Comparative structural analysis of biarylphosphine ligands in arylpalladium bromide and malonate complexes

Article abstract of DOI:10.1021/acs.organomet.6b00535

The substitution of biarylphosphine ligands was shown to have a marked impact on the α/β selectivity of the arylation of ester enolates. To get further insight into this effect, the solid-state structures of arylpalladium bromide and malonate complexes with four different biarylphosphine ligands were obtained by X-ray diffraction analysis. Structural differences were not very pronounced except for the conformationally restricted CPhos ligand, which showed a bidentate coordination mode in the oxidative addition complex, whereas the other ligands form dimeric species.

Full text of DOI:10.1021/acs.organomet.6b00535

Article
pubs.acs.org/Organometallics
Comparative Structural Analysis of Biarylphosphine Ligands in
Arylpalladium Bromide and Malonate Complexes
Anne-Sophie Goutierre, Huu Vinh Trinh, Paolo Larini, Rodolphe Jazzar, and Olivier Baudoin*,†
́ ́ ́
Universite Claude Bernard Lyon 1, CNRS UMR 5246 - Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, CPE
Lyon, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France
S
* Supporting Information
ABSTRACT: The substitution of biarylphosphine ligands was shown to
have a marked impact on the α/β selectivity of the arylation of ester
enolates. To get further insight into this effect, the solid-state structures of
arylpalladium bromide and malonate complexes with four different
biarylphosphine ligands were obtained by X-ray diffraction analysis.
Structural differences were not very pronounced except for the conforma-
tionally restricted CPhos ligand, which showed a bidentate coordination
mode in the oxidative addition complex, whereas the other ligands form
dimeric species.
better understanding thereof should have important implica-
tions for the development of new variants.4,5 Herein, we
describe a structural study of model biarylphosphine−
arylpalladium bromide and malonate complexes, which
represents a first step toward this goal.
INTRODUCTION
■
The achievement of catalyst-controlled site selectivity in
catalytic transformations is a topic of increasing interest.1
However, the rational design of selective catalysts is often
hampered by a lack of precise information on substrate−
catalyst interactions during the selectivity-determining step(s).
We have recently developed a Pd-catalyzed migrative arylation
of ester enolates2a−c and silyl ketene acetals,2d which allows
functionalization of remote C−H bonds of linear alkyl chains of
esters. In this process, the arylation selectivity was shown to be
both ligand and substrate controlled (Scheme 1). In particular,
RESULTS
■
Catalytic Reactions with Representative Biarylphos-
phines. The effect of four representative biarylphosphine
ligands on the selectivity of the arylation of the lithium enolate
of tert-butyl isobutyrate (1) with two different aryl bromides is
shown in Table 1. With m-fluorobromobenzene (2a) as the
electrophile, ligand L1 (DavePhos)6 furnished an α/β (3a/4a)
Scheme 1. α- vs β-Arylation of Ester Enolates
ratio of 47:53, in line with previous results (entry 1).2a,b
A
similar ratio was obtained with second-generation imidazole-
based ligand L2 (entry 2).2c,d Ligand L3,7 which is isosteric with
L1, significantly altered the α/β ratio in favor of α-arylated
product 3a (entry 3). CPhos L4, bearing two NMe2 groups on
the non-phosphine-containing ring,8 had a dramatic effect on
the selectivity, with 3a being exclusively obtained (entry 4).
This is consistent with the fact that this ligand was developed to
avoid Pd migration in Negishi-type cross-couplings. The same
overall trend was observed with aryl bromide 2b bearing two
strong electron-withdrawing CF3 groups at the meta positions
(entries 5−8). Indeed, ligands L1 and L2 bearing only one
NMe2 group mainly gave β-arylated product 4b (entries 5 and
6), whereas ligand L4 gave 3b as the major product (entry 8),
and ligand L3 was somewhat in between (entry 7). However,
the impact of the ligand on the arylation selectivity was less
pronounced for aryl bromide 2b in comparison to 2a, in line
by testing a number of analogous biarylphosphine ligands on
the arylation of isobutyric ester enolates (R1 = Me), we found
that the substitution pattern of the former had a great influence
on the arylation selectivity.2b Previous studies from Barder and
Buchwald demonstrated the effect of binding modes and
conformations of biarylphosphine ligands on elementary steps
of various cross-coupling reactions.3 Such effects are likely to
operate as well in migrative cross-coupling reactions; hence, a
Special Issue: Hydrocarbon Chemistry: Activation and Beyond
Received: July 1, 2016
© XXXX American Chemical Society
A
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Table 1. Effect of Representative Biarylphosphine Ligands
a
on the α/β Selectivity of the Arylation of Ester Enolates
a
Reaction conditions: 1 (1.6 equiv), Cy2NLi (1.7 equiv), aryl bromide
(1 equiv), Pd2dba3 (5 mol %), ligand (10 mol %), toluene, 50 °C.
b
Determined by 19F NMR.
with previous results. This is due to a higher degree of
substrate-controlled selectivity for aryl bromide 2b containing
two strongly electron withdrawing CF3 groups. Hence, the
nature and number of ortho substituents on the non-
phosphine-containing ring of ligands L1−L4 have a marked
effect on the arylation selectivity, thereby pointing to the
influence of electronic and/or conformational factors within the
Pd intermediates during the reaction. To further investigate
these effects, ligands L1−L4 were chosen for the preparation
and study of arylpalladium bromide and malonate complexes.
