Synthesis of C2-symmetric and unsymmetrically substituted 2,2′-dipyridylamines and crystal structure of a chiral 2,2′-dipyridylamine copper(II) complex

Article abstract of DOI:10.1016/j.jorganchem.2004.06.032

C₂-symmetric and unsymmetrically substituted 2,2′-dipyridylamines have been synthesized by sequential Buchwald-Hartwig aminations of halo-pyridines. The X-ray crystal structure of a copper dichloride complex bearing a C₂-symmetric 2,

Full text of DOI:10.1016/j.jorganchem.2004.06.032

Journal of Organometallic Chemistry 689 (2004) 3767–3777
www.elsevier.com/locate/jorganchem
Synthesis of C2-symmetric and unsymmetrically substituted
2,20-dipyridylamines and crystal structure of a chiral
2,20-dipyridylamine copper(II) complex
*
´
Carsten Bolm , Jean-Cedric Frison, Jacques Le Paih, Christian Moessner, Gerhard Raabe
Institut fu¨r Organische Chemie der RWTH Aachen, Professor-Pirlet-Straße 1, D-52056 Aachen, Germany
Received 10 May 2004; accepted 7 June 2004
Available online 30 July 2004
Abstract
C2-symmetric and unsymmetrically substituted 2,20-dipyridylamines have been synthesized by sequential Buchwald–Hartwig am-
inations of halo-pyridines. The X-ray crystal structure of a copper dichloride complex bearing a C2-symmetric 2,20-dipyridylamine
reveals details of the binding properties of the ligand and the coordination geometry at the metal center. In preliminary experiments
the use of the new nitrogen chelates in asymmetric catalysis has been demonstrated.
ꢀ 2004 Elsevier B.V. All rights reserved.
Keywords: Allylic oxidation; N-Arylation reactions; Catalysis; 2,20-Dipyridylamines; Palladium
1. Introduction
R
R
Si
In the field of enantioselective catalysis, nitrogen-con-
taining compounds are regarded as privileged ligands
[1]. Important representatives are chiral oxazolines and
pyridines, which have found numerous applications in
various asymmetric transformations. Among bidentate
nitrogen-based ligands those with a bipyridine, phen-
anthroline, and terpyridine core have extensively been
studied [2]. As recently pointed out by Chelucci, the
chemistry of those compounds mostly relies on the effi-
cient formation of five-membered chelates upon metal
binding. Interestingly, only a few chiral pyridine-based
ligands with the potential to form six-membered chelates
with metals have been introduced. Wrightꢀs bis(pyr-
idyl)silane 1 [3], Chelucciꢀs dipyridylpropane 2 [4] and
Kwongꢀs dipyridylketone 3 [5] are rare examples of
those compounds.
N
N
N
N
O
O
2
1
O
R1
N
N
N
O
N
N
O
R2
R3
4
3
Recently, Kempe showed the applicability of another
class of dinitrogen ligands, 2,20-dipyridylamines 4, in tran-
sition metal-catalyzed transformations. Their nickel
*
Corresponding author. Tel.: +49-241-8094675; fax: +49-241-
8092391.
E-mail address: carsten.bolm@oc.rwth-aachen.de (C. Bolm).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.06.032

