Synthesis of a bis(phenoxyketimine) palladium(II) complex and its activity in the Suzuki-Miyaura reaction

Article abstract of DOI:10.1016/j.jorganchem.2009.04.044

The synthesis of a new charge-neutral, air- and moisture-stable fluorinated bis(phenoxyketimine) Pd(II) complex is presented. Its activity as a precatalyst in the Suzuki-Miyaura cross-coupling reaction of activated and unactivated bromides has been explor

Full text of DOI:10.1016/j.jorganchem.2009.04.044

Journal of Organometallic Chemistry 694 (2009) 3008–3011
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of a bis(phenoxyketimine) palladium(II) complex and its activity
in the Suzuki–Miyaura reaction
*
Daniel F. Brayton, Timothy M. Larkin, David A. Vicic, Oscar Navarro
Department of Chemistry, University of Hawai‘i at Manoa, 2545 McCarthy Mall, Honolulu, HI 96822, United States
¯
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of a new charge-neutral, air- and moisture-stable fluorinated bis(phenoxyketimine) Pd(II)
complex is presented. Its activity as a precatalyst in the Suzuki–Miyaura cross-coupling reaction of acti-
vated and unactivated bromides has been explored.
Received 13 March 2009
Received in revised form 29 April 2009
Accepted 30 April 2009
Ó 2009 Elsevier B.V. All rights reserved.
Available online 8 May 2009
Keywords:
Palladium catalyst
Suzuki–Miyaura reaction
Unactivated aryl bromides
Phenoxyketimine
1. Introduction
used for SHOP-type (SHOP = Shell Higher Olefin Process) [10]. A
search of the literature uncovered several related [Pd(PHI)2] and
Schiff bases are attractive ligands due to their facile preparation
and simple synthetic modification, both electronic and steric, and
have been used to prepare a broad range of organometallic com-
pounds with a wide variety of applications [1–4]. For instance,
bis-phenoxyketimine (PHI) titanium complexes were originally re-
ported for the polymerization of ethylene [5]. The improved activ-
ity over known metallocenes spurred further interest in these early
transition metal complexes, with general formula [M(PHI)2X2]
(M = Ti, Zr; X = Cl, Br). It was later discovered that activity increases
dramatically when two or more F or CF3 groups are introduced to
the imido phenyl ring. Both synthetic and computational methods
confirmed that in particular an ortho fluorine (or other lone pair
donating substituent) can inhibit b-hydride elimination and pro-
mote living catalyst conditions [6]. It is this feature that is believed
to promote high speed living polymerizations and lead to monodis-
perse high molecular weight polymers. A new derivative of PHI li-
gands with a phenyl ring on the N–O backbone, PKI-F5 (1), was
recently employed by Coates and co-workers, for the living, isose-
lective polymerization of propylene [7].
[Pd(PHI)(Me)(X)] compounds, not only for that use but for many
other applications [11]. However, only one other monofluorinated
example is known in the literature [12]. When attempting the syn-
thesis of a 1:1 PdCl2:1 complex, we obtained as a byproduct the
new, neutral, air- and moisture-stable bis(phenoxyketimine) Pd(II)
complex 2 (Fig. 1), whose synthesis we optimized and report in
here. The activity of the complex in the Suzuki–Miyaura cross-cou-
pling [13] of unactivated aryl bromides and boronic acids is also
discussed.
2. Results and discussion
2.1. Complex synthesis
The ligand was prepared following the reported procedure by
Mason and Coates [14], then deprotonated with n-butyllithium at
À78 °C and allowed to react with PdCl2 at room temperature over-
night. Elution of the unreacted ligand through a plug of silica with
pentane, followed by elution with methylene chloride, yielded the
desired complex 2 (81%) with no observable complex decomposi-
tion. X-ray quality crystals were obtained by slow diffusion of pen-
tane into a concentrated solution of 2 in methylene chloride at
room temperature, and the structure of the complex was deter-
mined by X-ray crystallography. An ORTEP plot of 2 is shown in
Fig. 2, and selected crystallographic parameters are listed in Table
1. The complex displays a nearly ideal square planar geometry, with
both ligands trans to each other. On each PKI-F5 ligand the pentaflu-
oro aryl ring and ketimine aryl ring have a centroid distance of
Recently, the growing interest on the development of systems
for the polymerization of polar vinyl monomers, such as acrylates,
has led to the synthesis of a variety of complexes of palladium and
nickel for this purpose [8], because of the tolerance to functional-
ities that late transition metals display [9]. Many of those com-
plexes include [N,O] chelating ligands that resemble [P,O] ligands
* Corresponding author. Fax: +1 808 956 5908.
E-mail address: oscarnf@hawaii.edu (O. Navarro).
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.04.044

