A Simple Synthesis of Densely Substituted Benzofurans by Domino Reaction of 2-Hydroxybenzyl Alcohols with 2-Substituted Furans

Article abstract of DOI:10.1055/s-0039-1690000

The Br?nsted acid-catalyzed cascade synthesis of densely substituted benzofurans from easily available salicyl alcohols and biomass-derived furans has been developed. The disclosed sequence includes the intermediate formation of 2-(2-hydroxybenzyl)furans

Full text of DOI:10.1055/s-0039-1690000

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–K
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A. S. Makarov et al.
Paper
Synthesis
A Simple Synthesis of Densely Substituted Benzofurans by Domino
Reaction of 2-Hydroxybenzyl Alcohols with 2-Substituted Furans
Anton S. Makarova
R1
R1
R1
Anna E. Kekhvaevaa
Petrakis N. Chalikidib
Vladimir T. Abaevb
Igor V. Trushkovc,d
Maxim G. Uchuskin*a
X
TfOH
O
OH
R2
R2
+
R2
DCE
80 °C
X
X
O
O
OH
OH
O
29 examples
up to 97%
0
0
0
0-0
0
0
1-9
0
0
8-
7
6
1
0
a Perm State University, Bukireva st. 15, 614990 Perm, Russian
Federation
mu@psu.ru
b K. L. Khetagurov North Ossetian State University, Vatutina st.
46, 362025 Vladikavkaz, Russian Federation
c Dmitry Rogachev National Research Center of Pediatric Hema-
tology, Oncology and Immunology, Samory Mashela st. 1,
117997 Moscow, Russian Federation
d N. D. Zelinsky Institute of Organic Chemistry Russian Academy
of Sciences, Leninsky pr. 47, 119991 Moscow, Russian Federa-
tion
Received: 17.04.2019
Accepted after revision: 13.06.2019
Published online: 03.07.2019
MeO
NMe2
O
O
NHOH
DOI: 10.1055/s-0039-1690000; Art ID: ss-2019-z0232-op
O
O
HN
NH
Br
Abstract The Brö nsted acid-catalyzed cascade synthesis of densely
substituted benzofurans from easily available salicyl alcohols and bio-
mass-derived furans has been developed. The disclosed sequence in-
cludes the intermediate formation of 2-(2-hydroxybenzyl)furans that
quickly rearrange into functionalized benzofurans. The established pro-
tocol was applied for the total synthesis of sugikurojinol B.
O
CN
abexinostat
brofaromine
N
OH
O
HN
N
t-Bu
Et
N
H
Key words furan, benzofuran, rearrangement, sugikurojinol B
O
O
bufuralol
vilazodone
NH2
Substituted benzofurans represent an important class of
organic compounds due to the abundance of this hetero-
cyclic motif in natural products, approved drugs, and other
bioactive molecules (Figure 1).1 Thus, anticancer agent
abexinostat,2 antidepressants vilazodone3 and serclorem-
ine,4 monoamine oxidase A inhibitor brofaromine,5 -adre-
noceptor antagonist bufuralol,6 antiarrhythmic agents
amiodarone7 and celivarone,8 -blocker befunolol,9 -opiod
agonist enadoline,10 as well as other pharmacological
agents contain the benzofuran scaffold. Additionally, the
benzofuran core is present in organic field-effect transis-
tors11 and fluorescent organic nanoparticles,12 electrolumi-
nescent13 and photoluminescent14 materials, etc. The un-
doubted importance of benzofuran-containing molecules
stimulates the development of new efficient methods for
the straightforward synthesis of functionalized benzo-
furans.
Figure 1 Some benzofuran-based medicines
of phenols, including ortho-functionalization.15 The princi-
pal synthetic strategies toward substituted benzofurans via
O–C(2) bond formation are based on the nucleophilic attack
of an activated sp2- or sp-hybridized carbon atom with an
oxygen atom (Scheme 1). This approach has been imple-
mented through the cyclodehydration of 2-hydroxybenzyl
ketones (path a);16 the cyclization of 2-ynylphenols (path
b),17 2-hydroxybenzylacetylenes (path c)18 or 2-hydroxy-
phenylacetonitriles (path d);19 the oxidative cyclization of
2-alkenylphenols (path e)20 and 2-allylphenols (path f).21
Furans are well known to be used in the synthesis of di-
verse carbo- and heterocycles due to their ability to react as
synthetic equivalents of 1,4-diketones providing either
both latent carbonyl groups for the formation of a new ring
or only one of them while the other is released in a free
form.22 Thus, 2-benzylfurans bearing a nucleophilic group
at the ortho-position of the phenyl ring can serve as syn-
thetic equivalents of the corresponding benzyl ketones. If
the nucleophilic moiety is tolerant to the conditions of the
The existing methods for the synthesis of benzofurans
are predominantly based on the construction of the O–C(2)
bond due to the high synthetic accessibility of the corre-
sponding phenols, their well-studied reactivity, and, as a re-
sult, a diversity of synthetic protocols for the modification
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. S. Makarov et al.
Paper
Synthesis
Accounting for the aforementioned value of benzofu-
rans as well as the growing interest in the reactivity of sim-
ple furans as biomass-derived building blocks in the indus-
trial organic synthesis, we decided to investigate this reac-
tion in more detail. Within this paper, we describe applied
aspects of the previously disclosed synthetic method to-
ward densely functionalized benzofurans 7 by the acid-cat-
alyzed domino reaction of 2-alkylfurans 1 and salicyl alco-
hols 5.
We started this project with additional screening of
acidic catalysts in a model reaction of 2-methylfuran (1a)
with -phenylsalicyl alcohol (5a). We discovered that under
the reaction conditions optimized earlier for the related
synthesis of indoles from furans 1 and 2-aminobenzyl alco-
hols 2 (10 mol% TfOH, DCE, 80 °C)23 the target product 7a
was formed in a quantitative yield. Moreover, we found that
this process could be scaled up to a gram-scale with a mi-
nor decrease of the reaction efficiency.
Next, we investigated the scope of this reaction by vary-
ing substituents at the benzene and furan rings as well as at
the benzylic position (Table 1). We found that a broad range
of substituted -phenylsalicyl alcohols 5a–o reacted with
2-methylfuran (1a) affording the desired products 7a–o in
up to 97% yield. Various functional groups (alkyl, alkoxy,
halogen, nitro) were well tolerated under the reaction con-
ditions used. We observed a slightly lower yield of benzofu-
ran 7j derived from salicyl alcohol 5j bearing the nitro
group at the vicinal position to the phenolic moiety. This
outcome is possibly imposed by the electron-withdrawing
effect of the nitro substituent, which results in a decrease of
the phenol nucleophilicity. The intramolecular OH···ON hy-
drogen bonding can be also responsible for the lower yield.
Next, we examined the reaction of 2-methylfuran (1a)
with salicyl alcohols 5p–w containing an alkyl substituent
at the benzylic position. In all these cases, the significant
tarring was observed under the optimized reaction condi-
tions. We found that this problem can be solved by decreas-
ing the TfOH loading to 5 mol%. The yields of -methyl de-
rivatives 7p–s were comparable with the ones obtained for
aryl-substituted analogues. Oppositely, the yields of benzo-
furans 7t–v that contain branched alkyl substituents were
moderate, presumably, due to steric effects. Moreover, side
reactions of the intermediate 2-hydroxybenzyl cations can
be responsible for the decreased yields: such benzyl cations
can be transformed to ortho-quinone methides25 or ortho-
hydroxystyrenes26 as well as can undergo 1,2-hydride or
1,2-alkyl shift affording tertiary homobenzylic carbenium
ions followed by cyclization to 2,3-dihydrobenzo[b]fu-
rans.27
R2
R1
R1
O
OH
OH
a
b
R2
R2
R2
R
c
R
f
OH
OH
R1
O
e
d
R2
R2
R1
N
OH
OH
Scheme 1 Principal synthetic strategies toward substituted benzofurans
via O–C(2) bond formation
Friedel–Crafts alkylation, a domino reaction of the appro-
priate benzyl alcohols with furans can take place. Indeed,
we recently developed the Brö nsted acid catalyzed synthe-
sis of polysubstituted indoles 4 from furans 1 and 2-amino-
benzyl alcohols 2 via the initial formation of the intermedi-
ate 2-(2-aminobenzyl)furans 3 followed by the intramolec-
ular ipso-attack of the C(2) atom of the protonated furan
ring by a nucleophilic amino group (Scheme 2).23
With the aim to extend further the scope of this Br̈onsted
acid catalyzed rearrangement of ortho-substituted benzyl-
furans to diverse benzannulated heterocycles, we have
screened some other nucleophilic functionalities at the or-
tho-position of the starting benzyl alcohols. Thus, we have
recently found that in the presence of CuBr2 some 2-hy-
droxybenzyl alcohols 5 react with 2-alkylfurans 1 affording
substituted benzofurans 7 via the intermediate formation
of 2-(2-hydroxybenzyl)furans 6 (Scheme 2).24
R2
R2
O
X
Previous work
R1
R1
X
R2
NH
Ts
3
N
O
Ts
OH
X
4
NH
Ts
2
R1
O
1
R2
OH
OH
X
R2
R2
O
X
5
R1
R1
X
This work
OH
O
O
We also studied the commercially available salicyl alco-
hol 5x as a starting material for the synthesis of 3-unsubsti-
tuted benzofuran. In this case, the yield of the target benzo-
furan 7x was only 15%. We failed to improve the yield of the
desired product by varying the reaction parameters. The
6
7
Scheme 2 Domino reaction of 2-substituted benzyl alcohols with fu-
rans: recent synthesis of substituted indoles and concept of this work
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

