Facile Ar-CF3 bond formation at Pd. strikingly different outcomes of reductive elimination from [(Ph3P)2Pd(CF 3)Ph] and [(Xantphos)Pd(CF3)Ph]

Article abstract of DOI:10.1021/ja064935c

Facile and highly selective perfluoroalkyl-aryl reductive elimination from a metal center (Pd) has been demonstrated for the first time. At temperatures as low as 50-80 °C, [(Xantphos)Pd(Ph)CF₃] undergoes remarkably clean decomposition to produce CF₃Ph in high yield and selectivity. In contrast, analogous trifluoromethylpalladium aryls stabilized by rigid cis-chelating ligands such as dppe are completely unreactive at temperatures up to 130-140 °C. Decomposition of [(Ph₃P)₂Pd(Ph)CF₃] in the presence of PhI in benzene at 60 °C does not produce PhCF₃ but rather leads to [(Ph₃P)₂Pd(Ph)I] and [Ph₄P]⁺[(Ph₃P)Pd(CF₃)₃]^- in a 2:1 ratio with high selectivity. Copyright

Full text of DOI:10.1021/ja064935c

Published on Web 09/12/2006
Facile Ar-CF3 Bond Formation at Pd. Strikingly Different Outcomes of
Reductive Elimination from [(Ph3P)2Pd(CF3)Ph] and [(Xantphos)Pd(CF3)Ph]
Vladimir V. Grushin* and William J. Marshall
Central Research & DeVelopment, E. I. DuPont de Nemours and Co., Inc.,† Experimental Station,
Wilmington, Delaware 19880-0328
Received July 11, 2006; E-mail: vlad.grushin-1@usa.dupont.com
Biological activity is commonly exhibited by selectively fluori-
nated molecules. “As many as 30-40% of agrochemicals and 20%
of pharmaceuticals on the market are estimated to contain fluorine,
including half of the top 10 drugs sold in 2005.”1 Hence, the demand
for new reactions to introduce fluorine and fluorine-containing
groups into organic molecules is increasingly high.1 New methods
to selectively fluorinate and trifluoromethylate aromatic compounds
are particularly important and intensely sought. Although a few
interesting findings have recently been reported,2-4 the problem is
Figure 1. ORTEP drawings of 4 (left) and 2 (right).
far from being solved and still represents a major synthetic
challenge.
Our previous attempts10 to synthesize 1 from [(Ph3P)2Pd(Ph)I]
and CF3SiMe3/CsF were unsuccessful owing to facile displacement
of the phosphines on Pd with the CF3 groups.15a Because 3 behaved
As an alternative to the Swarts reaction,5 it would be desirable
to develop Pd-catalyzed coupling of haloarenes with a CF3-
transferring nucleophile, for example Ruppert’s reagent, CF3SiMe3.
similarly,15b we attempted the synthesis of 1 and 2 from the
Such process must involve Ar-CF3 reductive elimination from
corresponding fluorides.16 Both known [(Ph3P)2Pd(Ph)F] and new
Pd(II) as the key product forming step. The feasibility of this step,
[(Xantphos)Pd(Ph)F] (4) were prepared using our previously
however, is in question because late transition metal-CF3 bonds
developed method for the synthesis of metal fluorides from the
are generally strong and notoriously inert.6 Unlike [(LL)Pd(CH3)-
corresponding iodides and AgF under sonication (eq 1).17 The I/F
(Ph)] (LL ) dppe7 or dppp8) that reductively eliminate toluene at
exchange on 3 (eq 1) smoothly produced 4 that was isolated pure
as low as 15-40 °C, their CF3 congeners [(dppbz)Pd(CF3)(o-Tol)]9
in 92% yield.
and [(LL)Pd(CF3)(Ph)] (LL ) dppe or dppp)10 do not produce
ArCF3 for days at 130 °C. Only at 145 °C was the low-yield
formation of PhCF3 from the dppe and dppp complexes observed
as a result of the sluggish and poorly selective reaction.10 In this
communication, we describe the first example of facile and clean
CF3-Ar reductive elimination from a Pd(II) complex under mild
conditions.
