The Journal of Organic Chemistry
Note
additive amount of HFIP can activate the benzylic fluorine
dithiolane. The difluorinated product was obtained in 55%
yield (Scheme 1).
23−26
group via hydrogen bonding.
We attributed this to the
hydrogen bonding interaction between the fluoride ion of CsF
with HFIP, which decreased the interaction of HFIP with the
benzylic fluoride.
1
,3-dithiolane
fluorinated product was also investigated (Table S2). KF was
applicable in the reaction instead of CsF, which is desirable
from an economic stand point (entry 2). Changing the charge
to 2.0 F/mol slightly decreased the yield to 83% (entry 3). A
lower concentration of CsF also reduced the product yield to
5
5% (Entry 4). Interestingly, the neat HFIP solution did not
give the fluorinated product (entry 5). In this case, we
observed the predominant formation of an ether product by
gas chromatography−mass spectrometry (GC−MS), formed
by nucleophilic attack of the alkoxide of HFIP. Although HFIP
is an inherently weak nucleophile, the interaction with Cs ions
may have increased the dissociation of the OH bonds, resulting
in the generation of the alkoxide. The use of TFE instead of
HFIP gave 65% yield of the product (entry 6). The reactions
without molecular sieves 4A or under air resulted in lower
yields, indicating that the reaction is moisture sensitive (entries
In conclusion, we have reported fundamental properties of
metal fluorides in fluorinated alcohols and demonstrated their
application to electrochemical fluorination. We believe that
this research will provide a new choice of reaction media for
the synthesis of fluorinated compounds.
EXPERIMENTAL SECTION
■
General Considerations. Reagents and dehydrated solvents were
obtained from commercial sources and used without further
purification unless otherwise noted. CsF and KF were dried by
7
and 8). The use of GC as the anode instead of Pt
significantly decreased the yield in this reaction, which is in
agreement with the potential window analysis (entry 9). Lastly,
a much smaller amount of HFIP, namely, 10 mL of MeCN
with 600 μL of HFIP, was found to dissolve 0.3 M CsF and
gave the desired product in good yield (entry 10).
With the optimized conditions in hand, we next investigated
the scope of this reaction. This method was found to fluorinate
various benzylic C−H bonds and C−H bonds adjacent to
1
19
heating under a vacuum overnight prior to use. H and F NMR
1
spectra were recorded on a Bruker biospin AVANCE III 400A ( H,
19
4
00.13 MHz; F, 376.31 MHz) spectrometer using CDCl3 or
CD CN as a solvent. Monofluorobenzene was used as an internal
3
1
9
1
standard for F NMR measurements. The chemical shifts for H and
1
9
F NMR spectra are given in δ (ppm) relative to internal TMS and
monofluorobenzene, respectively. Multiplicities are abbreviated as
singlet (s), doublet (d), triplet (t), quartet (q), sextet (sext), septet
(
sept), multiplet (m), and broad (br). The single-crystal X-ray
analyses were carried out on a Rigaku XtaLAB Synergy-DW (with)
hybrid photon counting (HPC) detector (Cu Kα radiation, λ =
1
.54184 Å). An empirical absorption correction was carried out by the
MULTI-SCAN method. The structures were solved by the SHELXT
27
(SHELX2014) using OLEX2 or Yadokari-XG softwares. The non-
hydrogen atoms were refined anisotropically. Hydrogen atoms were
refined using the riding model. Conductivity measurements were
performed on a portable LAQUAact D-74 (HORIBA) equipped with
−
1
a 3552−10D probe (cell constant: 1.026 cm ). Viscosity measure-
ments were performed on a VM-10A (SEKONIC). Linear sweep
voltammetry (LSV) measurements were performed using an ALS
6
005C electrochemical analyzer. All CV measurements were carried
out in the three-electrode system equipped with a glassy carbon (GC)
disk (φ = 3 mm) or a platinum disk (φ = 3 mm) working electrode, a
Pt plate counter electrode (10 mm × 10 mm), and a saturated
calomel electrode (SCE) as a reference electrode at a scan rate of 100
−
1
mV s . Electrochemical fluorination was performed using an HABF-
5
01A (Hokutodenko). Gas chromatography−mass spectrometry was
performed on a Shimadzu GSMS-QP2020 NX.
Single-Crystal X-ray Diffraction. Preparation of Single
Crystals. Single crystals of CsF/(HFIP) , CsF/(TFE) , and TBAF/
3
2
(TFE)4 were obtained from the oversaturated solutions of the
corresponding fluorinated alcohol. For the CsF-based crystals, oven-
dried CsF was added into fluorinated alcohols at room temperature to
give saturated solutions (ca. 2 M for HFIP, and ca. 3 M for TFE). The
solution was heated to boiling under stirring conditions, and then CsF
was added to reach oversaturation. The solutions were cooled to
room temperature, where the formation of crystals was observed. The
solutions were stored in a freezer to facilitate crystallization. Single
Figure 4. Electrochemical fluorination reactions using 0.3 M CsF in
MeCN+HFIP (8:2 in vol %) solution as an electrolyte.
to be formed more efficiently at a current density of 10 mA/
2
2
cm instead of 5 mA/cm . We attributed this to the
aforementioned concomitant decomposition of benzylic
fluorides by HFIP. In other words, the higher current density
shortened the reaction time to increase the yield of the
fluorinated products. The electrochemical fluorination of the
C−S bond was also demonstrated with 2,2-diphenyl-1,3-
crystals of TBAF/(TFE) were obtained by the similar procedure
4
described above using TBAF/3H O salt as a starting material instead
2
of CsF.
1
CsF/(HFIP) . H NMR (400.13 MHz, CD CN, ppm): δ 7.51 (br),
4.59 (sep, J
ppm): δ −74.89 (d, J
3
3
3
19
= 6.6 Hz, 1H). F NMR (376.31 MHz, CD CN,
H−F
3
3
= 6.6 Hz), 143.17 (s).
H−F
D
J. Org. Chem. XXXX, XXX, XXX−XXX