In SituAnodically Oxidized BMIm-BF4: A Safe and Recyclable BF3Source

Article abstract of DOI:10.1021/acs.joc.1c00932

The anodic oxidation of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF₄) efficiently generates BF₃from BF₄^-. This Lewis acid, strongly bound to the ionic liquids, can be efficiently used in classical BF₃-catalyzed reactions. We demonstrated the BF₃/BMIm-BF₄reactivity in four reactions, namely, a domino Friedel-Crafts/lactonization of phenols, the Povarov reaction, the Friedel-Crafts benzylation of anisole, and the multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-11-ones. In comparison with literature data using BF₃-Et₂O in organic solvents, in all the presented cases, analogous or improved results were obtained. Moreover, the noteworthy advantages of the developed method are thein situgeneration of BF₃(no storing necessity) in the required amount, using only the electron as redox reagent, and the recycling of BMIm-BF₄for multiple subsequent runs.

Full text of DOI:10.1021/acs.joc.1c00932

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In Situ Anodically Oxidized BMIm-BF4: A Safe and Recyclable BF3
Source
Martina Bortolami, Leonardo Mattiello, Vincenzo Scarano, Fabrizio Vetica, and Marta Feroci*
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ABSTRACT: The anodic oxidation of 1-butyl-3-methylimidazo-
lium tetrafluoroborate (BMIm-BF4) efficiently generates BF3 from
−
BF4 . This Lewis acid, strongly bound to the ionic liquids, can be
efficiently used in classical BF3-catalyzed reactions. We demon-
strated the BF3/BMIm-BF4 reactivity in four reactions, namely, a
domino Friedel−Crafts/lactonization of phenols, the Povarov
reaction, the Friedel−Crafts benzylation of anisole, and the
multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-11-
ones. In comparison with literature data using BF3-Et2O in organic
solvents, in all the presented cases, analogous or improved results
were obtained. Moreover, the noteworthy advantages of the
developed method are the in situ generation of BF3 (no storing
necessity) in the required amount, using only the electron as redox
reagent, and the recycling of BMIm-BF4 for multiple subsequent runs.
Scheme 1. BF3 Anodic Generation
oron trifluoride is a well-known Lewis acid, often used in
Borganic synthesis to carry out many acid-catalyzed
transformations.1
Although this reagent is very common, its use may face
problems and small accidents due to its high reactivity and
volatility. Additionally, this gas is highly toxic and corrosive
and has a suffocating odor.2
ILs are liquid salts formed by a large, nonsymmetrical
organic cation and (usually) a noncoordinating anion (organic
or inorganic).7 Their use as solvents in organic transformations
is growing in the past years, due to their ability to solubilize
organic and inorganic compounds and, mainly, to their
virtually null volatility, allowing for their easy recovery.8 In
organic electrochemistry, they can be used as supporting
electrolytes or also as solvents, permitting carrying out
electrolyses and, after workup, to recover the IL.9 In this
context, the most frequently used class of ILs is the
imidazolium one, which are cheap, liquid in a wide range of
temperatures, and possess good solvating properties. Never-
theless, imidazolium ILs are in some cases reactive under
electrochemical conditions.10 In fact, the cathodic limit of an
imidazolium IL (unsubstituted at the 2-position) is usually the
C2−H bond scission with formation of the corresponding N-
heterocyclic carbene (NHC), widely exploited,6,11 while the
anodic limit is the oxidation of the anion. In the case of 1-
To make BF3 easier to handle, liquid etherate complexes,
consisting of a 1:1 molar ratio of BF3 and ether (usually
dimethyl or diethyl), are used and dissociated under
appropriate temperature and pressure conditions.3
Nonetheless, these compounds show corrosive properties
and flammability, so it is necessary to use them under a hood,
wearing nitrile gloves and eye protection.4 Moreover, they are
sensitive to humidity and form acidic fumes in moist air.
The in situ generation of BF3 in the exact amount needed
minimizes these problems.
Organic electrochemistry can help with this scope.5 In fact,
−
BF3 can be easily obtained by anodic oxidation of the BF4
anion (Scheme 1).6
When using electrochemistry, the reagent is the electron
(inherently nonpolluting and cheap), very easy to dose simply
by closing or opening the electrical circuit.
The conductivity of the solution is normally ensured by a
supporting electrolyte in high concentration (up to 0.5 M).
The need of such salt in solution (one of the criticisms to
organic electrochemistry raised by organic chemists) can be
overcome by using an ionic liquid (IL) as both solvent and
supporting electrolyte.
