Single-Electron Transfer from Dimsyl Anion in the Alkylation of Phenols

Article abstract of DOI:10.1021/acs.joc.9b03237

While attempting to synthesize biaryl ethers we discovered the inadvertent formation of a methylsulfoxylmethyl ether byproduct. Formation of this unexpected byproduct presented an opportunity to streamline the synthesis of methylsulfoxylmethyl ethers. Mechanistic studies suggest a radical pathway with dimsyl potassium as a reducing agent.

Full text of DOI:10.1021/acs.joc.9b03237

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Note
Single Electron Transfer from Dimsyl Anion in the Alkylation of Phenols
Samantha Rohe, Guillaume Revol, Thomas Marmin, Daniel Barriault, and Louis Barriault
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03237 • Publication Date (Web): 08 Jan 2020
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The Journal of Organic Chemistry
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Single Electron Transfer from Dimsyl Anion in the Alkylation of
Phenols
Samantha Rohe,a Guillaume Révol,b Thomas Marmin,b Daniel Barriault,a Louis Barriaulta*
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aCentre for Catalysis, Research and Innovation Department of Chemistry and Biomolecular Sciences, University of
Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada
bOmegaChem, 480 Rue Perreault, Saint-Romuald, Québec G6W 7V6, Canada
K2CO3, DMSO
Cl
R
via SET
from dimsyl
anion
R
e-
O
S
I
OH
O
Cl
, 135 oC
2
1
4
2
source of aryl
radical for HAT
- 21 examples
- mechanistic studies
- K2CO3 as a mild base
- dimsyl anion as electron source
Supporting Information Placeholder
ABSTRACT: While attempting to synthesize biaryl ethers we discovered the inadvertent formation of a methylsulfoxylmethyl ether
byproduct. Formation of this unexpected byproduct presented an opportunity to streamline the synthesis of methylsulfoxylmethyl
ethers. Mechanistic studies suggest a radical pathway with dimsyl potassium as reducing agent.
Aryl ethers are an important class of organic molecules. In
particular, biaryl ether motifs which are found in many
biologically active molecules including natural products,
pharmaceutical and agrochemical products.1 Most synthetic
methods for the preparation of biaryl ethers are based on the
formation of C-O bond through a classic Ullman type coupling
reaction using copper (I) or palladium (II) complexes.2
Alternatively, nucleophilic SNAr reactions represent an
attractive and complementary method for the direct coupling of
phenols and aryl halides.3 As such, we attempted the formation
of biaryl 4 using phenol 1 and 2,6-dichloroiodobenzene 2 in
DMSO (Scheme 1 A). Surprisingly, the desired biaryl 4 was
not isolated but a single byproduct 3 was consistently formed.
The identification of this byproduct revealed the addition of
DMSO to the phenolic-OH moiety as opposed to the expected
arene. Though this result did not advance our immediate goals,
we realized this SNAr “failure” could represent an interesting
method to install methylsulfinylmethyl ether units in a one-step
process via a unique mechanism.
as a source of C1 and other alkyl groups in synthesis.7
Moreover, there is evidence that dimsyl anion can act as a single
electron reducing agent (Scheme 1C).6c
Scheme 1. Unexpected alkylation of DMSO
A
Cl
Cl
Failed SNAr
R
R
I
OH
O
Cl
1
2
K2CO3, DMSO
135 °C
4
Cl
Evidence for DMSO as
O
single electron reductant
of iodoarenes
S
R
3
O
B Two-step synthesis of sulfoxide ethers (ref 5)
O
O
R
X
S
[O]
S
R
R
O
X = halogen
OH
S
C Mechanistic precedent for DMSO as SET agent with iodoalkanes (ref 6c)
A
cursory survey of the literature reveals that aryl
methylsulfinylmethyl ethers are present in many bioactive
compounds and also serve as synthetic handles for the
installation of various other functional groups.4 In these
examples, the addition of methylsulfoxylmethyl ethers to
phenols is mainly conducted via a two-step process which
involves the formation of a methylthiomethyl ether (MTM)
followed by oxidation into the corresponding sulfoxide
(Scheme 1B).5 Although the first step is generally reliable, the
second step could be susceptible to overoxidation of the sulfide
and will restrict functional group tolerance in the scope.
KOtBu, hv
H
Ph
I
DMSO
RESULTS AND DISCUSSION
Optimization of the reaction conditions began by first
determining the role of the base counterion (entries 1-3).
Changing from potassium to sodium proved to
counterproductive as only starting materials were recovered
(entries 1 and 2). Use of cesium as a counterion, however, led
to moderate success (entry 3). Although this trend does not
follow the solubility of these carbonate bases in DMSO, one can
suggest that the counterion might influence the outcome of
electron transfer radical reactions.8 Lowering base loading
resulted in decreased yields (entry 4).
Preliminary discussions of the alkylation mechanism raised
further interest in this transformation. It was found that ample
mechanistic precedent exists for the involvement of DMSO in
radical reactions, sometimes as a redox agent,6 and other times
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Page 2 of 8
Secondly, the reaction was attempted at temperatures lower
than 135 C with no success (entry 5). When lowering
thioether remained intact under the reaction conditions. The
existing methods to alkylate phenols with sulfoxides would
likely oxidize any other thioethers, thiols, or sulfoxides
present.5 Finally, the reaction was amenable to large molecules
of biological relevance such as estrone 1t (25%) and α-
tocopherol 1u (29%).
°
1
2
3
4
5
6
7
8
equivalents of iodoarene 2 or reduced to zero, the reaction
suffered from reduced yields or failure (entries 6 and 7).
Furthermore, performing the reaction at higher concentration in
DMSO (entries 8 and 9) proved to be detrimental. Attempts to
run reactions in DMSO with various cosolvents resulted in a
halting of the reaction or prohibitively low yields (<15%) (see
Supporting Information for complete optimization tables).
Scheme 2. Substrate scopea
Table 1. Optimization of DMSO alkylation reaction.
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Entry
Base
Conc
(M)
Temp
(°C)
Time
(h)
Yield (%)a
1
K2CO3
0.1
135
135
135
135
22
16
16
16
16
16
16
16
16
16
96 (70)b
2
Na2CO3 0.1
Cs2CO3 0.1
0
3
4c
54
79
0
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.1
0.1
0.1
0.1
0.5
0.05
5
6d
7e
8
135
135
135
135
67
0
26
84
9
aYields determined by NMR internal standard using
trimethyl(phenyl)silane. bIsolated yield in brackets. c1.1
equivalents of base. 1.1 equivalents of 2. eReaction performed
d
without 2.
aReaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), K2CO3 (0.66
mmol), DMSO (3 mL), 135 C, 16h. Reaction run on 1g scale,
yield = 60%.
