Difluoro(aryl)(perfluoroalkyl)-λ4-sulfanes and Selanes: Missing Links of Trichloroisocyanuric Acid/Potassium Fluoride Chemistry

Article abstract of DOI:10.1002/anie.201910594

The TCICA/KF approach to oxidative fluorination of heteroatoms has emerged as a surprisingly simple, safe, and versatile surrogate to classically challenging fluorination reactions. Although polyfluorination (or chlorofluorination) of diaryl disulfides, diaryl diselenides, diaryl ditellurides, aryl iodides, and aryl(perfluoroalkyl)tellanes has been described, the application of this TCICA/KF methodology to aryl(perfluoroalkyl)sulfanes and selanes remains an area of unexplored chemical space. Accordingly, to address the “missing links” in the developing series of chalcogen-based substrate reactivity, we report mild syntheses of metastable difluoro(aryl)(perfluoroalkyl)-λ⁴-sulfanes and selanes. As only limited examples of these species exist in the current literature (accessible only by using F₂ or XeF₂/HF), we have carried out detailed structural analyses, primarily using NMR and SC-XRD data. In addition, we investigate the effect of the perfluoroalkyl chain on the outcome of oxidative fluorination, and, finally, we provide preliminary evidence that difluoro(aryl)(trifluoro-methyl)-λ⁴-sulfanes may act as fluorinating reagents.

Full text of DOI:10.1002/anie.201910594

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Difluoro(aryl)(perfluoroalkyl)-λ4-sulfanes and Selanes: Missing
Links of Trichloroisocyanuric Acid/Potassium Fluoride Chemistry
Authors: Antonio Togni, Fabian Brüning, Cody Ross Pitts, Jorna Kalim,
Dustin Bornemann, Clément Ghiazza, Jean de Montmollin,
Nils Trapp, and Thierry Billard
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201910594
Angew. Chem. 10.1002/ange.201910594
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10.1002/anie.201910594
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l4
Difluoro(aryl)(perfluoroalkyl)- -sulfanes and Selanes: Missing
Links of Trichloroisocyanuric Acid/Potassium Fluoride Chemistry
Fabian Brüning,† Cody Ross Pitts,† Jorna Kalim, Dustin Bornemann, Clément Ghiazza,‡ Jean de
Montmollin, Nils Trapp, Thierry Billard,‡* and Antonio Togni*
Abstract: The TCICA/KF approach to oxidative fluorination of
heteroatoms has emerged as a surprisingly simple, safe, and versatile
surrogate to classically challenging fluorination reactions. Although
polyfluorination (or chlorofluorination) of diaryl disulfides, diaryl
the like may find interesting applications in medicinal chemistry,
agrochemistry, materials, or reagent design.[4,5]
Following the chalcogen series, the reactivity of diaryl
disulfides,[1] diaryl diselenides,[1] and diaryl ditellurides[2] under
TCICA/KF conditions has been studied in our laboratory, as well
as the behavior of aryl(trifluoromethyl)tellanes (Figure 1).[2]
Conversely, the reactivity of aryl(trifluoromethyl)sulfanes and
selanes under similar conditions has yet to be explored. Herein,
we now report an application of the TCICA/KF approach to the
synthesis and study of difluoro(aryl)(trifluoromethyl)-l4-sulfanes
(aryl-SF2CF3 compounds) and difluoro(aryl)(trifluoromethyl)-l4-
selanes (aryl-SeF2CF3 compounds) – two virtually unexplored
fluorinated species. Only limited examples of each have been
synthesized by Yagupol'skii and Savina using XeF2/HF in 1979,[6]
and one example of an aryl-SF2CF3 compound has been
synthesized by Umemoto and Ishihara (though only as an
intermediate) using F2 gas in 1993.[7] Accordingly, we utilize this
newfound accessibility via TCICA/KF chemistry as an opportunity
to study the structure and properties of these compounds in detail.
