Carbon-fluorine reductive elimination from a high-valent palladium fluoride

Article abstract of DOI:10.1021/ja803187x

We have observed two high-valent arylpalladiumfluoride complexes that afford carbon-fluorine bond formation upon thermolysis. Copyright

Full text of DOI:10.1021/ja803187x

Published on Web 07/11/2008
Carbon-Fluorine Reductive Elimination from a High-Valent Palladium
Fluoride
Takeru Furuya and Tobias Ritter*
Department of Chemistry and Chemical Biology, HarVard UniVersity, 12 Oxford Street, Cambridge, Massachusetts
Received April 29, 2008; E-mail: ritter@chemistry.harvard.edu
Aryl fluorides are valuable compounds as pharmaceuticals1 and
Scheme 1. Fluorination of Arylboronic Acids via Stoichiometric
Arylpalladium Complexes Using Selectfluor
as tracers for positron-emission tomography.2 The general synthesis
of complex, highly functionalized aryl fluorides in which the
carbon-fluorine bond is introduced at a late stage of the synthesis
is a challenge unmet by conventional fluorination methods. We
recently communicated that aryl boronic acids can be converted
into aryl fluorides via reaction of stoichiometric aryl palladium
complexes with the electrophilic fluorination reagent Selectfluor3
(1) (eq 1).4 Two potential mechanisms for carbon-fluorine bond
formation are palladium-carbon bond cleavage by the electrophilic
fluorination reagent and oxidation of the palladium center to form
a discrete high-valent palladium fluoride followed by reductive
elimination to form a carbon-fluorine bond. In this Communication
we present the carbon-fluorine bond formation from two high-
valent aryl palladium fluoride complexes. The observation of high-
valent palladium fluorides may afford valuable mechanistic insight
to better understand carbon-fluorine bond formation mediated by
transition metals.
obtained in 99% yield from pyridyl-sulfonamide 2 and palladium(II)
acetate in the presence of 3 equiv of pyridine. Transmetalation using
Transition-metal-mediated carbon-fluorine bond formations are
rare.5 Three processes, including our own work,4 have been reported
using palladium complexes and electrophilic fluorination sources.
In 2006, Sanford published a palladium-catalyzed fluorination of
phenylpyridinederivativesandrelatedsubstratesinwhichcarbon-hydrogen
bonds proximal to the pyridine directing group were fluorinated
(microwave, 100-150 °C, 1-4 h, 33-75% yield).6 Vigalok
reported in 2008 the formation of 1,4-difluorobenzene and 4-flu-
oroiodobenzene in 10% and 90% yield, respectively, from an aryl-
iodo-bisphosphine palladium(II) complex upon treatment with
1-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate.7 For all three
processes, the intermediacy of a high-valent palladium fluoride
followed by reductive elimination to form the carbon-fluorine bond
and a palladium(II) complex was discussed as a potential reaction
pathway. In none of the cases, however, was a high-valent palladium
intermediate characterized or observed. In fact, a carbon-fluorine
bond formation to form an aryl fluoride by concerted aryl-fluorine
reductive elimination from a well-defined transition metal fluoride,
while implicated,8 has not been substantiated in the literature from
any transition metal in any oxidation state.8,9
Scheme 1 shows a reaction sequence to convert a boronic acid
into the corresponding arylfluoride. We found that pyridyl-
sulfonamide ligands such as 2 are well suited for the fluorination
reaction, because they serve as ancillary ligands to support
arylpalladium complexes such as 5, which afford arylfluorides
regiospecifically upon treatment with Selectfluor in high yield (87%
in the presented case). The palladium(II) acetate complex 3 was
4-tert-butylphenylboronic acid (4) afforded the air- and water-stable
yellow aryl palladium complex 5 in 80% yield. Fluorination of 5
with Selectfluor in acetone at 50 °C gave 4-tert-butylfluorobenzene
(6) in 87% yield within 30 min.
Under the reaction conditions that afforded 87% yield of 6
(acetone, 50 °C), we did not observe a high-valent palladium
fluoride intermediate by NMR, but a reversible color change from
yellow to orange upon addition of 5 to Selectfluor suggested the
