 396 (60) [M]+, 323 (100) [M – CO2Et]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H24O3: 397.1798; found:
1H NMR (300 MHz, CDCl3): δ = 1.08 (t, J = 7.1 Hz, 3 H, CH3), 1.89 (s, 3
H, CH3), 3.03–3.21 (m, 2 H, CH2), 3.94–4.17 (m, 4 H, CH+CH+CH2),
7.16–7.46 (m, 13 H, Harom), 7.85–8.01 (m, 2 H, Harom).
397.1782.
13C NMR (75 MHz, CDCl3): δ = 10.7, 14.1, 40.4, 43.4, 60.1, 61.0, 126.1
(2 C), 127.3, 127.6 (2 C), 127.7, 127.8, 128.0, 128.3, 128.5 (2 C), 128.6
(2 C), 128.9 (4 C), 129.8, 130.5, 139.5, 141.0, 146.8, 159.6, 160.3,
169.1, 192.7.
MS (EI, 70 eV): m/z (%) = 477 (60) [M]+, 404 (100) [M – CO2Et]+.
HRMS (ESI): m/z [M + H]+ calcd for C31H27NO4: 478.2013; found:
Ethyl 6′-(1-Naphthyl)-5′-oxo-2′,3′,4′,5′-tetrahydro-[1,1′:3′,1′′-ter-
phenyl]-4′-carboxylate (6b)
Pale-red powder; yield: 187 mg (34%); mp 225–226 °C.
IR (KBr): 3056, 1734, 1667, 1315, 1142, 779, 701 cm–1
.
(Double set of some signals in the 1H and 13C NMR spectra indicates
dynamic NMR effect.)
478.2025.
1H NMR (300 MHz, CDCl3): δ = 1.09 and 1.13 (t, J = 7.1 Hz, 3 H, CH3),
3.10–3.38 (m, 2 H, CH2), 4.00–4.20 (m, 4 H, CH+CH+CH2), 6.92–7.89
(m, 17 H, Harom).
13C NMR (75 MHz, CDCl3): δ = 14.1, 40.0, 40.4, 43.7, 43.8, 61.1, 61.2,
125.2, 125.4, 125.5, 125.7, 125.9, 126.1, 126.2, 126.7, 126.8, 127.1,
127.3, 127.4, 127.6, 127.9, 128.0, 128.1, 128.4, 128.5, 128.6, 128.8,
128.9, 129.0, 132.6, 132.9, 133.3, 133.4, 136.0, 136.1, 139.7, 139.8,
141.1, 141.2, 158.2, 158.3, 169.2, 169.4, 193.0, 193.2.
Ethyl 5′-(5-Methyl-2-phenyl-1,3-oxazol-4-yl)-3′-oxo-1′,2′,3′,6′-tet-
rahydro-[1,1′:4′,1′′-terphenyl]-2′-carboxylate (6f)
Yellow powder; yield: 370 mg (63%); mp 131–134 °C.
IR (KBr): 2978, 1731, 1668, 1261, 1136, 696 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.08 (t, J = 7.1 Hz, 3 H, CH3), 1.57 (s, 3
H, CH3), 2.99 (dd, J = 19.1, 9.1 Hz, 1 H, 0.5CH2), 3.53 (dd, J = 19.1, 3.8
Hz, 1 H, 0.5CH2), 3.91–4.11 (m, 4 H, CH+CH+CH2), 7.13–7.47 (m, 13 H,
Harom), 7.90–8.00 (m, 2 H, Harom).
MS (EI, 70 eV): m/z (%) = 446 (80) [M]+, 373 (100) [M – CO2Et]+.
13C NMR (75 MHz, CDCl3): δ = 11.2, 14.0, 38.3, 42.9, 60.5, 60.9, 126.0
(2 C), 127.0, 127.3 (3 C), 127.9, 128.0 (2 C), 128.1 (2 C), 128.7 (2 C),
130.3 (2 C), 130.8, 134.6, 134.9, 136.6, 141.1, 146.7, 148.2, 160.1,
169.2, 193.0.
MS (EI, 70 eV): m/z (%) = 477 (80) [M]+, 404 (100) [M – CO2Et]+.
HRMS (ESI): m/z [M + H]+ calcd for C31H27NO4: 478.2013; found:
HRMS (ESI): m/z [M + H]+ calcd for C31H26O3: 447.1955; found:
447.1952.