diselenides,
diaryl
ditellurides,
aryl
iodides,
and
aryl(perfluoroalkyl)tellanes has been described, the application of this
TCICA/KF methodology to aryl(perfluoroalkyl)sulfanes and selanes
remains an area of unexplored chemical space. Accordingly, to
address the "missing links" in the developing series of chalcogen-
based substrate reactivity, we report mild syntheses of meta-stable
difluoro(aryl)(perfluoroalkyl)-l4-sulfanes and selanes. As only limited
examples of these species exist in the current literature (accessible
only by using F2 or XeF2/HF), we have carried out detailed structural
analyses, primarily using NMR and SC-XRD data. In addition, we
investigate the effect of the perfluoroalkyl chain on the outcome of
oxidative fluorination, and, finally, we provide preliminary evidence
that difluoro(aryl)(trifluoro-methyl)-l4-sulfanes may act as fluorinating
reagents.
The trichloroisocyanuric acid/potassium fluoride (TCICA/KF)
approach to oxidative fluorination has opened up new frontiers in
the synthesis and study of highly fluorinated substituents.
Recently, TCICA/KF conditions have 1) obviated the reliance on
corrosive Cl2 gas in the synthesis of aryl-SF4Cl and aryl-SF3
compounds,[1] 2) replaced XeF2 in the synthesis of aryl-SeF3 and
aryl-TeF5 compounds,[1,2] and 3) circumvented extremely
hazardous reagents such as F2, HF, and SF4 in the synthesis of
aryl-IF2 and aryl-IF4 compounds,[3] thus demonstrating a powerful
ability to make fluorination chemistry more accessible to the
broader chemical community. Moreover, this approach has
created opportunities to synthesize/study previously unknown
fluorinated moieties, including the TeF4CF3 group.[3] Beyond
academic interest, unknown/underexplored fluorinated groups of
the developing TCICA/KF oxidative fluorination reactivity series
diaryl dichalcogenide series
(aryl)(perfluoroalkyl)chalcogen series
Ar-SF4Cl
or
Ar-SF3
Ar2S2
Ar-SRf
unexplored
space
Ar2Se2
Ar-SeF3
Ar-TeF5
Ar-SeRf
Ar2Te2
Ar-TeRf
Ar-TeF4Rf
aryl iodide reactivity
Ar-IF2
ArI
Ar-IF4
Figure 1. Identifying a gap in our understanding of the reactivity
of substrates in the (aryl)(perfluoroalkyl)chalcogen series under
TCICA/KF conditions; reactivity of diaryl dichalcogenides and aryl
iodides has been explored previously.
[*]
F. Brüning,† Dr. C. R. Pitts,† J. Kalim, D. Bornemann, J. de
Montmillon, Dr. N. Trapp, and Prof. Dr. A. Togni*
Department of Chemistry and Applied Biosciences
ETH Zürich
Adapted from the conditions used for oxidative fluorination of
diaryl
disulfides,[1]
we
began
screening
with
Vladimir-Prelog-Weg 2, 8093 Zürich (Switzerland)
E-mail: atogni@ethz.ch
phenyl(trifluoromethyl)sulfane using 9.0 equiv. TCICA, 16 equiv.
KF, and 10 mol% TFA in MeCN at room temperature overnight.
Under these conditions, we found that the substrate is converted
to difluoro(phenyl)(trifluoromethyl)-l4-sulfane (1) in 81% yield by
19F NMR analysis. Further attempts to decrease the amounts of
TCICA or KF at room temperature resulted in consistently lower
yields; however, the amounts could be decreased to 4.0 equiv.
TCICA and 8.0 equiv. KF by heating the reaction mixture to 40 °C
(i.e., 1 was obtained in ~80% yield by 19F NMR). Additionally, we
found that the reaction proceeds poorly (or not at all) in the
[†]
[‡]
These authors contributed equally.