Special Issue: Electrochemistry in Synthetic Organic
Chemistry
Received: April 22, 2021
© XXXX The Authors. Published by
American Chemical Society
https://doi.org/10.1021/acs.joc.1c00932
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A

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Note
Scheme 2. Exploited BF3-Catalyzed Reactions
a
Table 1. BF3-Catalyzed Reaction between Phenols and Diethyl Ketomalonate
b
c
c
entry
d
R
BF3 (%)
T/time
r.t./15 h
50 °C/4 h
r.t./24 h
r.t./2 h, 50 °C/2 h
50 °C/4 h
50 °C/4 h
50 °C/4 h
r.t./24 h
60 °C/6 h
60 °C/6 h
r.t./2 h
3
4
1
2
3
4
5
6
7
4-OCH3 (1a)
4-OCH3 (1a)
4-OCH3 (1a)
4-OCH3 (1a)
4-OCH3 (1a)
H (1b)
fused Ph (2-naphthol, 1c)
4-OCH3 (1a)
4-OCH3 (1a)
H (1b)
100
100
30
30
30
57% (3a)
63% (3a)
56% (3a)
32% (3a)
79% (3a)
88% (3b)
86% (3c)
36% (3a)
84% (3a)
87% (3b)
95% (3c)
17% (4a)
d
d
d
d
19% (4a)
17% (4a)
30
30
8, lit.13
9, lit.13
10, lit.13
11, lit.13
30, BF3-Et2O in CH2Cl2
TiCl4, 10% in CHCl3
TiCl4, 10% in CHCl3
TiCl4, 10% in CHCl3
traces
traces
fused Ph (2-naphthol, 1c)
a
BMIm-BF4 (divided cell) was electrolyzed (galvanostatic conditions: 10 mA cm−2) on platinum electrodes (r.t., N2). At the end of electrolysis,
phenol 1 (0.5 mmol) and diethyl ketomalonate 2 (0.5 mmol) were added to the anolyte. The mixture was stirred (T and time in table) and then
b
extracted with diethyl ether. Amount of electrogenerated BF3 with respect to starting phenol, admitting a 100% current efficiency (96.5 C: 1 mmol
c
d
of BF3). Isolated yields after column chromatography. Entries 1−5: the same recycled IL was used.
butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4), the
oxidation of the anion forms BF3,6 as previously stated
(Scheme 1). The relatively high potential for BF3 generation
prevents the presence of electroactive substrates in solution
during electrolysis (see cyclic voltammetries in the Supporting
Information). We were interested in an alternative, less
dangerous source of BF3, generated in situ and thus not
The main disadvantage derives from the use of the IL, i.e.,
the low solubility of apolar molecules.
The examples considered (Scheme 2) are intended to
demonstrate the efficiency of this system in classical BF3-
catalyzed reactions, and thus no extensive studies for the
optimization of yields and reaction scope are reported. It
should be underlined that, when more than one reaction was
carried out on a particular substrate, the same IL was used in
all reactions, recycled after ethereal extraction and submitted to
a new anodic oxidation. To the best of our knowledge,
anodically generated BF3 in IL was used only in one paper12
reporting the BF3 induced Michael addition of a 1,3-dicarbonyl
compound to methyl vinyl ketone, without IL recycling.
The reaction between a phenol 1 and diethyl ketomalonate
2, in the presence of a Lewis acid, leads to the formation of a 3-
hydroxybenzofuran-2-one 3 and, in the case of incomplete
reaction, of the 2-substituted phenol 4 (Table 1).13 These
products derive from a Friedel−Crafts phenol alkylation in the
2-position, followed by a cyclization with ethanol elimination.
The increase of the temperature to 60 °C promoted the
lactonization, giving selectively the 3-hydroxybenzofuran-2-one
3.
−
stored. The electrochemical oxidation of BF4 in IL seemed
the good choice, and we carried out some classical BF3-
catalyzed reactions in anodically oxidized BMIm-BF4, being
this IL really easy to recycle after ethereal extraction. In order
to avoid interferences from the cathodically generated NHC, a
divided cell was used.
The advantages in this BF3 source can be summarized in
• in situ generation, avoiding the storage (simple
galvanostatic electrolysis)
• easy to dose (current on/off)
• no fumes production (strong interaction with IL)
• no particular sensitivity to moisture (IL as moist
protector)
• easy IL recovery and multiple recycling after ethereal
extraction
B
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Note
a
Table 2. BF3-Catalyzed Povarov Reaction
b
c
d
e
entry
R1, R2
5/6/7
BF3 (%)
8
cis/trans
f
1
2
3
4
5
6
7
8
9
CH3/H
CH3/H
CH3/H
CH3/H
1/1/4
1/1/3
1/1/3
1/1/2
1/1/1
1/1/3
1/1/3
1/1/3
1/1/3
1/1/1
1/1/2
50
25
50
50
50
50
25
50
25
68% (8a)
96% (8a)
91% (8a)
82% (8a)
37% (8a)
79% (8b)
89% (8b)
69% (8c)
63% (8c)
15%
76/24
71/29
79/21
68/32
71/29
76/24
92/8
f
f
f
f
CH3/H
g
g
h
h
OCH3/H
OCH3/H
CH3/OCH3
CH3/OCH3
H/H
65/35
71/29
10, lit.14
11, lit.16
3, BF3-Et2O/Et2O
30, I2/MeCN
OCH3/H
95% (8b)
8/92
a
Aniline 5 (0.5 mmol), benzaldehyde 6 (0.5 mmol), and 3,4-dihydro-2H-pyran 7 (amount as in table) were added to the anodically generated BF3/
b
c
BMIm-BF4 (footnote a of Table 1). The mixture was stirred at r.t. for 3 h and then extracted with diethyl ether. 5 to 6 to 7, molar ratio. Amount
d
of electrogenerated BF3 with respect to starting aniline, admitting a 100% current efficiency (96.5 C: 1 mmol of BF3). Isolated yields after column
e
f
g
chromatography. Determined by the 1H NMR of the crude. Entries 1−5: the same recycled IL was used. Entries 6 and 7: the same recycled IL
h
was used. Entries 8 and 9: the same recycled IL was used.
