A simple synthesis of benzofurans by acid-catalyzed domino reaction of salicyl alcohols with N-tosylfurfurylamine

Article abstract of DOI:10.1016/j.tet.2017.09.043

A simple route to polysubstituted benzofurans based on the domino reaction of commercial or easily available salicyl alcohols with N-protected furfurylamine has been designed and developed. The reaction was found to proceed with reasonable yields under heating of substrates in acetic acid in the presence of catalytic amount of conc. HCl when tosyl was used as protecting group.

Full text of DOI:10.1016/j.tet.2017.09.043

Accepted Manuscript
A simple synthesis of benzofurans by acid-catalyzed domino reaction of salicyl
alcohols with N-tosylfurfurylamine
Anton A. Merkushev, Vladimir N. Strel'nikov, Maxim G. Uchuskin, Igor V. Trushkov
PII:
S0040-4020(17)30979-1
10.1016/j.tet.2017.09.043
TET 28994
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 June 2017
Revised Date: 18 September 2017
Accepted Date: 25 September 2017
Please cite this article as: Merkushev AA, Strel'nikov VN, Uchuskin MG, Trushkov IV, A simple
synthesis of benzofurans by acid-catalyzed domino reaction of salicyl alcohols with N-tosylfurfurylamine,
Tetrahedron (2017), doi: 10.1016/j.tet.2017.09.043.
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A simple synthesis of benzofurans by acid-
catalyzed domino reaction of salicyl alcohol
with N-tosylfurfurylamine
Leave this area blank for abstract info.
Anton A. Merkushev,a,b Vladimir N. Strel’nikov,b Maxim G. Uchuskin,a,c Igor V. Trushkovc,d
a Perm State University, Bukireva 15, Perm 614990, Russian Federation
b Institute of Technical Chemistry UB RAS, Academica Koroleva 3, Perm 614013, Russian Federation
c RUDN University, Miklukho-Maklaya 6, Moscow 117198, Russian Federation
d Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Samory
Mashela 1, Moscow 117997, Russian Federation

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
A Simple Synthesis of Benzofurans by Acid-Catalyzed Domino Reaction of Salicyl
Alcohols with N-Tosylfurfurylamine
Anton A. Merkusheva,b, Vladimir N. Strel'nikovb, Maxim G. Uchuskina,c and Igor V. Trushkovc,d
aPerm State University, Bukireva 15, Perm 614990, Russian Federation
bInstitute of Technical Chemistry UB RAS, Academica Koroleva 3, Perm 614013, Russian Federation
cRUDN University, Miklukho-Maklaya 6, Moscow 117198, Russian Federation
dDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Samory Mashela 1, Moscow 117997, Russian Federation
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple route to polysubstituted benzofurans based on the domino reaction of commercial or
easily available salicyl alcohols with N-protected furfurylamine has been designed and
developed. The reaction was found to proceed with reasonable yields under heating of substrates
in acetic acid in the presence of catalytic amount of conc. HCl when tosyl was used as protecting
group.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Furan
Benzofurans
Domino reaction
Salicyl alcohols
Bronsted acid catalysis
1. Introduction
Bearing a leaving group at the -position of the side chain,
furans can behave as synthetic equivalents of 1,3-dienes also in
An increasing attention towards furan chemistry during past
few decades is dictated by several reasons. Firstly, the furan core
is the key structural element of a large number of organic
materials, natural products and drugs.1 Secondly, simple furans
are easily available via processing of renewable sources such as
agricultural wastes and other carbohydrate-containing raw
materials.2 This allows one to use furans as inexpensive starting
materials for the synthesis of various useful products. The huge
diversity of such products is provided by the versatile reactivity
of the furan ring; thereby furans can serve as unique building
blocks in organic and medicinal chemistry research.3 They are
widely used as synthetic equivalents of 1,4-dicarbonyl
compounds for the preparation of various acyclic, carbocyclic
and heterocyclic compounds.4 What is more, processes wherein
only a single masked carbonyl groups is involved into new ring
formation, second one being released in a free form, were
developed for the synthesis of diverse heterocyclic products.5
Similarly, containing two C=C bonds, furans can react as either
2π- or 4π-component depending on the reaction partner and
conditions. Namely, furans appear as activated alkenes in [2+4]-,
[2+3]-, [2+2]-, and [2+1]-cycloadditions.6 At the same time,
furans exhibit the reactivity of 1,3-dienes in [4+2]-, [4+3]- and
[4+4]-cycloadditions7 as well as affording 1,4-addition products
in reaction with methanolic bromine and some other
electrophiles.8
reactions with nucleophiles affording products of nucleophilic
attack at the C(5) atom of the furan ring rather than typical
nucleophilic substitution (Scheme 1a). Since the first
announcement of this abnormal reactivity almost 90 years ago,9 a
number of examples of such reactions with various nucleophiles
(alkoxide, phenoxide, sodium diethyl phosphite, CH-acids,
ketene S,S-acetals, indoles etc.) were reported.10 It was shown
that this reaction proceeds through the initial leaving group
departure followed by attack of nucleophile onto the furan C(5)
atom producing 2-methylene-2,5-dihydrofuran intermediate.11
The same two steps are also involved in the Piancatelli
rearrangement.12 The intramolecular version of this anomalous
nucleophilic substitution furnishing substituted spirans was also
investigated (Scheme 1b).13 In some cases, the corresponding
spiroketal derivatives were isolated and it was showed that under
acidic conditions they undergo further rearrangement producing
the corresponding Piancatelli products.14 Wu and Yin used this
transformation in the total synthesis of antifeeding natural
compound tonghaosu and its structural analogues.15
Recently, we described an unusual domino reaction of N-
tosylfurfurylamine with 2-(tosylamino)benzyl alcohols providing
direct access to 2-(2-acylvinyl)indoles,16 an important class of
organic molecules, which could be used as versatile building
blocks for the synthesis of bioactive compounds (Scheme 1c).
This reaction proceeds through the acid-induced elimination of
———
 Corresponding author. Tel.: +7-342-239-6401; fax: +7-342-239-6862; e-mail: mu@psu.ru (Maxim G. Uchuskin)

2
Tetrahedron
ACCEPTED MANUSCRIPT
tosylamide, intramolecular nucleophilic attack on the formed
Metal halides and trifluoromethanesulfonates were found to be
oxonium providing 5-methylene-5H-spiro[furan-2,2'-indoline],
subsequent acid-promoted furan ring opening, and aromatization
of the indole core. We proposed that the use of 2-hydroxybenzyl
alcohols in this domino reaction should provide benzofurans that
would allow for further extending the synthetic concept toward
another class of internal nucleophiles. Herein we report our
development of the general protocol for the synthesis of densely
substituted 2-(2-acylvinyl)benzofurans in a highly stereoselective
manner.
less efficient in the initiation of the studied transformation
(entries 6-10). In the attempt to achieve a better yield of the
desired benzofuran 3a, we have changed the solvent to acetic
acid and screened several Bronsted acids again (entries 11-16).
We found that the best yield of 3a was observed when conc. HCl
was applied for the transformation (entry 16). Further variation of
the ratio of the reacting compounds, temperature and HCl loading
had no positive influence on the yield of the target benzofuran
3a.