C
A. S. Makarov et al.
Paper
Synthesis
Table 1 Domino Synthesis of Densely Substituted Benzofuransa
R2
R1
R2
R3
R4
R1
R3
R4
TfOH (10 mol%)
DCE, 80 °C
OH
R6
+
R6
O
OH
O
O
R5
R5
5
1
7
Me
R1
Ph
Ph
Me
Me
Me
Me
O
O
O
O
O
O
O
Cl
7a, R1 = Ph, 96% (91%)b
7b, R1 = 4-FC6H4, 92%
7c, R1 = 4-MeC6H4, 92%
7d, R1 = 3-F3CC6H4, 87%
7e, 92%
7f, 91%
R2
R3
Ph
Ph
Me
R3
O
O
Ph
O
R5
MeO
Me
7k, R2 = MeO, 66% (86%)c
7l, R2 = Br, 65% (85%)c
7i, R3 = Cl, R5 = MeO, 84%
7j, R3 = Me, R5 = O2N, 61%
O
O
Me
R3
Me
R1
Me
7g, R3 = MeO, 90%
7h, R3 = Br, 86%
Me
Me
Me
R1
O
O
O
O
7n, R1 = Ph, 93%
7o, R1 = 4-MeC6H4, 97%
7p, R3 = H, 79%d
7q, R3 = Me, 85%d
7r, R3 = Cl, 89%d
Me
Me
O
O
Me
7s, R3 = MeO, 86%d
7m, R1 = 4-MeC6H4, 89%
Ph
R1
Me
R6
Me
O
O
O
O
O
O
7y, R6 = Et, 96%
7x, 15%d
7t, R1 = i-Pr, 78%d
7z, R6 = t-Bu, 97%
7u, R1 = c-C6H11, 67%d
7v, R1 = t-Bu, 54%d
7w, R1 = Bn, 72%d
7aa, R6 = 4-ClC6H4, 90%e
7ab, R6 = CH2NPhth, 86%e
a Reaction conditions: salicyl alcohol 5 (0.5 mmol), 2-substituted furan 1 (1a: 0.75 mmol, 1.5 equiv; 1b–e: 0.5 mmol, 1 equiv), TfOH (10 mol%), DCE, 80 °C, 1 h.
b Using salicyl alcohol 5a (15 mmol).
c The isolated yield was reduced due to isolation problems. The NMR yield is given in parentheses.
d TfOH (5 mol%) was used.
e Reaction time was 20 h.
low yield of 7x might result from the insufficient stabiliza-
tion of the corresponding benzyl cation, which is formed
under acidic reaction conditions.
Finally, we tested various 2-substituted furans 1 in this
reaction. We found that all studied furans 1b–e were
smoothly converted into the corresponding benzofurans
7y–ab in excellent yields. However, the synthesis of benzo-
furans 7aa and 7ab required a longer heating of the reac-
tion mixture (ca. 20 h), whereas furans 1b,c were fully con-
verted into benzofurans 7y,z within 1 h.
A proposed mechanism for the domino transformation
of furans 1 to densely substituted benzofurans 7 is shown
in Scheme 3. The Br̈onsted acid-catalyzed Friedel–Crafts al-
kylation of 2-substituted furan 1 with salicyl alcohol 5 af-
fords the corresponding 2-(2-hydroxybenzyl)furan 6. It un-
dergoes protonation followed by the nucleophilic attack of
a protonated furan ring by the ortho-hydroxy group to pro-
duce spiro-intermediate 8. Subsequent acid-catalyzed furan
ring opening to dienol 9 and its aromatization accomplish
the formation of the desired benzofuran 7.
R1
R1
H
X
X
R2
O
O
OH
R2
1
H
OH
OH
R1
5
6
X
H
O
R2
O
R1
R1
8
X
X
R2
R2
OH
O
O
O
7
9
Scheme 3 A plausible reaction mechanism
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

D
A. S. Makarov et al.
Paper
Synthesis
In 2004 Arihara and co-workers isolated a bioactive
benzofuran terpenoid sugikurojinol B (10) from the black
heartwood of Cryptomeria japonica.28 This terpenoid re-
vealed moderate antimicrobial and termiticidal activities,
which make 10 a potential hit compound for further drug
development. To the best of our knowledge, a total synthe-
sis of sugikurojinol B has not been reported to date. A ret-
rosynthetic analysis of the sugikurojinol B leads to the ben-
zofuran 7ac through a modification of the alkanone moiety
(Scheme 4). In turn, benzofuran 7ac could be accessible via
the acid-catalyzed domino reaction of 2-methylfuran with
2-(1-hydroxyethyl)-5-methylbenzene-1,4-diol. Driven by
the idea of developing a straightforward method for the
synthesis of sugikurojinol B and its analogues, we decided
to test the proposed synthetic sequence.
Me
OH
HO
Me
O
HO
Me
Ref. 25
O
O
a,b
Me
O
Me
91%
Me
O
O
11
12
7ac
HO
HO
Me
Me
c
Me
d
Me
Me
Me
Me
Me
99%
99%
O
OH
13
10, 84%
+
HO
Me
Me
Me
O
14, 15%
a) BH3, THF, 0 ° → rt; b) 2-methylfuran (1a), TsOH (5 mol%), DCE, 65 °C;
c) MeMgI, Et2O, toluene, rt; d) TsOH, MS 4A, DCE, 80 °C
Me
Scheme 5 Synthesis of sugikurojinol B
HO
OH
OH
HO
HO
Me
Me
In conclusion, we have shown that the Br̈onsted acid
catalyzed rearrangement of 2-(2-hydroxybenzyl)furans
provides a shortcut to a wide range of polyfunctionalized
benzofurans in up to 97% yield starting from easily available
furans and salicyl alcohols. The developed synthesis of ben-
zofurans was applied to the total synthesis of sugikurojinol
B.
Me
Me
Me
+
O
O
Me
O
Me
O
Me
Me
10
7ac
Scheme 4 Retrosynthetic analysis of sugikurojinol B (10)
The commercially available 2-methyl-1,4-benzoquinone
(11) was transformed into 1-(2,5-dihydroxy-4-methylphe-
nyl)ethan-1-one (12) in an excellent yield according to
known procedures (Scheme 5).25 The resulting ketone 12
was reduced by BH3 producing the corresponding salicyl al-
cohol which was introduced into the title acid-catalyzed
domino reaction with 2-methylfuran (1a) to provide benzo-
furan 7ac in a high yield. In this reaction, TfOH was found to
induce extensive tarring of the reaction mixture; however,
the use of 5 mol% of TsOH allowed for the formation of the
target compound 7ac in quantitative yield. The subsequent
treatment of the obtained benzofuran 7ac with MeMgI led
quantitatively to the corresponding tertiary alcohol 13. Fi-
nally, this alcohol was treated with various acid catalysts to
perform its dehydration to sugikurojinol B. The target com-
pound 10 was formed under all studied conditions as a
mixture with its regioisomer, the terminal olefin 14. The
yield of alkenes and isomeric ratio of products were found
to depend on the conditions applied. We found that the use
of 5 mol% TsOH in DCE at 80 °C in the presence of molecular
sieves allowed for quantitative conversion of alcohol 13. As
a result, we obtained the target sugikurojinol B in 84% yield,
though it was inseparable from the isomeric alkene 14 us-
ing standard isolation techniques (Scheme 5).
1H and 13C NMR spectra were recorded with a Bruker Avance III HD
400 (400 MHz for 1H and 100 MHz for 13C NMR) spectrometer at rt
1
referenced to the solvent (CDCl3, H:  = 7.26, 13C:  = 77.16; DMSO-
d6, 1 H:  = 2.50, 13C:  = 39.52). GC/MS analysis was performed on an
Agilent 7890В interfaced to an Agilent 5977A mass selective detector.
HRMS measurements were carried out using a Bruker microTOF-QTM
ESI-TOF mass spectrometer. Column chromatography was performed
on silica gel Macherey Nagel (40–63 m). All the reactions were car-
ried out using freshly distilled and dry solvents from solvent stills.
Starting salicyl aldehydes, 2-alkylfurans and salicyl alcohol 5x were
purchased from chemical suppliers. 2-(4-Chlorophenyl)furan and 2-
(phthalimidomethyl)furan were synthesized via known literature
procedures.29a,c
Salicyl Alcohols 5a–i,k–w; General Procedure
Mg turnings (420 mg, 17.5 mmol) were placed in 25-mL round-bot-
tom flask followed by the addition of several crystals of molecular I2.