Different Lewis acids in catalytic amounts in CH2Cl2 at
room temperature were used, with good yields.13
dihydropyran 7. High yields of compounds 8a−c were
obtained (96%, 89%, and 69% yields, entries 2, 7, and 8,
respectively). In all the cases in this work, the yields obtained
are higher when compared with analogous literature data
(entry 10).14 Moreover, the cis isomer was synthesized
preferentially, in accordance with other methodologies which
employ Lewis acids in classical organic solvents15 and with
opposite diastereoselectivity observed by using I2 as catalyst
(Table 2, entry 11).16 Also in this case, it was possible to reuse
the same ionic liquid (entries 1−5, Table 2) in subsequent
runs without reactivity loss.
The third reaction considered is the Friedel−Crafts
benzylation of anisole 10 with benzyl alcohol 9 (Table 3), in
which anisole is monobenzylated in the ortho or para positions
(the meta isomer being present only in traces).17
Good yields in benzylated anisole 11 were obtained using a
stoichiometric (69%, entry 3) or overstoichiometric (80%,
entry 5) amount of catalyst. Moreover, milder reaction
conditions were used, with respect to the literature (r.t. vs
65−80 °C, Table 3), and more importantly, the efficient
recycling of the IL was demonstrated (entries 1−5).
The literature data here reported for comparison (entry 6,
Table 3) showed that the thermodynamic favorite product p-
11 can be obtained using a very large excess of anisole (10 to
9: 18/1) at 80 °C. The positive effect of an imidazolium IL as
solvent in this reaction, involving charged species as
intermediates, is confirmed by literature data, besides the
results obtained in this work (Table 3, entry 7).18
The last example is the multicomponent synthesis of
tetrahydro-11H-benzo[a]xanthen-1-one 13 from benzaldehyde
6, 2-naphthol 1c, and dimedone 12 (Table 4).
We tested the anodically generated BF3 in BMIm-BF4 in this
reaction, and the results are reported in Table 1, along with the
corresponding literature data, for a useful comparison.
As reported in Table 1, high yields in products 3a−c (entries
5−7) were obtained using a 30% maximum of catalyst
(calculated admitting a 100% current yield), comparable with
those obtained in the literature using the best experimental
conditions, i.e., TiCl4 as Lewis acid (entries 9−11). A direct
comparison with literature data can be made considering
entries 3 and 8, in which the same phenol (1a), amount of BF3
(30%), reaction time and temperature were used. 3a was
obtained in 56% in IL (with a 19% of intermediate 4a) with
respect to 36% of 3a obtained in CH2Cl2. Also in this case,
BMIm-BF4 demonstrated to be a solvent suitable for reactions
involving dipolar intermediates.11d Additionally, from the high
yield using 30% of BF3, we can infer that the IL acts as an
efficient solvent to bind this volatile reagent and ensures the
reiteration of the catalytic cycle. Moreover, the eco-friendly
character of this reaction in IL is demonstrated not only by the
use of electricity to generate the catalyst but also by the use of
the same IL sample in five subsequent runs (entries 1−5),
without reactivity loss.
The second reaction considered is the hetero-Diels−Alder
Povarov reaction.14 It is the reaction between an aryl amine 5,
an aryl aldehyde 6 (with formation of the corresponding
electron-poor imine), and an electron-rich dienophile (usually
3,4-dihydro-2H-pyran 7 or 2,3-dihydrofuran), yielding the
corresponding tetrahydroquinoline 8 in a cis/trans diastereo-
meric mixture (Table 2).
We tested the electrogenerated BF3/BMIm-BF4 system in
this reaction, the imine being obtained in quantitative yield by
simple addition of aniline 5 and benzaldehyde 6 to the IL (a
noteworthy dehydrating agent). As reported in Table 2, this
reaction works well using a theoretical 25% amount of BF3
(with respect to the imine), in the presence of 3 equiv of
The literature reaction was carried out in boiling ethanol (80
°C) with 20% of BF3-Et2O, obtaining high yields of 9,9-
dimethyl-12-aryl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-
11-ones 13 (Table 4, entries 6 and 7). When the reaction was
carried out in BMIm-BF4 using anodically generated BF3, good
yields of product 13 were obtained at room temperature
C
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Note
without any reactivity loss. We believe that this could be a safer
and easier approach to handle this toxic and volatile reagent
without storing need and to carry out organic transformations
in a sustainable way.