Ethyl 6′-(2,5-Dimethyl-3-thienyl)-5′-oxo-2′,3′,4′,5′-tetrahydro-
[1,1′:3′,1′′-terphenyl]-4′-carboxylate (6c)
Yellow crystals; yield: 206 mg (39%); mp 117–118 °C.
478.2005.
IR (KBr): 2917, 1732, 1662, 1147, 754, 702 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.11 (t, J = 7.1 Hz, 3 H, CH3), 1.81 (s, 3
H, CH3), 2.34 (s, 3 H, CH3), 3.03–3.20 (m, 2 H, CH2), 3.89–4.16 (m, 4 H,
CH+CH+CH2), 6.38 (s, 1 H, Hthiophene), 7.05–7.41 (m, 10 H, Harom).
13C NMR (75 MHz, CDCl3): δ = 13.8, 14.0, 15.2, 39.8, 43.4, 60.1, 60.9,
127.2 (2 C), 127.4, 127.7 (2 C), 127.8, 128.0 (2 C), 128.5, 128.8 (2 C),
130.6, 131.7, 134.3, 135.1, 139.9, 141.1, 157.1, 169.2, 193.3.
Ethyl 3-(2,5-Dimethyl-3-thienyl)-2-oxo-4,6-di-2-thienylcyclohex-
3-ene-1-carboxylate (6g)
Gray powder; yield: 245 mg (45%); mp 111–113 °C.
IR (KBr): 3096, 2915, 1734, 1656, 1371, 1277, 1150, 707 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.19 (t, J = 7.1 Hz, 3 H, CH3), 1.99 and
2.08 (s, 3 H, CH3), 2.43 (s, 3 H, CH3), 3.11–3.34 (m, 1 H), 3.43–3.61 (m,
1 H), 3.76–3.93 (m, 1 H), 4.03–4.30 (m, 3 H, CH+CH2), 6.31 (s, 1 H,
Hthiophene), 6.90–7.09 (m, 3 H, Hthiophene), 7.17–7.50 (m, 3 H, Hthiophene).
13C NMR (75 MHz, CDCl3): δ = 13.4, 14.1, 15.4, 38.0, 38.1, 60.9, 61.2,
124.1, 124.8, 126.3, 126.7, 126.9, 128.9, 130.3, 130.7, 132.3, 136.2,
137.3, 140.8, 144.7, 147.1, 169.0, 192.1.
MS (EI, 70 eV): m/z (%) = 430 (20) [M]+, 357 (35) [M – CO2Et]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H26O3S: 431.1675; found:
431.1663.
Ethyl 5′-(2,5-Dimethyl-3-thienyl)-3′-oxo-1′,2′,3′,6′-tetrahydro-
[1,1′:4′,1′′-terphenyl]-2′-carboxylate (6d)
MS (EI, 70 eV): m/z (%) = 442 (100) [M]+, 369 (75) [M – CO2Et]+.
HRMS (ESI-TOF) m/z [M + H]+ calcd for C23H23O3S3: 443.0804; found:
Yellow amorphous powder; yield: 180 mg (34%).
IR (KBr): 2914, 1737, 1663, 1258, 766, 698 cm–1
.
443.0792.
1H NMR (300 MHz, CDCl3): δ = 1.10 (t, J = 7.1 Hz, 3 H, CH3), 1.81 (s, 3
H, CH3), 2.33 (s, 3 H, CH3), 2.91–3.00 (m, 2 H, CH2), 3.86–4.13 (m, 4 H,
CH+CH+CH2), 6.46 (s, 1 H, Hthiophene), 7.00–7.09 (m, 2 H, Harom), 7.14–
7.40 (m, 8 H, Harom).
13C NMR (75 MHz, CDCl3): δ = 14.0, 14.2, 15.0, 40.5, 43.2, 60.4, 61.0,
125.3, 127.0, 127.2 (2 C), 127.4 (3 C), 128.8 (2 C), 130.6 (2 C), 133.6,
134.7, 136.3, 136.8, 137.2, 141.1, 153.1, 169.3, 192.9.
Ethyl 5′-(4-Fluorophenyl)-3′-oxo-3′,4′,5′,6′-tetrahydro-[1,1′:2′,1′′-
terphenyl]-4′-carboxylate (6h)
White powder; yield: 306 mg (60%); mp 153–155 °C.
