Friedel–Crafts Alkylation with Carbenium Ions Generated by Electrochemical Oxidation of Stannylmethyl Ethers

Article abstract of DOI:10.1002/ejoc.202000568

The electrochemical activation of stannylmethyl ethers was exploited for Friedel–Crafts alkylation of arenes at near-neutral conditions. Single cell anodic oxidation of stannylmethyl ethers leads to oxonium ions which fragment to carbenium ions in the pre

Full text of DOI:10.1002/ejoc.202000568

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Friedel-Crafts alkylation with carbenium ions generated by
electrochemical oxidation of stannylmethylethers
Authors: Anna Lielpetere and Aigars Jirgensons
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000568
Link to VoR: https://doi.org/10.1002/ejoc.202000568
0
1/2020

European Journal of Organic Chemistry
10.1002/ejoc.202000568
FULL PAPER
Friedel-Crafts alkylation of arenes with carbenium ions generated
by electrochemical oxidation of stannylmethylethers
[a]
[a]
Anna Lielpetere, and Aigars Jirgensons*
[
a]
Latvian Institute of Organic Synthesis, Aizkraukles Street 21, Riga, Latvia, LV-1006
E-mail: aigars@osi.lv ; http://osmg.osi.lv
Supporting information for this article is given via a link at the end of the document.
Abstract: The electrochemical activation of stannylmethylethers was
exploited for Friedel-Crafts alkylation of arenes at near-neutral condi-
tions. Single cell anodic oxidation of stannylmethylethers leads to ox-
onium ions which fragment to carbenium ions in the presence of elec-
tron rich arenes. Low oxidation potential of stannylmethylethers and
buffered conditions enable the Friedel-Crafts reaction with a wide
range of arenes including the substrates with acid-sensitive groups.
ion B. The proof of the concept was demonstrated for the reaction
of carbenium ions B with allylsilane providing olefins 2. With an
aim to complement the recent advances in electrochemical arene
functionalization[30-32],we explored Friedel-Crafts reaction using
stannylmethylethers 1 (Alk = n-Bu, Me) as precursors for electro-
chemical generation of carbenium ions B to form alkylated arenes
3 (Figure 1).
Results and Discussion
Introduction
In a model reaction, stannylmethylether 1a was subjected to an-
odic oxidation in the presence of O-TBS protected phenol 4 (Ta-
ble 1, entry 1). Weekly nucleophilic HFIP was found as appropri-
ate additive to secure the cathode reaction[33] without observable
competition with arene.[27,28] The electrochemically induced reac-
tion proceeded in a relatively short time providing the expected
product 3.1 in good yield and high para-selectivity (ortho-product
The Friedel-Crafts alkylation is a fundamental organic reaction for
functionalization of arenes in their reaction with in situ generated
carbenium ions.[1] Products of this reaction have found wide ap-
plication in drug discovery and material science.[2-4] Consequently,
a number of Friedel-Crafts alkylation versions has been devel-
oped, including the alkylation of arenes with alcohols,[5-10] halo-
gens,[11] ethers,[12,13] acetates,[14,15] phosphonates,[16] sul-
fones,[17,18] trichloroacetimidates,[12] tosylamides,[19] epoxides,[20]
and olefins.[21] Typically, these reactions rely on Broensted or
Lewis acid catalysis to promote the carbenium ion formation. Lim-
ited number of methods for Friedel-Crafts alkylation has been de-
veloped using weak or non-acidic conditions which offer wider
substrate scope for this useful transformation.[22-28]
5
formed <5% according to NMR: see Supporting Information).
However, the control reaction without electric current was also
productive, leading to observable formation of product 3.1 at
longer reaction time (Table 1, entry 1).
Table 1. Reaction conditions for selective electrochemical substrate activation
Electrochemical generation of carbenium ions avoids the use of
acidic conditions because the protons formed during the reaction
are reduced to hydrogen at the cathode.[27,28] This provides an op-
tion to perform reactions of carbenium ions at near-neutral condi-
tions which are compatible with acid-sensitive functionalities in
substrates.
Entry
Additive
Cond. A
Cond. B
Yield of 3.1,%
Yield[ of 3.1,%
a]
[a]
1
2
3
4
5
6
none
63
56
0
9
additional HFIP[b]
1 eq 2,6-lutidine
1 eq PivONa
74
0
Figure 1 Electrochemical generation of carbenium ions from stannylmethyleth-
ers and their reaction with nucleophiles.
38
51
0
1 eq PhCO
2
Li
0
Recently, we have reported an operationally simple carbenium
ion generation from stannylmethylethers 1 (Alk = n-Bu) in single
cell electrolysis at relatively low potential (Figure 1).[29] The
method is based on the oxidation of stannylmethyoxy group in
substrates 1 to form oxonium ions A which fragment to carbenium
1 eq NaHCO
3
64 (55[c]
)
0
[
a] NMR yield using ethyl acetate as an internal standard; [b] Solvent: HFIP/
DCM, 1:1 [c] Isolated yield.