Synthesis and Characterization of Oxidative Addition
Complexes Containing Ligands L1−L4. Palladium com-
plexes A1−A4 were prepared in one step by addition of 2b to a
1:1 mixture of the appropriate ligand and (COD)Pd-
(CH2SiMe3)2 in THF at 20 °C, and they were isolated as
pure solids in reasonable yields (48−86%). Aryl bromide 2b
was chosen after initial investigations with 2a due to a higher
stability of the corresponding bromide and malonate complexes
(vide infra). Indeed, the strongly electron withdrawing CF3
substituents in 2b should stabilize the corresponding aryl−
palladium complexes by strengthening the CAr−Pd bond.2b,9
Suitable monocrystals of A1−A3 were readily obtained from a
CDCl3/hexane mixture, and the corresponding X-ray structures
are shown in Figure 1. In the solid state, complexes A1−A3
display a bromo-bridged dimeric structure (A1dim−A3dim), with
Figure 1. X-ray crystal structures of oxidative addition complexes A1−
A4 showing selected distances (ellipsoids at the 50% probability level,
H atoms omitted for clarity).
biphenyl ipso carbon (C16). The presence of this type of Pd−
C
ipso bond in palladium(II)−biarylphosphine oxidative addition
complexes has been previously reported with CPhos L4 as the
ligand8b and in structurally related BrettPhos-type ligands
bearing i-Pr instead of NMe2 groups.10 The Pd−Cipso bond
length of 2.467(3) Å in A4 lies in the range of distances
reported in these CPhos (2.478 Å) and BrettPhos-based
complexes (2.439−2.527 Å). As expected, the Pd−Cipso
interaction causes a pyramidalization at C16 and an elongation
of the C16−C17 and C16−C24 aromatic bonds to 1.431(4) and
1.442(4) Å, respectively. In addition, the C24−N25 bond is
significantly shorter (1.383(4) Å) than the other ortho C17−
N18 bond (1.432(4) Å) and N25 is less pyramidalized than N18
(sum of the bond angles at N25 and N18: 355.0 and 338.6°,
respectively), thereby indicating a nonsymmetrical participation
A1 having a bent character between the two palladium units
dim
along the Br−Br axis (137.2°), presumably to minimize steric
repulsions between the respective L1 ligands. In all structures
the sum of the angles around the palladium center ranging
between 359.6 and 361.7° demonstrates planarity at the metal
with only minor distortions. In contrast, the X-ray crystallo-
graphic analysis of complex A4 revealed a monomeric species
featuring an interaction between the palladium center and the
B
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of these nitrogen atoms in the bonding interaction with Pd.11
palladium dimethyl malonate complexes B1−B3, which could be
fully characterized. The X-ray crystal structures of B1−B3 are
shown in Figure 2. No unusual angles at the palladium center
In contrast to the case for A4, complexes A1dim−A3 do not
dim
show any real bonding interaction between Pd and the non-
phosphine-containing ring of the ligand in the solid state.
Indeed, the Pd atom shows no pyramidalization in A1dim−A3
,
dim
with its coordination sphere being completed by the μ-bromo
ligand, and the shortest distance between Pd and the non-
phosphine-containing ring ranges from 3.06 (A2dim) to 3.42 Å
(A1dim) (Figure 1). In addition, the ortho NMe2 or i-Pr group
in A2dim and A3dim is pointing away from the metal, whereas the
NMe2 group is pointing toward Pd in A1dim. It should also be
noted that imidazole-based ligand L2 does not exhibit
coordination of Pd by the imidazole nitrogen atom, in contrast
to a previous X-ray structure with an analogous ligand.12
Thus, the above structures highlight a significant bonding
behavior between ligands L1−L3 and L4. In solution in CDCl3
at 20 °C, complex A1 mainly occurs as the bromo-bridged
dimer A1dim, as indicated by the presence of a sharp singlet
resonating at 29.8 ppm in 31P{1H} NMR (see the Supporting
Information). However, in C6D6, i.e. in a solvent that has
properties closer to the actual solvent employed in catalysis
(toluene), the 31P{1H} NMR spectrum of A1 shows a broad
signal resonating at 54 ppm, characteristic of a monomeric
species. This observation is in accordance with NMR studies by
Buchwald, Barder ,and co-workers.3c Similarly, 31P{1H} NMR
analyses indicate that complexes A2 and A3 occur as monomeric
species in C6D6 and as mixtures of a monomer and bromo-
bridged dimer in CDCl3. In contrast, complex A4 occurs as a
single monomeric species in CDCl3, in agreement with
previous data.8b However, its 31P{1H} NMR spectrum in
C6D6 shows two signals ascribed to two different monomeric
species.3c Unfortunately, we were unable to obtain additional
information from NMR data due to the fluxional behavior of
the above complexes, even by performing variable-temperature
experiments.