D.F. Brayton et al. / Journal of Organometallic Chemistry 694 (2009) 3008–3011
3009
and co-workers [15]. The authors obtained the complex when
attempting to isolate the active species involved in the in situ Su-
zuki–Miyaura cross-coupling of, mostly, activated aryl bromides
with boronic acids. Interestingly, their isolated complex performed
very poorly in these reactions, and better results were obtained
when in situ systems of 1:1 free ligand:Pd(OAc)2 were used. We
decided to test the activity of our complex in the same reaction
to determine whether electronic and/or steric variations in the li-
gand could have an effect on the performance of the complex.
Fig. 1. Ligand PKI-F5 (1) and (PKI-F5)2Pd (2).
2.2. Activity of 2 in the Suzuki–Miyaura reaction
The Suzuki–Miyaura reaction, involving the coupling of an or-
ganic halide or pseudo-halide with an organoboron reagent in
the presence of a base and a Pd or Ni catalyst, is arguably the most
used cross-coupling procedure for the formation of C–C bonds [16].
Key advantages of this reaction when compared to other cross-
coupling reactions are low toxicity and ready availability of the
organoboron reagents [17]. After an optimization process (Table
2), we found that our complex could perform the coupling of bro-
mobenzene with 1-naphthaleneboronic acid using 0.6 mol% cata-
lyst loading at 60 °C in very good yield in a couple of hours,
when using technical grade isopropanol as the solvent (Table 2, en-
try 9). As a control reaction, we attempted the coupling of those
substrates in the same conditions using nearly twice as much load-
ing of Pd(OAc)2 with no ligand, obtaining only 9% of the desired
product after 24 h and 22% after 3 days (Table 2, entry 10). In addi-
tion, using 2, upon decreasing the temperature to 40 °C or room
temperature, product formation was still observed, but the reac-
tion required 24–48 h for completion. Attempts to couple less reac-
tive aryl chlorides (chlorobenzene or the more activated 4-
nitrochlorobenzene) invariably failed.
To determine the scope of the reaction, our optimized condi-
tions were applied to a variety of aryl bromides and boronic acids
(Table 3). While the complex reported by Hong and co-workers
displayed very low activity even towards activated (electron-poor)
aryl bromides [15], we were glad to find that our system not only
also allowed for the coupling of activated bromides (Table 3, entry
1) but also of more challenging deactivated (electron-rich) aryl
bromides (Table 3, entries 4–9). Mono-ortho-substituted biaryls
can be synthesized in short reaction times (Table 3, entries 2, 4,
6, 7), while more challenging di-ortho-substituted biaryls require
longer reaction times, affording the desired coupling products in
lower yields (Table 3, entries 8, 9, 10). It is worth mentioning that,
Fig. 2. ORTEP plot of 2. Selected bond distances (Å): Pd–O1: 1.985(1) and Pd–N1:
2.033(1). Selected angles (°): O1–Pd–N1: 91.04 and O1–Pd–N2: 88.96.
3.921 Å, and a dihedral angle between their planes of 52.70°. Given
this distance and angle it seems highly unlikely that any p-stacking
contributes to the structure’s stability. The average plane created by
the phenolic aryl ring is nearly perpendicular to the both ketimine
and pentafluoro rings at 81.15° and 85.29°, respectively.
A search of the literature indicated that a similar but non-fluo-
Table 2
rinated palladium(II) complex had been recently reported by Hong
System optimization for the Suzuki–Miyaura reaction using 2.
Table 1
Crystallographic parameters.
Complex
2 [Pd(PKI-F5)2]
Empirical formula
Formula weight
Crystal size (mm3)
Crystal system
Space group
a (Å)
PdO2N5F10C42H26
887.05
0.48 Â 0.47 Â 0.27
Entry
Solvent
2 (mol%)
Temperature (°C)
Time (h)
Yield (%)a
Triclinic
ꢀ
1
2
3
4
5
6
7
8
Toluene
Dioxane
Ethanol
4.8
4.8
4.8
4.8
2.4
1.2
0.6
0.3
0.6
1
80
80
80
80
80
80
80
80
60
60
40
RT
48
48
19
2
2
2
2
4
14
38
57
92
93
91
94
39
P1
9.047(3)
9.052(4)
12.202(5)
77.184(6)
83.106(5)
66.659(5)
894.053
1.647
b (Å)
c (Å)
Isopropanol
Isopropanol
Isopropanol
Isopropanol
Isopropanol
Isopropanol
Isopropanol
Isopropanol
Isopropanol
a
(°)
b (°)
c
(°)
Volume (Å3)
Dcalc (Mg mÀ3
)
9
2
92
10
11
12
24(72)
24
48
9(22)b
91
Temperature (K)
h range (°)
173(2)
3.29–8.07
0.6
0.6
89
Index ranges
À11 to h to 11, À11 to k to 11, À15 to I to 15
Goodness-of-fit on F2
Wavelength (Å)
1131
0.71075
a
GC yields using hexamethylbenzene as internal standard, average of two runs.
Pd(OAc)2 instead of 2.
b

