Selective Monoarylation of Primary Anilines Catalyzed by Pd(dippf) and its Application in OLED Component Synthesis

Article abstract of DOI:10.1002/adsc.201501160

Palladium 1,1′-bis(diisopropylphosphino)-ferrocene [Pd(dippf)] complexes were found to promote the monoarylation of primary anilines with unprecedented selectivities. They also allow the sequential arylation of primary anilines with two different aryl bromides in one pot. The reactions can be performed at low catalyst loadings (0.2 mol%) and high substrate concentrations. The synthetic utility of the optimum catalyst was demonstrated by the synthesis of various di- and triarylamines. A particular focus was set on compounds with carbazole and fluorene moieties as employed in state-of-the-art small-molecule organic light emitting diodes (OLEDs). (Figure presented.).

Full text of DOI:10.1002/adsc.201501160

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DOI: 10.1002/adsc.201501160
Selective Monoarylation of Primary Anilines Catalyzed by
Pd(dippf) and its Application in OLED Component Synthesis
Matthias F. Grünberg,a Fan Jia,a Andreas Rivas-Nass,b and Lukas J. Gooßena,*
a
Department of Chemistry, University of Kaiserslautern, Erwin-Schrçdinger-Strasse 54, 67663 Kaiserslautern, Germany
Fax: (+49)-631-205-3921; phone: (+49)-631-205-2046; e-mail: goossen@chemie.uni-kl.de
Precious Metals Chemistry, Umicore AG & Co. KG, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany
b
Received: December 22, 2015; Revised: March 3, 2016; Published online: May 3, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201501160.
Abstract: Palladium 1,1’-bis(diisopropylphosphino)-
ferrocene [Pd(dippf)] complexes were found to pro-
mote the monoarylation of primary anilines with
unprecedented selectivities. They also allow the se-
quential arylation of primary anilines with two dif-
ferent aryl bromides in one pot. The reactions can
be performed at low catalyst loadings (0.2 mol%)
and high substrate concentrations. The synthetic
utility of the optimum catalyst was demonstrated by
Figure 1. Modern hole transport materials.[6f]
the synthesis of various di- and triarylamines. A
particular focus was set on compounds with carba-
zole and fluorene moieties as employed in state-of-
the-art small-molecule organic light emitting diodes
(OLEDs).
rene[7] substructures (Figure 1), since these have high
thermal stabilities (DT5%) and high glass transition
temperatures (Tg). However, these important parame-
ters strongly depend on the purity of the materials,
and longevity of the electronic devices at top per-
formance can only be assured if their chemical syn-
thesis proceeds with excellent selectivity. Thus, effi-
cient syntheses of triarylamines are constantly sought.
The Buchwald–Hartwig amination, a palladium-
mediated arylation of amines with aryl halides, is ar-
guably the most versatile and efficient synthetic entry
Keywords: amination; homogeneous catalysis;
OLEDs; organic light emitting diodes; palladium;
phosphine ligands
Within recent years, organic light emitting diode to this important substrate class (Scheme 1).[8,9] How-
(OLED) technology has undergone significant devel- ever, the arylation of fluorenylamines with bulky aryl
opment.[1] Since the first report by Tang and Van bromides proceeds rather sluggishly even with state-
Slyke in 1987,[2] tremendous research efforts have of-the-art catalysts. Usually, high loadings in excess of
vastly improved the performance and lifetime of elec-
troluminescent materials. This has enabled their
broad application in digital displays and solid-state
lighting.[3] Both polymer-based devices[4] and small-
molecule OLEDs are highly efficient and durable.[1c]
The advantage of the latter is that their molecular
design may be altered with great flexibility, and the
components can conveniently be deposited in precise
thin layers by vacuum sublimation techniques.[5]
Such small-molecule OLEDs have multilayered
structures in which emitter layers are positioned be-
tween electron- and hole-transporting layers and the
electrode materials. The hole transport materials
often contain triarylamines with carbazole[6] and fluo- Scheme 1. Traditional and targeted triarylamine syntheses.