Synthesis and Characterization of Malonate Com-
plexes Containing Ligands L1−L4. On the basis of DFT
calculations, we previously proposed that α-arylated products
(3a,b, Table 1) arise from the reductive elimination of O-bound
Pd enolate C (Scheme 1).2b On the other hand, the
equilibration of C to β-agostic complex D opens up the β-
arylation pathway, which proceeds through β-hydride elimi-
nation, rotation, insertion, and reductive elimination.2b Culkin
and Hartwig showed that the stability of arylpalladium enolate−
diphosphine complexes is inversely proportional to the
substitution at the α carbon.13 In accordance with these results,
we were unable to isolate Pd enolates from the reaction of the
potassium enolate of 1 with oxidative addition complexes
ArPdLBr (L = biarylphosphine). As a consequence, we turned
our attention to malonate complexes, as more stable surrogates
of Pd enolates C and D.14 We initially attempted to prepare
such a complex from the oxidative addition complex, obtained
from DavePhos L1 and 1-bromo-2-fluorobenzene, that we
previously reported.2b Unfortunately in this case, we were not
able to isolate the malonate complex and observed the
formation of the α-arylated product. Although it proved
difficult to prepare malonate complexes that were sufficiently
stable to be isolated and crystallized, we found that the
presence of the two electron-withdrawing CF3 groups on the
aryl ligand provided the required stability. Metathetical
exchange between the potassium salt of dimethyl malonate
(5a) and the bromide ligand in complexes A1−A3 readily
occurred in THF at 0 °C to generate the κ2O,O′-bound
Figure 2. X-ray crystal structures of malonate complexes B1−B3 and
B4′ showing selected distances (ellipsoids at the 50% probability level,
H atoms omitted for clarity).
were found in B1−B3. As expected, the Pd−O1 bonds trans to
the aryl ligand are longer than the Pd−O2 bonds trans to the
phosphine ligand (2.107(3) Å vs 2.091(1) Å for B1; 2.115(1) Å
vs 2.094(1) Å for B2; 2.115(2) Å vs 2.095(2) Å for B3). The
spatial orientations of the biaryl moieties of the phosphine
ligands observed in A1dim−A3dim are preserved in B1 and B3, but
a rotation of the non-phosphine-containing ring of the ligand is
observed in B2, thus placing the nitrogen atom of the NMe2
moiety at the pseudoapical position of the Pd center, similar to
C
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a
Scheme 2. Formation of Malonate Complex B4′
a
Ar = m-(CF3)2Ph.
the case for B1. The shortest distances between this aromatic
ring and Pd in B1−B3 range from 3.12 to 3.27 Å, with no
significant pyramidalization at the Pd center, and thus with no
particular bonding character, similar to the case for the
investigations with more dynamic reaction models3 will be
conducted in the future to address this challenging issue.
CONCLUSION
■
corresponding oxidative addition complexes A1dim−A3
.
dim
This study represents a first step toward the understanding of
the origins of the ligand-induced selectivity in the normal (α) vs
migrative (β) arylation of ester enolates. The solid-state
structures of two types of arylpalladium complexes, i.e.
oxidative addition and malonate, were solved with four
representative biarylphosphine ligands. These data highlight
the influence of the ligand rigidity, with CPhos (L4) showing
higher bidentate character and rigidity in comparison to ligands
L1−L3 bearing only one ortho substituent on the non-
phosphine-containing benzene ring. This rigidity (or con-
versely, flexibility) is likely a key factor in the control of the
arylation selectivity.
Finally, malonate complex B4 was readily obtained from
complex A4 under the same reaction conditions (Scheme 2).
However, when B4 was left to crystallize at 5 °C in a C6D6/
hexane mixture, we were surprised to obtain the crystal
structure of the parent complex B4′ bearing the arylated
malonate. Complex B4′ displays the same κ2O,O′ coordination
mode and overall structure as complexes B1−B3 (Figure 2,
bottom right). It is probably formed by displacement of the
malonate ligand in B4 by the in situ formed arylated malonate
anion 5b, arising from reductive elimination of the putative C-
enolate B4″. In addition, B4′ could be obtained directly from A4
and malonate anion 5b in a separate experiment. DFT
modeling of the isodesmic reaction between B4 and B4′
showed that the formation of B4′ is thermodynamically favored
by 4.6 kcal mol−1, which accounts for the isolation of B4′ rather
than B4.
