Efficient and recyclable Ir(i)-catalysts with the involvement of π-acceptor phosphines for N-alkylation of aryl amines with alcohols

Article abstract of DOI:10.1039/c6gc03096c

Mono-phosphines (L1 and L2) and diphosphines (L3 and L4) with typical π-acceptor character were prepared and applied in Ir(i)-catalyzed N-alkylation of amines with alcohols. It was found that the π-acceptor character of the applied phosphines is closely c

Full text of DOI:10.1039/c6gc03096c

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ARTICLE
Efficient and recyclable Ir(I)-catalysts with involvement of π-
acceptor phosphines for N-alkylation of aryl amines with
alcohols
Received 00th January 20xx,
Accepted 00th January 20xx
Huan Liu, DongꢀLiang Wang, Xia Chen, Yong Lu, XiaoꢀLi Zhao and Ye Liu*
DOI: 10.1039/x0xx00000x
The monoꢀphosphines (L1 and L2) and the diphosphines (L3 and L4) with typical πꢀacceptor character
were prepared and applied in Ir(I)ꢀcatalyzed Nꢀalkylation of amines with alcohols. It was found that the
πꢀacceptor character of the applied phosphines closely coꢀrelated to the catalytic efficiency of [Ir(COD)Cl]2
complex for this green reaction. Compared to PPh3 as the typical σꢀdonor (i.e. with the poor πꢀacceptor
character), L1-L4 all corresponded to the efficient Nꢀalkylation of aniline to benzylꢀaniline. While L1-L4
coordinating to Ir(I)ꢀcatalyst, the consolidated IrꢀP linkages due to πꢀbackdonation could well protect the
Irꢀcatalyst against deactivation, giving rise to the Nꢀalkylation of aniline. On the other hand, the
stabilized Irꢀcatalyst with the involvement of L2 could be recycled successfully at least 4 runs in the
ionic liquid of [MePh3P]Br without the detectable leaching of Ir and P elements in the organic products.
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believed that the nature of the involved ligands plays the
significant role in modulating the performance of the Ir(I,III)ꢀ
complexes for “borrowing hydrogen” in this reaction. Hence,
several kinds of ligands have been applied such as carbenes
[4,10], phosphaalkenes [11], P,Nꢀhemilabile ligands [12], and
Introduction
Conventionally, Nꢀalkylꢀamines are prepared via nucleophilic
substitution of amines with alkylating reagents such as alkyl
halides [1]. Since reported by Grigg [2] and Watanabe [3]
independently for the first time in the eighties, alkylation of
amines with alcohols via homogeneous catalysis has emerged
as an attractive alternative for the production of Nꢀalkylꢀ
amines, due to the advantages of avoided overalkylation,
readily available alcohols to replace the toxic alkylating agents,
and water as the only byꢀproduct [4]. Hence, this method
represents a greener synthesis route for alkylated amines with
high atomꢀeconomy [5]. A number of transition metal catalysts
such as Ru/Irꢀcomplexes have been exploited as the typical
homogeneous catalysts for alkylation of amines with alcohols
[6]. The overall transformation is based on a mechanism called
“borrowing hydrogen” or “hydrogen (auto)transfer” [4,7]. In
this “borrowing hydrogen” process, the oxidative
dehydrogenation (ꢀH2) of alcohol is followed by the
condensation of obtained aldehyde intermediate with amine to
give imine intermediate. The latter was hydrogenated (+H2) to
generate alkylated amine. Comparatively, Irꢀcomplexes have
been found more reactive than Ruꢀcomplexes [5,8] with the
supportive evidence by the DFT calculations [9]. It is also
cyclopentadienyl derivatives (Cp*) [11b,13]. Since the
πꢀ
acceptor character was basically required for the ligands like
phosphaalkenes and Cp* in this reaction, the uses of phosphines
with the typical
σꢀdonor character were rarely successful. On
the other hand, the recycling uses of the homogeneous Irꢀ
catalysts applied in
never been reported
Nꢀalkylation of amines with alcohols have
It is well known that the classical examples of Pꢀcontaining
ligands with ꢀacceptor character are phosphinites,
π
phosphonites and phosphites [14]. Anyway, the lability of PꢀO
bonds towards hydrolysis has limited their practical
applications [15,16]. So, the phosphine fragments linked to the
electronꢀwithdrawing groups such as ꢀF and ꢀCF3 with inert PꢀC
linkages are always considered as the alternatives [17]. The
objective of this work was to develop the typical phosphines
with
πꢀacceptor character and good stability to fulfill the
efficient Nꢀalkylation of amines with alcohols catalyzed by
simple Ir(I)ꢀcomplex of [Ir(COD)Cl]2. In order to develop such
phosphines, the electronꢀdeficient groups of imidazolyl and
imidazolium moieties were used to substitute one phenyl group
(ꢀPh) in PPh3. Then the obtained monoꢀphosphines (L1 and L2
)
were definitely featured with ꢀacceptor character at different
π
extent. For comparison, the corresponding diphosphines (L3
and L4) were prepared in parallel (Scheme 1). On the other
hand, the use of the ionic imidazoliumꢀbased phosphine (L2
)
with the RTIL solvent could fulfill the facile recovery and
recyclability of the Ir(I)ꢀcatalyst, which had become an efficient
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alternative to immobilize the homogeneous transition metal
catalysts [18].