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Table 1. Benchmarking of state-of-the-art amination cata-
lysts.[a]
Entry
Pd source
Ligand
Yield [%]
3a
5a
1
2
3
4
5
6
7
8
Pd[P(t-Bu)3]2
{Pd(mBr)[P(t-Bu)3]}2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
(IPr)Pd(allyl)Cl
(IPr)Pd(cinnamyl)Cl
Pd(dba)2
Pd(dba)2
Pd(dba)2
PdCl2
Pd(dippf)vs
Pd(dippf)maleimide
–
–
91
90
90
94
87
71
88
72
9
4
4
2
4
1
1
2
1
JohnPhos
XPhos
BrettPhos
BINAP
XantPhos
dppf
Figure 2. Selection of investigated ligands.
1% catalyst are required, and significant quantities of
hard-to-separate diarylation products are produced,
so that isolation and purification of the diarylamine
intermediates is indispensable.
9
–
–
n.d.
n.d.
trace
3
n.d.
n.d.
n.d.
n.d.
10
11
12
13
14
15
16
7
dcypf
dtbupf
dippf
dippf
–
76
92
94
5
92
93
The key towards enabling a straightforward, one-
pot synthesis of small-molecule OLEDs lies in the de-
velopment of a highly selective and easily scalable
monoarylation protocol that would proceed at high
substrate concentrations and low catalyst loadings
with only equimolar amounts of the coupling part-
ners.
In search of an efficient catalyst system, we investi-
gated various state-of-the-art amination ligands for
Pd (Figure 2) using the model reaction of aniline (1a)
with 4-bromotoluene (2a), with NaO-t-Bu as the base
and toluene as the solvent.[8] Table 1 shows that most
of the Pd/phosphine catalysts led to full conversion of
the starting materials within 20 h at 708C (entries 1–
8). Interestingly, the reaction proceeded more slowly
with Pd-NHC catalysts, resulting in low yields (en-
tries 9 and 10).
dippf
[a]
Conditions: 1.00 mmol of 1a, 1.00 mmol of 2a, 1.20 mmol
NaO-t-Bu, 0.2 mol% Pd source, 0.3 mol% of a monoden-
tate ligand or 0.2 mol% of a bidentate ligand, 1 mL of
toluene, 708C, 20 h. GC yields with n-tetradecane as in-
ternal standard; n.d.=not detected, vs=1,3-divinyl-
1,1,3,3-tetramethyldisiloxane.
However, the formation of the desired diarylamine
3a was always accompanied by the formation of 1–
4% of the diarylated by-product 5a, which could be
easily detected by GC.[10] Surprisingly, we found that
diarylation can completely be suppressed with 1,1’-
bis(diisopropylphosphino)ferrocene (dippf), a ligand
that has only rarely been employed in cross-coupling
reactions (entry 13).[11] However, further experiments
confirmed its unique selectivity among aryl- or alkyl-
substituted ferrocenyl phosphines (entries 11–13).
Pd(dippf) catalysts generated in situ from the Pd(0)
precursors Pd(dba)2 or Pd(vs) (vs=1,3-divinyl-1,1,3,3-
Scheme 2. Pd(dippf)maleimide (6) synthesis.
tetramethyldisiloxane) proved to be most active, adduct from a mixture of maleimide and Pd(dippf)vs
while in situ generated Pd(dippf)Cl2 showed almost in diethyl ether (Scheme 2). Pd(dippf)maleimide (6)
no activity (entry 14). In the presence of Pd(dippf) is an air-stable, yellow solid with slightly lower reac-
catalysts, product 5a was not even detected in traces. tivity than the catalysts generated in situ. However, in
Adding a dippf solution in toluene to Pd(vs) combination with additional dippf, it is superior to the
(10.87% Pd) results in a stable catalyst solution that catalysts generated in situ with regard to activity and
can be stored and handled easily. Alternatively, long-term stability, especially at elevated tempera-
Pd(dippf) can be precipitated as a defined maleimide tures (entry 16, see also the Supporting Information).