C. Ghiazza and Prof. Dr. T. Billard
Institute of Chemistry and Biochemistry
Université de Lyon
Université Lyon 1, CNRS
43 Bd du 11 Novembre 1918, F-69622 Villeurbanne (France)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201910594
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COMMUNICATION
absence of TFA, using increased amounts of TFA, or when
replacing it with certain Lewis acid additives. Moreover, it is
important to note that tetrafluoro(aryl)(trifluoromethyl)-l6-sulfanes
was not observed during the screening process.[8-11] See the
Supporting Information for additional details regarding reaction
screening.
of even mild electron-donating groups, as background ring and/or
benzylic chlorination often becomes competitive.[12] For instance,
previously, we observed unselective ring chlorination on biphenyl-
based substrates.[2] Yet, if the biphenyl moiety sports an electron-
withdrawing group, no ring chlorination is observed (17).
Although aryl(difluoromethyl)sulfane substrates are less
accessible, we were curious about how their reactivity compares
to aryl(trifluoromethyl)sulfanes. Fortuitously, (difluoromethyl)-
difluoro(phenyl)-l4-sulfane 18 was formed from its commercially
available starting material in 96% yield. Whereas 1 is identified in
the 19F NMR spectrum by diagnostic signals and F-F coupling
Table 1. Substrate scope of aryl(trifluoromethyl)sulfanes and
aryl(difluoromethyl)sulfanes.
O
Cl
O
Cl
O
N
N
3
constants at -14.38 ppm (2F, quartet, JF-F = 18 Hz) and -62.79
ppm (3F, triplet, 3JF-F = 18 Hz), 18 exhibits additional J-couplings
to the hydrogen atom and upfield shifts of both signals to -25.14
ppm (2F, td, 3JF-F = 12 Hz, 3JF-H = 4 Hz) and -105.84 ppm (2F, dt,
1JF-H = 55 Hz, 3JF-F = 12 Hz). To the best of our knowledge, this
species has not been reported previously.
N
S
SF2Rf
(TCICA)
Cl
Rf
X
X
KF, cat. TFA
MeCN, 18 h
SF2CF3
SF2CF3
75%a
SF2CF3
82%a
81%a
Once the difluoromethyl group on the sulfur atom is replaced
with a monofluoromethyl group, divergent reactivity occurs
(Scheme 1). After subjecting fluoromethyl(phenyl)sulfane to
TCICA/KF conditions, a doublet at -3.64 ppm and triplet at -39.16
ppm are observed in the 19F NMR spectrum, each with 3JF-F = 22.0
F
Cl
Br
1
2
5
3
6
SF2CF3
77%a
F
SF2CF3
90%b
SF2CF3
80%b
Br
4
7
Hz (confirmed in the 19F{1H} spectrum).
These signals
SF2CF3
72%b
SF2CF3 EtO2C
SF2CF3
61%b
68%b
correspond to formation of an SF2CFCl2 group (19), indicating that
a,a-dichlorination of this substrate occurs readily. Taking it one
step further, we discovered that the reaction employing
thioanisole is notably exothermic, and the major product contains
an SF2CCl3 group (20) with a singlet at +10.14 ppm in the 19F
NMR spectrum (the SF2CH3 derivative is not formed). Such
a-chlorination chemistry on thioanisole has been described using
reagents such as Cl2 and N-chlorosuccinimide and may be
expected for TCICA;[13,14] however, note that neither di- nor tri-
chlorination stifles difluorination of the sulfur atom under our
conditions. Additionally, some minor products indicate S–C(sp3)
bond cleavage occurs, including phenyl-SF3, phenyl-SOF3,
phenyl-SF4Cl, and C2Cl6 (when employing thioanisole). No
evidence of S–C(sp3) bond cleavage was observed for 1 or 18.