IR (KBr): 2978, 1735, 1665, 1510, 1141, 843, 700 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.13 (t, J = 7.1 Hz, 3 H, CH3), 3.05–3.17
(m, 2 H, CH2), 3.86–4.24 (m, 4 H, CH+CH+CH2), 6.97–7.25 (m, 12 H,
Harom), 7.30–7.47 (m, 2 H, Harom).
MS (EI, 70 eV): m/z (%) = 430 (100) [M]+, 357 (95) [M – CO2Et]+.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H26O3S: 431.1675; found:
13C NMR (75 MHz, CDCl3): δ = 14.0, 40.4, 42.7, 60.3, 61.1, 115.7 (d,
431.1669.
2JCF = 21.4 Hz, 2 C), 127.1, 127.7 (2 C), 128.1 (4 C), 128.3, 128.5, 128.8
3
1
(d, JCF = 8.1 Hz, 2 C), 131.0 (2 C), 134.5, 136.8, 156.5, 162.0 (d, JCF
=
Ethyl 6′-(5-Methyl-2-phenyl-1,3-oxazol-4-yl)-5′-oxo-2′,3′,4′,5′-tet-
rahydro-[1,1′:3′,1′′-terphenyl]-4′-carboxylate (6e)
245.8 Hz), 169.1, 193.0.
HRMS (ESI): m/z [M + H]+ calcd for C27H23FO3: 415.1704; found:
415.1691.
Yellow crystals; yield: 235 mg (40%); mp 129–130 °C.
IR (KBr): 2981, 1734, 1681, 1266, 1256, 698 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

G
V. Z. Shirinian et al.
Paper
Synthesis
Ethyl 5′-(4-Chlorophenyl)-3′-oxo-3′,4′,5′,6′-tetrahydro-[1,1′:2′,1′′-
terphenyl]-4′-carboxylate (6i)
day, NH4Cl (107 mg, 2 mmol) and CuBr2 (685 mg, 3.06 mmol) were
added and the mixture was refluxed for 6 h. Then the reaction mix-
ture was cooled, poured into H2O (100 mL), and extracted with CH2Cl2
(3 × 50 mL); the combined organic phases were washed with brine (2
× 50 mL), dried (MgSO4), and evaporated. The residue was dissolved in
CH2Cl2 (30 mL) and then DBU (0.37 mL, 2.45 mmol) was added; the
resulting solution was then washed with 5% aq HCl, evaporated, and
purified by flash chromatography (silica gel, PE–EtOAc, from 20:1 to
30:1). (Overall yields of phenols 8 obtained by one-pot protocol are
given in Table 1).
White powder, yield: 333 mg (63%); mp 105–107 °C (dec.).
IR (KBr): 2923, 1660, 1734, 1315, 1139, 698 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.00–1.20 (m, 3 H, CH3), 3.00–3.17 (m,
2 H, CH2), 3.85–4.30 (m, 4 H, CH+CH+CH2), 6.90–7.25 (m, 12 H, Harom),
7.26–7.52 (m, 2 H, Harom).
13C NMR (75 MHz, CDCl3): δ = 14.1, 40.2, 42.8, 60.0, 61.2, 127.2, 127.7
(2 C), 128.1, 128.2 (2 C), 128.4 (2 C), 128.5 (2 C), 128.7 (2 C), 129.0,
131.0 (2 C), 133.2, 134.5, 136.8, 139.6, 156.4, 169.1, 192.9.
HRMS (ESI-TOF) m/z [M + H]+ calcd for C27H23ClO3: 431.1408;
found:431.1393.
Ethyl 4′-Bromo-3′-oxo-5′-phenyl-3′,4′,5′,6′-tetrahydro-[1,1′:2′,1′′-
terphenyl]-4′-carboxylate (7a)
Pale grey powder; yield: 114 mg (80%); mp 222–225 °C.
IR (KBr): 3057, 3029, 2981, 1756, 1730, 1670, 1263, 1221, 698 cm–1
.