The flask was heated upon shaking until violet vapor appeared. The
flask was cooled to rt, and Et2O (10 mL) was added. The organic bro-
mide (17.5 mmol; for the synthesis of 5p–s MeI was used) was added
dropwise to the resulting suspension of Mg turnings in Et2O over 30
min. The suspension was stirred until metallic Mg fully reacted with
the organic halide, at which point it was transferred into a solution of
salicyl aldehyde (7 mmol) in Et2O/THF (1:1, 30 mL) through a cannula
at 0 °C. The resulting mixture was stirred for 2 h at this temperature
and a further 12 h at r.t. Upon completion, the mixture was cooled to
0 °C, quenched with sat. NH4Cl (10 mL, portionwise addition), and di-
luted with water (100 mL). The organic phase was separated and the
aqueous phase was extracted with EtOAc (2 × 20 mL). The combined
organic fractions were washed with water (2 × 20 mL) and brine (2 ×
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

E
A. S. Makarov et al.
Paper
Synthesis
10 mL), dried (anhyd Na2SO4), and concentrated. The oily residue was
subjected to column chromatography (silica gel, gradient elution pe-
troleum ether/EtOAc 50:1 to 10:1) to afford the target alcohol.
13C{1H} NMR (CDCl3):  = 149.9, 142.2, 130.0, 128.9, 128.7 (2 C), 128.2,
126.8 (2 C), 126.7, 121.2, 120.8, 74.4.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C13H10ClO: 217.0415; found:
217.0410.
2-[Hydroxy(phenyl)methyl]phenol (5a)29b
Colorless oil; yield: 1.274 g (91%).
2-[Hydroxy(phenyl)methyl]-4-methoxy-6-methylphenol (5g)
1H NMR (CDCl3):  = 7.82 (br s, 1 H, OH), 7.40–7.30 (m, 5 H, HAr), 7.21–
7.17 (m, 1 H, HAr), 6.90–6.87 (m, 2 H, HAr), 6.84–6.80 (m, 1 H, HAr), 6.00
(s, 1 H, CH), 3.03 (br s, 1 H, OH).
Colorless oil; yield: 1.435 g (84%).
1H NMR (CDCl3):  = 7.45 (br s, 1 H, OH), 7.39–7.30 (m, 5 H, HAr), 6.65
(d, 4J = 2.8 Hz, 1 H, HAr), 6.30 (d, 4J = 2.8 Hz, 1 H, HAr), 5.89 (s, 1 H, CH),
3.67 (s, 3 H, CH3), 3.17 (br s, 1 H, OH), 2.24 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 155.6, 142.1, 129.4, 128.9 (2 C), 128.4, 128.3,
127.0 (2 C), 126.9, 120.1, 117.4, 77.1.
13C{1H} NMR (CDCl3):  = 152.6, 147.7, 142.0, 128.8 (2 C), 128.2, 127.1,
127.0, 126.9 (2 C), 116.1, 111.6, 77.0, 55.8, 16.2.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C15H15O2: 227.1067; found:
227.1062.
2-[(4-Fluorophenyl)(hydroxy)methyl]phenol (5b)
Colorless oil; yield: 1.236 g (81%).
1H NMR (CDCl3):  = 7.68 (br s, 1 H, OH), 7.37–7.34 (m, 2 H, HAr), 7.23–
7.18 (m, 1 H, HAr), 7.07–7.02 (m, 2 H, HAr), 6.91–6.82 (m, 3 H, HAr), 5.99
(s, 1 H, CH), 2.97 (br s, 1 H, OH).
4-Bromo-2-[hydroxy(phenyl)methyl]-6-methylphenol (5h)29b
Colorless oil; yield: 1.969 g (96%).
1
13C{1H} NMR (CDCl3):  = 162.7 (d, JC-F = 247.0 Hz), 155.5, 137.8,
1H NMR (CDCl3):  = 8.01 (br s, 1 H, OH), 7.38–7.32 (m, 5 H, HAr), 7.19
(s, 1 H, HAr), 6.84 (br s, 1 H, HAr), 5.93 (s, 1 H, CH), 2.88 (br s, 1 H, OH),
2.22 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 153.1, 141.4, 133.2, 129.1 (2 C), 128.8, 128.7,
128.5, 127.8, 126.9 (2 C), 111.5, 77.0, 15.8.
129.6, 128.8 (d, 3JC-F = 8.3 Hz, 2 C), 128.3, 126.7, 120.2, 117.5, 115.7 (d,
2JC-F = 21.7 Hz, 2 C), 76.4.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C13H10FO: 201.0710; found:
201.0704.
2-[Hydroxy(4-methylphenyl)methyl]phenol (5c)29b
4-Chloro-2-[hydroxy(phenyl)methyl]-6-methoxyphenol (5i)
Colorless oil; yield: 1.318 g (88%).
Colorless oil; yield: 1.555 g (84%).
1H NMR (CDCl3):  = 7.86 (br s, 1 H, OH), 7.32–7.28 (m, 2 H, HAr), 7.23–
7.19 (m, 3 H, HAr), 6.94–6.81 (m, 3 H, HAr), 6.02 (s, 1 H, CH), 2.73 (br s,
1 H, OH), 2.38 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 155.8, 139.2, 138.3, 129.6 (2 C), 129.4, 128.4,
127.0 (2 C), 126.8, 120.0, 117.5, 77.3, 21.3.
1H NMR (CDCl3):  = 7.42–7.40 (m, 2 H, HAr), 7.36–7.26 (m, 3 H, HAr),
6.89 (d, 4J = 2.2 Hz, 1 H, HAr), 6.78 (d, 4J = 2.2 Hz, 1 H, HAr), 6.24 (br s, 1
H, OH), 6.04 (s, 1 H, CH), 3.84 (s, 3 H, OCH3), 3.02 (br s, 1 H, OH).
13C{1H} NMR (CDCl3):  = 147.4, 142.5, 141.9, 130.5, 128.5 (2 C), 127.8,
126.6 (2 C), 124.8, 119.5, 110.9, 72.2, 56.4.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C14H12ClO2: 247.0520;
found: 247.0515.
2-{Hydroxy[3-(trifluoromethyl)phenyl]methyl}phenol (5d)
Colorless oil; yield: 1.801 g (96%).
1H NMR (DMSO-d6):  = 9.53 (br s, 1 H, OH), 7.72 (br s, 1 H, HAr), 7.67–
7.65 (m, 1 H, HAr), 7.55–7.49 (m, 2 H, HAr), 7.41–7.39 (m, 1 H, HAr),
7.08–7.04 (m, 1 H, HAr), 6.83–6.79 (m, 2 H, HAr), 6.08 (s, 1 H, CH), 5.91
(br s, 1 H, OH).
2-[Hydroxy(phenyl)methyl]-3,6-dimethoxyphenol (5k)
Colorless oil; yield: 1.383 g (76%).
1H NMR (CDCl3):  = 7.43–7.41 (m, 2 H, HAr), 7.33–7.26 (m, 2 H, HAr),
7.25–7.18 (m, 1 H, HAr), 6.74 (d, 3J = 8.9 Hz, 1 H, HAr), 6.64 (s, 1 H, CH),
6.38 (d, 3J = 8.9 Hz, 1 H, HAr), 6.33 (br s, 1 H, OH), 4.19 (br s, 1 H, OH),
3.84 (s, 3 H, OCH3), 3.72 (s, 3 H, OCH3).
13C{1H} NMR (CDCl3):  = 151.8, 144.5, 144.1, 142.0, 128.2 (2 C), 127.0,
126.1 (2 C), 118.1, 110.2, 101.9, 69.9, 56.6, 56.1.
13C{1H} NMR (DMSO-d6):  = 153.6, 147.0, 130.3, 130.2, 128.8, 128.6
(q, 2JC-F = 31.3 Hz), 127.8, 126.5, 124.3 (q, 1JC-F = 272.3 Hz), 123.1 (q, 3JC-F
3.8 Hz), 122.5 (q, 3JC-F = 3.9 Hz), 119.0, 115.0, 67.8.
=
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C14H10F3O: 251.0678; found:
251.0672.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C15H15O3: 243.1016; found:
243.1014.
2-[Hydroxy(phenyl)methyl]-4-methylphenol (5e)29b
Colorless oil; yield: 1.318 g (88%).
3-Bromo-2-[hydroxy(phenyl)methyl]-6-methoxyphenol (5l)
1H NMR (DMSO-d6):  = 7.51 (br s, 1 H, OH), 7.41–7.32 (m, 5 H, HAr),
6.99 (br d, 3J = 8.2 Hz, 1 H, HAr), 6.80 (d, 3J = 8.2 Hz, 1 H, HAr), 6.70 (br s,
1 H, HAr), 5.97 (s, 1 H, CH), 2.82 (br s, 1 H, OH), 2.21 (s, 3 H, CH3).
13C{1H} NMR (DMSO-d6):  = 153.3, 142.2, 129.9, 129.3, 128.9 (2 C),
128.8, 128.3, 127.0 (2 C), 126.5, 117.3, 77.2, 20.6.
Colorless oil; yield: 1.752 g (81%).
1H NMR (CDCl3):  = 7.43–7.41 (m, 2 H, HAr), 7.34–7.24 (m, 3 H, HAr),
7.10 (d, 3J = 8.7 Hz, 1 H, HAr), 7.08 (br s, 1 H, OH), 6.71 (d, 3J = 8.7 Hz, 1
H, HAr), 6.33 (s, 1 H, CH), 3.95 (br s, 1 H, OH), 3.87 (s, 3 H, OCH3).
13C{1H} NMR (CDCl3):  = 147.2, 145.4, 142.1, 128.5 (2 C), 127.7, 127.6,
126.4 (2 C), 124.1, 114.3, 111.8, 75.9, 56.4.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C14H12BrO2: 291.0015;
found: 291.0013.