Trifluoromethyl palladium aryls reported to date are all deriva-
1
The new fluoride 4 was fully characterized, including H, 19F,
and 31P NMR spectra and single-crystal X-ray diffraction. In the
solid state and in solution, 4 is trans, as established by the X-ray
(Figure 1) and NMR data.18 Thermolysis of 4 in dry benzene under
N2 at 60 °C overnight led, as expected,19 to only P-F bond
formation and no Ph-F reductive elimination.
tives of strongly chelating bidentate ligands.9,10 In this work, we
prepared analogous complexes, stabilized by a monodentate phos-
phine and a trans-chelating phosphine, to determine how these
ligands would influence the ability of the Pd center to reductively
eliminate Ar-CF3. Triphenylphosphine was chosen because of the
reported11 formation of perfluoroalkylarenes from perfluoroalkyl
iodides, iodoarenes, and Zn in the presence of [(Ph3P)2PdCl2] under
sonication. The choice of Xantphos as a bidentate phosphine was
determined by its wide bite angle12 and both cis- and trans-chelating
ability,12,13 factors that are expected8,12 to strongly influence
reductive elimination from Pd(II).14
Treatment of [(Ph3P)2Pd(Ph)F]17 or 4 with CF3SiMe3 in benzene
afforded, within the time of mixing, [(Ph3P)2Pd(Ph)CF3] (1) and
[(Xantphos)Pd(Ph)CF3] (2), respectively. More conveniently, 1 and
2 were made without isolation of the fluoride intermediates. After
the I/F exchange had gone to completion, the reaction mixtures
were quickly filtered through Celite in air, and the filtrates were
treated with CF3SiMe3 to afford pure 1 and 2 in high yield (eq 2).
Complex 1 was trans in solution20 and as a solid (X-ray; see
Supporting Information). The Xantphos derivative 2 was a 10:1
mixture of cis and trans isomers in benzene but exclusively cis in
more polar CH2Cl2 or THF and in the crystal structure (Figure 1).20
The starting materials for the synthesis of [(Ph3P)2Pd(Ph)CF3]
(1) and [(Xantphos)Pd(Ph)CF3] (2) were well-known [(Ph3P)2Pd-
(Ph)I] and new [(Xantphos)Pd(Ph)I] (3). The latter was prepared
by reacting [Pd2(dba)3] with Xantphos and PhI in toluene at room
temperature, a standard procedure for the synthesis of various
palladium aryls, including a few Xantphos derivatives.13,14 Complex
3 was trans in solution and in the solid state (NMR, X-ray; see
Supporting Information).
† Contribution No. 8741.
9
12644
J. AM. CHEM. SOC. 2006, 128, 12644-12645
10.1021/ja064935c CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Proposed Mechanism for Reaction 3.
reactivity of [L2Pd(Ar)CF3] when going from the rigid L2 (dppbz,
dppe, dppp) to adaptable Xantphos is remarkably reminiscent of
the key importance of flexibility for the reactions of cyclic iodonium
cations with nucleophiles, which proceed via reductive elimination
from tricoordinate iodine.24
Supporting Information Available: Experimental details, NMR
data (pdf), and X-ray analysis data (cif) for 1-5, [Ph4P]+[(Ph3P)Pd-
(CF3)3]-, and [(Xantphos)2Pd]. This material is available free of charge
via the Internet at http://pubs.acs.org.
