Reagent-dependent formation of C-C and C-F bonds in Pt complexes: An unexpected twist in the electrophilic fluorination chemistry

Article abstract of DOI:10.1021/ja101436w

Cyclometalated platinum(II) complexes (C-P)Pt(Aryl)py undergo oxidative addition reaction upon treatment with electrophilic fluorination reagents, XeF₂ or N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, giving eventually products of C-C c

Full text of DOI:10.1021/ja101436w

Published on Web 07/16/2010
Reagent-Dependent Formation of C-C and C-F Bonds in Pt Complexes: An
Unexpected Twist in the Electrophilic Fluorination Chemistry
Ariela W. Kaspi, Israel Goldberg, and Arkadi Vigalok*
School of Chemistry, The Sackler Faculty of Exact Sciences, Tel AViV UniVersity, Tel AViV 69978, Israel
Received February 18, 2010; E-mail: avigal@post.tau.ac.il
Scheme 1
Abstract: Cyclometalated platinum(II) complexes (C-P)Pt(Aryl)py
undergo oxidative addition reaction upon treatment with electro-
philic fluorination reagents, XeF2 or N-fluoro-2,4,6-trimethylpyri-
dinium tetrafluoroborate, giving eventually products of C-C
coupling. However, when aryl ) mesityl, the two reagents give
completely different products: the N-F salt still favors the C-C
coupling reaction while XeF2 gives the unprecedented benzylic
fluorination of one of the ortho-methyl groups of the mesityl ligand.
Transition-metal-mediated formation of carbon-fluorine bonds has
recently become the topic of much interest1 primarily due to the
importance of the fluoroorganic compounds in the pharmaceutical and
agrochemical industries. These compounds are traditionally prepared
via a nucleophilic substitution reaction at an sp2- or sp3-hybridized
carbon atom containing a halide or sulfonate leaving group.2,3 More
recently, a palladium-catalyzed ligand-assisted electrophilic fluorination
emerged as a complementary technique to the nucleophilic exchange.4
In these reactions, the C-F bond formation was proposed to take place
from a Pd(IV) intermediate.5-7 The electrophilic path offers an
advantage of directly utilizing the C-H bonds in the fluorination
reaction, thus reducing the number of synthetic steps and amount of
waste associated with them. However, the necessity to utilize a
heteroatom containing directing group (usually nitrogen) makes the
palladium-assisted electrophilic fluorination relatively limited in scope.
In this work, we present the first example of (1) use of Pt in making
a C-F bond and (2) different reactivity patterns of different electro-
philic fluorinating reagents.
Scheme 2
A few years ago, we reported that chelating diphosphine complexes
of the formula (R2P(CH2)nPR2)Pt(Ar)2 (R ) Alkyl, Aryl, n ) 2, 3)
react with XeF2 to give products of the C-C reductive elimination:
diaryl and the corresponding Pt(II) difluoride.8 No oxidative addition
Pt(IV) intermediate was observed during the reaction course. To study
the reaction mechanism in more detail, we decided to slow down the
C-C elimination process by making one of the aryl groups of a Pt(II)
complex a part of a stable five-membered chelate. We found that
reacting ligand 19 with (COD)PtCl2 (COD ) 1,5-cyclooctadiene) gives
a cyclometalated Pt(II) dimer 2, which was fully characterized,
including by X-ray analysis. Complex 2 reacted with ArMgBr giving,
after the addition of pyridine, the corresponding monomeric Pt(II) diaryl
precursors 3a,b (Scheme 1). A typical 31P{1H} NMR spectrum of these
complexes showed a singlet at ca. 62 ppm with a small JPtP of ca.
1840 Hz, indicating the mutual trans-arrangement of the nonchelated
aryl and phosphine ligands. The X-ray structure of the mesityl complex
3b (Scheme 1) confirms the cis-positioning of the two aryl ligands,
with the mesityl group being at a slightly longer distance from the Pt
center than the chelated aryl group (2.057(8) Å vs 1.988(8) Å), likely
due to a stronger trans-influence of the phosphine ligand compared
with that of the pyridine.
The reaction of 3a with XeF2 provided the stable oxidative addition
complex 4 as the only organometallic product, which was isolated in
a 92% yield after precipitation with pentane (Scheme 2). The 19F NMR
spectrum of 4 exhibits two multiplets due to the inequivalent fluoro
ligands at -231 and -234 ppm, with an additional signal at -120
ppm due to the para-fluoro substituent of the nonchelated aryl ligand.
The X-ray structure of 4 also shows two inequivalent fluorides, with
bond distances of 2.077(3) Å and 2.167(3) Å. As the Pt-C distances
for the two aryl ligands are in the same range (2.013(6) Å vs 2.041(6)
Å), we can tentatively attribute the large difference in the Pt-F bond
lengths to the nonlinear positioning of the axial F1 and C1 ligands
(Scheme 3, C1-Pt-F1 angle of 167.77(17)°) which decreases the
trans-influence of the aryl group. The significant deviation from the
linearity can be the result of the steric repulsions involving the bulky
adamantyl groups.
Interestingly, the removal of one of the fluoro ligands from the
Pt coordination sphere by 1 equiv of trimethylsilyl triflate (TMS-
OTf) resulted in instantaneous C-C reductive elimination, followed
by cyclometalation at the other side of aromatic ring.10 The
consequent elimination of HF gave an unsaturated Pt(II) product,
which was characterized in solution. Addition of pyridine11 and
9
10626 J. AM. CHEM. SOC. 2010, 132, 10626–10627
10.1021/ja101436w  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
Scheme 4
to that of 3b (taking into account a different auxiliary ligand). For
example, the Pt-mesityl distance of 2.057(6) Å remained virtually
unchanged when compared with that in 3b. The long 4.028 Å distance