Scheme 1. Nucleophilic Conjugate Substitution of furfuryl
derivatives
Under the optimized conditions, we have screened a series of
furans containing leaving groups of a different nature. The
furfurylamine 2b and its derivatives 2c-e, furfuryl alcohol 2f and
its derivatives 2g-j and 5-(furan-2-ylmethyl)-2,2-dimethyl-1,3-
dioxane-4,6-dione 2k applied to this reaction. We have found
that only N-tosylfurfurylamine 2a has a good balance between
the stability in the first step of the domino reaction (Friedel-
Crafts alkylation) and reactivity in the leaving group elimination.
On the contrary, furans 2b-k gave either products of Piancatelli
rearrangement or significant tarring of the reaction mixture.
Therefore, the optimal reaction procedure can be summarized as
follows: 2-hydroxybenzyl alcohol 1 is heated under reflux with
N-tosylfurfurylamine 2a (1.2 eq.) in acetic acid containing conc.
HCl (1 eq.) for 1 h under air atmosphere. Furthermore, we have
successfully carried out the studied reaction using 1 mmol of
starting alcohol 1 and obtained the desired product 3a in 56%
yield. Thus, the reaction can be easily scaled up without the loss
of efficiency. It is worth noting that the benzofuran 3a was
2. Results/Discussion
The reaction of 2-hydroxybenzhydryl alcohol 1a with N-
tosylfurfurylamine 2a was selected as a model process for the
optimization of reaction conditions. Based on our previous
findings, benzofuran 3a was expected to be formed under acidic
conditions.16 The initial experiment showed that heating of
starting compounds with H3PO4 in toluene under reflux afforded
target product 3a in low yield (Table 1, entry 1). Encouraged by
this result, we have screened various Brønsted and Lewis acids
using the same solvent and temperature regime and found that the
yield of product could be improved to 40% when TMSCl was
used (Table 1, entry 5).
3
obtained as a single (E)-isomer as deduced on the basis of J
values for the olefinic protons.17
Table 2. Screening of leaving groups in furfuryl derivatives
Entry[a]
Furan 2
2a
LG
TsNH
NH2
Yield of 3a (%)[b]
1
2
58 (56[c])
traces
ND
2b
2c
Table 1. Screening of reaction conditions
3
PhNH
BnNH
Bn2N
4
2d
2e
traces
traces
20
5
6
2f
HO
7
2g
PhO
27
Entry[a]
1
Acid
H3PO4
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
AcOH
Time (h)
Yield of 3a (%)[b]
8
2h
2i
4-MeC6H4O
4-ClC6H4O
TsO
29
9
30
0.5
12
12
0.5
24
6
16
25
32
22
40
33
30
28
21
26
16
24
27
25
21
58
10
2j
ND
2
AcOH
3
TFA
11
2k
ND
4
H2SO4
5
TMSCl
Yb(OTf)3
CuBr2
[a]Reaction was performed at 0.1 mmol scale of 1a with 1.2 eq.
of 2a and 1 eq. of acid. [b]Conversion and yield was detected
by GS-MS with an internal standard. [c]Reaction was
performed at 1 mmol scale. Isolated yield.
6[c]
7[c]
8[c]
9[c]
10[c]
11
12
13
14
15
16
3
Cu(OTf)2
PdCl2
0.5
3
With the optimized conditions in hand, we next examined the
scope of the reaction. We have found that the reaction of various
salicyl alcohols 1 with 2a led to the formation of benzofurans 3a-
o in moderate to good yields (Table 3). Various functional groups
at the para-, meta- or ortho-positions of the starting salicyl
alcohols (1a-c,e-j,l-n) were found to be well tolerated under the
optimized reaction conditions. More electron-deficient salicylic
alcohol 1k (R3 = Cl) afforded benzofuran 3k in moderate yield. A
similar effect was previously observed in the reaction of N-
tosylfurfurylamine with 2-(tosylamino)benzyl alcohols and could
be explained by the reduced nucleophilicity of the corresponding
AgOTf
-
0.5
1
2-O2NC6H4CO2H
TSA
AcOH
6
AcOH
0.5
6
Amberlyst 15
H2SO4
AcOH
AcOH
0.5
1
HCl
AcOH
[a]Reaction was performed at 0.1 mmol scale of 1a with 1.2 eq. of 2a and 1
eq. of acid. [b]Conversion and yield was detected by GS-MS with an internal
standard. [c]20 mol. % of catalyst was used.

3
substrate.16 Salicyl alcohol 1d bearing branched alkyl substituent
at the α-position was found to be unsuitable substrate for the
discussed reaction on the contrary to benzhydryl alcohols; the
corresponding benzofuran 3d was isolated in 35% yield only.
The moderate yield of product 3d could be explained by the side
intramolecular cyclodehydration affording to 2,2-dimethyl-2,3-
dihydro-1-benzofuran.18 Nevertheless, 3-alkyl-2-(2-acylvinyl)-
benzofuran 3o was obtained in reasonable yield starting from
salicyl alcohol 1o possessing electron-donating substituents.
appropriately located amine moiety on the ipso carbon atom of
ACCEPTED MANUSCRIPT
the furan ring, dihydrofuran ring opening and benzofuran
aromatization.
4. Experimental
4.1. General Information
NMR spectra were recorded with a «Bruker Avance III HD
400» (400 MHz for 1H and 100 MHz for 13C NMR) spectrometer
at room temperature; the chemical shifts (δ) were measured in
ppm with respect to the solvent (CDCl3, 1Н: δ = 7.26 ppm, 13C: δ
= 77.16 ppm; DMSO-d6, 1Н: δ = 2.50 ppm, 13C: δ = 39.52 ppm).
Coupling constants (J) are given in Hertz. Splitting patterns of an
apparent multiplets associated with an averaged coupling
constants were designated as s (singlet), d (doublet), t (triplet), q
(quartet), sept (septet), m (multiplet), dd (doublet of doublets)
and br (broadened). IR spectra were measured in nujol using a
«FSM 1202» spectrophotometer. High-resolution mass
measurements were carried out using a BrukermicroTOF-QTM
ESI-TOF (Electro Spray Ionization/Time of Flight) mass
spectrometer. GC/MS analysis was performed on an «Agilent
7890В» interfaced to an «Agilent 5977А» mass selective
detector. Melting points were determined with a «Stuart SMP
30», the values are uncorrected. Column chromatography was
performed on silica gel Macherey Nagel (40-63 μm). Starting
furans 2 were synthesized according to published procedures.17b,19
All the reactions were carried out using freshly distilled and dry
solvents from solvent stills.
Table 3. Scope of the acid-catalyzed synthesis of benzofurans[a]
Entry 1,3
R1
H
R2
H
H
H
H
H
H
R3
H
R4
Ph
Yield of 3 (%)[b]
1
2
a
b
c
56
55
54
35
60
58
55
58
58
57
46
55
60
53
57
H
H
4-MeC6H4
4-MeOC6H4
i-Pr
3
H
H
4
d
e
H
H
5
Me
Me
Br
Br
H
Ph
6
f
4-MeC6H4
Ph
7
g
h
i
Me Me
Me Me
8
H
4-MeC6H4
Ph
9
H
H
H
H
H
H
H
Me
Me
H
Me
Me
Cl
10
11
12
13
14
15
j
4-MeC6H4
Ph
k
l
H
Me
Me
Br
MeO
Ph
4.2. General procedure for the synthesis of starting salicylic
m
n
o
H
4-MeC6H4
Ph
alcohols 1.
