Pd-indenyl-diphosphine: An effective catalyst for the preparation of triarylamines

Article abstract of DOI:10.1039/c5ob01934f

A new Buchwald-type diphosphine ligand has been developed for applications in Pd-catalyzed amination reactions towards the preparation of triarylamines. The catalyst can be used to perform the amination of a diverse array of aryl and heteroaryl chlorides.

Full text of DOI:10.1039/c5ob01934f

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Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2015,
Accepted 00th January 2015
Pd-Indenyl-diphosphine: An Effective Catalyst for
the Preparation of Triarylamines†
Meng-Qi Yan,a Jia Yuan,b Yun-Xiao Pi,a Jin-Hua Liang,a Yan Liu,c Qing-Guo
Wu, a Xue Luo, a Sheng-Hua Liu, a Jian Chen, a Xiao-Lei Zhu,*a and Guang-Ao
Yu*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
monophosphine ligand 1 was deprotonated using nBuLi and reacted
with dicyclohexyl phosphine chloride to obtain the bidentate
phosphine 2 in 45 % yield. 2 could also be obtained in one-pot from
5 in 30 % total yield. Ligands 1 and 2 were found to be air-sensitive.
Therefore, treatment of the reaction mixtures with BH3 led to their
corresponding air-stable phosphine•BH3 complexes.4
A new Buchwald-type diphosphine ligand has been developed
for applications in Pd-catalyzed amination reactions towards the
preparation of triarylamines. The catalyst can be used to perform
the amination of a diverse array of aryl and heteroaryl chlorides.
This diphosphine ligand can be changed into an anionic ligand in
situ. The advantages and importance of this catalyst system
outline herein make it a valuable contribution to applications
in Pd-catalyzed amination reactions with aryl chlorides.
The ligand structure defines the steric and electronic
properties of the palladium catalyst and therefore plays a crucial
role in the efficiency of the Buchwald–Hartwig cross-coupling
reaction. The biaryl dialkyl monophosphine ligands developed by
Buchwald and co-workers, such as Brettphos, RuPhos, and JohnPhos
have demonstrated a broad substrate scope in the Buchwald–Hartwig
cross-coupling reaction.1 However, the development of anionic
phosphine ligands for cross-coupling reactions have rarely been
explored.2 Herein, we report a class of novel aryl substituted indenyl
monophosphine ligands and diphosphine ligands, which can react
with base and generate anionic phosphine ligands in situ;3 the
electron-donor ability of the indenyl anion may increase the electron
density at the phosphorus atom and improve the activity of the
catalytic system. We expect that these unique structural and
electronic properties of 1 and 2 would afford excellent reactivity and
Scheme 1. Syntheses of Phosphine Ligands 1 and 2
substrate scope towards the synthesis of triarylamines via
a
Buchwald–Hartwig coupling reaction and would be complementary
to those known catalytic systems.
Ligands 1 and 2 were applied in the palladium-catalyzed
Buchwald–Hartwig coupling reaction of diphenyl amine with aryl
chloride. The cross-coupling reaction between diphenyl amine and
chlorobenzene was chosen as the model system (Scheme 2). Besides
ligands 1 and 2, various structural monophosphine ligands were also
examined for comparison. The reactions were carried out at 90 °C in
DME for 24 h with Pd(dba)2 as the catalyst precursor. Whereas low
conversions were generally observed in this challenging cross-
coupling reaction with ligands such as (2-mesityl-1H-inden-3-yl)
dicyclohexylphosphine (6), CyJohnPhos (7), DavePhos (8),
The synthesis of 1 was accomplished in three steps from indenyl
boronic ester 3 (Scheme 1), which could be prepared on a kilogram
scale from 2-bromoindene. The palladium-catalyzed Suzuki–
Miyaura coupling of 3 with 2-bromoaniline provided 4 in 73 %
yield. Methylation of 4 with methyl iodide afforded 5 in 85 % yield.