1
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European Journal of Organic Chemistry
10.1002/ejoc.202000568
FULL PAPER
Notably, the increased amount of HFIP facilitated non-electro-
chemical reaction leading to product 3.1 formation in good yield
products 3.13-3.15 in good yields. The reaction of fluorine-con-
taining stannylmethylether 1d provided alkylated protected phe-
nol 3.16, however, in slightly lower yield compared to non-fluori-
nated analogue 1a. Alkylarylmethyl cations generated from
stannylmethylethers 1e,f gave furan, tiophene and phenol alkyla-
tion products 3.17-3.19. Methoxy-substituted benzylic cation pro-
duced from substrate 1g provided thiophene derivative 3.20 effi-
ciently. However, chloro-substituted analogue 1h failed to give the
expected product 3.21, likely due to the reduced stability of the
intermediate carbenium ion. Tertiary carbenium ion precursors 1i-
k provided furan and tiophene alkylation products 3.22-3.24 in
moderate yields. However, stannylmethylethers 1l,m bearing
EWG groups were considerably less productive, giving products
3.25, 3.26 in low yield. Also, the electrochemical activation of less
stable adamantyl cation precursor 1n failed to give the expected
alkylation product 3.27.
(
Table 1, entry 2). This indicated the susceptibility of trime-
thylstannylmethylether 1a to undergo ionization in the presence
of HFIP. Moreover, such a result implied that the reaction condi-
tions are not compatible with acid-labile functional groups.
To buffer the reaction media, various basic additives were tested.
2,6-Lutidine suppressed both electrochemically induced and sol-
volytic carbenium ion generation (Table 1, entry 3). Addition of
sodium pivaloate and lithium benzoate to the reaction media gave
Friedel-Crafts product 3.1 in medium yield and suppressed the
3
solvolysis induced reaction (Table 1, entries 4,5). NaHCO as ad-
ditive induced the best yield of product 3.1 at electrochemical con-
ditions and completely suppressed solvolytic carbenium ion gen-
eration (Table 1, entry 6).
With optimized conditions in hand, the stannylmethylether 1a was
subjected to electrochemically induced reaction with a range of
arenes (Table 2). Alkylated furan derivatives 3.2 and 3.3 were pre-
pared in good yield. Moreover, furfuryl alcohol derivatives bearing
acid-labile O-protecting groups, such as MOM, Tr, THP and
Table 3. Scope of stannylmethylethers for the electrochemically induced
Friedel-Crafts reaction
Ph
the
.4-3.7. To the best of our knowledge, these are the first examples
2
CH, could also be alkylated with stannylmethylether 1a to give
corresponding products
3
of the compatibility of the acid-sensitive O-protecting groups with
Friedel-Crafts alkylation conditions. Acid-sensitive heterocycles,
such as thiophene and N-protected indole, also provided the de-
sired alkylation products 3.8 and 3.9. Electron rich phenols with
low electrochemical potentials were also tested as substrates. In-
terestingly, unprotected phenol turned out to be a competent sub-
strate to give C-alkylation product 3.10. Anisole derivative and
1,3-dimethoxybenzene with low oxidation potentials were also
successfully alkylated to give products 3.11 and 3.12 in good
yields.
Table 2. Nucleophile scope for the electrochemically induced Friedel-Crafts re-
action
[
a] NMR yield using ethyl acetate as an internal standard [b] 10 equiv HFIP
The scope of stannylmethylethers 1 for alkylation of arenes was
also investigated (Table 3). Diarylmethyl cations generated from
stannylmethylethers 1b,c gave furan and thiophene alkylation
2
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European Journal of Organic Chemistry
10.1002/ejoc.202000568
FULL PAPER
General Procedure for Electrochemical Friedel-Crafts Alkylation.
Anodic oxidation was performed in Electrasyn beaker–type undivided
cell (5 mL) equipped with two standard Electrasyn graphite plate elec-
trodes (8×40 mm, ~15 mm submerged in the solution) in 0.1 M
[
a] NMR yield using ethyl acetate as an internal standard [b] oxonium ion reac-
tion product in 35% by NMR
The proposed mechanism of electrochemically induced Friedel-
Crafts reaction is shown in Figure 2. The cathode reaction in-
volves the reduction of HFIP to generate the corresponding alkox-
ide and hydrogen. Stannate complex formed from substrate 1 un-
dergoes anodic oxidation at low oxidation potential to form oxo-
nium ion A with stannate X as the counterion. Fragmentation of
oxonium ion A forms cation B which reacts with activated arene
(
TBABF
4
/dry DCM (2 mL) solution with the addition of HFIP (0.41 mL,
(17.0 mg, 0.2 mmol).
4.0 mmol unless noted otherwise) and NaHCO
3
The trialkylstannylmethyl group bearing substrate (0.2 mmol) and nu-
cleophile (2-5 equiv) were added to the solution. Constant current elec-
trolysis (5-30 mA) was carried out in air at ambient temperature with
magnetic stirring and change of polarization every minute until approx.
-
2.5 F/mol were consumed. After the electrolysis, the reaction mixture
ArH) providing Friedel-Crafts alkylation product 3 and non-acidic
was concentrated in vacuo and purified by flash column chromatog-
raphy on silica gel.
by-products (HX).