Me
Ph
8
9
O
O
SF2CF3
84%a
SF2CF3
SF2CF3
87%b
67%b
AcO
F
BzO
MeO2C
10
11
12
SF2CF3
O
SF2CF3
SF2CF3
30%b
N
68%b
72%b
F
PhthN
O2N
O
13
14
17
15
18
F
F
SF2CF3
SF2CF3
SF2CF2H
76%a
85%a
96%a
CO2Me
F
16
19F NMR yields reported. Yields in parentheses based on conversion. All reactions
carried out using 9.0 equiv. TCICA, 16 equiv. KF, and 10 mol% TFA. aReaction was
carried out at rt. bReaction was carried out at 40 oC.
SF2CF3
1
SF2CFCl2
19
R = CF3
R = CH2F
Subsequently, we examined the scope of the reaction on a
+ S-C(sp3) cleavage
S
R
variety of aryl(trifluoromethyl)sulfanes (Table 1). For one, the
corresponding difluorinated products containing halogens in the
para-position (2-4) were obtained in 75-82% yields by 19F NMR.
Yet, the first attempts at synthesizing meta-fluoro- and meta-
bromo-derivatives 5 and 6 resulted in yields below 40%, with the
majority of the material balance being unreacted starting material.
It is possible that the stronger inductive effect of a halogen in the
meta-position slows the rate of oxidation of the sulfur atom. We
later found that better yields can be obtained overnight by heating
to 40 °C. A similar tactic was used to obtain favorable yields of
meta- or para-substituted compounds decorated with ketones (7-
8), esters (9-12), amides (13-14), and a nitro group (15). However,
substrates containing a nitro substituent were particularly finicky,
resulting in low yields and/or reproducibility issues.
SF2CF2H
18
SF2CCl3
R = CF2H
R = CH3
20
oxidative
fluorination
competitive
α-chlorination
+ S-C(sp3) cleavage
vs.
Scheme 1. Divergent reactivity of sulfane substrates bearing CH3
vs. CH2F vs. CF2H vs. CF3 groups under TCICA/KF conditions.
One major reactivity question remained: does the selenium
derivative behave more like sulfur or tellurium (i.e. with Se in the
+4 or +6 oxidation state in the final product)? A small number of
aryl(trifluoromethyl)-selanes were synthesized and subjected to
TCICA/KF conditions (Table 2).[15-18] As Yagupol'skii's results with
XeF2/HF suggest,[6] we found that the selanes undergo
difluorination similar to sulfanes. Thus, compounds 21-26 were
formed in good yields. The 19F NMR data of 15, for instance, can
be compared to 25: in 15, signals at -11.89 ppm (2F, q, 3JF-F = 18
Initial attempts at difluorinating substrates garnished with
fluorine, bromine, or nitro substituents in the ortho-position were
unsuccessful, though 16, containing an ortho-methyl ester,
formed in 76% yield. Another limitation of this method is the use
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Hz) and -61.74 ppm (3F, t, 3JF-F = 18 Hz) are observed, and in 25,
the literature to date. Accordingly, after some difficulty, we
obtained single crystals of 8 and 25 for X-ray diffraction, as well
as other derivatives for comparative analyses (Figures 2 and 3).
As anticipated from the 19F NMR data, both 8 and 25 exhibit
distorted seesaw geometries with the chalcogen-bound fluorine
atoms arranged in the axial positions.
the corresponding signals appear upfield at -58.30 ppm (3F, t, 3JF-
3
= 12 Hz) and -73.21 ppm (2F, q, JF-F = 12 Hz). Additionally,
F
from the 77Se satellite signals, 1JSe-F = 420 Hz and 2JSe-F = 52 Hz.
Table 2. Showcasing reactivity of aryl(perfluoroalkyl)selanes.
Table 3. Estimating Hammett parameters of SF2CF3 and
SeF2CF3 groups.