EXPERIMENTAL SECTION
■
General Considerations. Reactions were performed under an
atmosphere of argon with rigorous exclusion of moisture from reagents
and glassware using standard techniques. Commercially available
reagents were used without further purification unless otherwise
stated. All bases, phosphines, and palladium sources were stored in a
glovebox. Anhydrous solvents were obtained by distillation over
calcium hydride (n-hexane) or sodium/benzophenone (THF,
toluene). IR spectra were recorded on an FTIR spectrometer and
data are reported in reciprocal centimeters (cm−1). NMR spectra (1H,
13C, 19F, and 31P) were recorded on a 300, 400, or 500 MHz
DISCUSSION
■
The above results show that CPhos L4 behaves differently from
the other studied ligands in both oxidative addition, where it
adopts a bidentate binding mode, and malonate, where it seems
to favor reductive elimination, complexes. This behavior can be
ascribed to the reduced conformational freedom at the biaryl
bond of L4 in comparison to L1−L3, which should lower the
energy barrier of C−C reductive elimination by virtue of steric
decompression.13,14 This property allows to explain the high α
selectivity in the arylation of tert-butyl isobutyrate (1) with this
ligand (Table 1). Indeed, the two selectivity-determining steps
were shown to be the α reductive elimination and the olefin
insertion with DavePhos L1 as the ligand.2b With a more rigid
ligand such as CPhos L4, α reductive elimination should
become energetically more favorable and Pd migration less
favorable, thereby favoring the α-arylated product (3a,b).
Nevertheless, other factors must be involved, as shown with the
selectivity differences observed among ligands L1−L3, which
form structurally similar oxidative addition and malonate
complexes. In particular, the hemilabile character of NMe2-
containing ligands L1 and L2 seems to be an important
parameter in comparison with L3, which is isosteric but lacks
the nitrogen coordinating group. The current study does not
allow us to decipher this more subtle effect, and further
spectrometer in CDCl3 (residual peaks H δ 7.26, 13C δ 77.16) or
1
1
C6D6 (residual peaks H δ 7.16, 13C δ 128.06). Chemical shifts are
1
reported relative to the chemical shift of the residual solvent for H
and 13C NMR. 19F NMR and 31P NMR spectra are calibrated with an
external reference (CFCl3 δ 0.0 and H3PO4 δ 0.0, respectively) and
recorded with complete proton decoupling. Data are reported as
follows: chemical shift in parts per million (ppm), multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, and br =
broad), integration value, coupling constant in Hz if applicable.
General Procedure A for the Synthesis of Oxidative
Addition Complexes. A Schlenk tube was charged with [Pd(COD)-
(CH2SiMe3)2]15 (200 mg, 0.52 mmol, 1.0 equiv) and phosphine
ligand (0.52 mmol, 1.0 equiv), and the solids were dissolved in THF
(20 mL). 1-Bromo-3,5-bis(trifluoromethyl)benzene (0.44 mL, 754.0
mg, 2.58 mmol, 5.0 equiv) was then added to the solution and the
reaction mixture was stirred for 16 h at room temperature. All of the
volatiles were then removed under vacuum, and n-hexanes was added.
After filtration by cannula transfer under a positive pressure of argon,
the solid was dried under vacuum. Crystallization was achieved using
NMR Young tubes with CDCl3/n-hexanes or C6D6/n-hexanes solvent
mixtures.
D
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2
Complex A1. Complex A1 was synthesized according to general
procedure A using DavePhos L1 (204 mg) as the ligand. The title
complex was obtained as a gray solid in 86% yield and was crystallized
CH), 127.8 (d, JCP = 25.0 Hz, Cq), 128.6 (q, JCF = 31.8 Hz, 2Cq),
131.3 (CH), 133.5 (Cq), 133.8 (d, JCP = 12.3 Hz, CH), 134.1 (CH),
135.6 (CH), 136.4 (2CH), 140.8 (Cq), 146.9 (d, JCP = 18.6 Hz, Cq),
157.5 (Cq). 31P NMR (162 MHz, CDCl3, 293 K): δ 33.1. 19F NMR
(376 MHz, CDCl3, 293 K): δ − 62.4. IR (neat): ν 2933, 2855, 1339,
1272, 1123. HRMS (ESI): m/z calcd for C36H44F6N2PPd ([M −
Br]+), 755.2189; found 755.2169.
1
in CDCl3/n-hexanes. H NMR (400 MHz, CDCl3, 293 K): δ 0.95−
1.15 (m, 4H), 1.42−1.62 (m, 6H), 1.64−1.74 (m, 3H), 1.77−1.83 (m,
2H), 1.88−1.97 (m, 3H), 1.99−2.09 (m, 1H), 2.26−2.35 (m, 1H),
2.59−2.72 (m, 2H), 3.01 (s, 6H), 6.94−7.03 (m, 2H), 7.07−7.11 (m,
1H), 7.13−7.17 (m, 1H), 7.31−7.44 (m, 4H), 7.56−7.62 (m, 1H),
7.64−7.71 (m, 2H). 13C NMR (100.6 MHz, CDCl3, 293 K): δ 25.4
Synthesis of Potassium Dimethyl Malonate (5a). Potassium
dimethyl malonate was formed by the addition of 1 equiv of dimethyl
malonate to a suspension of 1 equiv of KH in THF. The reaction
mixture was stirred until no more degassing of H2 was observed.
Volatiles were removed from the resulting solution. The resulting solid
was washed with n-hexanes and stored in the glovebox at −5 °C.