(
4-Benzhydrylphenoxy)(tert-butyl)dimethylsilane (3.1). Electro-
chemical oxidation of ((benzhydryloxy)methyl)trimethylstannane (1a)
72.6 mg, 0.20 mmol) in the presence of tert-butyldimethyl(phenoxy)-
silane (4) (84.0 mg, 0.40 mmol) according to the general procedure at
0 mA and purification by column chromatography on silica gel (eluent
petroleum ether/Et O 40:1) afforded 41.5 mg (55%) of product as a
(
3
2
white solid (m.p. 80–82 °C).
1
3
H NMR (300 MHz, CDCl ) δ 7.33 – 7.25 (m, 4H), 7.24 – 7.16 (m, 2H),
7.14 – 7.07 (m, 4H), 6.99 – 6.92 (m, 2H), 6.78 – 6.72 (m, 2H), 5.49 (s,
1
H), 0.98 (s, 9H), 0.19 (s, 6H).
C NMR (101 MHz, CDCl ) δ 154.12, 144.46, 136.70, 130.46, 129.55,
3
1
3
1
28.38, 126.33, 119.86, 56.23, 25.83, 18.32, -4.25.
+
HR-MS (ESI-TOF) m/z: calcd. for C25
H29OSi [M-1] 373.1988; found:
Figure 2. Proposed mechanism of electrochemically induced Friedel-Crafts re-
action.
373.1972.
Anal. calcd. for C25
H30OSi: C, 80.16; H, 8.07. Found: C, 79.17; H, 8.08.
2-Benzhydrylfuran (3.2) Electrochemical oxidation of ((benzhydryl-
Conclusion
oxy)methyl)trimethylstannane (1a) (71.9 mg, 0.2 mmol) in the pres-
ence of furan (0.1 mL, 1 mmol) according to the general procedure at
5
(
mA and purification twice by column chromatography on silica gel
eluent petroleum ether/diethyl ether 20:1) afforded 28.4 mg (61%) of
product as a colourless oil. This compound has been reported in the
In summary, it was demonstrated that Friedel-Crafts reaction can
be achieved by electrochemical activation of stannylmethylethers
in the presence of electron rich arenes. The buffered electrolytic
mixture contained HFIP as the cathode reactant and NaHCO as
3
proton scavenger. These conditions were found to be compatible
[
30]
literature.
1
H NMR (400 MHz, CDCl
.6 Hz, 4H), 7.27 – 7.22 (m, 2H), 7.18 (dd, J = 7.0, 1.9 Hz, 4H), 6.31
dd, J = 3.3, 1.9 Hz, 1H), 5.92 (d, J = 3.2 Hz, 1H), 5.46 (s, 1H).
3
) δ 7.39 (d, J = 1.8 Hz, 1H), 7.31 (dd, J = 8.2,
6
(
with acid-labile O-protecting groups such as MOM, Tr, THP and
Ph CH. We believe that electrochemical activation of substrates
2
to form carbenium will expand the application of Friedel-Crafts re-
action in the synthesis of useful products.
2
(
-Benzhydryl-5-methylfuran (3.3) Electrochemical oxidation of
(benzhydryloxy)methyl)trimethylstannane (1a) (72.6 mg, 0.20 mmol)
was carried out in the presence of 2-methylfuran (0.09 mL,
.00 mmol) according to the general procedure at 5 mA until
2.87 F/mol has been consumed. Purification by column chromatog-
raphy on silica gel (eluent petroleum ether/Et O 20:1) afforded
36.7 mg (74%) of product as an yellowish oil. This compound has
1
Experimental Section
2
General Remarks. All procedures were performed in oven-dried
glassware under argon atmosphere unless noted otherwise. Rea-
gents and starting materials were obtained from commercial sources
and used as received unless otherwise noted. Tetrabutylammonium
tetrafluoroborate (Fluorochem) was recrystallized from ethyl acetate
and dried at 80 °C for 8 h before use. Solvents were purified and dried
by standard procedures before use. Flash column chromatography
was carried out using silica gel (230−400 mesh). Thin-layer chroma-
tography (TLC) was performed on Merck TLC Silica gel 60 F254 Alu-
[
31]
been reported in literature.
1
H NMR (300 MHz, CDCl ) δ 7.35 – 7.12 (m, 10H), 5.88 (m, 1H), 5.74
3
(m, 1H), 5.39 (s, 1H), 2.25 (m, 3H).
2-Benzhydryl-5-((methoxymethoxy)methyl)furan (3.4) Electro-
chemical oxidation of ((benzhydryloxy)methyl)trimethylstannane (1a)
(71.8 mg, 0.20 mmol) was performed in the presence of
2-((methoxymethoxy)methyl)furan (56.5 mg, 0.40 mmol) according to
the general procedure at 5 mA. Purification by column chromatog-
raphy on silica gel (eluent petroleum ether/EtOAc 10:1) afforded 27.2
mg (44%) of product as an yellowish oil.
4
minium sheets and was visualized by UV lamp or staining with KMnO .
NMR spectra were recorded on 300 or 400 MHz spectrometers with
chemical shift values (δ) in parts per million using the residual solvent
as an internal standard. HRMS analyses were performed on a hybrid
quadrupole time-of-flight mass spectrometer equipped with an elec-
trospray ion source. Electrochemical experiments were performed us-
ing electrochemical system Electrasyn 2.0.
