A phosphine-accelerated ArF-chloride bond activation process by palladium

Article abstract of DOI:10.1021/om400295p

We present a mechanistic study demonstrating selective Ar_f-Cl bond activation preceded by η² coordination of Pd(PEt ₃)₂ to a C=C moiety of a partially fluorinated substrate. An intramolecular ring-walking process to activate the Ar_f-Cl bond is plausible, but an intermolecular reaction becomes dominant in the presence of PEt₃. The latter pathway is significantly enhanced, since PEt ₃ promotes dissociation of Pd(PEt₃)₃ from the C=C moiety followed by activation of the Ar_f-Cl bond. Our observations also show that PEt₃ can be used to control reaction selectivity. The experimental observations are supported by density functional theory (DFT) calculations (at the SMD(toluene)-DSD-PBEP86/cc-pV(D+d)Z-PP//DF- PBE+d_v2/SDD(d) level of theory).

Full text of DOI:10.1021/om400295p

Article
pubs.acs.org/Organometallics
A Phosphine-Accelerated ArF−Chloride Bond Activation Process by
Palladium
Meital Orbach,† Olena V. Zenkina,† Yael Diskin-Posner,‡ Mark A. Iron,‡ and Milko E. van der Boom*,†
‡
†Department of Organic Chemistry and Department of Chemical Research Support, The Weizmann Institute of Science, 76100
Rehovot, Israel
S
* Supporting Information
ABSTRACT: We present a mechanistic study demonstrating
selective Arf−Cl bond activation preceded by η2 coordination of
Pd(PEt3)2 to a CC moiety of a partially fluorinated substrate.
An intramolecular ring-walking process to activate the Arf−Cl
bond is plausible, but an intermolecular reaction becomes
dominant in the presence of PEt3. The latter pathway is
significantly enhanced, since PEt3 promotes dissociation of
Pd(PEt3)3 from the CC moiety followed by activation of the
Arf−Cl bond. Our observations also show that PEt3 can be used to control reaction selectivity. The experimental observations are
supported by density functional theory (DFT) calculations (at the SMD(toluene)-DSD-PBEP86/cc-pV(D+d)Z-PP//DF-PBE
+dv2/SDD(d) level of theory).
oxidative addition of C−halides and many other bonds is well
known to involve unsaturated metal complexes.5,6,24−26 More-
over, we show that the addition of PEt3 to a reaction mixture
containing two different substrates significantly affects the
reaction selectivity. Our previous findings showed that the
reactions of analogous non-fluorinated substrates with plati-
num-group metals proceed independently of the phosphine
concentration.27−30 Therefore, the Arf moiety has an active role
in determining the reaction pathway and how the metal
fragment reaches the Arf−Cl bond.
INTRODUCTION
■
Metal-mediated functionalization of arenes in solution is one of
the most important classes of chemical reactions.1−4 Aryl
halides and alkenes/alkynes are frequently used as starting
materials in diverse cross-coupling reactions and many other
homogeneous catalytic processes selectively forming carbon−
carbon single bonds. Two key steps often are C−halide bond
activation by oxidative addition to a low-valent metal center and
metal−olefin coordination.3,5−11 In contrast to hydrocarbon
chemistry, the reactivity of fluorinated arenes with late
transition metals remains largely unexplored. Cross-coupling
reactions of fluorinated arenes (RC6F4-X; X = Cl, Br) compete
with substrate hydrodehalogenation.12−14 We recently showed
that this undesired process is caused by the use of nucleophilic
phosphines and the presence of adventitious water.15 The
formation of a relatively strong M−Arf σ-bond, after C−halide
oxidative addition, is another factor that hampers efficient
catalysis.13,16−19 Nevertheless, fluorinated arenes are frequently
used. For example, catalytic arylation, alkenylation, and
alkylation of polyfluoroarenes by C−H bond activation have
been reported.20−23
In this combined experimental and computational work, we
provide mechanistic insight into the reactivity of a partially
fluorinated substrate (1; Scheme 1) with Pd(PEt3)4. The use of
this stilbazole derivative allows us to study two competing
processes: η2 coordination and Arf−Cl bond activation. We
found that η2 coordination of Pd(PEt3)2 to a CC moiety is
kinetically favored and is followed by an irreversible Arf−Cl
bond activation. The latter step is likely to be rate determining.
Interestingly, the overall rate of this quantitative transformation
is strongly dependent on the PEt3 concentration. PEt3 enhances
the rate of the overall process without affecting the reaction
outcome. This effect is somewhat counterintuitive, since the
EXPERIMENTAL SECTION
■
General Procedures. All reactions were carried out in an N2-filled
M. Braun glovebox with O2 and H2O levels <2 ppm. Solvents were
reagent grade or better, dried, distilled, and degassed before being
introduced into the glovebox. Deuterated solvents were purchased
from Sigma−Aldrich and degassed with argon. Pd(PEt3)4 was
prepared according to a published procedure.31 Reaction flasks were
washed with deionized (DI) water followed by acetone and then oven-
dried prior to use. Mass spectrometry (MS) analyses were performed
on a Waters Micromass GCT Primer high-resolution (HR) mass
spectrometer. Elemental analyses were performed by H. Kolbe,
Mikroanalytisches Laboratorium, Germany.
Computational Methods. Calculations were performed using
Gaussian09 Rev. A.02 and C.01.32 Two density functional theory
(DFT) exchange-correlation functionals were used. The first is the
Perdew−Burke−Ernzerhof (PBE) generalized gradient approximation
(GGA) functional.33,34 This functional was used for geometry
optimizations and vibrational frequency calculations. The second is
the latest double-hybrid functional by Kozuch and Martin: DSD-
PBEP86.35 This double-hybrid functional incorporates the Perdew−
Burke−Ernzerhof (PBE)33,34,36 DFT exchange functional with “exact”
Received: April 8, 2013
Published: May 14, 2013
© 2013 American Chemical Society
3074
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
Hartree−Fock exchange, the Perdew−86 correlation functional37 with
H, 2.12. HRMS (FD-TOF): m/z calcd for C13H6ClF4N 287.0125,
found 287.0131.
“exact” spin component scaled38,39 second-order Møller−Plesset40
(SCS-MP2) correlation, and an empirical dispersion correction41−44
−
Formation of Complex 2. A benzene solution (0.35 mL) of
Pd(PEt3)4 (5.4 mg, 9.3 μmol) was added to a benzene solution (0.35
mL) of compound 1 (2.4 mg, 8.3 μmol). Removal of all volatiles under
vacuum for ∼5 h at 195 K resulted in quantitative formation of
complex 2 as an oily residue, which is stable in C6D6 at 283 K for at
least 14 h. 1H NMR (C6D6): δ 8.46 (br d, 3JHH = 5.6 Hz, 2H, Pyr-H),
specifically Grimme’s third version of his empirical dispersion
correction (DFTD3)41,45 with Becke−Johnson (BJ) dampening.45−47
Two basis set−RECP (relativistic effective core potential)
combinations were used. The first, denoted SDD(d), is the
combination of the Huzinaga−Dunning double-ζ basis set48 on lighter
elements with the Stuttgart−Dresden basis set−RECP combination49
on transition metals; polarization functions (i.e., the D95(d) basis set)
were added to second-row (i.e., phosphorus) atoms. The second is cc-
pV(D+d)Z-PP, which includes Dunning’s cc-pVDZ50 on the main-
group elements (Wilson’s cc-pV(D+d)Z51 modification on phospho-
rus) and Peterson’s cc-pVDZ-PP basis set−RECP52 on palladium.
Geometry optimization and vibrational frequency analyses were
carried out using the former basis set, while the energetics of the
reactions were calculated at these geometries with the latter basis set.