Ethyl 5′-(4-Methyl-2-phenyl-1,3-thiazol-5-yl)-3′-oxo-1′,2′,3′,6′-tet-
rahydro-[1,1′:4′,1′′-terphenyl]-2′-carboxylate (6j)
1H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.0 Hz, 3 H, CH3), 3.06 (dd,
J = 4.3, 19.2 Hz, 1 H, 0.5CH2), 3.43 (dd, J = 10.7, 19.2 Hz, 1 H, 0.5CH2),
4.17–4.28 (m, 3 H, CH+CH2), 7.00–7.54 (m, 15 H, Harom).
Pale-yellow powder; yield: 412 mg (68%); mp 162–164 °C.
IR (KBr): 2978, 1733, 1670, 1258, 1023, 700 cm–1
.
13C NMR (75 MHz, CDCl3): δ = 14.0, 37.5, 47.1, 63.2, 72.5, 127.3, 127.5,
127.7 (2 C), 128.1 (2 C), 128.2 (2 C), 128.4 (3 C), 128.9 (2 C), 130.8 (2
C), 134.0, 134.5, 137.2, 139.5, 157.3, 165.9, 188.4.
1H NMR (300 MHz, CDCl3): δ = 1.11 (t, J = 7.1 Hz, 3 H, CH3), 1.99 (s, 3
H, CH3), 3.03–3.23 (m, 2 H, CH2), 3.94–4.22 (m, 4 H, CH+CH+CH2),
7.05–7.60 (m, 13 H, Harom), 7.77–7.92 (m, 2 H, Harom).
MS (EI, 70 eV): m/z (%) = 396 (90) [M + H – Br]+, 349 (85), 323 (100).
13C NMR (75 MHz, CDCl3): δ = 14.0, 16.8, 41.7, 43.1, 60.2, 61.1, 126.4
(2 C), 127.2 (2 C), 127.6, 127.8, 127.9 (2 C), 128.8, 128.9 (4 C), 130.3,
130.4, 130.5 (2 C), 133.0, 134.1, 140.6, 147.2, 150.7, 167.4, 168.9,
192.3.
HRMS (ESI-TOF) m/z [M + H]+ calcd for C27H23BrO3: 475.0903 (79Br),
477.0884 (81Br); found: 475.0892 (79Br), 477.0873 (81Br).
HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H27NO3S: 494.1784; found:
Ethyl 5′-Hydroxy-6′-phenyl-1,1′:3′,1′′-terphenyl-4′-carboxylate
494.1775.
(8a)
White powder; method A: yield: 87 mg (74%), method B: yield: 75 mg
(63%), method C: yield: 85 mg (72%); mp 173–176 °C.
Phenols 8
IR (KBr): 3058, 2989, 1651, 1379, 1303, 1224, 755, 696 cm–1
.
Method A: Cyclohexenone 6 (0.3 mmol) was dissolved in CHCl3 (2 mL),
then Br2 (16 μL, 0.3 mmol) was added, and the resulting mixture was
refluxed for 3 h. Then the reaction mixture was poured into H2O (50
mL) and extracted with EtOAc (3 × 30 mL) and the combined organic
phases were washed with H2O (50 mL), dried (MgSO4), and evaporat-
ed under vacuum. The residue was purified by flash chromatography
(silica gel, PE–EtOAc 20:1).
1H NMR (300 MHz, CDCl3): δ = 0.80 (t, J = 7.1 Hz, 3 H, CH3), 4.04 (q, J =
7.1 Hz, 2 H, CH2), 6.96 (s, 1 H, Harom), 7.07–7.44 (m, 15 H, Harom), 11.12
(s, 1 H, OH).
13C NMR (75 MHz, CDCl3): δ = 13.1, 61.2, 111.2, 124.3, 126.9, 127.1,
127.5, 127.7 (2 C), 127.8 (4 C), 128.3 (2 C), 128.8, 129.6 (2 C), 131.2 (2
C), 135.9, 140.4, 142.9, 143.8, 146.3, 159.1, 171.2.
Method B: Cyclohexenone 6 (0.3 mmol) was dissolved in EtOH (2 mL)
and CuBr2 (168 mg, 0.75 mmol) was added. The reaction mixture was
refluxed for 6 h. The resulting mixture was poured into H2O (75 mL)
and extracted with EtOAc (3 × 40 mL); then the combined organic
phases were washed with brine (4 × 70 mL), dried (MgSO4), and evap-
orated under vacuum (compound 7a was isolated by recrystallization
from EtOH). The residue was dissolved in pyridine (2 mL) and stirred
at 90 °C for 3 h; the mixture was subsequently evaporated under vac-
uum and purified by flash chromatography (silica gel, PE–EtOAc
20:1).
