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P,N-Ligand Project
(Homogeneous Catalysis & Organic Synthesis)
Universität Bayreuth
IrIr-Catalyzed Alkylation of (Hetero)aromatic
(Hetero)aromatic Amines with Alcohols[4]
Introduction
The development of new ligands that efficiently stabilize transition metal centers is of great
academic and industrial interest. Our goal is the preparation of novel hybrid P,N-ligands and
their corresponding metal complexes and the application of these new catalysts in
homogeneous catalysis. Another focus lies on the development of synthetic methodologies for
the preparation of organic compounds in a highly efficient and selective fashion.
N
N
P
N
+
1
Ligand Development and Combinatorial Screenings[1]
1
N
N
N
N
P
1) BuLi
2) Ph2PCl
N
N
N
H
N
N
N
PPh2
N
Cl
Ir
[IrCl(cod)]2 (0.05-1.0 mol%)
P,N ligand (0.1-2.0 mol%)
KOtBu (1.1 equiv)
R
+
Y
N
P
70 °C, 24 h; for [Cp*IrHCl]2: 80 °C and 30 h reaction time
NH2
1
N
THF, rt
/2 [IrCl(cod)]2
H
N
diglyme, 70°C, 24 h
Y= C, N
R
OH
Y
R = aryl, alkyl, H
Scheme 2: Catalytic N-alkylation of aromatic amines with primary alcohols.
Cl
B(OH)2
[Pd]
+
N
N
P-functionalized aminopyridines can be prepared in
a great variety which makes them ideal candidates
for catalyst libraries and combinatorial screening
(Suzuki Coupling).[2]
RhRh-catalyzed Direct Arylation of Unactivated Arenes[2]
Rh
X +
O2N
Br
N
H
75
N
83
N
H
P2
H 2N
Cl
NO2
N
O2N
Cl
N
Cl
C-Cl Bond Activation of CH2Cl2 by P,NP,N- Rh Complexes[3]
Further development of the rhodium-P,N complex chemistry with regard to the development of
a more efficient catalyst for the direct-arylation reaction and a better understanding of the
reactivity of the latter afforded a surprising reactivity of these P,N-Rhodium complexes with
the activation of the solvent CH2Cl2. A combination of X-Ray and NMR-studies were
performed in order determine the active species of the reaction and to elucidate the reaction
pathway of the single and double CH2Cl2-activation.
N
+ [RhCl(cod)]2
P
CH2Cl2, rt
Cl
N
Cl
Rh
Cl
Cl
Cl P
Rh
Ph
Cl
single C-Cl bond activation
N Cl
Rh
Rh
P
+
R2
N
N
H
or
R1 ≠ R2
Isolated
Yield [%]
Product
O2N
N
P
N
H
R1 = R2
Isolated
Yield [%]
Product
Cl
O2N
R1
Scheme 3: Selective N,N‘-dialkylation of diamines in symmetric and nonsymmetric ways using alcohols.
O2N
N
2.2 Equiv Alcohol & KOtBu
Diglyme, 70 °C, 48h
NH2
NO2
Cl
P
N
[IrCl(cod)]2 (0.3-0.7 mol%)
P,N ligand (0.6-1.4 mol%)
N
Br
N3
2
90
71
O2 N
N
N4
N
H
CF 3
N
H
Rh1
Cl4
N
One of the outstanding properties of our Ir-catalyst is its high selectivity for monoalkylation of (hetero)aromatic
amines. Even with prolongated reaction times and high catalyst loadings the formation of tertiary amines could
not be observed. This excellent selectivity for monoalkylation could hence be exploited for the preparation of
symmetrically as well as nonsymmetrically N,N’-dialkylated diamines, providing the first simple and general
protocol for the synthesis of these compounds.
NO2
Br
89
86
N
H
N
N1
O2 N
92 b
Selectivity towards Monoalkylation – N,N‘N‘-Dialkylation of Diamines[5]
O2 N
Rh4
N
H
OMe
FG
Br
P1
N
N
Cl
NO2
Cl3
N
H
93
Rh
KOtBu, 70 °C
Br
N2
N
H
N
A novel P,N-ligand stabilized bimetallic Rh complex accomplishes the efficient nondirected
arylation of inactivated arenes like benzene. Not just iodides but also bromides and chlorides
undergo these coupling reactions and several functional groups (= FG) are tolerated. The key
to the catalytic efficiency is the bimetallic nature of the coordination compound used as
catalyst.
X = I, Br, Cl
Isolated
Yield [%]
Product
OMe
N
FG
Isolated
Yield [%]
Product
N
+
P
N
H
N
N
H
94
N
H
N
N
H
90
N
H
N
N
H
N
N
H
N
H
N
N
H
N
H
N
N
N
H
90
88
95
N
H
OMe
N
H
Cl
97
MeO
N
H
N
87
N
H
Cl
N
H
98
Cl
Rh
Cl
Cl
P Cl
Cl Cl N
Rh
Rh
N
P
H H
double C-Cl bond activation
Preparation of N-Aryl Diamines using Amino Alcohols[6]
In the course of our studies another important selectivity of catalyst 1 was observed. In comparison to
(hetero)aromatic amines, that are efficiently alkylated with alcohols, the reaction with aliphatic amines proceeds
rather poorly. As a consequence, the selective preparation of mono-N-aryl aliphatic diamines via alkylation of
aromatic amines with unprotected amino alcohols was attempted.
[IrC l(cod )]2 (0.05 m ol% )
P,N ligand (1.0 m ol% )
R2
Ar-N H 2
+
nNH2
HO
R1
Ar
N aO tB u, 110 °C , 24h
R2
N
H
nN H 2
R1
R 1, R 2 = H , alkyl, aryl
Scheme 4: Preparation of mono-N-aryl aliphatic diamines using amino alcohols.
Isolated
Yield [%]
Product
N
References
[1] T. Schareina, R. Kempe, Angew. Chem. Int. Ed. 2002, 41, 1521–1523
[2] S. Proch, R. Kempe, Angew. Chem. Int. Ed. 2007, 46, 3135–3138.
[3] B. Blank, G. Glatz, R. Kempe, Chem. Asian J. 2009, 4, 321–327
[4] B. Blank, M. Madalska, R. Kempe, Adv. Synth. Catal. 2008, 350, 749–758
[5] B. Blank, S. Michlik, R. Kempe, Chem. Eur. J. 2009, 15, 3790–3799
[6] B. Blank, S. Michlik, R. Kempe, Chem. Eur. J. submitted
N
H
N
N
H
N
N
H
N
N
H
NH2
81
NH2
83
NH2
93
NH2
N
N
89
Isolated
Yield [%]
Product
N
H
N
H
NH2
93
NH2
71
Ph
91
N
N
H
NH2
N
N
H
4 NH2
82