Synthesis of Sterically Congested Triarylamines by Palladium-Catalyzed Amination

Article abstract of DOI:10.1002/ejoc.201400046

An efficient protocol for the palladium-catalyzed synthesis of sterically congested triarylamines from commercially available 1-chloro- or 1-bromonaphthalenes and diarylamines is described. The application of alkyllithium reagents as strong bases and a combination of Pd(OAc)₂ and SPhos (2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl) plays a crucial role in the success of this otherwise difficult to achieve C-N coupling reaction. A variety of secondary aromatic amines with versatile steric and electronic properties can be successfully used in this transformation to give the desired triarylamines in up to 99 % yield. The obtained products are important structural motifs in hole-transport materials for organic light-emitting diode applications.

Full text of DOI:10.1002/ejoc.201400046

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201400046
Synthesis of Sterically Congested Triarylamines by Palladium-Catalyzed
Amination
Stefan Riedmüller,[a,b] Oliver Kaufhold,[b] Hubert Spreitzer,[b] and Boris J. Nachtsheim*[a]
Keywords: Homogenous catalysis / Amination / Palladium / Cross-coupling / Steric hindrance
An efficient protocol for the palladium-catalyzed synthesis of
sterically congested triarylamines from commercially avail-
able 1-chloro- or 1-bromonaphthalenes and diarylamines is
described. The application of alkyllithium reagents as strong
bases and a combination of Pd(OAc)2 and SPhos (2-dicyclo-
coupling reaction. A variety of secondary aromatic amines
with versatile steric and electronic properties can be success-
fully used in this transformation to give the desired triaryl-
amines in up to 99% yield. The obtained products are impor-
tant structural motifs in hole-transport materials for organic
light-emitting diode applications.
hexylphosphino-2Ј,6Ј-dimethoxybiphenyl) plays
a crucial
role in the success of this otherwise difficult to achieve C–N
ested in the synthesis of sterically congested triarylamines
in which one of the three aryl groups was a 1-naphthyl sub-
stituent and the other two aryl groups had at least one ad-
ditional substituent in the ortho position of the aromatic
rings. Couplings of 1-halogenated naphthalenes with ortho-
unsubstituted diarylamines are known (Scheme 1, a).[2f,6b,6c]
Introduction
Triarylamines are important core motifs as structural ele-
ments for optoelectronic applications as host, transport, or
emitter materials in organic light-emitting diodes
(OLEDs).[1] Modern synthetic routes to triarylamines uti-
lize well-established palladium-catalyzed Buchwald–
Hartwig couplings,[2,3] copper-catalyzed Ullmann reac-
tion,[4] and other transition-metal-mediated reactions
mainly utilizing iron-[5] or nickel-based catalysts.[6] Transi-
tion-metal-free approaches are known as well.[7]
We are highly interested in the synthesis of sterically con-
gested triarylamines bearing additional alkyl substituents in
the 2-position of the aryl group, as it was demonstrated that
materials based on these substrates show improved device
lifetime, enhanced color coordinates, and significantly
higher thermal stability than the 2-unsubstituted deriva-
tives.[8a] Examples for privileged structures that are under
heavy investigation by a variety of chemical companies are
shown in Figure 1.[8b–8e] Unfortunately, for the synthesis of
these sterically hindered triarylamines,[9] the standard amin-
ation protocols mentioned above deliver unsatisfactory re-
sults. A rare example for a successful synthesis of 2-substi-
tuted triarylamines was reported recently by Kuwano and
co-workers. With a catalyst system comprising Pd(OAc)2/
P(tBu)3, aryl bromides could be coupled with a variety of
bis(2-methylphenyl)amines to give the desired triarylamines
in good yields.[10,11] However, we were particularly inter-
Figure 1. Representative examples of sterically congested triaryl-
amines used as dopant or emitting materials in organic electronic
devices.
[a] Institut für Organische Chemie, Universität Tübingen,
Auf der Morgenstelle 18, 72076 Tübingen, Germany
E-mail: boris.nachtsheim@uni-tuebingen.de
http://www.mnf.uni-tuebingen.de/fachbereiche/chemie/institute/
organische-chemie/institut/ag-nachtsheim.html
[b] Perfomance Materials Division, Merck KGaA,
Frankfurter Strasse 250, 64293 Darmstadt, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201400046.
However, coupling reactions between 1-halogenated
naphthalenes and diarylamines bearing substituents in the
2-position seem to be challenging, as no procedure is
known so far for this transformation. In this article we want
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S. Riedmüller, O. Kaufhold, H. Spreitzer, B. J. Nachtsheim
Table 1. Optimization studies.