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Selective Monoarylation of Primary Anilines Catalyzed by Pd(dippf)
with P(t-Bu)3 or Buchwald-type biarylphosphine li-
gands, the dippf systems were somewhat less reactive,
but displayed unparalleled selectivity.[13]
With the optimal catalyst system in hand, we exam-
ined the scope of the monoarylation (Table 2). Sever-
al mono- and polycyclic aromatic amines, as well as
amines with dibenzofuran, dibenzothiophene, pyri-
dine, carbazole, and fluorene residues were converted
to the corresponding secondary amines in excellent
yields and selectivities. Many of these structures are
currently under investigations for use in OLEDs. In
the presence of the strong base NaO-t-Bu, only
robust functionalities such as chlorine, methyl sulfide,
and methoxy remain unchanged. However, when
switching to cesium carbonate as the base, even sensi-
tive functionalities such as ester, keto, and cyano
groups are tolerated. The catalyst has only moderate
reactivity because of its tremendous selectivity. In all
cases, the selectivity for the monoarylated product is
exceptionally high. The diarylation by-product is ob-
tained in no case. It is even possible to perform mon-
oarylations of primary anilines in the presence of sec-
Figure 3. ORTEP drawing of Pd(dippf)maleimide 6 (50%
probability ellipsoids).
The structure of complex 6 features a dippf bite ondary amine functionalities (Table 2, 3t).[15]
angle of 105.98 and an h2-coordinated maleimide
The reaction was scaled up to a preparative scale.
Thus, 7.97 g (20 mmol) of 3-(4-bromophenyl)-9-
ligand (Figure 3).[12]
After the encouraging findings with the simple test phenyl-9H-carbazole (2b) were converted to 3b in
system, we probed the activity of various catalysts in 97% isolated yield in the presence of 0.2 mol% of 6/
the synthesis of large conjugated p-systems as used in dippf.
OLEDs (Scheme 3).[13] Because even trace impurities
We next investigated how the selective monoaryla-
may strongly affect the conductivity of these electrical tion of primary anilines can be combined with
materials or lead to their premature deterioration re- a second arylation into a one-pot synthesis of unsym-
sulting in so-called “black spots”,[14] an unusually high metrically substituted triarylamines. The arylation of
level of selectivity needed to be ensured in this reac- aniline (1a) with 4-bromotoluene (2a), then with p-
tion.
anisyl chloride (2l) in the presence of NaO-t-Bu was
Simple TLC analysis proved to be most sensitive in used as a test reaction. The combination of 6 and
the detection of diarylated by-products because of dippf was again validated as a uniquely selective cata-
their extreme absorption under UV light.
lyst. Equimolar amounts of 1a and 2a were initially al-
In the arylation of 1b with 2b, the dippf catalysts lowed to react for 20 h at 808C in the presence of
led to full conversion within 16 h at 708C. The unde- 0.5 mol% catalyst, then 2l was added in a small
sired diarylation product was not detected even in excess, the temperature was increased to 1208C, and
traces by TLC. Against a benchmark of Pd catalysts stirring was continued for another 24 h. In this way,
the triarylamine 4a was obtained in high yield and se-
lectivity. The same reaction protocol can also be ap-
plied to the coupling of the aniline 1a with two differ-
ent aryl bromides. The advantage of using an aryl
chloride as the second electrophile is its lower reactiv-
ity. As a result, 2l may also be added directly at the
beginning without substantially impacting the selectiv-
ity.
Table 3 illustrates the scope of the one-pot unsym-
metrical diarylation procedure. A particular focus was
set on molecules with quinolinyl, quinazolyl and N-ar-
ylpyrrole moieties as used in contemporary hole
transport materials within OLEDs. Aryl chlorides and
bromides proved to be equally suited as coupling
partners for the second step. All products were ob-
Scheme 3. Synthesis of p-conjugated amines.
tained in high yields and purities.
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Matthias F. Grünberg et al.