It has been claimed that an increase of 1J
indicates an
31Pꢀ77Se
increase in the character of
π
ꢀacceptor ability (i.e., less
σ
ꢀdonor
character) of a phosphine [21ꢀ23]. The value of 1J
for the
31Pꢀ77Se
phosphine fragments in L1-L4 in comparison to PPh3 is in an
1J Se = 780 Hz), L4 1J
order of L2 = 782 Hz) > L1
1J Se = 753 Hz), L3
Se = 729
31Pꢀ77
H
[Ir(cod)Cl]2-L
N
R2
N
R2
NH2
31Pꢀ77
31Pꢀ77Se
(
+
(
+
R2
OH
KO(t-Bu), diglyme
R1
R1
1J Se = 751 Hz) > PPh3 (1
J
R1
31Pꢀ77
31Pꢀ77
Amine
(
(
Imine
Hz) (Fig. 1) [19,20]. Hence, it was indicated that L1-L4 were
definitely featured with stronger ꢀacceptor character (i.e. less
ꢀdonor character) than PPh3. Among them, the ionic L2 and
PPh2
π
Cl
IrII
CO
IrI
N
N
N
N
N
[Ir(cod)Cl]2
CO
auto-oxidation
N
N
P
P
P
P
σ
Ph2
Ph2
Ph2
Ph2
N
N
N
Cl
L4 are the strongest
π
ꢀacceptor phosphines with 1J
of 782
Cl
L1
31Pꢀ77Se
Ir-L1A
Ir-L1
Hz due to the most intensive electronꢀwithdrawing effect from
the positiveꢀcharged imidazoliums. It was also found that only
the electronic effect rather than steric effect of the organic
Me
N+
OTf-
PPh2
N+
CO
IrI
N
Ph2
P
[Ir(cod)Cl]2
CO
2OTf-
P
Me
N
N+
Me
N
Ph2
groups like imidazolyl or imidazolium would affect the
acceptor character of the neighboured phosphinoꢀfragments.
Hence, nearly the same 1J
of ~ 750 Hz was observed for
πꢀ
Cl
L2
Ir-L2
31Pꢀ77Se
PPh2 Ph2
P
L1 and L3 both tailed imidazolyl groups without discrimination
N
N
N
Ph2
N
[Ir(cod)Cl]2
CO
CO
N
N
N
N
to their steric skeleton. The same phenomenon was observed
P
IrI PPh2
Cl
over the imidazoliumꢀtailed L2 and
L
4 with 1J
of ~ 780
31Pꢀ77Se
L3
Ir-L3
Hz.
PPh2 Ph2P
2OTf-
Me
Me
The influence of L1-L4 and PPh3 with different
πꢀacceptor
N+
N
N
N+
[Ir(cod)Cl]2
CO
2OTf-
CO
IrI PPh2
N+
Me
N
N+
Ph2
N
character on the catalytic performance of [Ir(COD)Cl]2 was
investigated in the model reaction of ꢀalkylation of aniline
with benzyl alcohol. Firstly, the strong alkali of KO( ꢀBu) after
screening from Et3N, NaHCO3 and KOH corresponded to the
best reaction rate, resulting in 100% aniline conversion and 90%
P
Me
Cl
Ir-L4
N
L4
t
Scheme 1 The phosphines (L1-L4) with πꢀacceptor character and the
corresponding Irꢀcomplex catalyzed Nꢀalkylation of aryl amines with
alcohols
selectivity to benzylꢀaniline. The strong basicity of KO(tꢀBu)
did facilitate the condensation of aldehyde with alcohol to
afford imine intermediate, as well as enhanced the
nucleophilicity of –C=N to favor the subsequent hydrogenation
of imine. Then under the selected conditions [P/Ir = 1 molar
Results and discussion
ratio, 4 h, 120 oC, KO(
tꢀBu) as an additive, diglyme as a
solvent], the reaction data over the different phosphines (L1-
L4) were given in Table 1. Obviously over [Ir(COD)Cl]2
without the involvement of any ligand, only 70% conversion of
aniline and 73% selectivity to benzylꢀaniline were obtained
37.40
33.79
P
JSeꢀP = 729 Hz
Se
e
Selenide of PPh
3
2OTf-
Me
Me
Ph
N+
P
N+
(Entry 1). While the monoꢀphosphines with the enhanced
πꢀ
N
N
Ph
Se
P
77
31Pꢀ77
= 753 Hz; L2,
1J Se = 780
Pꢀ Se
1J31
Ph
Ph
Se
acceptor character (L1
,
20.96
JSeꢀP = 782 Hz
17.24
d
c
b
Selenide of L4
Hz) were added, L1 and L2 based Irꢀcatalysts both resulted in
N
N
N
N
Ph
Se
Ph
Se
23.58
P
much higher yields of benzylꢀaniline (~ 90%; Entries 2 and 3).