1
H NMR (400 MHz, CDCl ) δ 7.24 (dd, J = 8.1, 6.5 Hz, 4H), 7.22 –
3
7.13 (m, 2H), 7.12 (dd, J = 7.0, 1.9 Hz, 4H), 6.21 (d, J = 3.1 Hz, 1H),
5.82 – 5.76 (m, 1H), 5.40 (s, 1H), 4.60 (s, 2H), 4.43 (s, 2H), 3.30 (s,
3H).
13
C NMR (101 MHz, CDCl
3
) δ 157.36, 150.90, 141.81, 128.90, 128.54,
Experimental Details. Synthesis of starting materials and characteri-
zation of side products is described in Supporting Information.
126.84, 110.24, 109.33, 95.34, 77.36, 61.15, 55.46, 51.08.
3
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European Journal of Organic Chemistry
10.1002/ejoc.202000568
FULL PAPER
+
HR-MS (ESI-TOF) m/z: calcd. for C29
H O
19 3
[M-1] 307.1334; found:
mg, 0.21 mmol) was performed in the presence of 1-Boc-1H-indole
3
07.1341.
(43.4 mg, 0.20 mmol) and NaHCO
the general procedure at 5 mA. Purification by column chromatog-
raphy on silica gel (eluent petroleum ether/Et O 9:1) afforded 40.0 mg
(52%) of product as an yellowish oil. Product has been reported in
3
(16.8 mg, 0.2 mmol) according to
2-Benzhydryl-5-((trityloxy)methyl)furan (3.5) Electrochemical oxi-
2
dation of ((benzhydryloxy)methyl)trimethylstannane (1a) (71.4 mg,
[
33]
0.20
mmol)
was
performed
in
the
presence
of
literature.
1
2-((trityloxy)methyl)furan (135.0 mg, 0.40 mmol) in a modified general
3
H NMR (300 MHz, CDCl ) δ 8.08 (d, J = 8.2 Hz, 1H), 7.32 (s, 9H),
procedure using 0.2 mL of HFIP at 5 mA. Purification by column chro-
matography on silica gel (eluent petroleum ether/EtOAc 20:1 with 3%
7.22 (m, 2H), 7.19 – 7.06 (m, 2H), 7.02 (s, 1H), 5.57 (s, 1H), 1.64 (s,
9H).
triethylamine) afforded 54.1 mg (54%) of product as a white solid.
1
H NMR (400 MHz, CDCl
.19 (d, J = 3.1 Hz, 1H), 5.87 (d, J = 3.3 Hz, 1H), 5.46 (s, 1H), 4.02 (s,
H).
C NMR (101 MHz, CDCl ) δ 156.43, 151.92, 144.06, 142.10, 128.97,
3
28.85, 128.53, 127.98, 127.14, 126.81, 109.08, 108.70, 87.15, 59.57,
1.13.
3
) δ 7.49 (d, J = 7.7 Hz, 8H), 7.27 (m, 22H),
4-Benzhydrylphenol (3.10) Electrochemical oxidation of ((benzhy-
dryloxy)methyl)trimethylstannane (1a) (72.9 mg, 0.20 mmol) in the
presence of phenol (45.6 mg, 0.48 mmol) according to the general
procedure at 20 mA and purification by column chromatography on
silica gel (eluent DCM) afforded 23.8 mg (45%) of product as a white
6
2
13
1
5
[
34]
solid. Product has been reported in literature.
+
1
HR-MS (ESI-TOF) m/z: calcd. for C37
H
29O [M-1] 505.2168; found:
H NMR (300 MHz, CDCl
3
) δ 7.36 – 7.11 (m, 7H), 7.12 – 7.00 (m, 4H),
505.2180.
6.98 – 6.85 (m, 2H), 6.76 – 6.61 (m, 2H), 5.44 (s, 1H), 4.65 (br.s, 1H).
2-((5-Benzhydrylfuran-2-yl)methoxy)tetrahydro-2H-pyran
(3.6)
((4-Methoxy-3,5-dimethylphenyl)methylene)dibenzene (3.11)
Electrochemical oxidation of ((benzhydryloxy)methyl)trimethyl-stan-
nane (1a) (72.5 mg, 0.20 mmol) was performed in the presence of 2-
Electrochemical oxidation of ((benzhydryloxy)methyl)trimethyl-stan-
nane (1a) (72.7 mg, 0.20 mmol) in the presence of
2,6-dimethylanisole (0.14 mL, 1.00 mmol) according to the general
procedure at 30 mA and purification by column chromatography on
(
furan-2-ylmethoxy)tetrahydro-2H-pyran (73.2 mg, 0.40 mmol) ac-
cording to the general procedure at 5 mA. Purification by column chro-
matography on silica gel (eluent petroleum ether/Et O 5:1) afforded
2
2
silica gel (eluent petroleum ether/Et O 20:1) afforded 34.9 mg (57%)
2
2.2 mg (38%) of product as an yellowish oil.
of product as a colourless oil.