2-Chloro-6-[hydroxy(phenyl)methyl]phenol (5f)
Colorless oil; yield: 1.395 g (85%).
1H NMR (CDCl3):  = 7.38–7.24 (m, 6 H, HAr, OH), 7.04–7.00 (m, 2 H,
HAr), 6.82–6.78 (m, 1 H, HAr), 6.03 (s, 1 H, CH), 2.96 (br s, 1 H, OH).
6-[Hydroxy(4-methylphenyl)methyl]-2,3-dimethylphenol (5m)29b
Colorless oil; yield: 1.406 g (83%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

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Synthesis
1H NMR (DMSO-d6):  = 8.72 (br s, 1 H, OH), 7.24–7.22 (m, 2 H, HAr),
7.10–7.08 (m, 2 H, HAr), 6.84 (d, J = 7.7 Hz, 1 H, HAr), 6.59 (d, J = 7.7
Hz, 1 H, HAr), 6.39 (br s, 1 H, OH), 5.90 (s, 1 H, CH), 2.26 (s, 3 H, CH3),
2.16 (s, 3 H, CH3), 2.05 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 153.2, 149.3, 129.6, 117.7, 113.9, 112.6, 71.3,
56.0, 23.4.
3
3
2-(1-Hydroxy-2-methylpropyl)phenol (5t)29b
13C{1H} NMR (DMSO-d6):  = 152.3, 141.7, 135.6, 135.5, 128.3 (2 C),
Colorless oil; yield: 1.104 g (95%).
127.5, 126.2 (2 C), 124.0, 122.9, 120.4, 72.1, 20.5, 19.6, 11.5.
1H NMR (CDCl3):  = 7.99 (br s, 1 H, OH), 7.18–7.14 (m, 1 H, HAr), 6.91–
6.90 (m, 1 H, HAr), 6.86–6.79 (m, 2 H, HAr), 4.51 (d, 3J = 7.0 Hz, 1 H, CH),
2.73 (br s, 1 H, OH), 2.06–2.15 (m, 1 H, CH), 1.05 (d, 3J = 6.8 Hz, 3 H,
CH3), 0.86 (d, 3J = 6.8 Hz, 3 H, CH3).
2-[Hydroxy(phenyl)methyl]-4,5-dimethylphenol (5n)29b
Colorless oil; yield: 1.389 g (87%).
1H NMR (CDCl3):  = 7.51 (br s, 1 H, OH), 7.41–7.31 (m, 5 H, HAr), 6.69
(s, 1 H, HAr), 6.64 (s, 1 H, HAr), 5.93 (s, 1 H, CH), 2.96 (br s, 1 H, OH),
2.20 (s, 3 H, CH3), 2.12 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 155.9, 128.9, 128.4, 126.3, 119.5, 117.3, 82.2,
34.5, 19.4, 18.3.
13C{1H} NMR (CDCl3):  = 153.3, 142.5, 137.8, 129.3, 128.8 (2 C), 128.2,
2-[Cyclohexyl(hydroxy)methyl]phenol (5u)
127.9, 126.9 (2 C), 124.1, 118.6, 76.9, 19.6, 18.8.
Colorless oil; yield: 1.182 g (82%).
1H NMR (CDCl3):  = 8.05 (br s, 1 H, OH), 7.18–7.14 (m, 1 H, HAr), 6.89–
6.79 (m, 3 H, HAr), 4.51 (d, 3J = 7.2 Hz, 1 H, CH), 2.78 (br s, 1 H, OH),
2.03–1.99 (m, 1 H, CH), 1.80–1.64 (m, 4 H, CH2), 1.45–1.42 (m, 1 H,
CH2), 1.27–0.94 (m, 5 H, CH2).
13C{1H} NMR (CDCl3):  = 155.9, 128.9, 128.5, 126.1, 119.4, 117.2, 81.4,
43.8, 29.6, 28.9, 26.4, 26.1, 26.0.
2-[Hydroxy(4-methylphenyl)methyl]-4,5-dimethylphenol (5o)29b
Colorless oil; yield: 1.423 g (84%).
1H NMR (DMSO-d6):  = 8.91 (br s, 1 H, OH), 7.22–7.20 (m, 2 H, HAr),
7.06–7.04 (m, 2 H, HAr), 7.02 (s, 1 H, HAr), 6.54 (s, 1 H, HAr), 5.88 (d,
3J = 3.4 Hz, 1 H, CH), 5.49 (d, 3J = 3.4 Hz, 1 H, OH), 2.24 (s, 3 H, CH3),
2.09 (s, 3 H, CH3), 2.07 (s, 3 H, CH3).
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C13H17O: 189.1274; found:
189.1267.
13C{1H} NMR (DMSO-d6):  = 151.5, 142.8, 135.1, 134.7, 128.7, 128.1
(2 C), 127.8, 126.0 (2 C), 125.7, 116.3, 68.3, 20.5, 19.0, 18.5.
2-(1-Hydroxy-2,2-dimethylpropyl)phenol (5v)32
2-(1-Hydroxyethyl)phenol (5p)25c
Colorless oil; yield: 48% (NMR yield). We were not able to isolate the
phenol 1v in a pure form; the crude material was used directly for the
next step after determination of the actual amount by NMR with
CH2Br2 as an internal standard.
Colorless oil; yield: 918 mg (95%).
1H NMR (CDCl3):  = 7.93 (br s, 1 H, OH), 7.19–7.15 (m, 1 H, HAr), 7.00–
6.98 (m, 1 H, HAr), 6.87–6.82 (m, 2 H, HAr), 5.05 (q, 3J = 6.6 Hz, 1 H, CH),
2.80 (br s, 1 H, OH), 1.58 (d, 3J = 6.6 Hz, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 155.5, 129.0, 128.7, 126.6, 120.1, 117.2, 71.6,
23.5.
2-(1-Hydroxy-2-phenylethyl)phenol (5w)33
Colorless oil; yield: 1.453 g (97%).
1H NMR (CDCl3):  = 7.91 (br s, 1 H, OH), 7.38–7.30 (m, 3 H, HAr), 7.26–
2-(1-Hydroxyethyl)-4-methylphenol (5q)30a
7.19 (m, 3 H, HAr), 6.98–6.92 (m, 2 H, HAr), 6.87–6.83 (m, 1 H, HAr), 5.06
3
(t, J = 7.0 Hz, 1 H, CH), 3.15 (d, 3J = 7.0 Hz, 2 H, CH2), 2.60 (br s, 1 H,
Colorless oil; yield: 1.000 g (94%).
OH).
1H NMR (CDCl3):  = 7.63 (br s, 1 H, OH), 6.96 (d, 3J = 8.2 Hz, 1 H, HAr),
6.79 (br s, 1 H, HAr), 6.76 (d, 3J = 8.2 Hz, 1 H, HAr), 5.02 (q, 3J = 6.6 Hz, 1
H, CH), 2.53 (br s, 1 H, OH), 2.25 (s, 3 H, CH3), 1.58 (d, 3J = 6.6 Hz, 3 H,
CH3).
13C{1H} NMR (CDCl3):  = 155.7, 137.4, 129.7 (2 C), 129.2, 128.9 (2 C),
127.3, 127.2, 126.5, 120.0, 117.5, 77.0, 44.4.
2-[Hydroxy(phenyl)methyl]-4-methyl-6-nitrophenol (5j)
13C{1H} NMR (CDCl3):  = 153.2, 129.5, 129.2, 128.4, 127.1, 117.1, 71.7,
23.6, 20.6.
To
a solution of (2-hydroxy-5-methylphenyl)(phenyl)methanone
(1060 mg, 5 mmol) in glacial AcOH (10 mL) was added fuming HNO3
(2 mL) dropwise at 15 °C over 1 min upon vigorous stirring. The
course of the reaction was monitored by TLC. Once the starting mate-
rial had been consumed (5 min), the mixture was poured into water
(200 mL). The crude nitro derivative was filtered, washed with water,
and dried. The residue was dissolved in EtOH (30 mL) and NaBH4 (380
mg, 10 mmol) was added portionwise at rt. The mixture was stirred
for 3 h, poured into water (350 mL), acidified with 0.5 M HCl up to
pH ~5, and extracted with CH2Cl2 (3 × 40 mL). The combined organic
fractions were washed with water (2 × 30 mL) and brine (2 × 20 mL),
dried (anhyd Na2SO4), and concentrated. The residue was purified by
column chromatography (silica gel, gradient elution petroleum
ether/CH2Cl2 10:1 to 5:1) to give the product as a colorless oil; yield:
1101 mg (85%).
4-Chloro-2-(1-hydroxyethyl)phenol (5r)31
Colorless oil; yield: 1.159 g (96%).
1H NM (CDCl3):  = 7.89 (br s, 1 H, OH), 7.11 (d, 3J = 8.6 Hz, 4J = 2.4 Hz,
1 H, HAr), 6.96 (d, 4J = 2.4 Hz, 1 H, HAr), 6.79 (d, 3J = 8.6 Hz, 1 H, HAr),
5.02 (q, 3J = 6.6 Hz, 1 H, CH), 2.61 (br s, 1 H, OH), 1.57 (d, 3J = 6.6 Hz, 3
H, CH3).
13C{1H} NMR (CDCl3):  = 154.2, 130.0, 128.8, 126.4, 124.8, 118.6, 71.3,
23.5.