MS (EI, 70 eV): m/z (%) = 394 (70) [M]+, 348(100) [M – EtOH]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H22O3: 395.1642; found:
395.1636.
Ethyl 5′-Hydroxy-6′-(1-naphthyl)-1,1′:3′,1′′-terphenyl-4′-carboxyl-
ate (8b)
Colorless crystals; method A: yield: 73 mg (55%); mp 195–196 °C.
IR (KBr): 3055, 3036, 2958, 2927, 1657, 1602, 1377, 1223, 1129, 778,
700 cm–1
.
Method C: Cyclohexenone 6 (0.3 mmol) was suspended in EtOH (2 mL)
and CuBr2 (168 mg, 0.75 mmol) was added. The reaction mixture was
refluxed for 6 h. The resulting mixture was poured into H2O (75 mL)
and extracted with EtOAc (3 × 40 mL), and the combined organic
phases were washed with brine (4 × 70 mL), dried (MgSO4), and evap-
orated under vacuum. The residue was dissolved in CH2Cl2 (20 mL)
and then DBU (90 μL, 0.6 mmol) was added to the solution; the re-
sulting solution was then washed with 5% aq HCl, evaporated, and pu-
rified by flash chromatography (silica gel, PE–EtOAc, 20:1 or 30:1).
1H NMR (300 MHz, CDCl3): δ = 0.84 (t, J = 7.1 Hz, 3 H, CH3), 4.07 (q, J =
7.1 Hz, 2 H, CH2), 7.00–7.11 (m, 5 H, Harom), 7.19 (d, J = 7.0 Hz, 1 H,
Harom), 7.33–7.51 (m, 9 H, Harom), 7.19 (d, J = 7.8 Hz, 2 H, Harom),7.83–
7.92 (m, 1 H, Harom), 11.01 (s, 1 H, OH).
13C NMR (75 MHz, CDCl3): δ = 13.1, 61.2, 111.1, 124.3, 125.3, 125.6,
126.0, 126.1, 126.5, 126.9, 127.1, 127.6 (2 C), 127.7 (2 C), 127.8, 128.3
(2 C), 128.4, 128.6, 128.7 (2 C), 132.8, 133.3, 134.2, 140.2, 142.9,
144.2, 147.4, 159.6, 171.1.
MS (EI, 70 eV): m/z (%) = 444 (90) [M]+, 398 (100) [M – EtOH]+.
HRMS (ESI): m/z [M + H]+ calcd for C31H24O3: 445.1798; found:
One-pot method: KOH (1.1 mmol) was added to a solution of ketone 1
(1.23 mmol) and aldehyde 2 (1.23 mmol) in EtOH (4 mL). The mixture
was stirred at r.t. for 2 h. Then keto ester 5 (1.23 mmol) was added to
the obtained suspension and the mixture was left overnight. The next
445.1798.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

H
V. Z. Shirinian et al.
Paper
Synthesis
Ethyl 6′-(2,5-Dimethyl-3-thienyl)-5′-hydroxy-1,1′:3′,1′′-terphenyl-
4′-carboxylate (8c)
Ethyl 3-(2,5-Dimethyl-3-thienyl)-2-hydroxy-4,6-di-2-thienylben-
zoate (8g)
Yellow amorphous powder; method B: yield: 77 mg (60%).
Brownish amorphous powder; method C: yield: 81 mg (61%).
IR (KBr): 2957, 2919, 1731, 1657, 1599, 1375, 1261, 1142, 699 cm–1
.
IR (KBr): 2957, 2917, 1655, 1599, 1396, 1257, 689 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.80 (t, J = 7.1 Hz, 3 H, CH3), 1.93 (s, 3
H, CH3), 2.40 (s, 3 H, CH3), 4.04 (q, J = 7.1 Hz, 2 H, CH2), 6.51 (s, 1 H,
Hthiophene), 6.95 (s, 1 H, Harom), 7.12–7.41 (m, 10 H, Harom), 11.06 (s, 1 H,
OH).