°
b
Following determination of optimal conditions, the scope of the
reaction was examined (Scheme 2). Overall, yields varied
widely from poor to good (25-75%). The reaction was not
contingent to phenol electronics, good yields were obtained
with electronically opposite substrates 1d and 1e (59% and 45%
yields respectively). Interestingly, the reaction was amenable to
steric hindrance, such as the hindrance exhibited in ortho-
substituted phenols 1a, 1b, and 1r (70%, 62% and 75% yields),
though the presence of bulky groups such as the 2-adamantyl-
4-methylphenol 1k led to reductions in yield (33%).
A few sulfoxides other than DMSO were examined as solvents
to expand the sulfoxide scope (see SI). Though product was
observed by NMR and GC-MS, this product was inseparable
from the parent sulfoxide. Unusual results were observed when
diethyl sulfoxide (DESO) was employed as the solvent, forming
complex mixtures of products in which tarry black polymer
dominated. This may be due to slower single electron reduction
from highly aliphatic sulfoxides such as DESO.9
All reactions went to completion except when phenol 1f was
used, which resulted in isolation of 5% of the phenol starting
material. No major byproduct was observed and haloarene 2
was completely consumed in every case, though occasionally
traces of SNAr product 4 were detected via GC-MS. Notably,
iodophenols 1b and 1l were converted to the desired products
in 62% and 53% yields, respectively. These results showed that
aryl-halogen bonds are resilient towards the reaction conditions
aside from the required haloarene 2. The conditions were also
tolerant of functionally important substrates 2-propenylphenol
1q (43%), which exhibited minimal thermal cis-trans
isomerization (starting material 72:28 E:Z, see SI), and 2-
hydroxyphenylacetylene 1o (51%), where the alkyne remained
untouched throughout the transformation. The substrate 1s
(75%) demonstrates the utility of this transformation, as the
We then delved into mechanistic elucidation by considering
many possibilities. Firstly, the role of the iodoarene was probed
(Scheme 3). The 2,6-dichloroiodobenzene 2 proved essential to
the transformation, as attempts to substitute it with 2-
chloroiodobenzene and iodobenzene did not produce any
desired products and simply resulted in decomposition of the
phenol (eq. 1). We then considered that the iodine on 2 may be
oxidizing DMSO and attempted other sources of iodine in the
reaction. Use of N-iodosuccinimide (NIS) and molecular
iodine, in place of the iodoarene, also resulted in decomposition
of the phenol or inseparable mixtures of products respectively.
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can undergo dissociative electron transfer, forming iodide and
a corresponding high-energy aryl radical. Indeed, 2,2',6,6'-
tetrachloro-1,1'-biphenyl, the dimer of this aryl radical, was
detected in low yields in all scope reactions (see Supporting
Information). Attempts to quantitatively trap aryl radical
intermediates have thus far met with failure.14
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Scheme 3. Additional mechanistic studies
O
S
R
I
Br
OH
K2CO3, DMSO
135 °C, 6 h
Br
O
+
eq. 1
eq. 2
Consideration of a radical mechanism imparts an explanation
for some unusual scope results. As steric hindrance tends to
decrease nucleophilicity of a compound, yet several sterically
encumbered examples in the scope provide excellent yields (1c,
53% yield and 1r, 75% yield), nucleophilic substitution is not
indicated as a major mechanistic factor. However, bis-ortho
substitution of phenols can stabilize the associated O-centered
radical, increasing its longevity to the point where it may react
with a nucleophilic species.15 Our attempts to trap such a
phenoxyl radical with 2-allylphenol have unfortunately met
with failure due to the substrate’s slow cyclization rate.16
4
5
R = H
R = Cl
1a
CF3
OH
3a
, 0%
Cl
O
9
CF3
S
K2CO3, DMSO
135 °C, 6 h
+
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F3C
I
F3C
O
0%
pKa 17.2
Cl
2
O
S
Br
OH
Cl
I
Br
O
+
K2CO3, DMSO
eq. 3
TEMPO (2 equiv.)
135 °C, 6 h
Cl
Cl
2
3a
, 0%
Scheme 4. Deuterium studiesa
Cl
I
O
KOtBu (0.75 equiv),
S
O
S
+
eq. 4
OH
DMSO, 135 °C, 6 h
O
Br
OH
standard conditions
3h
1h
, 35%
2
Br
O
in DMSO-d6
An ionic mechanism was then considered. Intermediacy of an
alkoxide was probed by using aliphatic alcohol HFIP in place
of phenol, as the pKa’s in DMSO are similar (pkaphenol = 18,
pKaHFIP = 17.2) (eq. 2).10 However, no product was observed.
The use of nucleophiles such as anilines, thiophenols, and
cyclopentanol afforded only decomposition or recovery of
starting material, indicating that the mechanism is not simply
bimolecular substitution on iodomethyl methyl sulfoxide. A
putative benzyne intermediate, generated via an ionic pathway,
was then probed using trapping experiments. Trihalogenated
arenes such as 2 can form benzyne relatively slowly,11 however,
studies of similar substrates indicate that the aryl radical can be
formed more rapidly.6a,12 Our attempts to trap a benzyne
intermediate with furan or 1,3-cyclohexadiene resulted in
complex mixtures containing no Diels-Alder adduct. However,
these experiments do not completely rule out involvement of
phenoxide or diradical benzyne intermediates.
1a
d-3a
, 62%
= 95% 2
H
xd
O
S
Br
OH
Br
O
standard conditions
1:1 DMSO:DMSO-d6
d-3a
, 52%
1a
= 32% 2
= 24% and
10% 2
H
H
a Ratios of H:D determined by comparison of 1H NMR integrals
between aromatic or aliphatic C-H bonds and alpha-sulfoxide C-H
bonds. See Supporting Information for details.
