Deoxygenative Fluorination of Phosphine Oxides: A General Route to Fluorinated Organophosphorus(V) Compounds and Beyond

Article abstract of DOI:10.1002/anie.202010943

Fluorinated organophosphorus(V) compounds are a very versatile class of compounds, but the synthetic methods available to make them bear the disadvantages of 1) occasional handling of toxic or pyrophoric P^III starting materials and 2) a dependence on hazardous fluorinating reagents such as XeF₂. Herein, we present a simple solution and introduce a deoxygenative fluorination (DOF) approach that utilizes easy-to-handle phosphine oxides as starting materials and effectively replaces harsh fluorinating reagents by a combination of oxalyl chloride and potassium fluoride. The reaction has proven to be general, as R₃PF₂, R₂PF₃, and RPF₄ compounds (as well as various cations and anions derived from these) are accessible in good yields and on up to a multi-gram scale. DFT calculations were used to bolster our observations. Notably, the discovery of this new method led to a convenient synthesis of 1) new difluorophosphonium ions, 2) hexafluorophosphate salts, and 3) fluorinated antimony- and arsenic- compounds.

Full text of DOI:10.1002/anie.202010943

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Deoxygenative Fluorination of Phosphine Oxides: A General
Route to Fluorinated Organophosphorus(V) Compounds and
Beyond
Authors: Antonio Togni, Dustin Bornemann, Fabian Brüning, Lionel
Wettstein, Sebastian Küng, Hansjörg Grützmacher, Cody
Ross Pitts, Liangyu Guan, and Nils Trapp
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202010943
Link to VoR: https://doi.org/10.1002/anie.202010943

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
Deoxygenative Fluorination of Phosphine Oxides: A General Route
to Fluorinated Organophosphorus(V) Compounds and Beyond
Dustin Bornemann, Cody Ross Pitts,‡ Lionel Wettstein, Fabian Brüning, Sebastian Küng, Liangyu Guan,‡
Nils Trapp, Hansjörg Grützmacher,* and Antonio Togni*
XeF2 (although other equally, if not more, hazardous fluorinating
reagents have been employed).[1,10–12]
Dedicated to Professor Herbert Roesky
Abstract: Fluorinated organophosphorus(V) compounds are a
very versatile class of compounds, but the synthetic methods
available to make them bear the disadvantages of 1) occasional
handling of toxic or pyrophoric P(III) starting materials and 2) a
dependence on hazardous fluorinating reagents such as XeF2.
opening the doors to fluorinated organophosphorus(V) compounds
challenge: P(III) substrates often pyrophoric, or made from pyrophoric materials
solution: application of user-friendly P(V) substrates (phosphine oxides)
oxidative
fluorination
cationic species
Herein, we present
a
simple solution and introduce
a
RPX2 or R2PX or R3P
P(III) starting materials
deoxygenative fluorination (DOF) approach that utilizes easy-to-
handle phosphine oxides as starting materials and effectively
replaces harsh fluorinating reagents by a combination of oxalyl
chloride and potassium fluoride. The reaction has proven to be
general, as R3PF2, R2PF3, and RPF4 compounds (as well as
various cations and anions derived from these) are accessible in
good yields and on up to a multi-gram scale. DFT calculations
were used to bolster our observations. Notably, the discovery of
this new method led to a convenient synthesis of 1) new
difluorophosphonium ions, 2) hexafluorophosphate salts, and 3)
fluorinated antimony- and arsenic- compounds.
- F
RPF4 or R2PF3 or R3PF2
deoxygenative
fluorination
+ F
RP(O)X2 or R2P(O)X or R3P(O)
P(V) starting materials
anionic species
challenge: oxidative fluorination requires harsh reagents (e.g. XeF2, F2, etc.)
solution: deoxygenative fluorination now accomplished with (COCl)2 and KF
Scheme 1.
The current two-fold accessibility problem
surrounding fluorinated organophosphorus(V) compounds and
one general solution using the oxalyl chloride/KF approach.
Either in neutral, anionic, or cationic forms, fluorinated
organophosphorus(V)
compounds
have
demonstrated
Herein, we present a simple solution to these challenges in
the form of a mild deoxygenative fluorination (DOF) strategy (see
Scheme 1) using oxalyl chloride and potassium fluoride that
employs phosphine oxides as starting materials. Phosphine
oxides are usually bench-stable, easy to handle, and storable for
longer times compared to their phosphorus(III) congeners. Harsh
fluorination reagents such as XeF2, HF, SbF5, and SF4 are
replaced by an innocuous fluoride salt (KF) and oxalyl chloride (a
cheap and commercially available reagent due to its applications,
e.g., in acid chloride synthesis and Swern oxidation). This new
method allows to perform the reactions safely on up to a multi-
gram scale. Moreover, purification is often achieved through a
straightforward filtration/evaporation procedure.