Table 3. BF3-Catalyzed Friedel−Crafts Benzylation of
a
Anisole
EXPERIMENTAL SECTION
■
General Infomation. All chemicals were commercial (Fluo-
rochem, Aldrich) and used without further purification. BMIm-BF4
(1-butyl-3-methylimidazolium tetrafluoroborate, Iolitec) was kept at
b
c
d
e
entry
9/10
BF3 (%)
11 (%) 11, p/o
f
40 °C under vacuum for 3 h before use. H and 13C spectra were
1
1
2
3
4
5
1/2
1/3
1/4
1/4
1/4
1/18
1/4
100
100
100
50
18
60
69
16
80
61
71
53/47
57/43
54/46
58/42
58/42
>99/1
57/43
f
f
f
f
recorded at ambient temperature on a Bruker Avance spectrometer
(400 MHz) or with a Gemini Varian spectrometer (300 MHz), using
the solvent as internal standard. The chemical shifts (δ) are given in
ppm relative to TMS. GC−MS analyses have been run on an HP
5892 series II GC, equipped with a 5% phenyl silicone 30m × 0.25
mm × 25 mm capillary column and coupled to an HP 5972 MSD
instrument operating at 70 eV. Flash column chromatography was
carried out using a Merck 60 kieselgel (230−400 mesh) under
pressure. Starting compounds 1, 2, 5, 6, 7, 9, 10, and 12 were
commercially available (Sigma-Aldrich) and used as received.
150
6, lit.17c
7, lit.18
120, BF3-Et2O/H2O, 80 °C
30, Yb(OTf)3/BMIm-OTf,
65 °C
g
a
Anisole 10 (amount as in table) and benzyl alcohol 9 (0.5 mmol)
were added to the anodically generated BF3/BMIm-BF4 (footnote a
of Table 1). The mixture was stirred at r.t. for 4 h and then extracted
with diethyl ether. 9 to 10, molar ratio. Amount of electrogenerated
BF3 with respect to starting 9, admitting a 100% current efficiency
(96.5 C: 1 mmol of BF3). Isolated yields after column
chromatography. Determined by the H NMR of the crude. Entries
1−5: the same recycled IL was used. 2,4-Dichlorobenzyl alcohol was
used as benzylating agent.
General Procedure for Electrochemical BF3 Production. All
the experiments were carried out in a homemade divided glass cell
separated through a porous glass plug; Pt spirals (apparent area 0.8
cm2) were used as anode and cathode. Electrolyses were performed at
constant current (I = 10 mA cm−2), at room temperature, under a
nitrogen atmosphere, using an Amel Model 552 potentiostat equipped
with an Amel Model 731 integrator. 3.0 mL of BMImBF4 was put in
the anodic compartment, 1.0 mL of BMImBF4 in the cathodic one.
After a predetermined number of Coulombs (as reported in tables)
passed through the electrolysis cell, the current was switched off, the
cathodic compartment was removed, and the reagents were added to
the anolyte under an inert atmosphere, as specified below. At the end
of the reaction, the anolyte was extracted with diethyl ether (3 × 10
mL). The solvent was eliminated from the combined organic phases
b
c
d
e
f
1
g
(Table 4, entry 1), while better results were achieved at 60 °C
(Table 4, entries 2 and 3). When 4-clorobenzaldehyde was
used, the yield was slightly lower (Table 4, entries 4 and 5),
but comparable with the literature (entry 7).
In conclusion, we efficiently in situ generated BF3 via direct
anodic oxidation of BMIm-BF4 solutions. By simply using
electrons as redox reagents, precise control of the amount of
formed BF3 could be reached and the anolyte could be used
directly to carry out organic reactions. This setup was
successfully applied to four classically BF3-catalyzed trans-
formations, affording similar or improved yields compared with
literature results. Moreover, the eco-friendly nature of the
developed methodology was demonstrated by the recycling of
the IL, which was submitted to up to five subsequent runs
1
under reduced pressure, the crude was analyzed by H NMR, and
then the products were purified by flash column chromatography.
When the same anolyte was reused in subsequent electrolyses/
experiments, prior to its reuse it, was kept under vacuum for 30 min to
eliminate diethyl ether residues.
All products were known, and their spectral data were in
accordance with those reported in the literature.