P
19.71
Ph
Ph
31Pꢀ77
And the diphosphines of L3 and L4 (L3, ,
1J Se = 751 Hz; L4
JSeꢀP = 751 Hz
JSeꢀP = 780 Hz
Selenide of L3
Me
1J Se = 782 Hz) also corresponded to the comparable yields
31Pꢀ77
N+
OTf-
N
Ph
20.15
24.01
P
under the same reaction conditions (Entries 4 and 5). While the
reaction time was shortened to 2 h, the excellent yields of
benzylꢀaniline (~ 90%) were still obtained over L1 and L3
based Irꢀcatalysts (Entries 7 and 9), whereas L2 and L4 with
Ph
Se
Selenide of L2
N
N
Ph
P
17.30
21.03
Ph
Se
JSeꢀP = 753 Hz
a
Selenide of L1
the strongest
π
ꢀacceptor character (1
J
~ 780 Hz) showed
31Pꢀ77Se
40
30
20
10
0
-10
-20
-30
-40
the relatively sluggish reaction rate (Entries 8 and 10). In
contrast, over PPh3ꢀbased Irꢀcatalyst, not only the conversion of
aniline but also the selectivity to benzylꢀaniline was universally
lower than those over L1-L4 (Entries 6 and 11). In addition,
diglyme was indeed to be the best choice as a solvent after
Chemical shift (ppm)
Fig. 1 31P NMR spectra of the selenides of L1-L4 in comparison to that
of PPh3 (202 MHz): a) reacting elemental selenium with L1 in CDCl3 at
70 oC for 10 h; b) reacting elemental selenium with L2 in CDCl3 at 70
oC for 10 h; c) reacting elemental selenium with L3 in CDCl3 at 70 oC
for 10 h; d) reacting elemental selenium with L4 in DMSOꢀd
6 at 70 oC
for 10 h; e) reacting elemental selenium with PPh3 in CDCl3 at 70 oC for
10 h [19, 20]
screening from pꢀxylene and anisole (or no solvent) (Entries
14ꢀ16), due to its high boiling point and high polarity to provide
a homogenous catalytic process carried out at 120 oC in a
heavyꢀwalled safe glass reactor. The data in Table 1 all
2 | J. Name., 2012, 00, 1-3
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demonstrated the presence of
N
ꢀbenzylideneꢀaniline byꢀproduct,
The molecular structural information of the corresponding Irꢀ
further confirming that Nꢀalkylation of benzylꢀaniline with complexes ligated by L1-L4 could help us further understand
benzyl alcohol underwent the formation of imine intermediate the importance of ꢀacceptor character of the phosphine in
as found in many examples [4,7,9,10,11(b),13(c)]. modulating the behaviour of Irꢀcomplex. The Irꢀcomplexes
π
It was noted that, as for L1 (monoꢀphosphine) and L3 ligated by L1 and L2 (monoꢀphosphines) was successfully
(diphosphine), although they possessed the different prepared in this work and the Irꢀcomplexes ligated by L3 and
coordination mode to Irꢀcenter, nearly the same yields of L4 (diphosphines) had been obtained in our previous work [20]
benzylꢀaniline (~90%) were obtained (Entries 2 and 4) only if (Fig. 2). It was found that the complexation of L1-L4
31Pꢀ77Se
they possessed the same
Hz). The similar situation was observe over L2 (monoꢀ afforded the corresponding Ir(I)ꢀcomplexes (Ir-L1
phosphine) and L4 (diphosphine) both with the same high L3 and Ir-L4). However, Ir-L1 was irreversibly converted to
acceptor ability (1
~ 780 Hz). The results indicated that Ir-L1A at the ambient temperature during the crystal growth in
π
ꢀacceptor character (1
J
~ 750 respectively to [Ir(COD)Cl]2 dimer under CO atmosphere all
,
Ir-L2, Ir-
π
ꢀ
31Pꢀ77Se
J
only the
applied phosphines coꢀrelated to the catalytic efficiency of paramagnetic complex in which Irꢀcentr was in +2 valence state
[Ir(COD)Cl]2 precursor for
ꢀalkylation. L1-L4 with the higher without 31P NMR signal.
ꢀacceptor character indeed corresponded to the more efficient
transformation of aniline to benzylꢀaniline in comparison to
PPh3 with the poor Se = 729 Hz).
ꢀacceptor character (1
πꢀacceptor character but not the chelation mode of the coꢀsolvent of dichloromethane/diethyl ether. The latter was a
N
π
31Pꢀ77
J
π
It was also found that when Ir-L2 was used to replace the
mixture of [Ir(COD)Cl]2 and L2 as the preꢀcatalyst, nearly the
same conversion of aniline and selectivity to benzylꢀaniline
were obtained under the same conditions (Entries 12 vs 2 and
13). It was indicated the in situ formed Irꢀcomplex ligated by
L2 exhibited the same activity as the asꢀsynthesized Ir-L2
.
Table 1 Irꢀcatalyzed
Nꢀalkylation of aniline with benzyl alcohol in
presence of the different phosphinesa
H
N
N
[Ir(COD)Cl]2-Ligand
KO(t-Bu), diglyme
NH2
+
OH
+
N-benzylidene-aniline
N-benzyl-aniline
PPh2 Ph2P
PPh2 Ph2
2OTf-
N
P
Me
Me
N
N+
N
OTf-
Me
N+
PPh2
N+
PPh2
N
N
N
N
N
N
L2
L1
L3
L4
Sel. (%)b
Benzylꢀ NꢀBenzylidene
aniline ꢀaniline
Conv.
Time
Entry Ligand Sol.
of aniline (%)b (h)
1
2
3
4
5
6
7
8
--
Diglyme
Diglyme
Diglyme
Diglyme
Diglyme
Diglyme
diglyme
Diglyme
Diglyme
Diglyme
Diglyme
70
100
100
100
98
66
100
60
97
56
44
99
98
4
4
4
4
4
4
2
2
2
2
2
4
4
2
2
2
73
92
89
96
90
76
90
93
94
89
73
90
89
89
86
76
27
8
11
4
10
24
10
7
L1
L2
L3
L4
PPh3
L1
L2
L3
L4
PPh3
Fig. 2 The single crystal structures of Ir-L1A, Ir-L2, Ir-L3 [20] and
Ir-L4 [20] (The hydrogen atoms and the solvent molecules were
omitted for clarity)
9
6
10
11
12c
13d
14
15
11
27
10
11
11
14
27
Ir-L2 Diglyme
L2
L1
L1
L1
Diglyme
ꢀꢀ
pꢀXylene 84
Anisole 63
Table 2 The selected bond distances and bond angles for Irꢀcomplexes
83
Selected bond length/Ǻ
IrꢀP1 IrꢀP2 IrꢀCl
2.328(8) ꢀꢀ 2.147(2) 180.00(ꢀ)
Bond angle/o
Irꢀcomplex
16
∠
P1ꢀIrꢀP2
a
[Ir(COD)Cl]2 0.025 mmol (Ir 1 mol %), monoꢀphosphine 0.05 mmol (L1,
L2, and PPh3), diphosphine 0.025 mmol (L3 and L4), P/Ir = 1 (molar ratio),
aniline 5.0 mmol, KO(tꢀBu) 3.5 mmol, benzyl alcohol 7.5 mmol, solvent 2
mL, temperature 120 oC, time 4 h; b Determined by GC; c The complex of Ir-
L2 was used instead of the mixture of [Ir(COD)Cl]2 (0.025 mmol) and L2
Ir-L1A
Ir-L2
2.319(2) 2.309(2) 2.344(2) 176.67(7)
2.317(1) 2.310(2) 2.384(1) 176.35(5)
2.291(1) 2.309(1) 2.374(1) 176.31(4)
Ir-L3[20]
Ir-L4[20]
d
(0.1 mmol); P/Ir = 2 (molar ratio) ([Ir(COD)Cl]2 0.025 mmol, L2 0.1
Ir(CO)(PPh3)2Cl [24] 2.330(1) ꢀꢀ
2.382(3) 180.00(ꢀ)
mmol]).