Finally, deuterium studies were conducted to probe DMSO’s
involvement in the reaction (Scheme 4). As all positions alpha
to the sulfoxide are enolizable and will therefore exchange with
any water present, it was not feasible to determine accurate
KIEs.17 However, when the reaction was run in DMSO-d6, the
product contained 95% deuterium incorporation at both alpha-
sulfoxide positions. The yield (d-3a, 62%) is comparable to the
same reaction run in proteated DMSO (3a, 70%), indicating that
the presence of deuterium scarcely impacted reaction kinetics.
Likewise, when the reaction was run in a 1:1 mixture of
DMSO:DMSO-d6, the alpha-sulfoxide CH3 was 32%
deuterated and the alpha-oxo CH’s were 10% and 24%
deuterated. A small reduction in yield (52% compared to 70%
in DMSO) was observed, though no additional byproducts were
identified, and all starting materials were consumed. Due to the
elevated concentration of protons in the mixed solvent, it seems
that H-D exchange is so prevalent as to obfuscate meaningful
results in the second trial.
A radical mechanism was then considered. Addition of 2
equivalents of TEMPO or BHT to the standard conditions
resulted in exclusive formation of insoluble polymer containing
only traces of product, which indicates mechanistic
involvement of radicals (eq. 3). Peñéñory and co-workers
suggested that dimsyl anion can function as a single electron
reductant in the presence of KOtBu and can form complexes
that facilitate charge transfer to iodoalkanes, with electron
transfer occurring from dimsyl anion rather than potassium tert-
butoxide.8c, 12 One can suppose that dimsyl potassium generated
in the presence of K2CO3 may function similarly. Attempts to
reproduce these results in our system by replacing the carbonate
base with 0.75 equivalents of KOtBu resulted in 35% yield of
desired product (eq. 4). However, it is important to note that
using 2 equivalents of KOtBu or KH led to the recovery of the
starting material. These results suggest that the presence of the
phenol O-H bond is essential for the reaction to proceed.
Involvement of an aryl radical offers rationale for the
requirement of 2 as additive. Iodoarenes, especially those
vicinally bis-substituted with other halogens such as chlorine,
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Based on precedent and the above mechanistic studies, the
Page 4 of 8
General Information. All reactions were performed in Pyrex
glassware equipped with a magnetic stir bar, capped with a
septum, unless otherwise indicated. All commercial reagents
including HPLC-grade DMSO were obtained from Sigma
Aldrich, Alfa Aesar or Combi Blocks and used without further
purification, unless otherwise noted. Reactions were monitored
by thin layer chromatography (TLC) analysis. TLC plates were
viewed under UV light and stained with potassium
permanganate or p-anisaldehyde staining solution. Yields refer
to products isolated after purification, unless otherwise stated.
Proton nuclear magnetic resonance (1H NMR) spectra were
recorded on a Bruker AMX 400 MHz, Bruker Avance 500, or a
Bruker Avance III HD 600 MHz instrument. Carbon nuclear
magnetic resonance (13C NMR) spectra were recorded on the
same Bruker instruments (101, 126, and 151 MHz
respectively). Carbon peak assignments (CH3, CH2, CH, and C)
were completed using DEPT-135 and DEPT-90 NMR on the
same Bruker instruments (101, 126, and 151 MHz
respectively). Fluorine nuclear magnetic resonance (19F NMR)
spectra were recorded on a Bruker Avance 377 MHz
instrument. NMR samples were dissolved in chloroform-d
(unless specified otherwise) and chemical shifts are reported in
ppm referenced to residual non-deuterated solvent. IR spectra
were recorded with an Agilent Technologies Cary 630 FTIR
Spectrometer equipped with a diamond ATR module. GC-MS
(EI) were obtained on an Agilent 5975 series MSD instrument
(University of Ottawa Centre for Catalysis Research and
Innovation High-Throughput Experimentation Core Facility).
HRMS were obtained on a Kratos Analytical Concept
instrument (EI) and a Micromass Q-TOF I instrument (ESI) at
the University of Ottawa Mass Spectrum Centre.
1
2
3
4
5
6
7
8
following mechanism is proposed (Scheme 5). The mixture of
K2CO3 and DMSO produces a low concentration of dimsyl
potassium. We propose that this dimsyl anion can inject a single
electron into the weak carbon-iodine bond of 2 under these
conditions [BDE(iodobenzene) = 64], generating a stabilized
dichloroaryl radical i, a DMSO radical, and iodide.18 The aryl
radical (BDE ≈ 103 kcal/mol) is then able to perform H-atom
transfer (HAT) on the phenol (BDE ≈ 86),19,20 generating a more
stable radical species ii and 1,3-dichlorobenzene.21 The
resulting oxygen-centered radical ii reacts with dimsyl anion via
Path A, creating a powerfully reducing radical ion iii that
becomes oxidized by molecular oxygen or can propagate a
chain cycle by SET to iodoarene 2.22 Alternatively, the phenol
radical ii could recombine with the DMSO radical anion
generated during an initiating SET event as seen in Path B. As
the dimsyl anion is likely present in higher concentrations than
the DMSO radical, Path A is proposed to be the dominant
pathway. This mechanistic proposal involves reactions of
species present in relatively low concentrations, which
contextualizes the long reaction time and non-quantitative
yields. These results do not completely eliminate the possibility
that the iodoarene 2 may be oxidizing DMSO, making
iodomethyl methyl sulfoxide which then undergoes
nucleophilic substitution with a phenolate. If this pathway is
present, we suspect that it is minor based on available evidence.
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Scheme 5. Proposed mechanism
K2CO3
O
S
O
S
Cl
I
General Procedure: methylsulfoxyl methyl etherification of
phenols (Table 1, Scheme 2). To an open-air round-bottom
flask equipped with a stir bar was added K2CO3 (0.66 mmol, 2.2
eq.), 2,6-dichloroiodobenzene (0.45 mmol, 1.5 eq.), and phenol
substrate (0.3 mmol, 1 eq.). DMSO (0.1M, 3mL) was added and
the flask was fitted with a Vigreux column OR a reflux
condenser open at the top to ambient atmosphere. The reaction
was stirred at 135 °C in a bath of aluminum granules on a hot
plate with temperature probe for 16 hours. Upon completion,
the reaction was cooled to room temperature and diluted with
water (20 mL) and ethyl acetate (10 mL). The layers were
separated and the aqueous phase was extracted a further 2x with
10 mL ethyl acetate. The organic layers were combined and
washed successively with water (10 mL) and brine (10 mL).