This oxalyl chloride/KF protocol proved to be general enough
to afford alkyl-, aryl-, and heteroaryl-substituted phosphoranes
with varying degrees of fluorination (anywhere from 1 to 6 P-F
bonds), depending on the starting material employed.
Additionally, we note the ability to access assorted neutral,
anionic, and cationic P-F species either directly under our reaction
conditions, by highlighting applications of established chemistry
on new compounds, or by using workup alterations developed
over the course of this study. As our reaction conditions have also
expanded the scope of accessible products, this has presented
additional opportunities to study new P-F species both through
SC-XRD and DFT calculations and inspired the investigation of
this deoxygenative fluorination strategy on molecules containing
group 15 elements beyond phosphorus. Lastly, this study
remarkable applications in organocatalysis (e.g. in C-F bond
functionalization,[1–3] carbonyl activation,[2,4] hydrosilylation,[2,5]
CO2 sequestration[3] and olefin hydrogenation[6]), as Lewis acids,
in 18F-radiolabeling,[7] as ionic liquids,[8] as well as electrolytes,[9]
and may conceivably have untapped potential in other arenas.
Yet, despite these known and prospective applications of
fluorinated organophosphorus(V) compounds, there is a lack of
synthetic methods available to access them in juxtaposition with
other compound classes containing fluorinated heteroatoms.
Generally, it may be stated that research in fluorine chemistry is
notoriously dependent on reagents that are difficult to handle and
frequently hazardous reaction conditions must be applied.
An assessment of the state of the art indicates there are two
main challenges presented in modern synthesis of fluorinated
organophosphorus(V)
friendliness/scalability of the fluorination reaction itself and 2) the
prerequisite of handling hazardous starting materials. For
instance, the majority of compounds are synthesized via
fluorination of substituted phosphines, many of which are either
pyrophoric, prepared from pyrophoric materials, or otherwise toxic,
and this is accomplished most commonly on a small scale with
compounds:
1)
the
user-
[*]
D. Bornemann, C. R. Pitts, L. Wettstein, F. Brüning, Sebastian
Küng, L. Guan, N. Trapp, H. Grützmacher, A. Togni
Department of Chemistry and Applied Biosciences
ETH Zürich
Vladimir-Prelog-Weg 2, 8093 Zürich (Switzerland)
E-mail: hgruetzmacher@ethz.ch
atogni@ethz.ch
C. R. Pitts (current address), L. Guan
The Scripps Research Institute
[‡]
10550 N. Torrey Pines Rd., La Jolla, CA (USA)
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
F
F
F
F
P
F
F
P
F
F
P
F
3 eq. (COCl)2
excess KF
F
P
F
O
82%
(>99%)
76%
(88%)
71%
(81%)
F
R
R
R
P
F
R
R
R
67%
>4 g scale
MeCN, rt, 16 h
F
1
2
3
Cl
Me
CF3
Me
F
P
F
F
P
F
F
P
F
F
P
F
77%
(82%)
68%
(75%)
77%
(79%)
58%
(70%)
Cl
Me
F3C
Me
Me
Cl
Me
CF3
4
5
6
7
OMe
F
P
F
O
F
P
F
F
P
F
F
P
F
97%
(>99%)
O
77%
(80%)
70%
(77%)
79%
(>99%)
n-octyl
MeO
N
O
OMe
8
9
10
11
Ph
Me
F2P Ph
PF2Xyl2
PF2Ph2
6-9 eq. (COCl)2
excess KF
Ph
O
O
P
PF2Ph2
PF2Ph2
80%
(88%)
72%
(79%)
PF2
Me
P
PF2 F2P
R
R
R
R
R
R
R
Fe
MeCN, rt, 16 h
R
Ph
48%
(70%)
PF2 Ph
Ph
12
13
14
NMe2
OMe
3 eq. (COCl)2
excess KF
F
O
F
P
F
F
F
P
F
F
R
R
n-octyl
F
P
F
76%
(86%)
73%
(80%)
75%
(79%)
60%
(77%)
P
H
F
F
P
F
F
F
P
R
R
MeCN, rt, 16 h
n-octyl
F
NMe2
OMe
15
16
17
18
standard
conditions
F
P
F
F
Ph
CF3
O
R
R
F
F
P
F
F
P
F
P
H
F
P
F
F
R
R
then, TMSCl
70%
90%
83%
F
F
72%
F
F
P
via
F
R2PF4
(isolable)
F
Ph
CF3
19
20
21
22
Figure 1. Substrate scope of R3PF2 and R2PF3 compounds synthesized using oxalyl chloride/KF conditions. Isolated yields are
reported with 19F NMR yields in parentheses.
facilitated the synthesis and characterization of new "R2PF2+"
phosphonium ions.