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These Ir(I)ꢀcomplexes (Ir-L1
all in the typical squareꢀplanar geometry, in which Ir(I)(5
center was coordinated by the two phosphine fragments in
transꢀposition, one CO, and one Clꢀ ion. In L3 and L4 as the the catalysis of Irꢀcomplex towards
,
Ir-L2
,
Ir-L3 and Ir-L4) were obtain the product (benzylꢀaniline) yield up to ~90% (Table 1,
8)ꢀ Entries 3 and 5).
Although L1 and L2 exhibited dramatic promoting effect on
ꢀalkylation of aniline with
d
N
diphosphines, the bulky bis(imidazolyl)ꢀphenyl arms between benzyl alcohol in diglyme, the separation and recycling uses of
the two phosphine fragments allowed them to develop PꢀIrꢀP the involved IrꢀP catalyst was still a bottleneck problem.
linkages in transꢀposition with bite angle of 176o (Table 2) Recently, many examples have shown that the ionic phosphines
[20]. Hence, L1 and L3 (or L2 and L4) with the similar values can be applied together with ionic liquid (IL) solvents as the
of 1J
corresponded to the similar product yields due to the efficient alternative to immobilize the transition metal catalysts
31Pꢀ77Se
same coordination ability and transꢀcoordinating mode to Irꢀ for separation and recycling uses [18]. Herein, the ionic
center (Table 1, Entries 2 and 4; Entries 3 and 5). However, as phosphine of L2 also highlighted us to explore the separation
for Ir-L3 and Ir-L4, the different
1J 1J
= 751 Hz) and L4
π
ꢀacceptor character in L3 and recycling of the IrꢀP catalyst by using the IL solvent in
= 782 Hz) made the IrꢀP place of diglyme. To demonstrate this issue, [Ir(COD)Cl]2 and
31Pꢀ77Se
31Pꢀ77Se
(
(
bond strength quite different (Table 2). The IrꢀP linkages in the L2 were applied with the IL of [MePh3P]Br
analogues of Ir-L2, Ir-L3 and Ir-L4 [IrꢀP, 2.291~2.319 Å] (methyltriphenylphosphonium bromide) for Nꢀalkylation of
were universally shorter than that in Ir(CO)(PPh3)2Cl [2.330(1) aniline (Table 3). It was found the catalytic system of
Å] [24], due to the stronger
acceptor ligands. It was noted that, the stronger
character was, the more intensive ꢀbackdonation was observed leaching of Ir and P in the combined organic phase after 4 runs
with the indication of the shortened IrꢀP bond length. For was nonꢀdetectable (below the detection limit of 0.1 g/g).
example, L4 was the strongest Se of Anyway, in the fifth run the yield of benzylꢀaniline dropped to
ꢀacceptor ligand with 1
π
ꢀbackdonation derived from the
π
ꢀ
[Ir(COD)Cl]2ꢀL2 could be recycled at least 4 runs without
π
ꢀacceptor obvious deactivation. The ICPꢀAES analysis indicated that the
π
<
ꢀ
31Pꢀ77
J
π
782 Hz, the corresponding IrꢀP bond lengths in Ir-L4 were 56% along with the precipitation of Irꢀblack, indicating the
shortest [IrꢀP, 2.2913(11) and 2.3086(11) Å]. Consequently, the deactivation of Irꢀcatalyst. When the imidazoliumꢀbased RTIL
consolidated IrꢀP linkages could well protect the Irꢀcatalyst of [Bmim]BF4 or [Bmim]PF6 was applied in place of
against deactivation. However, the too stable IrꢀP bond in L4 [MePh3P]Br as the IL solvent, the Nꢀalkylation was completely
(or L2) didn’t favour the timely dissociation of the phosphine to inhibited under the same reaction conditions, probably due to
make a vacancy for the accommodation of the substrate the complexation of Ir with [Bmim]+ cation as the potential
(alcohol), leading to the sluggish transformation of benzyl NHCꢀcarbene ligand. Comparatively, the recycling experiment
alcohol with aniline to benzylꢀaniline (Table 1, Entries 8 and of [Ir(COD)Cl]2 and L1 in [MePh3P]Br was unsuccessful. Due
10). Hence, over L2 and L4 able to develop the most stable IrꢀP to the serious leaching of Ir and P into the organic phase and
linkages, the prolonged reaction time of 4 h was enough to the quick deactivation of the catalyst, the yield of benzylꢀ
aniline dropped to 50% even in the 2nd run.