13C NMR (75 MHz, CDCl3): δ = 13.0, 13.8, 15.3, 61.1, 111.1, 123.0,
123.9, 126.8, 127.2, 127.7 (2 C), 127.8 (2 C), 128.0, 128.2 (2 C), 128.9
(2 C), 129.3, 131.5, 134.3, 135.3, 140.4, 142.9, 146.8, 159.6, 171.1.
1H NMR (300 MHz, CDCl3): δ = 0.98 (t, J = 7.1 Hz, 3 H, CH3), 2.07 (s, 3
H, CH3), 2.46 (s, 3 H, CH3), 4.13 (q, J = 7.1 Hz, 2 H, CH2), 6.49 (s, 1 H,
Hthiophene), 6.90–6.95 (m, 1 H, Hthiophene), 6.97–7.09 (m, 3 H, Harom+Hthiophene),
7.25–7.30 (m, 2 H, Hthiophene), 7.33–7.37 (m, 1 H, Hthiophene), 10.76 (s, 1
H, OH).
13C NMR (75 MHz, CDCl3): δ = 13.3, 13.6, 61.5, 112.3, 123.0, 123.7,
125.2, 126.1, 126.2, 126.7, 126.9, 127.4, 127.5, 127.8, 128.0, 131.3,
135.8, 136.6, 138.9, 141.5, 143.4, 159.7, 170.6.
MS (EI, 70 eV): m/z (%) = 428 (75) [M]+, 382 (100) [M – EtOH]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H24O3S: 429.1519; found:
MS (EI, 70 eV): m/z (%) = 440 (100) [M]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H20O3S3: 441.0647; found:
429.1520.
441.0636.
Ethyl 5′-(2,5-Dimethyl-3-thienyl)-3′-hydroxy-1,1′:4′,1′′-terphenyl-
2′-carboxylate (8d)
Ethyl 5′-(4-Fluorophenyl)-3′-hydroxy-[1,1′:2′,1′′-terphenyl]-4′-car-
boxylate (8h)
Yellow amorphous powder; method B: yield: 63 mg (49%).
White powder; method C: yield: 62 mg (50%); mp 139–141 °C.
IR (KBr): 2958, 2924, 1741, 1658, 1601, 1378, 1251, 1177, 699 cm–1
.
IR (KBr): 2978, 1668, 1603, 1513, 1380, 1214, 1155, 698 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.80 (t, J = 7.1 Hz, 3 H, CH3), 2.02 (s, 3
H, CH3), 2.28 (s, 3 H, CH3), 4.04 (q, J = 7.1 Hz, 2 H, CH2), 6.28 (s, 1 H,
Hthiophene), 6.85 (s, 1 H, Harom), 7.18–7.42 (m, 10 H, Harom), 11.13 (s, 1 H,
OH).
1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.2 Hz, 3 H, CH3), 4.08 (q, J =
7.2 Hz, 2 H, CH2), 6.93 (s, 1 H, Harom), 7.08–7.34 (m, 14 H, Harom), 11.21
(s, 1 H, OH).
13C NMR (75 MHz, CDCl3): δ = 13.0, 13.9, 15.0, 61.2, 111.1, 124.6,
126.7, 126.8, 127.5 (2 C), 127.6 (2 C), 128.2 (2 C), 128.3, 128.9, 130.7
(2 C), 135.1, 135.9, 136.7, 141.9, 142.9, 143.3, 158.9, 171.2.
MS (EI, 70 eV): m/z (%) = 428 (90) [M]+, 382 (100) [M – EtOH]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H24O3S: 429.1519; found:
13C NMR (75 MHz, CDCl3): δ = 13.2, 61.3, 114.5 (d, 2JCF = 21.6 Hz, 2 C),
124.3, 126.9, 127.1, 127.8 (4 C), 128.4, 129.6 (2 C), 129.8 (d, 3JCF = 7.8
Hz, 2 C), 131.1 (2 C), 135.7, 138.9, 140.3, 142.6, 144.3, 146.4, 159.3,
171.0.
HRMS (ESI): m/z [M + H]+ calcd for C27H21FO3: 413.1547; found:
413.1538.
429.1511.
Ethyl 5′-(4-Chlorophenyl)-3′-hydroxy-[1,1′:2′,1′′-terphenyl]-4′-
carboxylate (8i)
Ethyl 5′-Hydroxy-6′-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-
1,1′:3′,1′′-terphenyl-4′-carboxylate (8e)
White powder; method C: yield: 45 mg (35%); mp 178–181 °C.