The organic layer was dried, filtered, and concentrated under
reduced pressure to afford the crude brown oil product. The
crude residue was purified via silica gel chromatography to
afford the final product (solvent system: gradient of 5 – 80%
ethyl acetate in hexanes).
SET
Cl
O
O
2
S
R
Cl
R
3
I
OH
1
i
Cl
Cl
SET
HAT
Cl
H
O
I
S
Cl
2
Cl
O
O
Path B
Path A
S
R
R
O
ii
iii
O
S
O
S
CONCLUSIONS
4-Bromo-1-methyl-2-(((methyl-d3)sulfinyl)methoxy-
In summary, the examination of a curious byproduct of SNAr
has led to a serendipitous streamlining of methylsulfoxylmethyl
ether synthesis. Submitting this unusual transformation to
mechanistic studies suggests the role of DMSO as not only
solvent but also possibly single electron reducing agent in the
presence of base. Investigations into the capacity of DMSO as
a radical reducing agent are currently under investigation by our
group.
d2)benzene (d-3a). From 5-bromo-2-methylphenol (1a, 56 mg,
0.3 mmol) and DMSO-d6 as solvent (3 mL, 0.1M), d-3a was
obtained as an amorphous off-white solid (in DMSO-d6: 49 mg,
0.19 mmol, 62% yield; in 1:1 DMSO:DMSO-d6: 42 mg, 0.16
mmol, 52% yield). IR (neat, cm-1): 3060, 2964, 2919, 2916,
2844, 2280, 1582; 1H NMR (400 MHz, Chloroform-d) δ = 7.12
– 7.06 (m, 2H), 7.03 – 7.00 (m, 1H), 4.96 (s, 1H), 4.85 (s, 1H),
2.66 (t, J = 1.9 Hz, 3H), 2.19 (d, J = 0.7 Hz, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ = 156.2 (C), 132.3 (CH), 126.4 (C), 125.7
(CH), 119.6 (C), 116.3 (CH), 83.9 (CD2), 34.9 (CD3), 15.9
EXPERIMENTAL SECTION
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(CH3); HRMS (ESI): m/z [M + Na, 79Br]+ calc’d for
C9H6D5BrO2SNa, 289.9875; found, 289.9887.
amorphous colorless solid (41 mg, 0.21 mmol, 70% yield). IR
1
(neat, cm-1): 3068, 3009, 3003, 2918, 2852, 2221, 1594; H
1
2
3
4
5
6
7
8
9
NMR (400 MHz, CDCl3) δ = 7.66 – 7.59 (m, 2H), 7.18 – 7.10
(m, 2H), 4.99 (d, J = 0.9 Hz, 2H), 2.70 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ = 160.6 (C), 134.2 (2 X CH), 118.5 (C),
116.3 (2 X CH), 106.5 (C), 83.6 (CH2), 35.4 (CH3); HRMS
(ESI): m/z [M + Na]+ calc’d for C9H9NO2SNa, 218.0268;
found, 218.0252.
4-Bromo-1-methyl-2-((methylsulfinyl)methoxy)benzene
(3a). From 5-bromo-2-methylphenol (1a, 56 mg, 0.3 mmol; or
0.5g, 2.67 mmol; or 1g, 5.35 mmol), 3a was obtained as an
amorphous pale red solid (56 mg scale: 49 mg, 0.19 mmol, 70%
yield; 0.5 g scale: 0.55 g, 2.1 mmol, 79% yield; 1 g scale: 0.84
g, 3.2 mmol, 60% yield). IR (neat, cm-1): 3062, 2922, 2914,
2089, 1582; 1H NMR (400 MHz, CDCl3) δ = 7.12 – 7.07 (m,
2H), 7.01 (dt, J = 7.8, 0.7 Hz, 1H), 4.98 (d, J = 10.0 Hz, 1H),
4.86 (d, J = 10.0 Hz, 1H), 2.69 (s, 3H), 2.19 (d, J = 0.7 Hz, 3H);
13C{1H} NMR (126 MHz, CDCl3) δ = 156.2 (C), 132.3 (CH),
126.4 (C), 125.8 (CH), 119.6 (C), 116.3 (CH), 84.4 (CH2), 35.8
(CH3), 15.9 (CH3); HRMS (ESI): m/z [M + Na, 81Br]+ calc’d for
C9H11BrO2SNa, 286.9540; found, 286.9556.
Methyl 4-((methylsulfinyl)methoxy)benzoate (3g). From
methyl 4-hydroxybenzoate (1g, 47 mg, 0.3 mmol) 3g was
obtained as an amorphous pale yellow solid (49 mg, 0.22 mmol,
72% yield). Characterized by NMR comparison.5c 1H NMR
(400 MHz, CDCl3) δ = 8.11 – 7.95 (m, 2H), 7.14 – 6.96 (m,
2H), 5.04 (d, J = 10.2 Hz, 1H), 4.93 (d, J = 10.2 Hz, 1H), 3.88
(s, 3H), 2.70 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ =
166.3 (C), 160.9 (C), 131.8 (2 X CH), 124.9 (C), 115.0 (2 X
CH), 83.6 (CH2), 52.1 (CH3), 35.7 (CH3).
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1-Iodo-2-((methylsulfinyl)methoxy)benzene (3b). From 2-
iodophenol (1b, 89 mg, 0.3 mmol) 3b was obtained as an
amorphous pale yellow solid (55 mg, 0.19 mmol, 62% yield).
IR (neat, cm-1): 3055, 2995, 2915, 2909, 1582, 1034; 1H NMR
(400 MHz, CDCl3) δ = 7.77 (dd, J = 7.8, 1.6 Hz, 1H), 7.33 (ddd,
J = 8.2, 7.4, 1.6 Hz, 1H), 7.06 (dd, J = 8.2, 1.4 Hz, 1H), 6.82
(ddd, J = 7.8, 7.4, 1.3 Hz, 1H), 5.07 (d, J = 10.0 Hz, 1H), 4.89
(d, J = 10.0 Hz, 1H), 2.78 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ = 156.3 (C), 139.9 (CH), 129.9 (CH), 124.9 (CH),
114.4 (CH), 86.6 (C), 84.5 (CH2), 36.3 (CH3); HRMS (ESI):
m/z [M + Na]+ calc’d for C8H9IO2SNa, 318.9260; found,
318.9264.