Table 3 Recycling uses of the catalytic system of [Ir(COD)Cl]2ꢀL2 with the presence of the phosphoniumꢀbased IL of [Ph3MeP]Br for Nꢀ
alkylation of aniline with benzyl alcohola
Sel.(%) b
Benzylꢀaniline
98
Run
Ionic salt
Conv. (%)b
Yield to benzylꢀaniline (%)
NꢀBenzylidenꢀaniline
1st (Fresh)
2nd
[MePh3P]Br
[MePh3P]Br
[MePh3P]Br
[MePh3P]Br
[MePh3P]Br
[Bmim]BF4
[Bmim]PF6
98
97
95
91
82
<5
<5
2
96
94
91
84
56
ꢀꢀ
97
96
92
68
ꢀꢀ
3
3rd
7
4th
8
5th*
32
ꢀꢀ
ꢀꢀ
Fresh
Fresh
ꢀꢀ
ꢀꢀ
a [Ir(COD)Cl]2 0.025 mmol (Ir 1 mol %), L2 0.05 mmol, [MePh3P]Br 5.6 mmol (2.0 g), aniline 5.0 mmol, benzyl alcohol 6.0 mmol, KO(tꢀBu) 3.5 mmol, 4 h,
120 oC; b Determined by GC; * Irꢀblack precipitated upon reaction.
The generality of [Ir(COD)Cl]2 with the involvement of L1 yields of amine products (Entries 1ꢀ3). 2ꢀPyridinemethanol with
for the Nꢀalkylation of amines with several kinds of alcohols the electronꢀwith drawing group of pyridyl reacted efficiently
was examined in Table 4. It was found that the quite narrow with aniline to afford the desired product in 98% yield (Entry
scope of substrates was suitable for this reaction. Only aniline 4). Under the similar reaction conditions, Aniline derivatives
derivatives and benzyl alcohol derivatives could be applied to with pꢀMeO, pꢀMe, and pꢀCl substituents successfully reacted
perform the corresponding Nꢀalkylation. The similar with benzyl alcohol to afford Nꢀbenzylated products in high
phenomenon had been found in many examples [4, 11 and 25]. yields without discrimination to the electronicꢀeffect (Entries 5ꢀ
The electronic substituent groups such as ꢀOCH3, ꢀCH3, and ꢀCl 7). However, the alkylation of phenethylamine with benzyl
at the paraꢀposition of benzyl alcohol barely influenced the alcohol resulted in the formation of the imine [(E)ꢀNꢀ
4 | J. Name., 2012, 00, 1-3
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ARTICLE
31Pꢀ77
Se =729 Hz), L1-
benzylidene(phenyl)methanamine] in 89% yield, indicating that PPh3 with the poor
the increased basicity of the imine without the superꢀconjugated L4 all corresponded to the efficient
structure badly depressed its subsequent hydrogenation to the benzylꢀaniline. While L1-L4 as the
π
ꢀacceptor character (1
J
N
ꢀalkylation of aniline to
ꢀacceptor phosphines
were coordinated to Irꢀcenter, the resultant consolidated IrꢀP
linkages due to ꢀbackdonation could well protect the Irꢀ
catalyst against deactivation, giving rise to the catalytic
efficiency for ꢀalkylation of benzyl alcohol with aniline. On
π
targeted amine product (Entry 8).
π
Conclusions
N
the other hand, the stabilized Irꢀcatalyst with the
involvement of L2 could be recycled successfully at least 4
runs in the IL of [MePh3P]Br without the detectable leaching
of Ir and P elements in the organic products. The generality
of [Ir(COD)Cl]2ꢀL1 catalytic system was not improved
herein. Only the narrow scope of the substrates such as
aniline derivatives and benzyl alcohol derivatives was
While one ꢀPh group in PPh3 was substituted by imidazolyl
and imidazolium respectively, the resultant monoꢀ
phosphines of L1 and L2 were developed with the obviously
enhanced
corresponding diphosphines of L3 with the similar
acceptor character to L1
1J Se ~ 750 Hz) and L4 with the
similar ꢀacceptor character to L2
prepared in parallel. It was found that the
πꢀacceptor character. For comparison, the
π
ꢀ
31Pꢀ77
(
π
(
1J
31Pꢀ77Se
~ 780 Hz) were
ꢀacceptor character
applicable for this type of
Nꢀalkylation.
π
of the applied phosphines coꢀrelated to the catalytic
performance of [Ir(COD)Cl]2 for Nꢀalkylation. Compared to
Table 4 NꢀAlkylation of amines with alcohol catalyzed by [Ir(COD)Cl]2 with the involvement of L1a
[Ir(COD)Cl]2/ L1
+
RNH2
+
HO
R'
R'
RHN
R'
RN
base, diglyme
Amine
Imine
.
Yield (%)b
Amine
Entry
RNH2
ROH
H3CO
H3C
Cl
Time (h)
Conv. (%)b
Imine
8
OH
1
2
3
NH2
NH2
NH2
4
4
4
95
87
90
89
OH
99
9
OH
100
11
OH
OH
4
5
NH2
4
6
100
100
98
77
2
N
H3CO
H3C
Cl
NH2
23
OH
OH
OH
NH2
6
7
8
6
6
6
100
100
99
92
89
10
8
NH2
11
89
NH2
o
a [Ir(COD)Cl]2 0.025 mmol (Ir 1 mol %), L1 0.05 mmol, aniline 5.0 mmol, alcohol 7.5, mmol, KO(tꢀBu) 3.5 mmol, diglyme 2 mL, 120 C; b Determined by
GC.
SHIMADZUꢀ2014 equipped with a DMꢀWax capillary column
Experimental
(30 m
× 0.25 mm × 0.25 ꢀm).