The straightforward deprotonation of 5 using nBuLi and trapping the
resulting lithiated intermediate with dicyclohexyl phosphine chloride
Cy2PCl afforded the monophosphine ligand 1 in 70 % yield. The
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DOI: 10.1039/C5OB01934F
BrettPhos (10) and RuPhos (11), it is gratifying to report that ligand crystallography. Thus, we turned to DFT calculations in order to
2 and XPhos (9) provided a rapid conversion and excellent yields gather insight into the structural framework of the oxidative
(81 % and 85 %, respectively). Since ligand 1, 2, and 8 possess the addition complexes based upon
1
(anion)-Pd(Ph)Cl, (anion)-
2
same lower aryl ring, their dramatic difference in reactivity clearly Pd(Ph)Cl, and
8
-Pd(Ph)Cl. The starting structure of 8-Pd(Ph)Cl
demonstrates the influence of the steric and electronic properties was obtained from Buchwald et al.6 In this case, we located two
of the upper ring on their reactivity. We hypothesized that the possible complexes by performing ground-state energy
bulky sterically hindered and relatively electron-rich nature of 2 optimization on the oxidative addition product of
1
-Pd and
compared to DavePhos (8) facilitates the key transmetallation step of chlorobenzene (Figure 1). Complex
2
(anion)-Pd(Ph)Cl
this reaction.5
possesses two Pd-arene interactions with the non-phosphine-
containing ring of the ligand: Pd-C (2.85 Å) and Pd-N (2.61 Å).
On the contrary, complex
(2.83 Å) and/or Pd-N (3.33 Å) interactions with the non-
phosphine-containing ring of the ligand and complex -Pd(Ph)Cl
1(anion)-Pd(Ph)Cl only possesses Pd-C
8
only shows a Pd-N (2.59 Å) interaction with the non-phosphine-
containing ring of the ligand. The larger the distance between
Pd-arene, the lower the catalyst rate. Therefore,
largest catalyst rate (81%) compared to (47%) and
believe that the ability of anionic to stabilize the Pd(II) center
of the oxidative addition complex through labile Pd-C and Pd-N
interactions was mainly responsible for the effectiveness of as
2
took on the
1
8 (68%). We
2
2
a supporting ligand in Pd-catalyzed cross-coupling reactions.
Scheme 2. Ligand Screening for Buchwald-Hartwig Coupling
of Chlorobenzene and Diphenylamine
Deprotonation of indene by base has been well-documented. We
believe that the reaction of 1 and 2 with tBuONa in DME can
generate the anionic ligand in situ, and the strong electron-donor
ability of the indene anion may increase the electron density at
phosphorus and improve the reaction rate as a result. To provide
support for this finding, we undertook a series of 31P NMR studies.
When two equivalents of tBuONa was added to a solution of ligand
1 in DME, a red solution was formed immediately, the resonance for
the ligand (δ = -15.65 ppm) disappeared, and another new signal
appeared ( δ = -19.65 ppm), corresponding to anionic phosphine
ligand. Whereas, when two equivalents of tBuONa was added to a
solution of ligand 2 in DME, a black-red solution was formed
immediately, the two resonances for the ligand (δ = 9.19 ppm and δ
= -20.18 ppm) disappeared, and another new signal appeared (δ = -
15.79 ppm) corresponding to the anionic diphosphine ligand (See
Supporting Information).
Figure 1 . The Optimized Oxidation Addition Complexes
Composed of 1-Pd(Ph)Cl (A, B), 2-Pd(Ph)Cl (C),
and 8-Pd(Ph)Cl (D)
The high effectiveness of ligand 2 observed in the coupling
reaction between
chlorobenzene
and
diphenyl
amine
encouraged us to study the substrate scope in the Buchwald–Hartwig
coupling reaction of substituted aryl chlorides and the results
summarized in Scheme 3. In most cases, different aryl chlorides
reacted with diphenyl amine leading to their corresponding
products in good yield. For example, the reaction of chlorobenzene
with diphenyl amine gave rise to the corresponding tertiary amine in
81 % yield (10), coupling reactions of aryl chlorides bearing
electron-donating substituents such as –Me and –OMe at the para
and meta positions with diphenyl amine went smoothly, providing
moderate to high yields of the expected products (70 %–80 % yield)
(11, 12, 13, 14). The reaction of aryl chlorides bearing electron-
withdrawing groups such as –CF3 and –F at the para position also
permit the coupling reaction with diphenyl amine, giving the
required products in moderate to good yields (15, 16). Moreover, the
Many researchers have proved that the Pd-arene interaction is
very important in Pd-catalyzed cross-coupling reactions. Despite
numerous attempts employing various conditions, we have not
been able to obtain structural information on the
1
(anion)/2(anion)-Pd oxidative addition complex using X-ray
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DOI: 10.1039/C5OB01934F
base-sensitive –CN group was tolerated using our catalytic system the coupling reaction gave the desired products in moderate yield
and the corresponding triarylamine (17) was obtained in 62 % yield. (28, 29).