TCICA
KF
cat. TFA
Se
SeF2Rf
Rf
X
X
MeCN, 18 h
p-X
m-X
0
0
0
X
δH
δH
σΙ
σR
σm
σp
SeF2CF3
F
SeF2CF3
93%a
MeO2C
SeF2CF3
-7.92
-4.08
0.66
0.13
0.10
0.73
0.75
0.79
0.80
SF2CF3
86%a
97%
F
21
22
25
23
26
SeF2CF3 -7.40
-4.39
0.70
EtO2C
SeF2CF3
82%
SeF2CF3
SeF2CF2CF3
79%b
p-X
m-X
Negative values of δH
and δH
denote downfield 19F NMR shifts (deshielding) of para-
71%
and meta-substituted fluorobenzene derivatives, respectively, relative to a fluorobenzene
standard in < 0.02 M solutions in CD3CN. The σΙ and σR0 parameters were calculated by
the method of Taft and used to estimate σm and σp0 constants according to Eq. 1-4 in the
O2N
O2N
24
0
19F NMR yields reported. Reactions were carried out using 9.0 equiv. TCICA, 16 equiv.
KF, and 10 mol% TFA at rt. aYield determined based on conversion of material balance
by 19F NMR. bIsolated yield.
SI.
With respect to the sulfur-based compounds in Figure 2, some
features of the molecular structure of aryl-SF2CF3 compound 8
were compared to its aryl-SCF3 starting material 27. Although the
Cipso–S bond length is virtually unaffected between the S(II) and
S(IV) species, the S–CF3 bond of 8 (ca. 1.874 Å) is 5% longer
than that of 27 (ca. 1.785 Å). In addition, the Cipso-S-CF3 bond
angle (qC-S-C) in 8 of ca. 104.5° is 4% greater than that displayed
in the bent structure of 27 (ca. 100.3°). Lastly, there are a few
important features to highlight regarding the sulfur-bound fluorine
atoms of 8: 1) an average S–F bond length of 1.713 Å was
observed, which is significantly longer than, for instance, an S–F
bond on a stable SF5 group on the same benzophenone core (ca.
1.566 Å),[1] 2) the F-S-F bond angle deviates somewhat from
linearity (qF-S-F ≈ 173.5°), and 3) the average Cipso-S-F bond angle
(qC-S-F ≈ 90.1°) is near ideal perpendicularity for seesaw-type
structures.
Next, we compared the reactivity of substrates with CF3
versus CF2CF3 substituents on the selenium atom. Interestingly,
26 formed in 79% yield, which allows for a comparison between
the SeF2CF3 group and a novel SeF2CF2CF3 group. Evidently,
the selenium-bound fluorine atoms have similar 19F NMR shifts
(i.e. -73.21 ppm for 25 and -72.10 ppm for 26) and identical 1JSe-
F-values of 420 Hz. The change in perfluoroalkyl chain length also
has a minimal effect on the 77Se NMR shifts, which were observed
at 1112 ppm for 25 and 1108 ppm for 26.[19]
On another note, two properties that are often of general
interest in polyfluorinated substituents are their lipophilicity and
their electron-withdrawing effect.[20] However, the aryl-SF2CF3
and aryl-SeF2CF3 compounds are unstable in water; they
hydrolyze to their aryl-SOCF3 and aryl-SeOCF3 derivatives.
Rapid decomposition of these compounds in water renders
determining
a
Hansch lipophilicity parameter somewhat
meaningless,[21] and complicates the determination of Hammett
parameters using classical techniques.[22] Alternatively, the
Hammett parameters can be estimated by adapting the 19F NMR
approach developed by Taft.[23,24]
By measuring the chemical shift differences between meta- or
para-substituted fluorobenzenes and a fluorobenzene internal
standard at low concentrations, we determined inductive (sI) and
resonance (sR) parameters, and thus meta- and para-s constants
(sm and sp), as per Eq. 1-4 in the SI. The electron-withdrawing
effect of the SF2CF3 group, with sm ≈ 0.73 and sp ≈ 0.79, is on the
order of that of a nitro group (Table 3).[25] These values also can
be benchmarked against values for the SCF3 group (sm ≈ 0.40
27
8
Figure 2. Molecular structures of 27 (left) and 8 (right), for
comparison of the SCF3 and SF2CF3 groups on the same scaffold,
determined by single-crystal X-ray diffraction (displacement
ellipsoids depicted at 50% probability level).