Friedel−Crafts/Lactonization Reaction. The electrolysis was
carried out as previously reported, and after the number of Coulombs
reported in Table 1, the current was switched off. Then phenol 1 (0.5
a
Table 4. BF3-Catalyzed Synthesis of Substituted Tetrahydro-11H-benzo[a]xanthen-11-ones
b
c
entry
R
BF3 (%), T (°C), t (h)
13
d
1
H
H
H
4-Cl
4-Cl
H
25, r.t., 3 h
25, 60 °C, 1 h
25, 60 °C, 2 h
25, 60 °C, 1 h
25, 60 °C, 2 h
20, BF3-Et2O/EtOH, 80 °C, 45 min
20, BF3-Et2O/EtOH, 80 °C, 45 min
68% (13a)
85% (13a)
87% (13a)
67% (13b)
76% (13b)
82% (13a)
80% (13b)
d
d
e
2
3
4
5
e
6, lit.19
7, lit.19
4-Cl
a
2-Naphthol 1c (0.5 mmol), benzaldehyde 6 (0.5 mmol), and dimedone 12 (0.5 mmol) were added to the anodically generated BF3/BMIm-BF4
b
(footnote a of Table 1). The mixture was stirred (time and temperature as in table) and then extracted with diethyl ether. Amount of
electrogenerated BF3 with respect to starting 2-naphthol, admitting a 100% current efficiency (96.5 C: 1 mmol of BF3). Isolated yields after
column chromatography. Entries 1−3: the same recycled IL was used. Entries 4 and 5: the same recycled IL was used.
c
d
e
D
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Note
mmol, 1 equiv) and diethyl ketomalonate 2 (87 mg, 0.5 mmol, 1
equiv) were added to the anolyte. The mixture was kept at room
temperature under stirring at the temperature and for the time
reported in Table 1 and then was extracted with diethyl ether (3 × 10
mL).
142.9, 141.4, 128.9, 128.4, 127.9, 127.6, 126.9, 120.0, 114.7, 73.0,
60.8, 59.6, 39.2, 25.6, 20.8, 18.1. GC−MS, m/z (%): 280 (M+· +1,
21), 279 (M+·, 100), 264 (4), 248 (16) 239 (19), 220 (81), 208 (43),
144 (31).
Trans, light yellow oil, 39 mg (28%): 1H NMR (400 MHz, CDCl3)
δ 7.38 (ddd, J = 21.8, 16.3, 7.3 Hz, 5H), 7.06 (s, 1H), 6.92 (d, J = 8.1
Hz, 1H), 6.47 (d, J = 8.1 Hz, 1H), 4.70 (d, J = 10.8 Hz, 1H), 4.37 (d,
J = 2.5 Hz, 1H), 4.15−4.08 (m, 1H), 3.99 (bs, 1H), 3.73 (td, J = 11.6,
2.4 Hz, 1H), 2.25 (s, 3H), 2.13−2.04 (m, 1H), 1.85 (dddd, J = 17.5,
13.6, 9.0, 4.6 Hz, 1H), 1.65 (tt, J = 13.3, 4.6 Hz, 1H), 1.47 (d, J = 13.6
Hz, 1H), 1.33 (d, J = 13.3 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 142.5, 142.5, 131.1, 130.1, 128.6, 127.9, 126.7, 120.7,
114.3, 74.6, 68.7, 54.9, 39.1, 24.2, 22.0, 20.4. GC−MS, m/z (%): 280
(M+· +1, 14), 279 (M+·, 70), 248 (9) 234 (13), 220 (100), 208 (22),
144 (24).
Ethyl 3-Hydroxy-5-methoxy-2-oxo-2,3-dihydrobenzofuran-3-
carboxylate (3a).13 The product was isolated after flash chromatog-
raphy on silica gel (light petroleum ether/EtOAc 7:3) as a yellow oil,
1
100 mg (79%). H NMR (300 MHz, CDCl3) δ 7.08 (d, J = 8.8 Hz,
1H), 6.95 (d, J = 8.8 Hz, 1H), 6.84 (s, 1H), 4.44 (s, 1H), 4.16−4.39
(m, 2H), 3.79 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (75
MHz, CDCl3) δ 172.1, 168.5, 157.1, 148.1, 126.0, 117.4, 112.2, 109.3,
76.8, 64.1, 55.9, 13.7. GC−MS, m/z (%): 253 (M+· +1, 3), 252 (M+·,
21), 224 (8), 180 (11), 179 (28), 152 (9), 151 (100), 150 (21), 135
(6), 123 (11), 108 (13), 106 (7), 95 (15), 80 (8), 79 (12), 65 (8), 63
(12), 55 (5), 54 (7), 53 (19), 52 (20), 51 (11), 43 (5), 41 (6).
Diethyl 2-Hydroxy-2-(2-hydroxy-5-methoxyphenyl)malonate
(4a).13 The product was isolated after flash chromatography on silica
gel (light petroleum ether/EtOAc 7:3) as a white solid, 28 mg (19%).
1H NMR (300 MHz, CDCl3) δ 7.14 (s, 1H), 6.97−6.75 (m, 3H),
9-Methoxy-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-
c]quinoline (8b).16 The cis product was isolated after crystallization
from ethanol, the trans product after chromatography on silica gel
(light petroleum ether/EtOAc 9:1) of the mother liquor.