SHORT COMMUNICATION
Entry Phosphine ligand Base
1[a]
PPh3 NaOtBu
RuPhos
Solvent Yield [%]
toluene trace
2[a]
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
K3PO4
Cs2CO3
NaH
toluene
toluene
0
0
3[a]
P(o-tolyl)3
ClP(tBu)2
SPhos
P(tBu)3
SPhos
SPhos
SPhos
SPhos
SPhos
SPhos
SPhos
4[a]
toluene trace
toluene 10[b]
toluene 30[b]
5[a]
6[a]
7[c,d]
8[c,d]
9[d]
xylene
xylene
toluene
toluene
toluene
trace
trace
0
0
0
Scheme 1. (a) Known literature procedures for the amination of 2-
halonaphthalenes with unsubstituted diarylamines. (b) The present
work in comparison.
10[c]
11[c]
12[e]
13[e]
14[e]
NEt3
DBU
LiHMDS
LDA
toluene 85[f]
toluene 87[f]
to report such a reaction, which gives direct access to steri-
cally congested triarylamines needed as materials with
unique properties for OLED applications (Scheme 1, b).
SPhos
n-hexyllithium toluene 92[f]
[a] Reaction conditions: 1a (0.455 mmol, 1.1 equiv.), 2a
(0.414 mmol, 1.0 equiv.), NaOtBu (0.538 mmol, 1.3 equiv.), solvent
(4 mL), 6 h. [b] Yield determined by GC–MS. [c] Reaction condi-
tions: 1a (0.46 mmol), 2a (0.683 mmol, 1.5 equiv.), base
(0.68 mmol, 1.5 equiv.), solvent (5 mL), 60 h. [d] Reaction tempera-
ture was 130 °C. [e] Reaction time was 1 h. [f] Yield of isolated
product. RuPhos = 2-dicyclohexylphosphino-2Ј,6Ј-diisopropoxybi-
Results and Discussion
Initially, we investigated the amination reaction of 1-
bromonaphthalene (1a) with bis(2,4-dimethylphenyl)amine
(2a) by using standard Buchwald–Hartwig amination con-
ditions. A variety of common phosphine ligands such as
PPh3, RuPhos, P(o-tolyl)3, and ClP(tBu)2[12] in combination
with NaOtBu as a typical base gave only disappointing re-
sults, as no reasonable formation of 3a was observed
phenyl, SPhos
=
2-dicyclohexylphosphino-2Ј,6Ј-dimethoxybi-
phenyl, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, LiHMDS =
lithium bis(trimethylsilyl)amide, LDA = lithium diisopropylamide.
The generally accepted catalytic cycle for the Buchwald–
(Table 1, entries 1–4). Only the SPhos[13] ligand, which was Hartwig amination suggests an oxidative addition of Pd0
introduced by Buchwald and co-workers in 2005 for Su- into the aryl halogen bond followed by coordination of the
zuki–Miyaura couplings, gave 3a in 10% yield (Table 1, en- amine. Upon coordination of the amine, its NH acidity is
try 5).[14] In addition to the desired product, substantial for- supposed to increase significantly. Therefore, even weak
mation (15%, measured by GC) of the naphthyl ether 1- bases can deprotonate the coordinated amine. After depro-
tert-butoxynaphthalene was observed as a result of an un- tonation, the coupling product is released by reductive eli-
desired coupling reaction between 1-naphthtylbromide and mination.[17] We assume that for the coupling of bulky sec-
NaOtBu. In the absence of primary and secondary amines, ondary amines and bulky aryl halogenides, the deproton-
the formation of aryl ethers is a well-known process. Their ation process of the amine plays a determining role. If both
competing formation during an amination reaction is in ge- the amine and the aryl moiety are coordinated to the palla-
neral negligible.
dium center, the key NH proton is sterically protected
An even better yield of 3a (30%) was observed upon against deprotonation at this stage of the catalytic cycle.[18]
[15]
using P(tBu)3
as a ligand (Table 1, entry 6). However, A different approach, which would circumvent the NH-de-
given that P(tBu)3 is air sensitive, highly flammable and py- protonation step at the sterically congested Pd site, would
rophoric, difficult to handle on a large scale, and subject to be the deprotonation of the amine before entering the cata-
drastic transport regulations, the easier-to-handle, air-stable lytic cycle. Secondary amines typically have pKa values of
SPhos ligand was used for further optimizations instead.[16] approximately 23 in benzene.[19] NaOtBu, the strongest base
To avoid formation of the undesired aryl ethers, other non- we used so far (pKa ≈ 19),[19,20] is not strong enough to de-
nucleophilic bases were investigated. Unfortunately, com- protonate the amine without coordinating to palladium.