General Procedure B for the Synthesis of Malonate
Complexes. A Schlenk flask was charged with potassium dimethyl
malonate 5a (3.0 equiv) and THF and cooled to 0 °C. The oxidative
addition complex (1.0 equiv) in THF was then added at 0 °C. The
reaction mixture was stirred for 2 h at 0 °C. After the volatiles were
removed under vacuum, toluene was added. The solution was filtered
by cannula transfer under a positive pressure of argon. The resulting
solution was concentrated, and precipitation was attempted by the
addition of n-hexanes. When the product did not precipitate, it was
directly crystallized in NMR Young tubes with CDCl3/n-hexanes or
C6D6/n-hexanes solvent mixtures.
(CH2), 26.0 (CH2), 26.4 (CH2), 26.9−27.5 (m, CH2), 28.9 (d, JCP
=
3.6 Hz, CH2), 30.6 (CH2), 35.2 (d, 1JCP = 23.9 Hz, CH), 36.3 (d, 1JCP
= 29.5 Hz, CH), 44.3 (2CH3), 117.5 (CH), 118.3 (CH), 120.2 (CH),
1
123.7 (q, JCF = 272.8 Hz, 2Cq), 125.9 (CH), 127.1 (d, JCP = 5.7 Hz,
2
CH), 128.4 (d, JCP = 35.0 Hz, Cq), 128.6 (q, JCF = 31.7 Hz, 2Cq),
129.5 (CH), 131.7 (CH), 132.8 (CH), 135.2 (CH), 136.0 (CH),
138.4 (CH), 141.7 (Cq), 145.5 (Cq), 151.1 (d, JCP = 17.7 Hz, Cq),
156.3 (Cq). 31P NMR (121.5 MHz, C6D6, 293 K): δ 54.0. 19F NMR
(282 MHz, C6D6, 293 K): δ −61.7. IR (neat): ν 2931, 2855, 1338,
1270, 1120. HRMS (ESI): m/z calcd for C34H39F6NPPd ([M − Br]+),
712.1767; found, 712.1776.
Complex A2. Complex A2 was synthesized according to general
procedure A using 2-(2-(dicyclohexylphosphino)-1H-imidazol-1-yl)-
N,N-dimethylaniline L2 (199 mg) as the ligand. After evaporation of
THF, n-hexanes were added and the reaction mixture was filtered.
After evaporation of the filtrate, the title complex was obtained as a
yellow solid in 46% yield and was crystallized in CDCl3/n-hexanes. 1H
NMR (400 MHz, C6D6, 293 K): δ 0.75−0.96 (m, 2H), 1.06−1.16 (m,
4H), 1.20−1.30 (m, 1H), 1.46−1.75 (m, 8H), 1.79−2.13 (m, 4H),
2.16−2.36 (m, 3H), 2.27 (br s, 6H), 6.49 (br s, 1H), 6.83−6.91 (m,
1H), 6.93−7.05 (m, 2H), 7.14−7.23 (m, 3H), 7.48 (s, 1H), 7.72−7.93
(br s, 1H). 13C NMR (100.6 MHz, C6D6, 293 K): δ 26.4 (4CH2), 27.6
Complex B1. Complex B1 was synthesized according to procedure B
from A1 as the oxidative addition complex. Crystallization was
1
performed in C6D6/n-hexanes. H NMR (500 MHz, C6D6, 293 K): δ
0.63−0.72 (m, 1H), 0.85−1.03 (m, 4H), 1.08−1.19 (m, 1H), 1.22−
1.61 (m, 12H), 1.70−1.77 (m, 1H), 1.80−1.93 (m, 2H), 2.10−2.18
(m, 1H), 2.53 (s, 6H), 3.17 (s, 3H), 3.23 (s, 3H), 4.91 (s, 1H), 6.85−
6.89 (m, 1H), 6.97−7.04 (m, 2H), 7.06−7.11 (m, 2H), 7.12−7.19 (m,
3H), 7.65 (s, 1H), 7.92 (s, 2H). 13C NMR (126 MHz, C6D6, 293 K): δ
26.6 (d, JCP = 1.8 Hz, 2CH2), 27.4 (d, JCP = 9.0 Hz, CH2), 27.7 (d, JCP
= 7.4 Hz, CH2), 28.1 (d, JCP = 13.9 Hz, CH2), 28.6 (d, JCP = 16.4 Hz,
CH2), 30.1 (2CH2), 31.5 (d, JCP = 5.9 Hz, CH2), 34.0 (CH2), 34.7 (d,
1JCP = 20.3 Hz, CH), 39.2 (m, CH), 45.3 (2CH3), 50.7 (CH3), 51.1
(CH3), 66.7 (CH), 117.3 (m, CH), 119.8 (CH), 121.8 (CH), 124.7
(2CH2), 27.8 (4CH2), 27.9 (2CH2), 30.6 (br), 31.7 (br), 38.1 (br),
1
43.9 (2CH3), 117.3 (CH), 120.3 (CH), 122.5 (CH), 124.6 (q, JCF
=
2
273 Hz, 2Cq), 126.6 (CH), 128.4 (CH), 128.5 (q, JCF = 31.8 Hz,
2Cq), 128.7 (Cq), 130.3 (Cq), 130.9 (CH), 131.0 (CH), 131.1 (CH),
137.0 (CH), 150.0 (Cq), 152.7 (Cq). 31P NMR (121 MHz, C6D6, 293
K): δ 33.8. 19F NMR (282 MHz, C6D6, 293 K): δ −61.7. IR (neat): ν
2937, 2856, 1340, 1272, 1121. HRMS (ESI): m/z calcd for
C31H37BrF6N3PPdNa ([M + Na]+), 804.0745; found, 804.0708.