2-(1-Hydroxyethyl)-4-methoxyphenol (5s)29b
Colorless oil; yield: 1.141 g (97%).
1H NMR (CDCl3):  = 7.49 (br s, 1 H, OH), 6.77 (d, 3J = 8.7 Hz, 1 H, HAr),
1H NMR (CDCl3):  = 10.84 (br s, 1 H, OH), 7.84 (br s, 1 H, HAr), 7.61 (br
s, 1 H, HAr), 7.44–7.42 (m, 2 H, HAr), 7.37–7.34 (m, 2 H, HAr), 7.31–7.26
(m, 1 H, HAr), 6.19 (s, 1 H, CH), 2.63 (br s, 1 H, OH), 2.35 (s, 3 H, CH3).
6.71 (dd, 3J = 8.7 Hz, 4J = 2.1 Hz, 1 H, HAr), 6.55 (d, 4J = 2.1 Hz, 1 H, HAr),
3
4.98 (q, J = 6.5 Hz, 1 H, CH), 3.73 (s, 3 H, OCH3), 2.89 (br s, 1 H, OH),
1.55 (d, 3J = 6.5 Hz, 3 H, CH3).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

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A. S. Makarov et al.
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Synthesis
13C{1H} NMR (CDCl3):  = 150.4, 142.4, 136.4, 134.5, 133.5, 129.9,
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H16F3O2: 333.1097; found:
128.7 (2 C), 128.1, 126.7 (2 C), 123.8, 70.9, 20.7.
333.1103.
HRMS (ESI/TOF): m/z [M – OH]+ calcd for C14H12NO3: 242.0812;
found: 242.0806.
4-(5-Methyl-3-phenylbenzo[b]furan-2-yl)butan-2-one (7e)24a
Pale yellow oil; yield: 128 mg (92%).
1H NMR (CDCl3):  = 7.51–7.50 (m, 4 H, HAr), 7.41–7.38 (m, 1 H, HAr),
7.35–7.33 (m, 2 H, HAr), 7.10 (br d, 3J = 8.1 Hz, 1 H, HAr), 3.17 (t, 3J = 7.4
Hz, 2 H, CH2), 2.92 (t, 3J = 7.4 Hz, 2 H, CH2), 2.44 (s, 3 H, CH3), 2.17 (s, 3
H, CH3).
13C{1H} NMR (CDCl3):  = 207.0, 153.3, 152.6, 132.7, 132.3, 129.2 (2 C),
129.0, 128.9 (2 C), 127.3, 125.1, 119.6, 117.3, 110.5, 41.6, 29.9, 21.5,
21.3.
Benzofurans 7a–ab; General Procedure
A 3-mL Wheaton microreactor vial equipped with Teflon pressure cap
was charged with salicyl alcohol 5 (0.5 mmol), 2-substituted furan 1
(for 1a: 0.75 mmol, 1.5 equiv; for 1b–e: 0.5 mmol, 1 equiv), and DCE
(1.7 mL). TfOH (for 5a–o: 4.4 L, 10 mol%; for 5p–x: 2.2 L, 5 mol%)
was added in one portion to the resulting solution at rt with vigorous
stirring. The vial was placed into a preheated (80 °C) aluminum block
and stirred for 1 h (TLC control; for benzofurans 7aa,ab, 20 h). After
completion of the reaction, the resulting solution was concentrated in
vacuo, and the remaining oily crude mixture was subjected to column
chromatography (silica gel, gradient elution with petroleum
ether/EtOAc 99:1 to 20:1) to afford the target benzofuran.
4-(7-Chloro-3-phenylbenzo[b]furan-2-yl)butan-2-one (7f)
Pale yellow oil; yield: 136 mg (91%).
1H NMR (CDCl3):  = 7.49–7.48 (m, 4 H, HAr), 7.44–7.38 (m, 2 H, HAr),
3
7.28–7.26 (m, 1 H, HAr), 7.17–7.13 (m, 1 H, HAr), 3.20 (t, J = 7.5 Hz, 2
H, CH2), 2.96 (t, 3J = 7.5 Hz, 2 H, CH2), 2.19 (s, 3 H, CH3).
4-(3-Phenylbenzo[b]furan-2-yl)butan-2-one (7a)24a
Pale yellow oil; yield: 127 mg (96%).
13C{1H} NMR (CDCl3):  = 206.7, 154.3, 150.0, 132.0, 130.7, 129.2 (2 C),
129.1 (2 C), 127.7, 124.2, 123.8, 118.3, 118.2, 116.6, 41.4, 30.0, 21.3.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C18H16ClO2: 299.0833; found:
299.0833.
1H NMR (CDCl3):  = 7.61–7.59 (m, 1 H, HAr), 7.56–7.48 (m, 5 H, HAr),
3
7.43–7.39 (m, 1 H, HAr), 7.33–7.24 (m, 2 H, HAr), 3.21 (t, J = 7.6 Hz, 2
H, CH2), 2.95 (t, 3J = 7.6 Hz, 2 H, CH2), 2.19 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 206.9, 154.1, 153.1, 132.4, 129.1 (2 C), 128.9
(2 C), 128.8, 127.3, 123.9, 122.8, 119.7, 117.4, 110.9, 41.5, 29.9, 21.1.
4-(5-Methoxy-7-methyl-3-phenylbenzo[b]furan-2-yl)butan-2-one
(7g)
Pale yellow oil; yield: 139 mg (90%).
4-(3-(4-Fluorophenyl)benzo[b]furan-2-yl)butan-2-one (7b)
1H NMR (CDCl3):  = 7.53–7.49 (m, 4 H, HAr), 7.42–7.38 (m, 1 H, HAr),
6.89 (d, 4J = 2.0 Hz, 1 H, HAr), 6.75 (d, 4J = 2.0 Hz, 1 H, HAr), 3.82 (s, 3 H,
OCH3), 3.19 (t, 3J = 7.5 Hz, 2 H, CH2), 2.93 (t, 3J = 7.5 Hz, 2 H, CH2), 2.54
(s, 3 H, CH3), 2.19 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 206.9, 156.3, 153.6, 148.2, 132.8, 129.1 (2 C),
128.9 (2 C), 128.7, 127.2, 121.8, 117.8, 113.5, 99.9, 56.0, 41.5, 29.8,
21.4, 15.1.
Pale yellow oil; yield: 130 mg (92%).
1H NMR (CDCl3):  = 7.54–7.47 (m, 4 H, HAr), 7.33–7.19 (m, 4 H, HAr),
3.16 (t, 3J = 7.5 Hz, 2 H, CH2), 2.96 (t, 3J = 7.5 Hz, 2 H, CH2), 2.20 (s, 3 H,
CH3).
13C{1H} NMR (CDCl3):  = 206.9, 162.2 (d, JC-F = 246.5 Hz), 154.1,
1
3
4
153.2, 130.8 (d, JC-F = 8.0 Hz, 2 C), 128.8, 128.4 (d, JC-F = 3.1 Hz),
2
124.1, 123.0, 119.5, 116.6, 116.0 (d, JC-F = 21.4 Hz, 2 C), 111.0, 41.4,
30.0, 21.1.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C20H21O3: 309.1485; found:
309.1487.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C18H16FO2: 283.1129; found:
283.1122.
4-(5-Bromo-7-methyl-3-phenylbenzo[b]furan-2-yl)butan-2-one
(7h)
4-[3-(4-Methylphenyl)benzo[b]furan-2-yl]butan-2-one (7c)24b
Pale yellow oil; yield: 154 mg (86%).
Pale yellow oil; yield: 128 mg (92%).
1H NMR (CDCl3):  = 7.50–7.44 (m, 5 H, HAr), 7.40–7.36 (m, 1 H, HAr),
7.20 (br s, 1 H, HAr), 3.16 (t, 3J = 7.5 Hz, 2 H, CH2), 2.91 (t, 3J = 7.5 Hz, 2
H, CH2), 2.50 (s, 3 H, CH3), 2.18 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 206.6, 154.1, 151.9, 132.0, 130.2, 129.1 (2 C),
129.0 (2 C), 127.6, 127.5, 123.0, 119.9, 117.4, 115.9, 41.4, 30.0, 21.3,
14.8.
1H NMR (CDCl3):  = 7.58–7.56 (m, 1 H, HAr), 7.48–7.46 (m, 1 H, HAr),
7.43–7.41 (m, 2 H, HAr), 7.33–7.31 (m, 2 H, HAr), 7.30–7.23 (m, 2 H,
HAr), 3.19 (t, 3J = 7.5 Hz, 2 H, CH2), 2.94 (t, 3J = 7.5 Hz, 2 H, CH2), 2.46 (s,
3 H, CH3), 2.19 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 205.9, 153.2, 152.0, 136.1 (2 C), 128.7 (2 C),
128.5, 128.1 (2 C), 122.9, 121.8, 118.8, 116.4, 110.0, 40.7, 29.0, 20.4,
20.3.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H18BrO2: 357.0485; found:
357.0483.
4-{3-[3-(Trifluoromethyl)phenyl]benzo[b]furan-2-yl}butan-2-one
(7d)
4-(5-Chloro-7-methoxy-3-phenylbenzo[b]furan-2-yl)butan-2-one
(7i)
Pale yellow oil; yield: 144 mg (87%).
Pale yellow oil; yield: 138 mg (84%).