H
H
Me
To a solution of Grignard reagent (4 mmol) in dry ether (4
mL) a solution of corresponding salicylaldehyde (2 mmol) in dry
ether (2 mL) was added dropwise. The mixture was stirred for 60
minutes (TLC control) and then a saturated solution of aq. NH4Cl
(5 mL) was added slowly. The layers were separated and the
aqueous layer was extracted with ethyl acetate (2  3 mL). The
combined organic fractions washed with water (2  5 mL), brine
(2 × 5 mL), dried with Na2SO4 and evaporated to dryness. The
residue was dissolved in ethyl acetate/petroleum ether mixture,
passed through thin layer of silica gel and left to crystallization.
[a]Reaction was performed at 1 mmol scale. [b] Isolated yield.
The proposed reaction mechanism for rearrangement is given
in Scheme 2. This includes Friedel-Crafts alkylation of N-
tosylfurfurylamine 2a with 2-hydroxybenzyl alcohol 1 to form
intermediate 2-(2-hydroxybenzyl)furan A. Then subsequent acid-
initiated elimination of TsNH2 produces intermediate B;
intramolecular nucleophilic attack of the phenolic hydroxyl
moiety onto the ipso-carbon atom of the furan ring affords spiro-
conjugated species C, protonation of which induces dihydrofuran
ring opening and aromatization of the benzofuran core. Fast acid-
catalyzed isomerization of (Z)-3 to (E)-isomer accomplishes the
formation of (E)-3.
4.2.1. 2-[Hydroxy(phenyl)methyl]phenol (1a)20
White solid (340 mg, 85% yield); mp 90–91 °C (ethyl
acetate/petroleum ether), lit. 84–86 °C; 1H NMR (400 MHz,
CDCl3) δ 7.82 (br.s, 1H, OH), 7.40–7.30 (m, 5H, HAr), 7.21–7.17
(m, 1H, HAr), 6.90–6.87 (m, 2H, HAr), 6.84–6.80 (m, 1H, HAr),
6.00 (s, 1H, CH), 3.03 (br.s, 1H, OH); 13C NMR (100 MHz,
CDCl3) δ 155.6, 142.1, 129.4, 128.9 (2C), 128.4, 128.3, 127.0
(2C), 126.9, 120.1, 117.4, 77.1.
Scheme 2. Proposed reaction mechanism
4.2.2. 2-[Hydroxy(4-methylphenyl)methyl]phenol (1b)20
White solid (368 mg, 86% yield); mp 104–105 °C (ethyl
acetate/petroleum ether), lit. 94–96 °C; 1H NMR (400 MHz,
CDCl3) δ 7.86 (br.s, 1H, OH), 7.32–7.28 (m, 3H, HAr), 7.21–7.19
(m, 2H, HAr), 6.94–6.88 (m, 2H, HAr), 6.84–6.81 (m, 1H, HAr),
6.02 (s, 1H, CH), 2.73 (br.s, 1H, OH), 2.38 (s, 3H, CH3); 13C
NMR (100 MHz, CDCl3) δ 155.8, 139.2, 138.3, 129.6 (2C),
129.4, 128.4, 127.0 (2C), 126.8, 120.0, 117.5, 77.3, 21.3.
3. Conclusion
In conclusion, we have developed an acid-catalyzed domino
reaction of salicylic alcohols with N-tosylfurfurylamine to afford
2-(2-acylvinyl)benzofurans. This novel and simple method
provides easily accessible starting compounds, a general and
straightforward route to prepare densely substituted benzofurans
via Friedel-Crafts alkylation step, acid-induced leaving group
elimination followed by intramolecular nucleophilic attack of the
4.2.3. 2-[Hydroxy(4-methoxyphenyl)methyl]phenol (1c)21
Colorless oil (396 mg, 86% yield); 1H NMR (400 MHz,
CDCl3) δ 7.91 (br.s, 1H, OH), 7.28–7.23 (m, 2H, HAr), 6.98–6.95
(m, 2H, HAr), 6.89–6.87 (m, 4H, HAr), 5.65 (s, 1H, CH), 3.79 (s,
3H, OCH3), 2.75 (br.s, 1H, OH); 13C NMR (100 MHz, CDCl3) δ

4
Tetrahedron
159.8, 154.9, 131.9, 129.8, 129.4, 129.0 (2C), 128.5 (2C),
142.5, 137.8, 129.3, 128.8 (2C), 128.2, 127.9, 126.9 (2C), 124.1,
ACCEPTED MANUSCRIPT
120.6, 117.4, 114.4, 77.1, 55.4.
118.6, 76.9, 19.6, 18.8; IR (nujol, v/cm-1): 3337, 3168, 1618,
1494, 1408, 1281, 1227, 1198, 1186, 1069, 1007; HRMS (ESI)
4.2.4. 2-(1-Hydroxy-2-methylpropyl)phenol (1d)22
calcd for C15H15O+ [M-OH]+ 211.1117, found 211.1113.
White solid (282 mg, 85% yield); mp 50–51 °C (ethyl
acetate/petroleum ether), lit. 48–49 °C; 1H NMR (400 MHz,
CDCl3) δ 7.99 (br.s, 1H, OH), 7.18–7.14 (m, 1H, HAr), 6.92–6.89
4.2.10. 2-[Hydroxy(4-methylphenyl)methyl]-4,5-dimethylphenol
(1j)
3
White solid (407 mg, 84% yield); mp 89–91 °C (ethyl
(m, 1H, HAr), 6.86–6.79 (m, 2H, HAr), 4.51 (d, J = 6.8 Hz, 1H,
1
3
acetate/petroleum ether); H NMR (400 MHz, DMSO-d63) δ 8.91
CH), 2.73 (br.s, 1H, OH), 2.11 (m, 1H, CH), 1.05 (d, J = 6.8 Hz,
3
3
3H, CH3), 0.86 (d, J = 6.8 Hz, 3H, CH3); 13C NMR (100 MHz,
(br.s, 1H, OH), 7.21 (d, J = 7.8 Hz, 2H, HAr), 7.05 (d, J = 7.8
Hz, 2H, HAr), 7.02 (s, 1H, HAr), 6.53 (s, 1H, HAr), 5.88 (s, 1H,
CH), 5.49 (br.s, 1H, OH), 2.24 (s, 3H, CH3), 2.09 (s, 3H, CH3),
2.07 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ 151.5,
142.8, 135.0, 134.7, 128.7, 128.1 (2C), 127.8, 126.0 (2C), 125.7,
116.3, 68.3, 20.5, 19.0, 18.5; IR (nujol, v/cm-1): 3341, 3102,
1508, 1339, 1277, 1188, 1072, 1000; HRMS (ESI) calcd for
C16H17O+ [M-OH]+ 225.1274, found 225.1271.