Complex A3. Complex A3 was synthesized according to general
procedure A using dicyclohexyl(2′-isopropylbiphenyl-2-yl)phosphine
L3 (204 mg) as the ligand. The title complex was obtained as a yellow
solid in 48% yield and was crystallized in CDCl3/n-hexanes. 1H NMR
(400 MHz, C6D6, 323 K): δ 0.93−1.07 (m, 6H), 1.15−1.33 (m, 6H),
1.37−1.75 (m, 11H), 1.78−2.09 (m, 3H), 2.16−2.50 (m, 2H), 2.56−
2.76 (m, 1H), 6.87−7.05 (m, 3H), 7.06−7.14 (m, 1H), 7.17−7.38 (m,
4H), 7.44 (s, 1H), 7.67−7.86 (m, 2H). 13C NMR (100.6 MHz, C6D6,
293 K): δ 23.2 (CH3), 23.4 (CH3), 25.8 (br, CH2), 26.1−26.4 (br,
CH2), 26.4 (CH), 27.1−27.9 (br, CH2), 30.2−30.6 (br, CH2), 30.4 (d,
1JCP = 4.5 Hz, CH), 31.8 (br s, CH2), 32.7−33.4 (br, CH2), 36.8−38.9
(q, 1JCF = 273.2 Hz, 2Cq), 126.7 (d, JCP = 41.7 Hz, Cq), 127.0 (d, JCP
=
7.1 Hz, CH), 127.9 (q, 2JCF = 32.3 Hz, 2Cq), 129.9 (CH), 130.0 (d, JCP
= 1.9 Hz, CH), 131.7 (CH), 132.4 (CH), 135.1 (d, JCP = 8.6 Hz, CH),
135.2 (Cq), 136.6 (2CH), 146.7 (d, JCP = 10.1 Hz, Cq), 149.9 (d, JCP
=
6.7 Hz, Cq), 153.6 (Cq), 174.5 (Cq), 174.9 (Cq). 31P NMR (121 MHz,
C6D6, 293 K): δ 53.2. 19F NMR (282 MHz, C6D6, 293 K): δ −61.9. IR
(neat): ν 2941, 1620, 1498, 1342, 1273, 1120. HRMS (ESI): m/z calcd
for C34H39F6NPPd ([M − malonate]+), 712.1767; found, 712.1783.
Complex B2. Complex B2 was synthesized according to procedure B
from A2 as the oxidative addition complex. Crystallization was
1
performed in C6D6/n-hexanes. H NMR (300 MHz, C6D6, 293 K): δ
0.69−0.84 (m, 2H), 0.88−1.05 (m, 5H), 1.26−1.37 (m, 3H), 1.39−
1.61 (m, 10H), 2.00−2.09 (m, 2H), 2.36 (s, 6H), 3.19 (s, 3H), 3.26 (s,
3H), 4.86 (s, 1H), 6.71−6.78 (m, 2H), 6.86−6.90 (m, 1H), 6.98−7.04
(m, 2H), 7.09−7.13 (m, 1H), 7.65 (br s, 1H), 7.71 (br s, 2H). 13C-
{1H} NMR (100.6 MHz, C6D6, 293 K): δ 25.9−28.5 (m, CH2), 30.9
1
(br, CH), 117.2 (br, CH), 124.5 (q, JCF = 272.3 Hz, 2Cq), 125.8
(CH), 126.5 (CH), 126.7 (br, CH), 128.3 (CH), 128.5 (q, 2JCF = 33.4
Hz, 2Cq), 129.2 (CH), 129.4 (d, JCP = 6.4 Hz, CH), 130.7 (d, JCP
=
(br, CH2), 37.6 (br, CH), 44.1 (2CH3), 50.8 (CH3), 51.0 (CH3), 66.7
(CH), 117.4 (m, CH), 120.2 (CH), 121.5 (CH), 124.6 (q, JCF
10.9 Hz, CH), 133.8 (CH), 134.4−135.1 (CH), 137.0 (Cq), 137.1
(CH), 139.9 (Cq), 144.4 (Cq), 147.0 (Cq), 153.0 (Cq). 31P NMR (202
MHz, C6D6, 293 K): δ 44.0. 19F NMR (376 MHz, C6D6, 293 K): δ
−61.8. IR (neat): ν 2934, 2857, 1340, 1273, 1123. HRMS (ESI): m/z
calcd for C35H40F6PPd ([M − Br]+), 711.1814; found, 711.1798.