formation of a discrete intermediate. To evaluate the mechanistic
hypothesis that pyridyl-sulfonamide-stabilized aryl palladium
complexes such as 5 can afford carbon-fluorine bond formation
via well-defined discrete palladium fluorides, we sought to design
an analogue of 5 that would afford an observable palladium(IV)
fluoride upon oxidation with Selectfluor. Rigid ligands have been
shown to stabilize high-valent metal centers including palla-
dium(IV).10 We therefore synthesized the palladium(II) derivative
8, in which a rigid, chelating benzoquinolinyl ligand substitutes
the aryl and pyridyl ligands of 5 (eq 2). Treatment of the
benzoquinolinyl palladium acetate dimer 711 with 1 equiv of the
pyridyl-sulfonamide ligand 2 in methylene chloride at room
temperature afforded the aryl palladium complex 8 in 95% yield
as an analytically pure yellow solid within 20 min.
9
10060 J. AM. CHEM. SOC. 2008, 130, 10060–10061
10.1021/ja803187x CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Carbon-Fluorine Bond Formation by Reductive
Elimination
Figure 1. ORTEP drawing of the palladium(IV) difluoride 11 with 50%
probability ellipsoids (hydrogen atoms and solvent omitted for clarity).
Selected bond lengths [Å] and angles [deg]: Pd-F(1), 2.040(3); Pd-F(2),
1.955(3); Pd-C(35), 2.008(5); Pd-N(13), 2.019(4); Pd-N(1), 2.027(5);
Pd-N(26), 2.012(5); F(1)-Pd-F(2), 88.27(13); F(2)-Pd-N(13),
173.48(15).
Scheme 3. Independent Synthesis of the Cationic Palladium
Tetrafluoroborate 12
mutually cis and have bond lengths to palladium of 1.955(3)Å (F2)
and 2.040(3)Å (F1), respectively. To our knowledge, a high-valent
organometallic palladium difluoride has not been reported previously.
In conclusion we have shown carbon-fluorine bond formation from
two discrete palladium(IV) fluoride complexes. Our data is consistent
with a well-defined reductive elimination and provides insight into
carbon-fluorine bond formation from arylpalladium complexes.
Acknowledgment. We thank Dr. Shaw Huang for NMR
analysis, Dr. Imhyuck Bae and Christian Kuttruff for discussions,
Merck & Co. and Amgen Inc. for unrestricted support, Eli Lilly
for a graduate fellowship for T.F., and Dr. Douglas M. Ho and
Jessica Y. Wu for X-ray crystallographic analysis.
Fluorination of 8 in acetonitrile at 50 °C afforded 10-fluoroben-
zo[h]quinoline (10) in 94% yield (Scheme 2). Moreover, we
1
observed a deep purple, well-defined intermediate by H and 13C
NMR, which was not contaminated with either 8 or 10 and had a
half-life of ca. 70 min in acetonitrile solution at 23 °C.12 The NMR
resonances, including an 19F NMR resonance at -278 ppm, are
consistent with the terminal palladium(IV) fluoride 9; the instability
of 9 precluded isolation and purification for additional characteriza-
tion. When the acetonitrile solution of 9 was subsequently heated
to 50 °C, reductive elimination ocurred to form 10. Additional
evidence for the formation of a high-valent palladium fluoride was
obtained, when the intermediate 9 was treated with tetramethylam-
monium fluoride tetrahydrate at room temperature to form the
palladium(IV) difluoride 11 that we independently synthesized by
oxidation of 8 with XeF2.
Reductive elimination from 9 afforded a cationic palladium(II)
tetrafluoroborate that was trapped with pyridine to afford the
cationic palladium bispyridine tetrafluoroborate 12, which was
observed by NMR and mass spectrometry in the reaction mixture,
and independently synthesized from the palladium acetate 3 in 94%
yield (Scheme 3). The isolation of 12 with the pyridyl-sulfonamide
ligand coordinated to palladium is consistent with a reductive
elimination from 9.
Supporting Information Available: Detailed experimental proce-
dures and spectroscopic data for all new compounds as well as
crystallographic analysis of 11. This material is available free of charge
via the Internet at http://pubs.acs.org.
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yield when heated in DMSO at 150 °C for 10 min (Scheme 2).
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stable at 23 °C for at least 1 week and in chloroform solution at
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