(COCl)2 and KF that still afford complete conversion of the starting
material. However, the following observations are noteworthy: 1)
other metal fluorides, such as CsF and CaF2 may be employed in
place of KF, 2) thionyl chloride may be a suitable surrogate for
oxalyl chloride, 3) additives such as TFA and ZnCl2, which have
benefitted our TCICA/KF chemistry, only lowered product yields,
4) the reaction can also be performed in acetone, toluene, and
EtOAc, though lower yields were observed in some instances,
and 5) to circumvent etching of glassware by adventitious HF,
polypropylene vessels can be used instead of borosilicate.
Additionally, the reaction performed well on a >4-gram scale,
providing 1 in 67% yield, thus demonstrating a level of scalability.
With optimized conditions in hand, we proceeded to explore
the scope of the reaction with respect to trisubstituted phosphine
oxides (Figure 1). Triarylphosphine oxides adorned with either
electron withdrawing (2-5) or electron donating (6-8) substituents
are well tolerated, and the representative examples indicate that
ortho-, meta-, or para-substituted Ar3PF2 compounds may be
accessed in good yields. However, an interesting departure from
Ar3PF2 compound formation was observed in the presence of an
even more potent electron donating group. That is, under
standard reaction conditions, the p-NMe2-substituted starting
material 23 provided fluorophosphonium compound 24
exclusively in 90% yield (Scheme 2). No Ar3PF2 25 formation was
The initial inspiration for this transformation stems from our
recent work involving oxidative fluorination of heteroatoms (i.e. S,
Se, Te, and I) in organic frameworks using trichloroisocyanuric
acid (TCICA) and KF.[13–16] Although in-depth mechanistic studies
have not yet been conducted, the formation of heteroatom-
chlorine bonds followed by Cl-F exchange processes is
suspected to play an important role in these TCICA/KF-based
reactions. In previous work by Masaki and Fukui,[17] and later
Grimme and coworkers,[18] it was established that P-Cl bonds can
be constructed concomitant with deoxygenation by exposing
phosphine oxides to oxalyl chloride. Thus, it seemed logical to
explore whether P-F bonds could be forged in a similar fashion in
the presence of a fluoride source – either through putative
generation of oxalyl fluoride in situ, Cl-F exchange processes, or
otherwise direct fluorination of phosphorus.
Fortunately, we found that triphenylphosphine oxide
underwent virtually quantitative conversion to difluorotriphenyl-λ5-
phosphorane (1) in the presence of 3 eq. (COCl)2 and 6 eq. KF in
MeCN at rt overnight, as assessed by 19F NMR (Figure 1).
Complete details of the reaction screening and optimization can
be found in the Supporting Information. The chosen optimal
conditions are characterized by the lowest possible amounts of
This article is protected by copyright. All rights reserved.

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
observed – also not at longer reaction times (see SI for details).
Conceivably, this phenomenon is easily rationalized by the
increased ability of the p-NMe2 groups to stabilize the positive
charge on the phosphonium ion. At a glance, it is curious that no
phosphonium ion formation was observed when employing other
strong donating groups, such as p-OMe groups (hypothetically
producing compound 26), but the notable disparity in Hammett
P-F, C-P-C and C-P-F angles only slightly deviating from the ideal
180°, 120°, and 90° angles, respectively (θ(F-P-F) = 176.23(5)°-
179.43(7)°, θ(C-P-C)
= 116.17(7)°-125.05(7)°, θ(C-P-F) =
87.95(6)°-92.03(6)°). The P-F and P-C bond lengths are in good
agreement with previously characterized R3PF2 species (see SI
for details). Notably, all furanyl groups in 10 are disordered
around the P-C bonds indicating no preferential orientation of this
group.
s
para constants (spara(OMe) = -0.27 vs. spara(NMe2) = -0.83) seems
to account for the unique reactivity of compound 23.[19]
A
calculation of the energy of the isodesmic reaction shown in
Scheme 2 is consistent with the experimental observation and
shows that the formation of phosphonium ion 24 is 13.4 kcal/mol
more favorable than 26 (DFT wB97XD/6-311++G**).[20,21]
Beyond substituted benzene derivatives, we also discovered
that heteroaryl-substituted phosphine oxides are suitable
4
10
14
substrates.