Yellow crystals; method C: yield: 70 mg (49%); mp 189–191 °C.
IR (KBr): 2985, 1649, 1492, 1374, 1219, 1089, 698 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.89 (m, 3 H, CH3), 1.80 (s, 3 H, CH3),
4.09 (m, 2 H, CH2), 7.00 (s, 1 H, Harom), 7.25–7.45 (m, 13 H, Harom),
8.02–8.12 (m, 2 H, Harom), 11.00 (s, 1 H, OH).
13C NMR (75 MHz, CDCl3): δ = 10.6, 13.2, 61.2, 114.1, 117.2, 126.2,
127.8 (2 C), 128.2 (4 C), 128.3, 128.5 (2 C), 128.7 (2 C), 129.0 (2 C),
129.5, 130.1, 131.2, 140.4, 142.1, 144.2, 146.4 (2 C), 158.9, 159.8,
170.2.
1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.2 Hz, 3 H, CH3), 4.09 (q, J =
7.2 Hz, 2 H, CH2), 6.90 (s, 1 H, Harom), 7.08–7.34 (m, 12 H, Harom), 7.36–
7.43 (m, 2 H, Harom), 11.26 (s, 1 H, OH).
13C NMR (75 MHz, CDCl3): δ = 13.2, 61.4, 110.9, 124.1, 127.0, 127.1,
127.8 (6 C), 128.6, 129.5 (2 C), 129.6 (2 C), 131.1 (2 C), 132.9, 135.7,
140.2, 141.4, 142.4, 146.5, 159.4, 171.0.
HRMS (ESI): m/z [M + H]+ calcd for C31H25NO4: 476.1856; found:
HRMS (ESI): m/z [M + Na]+ calcd for C27H21ClO3: 451.1071; found:
476.1765.
451.1064.
Ethyl 3′-Hydroxy-5′-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-
1,1′:4′,1′′-terphenyl-2′-carboxylate (8f)
Ethyl 3′-Hydroxy-5′-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-
1,1′:4′,1′′-terphenyl-2′-carboxylate (8j)
Yellow crystals; method B: yield: 91 mg (64%), mp 111–113 °C.
Pale-yellow powder; method C: yield: 105 mg (71%); mp 143–145 °C.
IR (KBr): 3059, 2978, 2927, 1656, 1598, 1374, 1244, 698 cm–1
.
IR (KBr): 2963, 1683, 1656, 1312, 1261, 1108, 1014, 698 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.80 (t, J = 7.1 Hz, 3 H, CH3), 1.74 (s, 3
H, CH3), 4.03 (q, J = 7.1 Hz, 2 H, CH2), 7.16 (s, 1 H, Harom), 7.22–7.45 (m,
13 H, Harom), 7.91–8.00 (m, 2 H, Harom), 11.20 (s, 1 H, OH).
1H NMR (300 MHz, CDCl3): δ = 0.84 (t, J = 7.2 Hz, 3 H, CH3), 2.23 (s, 3
H, CH3), 4.07 (q, J = 7.2 Hz, 2 H, CH2), 7.02 (s, 1 H, Harom), 7.25–7.52 (m,
13 H, Harom), 7.80–8.94 (m, 2 H, Harom), 11.16 (s, 1 H, OH).
13C NMR (75 MHz, CDCl3): δ = 10.7, 13.0, 61.2, 111.8, 124.5, 126.0 (2
C), 126.8, 127.0, 127.5, 127.6 (2 C), 127.9 (2 C), 128.3 (2 C), 128.7 (2 C),
129.9, 131.0 (2 C), 132.6, 134.1, 135.7, 136.8, 139.4, 143.8, 145.7,
159.0, 159.6, 171.2.
13C NMR (75 MHz, CDCl3): δ = 13.0, 16.1, 61.4, 112.4, 125.2, 126.3 (2
C), 127.1, 127.6, 127.8 (2 C), 128.0 (2 C), 128.2 (2 C), 128.8 (2 C), 129.9,
130.1, 130.2, 130.6 (2 C), 133.4, 135.2, 136.3, 142.4, 143.7, 150.4,
159.1, 166.7, 170.9.