and sp ≈ 0.50)[26] and the SO2CF3 group (sm ≈ 0.83 and sp
≈
The selenium-based structures in Figure 3 also offer an
opportunity to make additional comparisons. For one, the aryl-
SeCF3 precursor (28) to aryl-SeF2CF3 compound 25 has, on
average, a slightly shorter Cipso–Se bond length (ca. 1.924 Å vs.
1.943 Å), unlike what we observed when comparing sulfur-based
structures 8 and 27. However, similar to the comparison between
8 and 27, the Se–CF3 bond of 25 (ca. 2.009 Å) is 3% longer than
that of 28 (ca. 1.953 Å). Additionally, the Cipso-Se-CF3 bond angle
of 25 (qC-Se-C ≈ 97.5°) is greater than that of aryl-SeCF3 compound
0.96).[22] For the SeF2CF3 group, we determined similar values of
sm ≈ 0.75 and sp ≈ 0.80, which likewise sit between those for
SeCF3 group (sm ≈ 0.44 and sp ≈ 0.45)[27] and the SeO2CF3 group
(sm ≈ 1.08 and sp ≈ 1.21).[28] Expectedly, the inductive influence
of SeF2CF3 is slightly greater than that of SF2CF3, while the
opposite is true for the resonance contributions.
To the best of our knowledge, solid-state structures of neither
aryl-SF2CF3 nor aryl-SeF2CF3 compounds have been reported in
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10.1002/anie.201910594
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28 (qC-Se-C ≈ 94.7°). Here, note that both Cipso-Se-CF3 angles are
significantly smaller than for the sulfur-based structures, due to a
larger influence of the selenium lone pairs. Furthermore, the
average Se–F bond lengths of 1.857 Å in 25 are unsurprisingly
longer than the S–F bonds in 8, and its average qF-Se-F of 169.2°
deviates further from linearity than the aforementioned qF-S-F in 8.
Yet, the average Cipso-Se-F bond angle (qC-Se-F ≈ 89.7°) is similarly
near ideal perpendicularity.
to be seen whether aryl-SF2CF3 compounds will carry any
advantages over aryl-SF3 compounds as fluorinating reagents at
all; however, we hope this initial result will encourage further
investigations in due course.
preliminary evidence for aryl-SF2CF3 compounds as reactive species
SF2CF3
4
Br
For another vantage point, we also obtained an X-ray crystal
structure of aryl-SeF2CF2CF3 compound 26 (Figure 3). For the
OH
F
83%
EtOAc, overnight
F
F
29
30
most
part,
25
and
26
display
similar
features.
However, the average Se–CF2CF3 bond length (ca. 2.034 Å) is
slightly longer than the Se–CF3 bond, the average Cipso-Se-
CF2CF3 bond angle (ca. 95.8°) is smaller than the Cipso-Se-CF3
angle, and the F-Se-F bond angle of 26 (qF-Se-F ≈ 172.2°) is closer
Scheme 2. Initial result suggesting behavior of aryl-SF2CF3
compounds as potential fluorinating reagents.
to linearity than the F-Se-F angle of 25.
comparisons of all SC-XRD data can be found in the Supporting
Information.