References
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Decomposition of 1 in the presence of PhI in benzene-d6 at
60 °C (eq 3) gave a mixture of two complexes, [(Ph3P)2Pd(Ph)I]
(NMR) and [Ph4P]+[(Ph3P)Pd(CF3)3]- (X-ray).21
(5) The displacement of aliphatic Cl with F, first discovered by Swarts over
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Extra PPh3 was found to strongly inhibit reaction 3. This points
to P-C reductive elimination as the first step (Scheme 1) that is
known19,22 to require phosphine predissociation. The resulting Pd(0)
species A oxidatively adds PhI to give B, followed by well-
established10 transmetalation resulting in C and D, with the latter
undergoing reductive elimination of Ph2 to reform A. Complex C
is fully expected15a to easily exchange its I and PPh3 ligands for
CF3 in the presence of a strongly nucleophilic CF3-donor, such as
A (as shown in Scheme 1) or B. Both byproducts of this exchange,
[(Ph3P)2Pd] and [Ph4P]+[(Ph3P)Pd(I)]-, transform to [(Ph3P)2Pd-
(Ph)I] upon oxidative addition of PhI and the [Ph4P]+, respectively.
In sharp contrast with 1 and [L2Pd(CF3)(Ar)] (L2 ) dppbz,9
dppe,10 and dppp;10 see earlier), 2 underwent remarkably clean and
smooth Ph-CF3 reductive elimination at as low as 50-80 °C.
Heating a benzene solution of 2 and Xantphos (1:1) under N2 at
80 °C for 3 h led to the exclusive formation of PhCF3 and
[(Xantphos)2Pd]23 (X-ray) at ca. 100% conversion (eq 4).
(12) Kamer, P. C. J.; van Leeuwen, P. W. N.; Reek, J. N. H. Acc. Chem. Res.
2001, 34, 895.
(13) (a) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (b)
Zuideveld, M. A.; Swennenhuis, B. H. G.; Boele, M. D. K.; Guari, Y.;
van Strijdonck, G. P. F.; Reek, J. N. H.; Kamer, P. C. J.; Goubitz, K.;
Fraanje, J.; Lutz, M.; Spek, A. L.; van Leeuwen, P. W. N. M. J. Chem.
Soc., Dalton Trans. 2002, 2308.
(14) During the preparation of our manuscript, a brief report appeared,
describing the accelerating effect of Xantphos on reductive elimination
of N-aryl amidates from Pd(II): Fujita, K.; Yamashita, M.; Puschmann,
F.; Martinez Alvarez-Falcon, M.; Incarvito, C. D.; Hartwig, J. F. J. Am.
Chem. Soc. 2006, 128, 9044.
(15) (a) Naumann, D.; Kirij, N. V.; Maggiarosa, N.; Tyrra, W.; Yagupolskii,
Y. L.; Wickleder, M. S. Z. Anorg. Allg. Chem. 2004, 630, 746. (b)
Treatment of 3 with CF3SiMe3/CsF in THF resulted in nonselective
reaction and formation of large quantities of free Xantphos (31P NMR:
-17 ppm) even at low conversions.
(16) For the synthesis of CF3 derivatives of metals from the corresponding
fluorides and CF3SiMe3, see: (a) Huang, D.; Caulton, K. G. J. Am. Chem.
Soc. 1997, 119, 3185. (b) Huang, D.; Koren, P. R.; Folting, K.; Davidson,
E. R.; Caulton, K. G. J. Am. Chem. Soc. 2000, 122, 8916. (b) Taw, F. L.;
Scott, B. L.; Kiplinger, J. L. J. Am. Chem. Soc. 2003, 125, 14712. (c)
Vicente, J.; Gil-Rubio, J.; Guerrero-Leal, J.; Bautista, D. Organometallics
2004, 23, 4871; 2005, 24, 5634.
(17) (a) Fraser, S. L.; Antipin, M. Yu.; Khroustalyov, V. N.; Grushin, V. V. J.
Am. Chem. Soc. 1997, 119, 4769. (b) Pilon, M. C.; Grushin, V. V.
Organometallics 1998, 17, 1774.
(18) NMR data for 4 (C6D6, 25 °C): 19F: δ ) -300.7 ppm (br. t). 31P: δ )
4.4 ppm (d); JP-F ) 10 Hz.