Reagents and analysis
All the reagents used in this work were purchased from Synthesis
Shanghai Aladdin Chemical Reagent Co. Ltd. and Acros China,
L1-L4 were prepared according to the procedures reported by
our group previously [19,20].
and used as received. THF was purified by refluxing, and
distilling from sodium which removes water, peroxides,
inhibitors and other impurities. Dichloromethane was dried by
Complex Ir-L1
1
CaH2 and DMSO by anhydrous sodium sulphate. The H and
Under nitrogen atmosphere, a solution of [Ir(COD)Cl]2 [dimer
of dichloro(1,5ꢀcyclooctadiene)iridium(I), 33.6 mg, 0.05 mmol]
in dry CH2Cl2 (5 mL) was stirred vigorously at room
temperature for ca. 10 min, and then the atmospheric CO (in a
balloon) was introduced into the reaction mixture for 50 min.
The obtained mixture was treated with a solution of L1 (32.8
mg, 0.1 mmol) in acetonitrile (5 mL) and stirred vigorously for
31P NMR spectra were recorded on a Bruker Avance 500
spectrometer. The 31P NMR spectra were referenced to 85%
H3PO4 sealed in a capillary tube as an internal standard. CHNꢀ
elemental analysis was performed on a Vario EL III Element
Analyzer. Gas chromatography (GC) was performed on a
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Journal Name
5 h. Then diethyl ether was added to afford the yellow h in the sealed reactor. Upon completion, the reaction solution
precipitates, which were collected after dryness under vacuum was analyzed by GC to determine the conversions ( ꢀdodecane
, ppm, as internal standard) and the selectivities (normalization
imi), 7.34ꢀ method). The retention time for the products of benzylꢀaniline
Ph), 6.91ꢀ6.94 (m, 4H, (amine) and Nꢀbenzylideneaniline (imine) in GC analysis were
, ppm, CD3Cl3): 12.06 (s, Ph2). calibrated by the authentic samples which were commercially
n
1
with the yield of 90 % (41.4 mg). H NMR (500 MHz,
CD3Cl3): 7.71ꢀ7.75 (m, 8H, Ph), 7.40ꢀ7.43 (m, 4H,
7.37 (m, 10H, Ph), 7.02ꢀ7.18 (m, 8H,
Ph). 31P NMR (202.4 MHz,
P
δ
H
H
H
H
H
δ
When the sample of Ir-L1 was dissolved in coꢀsolvent of available. The temperatureꢀprogrammed analysis for the
dichloromethane/diethyl ether to grow crystals for several days, samples was performed on GCꢀSHIMADZUꢀ2014 with a flame
the obtained complex was found to be Ir-L1A upon the single ionization detector (FID). The analysis conditions were as
crystal Xꢀray diffraction analysis, in which Irꢀcenter was in +2 follows: Injector temperature, 250 °C; Detector temperature,
valence state which was coordinated by two Clꢀ and two L1
.
250 °C; Initial oven temperature at 60 °C with retention time of
Consistently, the 31P NMR spectrum of Ir-L1A crystal was 2 min and then rising up to 240 °C with a temperature ramp of
broadened to flatness due to the paramagnetic nature of Ir(II)ꢀ 5 °C minꢀ1; Final oven temperature 240 °C with retention time
center.
of 25 min.
As for the recycling experiments, in a heavyꢀwalled safe glass
reactor charged with atmospheric N2 were added [Ph3MeP]Br
Complex Ir-L2
Under nitrogen atmosphere, a solution of [Ir(cod)Cl]2 (33.6 mg, (5.3 mmol), [Ir(COD)Cl]2 (0.025 mmol, 1.0 mol % Ir), L2
0.05 mmol) in dry CH2Cl2 (2 mL) was stirred vigorously at (0.05 mmol), KO(
ꢀBu) (3.5 mmol), aniline (5.0 mmol), and
t
room temperature for 10 min. Then the atmospheric CO (in a benzyl alcohol (6.0 mmol) in sequential. The mixture was
balloon) was introduced into the reaction mixture for 50 min. stirred at 120 oC for 4 h in the sealed reactor. Upon completion,
Afterwards, the reaction mixture was treated with a solution of the reaction solution was added with methanol (1.0 mL) and
nꢀ
L2 (49.2 mg, 0.1 mmol) in dry CH2Cl2 (3 mL). The resultant hexane (18 mL). Then the upper organic phase was decanted
mixture was stirred for another 3.5 h and then nꢀhexane was from the obtained biphasic reaction mixture, and the remaining
added to precipitate the yellow solids. The yellow solids were IL phase was washed with
nꢀhexane (3 mL × 3) to completely
collected after dryness under vacuum with the yield of 89 % extract the reactants and products. The combined organic phase
(55.2 mg). The sample suitable for single crystal Xꢀray was analyzed by GC and ICPꢀAES. The IL residue after the
diffraction analysis was obtained by slow volatilization from removal of methanol under vacuum was reused for the next run.
acetonitrile. 1H NMR (500 MHz, δ, ppm, CD3OD): 8.08 (s, 2H,
H
imi), 7.94ꢀ7.98 (m, 10H,
7.64 (m, 4H, Ph), 7.52ꢀ7.55 (m, 8H,
imi), 7.35ꢀ7.37 (m, 4H, Ph), 7.22ꢀ7.26 (m, 4H,
3). 31P NMR (202.4 MHz,
, ppm, CD3OD): 27.73
H
Ph), 7.61ꢀ7.64 (m, 4H,
Ph), 7.39ꢀ7.42 (s, 2H,
Ph), 3.32ꢀ3.34
HPh), 7.61ꢀ
Table 5 The crystal data and structure refinement for Ir-L1A and Ir
ꢀL2
H
H
Ir-L1A
IrꢀL2⋅2(CH2Cl2)
H
H
H
Empirical formula
C42H34Cl2Ir1N4P2 C49H44Cl5Ir1N4O1P2
(m, 6H, NC
H
δ
⋅2(CF3SO3)⋅2(CH2Cl2)
(s,
P
Ph2).