The accuracy of the DFT method was improved by adding the
empirical dispersion correction as recommended by Grimme.41,43 The
older version (DFTD2)43 is available, with analytical gradients and
Hessians, in Gaussian09 and was used during geometry optimizations
and frequency calculations. As noted above, DSD-PBEP86 includes,
per definition, a DFTD3 correction with BJ scaling in its functional
form, which was calculated using a program written by Grimme.41
Bulk solvent effects were approximated by single-point energy
calculations using a polarizable continuum model (PCM),53−56
specifically the integral equation formalism model (IEF-PCM)55−58
with toluene as the solvent as in the experiments. Specifically, Truhlar
and co-workers’ empirically parametrized Solvation Model−Dispersion
(SMD)59 was used. Because the transition states were found to have
relatively small imaginary frequencies, the “ultrafine” (i.e., a pruned
(99,590)) grid was used throughout the calculations.
3
6.88 (br d, JHH = 4.6 Hz, 2H, Pyr-H), 4.66 (m, 2H, η2-CHCH),
1.07 (m, 12H, PCH2CH3), 0.67 (m, 18H, PCH2CH3). 13C{1H} NMR
(C6D6): δ 154.21 (m, Cq, C-Pyr), 149.91 (d, C-Pyr), 145.53 (m, Cq,
CF), 144.72 (m, Cq, CF), 143.59 (m, Cq, CF), 142.79 (m, Cq, CF),
135.29 (m, Cq, C-Arf), 125.66 (m, Cq, CCl), 119.18 (d, 4JPC = 2.1 Hz,
2
2
3
C-Pyr), 58.23 (m, JPC = 26.4 Hz, JPC = 10.2 Hz, JFC = 6.2 Hz, η2-
CHCH), 46.28 (br d, 2JPC = 26.8 Hz, η2-CHCH), 18.97 (dd, 1JPC
= 14.7 Hz, 3JPC = 1.8 Hz, PCH2CH3), 18.11 (dd, 1JPC = 14.5 Hz, 3JPC
1.6 Hz, PCH2CH3), 8.44 (d, 2JPC = 2.9 Hz, PCH2CH3), 8.33 (d, 2JPC
=
=
=
2.6 Hz, PCH2CH3). 19F{1H} NMR (C6D6): δ −144.53 (br d, JFF
3
19.4 Hz, 2F), −145.82 (dd, 3JFF = 20.8 Hz, 5JPF = 6.1 Hz, 2F). 31P{1H}
NMR (C6D6): δ 14.73 (d, 2JPP = 8.5 Hz, 1P), 11.98 (br m, 1P). HRMS
(FD-TOF): m/z calcd for C25H36ClF4NP2Pd 631.0982, found
631.0992.
Formation of Complex 3. A THF solution (5 mL) of Pd(PEt3)4
(16 mg, 27 μmol) was added to a THF solution (5 mL) of
2′,3′,4′,5′,6′-pentafluorostilbazole (4; 6.7 mg, 25 μmol) at room
temperature. The formation of complex 3 was observed after 5 min by
31P{1H} NMR spectroscopy. Complex 3 was isolated as an orange oil
by removing all volatiles under vacuum (>95%). Colorless crystals
suitable for X-ray analysis were obtained from slow evaporation of a
C6D6 solution of complex 3 at room temperature. 1H NMR (C6D6): δ
8.45 (dd, 3JHH = 4.5 Hz, 4JHH = 1.5 Hz, 2H, Pyr-H), 6.89 (d, 3JHH = 4.7
Hz, 2H, Pyr-H), 4.61 (m, 2H, η2-CHCH), 1.09 (m, 12H,
PCH2CH3), 0.69 (m, 18H, PCH2CH3). 13C{1H} NMR (C6D6): δ
154.26 (m, Cq, C-Pyr), 149.91 (s, C-Pyr), 144.61 (m, Cq, CF), 142.70
(m, Cq, CF), 139.17 (m, Cq, CF), 137.30 (m, Cq, CF), 135.43 (m, Cq,
Spectroscopic Analysis. The 1H, 13C{1H}, 19F{1H}, and 31P{1H}
NMR spectra were recorded at 500.13, 125.77, 470.52, and 202.46
MHz on a Bruker Avance 500 NMR spectrometer or at 400.13,
100.62, 376.45, and 161.97 MHz on a Bruker Avance 400 NMR
2
CF), 121.73 (m, Cq3, C-Arf), 119.13 (s, C-Pyr), 58.38 (m, JPC = 26.2
2
2
Hz, JPC = 6.1 Hz, JPF = 4.4 Hz, η2-CHCH), 44.07 (br d, JPC
=
1
spectrometer, respectively. In addition, the H, 19F{1H}, and 31P{1H}
27.8 Hz, η2-CHCH), 19.19 (d, JPC = 14.4 Hz, PCH2CH3), 18.31
1
NMR spectra were also recorded at 300.13, 282.36, and 121.50 MHz,
respectively, on a Bruker Avance 300 NMR spectrometer. All chemical
shifts (δ) are reported in ppm, and coupling constants (J) are in Hz.
The 1H, 13C{1H} and 13C-DEPTQ60 NMR chemical shifts were
calibrated using residual solvent peaks. The 31P{1H} NMR chemical
shifts were calibrated using an external reference sample of 85%
H3PO4 in D2O. The 19F{1H} NMR chemical shifts were calibrated
using an external reference sample of C6F6 in CDCl3 (δ −163 ppm).
Ph3PO was used as an internal standard in follow-up experiments.
Assignments in the 1H and 13C{1H} NMR spectra were aided by
1H{31P} and 13C-DEPT-135 NMR spectroscopy. All NMR measure-
ments were carried out at 298 K unless stated otherwise.
Preparation of 4′-Chloro-2′,3′,5′,6′-tetrafluorostilbazole (1).
4-Chloro-2,3,5,6-tetrafluorobenzaldehyde (2.43 g, 11.5 mmol) and γ-
picoline (1.1 mL, 12 mmol) in 10 mL of acetic anhydride were stirred
at room temperature under argon for 60 h. The reaction mixture
turned black, and a precipitate formed during this time period.
Subsequently, the mixture was poured into water at 273 K and was
basified to pH 8−9 by addition of a 15% aqueous solution of Na2CO3.
The crude product was extracted with dichloromethane (3 × 50 mL),
the combined fractions were dried (Na2SO4) and filtered, and the
resulting solution was treated with decolorizing charcoal overnight.
Filtration over Celite and evaporation of the solvent yielded a yellow
oil (1.1 g, 32% yield). An off-white solid formed upon addition of
1
2
(d, JPC = 14.3 Hz, PCH2CH3), 8.44 (d, JPC = 2.9 Hz, PCH2CH3),
8.34 (d, 2JPC = 2.5 Hz, PCH2CH3). 19F{1H} NMR (C6D6): δ −145.50
(br d, 3JFF = 22.5 Hz, 2F), −166.18 (dt, 3JFF = 21.9 Hz, 3JFF = 5.3 Hz,
2F), −167.21 (t, JFF = 21.1 Hz, 1F). 31P{1H} NMR (C6D6): δ 14.87
3
2
2
5
(d, 1P, JPP = 10.4 Hz), 11.70 (m, 1P, JPP = 9.8 Hz, JPF = 4.6 Hz).
HRMS (FD-TOF): m/z calcd for C25H36F5NP2Pd 613.1288, found
613.1286.