Pyridine-substituted compound 9 and furan-
substituted compound 10 were both formed in good yields,
indicating both electron-rich and electron-deficient heteroaromatic
substituents are compatible (Figure 1). (Note that compound 9 is
a precursor to an established phosphonium ion catalyst used for
Figure 2. Molecular structures of 4, 10, and 14, determined by
single-crystal X-ray diffraction methods (displacement ellipsoids
depicted at 50% probability level; hydrogen atoms omitted for
clarity).
Friedel–Crafts
dimerization,
hydrodefluorination,
and
hydrodeoxygenation, among other reactions).[22] Additionally, we
found that alkyl substituents stay intact during deoxygenative
fluorination (compound 11).
Limitations of the substrate scope are as follows: 1) alkenyl
substituents on the central phosphorus atom promoted
undesirable and unselective background reactivity, 2) alkynyl
substituents were tolerated, but complete conversion of the
starting material was often not achieved, and 3) the synthesis of
Stephan's established fluorotris(perfluorophenyl)phosphonium
catalyst was unsuccessful (see SI for details).[1]
Subsequently, we turned our attention to secondary
phosphine oxides to find that either neutral or anionic fluorinated
phosphorus(V) compounds are accessible depending on the
nature of the starting material, using modified conditions (3 eq.
(COCl)2, 8 eq. KF). (Note that the reaction conditions were re-
optimized for this substrate class using diphenylphosphine oxide;
see SI for details.) The following trends were observed:
Substrates with aryl- or alkyl-based electron rich substituents
bound to the phosphorus atom provide R2PF3 compounds directly
(e.g. 15-18; Figure 1). Substrates with electron neutral or
withdrawing substituents bound to phosphorus favor conversion
to K[R2PF4] compounds. The preference for fluorophosphate
formation in the latter case is likely due to the enhanced Lewis
acidity and lower steric encumbrance at the central atom in R2PF3
compared to R3PF2.
NMe2
NMe2
standard
conditions
O
P
F
P
Me2N
Me2N
90%
phosphonium
ion formed
exclusively
NMe2
NMe2
NMe2
23
24
OMe
F
P
F
F
P
ΔE = -13.4 kcal/mol
+
Me2N
MeO
isodesmic
analysis
OMe
NMe2
25
26
OMe
NMe2
F
P
F
F
P
+
MeO
Me2N
OMe
NMe2
8
24
Scheme 2. Direct formation of a fluorophosponium ion under
standard reaction conditions (top). Isodesmic reaction calculated
with DFT (wB97XD/6-311++G**) comparing NMe2 vs. OMe
substituent stabilizing effects (bottom).
fluorophosphates prior to TMSCl treatment
It is also possible to achieve deoxygenative fluorination at
multiple phosphine oxide reaction sites simultaneously in one pot
by scaling the amounts of oxalyl chloride and KF proportionately.
For instance, tetra-fluorinated BINAP-derived compound 12 and
Xyliphos-derived compound 13 were both obtained from
substrates containing two phosphine oxide sites. These products
also demonstrate the tolerance of naphthalene, xylene, and
ferrocene substituents under standard reaction conditions.
Likewise, hexa-fluorinated compound 14 can be formed cleanly
from a substrate containing three phosphine oxide sites.
yet, 1.44:1 cis:trans
F
P
F
F
P
F
ΔG = -3.7 kcal/mol
ratio observed
upon deoxygenative
fluorination of
Ar
F
Ar
F
F
Ar
Ar
F
Ar = p-Ph-Ph
(p-Ph-Ph)2P(O)H
27-cis
27-trans
structure of
27-cis
confirmed
by SC-XRD
F
Ar
F
Ar
F
P
F
27-cis
Scheme 3. Top: Gibbs free energy analysis (DFT wB97XD/6-
311++G**) not in accordance with observed preference for 27-cis.
Bottom: Molecular structure of 27-cis determined by SC-XRD
(displacement ellipsoids depicted at 50% probability level;
hydrogen atoms omitted for clarity).
The structures of compounds 4, 10, and 14 in the solid state
were determined with single-crystal X-ray diffraction methods
(Figure 2). All three species exhibit an almost ideal trigonal
bipyramidal structure around the central phosphorus atom with F-
This article is protected by copyright. All rights reserved.