More detailed
In brief, by applying our recently developed TCICA/KF
oxidative fluorination strategy to aryl-SCF3 and aryl-SeCF3
substrates, we unveiled an easy synthetic route to relatively
unexplored aryl-SF2CF3 and aryl-SeF2CF3 compounds, among
other derivatives. Straightforward access to these polyfluorinated
compounds has also allowed for their detailed characterization in
1
both solution (via 19F, H, 13C, and 77Se NMR) and in the solid
state (via SC-XRD).30 Additionally, we have been able to estimate
Hammett parameters for the SF2CF3 and SeF2CF3 groups, and
we have preliminary evidence that aryl-SF2CF3 compounds can
28
mediate deoxyfluorination chemistry.
Given the inherent
hydrolytic instability of aryl-SF2CF3 and aryl-SeF2CF3 compounds
on direct contact with water, the utility of these groups (beyond
fundamental academic interest) may lie more so in the realm of
reagent design.
26
25
Figure 3. Molecular structures of 28 (top), 25 (bottom left), and
26 (bottom right), for comparison of the SeCF3, SeF2CF3 and
SeF2CF2CF3 groups on the same scaffold, determined by single-
crystal X-ray diffraction (displacement ellipsoids depicted at 50%
probability level).
Acknowledgements
We thank the ETH transfer office for support in filing a patent
application on this work, in which C.R.P. and A.T. are listed as
inventors. MoBiAS (ETH) is acknowledged for assistance with
HRMS analyses. C.G. acknowledges a doctoral fellowship from
the Région Auvergne-Rhône-Alpes. Financial support was
provided by ETH Zürich and the ETH Postdoctoral Fellowship
Program (C.R.P.).
Finally, we present very preliminary evidence that these
classes of compounds have potential applications as fluorinating
reagents. For one, analogies can be drawn between aryl-SF2CF3
compounds and aryl-SF3 compounds (e.g. Fluolead[29]), which are
known nucleophilic fluorinating reagents.[30-32]
Although a
complete study of the reactivity of the SF2CF3 and SeF2CF3
groups is beyond the scope of this work, we briefly studied the
reactivity of 4 with 4-fluorobenzyl alcohol (29) as a simple test
substrate. Note that 4 was chosen for this study as it is derived
from a fairly inexpensive starting material and proved easily
isolable. Thus, we synthesized and isolated 4 on a gram scale in
53% yield via extraction of the crude reaction mixture with
Conflict of Interest
The authors declare no conflict of interest.
Keywords: heteroatoms • oxidative fluorination • sulfanes •
selanes • trichloroisocyanuric acid
n-hexane (without column chromatography).
Quickly, we
discovered that 4 is capable of deoxyfluorination of 29, providing
4-fluorobenzyl fluoride (30) in 83% yield (Scheme 2). Initial
results suggest that the reaction is sensitive to solvent (e.g.
favorable results were only obtained using EtOAc or CHCl3) and
that there may be an induction period prior to deoxyfluorination.
Future work will focus on understanding/exploring the reactivity of
these compounds, as well as developing a full scope. It remains
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10.1002/anie.201910594
Angewandte Chemie International Edition
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Fabian Brüning,† Cody Ross Pitts,†
Jorna Kalim, Dustin Bornemann,
Clément Ghiazza,‡ Jean de Montmollin,
Nils Trapp, Thierry Billard,‡* and
Antonio Togni*
mild access to underexplored “SF2CF3” and “SeF2CF3” groups
using a TCICA/KF approach
Ar2S2 or
Ar2Se2
known
known
?
Ar-SF4Cl, Ar-SF3,
or Ar-SeF3
O
Cl
O
Cl
O
N
N
Ar2Te2
Ar-TeF5
Page No. – Page No.
N
Ar-SRf or
Ar-SeRf
Ar-SF2Rf or
Ar-SeF2Rf
Cl
Difluoro(aryl)(perfluoroalkyl)-l4
-
acid cat.
KF
known
Ar-TeRf
Ar-TeF4CF3
sulfanes and Selanes: Missing Links
of Trichloroisocyanuric
addressing “missing links” in the chalcogen-based reactivity series
Acid/Potassium Fluoride Chemistry
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Title
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This article is protected by copyright. All rights reserved.