X-ray Analysis of Complex 3. Crystal data: C25H36F5NP2Pd,
colorless prisms, 0.15 × 0.08 × 0.05 mm3, triclinic, space group P1, a =
̅
11.8580(5) Å, b = 16.1553(6) Å, c = 16.4658(6) Å, α = 66.663(2)°, β
= 75.207(2)°, γ = 79.340(2)°, T = 100(2) K, V = 2787.78(19) Å3, Z =
4, formula weight 613.88, Dc = 1.463 Mg m−3, μ = 0.827 mm−1. Data
collection and processing: Bruker APEX−II KappaCCD diffractom-
eter, Mo Kα (λ = 0.71073 Å) with MiraCol optics, 43894 reflections
collected, 12416 independent reflections (Rint = 0.045), −15 ≤ h ≤ 15,
−20 ≤ k ≤ 20, −20 ≤ l ≤ 21, 2θmax = 55.02°, frame scan width 0.5°,
scan speed 1.0° per 60 s, typical peak mosaicity 0.68°. The data were
processed with Bruker APEX-II. Solution and refinement: structure
solved by SHELXS-97,61 full-matrix least-squares refinement based on
F2 with SHELXL-97, 700 parameters with 0 restraints, final R1
=
0.0436 for data with I > 2σ(I) and R1 = 0.0785 on 12416 reflectionss,
goodness of fit on F2 1.041, largest electron density peak 1.417 e Å−3,
and largest electron density hole −1.164 e Å−3. Selected bond lengths
(Å) and angles (deg): C(1)−C(7) = 1.469(5), Pd(1)−C(7) =
2.121(3), Pd(1)−C(8) = 2.130(4), Pd(1)−P(1) = 2.3139(10),
Pd(1)−P(2) = 2.3044(11), C(7)−C(8) = 1.439(5); C(8)−Pd(1)−
P(2) = 107.55(10), C(7)−Pd(1)−C(8) = 39.57(14), C(7)−Pd(1)−
P(1) = 105.50(10), C(7)−Pd(1)−P(2) = 146.77(10), P(2)−Pd(1)−
P(1) = 107.50(4).
1
3
4
hexane. H NMR (CD2Cl2): δ 8.61 (br dd, JHH = 4.5 Hz, JHH = 1.6
Hz, 2H, Pyr-H), 7.41 (br d, 2H, Pyr-H), 7.34 (AB, 3JHH = 16.6 Hz, 2H,
CHCH). 13C{1H} NMR (CDCl3): δ 149.8 (s, C-Pyr), 146.1 (m, Cq,
CF), 145.5 (m, Cq, CF), 144.1 (s, Cq, C-Pyr), 143.6 (m, Cq, CF),
3
143.0 (m, Cq, CF), 134.7 (t, JFC = 8.3 Hz, CHCH), 121.2 (s, C-
2
Pyr), 118.0 (m, HCCH), 114.5 (t, Cq, JFC = 13.1 Hz, CCl), 111.7
Formation of Complex 5. A THF solution (0.7 mL) of Pd(PEt3)4
(20.9 mg, 36.1 μmol) was slowly added to a THF solution (0.7 mL) of
compound 1 (10.5 mg, 36.5 μmol) at room temperature. The reaction
(m, Cq, C-Arf). 19F{1H} NMR (CDCl3): δ −142.01 (m, 4F). Mp: 142
°C. Anal. Calcd for C13H6ClF4N: C, 54.28; H, 2.10. Found: C, 54.36;
3075
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
Table 1. 31P{1H} NMR Follow-up Experiments of the
Conversion of Complex 2 to Complex 5
mixture was heated to 320 K for 2 h; thereafter, all volatiles were
removed under vacuum and the oily residue was washed with cold
pentane (233 K; 2 × 1.5 mL), yielding colorless platelike crystals
1
temp
(K)
conc of 2
(mM)
amt of PEt3
(equiv)
suitable for X-ray analysis (19.5 mg, 86% yield). H NMR (dioxane-
k (s−1
)
d8): δ 8.54 (d, 3JHH = 5.7 Hz, 2H, Pyr-H), 7.44 (d, 3JHH = 5.9 Hz, 2H,
Pyr-H), 7.33 (s, 2H, CHCH), 1.62 (m, 12H, PCH2CH3), 1.10 (m, J
= 8.0 Hz 18H, PCH2CH3). 13C{1H} NMR (dioxane-d8): δ 151.14 (s,
C-Pyr), 148.41 (m, Cq, CF), 146.13 (m, Cq, CF), 145.71 (m, Cq, CF),
entry
solvent
1
318
323
328
333
333
333
303
308
313
313
313
313
313
318
318
323
313
313
313
313
12
12
12
12
24
12
12
12
12
20
5.9
12
12
12
12
12
12
12
12
12
0
0
0
0
0
0
2
2
2
2
2
4
4
2
10
2
2
4
6
8
C6D6
C6D6
C6D6
C6D6
C6D6
THF
C6D6
C6D6
C6D6
C6D6
C6D6
C6D6
THF
C6D6
C6D6
C6D6
C6D6
C6D6
C6D6
C6D6
3.1 × 10−6
6.3 × 10−6
1.1× 10−5
1.7 × 10−5
1.9 × 10−5
1.6 × 10−5
1.5 × 10−5
2.1 × 10−5
3.4 × 10−5
6.3 × 10−5
1.5 × 10−5
8.7 × 10−5
9.6 × 10−5
4.8 × 10−5
3.0 × 10−4
8.4 × 10−5
4.5 × 10−5
7.9 × 10−5
1.2 × 10−4
1.7 × 10−4
2
3
3
144.80 (s, Cq, C-Pyr), 143.28 (m, Cq, CF), 132.56 (t, JFC = 8.4 Hz,
4
CHCH), 121.26 (s, C-Pyr), 120.00 (s, CHCH), 111.92 (t, Cq,
5
1
2JPC = 13.9 Hz, CPd), 14.97 (t, JPC = 13.7 Hz, PCH2CH3), 8.01 (br,
6
PCH2CH3). The Cq of the Arf group was not observed. 19F{1H} NMR
7
4
(dioxane−d8): δ −117.44 (m, 2F), −145.27 (m, JFF = 13.2 Hz, 2F).
8
31P{1H} NMR (dioxane-d8): δ 22.81 (t, 4JPF = 5.0 Hz, 2P). Anal. Calcd
for C25H36ClF4NP2Pd: C, 47.63; H, 5.76; N, 2.22. Found: C, 47.57; H,
5.80; N, 2.20. HRMS (FD-TOF): m/z calcd for C25H36ClF4NP2Pd
631.0987, found 631.0988.
9
10
11
12
13
14
15
16
17
18
19
20
X-ray Analysis of Complex 5. Crystal data: C25H36ClF4NP2Pd,
colorless plates, 0.3 × 0.15 × 0.05 mm3, orthorhombic, space group
Pbca, a = 13.3124(4) Å, b = 11.0447(6) Å, c = 38.6137(16) Å, T =
120(2) K, V = 5677.5(4) Å3, Z = 8, formula weight 630.34, Dc = 1.475
Mg m−3, μ = 0.901 mm−1. Data collection and processing: Nonius
KappaCCD diffractometer, Mo Kα (λ = 0.71073 Å), 23205 reflections
collected, 7077 independent reflections (Rint = 0.086), 0 ≤ h ≤ 16, 0 ≤
k ≤ 13, 0 ≤ l ≤ 46, 2θmax = 51.36°, frame scan width 0.8°, scan speed
1.0° per 20 s, typical peak mosaicity 0.3570°. The data were processed
with Denzo-Scalepack. Solution and refinement: structure solved by
SHELX-97,61 full-matrix least-squares refinement based on F2 with
SHELX-97, 313 parameters with 0 restraints, final R1 = 0.0498 (based
on F2) for data with I > 2σ(I) and R1 = 0.1084 on 5318 reflections,
goodness of fit on F2 0.989; largest electron density peak 1.959 e Å−3.
Selected bond lengths (Å) and angles (deg): Pd(1)−Cl(3) =
2.3596(13), Pd(1)−P(2) = 2.3071(14), Pd(1)−P(4) = 2.3231(13),
Pd(1)−C(5) = 2.007(5); C(5)−Pd(1)−P(4) = 92.77(13), C(5)−
Pd(1)−P(2) = 92.11(13), C(5)−Pd(1)−Cl(3) = 177.54(15), P(2)−
Pd(1)−P(4) = 174.07(5); C(10)−C(15) = 1.466(7), C(17)−C(16) =
1.487(7), C(16)−C(15) = 1.304(7). The torsion angle between the
pyridine ring and the Arf ring is 5.52°. The coordination of the metal
center does not disrupt the aromatic system: the Pyr−C, Arf−C, and
CC bond lengths are 1.487(7), 1.466(7), and 1.304(7) Å,
respectively.