3010
D.F. Brayton et al. / Journal of Organometallic Chemistry 694 (2009) 3008–3011
Table 3
Substrate scope for the Suzuki–Miyaura reaction using 2 as precatalyst.
Entry
1
Aryl bromide
Boronic acid
Product
Time (h)
2
Yield (%)a
89
2
2
85
3
4
5
6
14
2
86
87
82
85
2
2
7
8
9
2
89
59
24
24
24
60
76
10
a
Isolated yields, average of two runs.
in most cases, no starting aryl bromide was recovered, and the cor-
responding amount of dehalogenated by-product was observed in
the GC traces. This competitive pathway in isopropanol-based sys-
tems has been described before [18]. As the coupling becomes
more challenging because of electronic and/or steric effects, the
dehalogenation path becomes favored.
in performance, allowing for the coupling of unactivated aryl bro-
mides with boronic acids to synthesize mono- and di-ortho-substi-
tuted biaryls in good yields, at mild temperature and short reaction
times. In addition, the ligand is air- and moisture-stable and can be
easily prepared. Studies on the catalyst activation and the effect of
ligand modifications in this and related C–C bond forming reac-
tions are currently ongoing in our labs.
3. Conclusion
4. Experimental
The synthesis of a new air- and moisture-stable bis(phenoxyk-
etimine) Pd(II) complex and its use in the Suzuki–Miyaura cross-
coupling reaction of activated and unactivated aryl bromides is
presented. We showed that simple ligand modifications from a
previously reported complex [15] allowed for a dramatic increase
4.1. General considerations
All commercially available reagents were used as received with-
out further purification. All synthesis and manipulations of air- and