H NMR (400 MHz, CDCl ) δ 7.34 – 7.28 (m, 4H), 7.26 – 7.20 (m, 2H),
3
1
1
H NMR (400 MHz, CDCl
3
) δ 7.29 (m, 4H), 7.26 – 7.15 (m, 6H), 6.25
(d, J = 3.0 Hz, 1H), 5.84 (d, J = 3.0 Hz, 1H), 5.45 (s, 1H), 4.69 (d, J =
7.19 – 7.11 (m, 4H), 6.78 (s, 2H), 5.46 (s, 1H), 3.73 (s, 3H), 2.24 (s,
3
.3 Hz, 1H), 4.61 & 4.47 (d & d, J = 12.9 Hz, 1H, 3.86 (m, 1H), 3.53 –
6H).
13
3
.42 (m, 1H), 1.60 (m, 8H).
C NMR (101 MHz, CDCl
129.53, 128.37, 126.31, 59.78, 56.46, 16.33.
HR-MS (ESI-TOF) m/z: calcd. for C22
3
) δ 155.49, 144.33, 139.11, 130.58, 129.86,
1
3
3
C NMR (101 MHz, CDCl ) δ 157.11, 151.33, 141.90, 128.93, 128.51,
+
126.81, 110.04, 109.26, 97.29, 62.16, 60.87, 51.08, 30.53, 25.55,
H21O [M-1] 301.1592; found:
1
9.37.
301.1593.
+
HR-MS (ESI-TOF) m/z: calcd. for C23
H
24
O
3
Na [M+Na] 371.1623;
found: 371.1622.
((2,4-Dimethoxyphenyl)methylene)dibenzene (3.12) Electrochemi-
cal oxidation of ((benzhydryloxy)methyl)trimethylstannane (1a)
(72.2 mg, 0.20 mmol) in the presence of 1,3-dimethoxybenzene (0.13
mL, 1.00 mmol) according to the general procedure at 20 mA and pu-
rification by column chromatography on silica gel (eluent petroleum
ether/EtOAc 20:1) afforded 38.3 mg (63%) of product as a white solid.
2
-Benzhydryl-5-((benzhydryloxy)methyl)furan (3.7) Electrochemi-
cal oxidation of ((benzhydryloxy)methyl) trimethylstannane (1b)
72.2 mg, 0.20 mmol) was performed in the presence of
-((benzhydryloxy)methyl)furan (105.8 mg, 0.40 mmol) in a modified
general procedure using 0.2 mL of HFIP at 5 mA. Purification by col-
(
2
[
30]
This compound has been reported in literature.
1
umn chromatography on silica gel (eluent petroleum ether/Et
2
O 9:1)
3
H NMR (300 MHz, CDCl ) δ 7.13 – 7.05 (m, 4H), 6.74 (d, J = 8.4 Hz,
afforded 45.5 mg (53 %) of product as an yellowish oil.
1H), 6.47 (m, 1H), 6.40 (m, 1H), 5.83 (s, 1H), 3.79 (s, 3H), 3.70 (s,
1
H NMR (400 MHz, CDCl
3
) δ 7.33 – 7.15 (m, 21H), 6.21 (d, J = 3.1 Hz,
3H).
+
1H), 5.85 (dd, J = 3.0, 0.9 Hz, 1H), 5.43 (s, 1H), 5.41 (s, 1H), 4.42 (s,
HR-MS (ESI-TOF) m/z: calcd. for C21
H O
19 2
[M-1] 303.1385; found:
2
H).
303.1382
1
3
3
C NMR (101 MHz, CDCl ) δ 157.14, 151.38, 141.90, 141.88, 128.95,
1
28.57, 128.48, 127.58, 127.45, 127.36, 126.85, 110.36, 109.17,
2-((4-Methoxyphenyl)(phenyl)methyl)-5-methylfuran (3.13) Elec-
trochemical oxidation of tributyl(((4-methoxyphenyl)(phenyl)meth-
oxy)methyl)stannane (1b) (103.5 mg, 0.20 mmol) was performed in
the presence of 2-methylfuran (0.09 mL, 1.0 mmol) according to the
general procedure at 5 mA. Purification by column chromatography
81.71, 62.63, 51.12.
+
HR-MS (ESI-TOF) m/z: calcd. for C31
found: 453.1832.
H O
26 2
Na [M+Na] 453.1830;
2-Benzhydryl-5-methylthiophene (3.8) Electrochemical oxidation of
2
on silica gel (eluent petroleum ether/Et O 20:1) afforded 41.5 mg
(
(benzhydryloxy)methyl)trimethylstannane (1a) (72.5 mg, 0.20 mmol)
(75%) of product as an yellowish oil. Product has been reported in
[
32]
was performed in the presence of 2-methylthiophene (0.1 mL, 1.00
mmol) according to the general procedure at 5 mA. Purification by col-
umn chromatography on silica gel (eluent petroleum ether/DCM 9:1)
afforded 36.4 mg (68%) of product as a colourless oil. Product has
literature.
1
3
H NMR (400 MHz, CDCl ) δ 7.29 (m, 2H), 7.25 – 7.19 (m, 1H), 7.17
(m, 2H), 7.13 – 7.06 (m, 2H), 6.90 – 6.80 (m, 2H), 5.87 (m, 1H), 5.77
– 5.70 (m, 1H), 5.34 (s, 1H), 3.79 (s, 3H), 2.25 (m, 3H).