((Methylsulfinyl)methoxy)benzene (3h). From phenol (1h, 28
mg, 0.3 mmol) 3h was obtained as a yellow oil (32 mg, 0.19
mmol, 63% yield). Characterized by NMR comparison.20 1H
NMR (400 MHz, CDCl3) δ = 7.33 – 7.26 (m, 2H), 7.07 – 6.98
(m, 3H), 5.00 (d, J = 10.1 Hz, 1H), 4.84 (d, J = 10.1 Hz, 1H),
2.65 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ = 157.4 (C),
129.8 (2 X CH2), 123.0 (CH), 115.6 (2 X CH), 84.4 (CH2), 35.8
(CH3).
1-Bromo-4-((methylsulfinyl)methoxy)benzene (3i). From 4-
bromophenol (1i, 52 mg, 0.3 mmol) 3i was obtained as an
amorphous pale yellow solid (46 mg, 0.19 mmol, 62% yield).
Characterized by NMR comparison.5c 1H NMR (400 MHz,
CDCl3) δ = 7.45 – 7.35 (m, 2H), 7.00 – 6.86 (m, 2H), 4.94 (d, J
= 10.3 Hz, 1H), 4.85 (d, J = 10.3 Hz, 1H), 2.65 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ = 156.7 (C), 132.7 (2 X CH), 117.5
(2 X CH), 115.5 (C), 84.4 (CH2), 35.6 (CH3).
1,3-Dimethyl-2-((methylsulfinyl)methoxy)benzene
(3c).
From 2,6-dimethylphenol (1c, 37 mg, 0.3 mmol) 3c was
obtained as an amorphous colorless solid (32 mg, 0.16 mmol,
53% yield). IR (neat, cm-1): 3040, 2998, 2919, 2852, 1031; 1H
NMR (400 MHz, CDCl3) δ = 7.04 – 6.99 (m, 2H), 6.99 – 6.94
(m, 1H), 4.76 (d, J = 9.5 Hz, 1H), 4.71 (d, J = 9.5 Hz, 1H), 2.71
(s, 3H), 2.29 (d, J = 0.7 Hz, 6H); 13C{1H} NMR (101 MHz,
CDCl3) δ = 155.1 (C), 130.1 (2 X C), 129.3 (2 X CH), 125.1
(CH), 88.3 (CH2), 35.9 (CH3), 16.7 (2 X CH3); HRMS (ESI):
m/z [M + Na]+ calc’d for C10H14O2SNa, 221.0612; found,
221.0604.
1-Fluoro-4-((methylsulfinyl)methoxy)benzene (3j). From 4-
fluorophenol (1j, 34 mg, 0.3 mmol) 3j was obtained as an
amorphous off-white solid (23 mg, 0.12 mmol, 41% yield). IR
(neat, cm-1): 3051, 2960, 2932, 2910, 2835, 1503;1H NMR (400
MHz, CDCl3) δ = 7.03 – 6.93 (m, 4H), 4.93 (d, J = 10.3 Hz,
1H), 4.84 (d, J = 10.4 Hz, 1H), 2.65 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ = 158.5 (d, J = 242.4 Hz, C), 153.7 (C),
117.2 (d, J = 8.1 Hz, CH), 116.2 (d, J = 23.2 Hz), 85.1 (CH2),
35.4 (CH3); 19F{1H} NMR (377 MHz, CDCl3) δ = -120.5 ppm;
HRMS (ESI): m/z [M + Na]+ calc’d for C8H9FO2SNa,
211.0205; found, 211.0215.
1-((Methylsulfinyl)methoxy)-4-nitrobenzene (3d). From 4-
nitrophenol (1d, 42 mg, 0.3 mmol) 3d was obtained as an
amorphous deep yellow solid (38 mg, 0.18 mmol, 59% yield).
Characterized by NMR comparison.5c 1H NMR (400 MHz,
CDCl3) δ = 8.31 – 8.13 (m, 2H), 7.18 – 7.10 (m, 2H), 5.04 (d, J
= 2.0 Hz, 2H), 2.71 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3)
δ = 162.2 (C), 143.1 (C), 126.0 (2 X CH), 115.7 (2 X CH), 83.7
(CH2), 35.5 (CH3).
1-(5-Methyl-2-
((methylsulfinyl)methoxy)phenyl)adamantane (3k). From 2-
(adamantan-1-yl)-4-methylphenol (1k, 73 mg, 0.3 mmol) 3k
was obtained as an amorphous yellow solid (32 mg, 0.10 mmol,
33% yield). IR (neat, cm-1): 3058, 2994, 2903, 2846, 1583,
1045;1H NMR (600 MHz, CDCl3) δ = 7.07 – 7.01 (m, 1H), 6.98
(ddd, J = 8.3, 2.2, 0.8 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 5.01
(d, J = 9.8 Hz, 1H), 4.86 (d, J = 9.8 Hz, 1H), 2.72 (s, 3H), 2.28
(s, 3H), 2.10 – 2.01 (m, 9H), 1.80 – 1.68 (m, 6H); 13C{1H}
NMR (151 MHz, CDCl3) δ = 154.7 (C), 138.7 (C), 132.1 (C),
127.9 (CH), 127.3 (CH), 114.2 (CH), 85.1 (CH2), 40.9 (3 X
CH2), 37.0 (3 X CH2), 36.9 (C), 36.0 (CH3), 29.0 (3 X CH), 20.9
(CH3); HRMS (ESI): m/z [M + Na]+ calc’d for C19H26O2SNa,
341.1551; found, 341.1542.
1-Methoxy-4-((methylsulfinyl)methoxy)benzene (3e). From
4-methoxyphenol (1e, 37 mg, 0.3 mmol) 3e was obtained as an
amorphous pale yellow solid (27 mg, 0.14 mmol, 45% yield).
Characterized by NMR comparison.5c 1H NMR (400 MHz,
CDCl3) δ = 7.06 – 6.90 (m, 2H), 6.90 – 6.73 (m, 2H), 4.96 (dd,
J = 10.2, 3.2 Hz, 1H), 4.86 – 4.75 (dd, J = 10.2, 1.6 Hz, 1H),
3.84 – 3.67 (m, 3H), 2.66 (d, J = 3.0 Hz, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ = 155.5 (C), 151.6 (C), 117.0 (2 X CH),
114.9 (2 X CH), 85.5 (CH2), 55.7 (CH3), 35.6 (CH3).