(b) The reaction progress was monitored at 313 K with different
concentrations of 2 (5.9 and 20 mM).
(c) The reaction was monitored with complex 2 (8.8 mg, 14 μmol)
and different concentrations of PEt3: at 313 K with 4 equiv of PEt3 in
C6D6 or in THF, and at 318 K with 10 equiv of PEt3 in C6D6. In all
cases, no intermediates were observed. Ph3PO was used as an internal
standard. The data is summarized in Table 1 (entries 7−16).
(d) The reaction 2 → 5 was monitored by 31P{1H} NMR
spectroscopy at 313 K in the presence of 2−8 equiv of PEt3. A solution
of complex 2 (5.4 mg, 8.6 μmol) in 0.7 mL of C6D6 (12 mM) was
loaded into a 5 mm screw-cap NMR tube and inserted into a
preheated NMR probe. Selective formation of complex 5 and the
concurrent disappearance of complex 2 were observed. In all cases, no
intermediates were observed. Ph3PO was used as an internal standard.
The data is summarized in Table 1 (entries 17−20).
Formation of Complex 8. A THF solution (0.5 mL) of Pd(PEt3)4
(34.7 mg, 60.0 μmol) was slowly added to a THF solution (0.7 mL) of
C6F5Cl (7; 12 mg, 59 μmol) at room temperature. The reaction
mixture was heated to 313 K for 2.5 h; thereafter, all volatiles were
removed under vacuum and the residue was washed with cold pentane
(233 K; 2 × 1.5 mL). This complex has been reported by Goggin and
Goodfellow.62 1H NMR (C6D6): δ 1.34 (m, 15H, PCH2CH3), 0.82
(m, 18H, PCH2CH3). 19F{1H} NMR (C6D6): δ −114.60 (m, 2F),
Thermolysis of Complex 2 in the Presence of nBu4NBr. A
THF solution (0.7 mL) of complex 2 (5.3 mg, 8.4 μmol) was added to
nBu4NBr (2.7 mg, 8.4 μmol). 31P{1H} NMR spectroscopy showed the
presence of complex 5 (74%) and complex 6 (the bromo-derivative of
complex 5) (26%) after heating the reaction mixture at 313 K for 4
days. Complex 6 was identified by the addition of an authentic sample.
3
n
−160.80 (t, JFF = 20.39 Hz, 1F), −162.86 (m, 2F). 31P{1H} NMR
The reaction of complex 5 with Bu4NBr under identical conditions
(C6D6): δ 19.74 (m, 2P).
afforded the same ratio of complexes 5 and 6.
31P{1H} NMR Follow-up Experiment of the Formation of
Complex 5 from Complex 2. (a) The reaction 2 → 5 was
monitored by 31P{1H} NMR spectroscopy at 318, 323, 328, and 333
K. A solution of complex 2 (5.4 mg, 8.6 μmol) in 0.7 mL of C6D6 (12
mM) was loaded into a 5 mm screw-cap NMR tube and inserted into a
preheated NMR probe. Selective formation of complex 5 and the
concurrent disappearance of complex 2 were observed.
Thermolysis of Complex 2 in the Presence of nBu4NBr and 2
equiv of PEt3. A THF solution (0.7 mL) of complex 2 (5.3 mg, 8.4
μmol) and PEt3 (2.5 μL, 2.0 mg, 17 μmol) was added to nBu4NBr (2.7
mg, 8.4 μmol). 31P{1H} NMR spectroscopy showed the presence of
complex 5 (79%) and complex 6 (21%) after heating the reaction
mixture at 313 K for 4 days. Complex 6 was identified by the addition
n
of an authentic sample. The reaction of complex 5 with Bu4NBr
under identical conditions afforded the same ratio of complexes 5 and
6.
(b) The reaction progress was monitored at 333 K with a different
concentration of 2 (24 mM) and in a different solvent (THF). In all
cases, no intermediates were observed. Ph3PO was used as an internal
standard. The data is summarized in Table 1 (entries 1−6).
In Situ 31P{1H} NMR Follow-up Experiments of the
Formation of Complex 5 from Complex 2 in the Presence of
PEt3. (a) The reaction 2 → 5 was monitored by 31P{1H} NMR
spectroscopy at 303, 308, 313, 318, and 323 K. A solution of complex
2 (8.8 mg, 14 μmol) and PEt3 (3.3 mg, 28 μmol) in 1.1 mL of C6D6
was loaded into a 5 mm screw-cap NMR tube and inserted into the
preheated NMR probe. Selective formation of complex 5 and the
concurrent disappearance of complex 2 were observed.
Competition Experiments with Complex 2 and C6F5Cl in
C6D6. (a) A C6D6 solution (0.35 mL) of complex 2 (1.3 mg, 2.1 μmol)
was added to a C6D6 solution (0.35 mL) of C6F5Cl (0.21 mg, 1.0
μmol). 19F{1H} NMR spectroscopy showed the presence of complexes
5 and 8 in a ratio of 3.8:1 after heating the reaction mixture at 313 K
for 14 days.
(b) This reaction was also performed at a higher concentration of
both complex 2 and C6F5Cl: a C6D6 solution (0.35 mL) of complex 2
(5.3 mg, 8.4 μmol) was added to a C6D6 solution (0.35 mL) of C6F5Cl
(0.90 mg, 4.4 μmol). 19F{1H} NMR spectroscopy showed the
3076
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
a
Scheme 1. Selective η2−CC Coordination of Pd(PEt3)2 to Compounds 1 and 4
a
Thermolysis of complex 2 in C6D6 at 320 K results in the quantitative formation of complex 5 by Arf−Cl bond activation. Complex 3 is stable under
these conditions.
Figure 1. ORTEP views of complexes 3 (left) and 5 (right) with thermal ellipsoids set at the 50% probability level. Hydrogen atoms are omitted for
clarity. Colors are as follows: black, C; red, Pd; orange, P; green, Cl; pink, F; blue, N. Selected bond lengths and angles are provided in the
Experimental Section.
presence of complexes 5 and 8 in a ratio of 3.7:1 after heating the
reaction mixture at 313 K for 14 days.
(Scheme 1). Complex 3 was isolated and characterized by
NMR spectroscopy, HRMS, and single-crystal X-ray analysis
(Figure 1). Complexes 2 and 3 exhibit similar NMR chemical
shifts. Similar spectral features were also observed for
structurally related Ni, Pd, and Pt complexes.15,27−30
(c) This reaction was also performed in the presence of 2 equiv of
PEt3: a C6D6 solution (0.35 mL) of complex 2 (1.3 mg, 2.1 μmol) and
PEt3 (0.60 μL, 0.48 mg, 4.1 μmol) was added to a C6D6 solution (0.35
mL) of C6F5Cl (0.21 mg, 1.0 μmol). 19F{1H} NMR spectroscopy
showed the presence of complexes 5 and 8 in a ratio of 1.2:1 after
heating the reaction mixture at 313 K for 3 days. About 10% of
complex 2 was still present in the reaction mixture after 14 days (a, b)
and after 3 days (c).