[
32]
been reported in literature.
1
H NMR (300 MHz, CDCl
3
) δ 7.28 (d, J = 6.7 Hz, 4H), 7.26 – 7.18 (m,
2-((4-Methoxyphenyl)(phenyl)methyl)-5-methylthiophene (3.14)
Electrochemical oxidation of tributyl(((4-methoxyphenyl)(phenyl)-
methoxy)methyl)stannane (1b) (104.1 mg, 0.20 mmol) was performed
in the presence of 2-methylthiophene (0.1 mL, 1.0 mmol) according to
6
2
H), 6.57 (d, J = 3.3 Hz, 1H), 6.45 (d, J = 3.3 Hz, 1H), 5.59 (s, 1H),
.42 (s, 3H).
t-Butyl-3-benzhydryl-1H-indole-1-carboxylate (3.9) Electrochemi-
cal oxidation of ((benzhydryloxy)methyl)trimethyl-stannane (1b) (75.7
4
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European Journal of Organic Chemistry
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the general procedure at 5 mA. Purification by column chromatog-
raphy on silica gel (eluent petroleum ether/EtOAc 20:1) afforded 36.5
en-1-yl)oxy)methyl)stannane (1f) (65.1 mg, 0.20 mmol) was per-
formed in the presence of 2-methylthiophene (0.10 mL, 1.0 mmol) ac-
cording to the general procedure at 5 mA. Purification by column chro-
matography on silica gel (eluent petroleum ether/EtOAc 20:1) af-
forded 27.2 mg (59%) of product as a colourless oil. Product has been
mg (62%) of product as a colourless oil.
1
3
H NMR (400 MHz, CDCl ) δ 7.36 – 7.28 (m, 2H), 7.28 – 7.21 (m, 3H),
7
1
.20 – 7.11 (m, 2H), 6.93 – 6.81 (m, 2H), 6.59 (dq, J = 3.5, 1.1 Hz,
H), 6.47 (dd, J = 3.4, 1.1 Hz, 1H), 5.57 (s, 1H), 3.81 (s, 3H), 2.44 (d,
[
35]
reported in literature.
1
J = 1.1 Hz, 3H).
3
H NMR (300 MHz, CDCl ) δ 7.21 – 7.06 (m, 4H), 6.61 – 6.53 (m, 1H),
13
C NMR (101 MHz, CDCl
3
) δ 158.39, 146.08, 144.31, 139.04, 136.25,
6.50 (d, J = 3.3 Hz, 1H), 4.34 (t, J = 6.1 Hz, 1H), 2.98 – 2.75 (m, 2H),
2.45 (s, 3H), 2.26 – 2.11 (m, 1H), 2.07 – 2.00 (m, 2H), 1.88 – 1.71 (m,
1H).
129.92, 128.87, 128.45, 126.67, 126.08, 124.64, 113.82, 55.34, 51.61,
1
5.46.
+
HR-MS (ESI-TOF) m/z: calcd. for C19
H
17OS [M-1] 293.1000; found:
2
93.1009.
4-(1,2,3,4-Tetrahydronaphthalen-1-yl)phenol (3.19) Electrochemi-
cal oxidation of trimethyl(((1,2,3,4-tetrahydronaphthalen-1-yl)oxy)-
methyl)stannane (1f) (65.4 mg, 0.20 mmol) was performed in the
presence of phenol (40.0 mg, 0.4 mmol) according to the general pro-
cedure at 5 mA. Purification by column chromatography on silica gel
(eluent petroleum ether/EtOAc 20:1) afforded 16.9 mg (37%) of prod-
2-Methyl-5-(phenyl(4-(trifluoromethyl)phenyl)methyl)thiophene
(3.15) Electrochemical oxidation of tributyl((phenyl(4-(trifluoro-me-
thyl)phenyl)methoxy)methyl)stannane (1c) (111.9 mg, 0.20 mmol)
was performed in the presence of 2-methylthiophene (0.1 mL,
[
38]
1.0 mmol) according to the general procedure at 5 mA. Purification by
uct as a white solid. Product has been reported in literature.
1
column chromatography on silica gel (eluent petroleum ether/EtOAc
3
H NMR (300 MHz, CDCl ) δ 7.20 – 6.90 (m, 5H), 6.84 (d, J = 7.7 Hz,
1
0:1) afforded 44.0 mg (66%) of product as an yellowish oil.
1H), 6.74 (d, J = 8.4 Hz, 2H), 4.56 (s, 1H), 4.05 (t, J = 6.5 Hz, 1H),
3.00 – 2.74 (m, 2H), 2.14 (m, 1H), 2.01 – 1.65 (m, 3H).
1
H NMR (400 MHz, CDCl
3
) δ 7.60 (d, J = 8.0 Hz, 2H), 7.43 – 7.33 (m,
H), 7.33 – 7.27 (m, 1H), 7.27 – 7.21 (m, 2H), 6.63 (m, 1H), 6.51 (m,
H), 5.69 (s, 1H), 2.47 (s, 3H).