CDCl3) δ 155.9, 128.9, 128.4, 126.3, 119.5, 117.3, 82.2, 34.5,
19.4, 18.3.
4.2.5. 4-Bromo-2-[hydroxy(phenyl)methyl]-6-methylphenol (1e)
White solid (504 mg, 86% yield); mp 126–127 °C (ethyl
1
acetate/petroleum ether); H NMR (400 MHz, CDCl3) δ 8.01
(br.s, 1H, OH), 7.38–7.31 (m, 5H, HAr), 7.19 (s, 1H, HAr), 6.83 (s,
1H, HAr), 5.93 (s, 1H, CH), 2.88 (br.s, 1H, OH), 2.22 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3) δ 153.1, 141.4, 133.2, 129.1
(2C), 128.8, 128.7, 128.5, 127.8, 126.9 (2C), 111.5, 77.0, 15.8;
IR (nujol, v/cm-1): 3382, 3288, 1496, 1418, 1333, 1254, 1217,
1204, 1036; HRMS (ESI) calcd for C14H12BrO+ [M-OH]+
275.0066, found 275.0067.
4.2.11. 4-Chloro-2-(hydroxy(phenyl)methyl)phenol (1k)23
White solid (427 mg, 86% yield); mp 87–88 °C (ethyl
1
acetate/petroleum ether), lit. 89–90.5 °C; H NMR (400 MHz,
CDCl3) δ 7.84 (br.s, 1H, OH), 7.40–7.32 (m, 5H, HAr), 7.15–7.12
(m, 1H, HAr), 6.84–6.82 (m, 2H, HAr), 5.97 (s, 1H, CH), 2.80
(br.s, 1H, OH); 13C NMR (100 MHz, CDCl3) δ 154.4, 141.4,
129.3, 129.1 (2C), 128.8, 128.2, 128.1, 127.0 (2C), 125.0, 118.9,
76.9.
4.2.6.
4-Bromo-2-[hydroxy(4-methylphenyl)methyl]-6-methyl-
phenol (1f)
White solid (mg, 87% yield); mp 121–122 °C (ethyl
1
acetate/petroleum ether); H NMR (400 MHz, CDCl3) δ 8.09
4.2.12. 2-[Hydroxy(phenyl)methyl]-4-methylphenol (1l)24
White solid (360 mg, 84% yield); mp 96–97 °C (ethyl
acetate/petroleum ether), lit 98–100 °C;24 1H NMR (400 MHz,
CDCl3) δ 7.51 (br.s, 1H, OH), 7.41–7.30 (m, 5H, HAr), 6.99 (br.d,
(br.s, 1H, OH), 7.28–7.26 (m, 2H, HAr), 7.21–7.19 (m, 3H, HAr),
6.83–6.82 (m, 1H, HAr), 5.90 (s, 1H, CH), 2.81 (br.s, 1H, OH),
2.38 (s, 3H, CH3), 2.24 (s, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ 153.2, 138.6, 138.5, 133.1, 129.7 (2C), 128.7, 128.5,
127.9, 126.9 (2C), 111.4, 77.0, 21.3, 15.8; IR (nujol, v/cm-1):
3410, 3208, 1512, 1253, 1213, 1177, 1033; HRMS (ESI) calcd
for C15H14BrO+ [M-OH]+ 289.0223, found 289.0223.
3
3J = 8.2 Hz, 1H, HAr), 6.80 (d, J = 8.2 Hz, 1H, HAr), 6.70 (br.s,
1H, HAr), 5.96 (s, 1H, CH), 2.82 (br.s, 1H, OH), 2.21 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3) δ 153.3, 142.2, 129.9, 129.3,
128.9 (2C), 128.8, 128.3, 127.0 (2C), 126.5, 117.3, 77.2, 20.6.
4.2.7. 6-[Hydroxy(phenyl)methyl]-2,3-dimethylphenol (1g)
White solid (365 mg, 80% yield); mp 101–103 °C (ethyl
acetate/petroleum ether); H NMR (400 MHz, DMSO-d6) δ 8.73
4.2.13. 2-[Hydroxy(4-methylphenyl)methyl]-4-methylphenol (1m)
White solid (410 mg, 90%); mp 93–94 °C (ethyl
1
1
acetate/petroleum ether); H NMR (400 MHz, DMSO-d64) δ 9.04
3
(br.s, 1H, OH), 7.38–7.36 (m, 2H, HAr), 7.31–7.27 (m, 2H, HAr),
7.22–7.18 (m, 1H, HAr), 6.89 (d, 3J = 7.8 Hz, 1H, HAr), 6.62 (d, 3J
= 7.8 Hz, 1H, HAr), 6.41 (br.s, 1H, OH), 5.96 (s, 1H, CH), 2.16
(s, 3H, CH3), 2.07 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6)
δ 152.3, 144.7, 135.7, 127.8 (2C), 127.6, 126.6, 126.2 (2C),
124.0, 123.0, 120.5, 72.0, 19.6, 11.6; IR (nujol, v/cm−1): 3432,
3185, 1687, 1667, 1595, 1294, 1262, 1244, 1206, 1165, 1080;
HRMS (ESI) calcd for C15H15O+ [M-OH]+ 211.1117, found
211.1118.
(br.s, 1H, OH), 7.24 (d, J = 7.9 Hz, 2H, HAr), 7.12 (d, J = 1.6
3
3
Hz, 1H, HAr), 7.06 (d, J = 7.9 Hz, 2H, HAr), 6.82 (dd, J = 8.1
Hz, 4J = 1.6 Hz, 1H, HAr), 6.65 (d, 3J = 8.1 Hz, 1H, HAr), 5.93 (d,
3J = 3.8 Hz, 1H, CH), 5.54 (d, J = 3.8 Hz, 1H, OH), 2.25 (s, 3H,
3
CH3), 2.17 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ
151.4, 142.6, 135.2, 131.4, 128.2 (2C), 127.6, 127.2, 127.0, 126.1
(2C), 114.8, 68.3, 20.5, 20.3; IR (nujol, v/cm-1): 3375, 3325,
1598, 1512, 1499, 1418, 1239, 1224, 1197, 1174, 1144, 1035;
HRMS (ESI) calcd for C15H15O+ [M-OH]+ 211.1117, found
211.1119.
4.2.8. 6-[Hydroxy(4-methylphenyl)methyl]-2,3-dimethylphenol
(1h)
4.2.14. 4-Bromo-2-[hydroxy(phenyl)methyl]phenol (1n)
White solid (411 mg, 85% yield); mp 122–123 °C (ethyl
White solid (452 mg, 81% yield); mp 104–105 °C (ethyl
acetate/petroleum ether); H NMR (400 MHz, CDCl3) δ 7.85
1
1
acetate/petroleum ether); H NMR (400 MHz, DMSO-d63) δ 8.72
3
(br.s, 1H, OH), 7.23 (d, J = 7.4 Hz, 2H, HAr), 7.09 (d, J = 7.4
(br.s, 1H, OH), 7.40–7.33 (m, 5H, HAr), 7.29–7.27 (m, 1H, HAr),
6.99–6.98 (m, 1H, HAr), 6.80–6.78 (m, 1H, HAr), 5.98 (s, 1H,
CH), 2.74 (br.s, 1H, OH); 13C NMR (100 MHz, CDCl3) δ 155.0,
141.4, 132.2, 131.0, 129.2 (2C), 128.9, 128.6, 127.0 (2C), 119.4,
112.0, 76.5; IR (nujol, v/cm-1): 3434, 3220, 1580, 1485, 1238,
1165, 1108, 1078, 1037, 1023; HRMS (ESI) calcd for
C13H10BrO+ [M-OH]+ 260.9910, found 260.9912.