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
Accordingly, the role of electron donating substituents is to
stabilize the neutral R2PF3 species over the anionic phosphate –
a noteworthy parallel to the aforementioned ability to stabilize the
cationic phosphonium over the neutral R3PF2 species by
leveraging substituent effects.
in a separate step, the TMSCl treatment was applied in order to
obtain PhPF4 (30). Notably, both steps must be carried out under
meticulously dry conditions to avoid irreversible formation of
PhPOF2 by hydrolysis of either 29 or 30. We also found that,
instead of 28, PhPCl2 can be used as a convenient starting
material to afford 29 and 30 (in 82% and 92% yield, respectively)
analogously under standard reaction conditions (see SI for
The K[R2PF4] compounds may be easily isolated. It is worth
mentioning that coordination of the additional fluoride opens up
the possibility of obtaining a mixture of isomers. (The geometry
about the phosphorus atom changes from trigonal bipyramidal to
octahedral.) For instance, bis(biphenyl)phosphine oxide provided
the bis(biphenyl)tetrafluorophosphate isomers 27-cis and 27-
trans in a 1.44:1 cis:trans ratio. While the trans isomer was
calculated to be 3.7 kcal/mol lower in energy than the cis isomer
(DFT wB97XD/6-311++G**), this was not consistent with our
observation (Scheme 3). In this light, it is possible that either the
preference for 27-cis is under kinetic control or the inconsistency
could be attributed to limitations of the computational method.
Additionally, we were able to obtain single crystals suitable
details).
Tetrafluoro(organyl)-λ5-phosphoranes are generally
more difficult to access than many of the fluorinated
organophosphorus(V) compounds mentioned in Figure 1, with
syntheses relying exclusively on hazardous reagents such as
AsF3, SbF3, SF5Cl, and PF5, among others.[10,12,24,25]
This result stimulated a brief investigation of the lability of a
number of P-X bonds under deoxygenative fluorination conditions,
where, for instance, X = H, OR, NR2, or SR (Figure 3).
Interestingly, this study showed that P-OR bonds are converted
to P-F bonds only under certain conditions in combination with
hydride or amino substituents at the phosphorus center. For
example, the P-OR bonds stay intact when the phosphorus-
bound hydrogen substituent of 28 is replaced with another alkoxy
substituent as in 31 and, furthermore, the deoxygenative
fluorination reaction shuts down entirely. A similar trend was
noted for diphenylphosphine oxide derivatives: When X = H as in
35, the reaction proceeds to form K[Ph2PF4] (34), though when X
= OR as in 32, no reaction occurs. However, when X = N of an
amino substituent like in morpholinyl and present in 33, K[Ph2PF4]
formation occurs in high yield. The behavior of P-S and P=S
bonds under fluorination conditions was also studied using
Lawesson's reagent 36; we found that all phosphorus-sulfur
bonds are readily cleaved to provide 37.
for
an
X-ray
diffraction
study
of
cis-di(biphenyl)tetrafluorophosphate 27-cis (Scheme 3). The
molecular structure exhibits the expected octahedral coordination
sphere around the central phosphorus atom, with almost ideal
bond angles (see SI for details). To the best of our knowledge,
this is the only (diaryl)tetrafluorophosphate solid-state structure
reported to date.
Although fluorophosphate(V) compounds may be of interest
in their own right, we sought to address the limitation of accessing
R2PF3 compounds with electron neutral or withdrawing R groups.
Taking inspiration from the fluoride abstraction capabilities of silyl
cations, we found that K[R2PF4] compounds can be converted to
their R2PF3 congeners by addition of TMSCl during the workup.[23]
This TMSCl treatment is a simple and elegant solution, as 1) the
resultant KCl precipitates out of solution rapidly and can be filtered
off, 2) both TMSF and remaining TMSCl are volatile and can be
removed in vacuo, and 3) TMSCl will not remove an additional
fluoride from R2PF3 compounds, providing the neutral species
exclusively. Using this approach, the previously inaccessible
"electron-deficient" R2PF3 compounds in the presence of KF were
isolated in good yields (e.g. 19-22; Table 1).
effect of substituents on phosphorus
X = OEt (31)
no reaction
O
P
OEt
X
Ph
X = H (28)
K[PhPF5]
82%
90%
29
X = OEt (32)
X = morpholinyl (33)
X = H (35)
no reaction
O
K[Ph2PF4]
P
Ph
X
Ph
Ar
34
user-friendly route to aryl-PF4 compounds
K[Ph2PF4]
(COCl)2
O
78%
72%
PF5
PF4
then, TMSCl
KF
76%
(99%)
92%
P
H
S
P
S
Ph
OEt
MeCN, rt, 16 h
K[ArPF5]
Ar = p-OMe-Ph
2
28
29
30
37
36
O
P
no reaction
OPh
OPh 38
Scheme 4. Oxalyl chloride/KF approach with TMSCl treatment
offers convenient access to both pentafluoro(aryl)phosphate(V)
and tetrafluoro(aryl)-λ5-phosphorane (aryl-PF4) compounds.