(19) Grushin, V. V. Organometallics 2000, 19, 1888.
When the experiment was repeated using PhI in place of
Xantphos as a trap for the Pd(0), the formation of Ph2 and
[(Xantphos)Pd(I)CF3] (5; X-ray) competed with the main pathway
leading to PhCF3 and [(Xantphos)Pd(Ph)I] (3). This result was
expected.10 As the Ph-CF3 reductive elimination occurs, the Pd(0)
formed oxidatively adds PhI to give [(Xantphos)Pd(Ph)I] (3). The
latter and the as yet unreacted 2 undergo transmetalation10 giving
rise to 5 and [(Xantphos)PdPh2] which is transformed back to 3
via Ph-Ph reductive elimination, followed by oxidative addition
of PhI. The transmetalation path is favored by higher concentrations,
conversion, and temperature. At 95-100% conversion of 1, the
PhCF3 to 5 ratio was measured (19F NMR) at 2.3 (60 °C, 20 h),
2.0 (70 °C, 8 h), and 1.2 (80 °C, 2 h).
In conclusion, facile and highly selective perfluoroalkyl-aryl
reductive elimination from a metal center (Pd) has been demon-
strated for the first time. The role of Xantphos on Pd for the CF3-
Ph bond formation is critical.14 Replacement of the Xantphos ligand
on Pd with PPh3 or cis-chelating dppbz,9 dppe,10 dppp,10 and tmeda10
blocks the Ar-CF3 bond forming path. The dramatic change in
(20) NMR data (benzene-d6; 25 °C; δ). For 1: 1H: 6.4 (m, 2H, m-PhPd); 6.6
(m, 1H, p-PhPd); 7.0 (m, 2H, o-PhPd); 7.1 (m, 18H, m, p-PhP); 7.8
(m, 12H, o-PhP). 19F: -16.1 (t, JP-F ) 13.9 Hz). 31P: 28.6 (q, JP-F
)
13.9 Hz). For trans-2: 19F: -13.1 (t, JP-F ) 16.0 Hz). 31P: 17.7 (q,
JP-F ) 16.0 Hz). For cis-2: 19F: -14.6 (br m); 31P: 4.8 (br m, 1P); 9.6
(br s, 1P). There is no fast exchange on the NMR time scale between cis-
and trans-2 in benzene at 25 °C. The 19F and 31P NMR spectra of 2 display
sharp multiplets from trans-2 but broadened resonances from cis-2. This
line broadening might be due to P-site exchange via dissociation (strong
trans effects of both Ph and CF3) and can be frozen out at lower
temperatures. 19F NMR (CD2Cl2, -70 °C), δ: -17.5 (dd, trans-JP-F
)
48 Hz, cis-JP-F ) 15 Hz). 31P NMR (CD2Cl2, -70 °C), δ: 8.4 (dq, trans-
JP-F ) 48 Hz, cis-JP-P ) 24 Hz, 1P); 12.6 (m, 1P). The -70 °C NMR
data is fully consistent with the cis solid-state structure.
(21) The anion [(Ph3P)Pd(CF3)3]- has been previously characterized.15a In the
structure of the [Ph4P]+ [(Ph3P)Pd(CF3)3]- from reaction 3, each CF3 group
is slightly disordered with iodide, with the percentages of CF3 being 84.3%
(trans to PPh3) and 93.2% and 89.1% (mutually trans). The sum of the
iodide and CF3 occupancies independently refined to 0.999, 1.003, and
0.997, indicating that each position is well represented by either CF3 or
iodide.
(22) Sakamoto, M.; Shimizu, I.; Yamamoto, A. Chem. Lett. 1995, 1101.
(23) Klingensmith, L. M.; Strieter, E. R.; Barder, T. E.; Buchwald, S. L.
Organometallics 2006, 25, 82.
(24) Grushin, V. V. Chem. Soc. ReV. 2000, 29, 315.
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