4-((Methylsulfinyl)methoxy)benzonitrile (3f). From 4-
cyanophenol (1f, 36 mg, 0.3 mmol) 3f was obtained as an
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1-Iodo-3-((methylsulfinyl)methoxy)benzene (3l). From 3-
iodophenol (1l, 66 mg, 0.3 mmol) 3l was obtained as an
amorphous off-white solid (31 mg, 0.16 mmol, 53% yield). IR
(neat, cm-1): 3055, 2992, 2915, 2909, 1582, 1034;1H NMR (600
MHz, CDCl3) δ = 7.44 – 7.35 (m, 2H), 7.07 – 6.97 (m, 2H), 4.96
(d, J = 10.2 Hz, 1H), 4.85 (d, J = 10.2 Hz, 1H), 2.68 (s, 3H);
13C{1H} NMR (151 MHz, CDCl3) δ = 157.9 (C), 132.3 (CH),
131.1 (CH), 125.0 (CH), 115.0 (CH), 94.3 (C), 84.0 (CH2), 35.7
(CH3); HRMS (ESI): m/z [M + Na]+ calc’d for C8H9IO2SNa,
318.9266; found, 318.9261.
(27 mg, 0.13 mmol, 43% yield, 78:22 E:Z). IR (neat, cm-1):
3030, 2941, 2923, 2853, 1972, 1685, 1599, 1048; H NMR
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(trans isomer) (400 MHz, CDCl3) δ = 7.41 (dd, J = 7.9, 1.7 Hz,
1H), 7.32 – 7.09 (m, 1H), 7.10 – 6.95 (m, 2H), 6.64 (dq, J =
15.8, 1.8 Hz, 1H), 6.21 (dq, J = 15.9, 6.6 Hz, 1H), 5.03 (dd, J =
10.0, 5.4 Hz, 1H), 4.83 (dd, J = 11.9, 10.0 Hz, 1H), 2.59 (s, 3H),
1.89 (dd, J = 6.6, 1.8 Hz, 3H); 13C{1H} NMR (trans isomer)
(101 MHz, CDCl3) δ = 154.0 (C), 130.7 (C), 128.0 (CH), 127.8
(CH), 126.8 (CH), 124.7 (CH), 123.3 (CH), 114.1 (CH), 85.1
(CH2), 41.0 (CH3), 18.9 (CH3); 1H NMR (cis isomer) (400 MHz,
CDCl3) δ = 7.32 – 7.09 (m, 2H), 7.10 – 6.95 (m, 2H), 6.47 (dd,
J = 11.5, 2.0 Hz, 1H), 5.85 (dq, J = 11.6, 7.1 Hz, 1H), 5.03 (dd,
J = 10.0, 5.4 Hz, 1H), 4.83 (dd, J = 11.9, 10.0 Hz, 1H), 2.68 (s,
3H), 1.79 (dd, J = 7.1, 1.8 Hz, 3H); 13C{1H} NMR (cis isomer)
(101 MHz, CDCl3) δ = 154.0 (C), 130.7 (C), 128.2 (CH), 128.1
(CH), 128.1 (CH), 124.5 (CH), 122.7 (CH), 114.2 (CH), 85.0
(CH2), 35.9 (CH3), 14.6 (CH3); HRMS (ESI): m/z [M + Na]+
calc’d for C11H14O2SNa, 233.0607; found, 233.0612.
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2-((Methylsulfinyl)methoxy)naphthalene
(3m).
From
naphthalen-1-ol (1m, 43 mg, 0.3 mmol) 3m was obtained as an
amorphous yellow solid (42 mg, 0.19 mmol, 64% yield).
Characterized by NMR comparison.5c 1H NMR (400 MHz,
CDCl3) δ = 7.76 (dd, J = 12.3, 8.4 Hz, 3H), 7.47 (ddd, J = 8.2,
6.8, 1.3 Hz, 1H), 7.39 (ddd, J = 8.1, 6.9, 1.3 Hz, 1H), 7.34 (d, J
= 2.6 Hz, 1H), 7.21 (dd, J = 9.0, 2.6 Hz, 1H), 5.16 (d, J = 10.1
Hz, 1H), 4.96 (d, J = 10.1 Hz, 1H), 2.72 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ = 155.2 (C), 134.1 (C), 130.1 (CH), 129.9
(C), 127.7 (CH), 127.1 (CH), 126.9 (CH), 124.8 (CH), 118.1
(CH), 109.0 (CH), 84.1 (CH2), 35.9 (CH).
1-Bromo-3-fluoro-2-((methylsulfinyl)methoxy)benzene
(3r). From 2-bromo-6-fluorophenol (1r, 57 mg, 0.3 mmol) 3r
was obtained as an amorphous colorless solid (60 mg, 0.23
mmol, 75% yield). IR (neat, cm-1): 3059, 3030, 2939, 2920,
2848, 1603, 1585, 1043; 1H NMR (400 MHz, CDCl3) δ = 7.46
(dd, J = 8.8, 6.0 Hz, 1H), 6.92 (dd, J = 9.7, 2.7 Hz, 1H), 6.67
(ddd, J = 8.8, 7.7, 2.7 Hz, 1H), 4.99 (d, J = 10.3 Hz, 1H), 4.92
(d, J = 10.3 Hz, 1H), 2.73 (s, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ = 162.4 (d, J = 250.5 Hz, C), 154.8 (d, J = 10.1 Hz,
C), 134.1 (d, J = 9.1 Hz, CH), 111.3 (d, J = 22.2 Hz, C), 107.0
(d, J = 4.0 Hz, C), 104.2 (d, J = 27.3 Hz, CH), 84.5 (CH2), 35.7
(CH3); 19F{1H} NMR (377 MHz, CDCl3) δ = -110.3 ppm;
HRMS (ESI): m/z [M + Na, 81Br]+ calc’d for C8H8BrFO2SNa,
290.9291; found, 290.9290.
1-Bromo-2-((methylsulfinyl)methoxy)benzene (3n). From 2-
bromophenol (1n, 52 mg, 0.3 mmol) 3n was obtained as an
amorphous colorless solid (44 mg, 0.18 mmol, 59% yield).