1
Cis, white solid, 121 mg (82%): H NMR (400 MHz, CDCl3) δ
7.44 (d, J = 7.0 Hz, 2H), 7.41−7.35 (m, 2H), 7.34−7.29 (m, 1H),
7.07−7.04 (m, 1H), 6.74 (ddd, J = 8.6, 2.9, 0.7 Hz, 1H), 6.58 (d, J =
8.6 Hz, 1H), 5.32 (d, J = 5.6 Hz, 1H), 4.63 (d, J = 2.2 Hz, 1H), 3.79
(s, 3H), 3.69 (bs, 1H), 3.64−3.58 (m, 1H), 3.45 (td, J = 11.4, 2.5 Hz,
1H), 2.21−2.13 (m, 1H), 1.64−1.41 (m, 3H), 1.38−1.29 (m, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 153.0, 141.4, 139.2, 128.4,
127.5, 126.9, 121.2, 115.8, 115.2, 112.0, 73.0, 61.0, 59.7, 56.0, 39.2,
25.5, 18.0. GC−MS, m/z (%): 296.1 (M+· +1, 24), 295.1 (M+·, 100),
236 (43), 236 (43), 224 (33), 159.9 (19), 90.9 (12).
4.57 (s, 1H), 4.43−4.24 (m, 4H), 3.76 (s, 3H), 1.32 (t, J = 7.1 Hz,
6H). 13C{1H} NMR (75 MHz, CDCl3) δ 169.5, 153.1, 148.8, 122.7,
119.1, 115.8, 113.3, 80.9, 63.5, 55.8, 14.0.
Ethyl 3-Hydroxy-2-oxo-2,3-dihydrobenzofuran-3-carboxylate
(3b).13 The product was isolated after flash chromatography on silica
gel (light petroleum ether/EtOAc 7:3) as a yellow oil, 98 mg (88%).
1H NMR (300 MHz, CDCl3) δ 7.52−7.05 (m, 4H), 4.25 (dtd, J =
24.9, 17.7, 7.3 Hz, 2H), 1.17 (t, J = 7.1 Hz, 3H). 13C{1H} NMR (75
MHz, CDCl3) δ 171.9, 168.6, 154.5, 131.9, 125.5, 125.2, 124.3, 111.6,
76.4, 64.2, 13.9. GC−MS, m/z (%): 222 (M+· +1, 2), 160 (2), 151
(5), 150 (67), 149 (100), 133 (2), 122 (7), 121 (74), 120 (6), 105
(23), 104 (6), 94 (2), 93 (28), 92 (20), 78 (2), 77 (14), 75 (14), 74
(4),72 (2), 66 (11), 65 (57), 64 (19), 63 (20), 61 (5), 55 (2), 53
(12), 51 (16), 49 (6), 44 (10), 43 (8), 40 (5).
1
Trans, orange oil, 10 mg (7%): H NMR (400 MHz, CDCl3) δ
7.45−7.28 (m, 5H), 6.82 (d, J = 2.9 Hz, 1H), 6.74 (dd, J = 8.7, 2.9
Hz, 1H), 6.51 (d, J = 8.7 Hz, 1H), 4.67 (d, J = 10.7 Hz, 1H), 4.38 (d,
J = 2.8 Hz, 1H), 4.13−4.06 (m, 1H), 3.77 (s, 3H), 3.72 (td, J = 11.5,
2.6 Hz, 1H), 2.15−2.07 (m, 1H), 1.65−1.41 (m, 5H). 13C{1H} NMR
(101 MHz, CDCl3) δ 152.3, 142.5, 135.3, 131.0, 128.8, 128.0, 125.2,
117.0, 115.8, 115.0, 74.1, 68.7, 56.1, 55.4, 39.1, 24.3, 22.2. GC−MS,
m/z (%): 296.1 (M+· +1, 20), 295 (M+·, 100), 277.1 (18), 237 (13),
236 (68), 224 (20), 193 (11), 160 (18), 146.9 (20), 117 (10), 115
(10), 91 (14).
Ethyl 1-Hydroxy-2-oxo-1,2-dihydronaphtho[2,1-b]furan-1-car-
boxylate (3c).13 The product was isolated after flash chromatography
on silica gel (light petroleum ether/EtOAc 7:3) as a yellow solid, 117
mg (86%). 1H NMR (300 MHz, CDCl3) δ 7.97 (d, J = 8.9 Hz, 1H),
7.90 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.57 (ddd, J = 8.3,
6.9, 1.2 Hz, 1H), 7.48 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.38 (d, J = 8.9
Hz, 1H), 4.62 (s, 1H), 4.24 (ddq, J = 55.1, 10.7, 7.1 Hz, 2H), 1.11 (t,
J = 7.1 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 172.4, 169.1,
153.2, 133.1, 131.2, 129.4, 129.0, 128.8, 125.6, 122.2, 117.5, 111.7,
77.3, 64.4, 13.9. GC−MS, m/z (%): 272 (M+· +1, 25), 200 (29), 199
(100), 172 (11), 171 (84), 155 (8), 143 (18), 127 (5), 126 (9), 116
(9), 115 (94), 114 (21), 113 (9), 89 (14), 88 (8), 65 (6), 63 (13), 62
(5).