Formula weight
Crystal system
Space group
a (Å)
b (Å)
c (Å)
919.77
Monoclinic
P21/n
9.0997(3)
15.2322(5)
13.1977(5)
90
1410.39
Triclinic
Pꢀ1
Ir-L3 and Ir-L4 were prepared according to the procedures
reported by our group previously [20].
12.17337(7)
12.9667(7)
19.5210(11)
93.601(2)
96.085(2)
111.847(2)
2826.4 (3)
2
X-ray Crystallography
Intensity data were collected at 296 K for Ir-L1A and IrꢀL2 on
a Bruker SMARTAPEX II diffractometer using graphite
monochromated MoꢀK radiation ( = 0.71073 Å). Data
reduction included absorption corrections by the multiꢀscan
method. The structures were solved by direct methods and
refined by full matrix leastꢀsquares using SHELXSꢀ97
(Sheldrick, 1990), with all nonꢀhydrogen atoms refined
α
β
γ
(o)
(o)
(o)
93.1090(10)
90
α
λ
V (Å3)
1826.62(11)
2
1.672
Z
dcalc (g cmꢀ3)
1.657
2.801
(MoꢀKα) (mmꢀ1)
3.926
ꢀ
anisotropically. Hydrogen atoms were added at their T (K)
296(2)
296(2)
0.71073
20971
3209 (0.0233)
0.0222
0.0522
910
0.71073
32873
9892(0.0576)
0.0582
λ
(A)
geometrically ideal positions and refined isotropically. The
crystal data and refinement details are given in Table 5.
Total reflections
Unique reflections (Rint
R1 [I>2σ(I)]
wR2 (all data)
F(000)
Goodnessꢀofꢀfit on F2
)
General procedures for N-alkylation of amines with alcohols
0.1798
1400
1.018
All reactions were carried out under nitrogen atmosphere by
using mercuryꢀfree vacuum Schlenk line techniques. In a
heavyꢀwalled safe glass reactor charged with atmospheric N2
were added diglyme (2.0 mL), [Ir(COD)Cl]2 (0.025 mmol, 1.0
1.089
mol % Ir), the ligand (0.05 mmol), KO(tꢀBu) (3.5 mmol),
aniline (5.0 mmol), and benzyl alcohol (7.5 mmol) in
o
sequential. The obtained mixture was stirred at 120 C for 2~6
6 | J. Name., 2012, 00, 1-3
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I. Kmentov
á
and
Š
. Toma, Green Chem., 2008, 10, 484; (d) W. Miao
Acknowledgements
and T. H. Chan, Acc. Chem. Res., 2006, 39, 897; (e) J. Zhang, Y.
Wang, X. Zhao and Y. Liu, Eur. J. Inorg. Chem., 2014, 6, 975; (f) H.
You, Y. Wang, X. Zhao, S. Chen and Y. Liu, Organometallics, 2013,
32, 2698; (g) S. Chen, Y. Wang, W. Yao, X. Zhao, G. VOꢀThanh and
Y. Liu, J. Mol. Catal. A: Chem., 2013, 378, 293.
This work was financially supported by the National Natural
Science Foundation of China (Nos. 21673077, 21473058, and
21273077)
.
19 Y. Li, P. Wang, H. Zhang, X. Zhao, Y. Lu, Z. Popović and Y. Liu, J.
Mol. Catal. A: Chem., 2015, 402, 37.
20 H. Zhang, Y. Li, P. Wang, Y. Lu, X. Zhao and Y. Liu, J. Mol. Catal.
A: Chem., 2016, 411, 337.
Notes and references
1
2
3
M. B. Smith and J. March, Advanced Organic Chemistry, Wiley, New
York, 2001, , 499.
R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit and N. Tongpenyai, J.
Chem. Soc. Chem. Commun., 1981, 611.
Y. Watanabe, Y. Tsuji, H. Ige, Y. Ohsugi and T. Ohta, J. Org. Chem.,
1984, 49, 3359.
21 D. W. Allen and B. F. Taylor, Dalton Trans., 1982, 51.
5
22 A. Su
árez, M. A. MéndezꢀRojas and A. Pizzano, Organometallics,
2002, 21, 4611.
23 B. Milde, D. Schaarschmidt, T. Rüffer and H. Lang, Dalton Trans.,
2012, 41, 5377.
24 M. R. Churchill, J. C. Fettinger, L. A. Buttrey, M. D. Barkan and J. S.
Thompson Organometallics, 1988, 340, 257.
25 (a) A. Bartoszewicz, R. Marcos, S. Sahoo, A. K. Inge, X. Zou and B.
4
5
J. Li and P. G. Andersson, Chem. Commun., 2013, 49, 6131.
S. Imm, S. Bähn, L. Neubert, H. Neumann and M. Beller, Angew.
Chem. Int. Ed., 2010, 49, 8126.
Mart
í
nꢀMatute, Chem. Eur. J., 2012, 18, 14510; (b) D. Wang, K.
, 3910.
6
7
For reviews, see: (a) T. D. Nixon, M. K. Whittlesey and J. M. J.
Zhao, C. Xu, H. Miao and Y. Ding, ACS Catal., 2014,
4
Williams, Dalton Trans., 2009,
Crabtree, Chem. Rev., 2010, 110, 681; (c) G. Guillena, D. J. Ram
and M. Yus, Chem. Rev., 2010, 110, 1611; (d) S. Bähn, S. Imm, L.
5, 753; (b) G. E. Dobereiner and R. H.