Characterized by NMR comparison.5c 1H NMR (400 MHz,
CDCl3) δ = 7.54 (dd, J = 7.9, 1.6 Hz, 1H), 7.29 (ddd, J = 8.2,
7.4, 1.6 Hz, 1H), 7.15 (dd, J = 8.3, 1.4 Hz, 1H), 6.95 (ddd, J =
7.9, 7.4, 1.4 Hz, 1H), 5.07 (d, J = 10.1 Hz, 1H), 4.90 (d, J = 10.1
Hz, 1H), 2.76 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ =
154.1 (C), 133.8 (CH), 128.9 (CH), 124.5 (CH), 115.9 (CH),
112.9 (C), 84.7 (CH2), 36.0 (CH3).
Methyl(4-((methylsulfinyl)methoxy)phenyl)sulfane
(3s).
1-Ethynyl-2-((methylsulfinyl)methoxy)benzene (3o). From
2-ethynylphenol (1o, 35 mg, 0.3 mmol) 3o was obtained as an
amorphous pale yellow solid (30 mg, 0.15 mmol, 51% yield).
IR (neat, cm-1): 3286, 3061, 2993, 2916, 2850, 2100, 1584,
1574; 1H NMR (400 MHz, CDCl3) δ = 7.24 (t, J = 7.9 Hz, 1H),
7.16 (dt, J = 7.6, 1.3 Hz, 1H), 7.12 (dd, J = 2.7, 1.4 Hz, 1H),
7.02 (ddd, J = 8.3, 2.7, 1.1 Hz, 1H), 4.97 (d, J = 10.2 Hz, 1H),
4.85 (d, J = 10.2 Hz, 1H), 3.07 (s, 1H), 2.65 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ = 157.2 (C), 129.8 (CH), 126.9
(CH), 123.7 (C), 118.9 (CH), 116.5 (CH), 84.1 (CH2), 82.8 (C),
78.0 (CH), 35.7 (CH3); HRMS (ESI): m/z [M + Na]+ calc’d for
C10H10O2SNa, 217.0294; found, 217.0299.
From 4-(methylthio)phenol (1s, 42 mg, 0.3 mmol) 3s was
obtained as an amorphous colorless solid (49 mg, 0.23 mmol,
75% yield). IR (neat, cm-1): 3057, 3002, 2981, 2919, 1592,
1585;1H NMR (400 MHz, CDCl3) δ = 7.28 – 7.17 (m, 2H), 7.04
– 6.91 (m, 2H), 4.98 (d, J = 10.2 Hz, 1H), 4.84 (d, J = 10.2 Hz,
1H), 2.66 (d, J = 1.8 Hz, 3H), 2.44 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ = 155.7 (C), 132.2 (C), 129.4 (2 X CH), 116.3
(2 X CH), 84.5 (CH2), 35.7 (CH3), 17.3 (CH3); HRMS (ESI):
m/z [M + Na]+ calc’d for C9H12O2S2Na, 239.0171; found,
239.0176.
3-((Methylsulfinyl)methoxy)-estrone (3t). From estrone (1t,
81 mg, 0.3 mmol) 3t was obtained as an amorphous colorless
solid (26 mg, 0.08 mmol, 25% yield). IR (neat, cm-1): 3030,
2923, 2863, 1734, 1606, 1496;1H NMR (400 MHz, CDCl3) δ =
7.21 (dd, J = 8.6, 1.1 Hz, 1H), 6.81 (dd, J = 8.6, 2.9 Hz, 1H),
6.76 (dd, J = 2.9, 1.2 Hz, 1H), 5.00 (d, J = 10.1 Hz, 1H), 4.81
(dd, J = 10.1, 1.5 Hz, 1H), 2.88 (dd, J = 8.8, 4.1 Hz, 2H), 2.66
(s, 3H), 2.53 – 2.43 (m, 1H), 2.37 (ddt, J = 9.0, 3.9, 1.8 Hz, 1H),
2.31 – 2.03 (m, 2H), 2.07 – 1.86 (m, 3H), 1.68 – 1.34 (m, 6H),
0.88 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ = 155.4 (C),
138.4 (C), 134.6 (C), 126.7 (CH), 115.6 (CH), 113.0 (CH), 84.3
(CH2), 50.4 (CH), 48.0 (C), 44.0 (CH), 38.2 (CH), 35.8 (CH2),
35.8 (CH3), 31.6 (CH2), 29.6 (CH2), 26.4 (CH2), 25.9 (CH2),
21.6 (CH2), 13.8 (CH3), -18.1 (C); HRMS (ESI): m/z [M + Na]+
calc’d for C20H26O3SNa, 369.1495; found, 369.1500.
1-Isopropyl-3-((methylsulfinyl)methoxy)benzene (3p). From
3-isopropylphenol (1p, 41 mg, 0.3 mmol) 3p was obtained as a
yellow oil (25 mg, 0.12 mmol, 39% yield). IR (neat, cm-1):
3031, 2957, 2924, 1589, 1585;1H NMR (400 MHz, CDCl3) δ =
7.21 (t, J = 7.9 Hz, 1H), 6.91 (ddt, J = 7.7, 1.5, 0.7 Hz, 1H), 6.88
(dd, J = 2.6, 1.7 Hz, 1H), 6.82 (ddd, J = 8.2, 2.7, 0.9 Hz, 1H),
5.02 (d, J = 10.0 Hz, 1H), 4.82 (d, J = 10.0 Hz, 1H), 2.86 (hept,
J = 6.9 Hz, 1H), 2.66 (s, 3H), 1.21 (d, J = 7.0 Hz, 6H); 13C{1H}
NMR (101 MHz, CDCl3) δ = 157.5 (C), 151.2 (C), 129.6 (CH),
121.2 (CH), 113.9 (CH), 112.4 (CH), 84.2 (CH2), 35.8 (CH3),
34.1 (CH), 23.9 (2 X CH3); HRMS (ESI): m/z [M + Na]+ calc’d
for C11H16O2SNa, 235.0764; found, 235.0769.