Prolonged reaction times and the use of elevated temper-
atures (303−333 K) resulted in the quantitative transformation
of complex 2 into complex 5 by metal insertion into the Arf−Cl
bond (∼9 h at 323 K in C6D6). Interestingly, removal of the
volatiles under vacuum at room temperature resulted also in the
formation of complex 5 (98%) after 2 h. Only traces of complex
2 (2%) were observed, as indicated by 1H, 19F{1H}, and
31P{1H} NMR spectroscopy. This unexpected rate-enhance-
ment might be caused by an increased concentration of 2 and/
or PEt3 (although the latter compound is expected to readily
evaporate). In contrast, a reaction mixture of complex 2 and
PEt3 exposed to 1 atm of N2 contained mainly unreacted
complex 2 (85%) after 2 h. The addition of an 8-fold excess of
PEt3 to the reaction mixture containing complex 2 and 2 equiv
of PEt3 at 318 K resulted in a 6-fold increase of the reaction
rate. This significant effect clearly demonstrates that PEt3 plays
an active role prior to or during the rate-determining step.
Complex 2 was isolated at 195 K by vacuum removal of PEt3
and benzene. Evidently, selective η2 coordination of Pd(PEt3)2
to the carbon−carbon double bond of compound 1 is
kinetically favored over the formation of complex 5.
RESULTS AND DISCUSSION
■
The reaction of an equimolar amount of Pd(PEt3)4 with 4′-
chloro-2′,3′,5′,6′-tetrafluorostilbazole (1) in C6D6 at room
temperature for 5 min resulted in the quantitative formation of
complex 2 (Scheme 1). Complex 2 was characterized in situ in
the presence of 2 equiv of PEt3 by H, H{31P}, 13C{1H},
19F{1H}, and 31P{1H} NMR spectroscopy and high-resolution
mass spectrometry (HRMS). Assignment of the 13C{1H} NMR
data was made with the aid of 13C-DEPT-135 NMR
spectroscopy. The η2 coordination of the central CC moiety
of compound 1 to the zerovalent metal center is clearly
1
1
1
observed by H, 13C{1H}, and 31P{1H} NMR spectroscopy.
The 1H NMR spectrum has a characteristic multiplet at δ ∼4.6
ppm, and the 1H{31P} NMR spectrum has a corresponding AB
system. The 13C{1H} spectrum contains typical signals at δ 46.3
2
2
ppm (d, JPC = 26.8 Hz) and 58.2 ppm (m, JPC = 26.4 Hz).
The 31P{1H} NMR spectrum displays two peaks, a broad signal
at δ 11.9 ppm and a doublet at 14.7 ppm with a coupling
constant of 2JPP = 8.5 Hz, indicating that the two cis phosphorus
atoms are magnetically nonequivalent. The molecular structure
of complex 2 was also confirmed by the preparation of the
analogous complex 3 (lacking the Arf−Cl moiety). The reaction
of an equimolar amount of Pd(PEt3)4 and 2′,3′,4′,5′,6′-
pentafluorostilbazole (4) in THF at room temperature for 5
min resulted in the quantitative formation of complex 3
1
The thermodynamic product 5 was characterized by H,
13C{1H}, 19F{1H}, and 31P{1H} NMR spectroscopy, HRMS,
and elemental analysis (C, H, N). This new Pd(II) complex (5)
was isolated by the removal of the volatiles under vacuum
followed by washing the solid residue with cold pentane (233
K). The 13C{1H} NMR spectrum of 5 lacks the multiplet
resonance of the C(Arf)−Cl moiety at δ 125.6 ppm. Instead, a
2
new triplet resonance is observed at δ 111.9 ppm with JPC
=
13.9 Hz, indicating the presence of a σ-bound Pd−Cipso moiety
3077
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
a
Scheme 2. Possible Pathways for the Formation of Complex 5 from Complex 2
a
Compound 1, Pd(PEt3)2 and A were not observed by 31P{1H} NMR spectroscopy during the reaction.
coupled by two mutually trans phosphorus atoms. Moreover, in
the 31P{1H} NMR spectrum there is a triplet resonance at δ
4
22.8 ppm with JPF = 5.0 Hz, corresponding to the two
magnetically equivalent phosphorus atoms. The structure of
complex 5 was further confirmed by single-crystal X-ray
analysis. Single crystals were obtained by crystallization of
complex 5 from pentane (Figure 1). The complex has a square-
planar geometry around the d8 metal center. The angle between
the two trans phosphorus atoms is 174.07°, and the C(5)−
Figure 3. (A) In situ variable-temperature 31P{1H} NMR spectroscopy
follow-up measurements of the conversion of complex 2 to complex 5
in C6D6 ([2] = 12 mM) in the presence of 2 equiv of PEt3. (B) The
corresponding Eyring plot; R2 = 0.985.
Pd(1)−Cl(3) angle is 177.54°.
Mechanistically, the transformation of complex 2 to complex
5 may proceed via Pd(PEt3)2 dissociation followed by
activation of the Arf−Cl bond or alternatively via an
intramolecular ring-walking process (Scheme 2).27−30,63−75
No intermediates were observed by 31P{1H} NMR spectros-
copy during the reaction.
entropy values, ΔS⧧, suggest that stilbazole (1) dissociation is
not the rate-determining step. These values might be consistent
with an intramolecular (ring-walking) process.27−30,63−75 The
difference in the entropy and enthalpy values (ΔΔS⧧ ≈ −17 eu
and ΔΔH⧧ = −7 kcal/mol) suggest different transition states.
We have communicated that reacting Pd(PEt3)4 and the Br
derivative of compound 1 results within 5 min at room
temperature in the activation of the Arf−Br bond.15 The η2
coordination complex was not observed, suggesting that in the
current system (2 → 5) the Arf−Cl bond activation step is rate-
determining.
The transformation 2 → 5, starting from isolated 2, was
monitored by variable-temperature (VT) 31P{1H} NMR
spectroscopy between 318 and 333 K. This transformation
follows first-order kinetics in complex 2 in C6D6 with ΔG⧧
=
298
26.4 1.6 kcal/mol, ΔH⧧ = 23.3 1.6 kcal/mol, and ΔS⧧ =
−10.4 5.1 eu (Figure 2). Monitoring this transformation in
The transformation 2 → 5, in the absence of PEt3, is not
affected by the concentration of complex 2 (12−24 mM; Figure
4A), which would be consistent with an intramolecular (ring-
walking) process.27−30,63−75 This hypothesis is in agreement
with the observed entropy value (ΔS⧧ = −10.4 5.1 eu). A
bimolecular pathway or a dissociative route is less likely.
However, this transformation (2 → 5) is significantly affected
by varying the starting concentration of 2 (5.9−20 mM) while
maintaining a constant 2:PEt3 ratio of 1:2 at the start of the
reaction. In particular, increasing the concentration of complex
2 from 5.9 to 20 mM increases kobs by ∼4.2 (Figure 4B).
Measuring the reaction rates of this transformation with varying
concentrations of phosphine, with constant [2], shows first-
order kinetics in the phosphine concentration (Figure 5).
These observations unambiguously demonstrate that PEt3
accelerates the overall process.
Figure 2. (A) In situ variable-temperature 31P{1H} NMR spectroscopy
follow-up measurements of the conversion of complex 2 to complex 5
in C6D6 ([2] = 12 mM). (B) The corresponding Eyring plot; R2 =
0.985.
the presence of 2 equiv of PEt3 between 303 and 323 K also
shows first-order kinetics and results in ΔG⧧ = 24.3 1.1
298
kcal/mol, ΔH⧧ = 16.0 1.1 kcal/mol, and ΔS⧧ = −27.8 1.6
eu (Figure 3). The transformation 2 → 5 is much faster in the
presence of PEt3 (t1/2 at 323 K is ∼24 h without PEt3 and ∼2.5
h with 2 equiv of PEt3); hence, slightly higher temperatures
were needed in the absence of PEt3. The negative activation
The solvent polarity (THF vs C6D6, dielectric constants εr =
7.5 and 2.3, respectively)76 did not affect the reaction kinetics
(Figure 6A; kTHF = 1.6 × 10−5 s−1 and kbenzene = 1.7 × 10−5 s−1).