Hz, 2H, HAr), 6.84 (d, 3J = 7.7 Hz, 1H, HAr), 6.59 (d, 3J = 7.7 Hz,
1H, HAr), 6.38 (br.s, 1H, OH), 5.89 (s, 1H, CH), 2.26 (s, 3H,
CH3), 2.16 (s, 3H, CH3), 2.05 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6) δ 152.3, 141.7, 135.6, 135.5, 128.3 (2C), 127.5, 126.2
(2C), 124.0, 122.9, 120.4, 72.1, 20.5, 19.6, 11.5; IR (nujol,
v/cm−1): 3399, 3317, 1580, 1511, 1249, 1224, 1172, 1082, 1029;
HRMS (ESI) calcd for C16H17O+ [M-OH]+ 225.1274, found
225.1271.
4.2.15. 2-(1-Hydroxyethyl)-4-methoxyphenol (1o)20
1
Yellow oil (289 mg, 86% yield); H NMR (400 MHz, CDCl3)
3
δ 7.35 (br.s, 1H, OH), 6.79 (d, J = 8.8 Hz, 1H, HAr), 6.72 (dd, 3J
4.2.9. 2-[Hydroxy(phenyl)methyl]-4,5-dimethylphenol (1i)
White solid (369 mg, 81% yield); mp 124–125 °C (ethyl
4
4
= 8.8 Hz, J = 2.9 Hz, 1H, HAr), 6.57 (d, J = 2.9 Hz, 1H, HAr),
5.02 (q, 3J = 6.6 Hz, 1H, CH), 3.74 (s, 3H, OCH3), 2.46 (br.s, 1H,
OH), 1.58 (d, 3J = 6.6 Hz, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ 153.2, 149.4, 129.4, 117.8, 114.0, 112.6, 71.6, 56.0,
23.5.
1
acetate/petroleum ether); H NMR (400 MHz, CDCl3) δ 7.51
(br.s, 1H, OH), 7.41–7.29 (m, 5H, HAr), 6.69 (s, 1H, HAr), 6.64 (s,
1H, HAr), 5.93 (s, 1H, CH), 2.96 (br.s, 1H, OH), 2.20 (s, 3H,
CH3), 2.12 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ 153.3,

5
4.3. General procedure for synthesis of benzofurans 3.
128.6, 127.8, 126.7, 125.1, 123.9, 120.2, 116.0, 28.1, 14.1; IR
ACCEPTED MANUSCRIPT
(nujol, v/cm-1): 1688, 1605, 1553, 1356, 1325, 1300, 1261, 1200,
1167; HRMS (ESI) calcd. for C19H16BrO2 [M+H]+ 355.0328,
+
A conc. HCl (12 M, 30 μl) was added to a solution of salicyl
alcohol 1 (1 mmol) and N-(furan-2-ylmethyl)-4-methylbenzene-
sulfonamide 2a (1.1 mmol, 276 mg) in glacial AcOH (5 ml). The
reaction mixture was stirred at 120 °C for 1 h (TLC control), then
evaporated to dryness under reduced pressure. After purification
by column chromatography on silica gel using CH2Cl2/petroleum
ether mixture (1:9) as an eluent, products was obtained as oils.
found 355.0324.
4.3.6. (3E)-4-[5-Bromo-7-methyl-3-(4-methylphenyl)-1-
benzofuran-2-yl]but-3-en-2-one (3f)
1
Pale orange oil (213 mg, 58% yield); H NMR (400 MHz,
DMSO-d6) δ 7.55 (br.s, 1H, HAr), 7.48–7.37 (m, 5H, HAr), 7.35
3
3
(d, J = 15.8 Hz, 1H, CH), 6.89 (d, J = 15.8 Hz, 1H, CH), 2.52
(s, 3H, CH3), 2.41 (s, 3H, CH3), 2.32 (s, 3H, CH3); 13C NMR
(100 MHz, DMSO-d6) δ 196.9, 152.0, 148.3, 138.3 (2С), 130.3,
129.9 (2C), 129.0 (2C), 127.6, 126.9, 126.8, 125.2, 123.9, 120.3,
116.0, 28.1, 20.8, 14.1; IR (nujol, v/cm-1): 1690, 1607, 1508,
1402, 1354, 1323, 1300, 1263, 1196, 1169, 1115; HRMS (ESI)
calcd. for C20H18BrO2+ [M+H]+ 369.0485, found 369.0485.
4.3.1. (3E)-4-(3-Phenyl-1-benzofuran-2-yl)but-3-en-2-one (3a)
Yellow oil (147 mg, 56% yield); 1H NMR (400 MHz, DMSO-
d6) δ 7.65–7.62 (m, 2H, HAr), 7.60–7.54 (m, 4H, HAr), 7.52–7.49
3
(m, 1H, HAr), 7.47–7.45 (m, 1H, HAr), 7.36 (d, J = 15.8 Hz, 1H,
3
CH), 7.31–7.29 (m, 1H, HAr), 6.85 (d, J = 15.8 Hz, 1H, CH),
2.29 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ 196.9,
154.2, 147.6, 130.2, 129.3 (2C), 129.2 (2C), 128.5, 127.5, 127.4,
127.1, 127.0, 125.8, 123.8, 120.7, 111.5, 28.2; IR (nujol, v/cm-1):
1688, 1664, 1614, 1597, 1572, 1359, 1281, 1250, 1204, 1165;
4.3.7. (3E)-4-(6,7-Dimethyl-3-phenyl-1-benzofuran-2-yl)but-3-
en-2-one (3g)
Yellow oil (160 mg, 55% yield); 1H NMR (400 MHz, DMSO-
d6) δ 7.61–7.55 (m, 4H, HAr), 7.52–7.49 (m, 1H, HAr), 7.40–7.36
+
HRMS (ESI) calcd. for C18H15O2 [M+H]+ 263.1067, found
263.1071.