D.F. Brayton et al. / Journal of Organometallic Chemistry 694 (2009) 3008–3011
3011
moisture-sensitive compounds were carried out in Schlenk glass-
ware that had been dried in an oven overnight, on dual-manifold
high-vacuum/nitrogen Schlenk lines. Suzuki–Miyaura reactions
were set up in oven-dried vials in an MBraun Unilab glovebox. Nu-
clear magnetic resonance spectra were recorded on a Varian Mer-
cury Plus 300 MHz or on a Varian Inova 500 MHz spectrometer.
Elemental analysis of 2 was performed at Columbia Analytical Ser-
vices, Tucson, AZ. X-ray diffraction was performed in a Rigaku SCX-
Mini CCD diffractometer. The 19F NMR spectrum of 2 was reported
affording the product in >95% purity. When necessary, the product
was purified by flash chromatography on silica gel using mixtures
ethyl acetate/hexanes as eluent. Yields reported for each substrate
are the average of at least two reactions.
Acknowledgements
The authors want to thank the University of Hawai‘i at Manoa
¯
for funding and support. Wesley Yoshida (UH Manoa) is acknowl-
¯
using
a,a
,a-trifluorotoluene as Ref. [19].
edged for assistance with the NMR spectra.
4.2. Synthesis of bis[2,4-dimethyl-6-[phenyl(pentafluorphenylimino)-
methyl]-phenolato]palladium, [Pd(PKI-F5)2] [Pd(NOF5C21H13)2] (2)
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jorganchem.2009.04.044.
In a Schlenk flask, a solution of PHK-F5 (1) (0.195 g, 0.5 mmol) in
THF (40 mL) was cooled to À78 °C using a dry ice acetone bath, and
then n-butyllithium (0.31 mL, 0.5 mmol, 1.6 M in hexanes) was
syringed in, dropwise. The reaction was allowed to warm to room
temperature and stirred for another 30 min. Keeping a nitrogen
flow, the septum was removed, palladium chloride (0.044 g,
0.248 mmol) was added, and the reaction was left to stir overnight.
The entire solution was filtered through a Celite plug. The solvent
was removed in vacuo and the resulting orange solid was placed on
a silica plug. Pentane was used to elute unreacted free ligand, and
then methylene chloride was used to bleed off an orange band. The
solvent was removed and the resulting solid was placed on a filter
frit and washed with copious amounts of pentane, yielding 0.179 g
(80.7%) of 2 as an orange solid. 1H NMR (299.84 MHz, CDCl3): d
7.29 (m, 6 H, Ar-H); 7.09 (m, 4 H, Ar-H), 6.90 (s, 2 H, Ar-H), 6.29
(s, 2 H, Ar-H), 1.93 (s, 6H, –CH3), 1.52 (s, 6H, –CH3). 13C NMR
(125.75 MHz, CD2Cl2): d 176.21, 164.49, 138.43, 138.04, 132.65,
129.85, 129.39, 128.75, 126.11, 124.14, 120.56, 20.85, 17.09
(note: pentafluoro aryl carbons were not observed due to poor sol-
ubility and C–F coupling). 19F NMR (CDCl3, 282.14 MHz): d =
À144.38 (m), À159.76 (t, J = 22 Hz), À165.10 (m). Anal. Calc. for
PdO2N2F10C42H26: C, 56.87; N, 3.16; H, 2.95. Found: C, 56.40; N,
3.03; H, 2.65%.
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In a glove box, the desired boronic acid (0.55 mmol), potassium
t-butoxide (0.55 mmol, 62 mg) and 2 (0.6 mol%, 2.7 mg) were
added in turn to a vial equipped with a magnetic bar and sealed
with a screw cap fitted with a septum. Outside the glovebox, tech-
nical grade isopropanol (1 mL) was syringed in the vial through the
septum. After 20 min of stirring at 60 °C the desired aryl bromide
(0.5 mmol) was injected through the septum, and the reaction
mixture was allowed to stir at that temperature. When the reaction
reached completion, or no further conversion was observed, the
mixture was placed in a plug of silica and eluted with hexanes,
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