ó
n
Neubert, M. Zhang, H. Neumann and M. Beller, ChemCatChem
2011, , 1853.
(a) G. Guillena, D. J. Ram
,
3
ó
n and M. Yus, Angew. Chem., Int. Ed.
,
2007, 46, 2358; (b) S. Ruch, T. Irrgang and R. Kempe, Chem. Eur. J.,
2014, 20, 1; (c) Kꢀi. Fujita, Y Enoki, R Yamaguchi, Tetrahedron
2008, 64, 1943.
,
8
9
S. Agrawal, M. Lenormand and B. MartínꢀMatute, Org. Lett., 2012,
14, 1456.
(a)D. Balcells, A. Nova, E. Colt, D. Gnanamgari, R. H. Crabtree and
O. Eisenstein, Organometallics, 2008, 27, 2529; (b) P. Fristrap, M.
Tursky and R. Madsen, Org. Biomol. Chem., 2012, 10, 2569.
10 Carbene: Q. Zou, C. Wang, J. Smith, D. Xue and J. Xiao, Chem. Eur.
J. 2015, 21, 9656.
11 Phosphaalkene: (a) Y. Chang, I. Tanigawa, H.ꢀO. Taguchi, K.
Takeuchi and F. Ozawa, Eur. J. Inorg. Chem., 2016, 5, 754; (b) Y.
Chang, Y. Nakajima and F. Ozawa, Organometallics, 2013, 32, 2210.
12 P,Nꢀhemilabile ligand: (a) B. Blank, S. Michlik and R. Kempe, Adv.
Synth. Catal., 2009, 351, 2903; (b) S. Michlik and R. Kempe, Chem.
Eur. J., 2010, 16, 13193.
13 [Cp*IrIIIX2]2 as precursor for Nꢀalkylation of amines: (a) K.ꢀi. Fujita,
K. Yamamoto and R. Yamaguchi, Org. Lett., 2002, 4, 2691; (b) R.
Kawahara, K.ꢀi. Fujita and R. Yamaguchi, J. Am. Chem. Soc., 2010,
132, 15108; (c) R. Kawahara, Kꢀi Fujita and R. Yamaguchi, Adv.
Synth. Catal., 2011, 353, 1161; (d) M. Zhu, K.ꢀi. Fujita and R.
Yamaguchi, Org. Lett., 2010, 12, 1336; (e) O. Saidi, A. J. Blacker, M.
M. Farah, S. P. Marsden and J. M. J. Williams, Chem. Commun.,
2010, 46, 1541; (f) S. Agrawal, M. Lenormand and B. MartínꢀMatute,
Org. Lett., 2012, 14, 1456; (g) C. Xu, L. Y. Goh and S. A. Pullarkat,
Organometallics, 2011, 30, 6499.
14 (a) N. Sakai, S. Mano, K. Nozaki and H. Takaya, J. Am. Chem. Soc.,
1993, 115, 7033; (b) Y. Yan, Y. Chi and X. Zhang, Tetrahedron:
Asymmetry., 2004, 15, 2173.
15 (a) Y. Canac, N. Debono, L. Vendier and R. Chauvin, Inorg. Chem.
,
2009, 48, 5562; (b) H. Tricas, O. Diebolt and P. W. N. M. van
Leeuwen, J. Catal., 2013 298, 198.
16 P. W. N. M. van Leeuwen and J. M. Chadwick, Homogeneous
Catalysts: ActivityꢀStabilityꢀ Deactivation, Wiley VCH, Weinheim
,
2012, , 1.
1
17 (a) C. L. Pollock, G. C. Saunders, E. C. M. S. Smyth and V. I.
Sorokin, J. Fluor. Chem., 2008, 129, 142; (b) M. L. Clarke, D. Ellis,
K. L. Mason, A. G. Orpen, P. G. Pringle, R. L. Wingad, D. A. Zaher
and R. T. Baker, Dalton Trans., 2005,
Paule, V. RatovelomananaꢀVidal., J. P. Gen
Dellis, Angew. Chem., Int. Ed., 2004, 43, 320.
18 (a) C. Huo and T. H. Chan, Chem. Soc. Rev., 2010, 39, 2977; (b) B.
7
, 1294; (c) S. Jeulin, S. D. D.
êt, N. Champion and P.
Ni and A. D. Headley, Chem. Eur. J., 2010, 16, 4426; (c) R. Šebesta,
This journal is © The Royal Society of Chemistry 20xx
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Graphical abstract
H
[IrCOD)Cl]2-L
N
R2
N
R2
NH2
+
+
R2
OH
KO(t-Bu), diglyme
R1
R1
R1
Amine
Imine
PPh2
Cl
IrII
CO
IrI
N
N
N
N
N
[Ir(COD)Cl]2
CO
auto-oxidation
N
N
P
P
P
P
Ph2
Ph2
Ph2
Ph2
N
N
N
Cl
Cl
L1
Ir-L1A
Ir-L1
Me
N+
OTf-
PPh2
N+
CO
IrI
N
Ph2
P
[Ir(COD)Cl]2
CO
2OTf-
P
Me
N
N+
Me
N
Ph2
Cl
L2
Ir-L2
PPh2 Ph2P
N
N
N
N
[Ir(COD)Cl]2
CO
CO
N
N
N
N
Ph2P IrI
PPh2
Cl
L3
Ir-L3
PPh2 Ph2P
2OTf-
Me
Me
N+
[Ir(COD)Cl]2
CO
N
N
N+
2OTf-
CO
N+
Me
N
N+
N
Ph2P IrI PPh2
Me
Cl
L4
Ir-L4
Efficient and recyclable Ir-catalyst with involvement of ionic π-acceptor phosphine in ionic liquid
solvent for N-alkylation of amines with alcohols
1