Isolated yields are reported with 19F NMR yields in parentheses.
PhO
EtO
O
P
K[PF6]
59%
OEt
H
39
40
Having successfully achieved the synthesis of R3PF2 and
R2PF3 species, as well as to some of their phosphonium and
phosphate congeners, with the DOF method, we next focused on
the preparation of RPF4 compounds. We examined the reactivity
of ethyl phenylphosphinate (28), which, we hoped, would have a
sufficiently labile ethoxy substituent that effectively could be
displaced by fluoride (Scheme 4). Indeed, K[PhPF5] (29) formed
quantitatively as indicated by 19F NMR spectroscopy. Moreover,
Figure 3. Effects of phosphorus substituents on deoxygenative
fluorination outcomes under standard reaction conditions.
Isolated yields are reported.
So far, these examples showed that various P-X bonds in
phosphine oxides can be converted to P-F bonds in the presence
of one or two P-C bonds. But will deoxygenative fluorination occur
This article is protected by copyright. All rights reserved.

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
in the absence of any P-C bonds? To investigate this, triphenyl
phosphate (PhO)3P=O 38 was reacted with (COCl)2/KF and,
unsurprisingly, it was found to be unreactive (Figure 3).
Conversely, diethyl phosphite 39, in which one alkoxy substituent
is replaced with a P-H bond, readily converts to K[PF6] (39). As a
complement to existing methodologies (e.g. fluorination of PCl5),
oxalyl chloride/KF conditions provide an alternative, viable
approach to the synthesis of hexafluorophosphate salts (which
have known applications as electrolytes in batteries and in
electrochemistry) in addition to fluorinated organophosphorus(V)
compounds.[9,26,27] Furthermore, the hexafluorophosphate ion can
be readily precipitated and obtained in pure form as Bu4NPF6 (41)
during the workup upon addition of Bu4NCl (Scheme 5) from 39
and our standard conditions. This demonstrates a novel and
straightforward route to Bu4NPF6 – a common electrolyte used in
electrochemistry – via a deoxygenative fluorination approach.
Although 47 and 48 could not be obtained a single-crystals and
their detailed structures are not yet known, some 19F and 31P NMR
features are noteworthy. For instance, 47 and 48 exhibit very
large 1JF-P coupling constants of 1131 and 1159 Hz respectively,
in good agreement with the dimesityldifluorophosphonium ion
with 1JF-P = 1204 Hz reported by by Olaru and coworkers. These
values are larger than in R3PF+ fluorophosphonium ions such as
[(C6F5)3PF][B(C6F5)4] (1JF-P = 1062 Hz), possibly indicating shorter
P-F bonds in 47 and 48.[1,33] The calculation of the enthalpy in an
isodesmic reaction involving 47 and 48 shows that the latter is
more stable by 8.1 kcal/mol [DFT wB97XD/6-311++G** (see SI
for details)], which we attribute to the electron donating effect of
the p-OMe-substituents in the arene ring]. The efficacy of such
difluorophosphonium ions as easily tunable Lewis-acidic catalysts
shall be explored in future work.
formation of novel
difluorophosphonium
ions enabled by this
methodology
[Et3Si][B(C6F5)4] (46)
standard
conditions
O
Ar2PF3
[Ar2PF2][B(C6F5)4]
Ar = Ph (47): 92%
direct isolation of a
common electrolyte
toluene, rt, 20 min.
P
Bu4N[PF6]
59%
OEt
H
EtO
then, Bu4NCl
= p-OMe-Ph (48): 96%
39
41
Scheme 7. Synthesis of novel difluorophosphonium cations 47
and 48. Isolated yields are reported.
Scheme 5.
Direct conversion of diethylphosphate 39 to
Bu4N[PF6] 41 using standard oxalyl chloride/KF conditions
followed by precipitation using Bu4NCl. Isolated yield is reported.