3
(m, 2H, HAr+CH), 7.16–7.14 (m, 1H, HAr), 6.89 (d, J = 15.6 Hz,
4.3.2. (3E)-4-[3-(4-Methylphenyl)-1-benzofuran-2-yl]but-3-en-2-
1H, CH), 2.45 (s, 3H, CH3), 2.38 (s, 3H, CH3), 2.32 (s, 3H, CH3);
13C NMR (100 MHz, DMSO-d6) δ 196.8, 153.6, 146.9, 135.9,
130.5, 129.1 (2C), 129.0 (2C), 128.4, 127.3, 126.4, 126.3, 125.9,
124.9, 119.5, 117.2, 28.1, 18.9, 11.2; IR (nujol, v/cm-1): 1667,
1595, 1294, 1242, 1206, 1165, 1079; HRMS (ESI) calcd. for
C20H19O2+ [M+H]+ 291.1380, found 291.1382.
one (3b)
1
Yellow oil (152 mg, 55% yield); H NMR (400 MHz, CDCl3)
δ 7.66–7.64 (m, 1H, HAr), 7.53–7.50 (m, 1Н, HAr), 7.51 (d, J =
3
15.7 Hz, 1H, CH), 7.44–7.40 (m, 3H, HAr), 7.36–7.34 (m, 2H,
3
HAr), 7.30–7.28 (m, 1H, HAr), 6.96 (d, J = 15.7 Hz, 1H, CH),
2.46 (s, 3H, CH3), 2.35 (s, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ 197.7, 155.1, 148.3, 138.6, 130.0 (2C), 129.5 (2C),
128.7, 128.6, 128.3, 127.2, 127.0, 126.9, 123.6, 121.2, 111.6,
28.5, 21.5; IR (nujol, v/cm-1): 1686, 1661, 1599, 1360, 1281,
4.3.8. (3E)-4-[6,7-Dimethyl-3-(4-methylphenyl)-1-benzofuran-2-
yl]but-3-en-2-one (3h)
1
Pale orange oil (176 mg, 58% yield); H NMR (400 MHz,
+
DMSO-d6) δ 7.47–7.45 (m, 2H, HAr), 7.41–7.35 (m, 4H,
1254, 1205, 1186, 1167; HRMS (ESI) calcd. for C19H17O2
3
[M+H]+ 277.1223, found 277.1221.
HAr+CH), 7.16–7.14 (m, 1H, HAr), 6.87 (d, J = 15.7 Hz, 1H,
CH), 2.45 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.39 (s, 3H, CH3),
2.32 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ 196.8,
153.6, 146.7, 137.9, 135.8, 129.7 (2С), 129.0 (2С), 127.6, 127.5,
126.4, 126.2, 125.8, 125.0, 119.5, 117.3, 28.0, 20.7, 18.9, 11.2;
IR (nujol, v/cm-1): 1674, 1607, 1589, 1311, 1261, 1162; HRMS
(ESI) calcd. for C21H21O2+ [M+H]+ 305.1536, found 305.1533.
4.3.3. (3E)-4-[3-(4-Methoxyphenyl)-1-benzofuran-2-yl]but-3-en-
2-one (3c)
1
Pale orange oil (158 mg, 54% yield); H NMR (400 MHz,
DMSO-d6) δ 7.66 (d, J = 8.2 Hz, 2H, HAr), 7.55–7.53 (m, 2H,
HAr), 7.52–7.48 (m, 1H, HAr), 7.39 (d, J = 15.8 Hz, 1H, CH),
3
3
7.35–7.33 (m, 1H, HAr), 7.17 (d, 3J = 8.2 Hz, 2H, HAr), 6.86 (d, 3J
= 15.8 Hz, 1H, CH), 3.86 (s, 3H, CH3), 2.32 (s, 3H, CH3); 13C
NMR (100 MHz, DMSO-d6) δ 196.8, 159.5, 154.2, 147.3, 130.5
(2C), 127.6, 127.3, 127.2, 126.6, 125.7, 123.7, 122.3, 120.7,
114.8 (2C), 111.4, 55.2, 28.1; IR (nujol, v/cm-1): 1691, 1601,
1570, 1556, 1510, 1360, 1288, 1271, 1248, 1207, 1165, 1113,
1034, 1014; HRMS (ESI) calcd. for C19H17O3+ [M+H]+ 293.1172,
found 293.1174.
4.3.9. (3E)-4-(5,6-Dimethyl-3-phenyl-1-benzofuran-2-yl)but-3-
en-2-one (3i)
Yellow oil (168 mg, 58% yield); 1H NMR (400 MHz, DMSO-
d6) δ 7.62–7.56 (m, 4H, HAr), 7.53–7.49 (m, 1H, HAr), 7.46 (s,
3
1H, HAr), 7.42 (s, 1H, HAr), 7.36 (d, J = 15.8 Hz, 1H, CH), 6.82
3
(d, J = 15.8 Hz, 1H, CH), 2.37 (s, 3H, CH3), 2.30 (s, 6H, 2 ×
CH3); 13C NMR (100 MHz, DMSO-d6) δ 196.8, 153.2, 146.9,
137.0, 132.4, 130.5, 129.2 (2C), 129.1 (2C), 128.4, 127.2, 126.2,
125.8, 125.4, 120.4, 111.6, 28.1, 20.1, 19.3; IR (nujol, v/cm-1):
1664, 1593, 1302, 1254, 1221, 1167; HRMS (ESI) calcd. for
C20H19O2+ [M+H]+ 291.1380, found 291.1376.
4.3.4. (3E)-4-[3-(1-Methylethyl)-1-benzofuran-2-yl]but-3-en-2-
one (3d)
1
Pale orange oil (80 mg, 35% yield); H NMR (400 MHz,
DMSO-d6) δ 7.85–7.83 (m, 1H, HAr), 7.64 (d, J = 15.8 Hz, 1H,
3
4.3.10. (3E)-4-[5,6-Dimethyl-3-(4-methylphenyl)-1-benzofuran-
2-yl]but-3-en-2-one (3j)
CH), 7.58–7.56 (m, 1H, HAr), 7.43–7.39 (m, 1H, HAr), 7.29–7.25
3
(m, 1H, HAr), 6.68 (d, J = 15.8 Hz, 1H, CH), 3.51–3.44 (m, 1H,
Yellow oil (173 mg, 57% yield); 1H NMR (400 MHz, DMSO-
3
CH), 2.37 (s, 3H, CH3), 1.41 (d, J = 7.0 Hz, 6H, 2 × CH3); 13C
3
d6) δ 7.48–7.46 (m, 3H, HAr), 7.41–7.40 (m, 3H, HAr), 7.35 (d, J
NMR (100 MHz, DMSO-d6) δ 197.4, 154.5, 146.3, 131.3, 127.4,
127.1, 126.8, 126.0, 123.0, 121.9, 111.5, 27.6, 24.7, 22.3 (2C);
IR (nujol, v/cm-1): 1688, 1664, 1605, 1273, 1258, 1165, 1040;
3
= 15.8 Hz, 1H, CH), 6.80 (d, J = 15.8 Hz, 1H, CH), 2.41 (s, 3H,
CH3), 2.37 (s, 3H, CH3), 2.30 (s, 6H, 2 × CH3); 13C NMR (100
MHz, DMSO-d6) δ 196.8, 153.2, 146.8, 137.9, 137.0, 132.4,
129.8 (2C), 129.0 (2C), 127.5, 127.4, 126.0, 125.9, 125.5, 120.5,
111.6, 28.0, 20.7, 20.1, 19.4; IR (nujol, v/cm-1): 1663, 1612,
+
HRMS (ESI) calcd. for C15H17O2 [M+H]+ 229.1223, found
229.1219.