Povarov Reaction. Imine Synthesis. Amine 5 (0.5 mmol, 1
equiv) and aldehyde 6 (0.5 mmol, 1 equiv) were added to 0.5 mL of
BMIm-BF4 and kept under stirring at room temperature for 1 h. Then
the mixture was extracted with diethyl ether (3 × 3 mL). The solvent
was eliminated from the combined organic phases under reduced
pressure, and the imine was used without purification (after 1H NMR
control spectrum) in the Povarov reaction.
5-(4-Methoxyphenyl)-9-methyl-3,4,4a,5,6,10b-hexahydro-2H-
pyrano[3,2-c]quinoline (8c).21 The cis product was isolated after
crystallization from ethanol, the trans product after chromatography
on silica gel (light petroleum ether/EtOAc 9:1) of the mother liquor.
1
Cis, white solid, 70 mg (45%): H NMR (400 MHz, CDCl3) δ
7.36−7.31 (m, 2H), 7.26−7.24 (m, 1H), 6.94−6.89 (m, 3H), 6.53 (d,
J = 8.0 Hz, 1H), 5.29 (d, J = 5.6 Hz, 1H), 4.60 (d, J = 2.4 Hz, 1H),
3.83 (s, 3H), 3.75 (bs, 1H), 3.64−3.56 (m, 1H), 3.44 (td, J = 11.4, 2.5
Hz, 1H), 2.28 (s, 3H), 2.17−2.06 (m, 1H), 1.57−1.33 (m, 4H).
13C{1H} NMR (101 MHz, CDCl3) δ 159.0, 143.0, 133.4, 128.8,
128.0, 127.9, 127.6, 120.0, 114.6, 113.8, 73.0, 60.9, 59.1, 55.4, 39.4,
25.6, 20.8, 18.1. GC−MS, m/z (%): 310.1 (M+·+1, 22), 309.1 (M+·,
100), 308.1 (10), 276 (17), 264.1 (11), 251 (14), 250 (71), 239 (14),
238 (71), 145 (19), 144 (28), 121 (35).
1
Trans, orange oil, 37 mg (24%): H NMR (400 MHz, CDCl3) δ
7.34 (d, J = 8.6 Hz, 2H), 7.04 (d, J = 1.5 Hz, 1H), 6.90 (d, J = 8.7 Hz,
3H), 6.45 (d, J = 8.1 Hz, 1H), 4.65 (d, J = 10.8 Hz, 1H), 4.36 (d, J =
2.7 Hz, 1H), 4.14−4.07 (m, 1H), 3.82 (s, 3H), 3.72 (td, J = 11.7, 2.4
Hz, 1H), 2.23 (s, 3H), 2.06 (d, J = 4.6 Hz, 1H), 1.65−1.55 (m, 5H).
13C{1H} NMR (101 MHz, CDCl3) δ 159.2, 135.2, 131.1, 130.1,
128.9, 125.0, 114.0, 74.7, 68.8, 55.3, 54.3, 29.7, 24.2, 21.9, 20.4. GC−
MS, m/z (%): 310 (M+· +1, 21), 309.1 (M+·, 83), 280.9 (12), 278
(18), 251.1 (12), 250 (57), 238.9 (24), 238.1 (11), 206.9 (29), 159.9
(0), 120.9 (0).
Friedel−Craft Benzylation of Anisole with Benzyl Alcohol.
The electrolysis was carried out as previously reported, and after the
number of Coulombs reported in Table 3, the current was switched
off. Then anisole 10 (2−4 equiv, amount as in Table 3) and benzyl
alcohol 9 (54 mg, 0.5 mmol, 1 equiv) were added to the anolyte. The
mixture was kept at room temperature under stirring and an inert
atmosphere for 4 h, then extracted with diethyl ether.
The electrolysis was carried out as previously reported, and after
the number of Coulombs reported in Table 2, the current was
switched off. Then imine (0.5 mmol, 1 equiv) and 3,4-dihydro-2H-
pyrane 7 (1−4 equiv, amount as in Table 2) were added to the
anolyte. The mixture was kept at room temperature under stirring and
an inert atmosphere for 3 h, then extracted with diethyl ether.
9-Methyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]-
quinoline (8a).20 The cis product was isolated after crystallization
from ethanol, the trans product after flash chromatography on silica
gel (light petroleum ether/EtOAc 9:1) of the mother liquor.