1H NMR (CDCl3):  = 7.80 (br s, 1 H, HAr), 7.72–7.70 (m, 1 H, HAr), 7.66–
7.60 (m, 2 H, HAr), 7.52–7.46 (m, 2 H, HAr), 7.33–7.24 (m, 2 H, HAr), 3.15
(t, 3J = 7.4 Hz, 2 H, CH2), 2.95 (t, 3J = 7.4 Hz, 2 H, CH2), 2.18 (s, 3 H, CH3).
1H NMR (CDCl3):  = 7.49–7.44 (m, 4 H, HAr), 7.39–7.35 (m, 1 H, HAr),
7.12 (d, 4J = 1.6 Hz, 1 H, HAr), 6.78 (d, 4J = 1.6 Hz, 1 H, HAr), 4.00 (s, 3 H,
OCH3), 3.14 (t, 3J = 7.5 Hz, 2 H, CH2), 2.92 (t, 3J = 7.5 Hz, 2 H, CH2), 2.14
(s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 206.6, 154.3, 153.8, 133.6, 132.5, 131.5 (q,
3
2JC-F = 32.4 Hz), 129.5, 128.5, 125.9 (q, JC-F = 3.8 Hz), 124.4, 124.3 (q,
3
1JC-F = 272.4 Hz), 124.2 (q, JC-F = 3.8 Hz), 123.2, 119.4, 116.4, 111.2,
41.3, 30.0, 21.2.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

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A. S. Makarov et al.
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13C{1H} NMR (CDCl3):  = 206.5, 154.5, 145.3, 141.9, 131.7, 131.2,
129.1 (2 C), 129.0 (2 C), 128.8, 127.6, 117.6, 111.8, 107.4, 56.4, 41.4,
29.8, 21.2.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H18ClO3: 329.0939; found:
329.0942.
1H NMR (CDCl3):  = 7.50–7.46 (m, 4 H, HAr), 7.39–7.34 (m, 1 H, HAr),
7.30 (s, 1 H, HAr), 7.24 (s, 1 H, HAr), 3.14 (t, 3J = 7.4 Hz, 2 H, CH2), 2.89 (t,
3J = 7.4 Hz, 2 H, CH2), 2.38 (s, 3 H, CH3), 2.33 (s, 3 H, CH3), 2.16 (s, 3 H,
CH3).
13C{1H} NMR (CDCl3):  = 207.1, 153.2, 152.3, 133.0 (2 C), 131.4, 129.2
(2 C), 128.9 (2 C), 127.2, 126.8, 119.9, 117.1, 111.5, 41.7, 30.0, 21.4,
20.5, 20.0.
4-(5-Methyl-7-nitro-3-phenylbenzo[b]furan-2-yl)butan-2-one
(7j)
HRMS (ESI/TOF): m/z [M + H]+ calcd for C20H21O2: 293.1536; found:
293.1530.
Pale yellow oil; yield: 99 mg (61%).
1H NMR (CDCl3):  = 7.91 (br s, 1 H, HAr), 7.60 (br s, 1 H, HAr), 7.53–7.46
(m, 4 H, HAr), 7.44–7.40 (m, 1 H, HAr), 3.21 (t, 3J = 7.4 Hz, 2 H, CH2),
3.00 (t, 3J = 7.4 Hz, 2 H, CH2), 2.49 (s, 3 H, CH3), 2.21 (s, 3 H, CH3).
4-[5,6-Dimethyl-3-(4-methylphenyl)benzo[b]furan-2-yl]butan-2-
one (7o)
Pale yellow oil; yield: 148 mg (97%).
13C{1H} NMR (CDCl3):  = 206.6, 156.2, 144.8, 133.3, 133.2, 133.1,
131.2, 129.3 (2 C), 129.2 (2 C), 128.1, 126.6, 121.0, 117.4, 41.0, 30.0,
21.2, 21.1.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H18NO4: 324.1230; found:
324.1238.
1H NMR (CDCl3):  = 7.39–7.37 (m, 2 H, HAr), 7.30–7.29 (m, 3 H, HAr),
7.22 (s, 1 H, HAr), 3.13 (t, 3J = 7.6 Hz, 2 H, CH2), 2.88 (t, 3J = 7.6 Hz, 2 H,
CH2), 2.43 (s, 3 H, CH3), 2.37 (s, 3 H, CH3), 2.32 (s, 3 H, CH3), 2.15 (s, 3
H, CH3).
13C{1H} NMR (CDCl3):  = 207.1, 153.2, 152.1, 136.9, 132.9, 131.3,
129.9, 129.6 (2 C), 129.1 (2 C), 127.1, 120.0, 117.0, 111.5, 41.8, 30.0,
21.4 (2 C), 20.5, 20.0.
4-(4,7-Dimethoxy-3-phenylbenzo[b]furan-2-yl)butan-2-one (7k)
Pale yellow oil; yield: 107 mg (66%).
HRMS (ESI/TOF): m/z [M + H]+ calcd for C21H23O2: 307.1693; found:
307.1699.
1H NMR (CDCl3):  = 7.47–7.45 (m, 2 H, HAr), 7.42–7.39 (m, 2 H, HAr),
3
3
7.35–7.32 (m, 1 H, HAr), 6.70 (d, J = 8.6 Hz, 1 H, HAr), 6.54 (d, J = 8.6
Hz, 1 H, HAr), 3.98 (s, 3 H, OCH3), 3.63 (s, 3 H, OCH3), 3.07 (t, 3J = 7.6 Hz,
2 H, CH2), 2.89 (t, 3J = 7.6 Hz, 2 H, CH2), 2.12 (s, 3 H, CH3).
4-(3-Methylbenzo[b]furan-2-yl)butan-2-one (7p)
Pale yellow oil; yield: 80 mg (79%).
13C{1H} NMR (CDCl3):  = 206.7; 152.7, 148.4, 144.4, 140.1, 132.7,
130.0 (2 C), 127.7 (2 C), 127.0, 119.7, 117.7, 106.3, 104.1, 56.6, 56.1,
41.7, 29.7, 20.9.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C20H21O4: 325.1434; found:
325.1436.
1H NMR (CDCl3):  = 7.44–7.42 (m, 1 H, HAr), 7.38–7.36 (m, 1 H, HAr),
7.24–7.18 (m, 2 H, HAr), 3.02 (t, 3J = 7.3 Hz, 2 H, CH2), 2.87 (t, 3J = 7.3
Hz, 2 H, CH2), 2.19 (s, 3 H, CH3), 2.17 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 207.1, 154.1, 152.5, 130.5, 123.4, 122.2,
118.9, 110.6, 110.3, 41.5, 30.0, 20.6, 7.9.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C13H15O2: 203.1067; found:
4-(4-Bromo-7-methoxy-3-phenylbenzo[b]furan-2-yl)butan-2-one
(7l)
203.1060.
Pale yellow oil; yield: 121 mg (65%).
4-(3,5-Dimethylbenzo[b]furan-2-yl)butan-2-one (7q)24a
Pale yellow oil; yield: 92 mg (85%).
1H NMR (CDCl3):  = 7.40–7.36 (m, 5 H, HAr), 7.24 (d, J = 8.5 Hz, 1 H,
3
3
3
HAr), 6.66 (d, J = 8.5 Hz, 1 H, HAr), 4.00 (s, 3 H, OCH3), 2.94 (t, J = 7.5
Hz, 2 H, CH2), 2.84 (t, 3J = 7.5 Hz, 2 H, CH2), 2.11 (s, 3 H, CH3).
1H NMR (CDCl3):  = 7.24 (d, 3J = 8.2 Hz, 1 H, HAr), 7.21 (br s, 1 H, HAr),
13C{1H} NMR (CDCl3):  = 206.5, 155.3, 144.9, 143.9, 131.6 (2 C), 131.4,
128.9, 127.9 (2 C), 127.8, 127.4, 118.8, 107.4, 104.4, 56.5, 41.6, 29.8,
21.1.
7.03 (br d, J = 8.2 Hz, 1 H, HAr), 3.00 (t, J = 7.3 Hz, 2 H, CH2), 2.86 (t,
3
3
3J = 7.3 Hz, 2 H, CH2), 2.45 (s, 3 H, CH3), 2.16 (s, 6 H, 2 CH3).
13C{1H} NMR (CDCl3):  = 207.2, 152.6, 152.5, 131.6, 130.5, 124.6,
118.9, 110.1, 110.0, 41.6, 30.0, 21.4, 20.6, 7.9.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H18BrO3: 373.0434; found:
373.0434.
4-(5-Chloro-3-methylbenzo[b]furan-2-yl)butan-2-one (7r)24a
4-[6,7-Dimethyl-3-(4-methylphenyl)benzo[b]furan-2-yl]butan-2-
one (7m)
Pale yellow oil; yield: 105 mg (89%).
1H NMR (CDCl3):  = 7.37 (d, 4J = 1.7 Hz, 1 H, HAr), 7.25 (d, 3J = 8.7 Hz, 1
H, HAr), 7.15 (dd, 3J = 8.7 Hz, 4J = 1.7 Hz, 1 H, HAr), 2.99 (t, 3J = 7.2 Hz, 2
H, CH2), 2.86 (t, 3J = 7.2 Hz, 2 H, CH2), 2.16 (s, 3 H, CH3), 2.14 (s, 3 H,
CH3).