+
4.3.5. (3E)-4-(5-Bromo-7-methyl-3-phenyl-1-benzofuran-2-
yl)but-3-en-2-one (3e)
1593, 1304, 1256, 1167; HRMS (ESI) calcd. for C21H21O2
[M+H]+ 305.1536, found 305.1534.
Yellow oil (212 mg, 60% yield); 1H NMR (400 MHz, DMSO-
3
4.3.11. (3E)-4-(5-Chloro-3-phenyl-1-benzofuran-2-yl)but-3-en-2-
d6) δ 7.61–7.52 (m, 6H, HAr3), 7.49 (br.s, 1H, HAr), 7.36 (d, J =
one (3k)
15.8 Hz, 1H, CH), 6.92 (d, J = 15.8 Hz, 1H, CH), 2.53 (s, 3H,
CH3), 2.33 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ
196.9, 152.0, 148.5, 130.3, 129.7, 129.3 (2C), 129.1 (2C), 128.9,
1
Pale orange oil (136 mg, 46% yield); H NMR (400 MHz,
DMSO-d6) δ 7.74–7.72 (m, 1H, HAr), 7.65 (br.s, 1H, HAr), 7.62–

6
Tetrahedron
3, 6244; (d) Bohre, A.; Dutta, S.; Saha, B.; Abu-Omar, M. M. ACS
7.59 (m, 4H, H ), 7.53–7.51 (m, 1H, H ), 7.38–7.34 (m, 2H,
ACCEPTED MANUSCRIPT
Ar
Ar
HAr+CH), 6.90 (d, J = 15.8 Hz, 1H, CH), 2.33 (s, 3H, CH3); 13
C
3
Sustain. Chem. Eng. 2015, 3, 1263; (e) Teong, S. P.; Yi, G. S.;
Zhang, Y. G. Green Chem. 2014, 16, 2015; (f) Boto, A.; Alvarez,
L. Furan and Its Derivatives. In Heterocycles in Natural Product
NMR (100 MHz, DMSO-d6) δ 197.0, 152.7, 149.1, 129.6, 129.4
(2C), 129.3 (2C), 129.0, 128.8, 128.5, 128.0, 127.4, 126.7, 125.0,
120.0, 113.3, 28.3; IR (nujol, v/cm-1): 1671, 1607, 1259, 1164,
Synthesis, Wiley-VCH Verlag GmbH
& Co. KGaA: 2011;
97−152.
1064; HRMS (ESI) calcd. for C18H14ClO2 [M+H]+ 297.0677,
+
2. (a) Mariscal, R.; Maireles-Torres, P.; Ojeda, M.; Sádaba, I.; López
Granados, M. Energy Environ. Sci. 2016, 9, 1144; (b) Dutta, S.;
De, S.; Saha, B.; Alam, M. I. Catal. Sci. Technol. 2012, 2, 2025;
(c) Karinen, R.; Vilonen, K.; Niemela, M. ChemSusChem 2011, 4,
1002; (d) Mamman, A. S.; Lee, J.-M.; Kim, Y.-C.; Hwang, I. T.;
Park, N.-J.; Hwang, Y. K.; Chang, J.-S.; Hwang, J.-S. Biofuels,
Bioprod. Biorefin. 2008, 2, 438.
found 297.0677.
4.3.12. (3E)-4-(5-Methyl-3-phenyl-1-benzofuran-2-yl)but-3-en-2-
one (3l)
1
Pale orange oil (152 mg, 55% yield); H NMR (400 MHz,
DMSO-d6) δ 7.62–7.56 (m, 5H, HAr), 7.54–7.52 (m, 1H, HAr),
7.45 (br.s, 1H, HAr), 7.36 (d, J = 15.8 Hz, 1H, CH), 7.32–7.30
3. (a) Tsupova, S.; Rominger, F.; Rudolph, M.; Hashmi, A. S. K.
Green Chem. 2016, 18, 5800; (b) Reiser, O. Isr. J. Chem. 2016,
56, 531; (c) Montagnon, T.; Kalaitzakis, D.; Sofiadis, M.;
Vassilikogiannakis, G. Org. Biomol. Chem. 2016, 14, 8636; (d)
Trushkov, I. V.; Uchuskin, M. G.; Butin, A. V. Eur. J. Org. Chem.
2015, 2999; (e) Lee, H. K.; Chan, K. F.; Hui, C. W.; Yim, H. K.;
Wu, X. W.; Wong, H. N. C. Pure Appl. Chem. 2005, 77, 139.
4. (a) Liu, F.; Audemar, M.; De Oliveira Vigier, K.; Clacens, J. M.;
De Campo, F.; Jerome, F. ChemSusChem 2014, 7, 2089; (b)
Sutton, A. D.; Waldie, F. D.; Wu, R.; Schlaf, M.; Silks III, L. A.;
Gordon, J. C. Nat. Chem. 2013, 5, 428; (c) Butin, A. V.; Nevolina,
T. A.; Shcherbinin, V. A.; Uchuskin, M. G.; Serdyuk, O. V.;
Trushkov, I. V. Synthesis 2010, 2969.
3
3
(m, 1H, HAr), 6.85 (d, J = 15.8 Hz, 1H, CH), 2.40 (s, 3H, CH3),
2.31 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ 196.8,
152.7, 147.7, 133.1, 130.3, 129.2 (2C), 129.1 (2C), 128.7, 128.4,
127.6, 127.1, 126.8, 125.6, 120.2, 111.0, 28.1, 20.7; IR (nujol,
v/cm-1): 1664, 1628, 1607, 1491, 1356, 1277, 1254, 1200; HRMS
(ESI) calcd. for C19H17O2+ [M+H]+ 277.1223, found 277.1228.
4.3.13. (3E)-4-[5-Methyl-3-(4-methylphenyl)-1-benzofuran-2-
yl]but-3-en-2-one (3m)
1
Pale orange oil (174 mg, 60% yield); H NMR (400 MHz,
DMSO-d6) δ 7.54 (d, 3J = 8.4 Hz, 1H, HAr), 7.47 (d, 3J = 8.0 Hz,
2H, HAr), 7.44 (br.s, 1H, HAr), 7.41 (d, 3J = 8.0 Hz, 2H, HAr), 7.36
(d, 3J = 15.8 Hz, 1H, CH), 7.30 (br.d, 3J = 8.4 Hz, 1H, HAr), 6.84
5. (a) Makarov, A. S.; Merkushev, A. A.; Uchuskin, M. G.;
Trushkov, I. V. Org. Lett. 2016, 18, 2192; (b) Shpuntov, P. M.;
Shcherbinin, V. A.; Abaev, V. T.; Butin, A. V. Tetrahedron Lett.
2016, 57, 1483; (c) Abaev, V. T.; Trushkov, I. V.; Uchuskin, M.
G. Chem. Heterocycl. Comp. 2016, 52, 973; (d) Dhiman, S.;
Ramasastry, S. S. J. Org. Chem. 2013, 78, 10427; (e) Yin, B. L.;
Yu, H. Y.; Li, Z. R.; Zhong, W. Q.; Gu, W. X. Synthesis 2012, 44,
3735; (f) Pilipenko, A. S.; Mel'chin, V. V.; Trushkov, I. V.;
Cheshkov, D. A.; Butin, A. V. Tetrahedron 2012, 68, 619; (g)
Nevolina, T. A.; Shcherbinin, V. A.; Serdyuk, O. V.; Butin, A. V.