3078
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
To better understand the reaction mechanism, the system
was studied using density functional theory (DFT) at the
SMD(toluene)-DSD-PBEP86/cc-pV(D+d)Z-PP//DF-PBE
+dv2/SDD(d) level of theory. Three potential pathways were
considered (Figure 7): (i) ring-walking (blue line), (ii) ligand
dissociation and oxidative addition of Arf−Cl by Pd(PEt3)2 (red
line), and (iii) coordination of a third phosphine followed by
stilbazole (1) dissociation and Arf−Cl oxidative addition by a
Pd(PEt3)3 species (green line).
The ring-walking pathway is similar to processes reported by
our group with non-fluorinated substrates and platinum and
nickel complexes.27−30 The first step is the transfer of the
Pd(PEt3)2 moiety from the central CC bond to the
fluorinated arene (S1 → S2). For this step, the transition
state TS(S1−S2) results in a barrier of ΔG⧧ = 17.5 kcal/mol.
The transition state was found but has an energy slightly lower
than S2 but is higher in energy at the level of theory used in the
optimization. This is likely an artifact of the composite method
used to evaluate the energy for cases such as these where there
is a very small barrier in one direction. Metal coordination to
the fluorinated arene is less favorable than to the central CC
bond (i.e., S2, ΔG298 = 17.5 kcal/mol, and S3, ΔG298 = 3.2
kcal/mol). Interestingly, S2 is significantly less stable than S3,
possibly due to increased steric interactions between the PEt3
ligands and the vinylpyridine fragment. The transition states for
ring-walking have been previously shown for various systems to
involve low barriers (<10 kcal/mol); the ring-walking transition
states for this system have not been found, but with PMe3
instead of PEt3 ligands, barriers of similar heights were
identified. TS(S3-S4) for the oxidative addition of the ring−
bound metal center results in a barrier of ΔG⧧ = 25.0 kcal/mol.
The computations suggest that the ring-walking pathway is
for the most part higher in energy than the Pd(PEt3)2 ligand
dissociation pathways ii and iii. Stilbazole (1) dissociation (S1
→ S5; Figure 7, red line) has a reaction energy of ΔG298 = 12.6
kcal/mol, and TS(S1-S5)80 results in a barrier of ΔG⧧ = 13.9
kcal/mol. The subsequent oxidative addition of Pd(PEt3)2
involves an intermediate where the metal fragment is
coordinated to the CCl−Cmeta bond of the phenyl ring prior
to oxidative addition (S3), and the associated TS would be
indistinguishable from TS(S3−S4) for oxidative addition in the
ring-walking pathway (blue line).
Figure 4. 31P{1H} NMR follow-up measurements of the thermolysis
of complex 2 in C6D6: (A) at 333 K with (a) [2] = 12 mM, k = 1.7 ×
10−5 s−1, R2 = 0.986 and (b) [2] = 24 mM, k = 1.9 × 10−5 s−1, R2 =
0.997. (B) in the presence of 2 equiv of PEt3 at 313 K with (a) [2] =
5.9 mM, kobs = 1.5 × 10−5 s−1, R2 = 0.988, (b) [2] = 12 mM, kobs = 3.4
× 10−5 s−1, R2 = 0.984, and (c) [2] = 20 mM, kobs = 6.3 × 10−5 s−1, R2
= 0.993.
Figure 5. (A) In situ 31P{1H} NMR follow-up measurements of the
transformation of complex 2 to complex 5 with different
concentrations of PEt3 at 313 K with [2] = 12 mM, x equiv of PEt3
in C6D6: (a) x = 2, k = 4.5 × 10−5 s−1, R2 = 0.995; (b) x = 4, k = 7.9 ×
10−5 s−1, R2 = 0.996; (c) x = 6, k = 1.2 × 10−4 s−1, R2 = 0.997; (d) x =
8, k = 1.7 × 10−4 s−1, R2 = 0.997. (B) Plot of initial rate vs [PEt3]
showing first-order dependence on PEt3; R2 = 0.989.
Free phosphine can assist in Pd(PEt3)2 dissociation from the
central CC bond (green line). The reaction energy for
coordination of a third phosphine to the bridge-coordinated
palladium center is ΔG298 = 3.5 kcal/mol (S1 → S6).
Dissociation of the resulting Pd(PEt3)3 unit (S6 → S7) was
found to have a reaction energy of ΔG298 = −3.8 or −7.3 kcal/
mol with repect to S1 or S6, respectively. Pd(PEt3)3 is the
energetically favored species in solution, with phosphine
coordination and dissociation energies of ΔG298 = 10.5 and
16.4 kcal/mol, respectively. Thus, Pd(PEt3)3 can then remain in
solution until it finds an Arf−Cl bond to react with. Prior to
oxidative addition, a coordination complex S8, similar to S3, is
formed. The reaction barrier for this oxidative addition by
Pd(PEt3)3 was found to be ΔG⧧ = 12.5 kcal/mol (TS(S8-S9)).
While S1 has been isolated experimentally (2), the S7 → S1
step is slightly uphill. This effect is likely a result of the
sensitivity of the metal−π bond to the level of theory used. We
indicated two crossover points (Figure 7, dashed lines) that can
facilitate the overall process. In pathway ii, the palladium center
in S5 can add an additional phosphine to fall to a more stable
point on pathway iii (i.e., S7). Likewise, S3 on pathways i/ii is
Figure 6. In situ 31P{1H} NMR follow-up measurements of the
thermolysis of complex 2: (A) 333 K, [2] = 12 mM with (a) C6D6, k =
1.7 × 10−5 s−1, R2 = 0.986 and (b) THF, k = 1.6 × 10−5 s−1, R2 =
0.989; (B) 313 K, [2] = 12 mM + 4 equiv of PEt3 with (a) C6D6, k =
8.7 × 10−5 s−1, R2 = 0.996 and (b) THF, k = 9.6 × 10−5 s−1, R2 =
0.992.
Likewise, the reaction starting with a 2:PEt3 ratio of 1:4
proceeds with similar rate constants for these two different
solvents (e.g., kTHF/kbenzene ≈ 1.1 at 313 K, Figure 6B). Thus,
the rate-determining step (or a step prior to it) does not
involve charged species (i.e., an ionic transition state or a
Meisenheimer-type/SNAr attack of the metal center on the Arf
moiety).77,78 A concerted three-centered transition state or
electron transfer processes are more likely. The formation of
ionic chloride during the transformation 2 → 5 could not be
verified by the addition of nBu4NBr to the reaction
mixtures.28,79 Halide exchange was observed (5-Cl:5-Br ≈
3:1), but complex 5 undergoes similar halide exchange when
n
treated with Bu4NBr.
3079
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
Figure 7. Calculated profiles for the reaction of compound 1 with Pd(PEt3)4. Three possible pathways were considered: (i) ring-walking (blue line),
(ii) ligand dissociation and oxidative addition of Arf−Cl by Pd(PEt3)2 (red line), and (iii) coordination of a third PEt3 ligand followed by stilbazole
(1) dissociation and Arf−Cl oxidative addition by Pd(PEt3)3 (green line). The dotted lines indicate possible crossover points. The ring-walking
transition states on pathway i are estimated.
Figure 8. Competitive formation of complexes 5 and 8. The product distribution is phosphine dependent.
more stable than S8, as is the associated transition state. In the
absence of excess phosphine, route iii is unlikely (green line),
but a dissociation pathway (i.e., pathway ii) is still possible; in
addition, the ring-walking mechanism (i.e., pathway i) is still a
viable, competative route. However, when free phosphine is
present, the phosphine dissociation route iii is dominant.
Competition experiments were carried out by performing the
thermolysis of complex 2 in the presence of C6F5Cl (7, 0.5
equiv; Figure 8). This reaction results in the formation of both
complexes 5 and 8 in a ratio of ∼4:1. No concentration effect
(3.0 vs 12 mM) was observed, suggesting that a direct reaction
of complex 2 with compound 7 does not play a significant role.