between the benzylic fluorine atom and platinum center suggests that
there is no interaction between the two atoms in the solid state.
While the mechanistic studies of the new fluorination reaction are
still underway, we believe that the formation of a transient Pt(IV)
difluoro species (similar to 4) takes place followed by the fluoride-
assisted metalation of one of the methyl groups of the mesityl ligand.17
The reaction is probably facilitated by high steric congestion around
the metal center. The benzylic C-F reductive elimination from a Pt(IV)
complex furnishes the final product (Scheme 4).
In summary, we demonstrated that Pt complexes can be used in
the electrophilic fluorination of a benzylic C-H bond. In addition,
using different electrophilic fluorinating reagents can lead to
different reaction outcomes, which can be important in the design
of new fluorination methods. Further studies on the reactivity of
Pt complexes in fluorination reactions are ongoing in our laboratory.
Acknowledgment. This work was supported by the US-Israel
Binational Science Foundation.
PPh3 to this species gave a 16-electron square-planar complex 5
which was isolated in a quantitative yield (Scheme 2). The 31P NMR
spectroscopy as well as X-ray structural analysis of 5 confirms the
trans-positioning of the two phosphine ligands in solution and the
solid state. As the reaction between TMS-OTf and 4 likely gives a
cationic monofluoro Pt(IV) intermediate,12 we thought that the
reaction of 3a with an electrophilic fluorinating reagent, such as
N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate (“N-F”+),
would directly result in the formation of 5, after the addition of
PPh3. Indeed, as shown in Scheme 2, complex 5 was obtained in
the sequence of reactions which likely involved electrophilic
fluorination, C-C reductive elimination, C-H activation, and H-F
elimination; however, the reaction was not as clean as the fluoride
removal from 4 with TMS-OTf giving ∼30% of unidentified
byproducts. Following the reaction by 19F NMR spectroscopy
revealed the formation of a new Pt monofluoride complex which
rapidly disappeared at RT to give the final product. This intermedi-
ate complex was assigned the structure of 6 (Scheme 2) based on
the 31P and 19F NMR data. Subsequent addition of 1.5 equiv of
Me4N+F- hydrate resulted in the formation of 4 as the major
product. While we did not observe 6 in the reaction between 4 and
TMS-OTf even at low temperatures, it is possible that the reaction
proceeds via a different, more reactive Pt(IV) isomer.13
Supporting Information Available: Synthesis and characterization of
complexes 2-9 (PDF). X-ray data for complexes 2, 3b, 4, 5, and 9 (CIF).
This material is available free of charge via the Internet at http://pubs.acs.org.
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16e configuration it was necessary to add more pyridine along with PPh3.
(12) Such cationic intermediates have been shown to be highly reactive in the
C-C reductive elimination from Pt(IV) complexes; for example, see:
Procelewska, J.; Zahl, A.; Liehr, G.; van Eldik, R.; Smythe, N. A.; Williams,
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(13) A nearly identical to 6 intermediate complex was also observed, along the
way to 5, when N-fluoro-2,4,6-trimethylpyridinium triflate was used,
suggesting that the anion has little role in the overall transformation.
(14) Several platinum(II) systems for C-F actiVation have been reported: (a)
Crespo, M.; Martinez, M.; Sales, J. Organometallics 1993, 12, 4291. (b)
Anderson, C. M.; Crespo, M.; Ferguson, G.; Lough, A. J.; Puddephatt,
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(15) Under the same conditions, no benzylic fluorination of mesitylene with
XeF2 takes place in the absence of platinum.
Unexpectedly, while the reaction of 3b with the “N-F”+ salt
proceeded similarly to the reaction of 3a, giving the product of the
C-C coupling and consequent cyclometalation 7 as the major species,
treating 3b with XeF2 did not give the analogous to 4 difluoro Pt(IV)
product. Instead, quantitative fluorination of one of the ortho-benzylic
positions of the mesityl ligand was obtained in this case giving complex
8 (Scheme 3). To the best of our knowledge, this is the first fluorination
of a C-H bond assisted by a platinum complex14 and first fluorination
at the ortho-position not requiring a heteroatom directing group.15
While the 31P{1H} NMR spectrum of 8 shows a signal very similar to
that of 3b, the triplet at 197.2 ppm (JHF ) 50 Hz) in the 19F NMR
spectrum unambiguously confirms the fluorination in the benzylic
position. The CH2F group gives rise to two low-field doublets of
doublets in the 1H NMR spectrum due to the inequivalent hydrogen
atoms (Scheme 3, insert). Unlike 3b, complex 8 shows considerable
solubility in nonpolar solvents, such as pentane, and proved extremely
difficult to crystallize. Fortunately, the replacement of pyridine in 8
with PPh3 gave complex 9, which was crystallized16 from
CH2Cl2-MeOH. The X-ray structure of 9 (Scheme 4) confirms the
selective fluorination of one of the ortho-methyl groups of the mesityl
ligand, with the overall geometry of the complex being very similar
(16) The complex cocrystallized with an additional PPh3 molecule, which was
omitted from Scheme 3 for clarity.
(17) A Pt(IV)-Cl interaction with the ligand CH3 group without cyclometallation
was recently reported: Mamtora, J.; Crosby, S. H.; Newman, C. P.; Clarkson,
G. J.; Rourke, J. P. Organometallics 2008, 27, 5559.
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