4
1
2-(4-Methoxybenzyl)-5-methylthiophene (3.20) Electrochemical
oxidation of (((4-methoxybenzyl)oxy)methyl)trimethylstannane (1g)
1
3
1
C NMR (101 MHz, CDCl
3
) δ 148.0 (q, JCF = 1 Hz), 144.29, 143.06,
2
139.65, 129.31, 129.1 (q, JCF = 32 Hz), 28.92, 128.70, 127.15, 126.60, (63.5 mg, 0.20 mmol) was performed in the presence of
3
2
1
25.5 (q, JCF = 4 Hz), 124.3 (q, JCF = 272 Hz),124.83, 52.18, 15.45.
2-methylthiophene (0.1 mL, 1.0 mmol) according to the general pro-
cedure at 5 mA. Purification by column chromatography on silica gel
(eluent petroleum ether/EtOAc 10:1) afforded 31.5 mg (72%) of prod-
19
F NMR (376 MHz, CDCl
HR-MS (ESI-TOF) m/z: calcd. for C19
31.0778.
3
) δ -62.36.
-
14 3
H F S [M-1] 331.0768; found:
[
31]
3
uct as a colourless oil. Product has been reported in literature.
1
3
H NMR (300 MHz, CDCl ) δ 7.16 (m, 2H), 6.84 (m, 2H), 6.55 (s, 2H),
Tert-butyl(4-((4-fluorophenyl)(phenyl)methyl)phenoxy)dimethyl-
silane (3.16) Electrochemical oxidation of tributyl(((4-fluorophenyl)-
4.01 (s, 2H), 3.79 (s, 3H), 2.41 (s, 3H).
(phenyl)methoxy)methyl)stannane (1d) (101.0 mg, 0.20 mmol) was
2-Methyl-5-tritylfuran (3.22) Electrochemical oxidation of tribu-
performed in the presence of t-butyldimethyl(phenoxy)silane (83.3 mg, tyl((trityloxy)methyl)stannane (1i) (112.9 mg, 0.20 mmol) was per-
0
.4 mmol) according to the general procedure at 20 mA. Purification
formed in the presence of 2-methylfuran (0.09 mL, 1.0 mmol) accord-
ing to the general procedure at 5 mA. Purification by column chroma-
tography on silica gel (eluent petroleum ether/DCM 9:1) afforded
45.6 mg (70%) of product as a white solid. Product has been reported
by column chromatography on silica gel (eluent petroleum ether/DCM
9
:1) afforded 32.2 mg (41%) of product as an yellowish oil.
1
H NMR (400 MHz, CDCl
3
) δ 7.29 (m, 2H), 7.25 – 7.19 (m, 1H), 7.12
[
30]
–
7.04 (m, 4H), 7.01 – 6.91 (m, 4H), 6.80 – 6.73 (m, 2H), 5.47 (s, 1H),
in literature.
1
0
.98 (s, 9H), 0.19 (s, 6H).
H NMR (400 MHz, CDCl
), 7.18 – 7.11 (m, 6H), 5.95 – 5.90 (m, 1H), 5.88 (d, J = 3.2 Hz,
1H), 2.31 (s, 3H).
3
) δ 7.33 – 7.25 (m, 10H including residual
1
3
1
C NMR (101 MHz, CDCl
3
) δ 161.51 (d, JCF = 244.8 Hz), 154.24,
CHCl
3
3
1
1
1
44.28, 140.21, 136.51, 130.93 (d,
28.47, 126.47, 119.95, 115.15 (d,
8.32, -4.26.
J
CF = 7.8 Hz), 130.37, 129.44,
CF = 21.3 Hz), 55.43, 25.81,
2
J
2-Methyl-5-(2-phenylpropan-2-yl)thiophene (3.23) Electrochemical
oxidation of trimethyl(((2-phenylpropan-2-yl)oxy)methyl)stannane (1j)
(62.4 mg, 0.20 mmol) was performed in the presence of
2-methylthiophene (0.10 mL, 1.0 mmol) according to the general pro-
cedure at 5 mA. Purification by column chromatography on silica gel
(eluent petroleum ether/EtOAc 20:1) afforded 22.5 mg (52%) of prod-
19
F NMR (376 MHz, CDCl
3
) δ -117.04.
+
HR-MS (ESI-TOF) m/z: calcd. for C25
H
28OFSi [M-1] 391.1893; found:
391.1888.
2-(Cyclopropyl(phenyl)methyl)-5-methylfuran (3.17) Electrochem-
[
37]
ical oxidation of ((cyclopropyl(phenyl)methoxy)methyl)trimethyl-stan-
nane (1d) (64.8 mg, 0.20 mmol) was performed in the presence of 2-
methylfuran (0.09 mL, 1.0 mmol) according to the general procedure
at 5 mA. Purification by column chromatography on silica gel (eluent
uct as a colourless oil. Product has been reported in literature.
1
3
H NMR (300 MHz, CDCl ) δ 7.37 – 7.27 (m, 4H), 7.23 – 7.14 (m, 1H),
6.60 (d, J = 3.4 Hz, 1H), 6.56 (m, 1H), 2.41 (d, J = 1.1 Hz, 3H), 1.74
(s, 6H).