1
Cis, white solid, 95 mg (68%): H NMR (400 MHz, CDCl3) δ
7.45−7.34 (m, 4H), 7.34−7.28 (m, 1H), 7.26 (s, 1H), 6.93 (dd, J =
8.1, 2.0 Hz, 1H), 6.54 (d, J = 8.0 Hz, 1H), 5.32 (d, J = 5.5 Hz, 1H),
4.66 (d, J = 2.4 Hz, 1H), 3.78 (bs, 1H), 3.63−3.57 (m, 1H), 3.45 (td,
J = 11.5, 2.5 Hz, 1H), 2.29 (s, 3H), 2.21−2.12 (m, 1H), 1.63−1.40
(m, 3H), 1.36−1.27 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
E
https://doi.org/10.1021/acs.joc.1c00932
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1-Benzyl-4-methoxybenzene (p-11).22 The product was isolated
after flash chromatography on silica gel (light petroleum ether/EtOAc
9:1), deliquescent light yellow solid, 46 mg (46%). H NMR (400
Rome, 00161 Rome, Italy; orcid.org/0000-0002-9517-
0226
Vincenzo Scarano − Department of Basic and Applied
Sciences for Engineering (SBAI), Sapienza University of
Rome, 00161 Rome, Italy; orcid.org/0000-0003-3503-
7156
Fabrizio Vetica − Department of Chemistry, Sapienza
University of Rome, 00185 Rome, Italy; orcid.org/0000-
0002-7171-8779
1
MHz, CDCl3) δ 7.32−7.25 (m, 2H), 7.19 (t, J = 7.6 Hz, 3H), 7.11
(d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.4 Hz, 2H), 3.94 (s, 2H), 3.79 (s,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 158.0, 141.6, 133.2, 129.9,
128.8, 128.4, 126.0, 113.9, 55.3, 41.0. GC−MS, m/z (%): 199 (M+·
+1, 15), 198 (M+·, 100), 183 (15) 167 (35), 165 (24), 153 (17), 121
(23), 91 (8).
1-Benzyl-2-methoxybenzene (o-11).22 The product was isolated
after flash chromatography on silica gel (light petroleum ether/EtOAc
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00932
1
9:1), deliquescent light yellow solid, 34 mg (34%). H NMR (400
MHz, CDCl3) δ 7.31−7.16 (m, 9H), 7.08 (d, J = 6.2 Hz, 1H), 6.89
(m, 2H), 3.99 (s, 2H), 3.83 (s, 3H). ppm. 13C{1H} NMR (101 MHz,
CDCl3) δ 157.3, 141.0, 130.3, 129.7, 129.0, 128.2, 127.4, 125.8,
120.5, 110.4, 55.4, 35.9. GC−MS, m/z (%): 199 (M+· +1, 16), 198
(M+·, 100), 183 (36) 167 (37), 165 (52), 152 (15), 121 (7), 91 (22).
Multicomponent Reaction to Tetrahydro-11H-benzo[a]-
xanthen-11-ones. The electrolysis was carried out as previously
reported, and after the number of Coulombs reported in Table 4, the
current was switched off. Then benzaldehyde 6 (0.5 mmol, 1 equiv),
2-naphthol 1c (72 mg, 0.5 mmol, 1 equiv), and dimedone 12 (70 mg,
0.5 mmol, 1 equiv) were added to the anolyte. The mixture was kept
at room temperature under stirring and an inert atmosphere for 3 h,
(or 60 °C using an oil bath for 1 or 2 h), then extracted with diethyl
ether. The products were crystallized from ethanol.
9,9-Dimethyl-12-phenyl-8,9,10,12-tetrahydro-11H-benzo[a]-
xanthen-11-one (13a).19 White solid, 154 mg (87%), 1H NMR (400
MHz, CDCl3) δ 8.00 (d, J = 8.5 Hz, 1H), 7.80−7.74 (m, 2H), 7.43
(ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.40−7.31 (m, 4H), 7.21−7.15 (m,
2H), 7.09−7.03 (m, 1H), 5.72 (s, 1H), 2.57 (s, 2H), 2.35−2.21 (m,
2H), 1.12 (s, 3H), 0.97 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
197.0, 164.0, 147.9, 144.9, 131.6, 131.5, 128.9, 128.5, 128.5, 128.3,
127.1, 126.3, 125.0, 123.8, 117.8, 117.2, 114.4, 51.0, 41.5, 34.8, 32.4,
29.4, 27.3. GC−MS, m/z (%): 354.1 (M+·, 33), 278.1 (21), 277.1
(100), 221 (10).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors would like to thank Mr. Marco Di Pilato for his
help with electrolysis apparatus and Sapienza University for the
financial support (RM11816411D00FB3).
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00932.
■
sı
1
Copies of H and 13C NMR of products (PDF)
AUTHOR INFORMATION
Corresponding Author
Marta Feroci − Department of Basic and Applied Sciences for
Engineering (SBAI), Sapienza University of Rome, 00161
Rome, Italy; orcid.org/0000-0002-3673-6509;
Email: marta.feroci@uniroma1.it
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Ionic Liquids. Chem. Rev. 2017, 117, 6633−6635.
(8) Mai, N. L.; Ahn, K.; Koo, Y.-M. Methods for recovery of ionic
liquidsA review. Process Biochem. 2014, 49, 872−881.
Authors
Martina Bortolami − Department of Basic and Applied
Sciences for Engineering (SBAI), Sapienza University of
Rome, 00161 Rome, Italy; orcid.org/0000-0001-5740-
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Leonardo Mattiello − Department of Basic and Applied
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