In conclusion, this report discloses a new and highly versatile
deoxygenative fluorination (DOF) protocol by which phosphine
oxides are converted to fluorinated organophosphorus(V)
compounds using the combination of oxalyl chloride and KF as
relatively user-friendly reagents. This approach is practical and
scalable, and can be applied to a wide range of substrates. This
new method also allows the preparation of hexafluorophosphate
salts and can be extended to fluorinated antimony- and arsenic-
compounds. Moreover, the easy access to Ar2PF3 compounds
now allows the synthesis and characterization of Ar2PF2+ ions
which are largely unexplored
We also briefly entertained the extension of this fluorination
chemistry to other group 15 elements, namely As and Sb. Notably,
triphenylstibane oxide 42 and triphenylarsane oxide 44 undergo
DOF to form 43 and 45, respectively, in good yields (Scheme 6).
Unlike many of their phosphorus congeners, difluorotriaryl-λ5-
stibanes may be subjected to purification via column
chromatography and have found applications as precursors to
pentavalent organoantimony compounds in main-group element
chemistry.[28–31] As a consequence of harsh starting materials
(AsF3) and reagents (IF5, HF, etc.), difluorotriaryl-λ5-arsanes are
less explored but have demonstrated some potential applications
as fluorinating reagents.[32] Although a complete investigation of
antimony- and arsenic-based substrate reactivity is beyond the
scope of this study, these initial results serve as proof of concept
that oxalyl chloride/KF-based deoxygenative fluorination can
translate beyond phosphorus in group 15 elements.
It is our hope that this method not only aids members of the
synthetic community working in this field already but enables
others who may not be willing to work with hazardous fluorinating
reagents on scale.
Acknowledgements
methodology translates to fluorination of stibane and arsine oxides
We thank the ETH Zürich for financial support. MoBiAs and
SMoCC are acknowledged for assistance with HRMS analyses
and X-ray diffraction measurements.
(COCl)2
KF
(COCl)2
KF
F
Ph Sb
F
F
Ph As
F
O
O
Ph
Ph
Ph
Ph
Sb
As
Ph
Ph
Ph
Ph
Ph
Ph
MeCN, rt, 16 h
MeCN, rt, 16 h
58%
77%
42
43
44
45
Conflict of Interest
Scheme 6.
Application of methodology to deoxygenative
fluorination of triphenylstibane oxide and triphenylarsine oxide.
Isolated yields are reported.
The authors declare no conflict of interest.
Key
words:
fluorine,
phosphorus,
deoxyfluorination,
Lastly, fluorophosphonium ions have a crucial role as
catalysts in C-F bond functionalization, and we contemplated
ways in which our deoxygenative fluorination chemistry could
contribute to advancements in this field.[1–3,5] We were able to
synthesize new "R2PF2+" difluorophosphonium ions as
tetra(pentafluorophenyl)borate salts 47 and 48 (from 19 and 16)
using silyl salt 46 (Scheme 7) as fluoride abstraction reagent.
fluorophosphates, phosphonium fluorides
References
[1]
C. B. Caputo, L. J. Hounjet, R. Dobrovetsky, D. W.
Stephan, Science 2013, 341, 1374–1377.
This article is protected by copyright. All rights reserved.

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
[2]
[3]
[4]
M. H. Holthausen, R. R. Hiranandani, D. W. Stephan,
Chem. Sci. 2015, 6, 2016–2021.
L. J. Hounjet, C. B. Caputo, D. W. Stephan, Angew. Chem.
Int. Ed. 2012, 51, 4714–4717.
M. Mehta, M. H. Holthausen, I. Mallov, M. Pérez, Z.-W. Qu,
S. Grimme, D. W. Stephan, Angew. Chem. Int. Ed. 2015,
54, 8250–8254.
[5]
[6]
[7]
M. H. Holthausen, M. Mehta, D. W. Stephan, Angew.
Chemie 2014, 126, 6656–6659.
M. Pérez, C. B. Caputo, R. Dobrovetsky, D. W. Stephan,
Proc. Natl. Acad. Sci. 2014, 111, 10917–10921.
B. Vabre, K. Chansaenpak, M. Wang, H. Wang, Z. Li, F. P.
Gabbaï, Chem. Commun. 2017, 53, 8657–8659.
R. L. Vekariya, J. Mol. Liq. 2017, 227, 44–60.
J. B. Goodenough, Y. Kim, Chem. Mater. 2010, 22, 587–
603.
[8]
[9]
[10]
[11]
W. C. Smith, J. Am. Chem. Soc. 1960, 82, 6176–6177.
J. A. Gibson, R. K. Marat, A. F. Janzen, Can. J. Chem.
1975, 53, 3044–3052.