2
petroleum ether/Et O 20:1) afforded 30.8 mg (78%) of product as a
colourless oil.
2
-Methyl-5-(1-phenylcyclohexyl)thiophene (3.24) Electrochemical
oxidation of tributyl(((1-phenylcyclohexyl)oxy)methyl)stannane (1k)
96.6 mg, 0.20 mmol) was performed in the presence of
-methylthiophene (0.1 mL, 1.0 mmol) according to the general pro-
cedure at 5 mA. Purification by column chromatography on silica gel
eluent petroleum ether/DCM 9:1) afforded 30.0 mg (58%) of product
1
H NMR (300 MHz, CDCl
m, 1H), 3.23 (d, J = 9.3 Hz, 1H), 2.25 (m, 3H), 1.38 – 1.28 (m, 1H),
.73 – 0.64 (m, 1H), 0.61 – 0.52 (m, 1H), 0.43 – 0.22 (m, 2H).
3
) δ 7.36 – 7.21 (m, 5H), 6.09 (m, 1H), 5.91
(
0
1
(
2
3
3
C NMR (101 MHz, CDCl ) δ 156.18, 151.07, 142.95, 128.41, 128.07,
126.59, 106.55, 105.86, 49.91, 16.02, 13.76, 5.30, 4.43.
(
+
HR-MS (ESI-TOF) m/z: calcd. for C15
H
17O [M+1] 213.1279; found:
as a colourless oil.
213.1281.
1
3
H NMR (400 MHz, CDCl ) δ 7.43 – 7.27 (m, 4H), 7.21 – 7.16 (m, 1H),
6
–
.63 – 6.53 (m, 2H), 2.42 (d, J = 1.2 Hz, 3H), 2.38 – 2.18 (m, 4H), 1.74
1.38 (m, 6H).
2
-Methyl-5-(1,2,3,4-tetrahydronaphthalen-1-yl)thiophene (3.18)
Electrochemical oxidation of trimethyl(((1,2,3,4-tetrahydronaphthal-
5
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European Journal of Organic Chemistry
10.1002/ejoc.202000568
FULL PAPER
1
3
C NMR (101 MHz, CDCl
3
) δ 152.79, 148.32, 137.83, 128.38, 126.70,
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25.92, 124.47, 123.30, 45.50, 38.76, 26.23, 23.03, 15.44.
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HR-MS (ESI-TOF) m/z: calcd. for C17
2
H
21S [M+1] 257.1364; found:
57.1356.
[
[
Ethyl 2-(5-methylthiophen-2-yl)-2,2-diphenylacetate (3.25) Elec-
trochemical oxidation of (80 mg, 0.18 mmol) was performed in the
presence of 2-methylthiophene (0.1 mL, 1.0 mmol) according to the
general procedure at 5 mA. Purification by twice column chromatog-
raphy on silica gel (eluent petroleum) afforded 13.2 mg (21%) of prod-
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wandte Chemie International Edition 2014, 53, 13835–13839
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H NMR (300 MHz, CDCl
3
) δ 7.36 – 7.27 (m, 6H), 7.17 – 7.06 (m, 4H),
6
.58 (dd, J = 3.6, 1.1 Hz, 1H), 6.43 (d, J = 3.6 Hz, 1H), 4.33 (q, J = 7.1
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Hz, 2H), 2.44 (d, J = 1.1 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H).
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3
+
21
H O
2
S [M+1] 337.1262; found:
2
37.1245.
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(
0
1
.20 mmol) was performed in the presence of 2-methylfuran (0.09 mL,
.0 mmol) according to the general procedure at 5 mA. Purification by
column chromatography on silica gel (eluent petroleum ether/Et
2
O
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[
[
[
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1
H NMR (400 MHz, CDCl
.98 (d, J = 8.5 Hz, 2H), 6.65 (d, J = 3.5 Hz, 1H), 6.59 (m, 1H), 4.37
s, 2H), 2.43 (s, 3H), 1.91 (s, 3H).
C NMR (101 MHz, CDCl
27.07, 127.01 (q, J = 3.8 Hz), 126.90, 124.5 (q, J = 271 Hz), 123.3
q, J = 32.8 Hz), 114.85, 46.13, 26.69, 15.38.
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Acknowledgements
This work was supported by internal student grants (IG-2018-07,
IG-2019-07) from the Latvian Institute of Organic Synthesis.
Keywords: Friedel-Crafts reaction • electrochemistry • carbe-
nium ion • anodic oxidation • stannylmethylethers
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6
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European Journal of Organic Chemistry
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FULL PAPER
Entry for the Table of Contents
Insert graphic for Table of Contents here. ((Please ensure your graphic is in one of following formats))
Friedel-Crafts alkylation of electron rich arenes can be achieved by stabilized carbenium ions which are generated by single cell an-
odic oxidation of stannylmethylethers at low potential. The use of NaHCO as an additive ensures close-to-neutral conditions enabling
3
the reaction with arenes bearing acid-sensitive groups such as O-TBS, O-Tr, O-MOM, O-THP.
Institute and/or researcher Twitter usernames: Latvian Institute of Organic Synthesis @osi_lv
7
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