In addition, 2-chloronaphthalene underwent the desired coupling
reaction with diphenylamine, giving the triarylamine product in 65
% yield (18).
Pd(dba)2 (1 mol%)
H
N
Ar
N
2 (2 mol%)
ArBr
BuONa (1.2 equiv)
DME, 90 °C, 24 h
+
t
OMe
nBu
Br
MeO
OMe
N
N
N
N
19
20
21
22
(80%)
(42%)
(55%)
(70%)
N
N
N
nBu
nBu
23
24
25
(75%)
(64%)
(85%)
Scheme 4. Synthesis of Triarylamines from Bromides and
Diphenyl amine
In summary, we have developed a novel class of Buchwald-
type bidentate phosphine ligand for the Buchwald–Hartwig
coupling reaction incorporating an indenyl diphosphine
framework. Ligand
phosphine ligand upon reaction with
2
, which could be changed into an anionic
BuONa in situ, has
t
Scheme 3. Synthesis of Triarylamines from Chlorides and
provided different steric and electronic properties in contrast to
the biaryl ligands reported by Buchwald and co-workers, which
have shown special applications towards the preparation of
Diphenyl amine
triaryl amines. Ligand
2 has demonstrated its catalytic ability for
To further demonstrate the general applicability of our catalyst
system, we studied the Buchwald–Hartwig amination reaction with
substituted aryl bromides (Scheme 4). We adopted the optimized
reaction conditions to the amination of various aryl bromides with
diphenylamine. 1-Bromo-4-butylbenzene, 1-bromo-3, 4, 5-
trimethoxybenzene, 1, 3-dibromobenzene and 4-bromostyrene could
be aminated smoothly to give the triarylamine products in
satisfactory yields (Scheme 4, 19, 20, 21, 22). In addition,
sterically hindered aryl bromides underwent smooth transformations
under the standard conditions to give the desired products in
moderate yield (23, 24). Furthermore, the reaction of 2-bromo-9, 9-
dibutylfluorene with diphenylamine gave the triarylamine product in
excellent yield (25).
the Buchwald–Hartwig coupling reaction with a broad substrate
scope, which includes sterically congested aryl halides,
compounds possessing a variety of functional groups, and
heteroaryl halides.
Heterocyclic triarylamine compounds are of particular interest
to materials science. The application of heterocyclic compounds in
cross-coupling reactions still remains
a synthetic challenge,
because the ligating ability of the heteroatoms present can lead
to catalyst deactivation.7 In addition, the electronic properties at
certain positions in the heterocycle used can be unfavorable for
the elementary reactions required in these catalytic processes.8 To
the best of our knowledge, only a few heterocyclic triarylamines
have been reported.9 We have examined the use of our catalytic
system in the coupling reaction for a range of heteroaryl halides
(Scheme 5). For example, 2-chloropyridine and 2-bromopyridine
underwent the desired coupling reaction with diphenylamine to
afford the corresponding products in moderate yield (26).
Unfortunately, 4-trifluoromethyl-2-chloropyridine coupled with
diphenylamine to give the triaryl amine in a low 30 % yield (27).
However, in the case of 2-chloropyrazine and 2-chloroquinoxaline,
Scheme 5. Synthesis of Heterocyclic Triarylamine From
Aryl halides and Diphenyl Amine
Acknowledgements
The authors would like to thank the National Natural Science
Foundation of China (Nos. 21472060, 21072071 and 21272088),
self-determined research funds of CCNU from the colleges’ basic
research and operation of MOE (Nos. CCNU15KFY001,
CCNU15A02012).
Notes and references
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DOI: 10.1039/C5OB01934F
aKey Laboratory of Pesticide & Chemical Biology, Ministry of Education,
Central China Normal University, Wuhan 430079, China. EꢀMail:
yuguang@mail.ccnu.edu.cn
bState Key Laboratory of ElementoꢀOrganic Chemistry, Nankai University,
Tianjin 300071, China
cState Key Laboratory of Catalysis, Dalian Institute of Chemical Physics,
Chinese Academy of Sciences, Dalian 116023, China
Electronic supplementary information (ESI) available: For ESI see DOI:
10.1039/b000000x
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