Synthesis of chiral 2,2′-dipyridylamines and their use in the copper-catalyzed asymmetric allylic oxidation of cyclohexene

Article abstract of DOI:10.1016/j.tetlet.2004.05.006

Chiral dipyridylamines have been synthesized by N-arylation reactions, and the applicability of those compounds to the copper-catalyzed asymmetric allylic oxidation of cyclohexene was demonstrated.

Full text of DOI:10.1016/j.tetlet.2004.05.006

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5019–5021
Synthesis of chiral 2,20-dipyridylamines and their use in the
copper-catalyzed asymmetric allylic oxidation of cyclohexene
*
ꢀ
Carsten Bolm, Jean-Cedric Frison, Jacques Le Paih and Christian Moessner
Institut f€ur Organische Chemie der RWTH Aachen, Professor-Pirlet-Str. 1, D-52056 Aachen, Germany
Received 9 April 2004; revised 30 April 2004; accepted 3 May 2004
Abstract—Chiral dipyridylamines have been synthesized by N-arylation reactions, and the applicability of those compounds to the
copper-catalyzed asymmetric allylic oxidation of cyclohexene was demonstrated.
Ó 2004 Elsevier Ltd. All rights reserved.
In recent years bidentate ligands containing pyridine
units have attracted much attention.1 A large variety of
chiral bipyridines and phenanthrolines has been pre-
pared and their applicability in asymmetric metal-cata-
lyzed transformations has been demonstrated.1;2 Often,
efficient catalysts are obtained with both high catalytic
activity and enantioselectivity. Bipyridines and phen-
anthrolines form five-membered chelates with transition
metals. Analogous pyridine-based ligands giving six-
membered chelates have been much less studied, and
only recently chiral dipyridyl ketone 13 and 2,2-disub-
stituted dipyridylpropane 24 were introduced. Their
applicability in asymmetric catalysis has also been
established, and it was shown that a palladium catalyst
derived from 2 was more efficient in an allylic alkylation
reaction compared to the one obtained from the ana-
logues bipyridine 3. Other compounds with the potential
to give six-membered chelates upon metal binding are
2,20-dipyridylamines 4. Taking into account that a
number of 2,20-dipyridylamines have already been
applied in metal catalyses,5 it is rather surprising that
only very few optically active derivatives have been
described. Here, we report on the synthesis of C1-sym-
metric 2,20-dipyridylamines 4 (with R ¼ R0 ¼ H and
R00 ¼ chiral unit at C6) and their application in copper-
catalyzed asymmetric allylic oxidation reactions.
O
N
O
N
O
N
N
N
N
1
2
3
R
X
Pd catalysis
NH2
N
N
+
N
N
N
for R = R' = H
and R'' at C6
R''
R'
R''
4
5
6
X = Br or Cl
6a: X = R'' = Br;
6b: X = Br, R'' = CO2H
Keywords: Allylic oxidation; N-Arylation; Copper catalysis; 2,20-Dipyridylamines.
* Corresponding author. Tel.: +49-241-8094-675; fax: +49-241-8092-391; e-mail: carsten.bolm@oc.rwth-aachen.de
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.05.006

5020
C. Bolm et al. / Tetrahedron Letters 45 (2004) 5019–5021
2,20-dipyridylamine 4a and sulfoximidoyl-substituted 4d
H
H
H
N
N
N
gave 9 in 83% and 84% yield, respectively. Unfortu-
nately, however, the enantioselectivities were low (4%
and 15% ee, respectively). The best result was achieved
with pinene-derived 2,20-dipyridylamine 4c, which
afforded the product with 17% ee in 91% yield after only
3 h.
N
N
N
N
N
N
O
HO
4a : 78%
4b: 82%
4c : 86%
In summary, we have synthesized novel 2,2-dipyridyl-
amines and demonstrated their applicability as chiral
ligands in asymmetric catalysis. Although the enanti-
oselectivities in the asymmetric allylic oxidation reac-
tions of cyclohexene are still low, we are confident that
further ligand variations will result in an increase of the
asymmetric induction in this synthetically important
catalysis.
H
H
N
N
N
N
N
N
N
O
N
S
O
Ph
Me
4d: 84%
4e : 78%
The desired compounds 4 are easily accessible by
Buchwald–Hartwig aminations.6;7 Thus, starting from
2-aminopyridine (5) and various 6-substituted 2-halo
pyridines (6) palladium-catalyzed cross-couplings using
Pd(dba)2 (5 mol %), BINAP (5 mol %), and 1.5 equiv of
NaOtBu in toluene at 80 °C gave 2,20-dipyridylamines
4a–e in good yields (78–86%). The substituted pyridines
6, which were required for the syntheses of 4a, 4b, and 4c
were known,8 and the other two, which were used in the
preparation of 4d and 4e, were obtained by palladium-
catalyzed coupling of 6a with (S)-phenylmethyl-sulfox-
imine9–11 and standard oxazoline synthesis12 starting
from 6-bromo-pyridine-2-carboxylic acid (6b), respec-
tively. Noteworthy is the fact that the palladium-cata-
lyzed amination of the bromopyridines possessing the
coordinating sulfoximidoyl and oxazolinyl groups also
proceeded well to give 4d and 4e, respectively, without
altering the reaction rate of the coupling.
Acknowledgements
We are grateful to the Deutsche Forschungsgemeins-
chaft, the Fonds der Chemischen Industrie, and the
Alexander von Humboldt-Stiftung (J.L.P.) for financial
support.
References and notes
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Lemaire, M. Chem. Rev. 2000, 100, 2159.
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€
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in asymmetric copper-catalyzed allylic oxidation reac-
tions was studied. In order to allow an immediate
comparison with known systems,13 cyclohexene (7) was
selected as test substrate (Eq. 1). The catalyses were
performed in acetone at ambient temperature with
5 mol % of each Cu(OTf)2 and 2,2-dipyridylamines 4
using a ratio of olefin 7 and tert-butylperoxy benzoate
(8) of 10:1. In order to generate the active copper(I)
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adducts were treated with 6 mol % of phenyl hydrazine.
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Catalysts obtained from 2,20-dipyridylamines 4b and 4e
were entirely ineffective in promoting the reaction.
Probably the presence of the additional coordinating
group inhibited the catalysis. In contrast, 2,20-dipy-
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reaction time (4–8 h). Thus, the use of menthyl-derived
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O
O
Cu(OTf)2, L*, PhNHNH2
acetone, r.t.
O
+
O
ð1Þ
O
7
9
8

C. Bolm et al. / Tetrahedron Letters 45 (2004) 5019–5021
5021
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