The formation of complex 8 might result from (reversible)
Pd(PEt3)2 dissociation from 1 followed by trapping by the
added substrate (7). DFT calculations showed that ring-walking
and stilbazole (1) dissociation are competing pathways (Figure
7, vide supra). Performing the same reaction in the presence of
2 equiv of PEt3 also results in the formation of complexes 5 and
8. PEt3 enhances metal transfer from complex 2 to C6F5Cl (7),
as complexes 5 and 8 were formed in a 1:1 ratio. Metal transfer
was not observed between C6F5Cl (7) and complex 5 under
identical reaction conditions. The outcome of these competi-
tion experiments is in agreement with our DFT calculations
(Figure 7). Phosphine can readily coordinate to complex 2 to
promote the dissociation pathway. Our observations indicate
that phosphines can be used to control reaction selectivity with
fluorinated substrates.
SUMMARY AND CONCLUSIONS
■
Selective palladium η2 coordination to the CC moiety of 1 is
kinetically favored over oxidative addition of an Arf−Cl bond.
Our group previously demonstrated that activation of an Arf−
Br bond by Pt(0) is kinetically and thermodynamically favored
over η2 coordination of Pt(PEt3)2 to a CC moiety.81
Apparently, there is a fine balance between η2 coordination of
a metal center to a CC bond and metal insertion into an
Arf−halide bond. The transformation 2 → 5 most likely
involves both intra- and intermolecular pathways, and PEt3 is
not an innocent bystander (Figure 7). An intramolecular ring-
walking process coupled with bond activation is consistent with
the work of Braun, Perutz, and co-workers, who showed that
C−F oxidative addition of C10F8 by zerovalent nickel proceeds
via initial formation of η2 complexes.82−84 Subsequently, the
metal center migrates along the CC double bonds of the
perfluoroarene prior to C−F bond activation. We recently
3080
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
(9) Rodrg
́
uez, G.; Albrecht, M.; Schoenmaker, J.; Ford, A.; Lutz, M.;
demonstrated that structurally related non-fluorinated systems
undergo a ring-walking process.27−30,63−75 Such intramolecular
processes are concentration independent and are not affected
by an excess of PEt3. In this study, we showed that the Arf
moiety in combination with phosphine directs the formation of
complex 5 toward a distinctly different pathway. The overall
process (2 → 5) is enhanced by PEt3 by promoting a
dissociation/association pathway (Scheme 2). This rate
enhancement is counterintuitive, as C−halide oxidative
addition reactions generally require unsaturated and low-valent
metal complexes.5,6,24−26 Excess of PEt3 would be expected to
trap reactive and unsaturated complexes and slow down the
overall bond activation process. In contrast, DFT calculations
suggest the possibility that PdP3 species might activate the Arf−
Cl bond, which is unusual. Interestingly, our observations show
that PEt3 also enhances metal transfer between substrates and
therefore might be used to control reaction selectivity. Our
findings show that palladium-catalyzed reactions involving
unsaturated fluorinated compounds that suffer from substrate
and/or product inhibition might benefit from the addition of
nucleophilic phosphines. However, such phosphines also can
induce hydrodehalogenation of fluorinated arenes.15 These
findings and the mechanistic insight presented here may have
implications involving functionalization of fluorinated aryl
halides by platinum group metals.
Spek, A. L.; van Koten, G. J. Am. Chem. Soc. 2002, 124, 5127−5138.
(10) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009−
3066.
(11) Belt, S. T.; Helliwell, M.; Jones, W. D.; Partridge, M. G.; Perutz,
R. N. J. Am. Chem. Soc. 1993, 115, 1429−1440.
(12) Collings, J. C.; Burke, J. M.; Smith, P. S.; Batsanov, A. S.;
Howard, J. A. K.; Marder, T. B. Org. Biomol. Chem. 2004, 2, 3172−
3178.
́
(13) Albeniz, A. C.; Espinet, P.; Martín-Ruiz, B.; Milstein, D. J. Am.
Chem. Soc. 2001, 123, 11504−11505.
(14) Nguyen, P.; Yuan, Z.; Agocs, L.; Lesley, G.; Marder, T. B. Inorg.
Chim. Acta 1994, 220, 289−296.
(15) Orbach, M.; Choudhury, J.; Lahav, M.; Zenkina, O. V.; Diskin-
Posner, Y.; Leitus, G.; Iron, M. A.; van der Boom, M. E.
Organometallics 2012, 31, 1271−1274.
(16) Sgarbossa, P.; Scarso, A.; Strukul, G.; Michelin, R. A.
Organometallics 2012, 31, 1257−1270.
́
(17) Clot, E.; Mergret, C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem.
Soc. 2009, 131, 7817−7827.
(18) Evans, M. E.; Burke, C. L.; Yaibuathes, S.; Clot, E.; Eisenstein,
O.; Jones, W. D. J. Am. Chem. Soc. 2009, 131, 13464−13473.
́
(19) Clot, E.; Besora, M.; Maseras, F.; Megret, C.; Eisenstein, O.;
Oelckers, B.; Perutz, R. N. Chem. Commun. 2003, 490−491.
(20) Sun, Z.-M.; Zhang, J.; Manan, R. S.; Zhao, P. J. Am. Chem. Soc.
2010, 132, 6935−6937.
(21) Kanyiva, K. S.; Kashihara, N.; Nakao, Y.; Hiyama, T.; Ohashi,
M.; Ogoshi, S. Dalton Trans. 2010, 39, 10483−10494.
(22) Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am.
Chem. Soc. 2008, 130, 16170−16171.
(23) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am.
Chem. Soc. 2006, 128, 8754−8756.
(24) Ribagnac, P.; Blug, M.; Villa-Uribe, J.; Le Goff, X.-F.; Gosmini,
ASSOCIATED CONTENT
* Supporting Information
■
S
CIF files giving crystallographic data for complexes 3 and 5 and
tables giving DFT optimized geometries (Cartesian coordi-
nates) of all calculated structures. This material is available free
of charge via the Internet at http://pubs.acs.org.
́
C.; Mezailles, N. Chem. Eur. J. 2011, 17, 14389−14393.
(25) Fu, G. C. Acc. Chem. Res. 2008, 41, 1555−1564.
(26) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366−
374.
AUTHOR INFORMATION
Corresponding Author
*E-mail for M.E.v.d.B.: milko.vanderboom@weizmann.ac.il.
■
(27) Zenkina, O. V.; Konstantinovski, L.; Freeman, D.; Shimon, L. J.
W.; van der Boom, M. E. Inorg. Chem. 2008, 47, 3815−3822.
(28) Zenkina, O. V.; Karton, A.; Freeman, D.; Shimon, L. J. W.;
Martin, J. M. L.; van der Boom, M. E. Inorg. Chem. 2008, 47, 5114−
5121.
Notes
The authors declare no competing financial interest.
(29) Zenkina, O.; Altman, M.; Leitus, G.; Shimon, L. J. W.; Cohen,
R.; van der Boom, M. E. Organometallics 2007, 26, 4528−4534.
(30) Strawser, D.; Karton, A.; Zenkina, O. V.; Iron, M. A.; Shimon, L.
J. W.; Martin, J. M. L.; van der Boom, M. E. J. Am. Chem. Soc. 2005,
127, 9322−9323.
ACKNOWLEDGMENTS
■
This research was supported by the Helen and Martin Kimmel
Center for Molecular Design. We thank Dr. J. Choudhury for
helpful discussions and Dr. L. J. W. Shimon for the X-ray
analysis of complex 3 (WIS). M.v.d.B is the incumbent of the
Bruce A. Pearlman Professorial Chair in Synthetic Organic
Chemistry.
(31) Schunn, R. A. Inorg. Chem. 1976, 15, 208−212.
(32) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.,
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09;
Gaussian, Inc., Wallingford, CT, 2011.