Table 2. Reaction scope of the monoarylation reaction.[a]
[a]
[b]
The residue originating from the aryl bromide is placed on the right-hand side. Conditions: 1.00 mmol of amine,
1.00 mmol of aryl bromide, 1.20 mmol of NaO-t-Bu, 0.2 mol% of 6, 0.2 mol% of dippf, 2 mL of toluene, 708C, 20 h, isolat-
ed yields.
1.20 mmol of Cs2CO3, 1108C.
trogen-vacuum cycles, a stock solution of Pd(dippf)male-
imide (1.24 mg, 0.002 mmol) and dippf (0.85 mg,
In conclusion, a catalyst system consisting of
Pd(dippf)maleimide and dippf efficiently promotes
the monoarylation of primary amines with unparal-
leled selectivity. At higher reaction temperatures, this
catalyst also promotes a further arylation of the re-
sulting diarylamines. This enables the one-pot, two-
step synthesis of unsymmetrically substituted triaryl-
amines in high yields and selectivities. This synthetic
approach is effective in the synthesis of high-purity
triarylamines with large conjugated p-systems as used
in modern OLEDs as hole transport materials.
0.002 mmol) in dry, distilled toluene (2 mL) was added via
syringe. The reaction mixture was stirred at 708C for 20 h,
cooled to room temperature and diluted with dichlorome-
thane (30 mL) and water (30 mL). The aqueous layer was
separated and extracted with dichloromethane (2”20 mL).
The combined organic layers were dried over MgSO4, fil-
tered and concentrated under vacuum (408C, 500 mbar).
The crude product was further purified by flash chromatog-
raphy (SiO2 or basic Al2O3, hexane/ethyl acetate or hexane/
diethyl ether), yielding the corresponding amine; yield: 70–
96%.
One-Pot Procedure for the Synthesis of Tertiary
Amines
Experimental Section
A dry 20-mL crimp-cap vessel was charged with the aryl
bromide (1.00 mmol), the primary amine (1.00 mmol),
sodium tert-butoxide (235 mg, 2.40 mmol) and a magnetic
stir bar and was kept in vacuum for 10 min. After three ni-
trogen-vacuum cycles, a stock solution of Pd(dippf)male-
imide (3.11 mg, 0.005 mmol) and dippf (2.13 mg,
0.005 mmol) in dry, distilled toluene (2 mL) was added via
Standard Procedure for the Selective Monoarylation
of Primary Amines
A dry 20-mL crimp-cap vessel was charged with the aryl
bromide (1.00 mmol), the primary amine (1.00 mmol),
sodium tert-butoxide (118 mg, 1.20 mmol) and a magnetic
stir bar and was kept in vacuum for 10 min. After three ni-
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Selective Monoarylation of Primary Anilines Catalyzed by Pd(dippf)
Table 3. Highly selective synthesis of tertiary amines.[a]
[a]
The residue originating from the aryl halide (Ar3-X) is placed on the right-hand side. Conditions: 1.00 mmol amine,
1.00 mmol Ar1-Br, 2.40 mmol NaO-t-Bu, 0.5 mol% 6, 0.5 mol% dippf, 2 mL toluene, 808C, 20 h. Then 1.10 mmol Ar3-X in
0.5 mL toluene, 1208C, 24 h, isolated yields.
syringe. The reaction mixture was stirred at 808C for 20 h,
followed by addition of a solution of the second aryl halide
(1.10 mmol) in toluene (0.5 mL) via syringe. The tempera-
ture was increased to 1208C and stirring was continued for
another 24 h. The mixture allowed to cool to room tempera-
ture and diluted with dichloromethane (30 mL) and water
(30 mL). The aqueous layer was separated and extracted
with dichloromethane (2”20 mL). The combined organic
layers were dried over MgSO4, filtered and concentrated
under vacuum (408C, 500 mbar). The crude product was fur-
ther purified by flash chromatography (basic Al2O3, hexane/
ethyl acetate), yielding the corresponding tertiary amine;
yield: 75–96%.
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Acknowledgements
We thank J. Tang for helpful discussion, the Chinese Scholar-
ship Council (fellowship to F.J.), and A. Leidner for technical
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