13C{1H} NMR (CDCl3):  = 206.9, 154.3, 152.5, 131.9, 128.0, 123.5,
118.7, 111.6, 110.2, 41.3, 30.0, 20.6, 7.8.
Pale yellow oil; yield: 136 mg (89%).
1H NMR (CDCl3):  = 7.42–7.40 (m, 2 H, HAr), 7.31–7.28 (m, 3 H, HAr),
7.06 (d, 3J = 7.9 Hz, 1 H, HAr), 3.19 (t, 3J = 7.6 Hz, 2 H, CH2), 2.92 (t,
3J = 7.6 Hz, 2 H, CH2), 2.47 (s, 3 H, CH3), 2.44 (s, 3 H, CH3), 2.42 (s, 3 H,
CH3), 2.19 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 207.2, 153.6, 152.1, 136.9, 132.3, 129.9,
129.6 (2 C), 129.0 (2 C), 126.4, 124.8, 119.5, 117.5, 116.4, 41.8, 29.9,
21.5, 21.3, 19.2, 11.7.
4-(5-Methoxy-3-methylbenzo[b]furan-2-yl)butan-2-one (7s)24a
Pale yellow oil; yield: 100 mg (86%).
HRMS (ESI/TOF): m/z [M + H]+ calcd for C21H23O2: 307.1693; found:
307.1695.
1H NMR (CDCl3):  = 7.24 (d, 3J = 8.8 Hz, 1 H, HAr), 6.87 (d, 4J = 2.4 Hz, 1
3
4
H, HAr), 6.81 (dd, J = 8.8 Hz, J = 2.4 Hz, 1 H, HAr), 3.85 (s, 3 H, OCH3),
2.98 (t, 3J = 7.3 Hz, 2 H, CH2), 2.86 (t, 3J = 7.3 Hz, 2 H, CH2), 2.16 (s, 3 H,
CH3), 2.15 (s, 3 H, CH3).
4-(5,6-Dimethyl-3-phenylbenzo[b]furan-2-yl)butan-2-one (7n)
Pale yellow oil; yield: 136 mg (93%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

I
A. S. Makarov et al.
Paper
Synthesis
13C{1H} NMR (CDCl3):  = 207.3, 155.8, 153.5, 148.9, 131.0, 111.7,
1-(3-Phenylbenzo[b]furan-2-yl)pentan-3-one (7y)
111.0, 110.5, 102.0, 56.1, 41.6, 30.1, 20.7, 8.0.
Pale yellow oil; yield: 133 mg (96%).
1H NMR (CDCl3):  = 7.59–7.58 (m, 1 H, HAr), 7.55–7.46 (m, 5 H, HAr),
4-[3-(1-Methylethyl)benzo[b]furan-2-yl]butan-2-one (7t)
3
7.41–7.38 (m, 1 H, HAr), 7.31–7.23 (m, 2 H, HAr), 3.20 (t, J = 7.6 Hz, 2
H, CH2), 2.92 (t, 3J = 7.6 Hz, 2 H, CH2), 2.46 (q, 3J = 7.3 Hz, 2 H, CH2),
1.09 (t, 3J = 7.3 Hz, 3 H, CH3).
Pale yellow oil; yield: 90 mg (78%).
1H NMR (CDCl3):  = 7.61–7.59 (m, 1 H, HAr), 7.38–7.36 (m, 1 H, HAr),
7.22–7.14 (m, 2 H, HAr), 3.18–3.08 (m, 1 H, CH), 3.03 (t, 3J = 7.4 Hz, 2 H,
13C{1H} NMR (CDCl3):  = 209.8, 154.1, 153.2, 132.5, 129.2 (2 C), 129.0
(2 C), 128.9, 127.3, 123.9, 122.8, 119.7, 117.4, 110.9, 40.2, 36.1, 21.3,
7.9.
3
3
CH2), 2.86 (t, J = 7.4 Hz, 2 H, CH2), 2.18 (s, 3 H, CH3), 1.40 (d, J = 7.0
Hz, 6 H, 2 CH3).
13C{1H} NMR (CDCl3):  = 207.1, 154.4, 151.1, 128.4, 123.2, 122.0,
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H19O2: 279.1380; found:
120.7, 120.5, 111.0, 42.0, 30.1, 25.5, 22.6 (2 C), 21.0.
279.1372.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C15H19O2: 231.1380; found:
231.1373.
4,4-Dimethyl-1-(3-phenylbenzo[b]furan-2-yl)pentan-3-one (7z)
Pale yellow oil; yield: 148 mg (97%).
4-(3-Cyclohexylbenzo[b]furan-2-yl)butan-2-one (7u)
1H NMR (CDCl3):  = 7.58–7.45 (m, 6 H, HAr), 7.40–7.36 (m, 1 H, HAr),
7.29–7.21 (m, 2 H, HAr), 3.17 (t, 3J = 7.5 Hz, 2 H, CH2), 2.99 (t, 3J = 7.5
Hz, 2 H, CH2), 1.17 (s, 9 H, 3 CH3).
13C{1H} NMR (CDCl3):  = 214.2, 154.2, 153.7, 132.7, 129.2 (2 C), 129.1,
129.0 (2 C), 127.3, 123.9, 122.9, 119.8, 117.3, 110.9, 44.3, 34.9, 26.6 (3
C), 21.6.
Pale yellow oil; yield: 90 mg (67%).
1H NMR (CDCl3):  = 7.65–7.63 (m, 1 H, HAr), 7.38–7.36 (m, 1 H, HAr),
7.21–7.15 (m, 2 H, HAr), 3.05 (t, 3J = 7.4 Hz, 2 H, CH2), 2.87 (t, 3J = 7.4
Hz, 2 H, CH2), 2.77–2.70 (m, 1 H, CH), 2.18 (s, 3 H, CH3), 1.90–1.82 (m,
7 H, CH2), 1.50–1.34 (m, 3 H, CH2).
13C{1H} NMR (CDCl3):  = 207.1, 154.3, 151.5, 128.7, 123.1, 121.9,
HRMS (ESI/TOF): m/z [M + H]+ calcd for C21H23O2: 307.1693; found:
120.6, 119.9, 110.9, 42.0, 35.9, 32.7 (2 C), 30.0, 27.1 (2 C), 26.3, 21.0.
307.1695.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C18H23O2: 271.1693; found:
271.1685.
1-(4-Chlorophenyl)-3-(3-phenylbenzo[b]furan-2-yl)propan-1-one
(7aa)
4-(3-tert-Butylbenzo[b]furan-2-yl)butan-2-one (7v)
Pale yellow oil; yield: 138 mg (90%).
1H NMR (CDCl3):  = 7.93–7.91 (m, 2 H, HAr), 7.60–7.49 (m, 5 H, HAr),
7.47–7.39 (m, 4 H, HAr), 7.33–7.24 (m, 2 H, HAr), 3.48–3.44 (m, 2 H,
CH2), 3.39–3.35 (m, 2 H, CH2).
13C{1H} NMR (CDCl3):  = 197.2, 154.2, 153.1, 139.7, 135.1, 132.5,
129.6 (2 C), 129.2 (2 C), 129.1 (2 C), 129.0 (2 C), 128.9, 127.4, 124.0,
122.9, 119.8, 117.6, 111.0, 36.9, 21.6.
Pale yellow oil; yield: 66 mg (54%).
1H NMR (CDCl3):  = 7.74–7.71 (m, 1 H, HAr), 7.36–7.34 (m, 1 H, HAr),
7.21–7.14 (m, 2 H, HAr), 3.22 (t, 3J = 7.5 Hz, 2 H, CH2), 2.89 (t, 3J = 7.5
Hz, 2 H, CH2), 2.19 (s, 3 H, CH3), 1.51 (s, 9 H, 3 CH3).
13C{1H} NMR (CDCl3):  = 207.2, 154.1, 150.7, 129.2, 123.1, 122.7,
122.3, 121.7, 110.8, 42.5, 32.4, 31.3 (3 C), 30.0, 23.2.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C23H18ClO2: 361.0990; found:
361.0992.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C16H21O2: 245.1536; found:
245.1529.
2-[2-Oxo-4-(3-phenylbenzo[b]furan-2-yl)butyl]-1H-isoindole-
1,3(2H)-dione (7ab)
4-(3-Benzylbenzo[b]furan-2-yl)butan-2-one (7w)
Pale yellow oil; yield: 100 mg (72%).
Pale yellow oil; yield: 176 mg (86%).
1H NMR (CDCl3):  = 7.41–7.39 (m, 1 H, HAr), 7.31–7.19 (m, 7 H, HAr),
7.15–7.11 (m, 1 H, HAr), 4.04 (s, 2 H, CH2), 3.07 (t, 3J = 7.4 Hz, 2 H, CH2),
2.86 (t, 3J = 7.4 Hz, 2 H, CH2), 2.16 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 206.9, 154.3, 153.6, 139.9, 129.7, 128.6 (2 C),
128.5 (2 C), 126.3, 123.6, 122.4, 119.6, 113.7, 110.8, 41.6, 30.0, 29.7,
20.8.
1H NMR (CDCl3):  = 7.92–7.90 (m, 2 H, HAr), 7.78–7.76 (m, 2 H, HAr),
7.60–7.58 (m, 1 H, HAr), 7.54–7.51 (m, 5 H, HAr), 7.43–7.39 (m, 1 H,
HAr), 7.34–7.24 (m, 2 H, HAr), 4.56 (s, 2 H, CH2), 3.27 (t, 3J = 7.5 Hz, 2 H,
CH2), 3.05 (t, 3J = 7.5 Hz, 2 H, CH2).