Synthesis 2011, 3547; (h) Butin, A. V.; Kostyukova, O. N.;
Tsiunchik, F. A.; Uchuskin, M. G.; Serdyuk, O. V.; Trushkov, I.
V. J. Heterocycl. Chem. 2011, 48, 684.
6. (a) Zhou, J.; Zhang, J.; Cheng, A.; Xiong, Y.; Liu, L.; Lou, H.
Org. Lett. 2015, 17, 3560; (b) Naganaboina, R. T.; Peddinti, R. K.
Tetrahedron 2015, 71, 6245; (c) Abaev, V. T.; Plieva, A. T.;
Chalikidi, P. N.; Uchuskin, M. G.; Trushkov, I. V.; Butin, A. V.
Org. Lett. 2014, 16, 4150; (d) Parr, B. T.; Green, S. A.; Davies, H.
M. J. Am. Chem. Soc. 2013, 135, 4716; (e) Chagarovskiy, A. O.;
Budynina, E. M.; Ivanova, O. A.; Grishin, Y. K.; Trushkov, I. V.;
Verteletskii, P. V. Tetrahedron 2009, 65, 5385; (f) Nair, V.;
Thomas, S.; Mathew, S. C.; Vidya, N.; Rath, N. P. Tetrahedron
2005, 61, 9533; (g) Nosse, B.; Chhor, R. B.; Jeong, W. B.; Bohm,
C.; Reiser, O. Org. Lett. 2003, 5, 941.
3
(d, J = 15.8 Hz, 1H, CH), 2.41 (s, 3H, CH3), 2.40 (s, 3H, CH3),
2.31 (s, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) δ 196.8,
152.7, 147.6, 138.0, 133.0, 129.8 (2C), 129.0 (2C), 128.6, 127.6,
127.4, 127.2, 126.6, 125.7, 120.3, 111.0, 28.1, 20.7 (2C); IR
(nujol, v/cm-1): 1604, 1592, 1286, 1253, 1204, 1169; HRMS
(ESI) calcd. for C20H19O2+ [M+H]+ 291.1380, found 291.1378.
4.3.14. (3E)-4-(5-Bromo-3-phenyl-1-benzofuran-2-yl)but-3-en-2-
one (3n)
Yellow oil (180 mg, 53% yield); 1H NMR (400 MHz, DMSO-
d6) δ 7.78 (br.s, 1H, HAr), 7.69–7.65 (m, 2H, HAr), 7.63–7.58 (m,
4H, HAr), 7.56–7.54 (m, 1H, HAr), 7.36 (d, 3J = 15.8 Hz, 1H, CH),
6.91 (d, 3J = 15.8 Hz, 1H, CH), 2.33 (s, 3H, CH3); 13C NMR (100
MHz, DMSO-d6) δ 196.9, 153.0, 148.9, 129.9, 129.6, 129.5,
129.3 (2C), 129.2 (2C), 128.7, 128.0, 126.6, 124.8, 122.9, 116.2,
113.6, 28.2; IR (nujol, v/cm-1): 1686, 1601, 1447, 1358, 1298,
1275, 1254, 1207, 1165, 1051; HRMS (ESI) calcd. for
C18H14BrO2+ [M+H]+ 341.0172, found 341.0173.
7. (a) Mukhina, O. A.; Kutateladze, A. G. J. Am. Chem. Soc. 2016,
138, 2110; (b) Zubkov, F. I.; Nikitina, E. V.; Galeev, T. R.;
Zaytsev, V. P.; Khrustalev, V. N.; Novikov, R. A.; Orlova, D. N.;
Varlamov, A. V. Tetrahedron 2014, 70, 1659; (c) Gao, X.;
Harmata, M. Tetrahedron 2013, 69, 7675; (d) Zubkov, F. I.;
Airiyan, I. K.; Ershova, J. D.; Galeev, T. R.; Zaytsev, V. P.;
Nikitina, E. V.; Varlamov, A. V. RSC Adv. 2012, 2, 4103; (e)
Zubkov, F. I.; Zaytsev, V. P.; Nikitina, E. V.; Khrustalev, V. N.;
Gozun, S. V.; Boltukhina, E. V.; Varlamov, A. V. Tetrahedron
2011, 67, 9148; (f) Zubkov, F. I.; Nikitina, E. V.; Varlamov, A. V.
Russ. J. Org. Chem. 2005, 74, 707; (g) Takao, K.; Munakata, R.;
Tadano, K. Chem. Rev. 2005, 105, 4779; (h) Kappe, C. O.;
Murphree, S. S.; Padwa, A. Tetrahedron 1997, 53, 14179.
4.3.15. (3E)-4-(5-Methoxy-3-methyl-1-benzofuran-2-yl)but-3-en-
2-one (3o)
1
Pale orange oil (131 mg, 57% yield); H NMR (400 MHz,
3
3
CDCl3) δ 7.48 (d, J = 15.6 Hz, 1H, CH), 7.32 (d, J = 8.9 Hz,
1H, HAr), 6.98 (dd, 3J = 8.9 Hz, 4J = 2.4 Hz, 1H, HAr), 6.94 (d, 3J
3
= 2.4 Hz, 1H, HAr), 6.82 (d, J = 15.6 Hz, 1H, CH), 3.86 (s, 3H,
OCH3), 2.37 (s, 3H, CH3), 2.35 (s, 3H, CH3); 13C NMR (100
MHz, CDCl3) δ 197.6, 156.4, 150.1, 149.4, 130.5, 127.4, 125.0,
121.9, 116.3, 112.0, 102.3, 56.1, 28.8, 8.6; IR (nujol, v/cm-1):
1658, 1624, 1257, 1221, 1179, 1024; HRMS (ESI) calcd. for
C14H15O3+ [M+H]+ 231.1016, found 231.1011.
8. (a) Harding, W. W.; Schmidt, M.; Tidgewell, K.; Kannan, P.;
Holden, K. G.; Gilmour, B.; Navarro, H.; Rothman, R. B.;
Prisinzano, T. E. J. Nat. Prod. 2006, 69, 107; (b) An, M.;
Toochinda, T.; Bartlett, P. A. J. Org. Chem. 2001, 66, 1326.
9. Kirner, W. R.; Richter, G. H. J. Am. Chem. Soc. 1929, 51, 3131.
10. (a) Xu, J.; Luo, Y.; Xu, H.; Chen, Z.; Miao, M.; Ren, H. J. Org.
Chem. 2017, 82, 3561; (b) Pevzner, L. M. Russ. J. Gen. Chem.
2016, 86, 62; (c) Miao, M.; Luo, Y.; Li, H.; Xu, X.; Chen, Z.; Xu,
J.; Ren, H. J. Org. Chem. 2016, 81, 5228; (d) Zhang, S.; Yu, X.;
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Acknowledgments
The work was supported by the Ministry of Education and
Science of the Russian Federation (Project № 4.5371.2017/8.9
and Agreement № 02.a03.0008).
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