REFERENCES
■
(1) Hartwig, J. F. Organotransition Metal Chemistry: From Bonding to
Catalysis; University Science Books: Sausalito, CA, 2010.
́
(2) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874−922.
(3) van der Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103, 1759−
1792.
(4) Ohff, M.; Ohff, A.; van der Boom, M. E.; Milstein, D. J. Am.
Chem. Soc. 1997, 119, 11687−11688.
(5) Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. J. Am. Chem.
Soc. 2009, 131, 8141−8154.
(6) Lam, K. C.; Marder, T. B.; Lin, Z. Organometallics 2006, 26, 758−
760.
(33) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1997, 78,
(7) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176−
4211.
(8) Alcazar-Roman, L. M.; Hartwig, J. F. Organometallics 2002, 21,
1396−1396.
(34) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77,
3865−3868.
491−502.
3081
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082

Organometallics
Article
(35) Kozuch, S.; Martin, J. M. L. Phys. Chem. Chem. Phys. 2011, 13,
20104−20107.
(76) Lide, D. R., Ed. CRC Handbook of Chemistry and Physics, 87th
ed.; CRC Press: Boca Raton, FL, 2006−2007.
́
(77) Mucsi, Z.; Szabo, A.; Hermecz, I.; Kucsman, A.; Csizmadia, I. G.
(36) Adamo, C.; Barone, V. J. Chem. Phys. 1999, 110, 6158−6170.
(37) Perdew, J. P. Phys. Rev. B 1986, 33, 8822−8824.
(38) Szabados, Å. J. Chem. Phys. 2006, 125, 214105.
(39) Grimme, S. J. Chem. Phys. 2003, 118, 9095−9102.
(40) Møller, C.; Plesset, M. S. Phys. Rev. 1934, 46, 618−622.
(41) Grimme, S.; Antony, J.; Ehrlich, S.; Kreig, H. J. Chem. Phys.
2010, 132, 154104.
J. Am. Chem. Soc. 2005, 127, 7615−7631.
(78) Broxton, T. J.; Chung, R. P. T. J. Org. Chem. 1990, 55, 3886−
3890.
(79) Gossage, R. A.; van de Kuil, L. A.; van Koten, G. Acc. Chem. Res.
1998, 31, 423−431.
(80) TS(S1-S5) is a second-order saddle point and has a very small
second imaginary frequency (9i cm−1 corresponding to rotation of one
ethyl group) that could not be removed. The energy point is fairly flat,
and repeated geometry optimization to remove this second imaginary
vibrational frequency resulted in unrelated transition states.
(81) Lucassen, A. C. B.; Shimon, L. J. W.; van der Boom, M. E.
Organometallics 2006, 25, 3308−3310.
(42) Schwabe, T.; Grimme, S. Acc. Chem. Res. 2008, 41, 569−579.
(43) Schwabe, T.; Grimme, S. Phys. Chem. Chem. Phys. 2007, 9,
3397−3406.
(44) Grimme, S. J. Comput. Chem. 2006, 27, 1787−1799.
(45) Grimme, S.; Ehrlich, S.; Goerigk, L. J. Comput. Chem. 2011, 32,
1456−1465.
(46) Johnson, E. R.; Becke, A. D. J. Chem. Phys. 2006, 124, 174104.
(47) Johnson, E. R.; Becke, A. D. J. Chem. Phys. 2005, 123, 024101.
(48) Dunning Jr., T. H.; Hay, P. J. In Modern Theoretical Chemistry;
Plenum Press: New York, 1976; Vol. 3, pp 1−28.
(49) Dolg, M. Effective Core Potentials. In Modern Methods and
Algorithms of Quantum Chemistry; John von Neumann Institute for
(82) Braun, T.; Wehmeier, F. Eur. J. Inorg. Chem. 2011, 2011, 613−
625.
(83) Braun, T.; Cronin, L.; Higgitt, C. L.; McGrady, J. E.; Perutz, R.
N.; Reinhold, M. New J. Chem. 2001, 25, 19−21.
(84) Rhodium-catalyzed C−F bond activation of perfluorinated
arenes under mild reaction conditions has been demonstrated:
Aizenberg, M.; Milstein, D. Science 1994, 265, 359−361.
Computing: Julich, Germany, 2000; Vol. 1, pp 479−508.
̈
(50) Dunning, T. H., Jr. J. Chem. Phys. 1989, 90, 1007−1023.
(51) Wilson, A. K.; Woon, D. E.; Peterson, K. A.; Dunning, T. H., Jr.
J. Chem. Phys. 1999, 110, 7667−7676.
(52) Figgen, D.; Peterson, K. A.; Dolg, M.; Stoll, H. J. Chem. Phys.
2009, 130, 164108.
(53) Cossi, M.; Scalmani, G.; Rega, N.; Barone, V. J. Chem. Phys.
2002, 117, 43−54.
(54) Cossi, M.; Barone, V.; Mennucci, B.; Tomasi, J. Chem. Phys. Lett.
1998, 286, 253−260.
(55) Cances
3032−3041.
(56) Mennucci, B.; Tomasi, J. J. Chem. Phys. 1997, 106, 5151−5158.
(57) Tomasi, J.; Mennucci, B.; Cances, E. J. Mol. Struct.
(THEOCHEM) 1999, 464, 211−226.
(58) Mennucci, B.; Cances, E.; Tomasi, J. J. Phys. Chem. B 1997, 101,
10506−10517.
̀
, E.; Mennucci, B.; Tomasi, J. J. Chem. Phys. 1997, 107,
̀
̀
(59) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B
2009, 113, 6378−6396.
(60) Bigler, P.; Kummerle, R.; Bermel, W. Magn. Reson. Chem. 2007,
̈
45, 469−472.
(61) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112−122.
(62) Goggin, P. L.; Goodfellow, R. J. J. Chem. Soc. A 1966, 1462−
1466.
(63) Nebra, N.; Ladeira, S.; Maron, L.; Martin-Vaca, B.; Bourissou, D.
Chem. Eur. J. 2012, 18, 8474−8481.
(64) Tkachov, R.; Senkovskyy, V.; Komber, H.; Sommer, J.-U.; Kiriy,
A. J. Am. Chem. Soc. 2010, 132, 7803−7810.
(65) Yokozawa, T.; Yokoyama, A. Chem. Rev. 2009, 109, 5595−5619.
(66) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc. 2008,
130, 15258−15259.
(67) Siegel, J. S.; Baldridge, K. K.; Linden, A.; Dorta, R. J. Am. Chem.
Soc. 2006, 128, 10644−10645.
(68) Top, S.; Vessier
2006, 25, 3293−3296.
́
es, A.; Jaouen, G.; Fish, R. H. Organometallics
(69) Cadenbach, T.; Gemel, C.; Schmid, R.; Fischer, R. A. J. Am.
Chem. Soc. 2005, 127, 17068−17078.
(70) Harman, W. D. Coord. Chem. Rev. 2004, 248, 853−866.
(71) Iverson, C. N.; Lachicotte, R. J.; Muller, C.; Jones, W. D.
̈
Organometallics 2002, 21, 5320−5333.
́
(72) Carbo, J. J.; Eisenstein, O.; Higgitt, C. L.; Klahn, A. H.; Maseras,
F.; Oelckers, B.; Perutz, R. N. Dalton Trans. 2001, 1452−1461.
(73) Bach, I.; Porschke, K.-R.; Goddard, R.; Kopiske, C.; Kruger, C.;
̈
́
Rufinska, A.; Seevogel, K. Organometallics 1996, 15, 4959−4966.
(74) Nambu, M.; Mohler, D. L.; Hardcastle, K.; Baldridge, K. K.;
Siegel, J. S. J. Am. Chem. Soc. 1993, 115, 6138−6142.
(75) Stanger, A. Organometallics 1991, 10, 2979−2982.
3082
dx.doi.org/10.1021/om400295p | Organometallics 2013, 32, 3074−3082