MS (EI, 70 eV): m/z (%) = 475 (100) [M]+.
HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H25NO3S: 492.1628; found:
492.1618.
HRMS (ESI): m/z [M + H]+ calcd for C31H25NO4: 476.1856; found:
476.1846.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

I
V. Z. Shirinian et al.
Paper
Synthesis
5′-Phenyl-5′,6′-dihydro-[1,1′:2′,1′′-terphenyl]-3′(4′H)-one (9)
References
A solution of KOH (112 mg, 2.0 mmol) in H2O (2 mL) was added to a
solution of cyclohexenone 6a (0.4 mmol) in EtOH (2 mL). The result-
ing mixture was refluxed until completion of the reaction (TLC con-
trol), poured into H2O (75 mL), and extracted with EtOAc (3 × 40 mL);
the combined organic phases were washed with brine, dried with
MgSO4, and evaporated under vacuum. The obtained residue was pu-
rified by column chromatography (silica gel, PE–EtOAc, 6:1); this gave
target compound 9.
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Colorless crystals; yield: 95 mg (73%); mp 184–186 °C.
IR (KBr): 3057, 3028, 1669, 1492, 751, 697 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.89–3.14 (m, 4 H, CH2+CH2), 3.57–
3.71 (m, 1 H, CH), 6.94–7.46 (m, 15 H, Harom).
13C NMR (75 MHz, CDCl3): δ = 40.4, 40.9, 44.8, 126.8 (2 C), 126.9,
127.1, 127.7 (2 C), 128.0 (2 C), 128.2 (2 C), 128.5, 128.8 (2 C), 131.0 (2
C), 135.3, 137.6, 140.5, 143.1, 157.0, 198.1.
MS (EI, 70 eV): m/z (%) = 324 (40) [M]+, 220 (100).
HRMS (ESI): m/z [M + H]+ calcd for C24H21O: 325.1587; found:
325.1590.
2′-Benzyl-1,1′:4′,1′′-terphenyl-3′-ol (10)
Cyclohexenone 9 (178 mg, 0.55 mmol) was suspended in EtOH (2 mL),
and benzaldehyde (56 μL, 0.55 mmol) was added; then a solution of
KOH (176 mg, 4.4 mmol) in H2O (1.5 mL) was added. The resulting
mixture was refluxed for 2 h. After completion of the reaction (TLC
control) the reaction mixture was cooled, poured into H2O (75 mL),
and extracted with EtOAc (3 × 40 mL); the combined organic phases
were washed with brine, dried (MgSO4), and evaporated under vacu-
um. The obtained residue was purified by flash chromatography (sili-
ca gel, PE–EtOAc, 15:1); this gave target compound 10.
(5) Ivanov, C.; Tcholakova, T. Synthesis 1981, 392.
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White powder; yield: 79 mg (35%); mp 210–212 °C.
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IR (KBr): 3530, 3056, 3025, 2923, 1599, 1493, 1392, 1262, 756, 700
cm–1
.
1H NMR (300 MHz, CDCl3): δ = 4.13 (s, 2 H, CH2), 5.34 (s, 1 H, OH), 7.05
(s, 1 H, Harom), 7.11–7.42 (m, 20 H, Harom).
13C NMR (75 MHz, CDCl3): δ = 33.3, 123.7, 123.9, 125.6, 126.4, 127.1,
127.5, 127.6 (2 C), 127.8, 128.0 (2 C), 128.1 (2 C), 128.3 (2 C), 129.1 (2
C), 129.3 (2 C), 129.7 (2 C), 131.1 (2 C), 131.4, 135.3, 139.8, 140.9,
141.4, 143.4, 151.4.
MS (EI, 70 eV): m/z (%) = 412 (100) [M]+.
HRMS (ESI): m/z [M + H]+ calcd for C31H25O: 413.1900; found:
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Acknowledgment
Financial support by the Russian Foundation for Basic Research (RFBR
grant 16-33-60013) is gratefully acknowledged.
Supporting Information
(17) CCDC 1498904 contains the supplementary crystallographic
data for this paper. The data can be obtained free of charge from
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588908.
The
Cambridge
Crystallographic
Data
Centre
via
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
www.ccdc.cam.ac.uk/getstructures.
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47, 6315.
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Nabatov, B. V. J. Org. Chem. 2014, 79, 3440.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I