[12]
[13]
[14]
W. C. Smith, Production of Inorganic Fluorine Compounds,
1959, US2904398.
C. R. Pitts, D. Bornemann, P. Liebing, N. Santschi, A.
Togni, Angew. Chem. Int. Ed. 2019, 58, 1950–1954.
D. Bornemann, C. R. Pitts, C. J. Ziegler, E. Pietrasiak, N.
Trapp, S. Kueng, N. Santschi, A. Togni, Angew. Chem. Int.
Ed. 2019, 58, 12604–12608.
[15]
[16]
J. Häfliger, C. R. Pitts, D. Bornemann, R. Käser, N.
Santschi, J. Charpentier, E. Otth, N. Trapp, R. Verel, H. P.
Lüthi, et al., Chem. Sci. 2019, 10, 7251–7259.
F. Brüning, C. R. Pitts, J. Kalim, D. Bornemann, C.
Ghiazza, J. de Montmollin, N. Trapp, T. Billard, A. Togni,
2019, 19113–19117.
[17]
[18]
M. Masaki, K. Fukui, Chem. Lett. 1977, 6, 151–152.
H. Zhu, Z. W. Qu, S. Grimme, Chem. Eur. J. 2019, 25,
4670–4672.
[19]
[20]
L. P. Hammett, J. Am. Chem. Soc. 1937, 59, 96–103.
M. J. Frisch, J. A. Pople, J. S. Binkley, J. Chem. Phys.
1984, 80, 3265–3269.
[21]
[22]
[23]
[24]
[25]
[26]
[27]
All Calculation Were Performed Using the Gaussian 09,
Revision D.01 Program Package.
J. M. Bayne, M. H. Holthausen, D. W. Stephan, Dalton
Trans. 2016, 45, 5949–5957.
J. B. Lambert, S. Zhang, S. M. Ciro, Organometallics 1994,
13, 2430–2443.
H. Coates, P. R. Carter, Production of Alkyl Phosphonyl
Fluorides, 1952, US2853515.
I. P. Komkov, S. Z. Ivin, K. V. Karavano, L. E. Smirno, Zh.
Obs. Khim. 1962, 32, 295–299.
A. Mauger, C. M. Julien, A. Paolella, M. Armand, K. Zaghib,
Mater. Sci. Eng. R Reports 2018, 134, 1–21.
M. M. Woyski, W. J. Shenk Jr., E. R. Pellon, Inorg. Synth.
1950, 111–117.
[28]
[29]
G. Doleshall, J. Organomet. Chem. 1971, 30, 369–375.
Y. Kitamura, M. Matsumura, Y. Murata, M. Yamada, N.
Kakusawa, M. Tanaka, H. Okabe, H. Naka, T. Obata, S.
Yasuike, J. Fluorine Chem. 2017, 199, 1–6.
K. V Domasevitch, N. N. Gerasimchuk, A. Mokhir, Inorg.
Chem. 2000, 39, 1227–1237.
G. Schröder, T. Okinaka, Y. Mimura, M. Watanabe, T.
Matsuzaki, A. Hasuoka, Y. Yamamoto, S. Matsukawa, K.
Akiba, Chem. Eur. J. 2007, 13, 2517–2529.
M. Cartwright, A. A. Woolf, J. Fluorine Chem. 1981, 19,
101–122.
[30]
[31]
[32]
[33]
[34]
M. Olaru, A. Schröder, L. Albers, D. Duvinage, S. Mebs, J.
Beckmann, Chem. Eur. J. 2019, 25, 9861–9865.
CCDC 2013558 (4), 2013559 (10), 2013560 (14), 2015080
(27-cis).
This article is protected by copyright. All rights reserved.

10.1002/anie.202010943
Angewandte Chemie International Edition
RESEARCH ARTICLE
Entry for the Table of Contents
R2PF2
RPF4 R2PF3
RPF5 R2PF4
R3PF
O
P
(COCl)2 / KF
MeCN
Z
Y
R3PF2
PF6
X
Fluorinating Phosphorus is No Fuss for Us! A mild, deoxygenative fluorination approach was
developed using only oxalyl chloride and potassium fluoride to access a broad variety of fluorinated
phosphorus(V) compounds in neutral, cationic, or anionic forms. The method circumvents working with
both pyrophoric starting materials and hazardous fluorinating reagents, making fluorinated group 15
heteroatoms in organic frameworks more accessible.
This article is protected by copyright. All rights reserved.