mon phosphate, carbonate, and hydride bases were com-
Therefore, we next focused on bases with comparable or
pletely ineffective (Table 1, entries 7–9). Also, nitrogen-con- significantly higher pKa values than those of secondary aro-
taining organic bases such as DBU and NEt3 proved to be matic amines, in particular LiHMDS, LDA, and n-hexyl-
totally inefficient for this transformation (Table 1, entries 10 lithium. To our great delight, addition of each of these
and 11).
bases immediately improved the yields of 3a (Table 1, en-
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Synthesis of Sterically Congested Triarylamines
tries 12–14), whereas the latter one proved to be the best alene 1b as a cheap alternative to 1-bromo derivative 1a.[22]
base; it gave the desired product in 92% yield.[21]
The results of these experiments are outlined in Table 2. In
With the optimized reaction parameters in hand, we next general, 1-bromonaphthalene showed slightly higher reac-
proved the general applicability of our novel amination pro- tivity than 1-chloronaphthalene. Bis(2-methylphenylamine)
tocol. Thus, we subsequently investigated the substrate 2b gave desired triarylamine 3b in moderate yields of 48 (X
scope of this reaction by using a variety of sterically de- = Br) and 32% (X = Cl), although the steric demand was
manding aromatic secondary amines. In addition, we suc- identical to that of substrate 2a. Similar yields were ob-
cessfully extended the substrate scope to 1-chloronaphth- served with bis(2,3-dimethylphenyl)amine 2c to give triaryl-
amine 3c. Mixed diarylamine 2d could also be used in this
transformation to yield 3d in moderate yields of 44 (X =
Table 2. Scope of the amination of 1-chloro- and 1-bromonaphthal-
ene with various diarylamines.
Cl) and 43% (X = Br). 2-Phenyl-substituted diarylamine 2e
reacted smoothly to give sterically congested triarylamine
3e in high yields of up to 71%. 1-Naphthyl- and 2-naphthyl-
substituted diarylamines could be used as well, and they
gave 3f and 3g in good to excellent yields of 86 and 94%
(X = Br), respectively. Unfortunately, dimesitylamine did
not react under these conditions (data not shown). How-
ever, less bulky diarylamines such as 2h and 2i gave corre-
sponding triarylamines 3h and 3i in 99 (X = Cl) and 90%
yield (X = Br), respectively. To finish our experiments, we
performed the amination reaction with secondary amines
with different electronic properties. Electron-rich methoxy-
substituted diarylamines 2j and 2k also reacted smoothly to
give desired amines 3j and 3k in nearly quantitative yields
(up to 98%). The use of 3-trifluoromethyl-substituted di-
arylamine 2l resulted in the formation of 3l in good yields
up to 68% (X = Br).
Conclusions
In summary, we demonstrated synthetic access to steri-
cally congested triarylamines through a novel Pd-catalyzed
amination protocol. The key to the success of this method
is initial deprotonation of the diarylamine by using alkyl-
lithium reagents as strong bases. 1-Chloro- and 1-bromo-
naphthalenes were used in this transformation to give a
variety of triarylamines in up to 99% yield. Detailed analy-
sis of the properties of the materials, in particular their
long-term stability in optical devices, is part of current re-
search.
Experimental Section
General Procedure: Bis(2,4-dimethylphenyl)amine (2a; 250 mg,
1.11 mmol, 1.0 equiv.), palladium(II) acetate (4.98 mg, 0.022 mmol,
2 mol-%), and SPhos (18.22 mg, 0.044 mmol, 4 mol-%) were
charged into a nitrogen-flushed vial, and the vial was sealed with
a septum. After adding dry toluene (5 mL), 1-chloronaphthalene
(1b; 0.167 mL, 1.22 mmol, 1.1 equiv.) was added dropwise to the
solution, which was stirred for another few minutes. Then, n-hexyl-
lithium (2.47 m in hexane, 0.58 mL, 1.442 mmol, 1.3 equiv.) was
carefully added dropwise to the reaction mixture at room tempera-
ture. The mixture was then heated up to 105 °C for 2 h. After cool-
ing down to room temperature, the mixture was diluted with water
and extracted with toluene. The organic phase was washed with
water, dried with MgSO4, and concentrated in vacuo. The crude
residue was purified by column chromatography on silica gel (hept-
ane/CH2Cl2, 10:1) to give 3a (336 mg, 86%) as a colorless solid.
[a] Extended reaction times (in parentheses) were necessary with
the use of secondary amine 2f in combination with 1b (62 h) and
1a (5 h).
Eur. J. Org. Chem. 2014, 1391–1394
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S. Riedmüller, O. Kaufhold, H. Spreitzer, B. J. Nachtsheim
SHORT COMMUNICATION
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Acknowledgments
Financial support by the Deutsche Forschungsgemeinschaft
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Received: January 10, 2014
Published Online: January 31, 2014
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Eur. J. Org. Chem. 2014, 1391–1394