1-((Methylsulfinyl)methoxy)-2-(prop-1-en-1-yl)benzene
(3q). From 3-(prop-1-en-1-yl)phenol (1q, 40 mg, 0.3 mmol,
72:28 E:Z) 3q was obtained as an amorphous pale yellow solid
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The Journal of Organic Chemistry
Amines or Ethers under Microwave Irradiation at Presence of
(2R)-2,5,7,8-Tetramethyl-6-((methylsulfinyl)methoxy)-2-
((4R,8R)-4,8,12-trimethyltridecyl)chromane (3u). From α-
tocopherol (1u, 130 mg, 0.3 mmol) 3u was obtained as a
viscous dark brown oil (44 mg, 0.09 mmol, 29% yield). IR
(neat, cm-1): 2952, 2922, 2895, 2844, 1457;1H NMR (400 MHz,
CDCl3) δ = 4.67 (d, J = 9.4 Hz, 1H), 4.61 (d, J = 9.3 Hz, 1H),
2.70 (s, 3H), 2.55 (t, J = 6.8 Hz, 2H), 2.16 (s, 3H), 2.13 (s, 3H),
2.06 (s, 3H), 1.78 (dp, J = 19.7, 6.9 Hz, 2H), 1.58 – 1.44 (m,
2H), 1.43 – 0.95 (m, 17H), 0.83 (dd, J = 9.7, 6.5 Hz, 16H);
13C{1H} NMR (101 MHz, CDCl3) δ = 148.7 (C), 147.7 (C),
127.0 (C), 125.2 (C), 123.5 (C), 117.9 (C), 89.3 (CH2), 75.1 (C),
40.0 (CH2), 39.4 (CH2), 37.6-37.3 (m, 4 X CH2), 35.9 (CH3),
32.8 (CH), 32.7 (CH), 31.2 (CH2), 28.0 (CH), 24.8 (CH2), 24.4
(CH2), 23.9 (2 X CH3), 22.7 (CH3), 21.0 (CH2), 20.7 (CH2),
19.8-19.6 (m, 2 X CH3), 13.2 (CH3), 12.3 (CH3), 11.8 (CH3);
HRMS (ESI): m/z [M + Na]+ calc’d for C31H54O3SNa,
529.3691; found, 529.3688.
KF/Al2O3 without Solvent and Their Anti-Fungal Biological
Activities against Six Phytopathogens. Int. J. Mol. Sci. 2013, 14,
18850-18860; f) Yuyang, D.; Lipschutz, M. I.; Tilley, T. D.
Regioselective, Transition Metal-Free C–O Coupling Reactions
Involving Aryne Intermediates. Org. Lett. 2016, 18, 1530−1533; g)
Wang, D.-Y.; Yang, Z.-K.; Wang, C.; Zhang, A.; Uchiyama, M. From
Anilines to Aryl Ethers: A Facile, Efficient, and Versatile Synthetic
Method Employing Mild Conditions. Angew. Chem. Int. Ed. 2018, 57,
3641-3645.
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4. a) Monković, I.; Brown, M.; Luke, G. M.; Standridge, R. T.;
Willner, D.; Crosswell, A. R.; Algieri, A.; Buyniski, J. P.; Crenshaw,
R. R.; Juby, P. F. Potential non-dopaminergic gastrointestinal
prokinetic agents in the series of substituted benzamides. Eur. J. Med.
Chem. 1989, 24, 233-239. For selected examples of
methylsulfoxylmethyl ether used as functional handle or protecting
group, see: b) Okada, Y.; Wang, J.; Yamamoto, T.; Yokoi, T.; Mu, Y.
Amino Acids and Peptides. L. Development of a Novel Nπ-Protecting
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π
Group for Histidine, N -2-Adamantyloxymethylhistidine, and Its
Application to peptide Synthesis. Chem. Pharm. Bull. 1997, 45, 452-
456; c) Ringom, R.; Benneche, T.; Colapietro, M.; Pieretti, A.;
Ramondo, F.; Møller, J.; Senning, A.; Yao, X.-K.; Wang, H.-G.;
Tuchagues, J. P.; Ögren, M. Synthesis and Nucleophilic Substitution
Reactions of Mono alpha-Fluoro Ethers. Acta Chem. Scand. 1999, 53,
41-47; d) Adachi, M.; Hashimoto, H.; Sakakibara, R.; Imazu, T.;
Nishikawa, T. A New Deprotection Procedure of MTM Ether. Synlett
2014, 25, 2498-2502; e) Geng, Y.; Liang, A.; Gao, X.; Niu, C.; Li, J.;
Zou, D.; Wu, Y.; Wu, Y. CuI-Catalyzed Fluorodesulfurization for the
Synthesis of Monofluoromethyl Aryl Ethers. J. Org. Chem. 2017, 82,
8604-8610.
ASSOCIATED CONTENT
Supporting Information
The complete optimization tables, additional mechanistic data, and
copies of 1H and 13C NMR spectra (PDF).
AUTHOR INFORMATION
Corresponding Author
*Email: louis.barriault@uottawa.ca
5. For examples of synthesis of methylsulfoxylmethyl ethers, see: a)
Dahnke, K. R.; Gajewski, R. P.; Jones, C. D.; Linebarger, J. H.; Lu, J.;
Ma, T.; Nagpal, S.; Simard, T. P.; Yee, Y. K.; Bunel, E. E.; Stites, R.
ORCID
Louis Barriault: 0000-0003-2382-5382
Samantha Rohe: 0000-0002-5323-1203
E. Phenyl-Thiophene Type Vitamin D Receptor Modulators.
WO03101978 (A1), 2003/12/11/, 2003; b) Burdi, D. F.; Tanaka, D.;
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2016/03/24/, 2016; c) Wu, Y.; Geng, Y.; Niu, C.; Liang, E.; Liu, J.;
Meng, Q.; Li, J.; Zou, D.; Wu, Y. Synthesis method of
monofluoromethoxyl or monofluoro-deuterated methoxyl compound.
CN106083539 (A), 2016/11/09/, 2016; d) Riesinger, S.; Lazarova, T.;
Ribovskaia, Z. Nitric Oxide Donors. WO2017223182 (A1),
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OuazzaniꢀChahdi, F.; Sotiropoulos, J.-M.; Ollevier, T.; Taillefer, M.
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as a Synthon in Organic Chemistry. Synthesis 2016, 48, 1421-1436; b)
Garza-Sanchez, R. A.; Patra, T.; Tlahuext-Aca, A.; Strieth-Kalthoff, F.;
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and Carbonylated Benzofurans under Transition-Metal-Free
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of Pyridinium Ylides for the Assembly of Indolizines. J. Org. Chem.
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ACKNOWLEDGMENT
We thank the Natural Sciences and Engineering Research Council
(NSERC) for the Discovery grant to L.B. S.R. thanks the
government of Ontario for an OGS scholarship. We thank
Professor Fabien Gagosz for helpful comments and the Centre for
Catalysis Research and Innovation for use of their GC-MS.
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