Complex A4. Complex A4 was synthesized according to procedure
A using CPhos L4 (227 mg) as the ligand. The title complex was
obtained as a yellow solid in 70% yield and was crystallized in C6D6/n-
1
=
272.8 Hz, 2Cq), 127.3 (CH), 129.5 (d, JCP = 27.5 Hz, Cq), 129.6 (Cq),
130.2 (CH), 130.9 (d, JCP = 10.2 Hz, CH), 131.2 (CH), 132.5 (q, 2JCF
= 33.9 Hz, 2Cq), 136.3 (2CH), 148.6 (d, JCP = 5.9 Hz, Cq), 151.1 (Cq),
174.4 (Cq), 174.9 (Cq). 31P NMR (121 MHz, C6D6, 293 K): δ 30.61.
19F NMR (282 MHz, C6D6, 293 K): δ −61.9. IR (neat): ν 2931, 2854,
1620, 1498, 1342, 1273, 1119. HRMS (ESI): m/z calcd for
C31H37F6N3PPd ([M − malonate]+), 702.1670; found, 702.1664.
Complex B3. Complex B3 was synthesized according to procedure B
from A3 as the oxidative addition complex. Crystallization was
performed in C6D6/n-hexanes. 1H NMR (400 MHz, CDCl3, 293 K): δ
0.77−0.92 (m, 2H), 0.96−1.29 (m, 5H), 1.07 (d, 3JHH = 6.7 Hz, 3H),
1.19 (d, 3JHH = 6.7 Hz, 3H), 1.34−1.47 (m, 2H), 1.55−1.91 (m, 10H),
1.98−2.13 (m, 2H), 2.19−2.31 (m, 1H), 2.71−2.84 (m, 1H), 3.21 (s,
3H), 3.33 (s, 3H), 4.20 (s, 1H), 7.15−7.21 (m, 1H), 7.28−7.34 (m,
3H), 7.35−7.44 (m, 5H), 7.47−7.52 (m, 1H), 7.54−7.63 (m, 1H). 13C
1
hexanes. H NMR (400 MHz, CDCl3, 293 K): δ 0.91−1.03 (m, 2H),
1.07−1.31 (m, 6H), 1.35−1.47 (m, 2H), 1.53−1.63 (m, 2H), 1.63−
1.80 (m, 6H), 2.00−2.09 (m, 2H), 2.13−2.26 (m, 2H), 2.62 (s, 12H),
6.86−6.92 (m, 2H), 7.08−7.13 (m, 1H), 7.31−7.37 (m, 2H), 7.43−
7.49 (m, 1H), 7.59−7.65 (m, 3H), 7.66−7.71 (m, 1H). 13C NMR
(100.6 MHz, CDCl3, 293 K): δ 25.9 (2CH2), 27.5 (d, JCP = 10.9 Hz,
2CH2), 27.6 (d, JCP = 11.7 Hz, 2CH2), 29.4 (2CH2), 30.2 (2CH2),
36.9 (d, 1JCP = 24.3 Hz, 2CH), 45.1 (4CH3), 112.5 (Cq), 114.9 (2CH),
1
117.3 (CH), 123.7 (q, JCF = 272.1 Hz, 2Cq), 126.1 (d, JCP = 5.5 Hz,
E
DOI: 10.1021/acs.organomet.6b00535
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
NMR (100.6 MHz, CDCl3, 293 K): δ 22.5 (CH or CH3), 26.2 (d, JCP
= 2.6 Hz, CH2), 26.8 (CH or CH3), 27.4 (CH2), 27.6 (CH2), 27.7
(CH2), 27.8 (CH2), 27.9 (CH2), 30.2 (CH2), 30.4 (CH2), 30.6 (CH
or CH3), 31.5 (br, CH2), 36.0 (d, 1JCP = 23.4 Hz, CH), 51.1 (2CH3),
structure solution and refinement. The structures were solved by direct
methods with SIR97,19 and the least-squares refinement on F2 was
achieved with the CRYSTALS software.20 All non-hydrogen atoms
were refined anisotropically. The hydrogen atoms were all located in a
difference map, but those attached to carbon atoms were repositioned
geometrically. The H atoms were initially refined with soft restraints
on the bond lengths and angles to regularize their geometry (C−H in
the range 0.93−0.98 Å, N−H in the range 0.86−0.89 Å, and O−H =
0.82 Å) and Uiso(H) values (in the range 1.2−1.5 times the Ueq value
of the parent atom), after which the positions were refined with riding
constraints. Complex A3 displayed solvent-accessible voids of 102 Å3
in the unit cell where residual electronic density was present. The
contribution of the disordered solvent was removed using the
SQUEEZE algorithm.21
1
65.3 (CH), 117.0 (m, CH), 123.9 (q, JCF = 272.8 Hz, 2Cq), 125.2
(CH), 126.0 (d, JCP = 40.4 Hz, Cq), 126.1 (CH), 126.8 (d, JCP = 8.3
Hz, CH), 127.9 (q, 2JCF = 32.3 Hz, 2Cq), 129.1 (CH), 129.5 (d, JCP
=
2.2 Hz, CH), 130.3 (CH), 133.3 (CH), 134.0 (d, JCP = 7.9 Hz, CH),
135.5 (2CH), 139.3 (d, JCP = 3.1 Hz, Cq), 145.7 (d, JCP = 8.6 Hz, Cq),
147.1 (Cq), 148.1 (d, JCP = 5.3 Hz, Cq), 173.9 (Cq), 174.3 (Cq). 31P
NMR (162 MHz, CDCl3, 293 K): δ 39.9. 19F NMR (376 MHz,
CDCl3, 293 K): δ −62.5. IR (neat): ν 2935, 2361, 1626, 1502, 1341,
1271, 1129. HRMS (ESI): m/z calcd for C35H40F6PPd ([M −
malonate]+), 711.1814; found, 711.1785.