13C{1H} NMR (CDCl3):  = 200.8, 167.7 (2 C), 154.3, 152.4, 134.3 (2 C),
132.4, 132.3 (2 C), 129.2 (2 C), 129.0 (2 C), 128.9, 127.5, 124.2, 123.7
(2 C), 123.0, 119.8, 117.8, 111.2, 46.7, 38.0, 21.0.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C19H19O2: 279.1380; found:
279.1373.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C26H20NO4: 410.1387; found:
410.1391.
4-(Benzo[b]furan-2-yl)butan-2-one (7x)30b
Pale yellow oil; yield: 14 mg (15%).
Gram-Scale Synthesis of 4-(3-Phenylbenzo[b]furan-2-yl)butan-2-
one (7a)
1H NMR (CDCl3):  = 7.48–7.46 (m, 1 H, HAr), 7.41–7.39 (m, 1 H, HAr),
7.23–7.16 (m, 2 H, HAr), 6.40 (s, 1 H, HAr), 3.06 (t, 3J = 7.3 Hz, 2 H, CH2),
2.89 (t, 3J = 7.3 Hz, 2 H, CH2), 2.19 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 206.8, 157.8, 154.9, 129.0, 123.5, 122.7,
120.5, 110.9, 102.5, 41.4, 30.0, 22.8.
A 100-mL round-bottom flask equipped with a rubber septum was
charged with 2-[hydroxyl(phenyl)methyl]phenol (5a; 3.0 g, 15
mmol), 2-methylfuran (1a; 1.99 mL, 22.5 mmol, 1.5 equiv), and DCE
(50 mL). TfOH (132 L, 10 mol%) was added to the resulting solution
at rt with vigorous stirring in one portion. The vial was placed into
preheated (80 °C) aluminum block and stirred for 2 h (TLC control).
After completion of the reaction, the resulting solution was concen-
HRMS (ESI/TOF): m/z [M + H]+ calcd for C12H13O2: 189.0910; found:
189.0904.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

J
A. S. Makarov et al.
Paper
Synthesis
trated in vacuo, and the remaining oily crude mixture was subjected
to column chromatography (silica gel, gradient elution petroleum
ether/EtOAc 99:1 to 20:1) to afford the product as a pale yellow oil;
yield: 3.603 g (91%).
13C{1H} NMR (CDCl3):  = 153.4, 149.7, 149.1, 133.7, 129.4, 120.1,
119.7, 112.2, 109.0, 103.8, 25.9, 25.8, 18.0, 16.6, 8.0.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C15H19O2: 231.1380; found:
231.1388.
4-(5-Hydroxy-3,6-dimethylbenzo[b]furan-2-yl)butan-2-one (7ac)
To a solution of ketone 1225b (332 mg, 2 mmol) in THF (15 mL) was
added dropwise 1.0 M BH3 in THF (6 mL, 6 mmol) at 0 °C. The result-
ing solution was stirred for 1 h at this temperature and 2 h at rt. Then
the mixture was quenched with water (1 mL) and concentrated in
vacuo. The crude salicyl alcohol was dissolved in DCE (30 mL); 2-
methylfuran (1a; 215 L, 2.4 mmol) and TsOH·H2O (19 mg, 0.1 mmol)
were added. The mixture was stirred at 55 °C for 1 h then at 80 °C for
a further 1 h. When the reaction was completed (TLC control), the
mixture was concentrated and subjected to column chromatography
(silica gel, petroleum ether/CH2Cl2 4:1 to 0:1) to afford 7ac as pale yel-
low oil; yield: 422 mg (91%).
Funding Information
This work was supported by the Russian Science Foundation (Grant
No. 17-73-10349).
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690000.
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1H NMR (CDCl3):  = 7.10 (s, 1 H, HAr), 6.77 (s, 1 H, HAr), 4.92 (br s, 1 H,
OH), 2.96 (t, 3J = 7.2 Hz, 2 H, CH2), 2.84 (t, 3J = 7.2 Hz, 2 H, CH2), 2.33 (s,
3 H, CH3), 2.16 (s, 3 H, CH3), 2.09 (s, 3 H, CH3).
13C{1H} NMR (CDCl3):  = 207.8, 152.5, 149.9, 149.0, 129.1, 120.6,
112.0, 110.0, 103.9, 41.6, 30.1, 20.7, 16.6, 8.0.
References
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Eur. J. Med. Chem. 2015, 97, 561. (d) Khanam, H.; Shamsuz-
zaman Eur. J. Med. Chem. 2015, 97, 483. (e) Hiremathad, A.; Patil,
M. R.; Chethana, K. R.; Chand, K.; Santos, M. A.; Keri, R. S. RSC
Adv. 2015, 5, 96809.
(2) Bhalla, S.; Balasubramanian, S.; David, K.; Sirisawad, M.; Buggy,
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(3) (a) Hughes, Z. A.; Starr, K. R.; Langmead, C. J.; Hill, M.; Bartoszyk,
G. D.; Hagan, J. J.; Middlemiss, D. N.; Dawson, L. A. Eur. J. Phar-
macol. 2005, 510, 49. (b) Page, M. E.; Cryan, J. F.; Sullivan, A.;
Dalvi, A.; Saucy, B.; Manning, D. R.; Lucki, I. J. Pharmacol. Exp.
Ther. 2002, 302, 1220.
(4) Delini-Stula, A.; Fischbach, R.; Gnirss, F.; Bures, E.; Pöldinger, W.
Drug Dev. Res. 1985, 6, 371.
(5) Lotufo-Neto, F.; Trivedi, M.; Thase, M. E. Neuropsychopharma-
cology 1999, 20, 226.
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221, 780.
HRMS (ESI/TOF): m/z [M + H]+ calcd for C14H17O3: 233.1172; found:
233.1174.
2-(3-Hydroxy-3-methylbutyl)-3,6-dimethylbenzo[b]furan-5-ol
(13)
To a solution of benzofuran 7ac (160 mg, 0.7 mmol) in toluene (10
mL) was added 3.0 M MeMgI in Et2O (1.16 mL, 3.5 mmol) at 0 °C. The
resulting suspension was slowly warmed to rt and stirred for 3 h.
When the reaction was complete (TLC control), the mixture was
quenched with sat. aq NH4Cl (2 mL) and diluted with water (40 mL).
The organic phase was separated and the aqueous phase was extract-
ed with EtOAc (2 × 30 mL). The combined organic fractions were
washed with water (2 × 20 mL) and brine (30 mL), dried (anhyd
Na2SO4), and concentrated. The residue was purified by column chro-
matography (silica gel, petroleum ether/EtOAc 30:1 to 10:1) to give
the product as pale yellow oil; yield: 172 mg (99%).
1H NMR (CDCl3):  = 7.11 (s, 1 H, HAr), 6.77 (s, 1 H, HAr), 4.78 (br s, 1 H,
OH), 2.80 (m, 2 H, CH2), 2.33 (s, 3 H, CH3), 2.09 (s, 3 H, CH3), 1.88 (m, 2
H, CH2), 1.39 (br s, 1 H, OH), 1.29 (s, 6 H, 2 CH3).
13C{1H} NMR (CDCl3):  = 154.2, 149.8, 149.0, 129.3, 120.3, 112.1,
109.2, 103.8, 70.9, 41.8, 29.4 (2 C), 21.6, 16.6, 8.0.
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HRMS (ESI/TOF): m/z [M + H]+ calcd for C15H21O3: 249.1485; found:
249.1485.
Sugikurojinol B (2-(3-Methylbut-2-enyl)-3,6-dimethylbenzo[b]fu-
ran-5-ol, 10)
(11) Rao, G. H.; Pandey, M.; Narayanaswamy, K.; Rao, R. S.; Pandey, S.
S.; Hayase, S.; Singh, S. P. ACS Omega 2018, 3, 13919.
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To a solution of alcohol 13 (100 mg, 0.4 mmol) in DCE (2.5 mL) were
added TsOH·H2O (3.8 mg, 0.02 mmol) and granulated MS 4Å (30 mg).
The mixture was stirred for 3 h at 80 °C, then cooled to rt, passed
through a pad of silica, washed with CH2Cl2, and concentrated to af-
ford a mixture of olefins 10 and 14 (91 mg, 99% combined yield; ratio
of isomers 5.6:1).
(14) (a) Galvani, G.; Harsha Vardhan Reddy, K.; Beauvineau, C.;
Ghermani, N.; Mahuteau-Betzer, F.; Alami, M.; Messaoudi, S.
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2-(3-Methylbut-2-enyl)-3,6-dimethylbenzo[b]furan-5-ol (10)28
1H NMR (CDCl3):  = 7.13 (s, 1 H, HAr), 6.77 (s, 1 H, HAr), 5.33 (t, 3J = 7.0
Hz, 1 H, =CH), 4.53 (br s, 1 H, OH), 3.40 (d, 3J = 7.0 Hz, 2 H, CH2), 2.33
(s, 3 H, CH3), 2.10 (s, 3 H, CH3), 1.75 (s, 3 H, CH3), 1.74 (s, 3 H, CH3).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K

K
A. S. Makarov et al.
Paper
Synthesis
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–K