Dimethyl 2-(3,5-Bis(trifluoromethyl)phenyl)malonate.16 Under
argon, a flame-dried Schlenk tube was charged with CuI (0.05 equiv,
19 mg, 0.1 mmol), 2-phenylphenol (0.1 equiv, 34 mg, 0.0281 mL, 0.2
mmol), and Cs2CO3 (1.5 equiv, 977 mg, 3 mmol). Then anhydrous
THF (2 mL), 3,5-bis(trifluoromethyl)iodobenzene (1 equiv, 680 mg,
0.356 mL, 2 mmol) and dimethyl malonate (2 equiv, 528 mg, 0.457
mL, 4 mmol) were added. The reaction mixture was stirred at 70 °C
for 24 h and then cooled to room temperature, quenched with a
saturated aqueous NH4Cl solution, and extracted with ethyl acetate.
The organic layer was washed with brine and dried over MgSO4.
Filtration through a plug of Celite and concentration on a rotary
evaporator afforded the crude product, which was purified by silica gel
chromatography (elution with cyclohexane/ethyl acetate 4:1). 1H
NMR (300 MHz, CDCl3, 293 K): δ 3.78 (s, 6H), 4.79 (s, 1H), 7.86 (s,
1H), 7.90 (s, 2H); 13C NMR (75 MHz, CDCl3, 293 K): δ 53.4
(2CH3), 56.9 (CH), 123.2 (q, 1JCF = 272 Hz, 2Cq), 122.6 (CH), 130.0
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00535.
■
S
NMR spectra of all complexes and details of DFT
calculations (Scheme 2) (PDF)
X-ray crystallographic data (CIF)
Cartesian coordinates of the calculated structures (XYZ)
AUTHOR INFORMATION
Corresponding Author
*E-mail for O.B.: olivier.baudoin@unibas.ch.
■
2
(2CH), 132.0 (q, JCF = 33 Hz, 2Cq), 135.1 (Cq), 167.4 (2Cq). 19F
NMR (282 MHz, C6D6, 293 K): δ −62.8; IR (neat): ν 1124, 1275,
1741, 2959. HRMS (ESI): m/z calcd for C13H10F6NaO4 ([M + Na]+),
367.0375; found, 367.0368.
Present Address
†Department of Chemistry, University of Basel, St. Johanns-
Ring 19, CH-4056 Basel, Switzerland.
Complex B4′. Complex B4′ was synthesized according to procedure
B from A4 as the oxidative addition complex. During the synthesis, all
vessels were kept at 0 °C. Crystallization was performed in C6D6/n-
hexanes at 0 °C. For characterization purposes, complex B4′ was also
synthesized according to procedure B from A4 as the oxidative
addition complex and the potassium salt of dimethyl 2-(3,5-
bis(trifluoromethyl)phenyl)malonate (5b). 1H NMR (400 MHz,
CDCl3, 293 K): δ 0.64−0.76 (m, 2H), 1.16 (m, 4H), 1.43−1.56 (m,
4H), 1.59−1.69 (m, 4H), 1.72−1.81 (m, 3H), 1.97−2.09 (m, 3H),
2.16−2.26 (m, 2H), 2.40 (s, 12H), 3.26 (s, 6H), 6.88 (m, 2H), 7.24
(m, 1H), 7.39 (br s, 1H), 7.42−7.47 (m, 1H), 7.48−7.52 (m, 2H),
7.62 (br s, 1H), 7.63 (br s, 2H), 7.77 (br s, 2H), 7.83 (m, 1H). 13C
NMR (100.6 MHz, CDCl3, 293 K): δ 26.2 (CH2), 27.5 (CH2), 27.6
(CH2), 27.7 (CH2), 29.7−30.6 (br, CH2), 31.8 (CH2), 35.6−35.9 (br,
CH), 46.1 (4CH3), 51.5 (2CH3), 80.6 (Cq), 115.4 (2CH), 116.9 (m,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Minister
Recherche and Institut Universitaire de France for financial
̀
e de l’Enseignement Super
́
ieur et de la
support, Johnson Matthey PLC for a loan of palladium salts,
and CCIR-ICBMS (Universite
allocation of computational resources. We are also grateful to E.
Jeanneau (Centre de Diffractometrie Henri Longchambon,
́
Claude Bernard Lyon 1) for the
́
UCBL) for X-ray diffraction analyses.
REFERENCES
CH), 118.7 (m, CH), 123.9 (q, 1JCF = 272.4 Hz, 2Cq), 124.0 (q, 1JCF
=
■
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