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C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
complexes are efficient catalysts in ethylene polymeriza-
tion [6] and palladium complexes catalyze Heck reactions
[7]. Despite these interesting examples, the chemistry of
2,20-dipyridylamines has mainly been limited to the study
of their coordination behaviour, and among the numerous
dipyridylamine/metal complexes prepared for this purpose
those of copper salts are the most dominant ones [8].
elements are closer to the coordinating nitrogens, allow-
ing a more direct control on the coordination sphere of
the metal. Such influence could be the key for a success-
ful asymmetric metal-catalyzed process.
Recently, we reported the synthesis of simple 2,20-di-
pyridylamines 4 with R1 =R2 =H [11]. We now extended
our synthetic program and prepared C2-symmetric as well
as unsymmetrically substituted derivatives with R2 =R3
and R2„R3„H, respectively. Furthermore, we investigated
the use of those new 2,20-dipyridylamines in copper-
catalyzed asymmetric allylic oxidation reactions.
2. Results and discussions
2.1. Synthesis of the starting materials
In order to synthesize C2-symmetric and unsymmetri-
cally substituted 2,20-dipyridylamines, chiral 2-halo-pyri-
dines were required (Scheme 1). Those compounds have
extensively been studied and their syntheses are well doc-
umented[2].Oneofthemostconvenientmethodsisthede-
symmetrization of 2,6-dibromo-pyridine (5) [2,12]. In this
manner, pyridines 6 [3] and 7 [12] wereprepared according
to literature protocols. Palladium-catalyzed N-arylation
of 5 with one equivalent of NH-sulfoximine 9 following
a method developed in our laboratories [13] afforded sul-
foximidoyl-substituted pyridine 10 [14,15]. With a Pd(0)/
BINAP catalyst, 10 was obtained in 84% yield.
2,6-Dibromopyridine (5) also served as starting mate-
rial for the synthesis of oxazolinyl-substituted pyridine
12. In the five-step reaction sequence, 5 was first con-
verted into 6-bromo-pyridine-2-carboxylic acid 11 [16].
Chlorination of 11 with oxalyl chloride (in THF and
in the presence of NEt3) followed by amide formation
with (S)-valinol and subsequent cyclization with thionyl
For the synthesis of 2,20-dipyridylamines 4 palladi-
um-catalyzed Buchwald–Hartwig amination reactions
[9] starting from 2-halo-pyridines can be used (Scheme 1)
[6,10]. With respect to the preparation of chiral com-
pounds two general approaches are possible: First, the
stereogenic center might be embedded in a substituent
R1 of the bridging amino unit. Alternatively, the pyri-
dine rings can bear chiral groups (R2 and R3). If both
of them are identical and homochiral, C2-symmetric
2,20 dipyridylamines result. The second approach ap-
pears more promising, since in this case the stereogenic
Scheme 1. 2-Halo-pyridines 6-12 used for the synthesis of chiral 2,20-dipyridylamines [dba=dibenzylidene acetone; BINAP=2,20-bis-
(dipenylphosphino)-1,10-binaphthyl].

C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
3769
chloride furnished 12 in 45% overall yield (from 5). The
only 6-chloropyridine applied in this study was com-
pound 8. This b-pinene-derived halo pyridine attracted
our attention since Kocovsky [17] reported on high
enantioselectivities in the copper catalyzed allylic oxida-
tion of cyclic alkenes with bipyridines prepared from 8.
Our initial attempts to prepare the 6-bromo analogue of
8 failed, and thus the subsequent 2,20-dipyridylamine
synthesis utilized Kocovskyꢀs chloropyridine 8.
ral 2,20-dipyridylamines with tertiary amino bridges (4
with R1 „H), we first studied the coupling of 8 with com-
mercially available N-benzyl-2-amino-pyridine (22). Us-
ing a catalyst prepared from 5 mol% of each Pd(dba)2
and DPPP [1,3-bis(diphenylphosphino)propane] in com-
bination with NaOtBu and Bu4NBr at 100 ꢁC, 2,20-di-
pyridylamine 23 was obtained in 81% yield after 24 h.
2.2. Synthesis of amino-bridged 2,20-dipyridylamines 4
with R1 =H
N
N
N
H
Our first targets were 2,20-dipyridylamines possessing
a bridging secondary amine (4 with R1 =H). An interest-
ing feature of those products is the presence of an acidic
NH function. The coordination properties of deproto-
nated 2,20-dipyridylamine ligand in Ir(I), Rh(I) and
Ru(II) complexes have already been investigated [18].
C1-symmetric dipyridylamines with R1 =R2 =H can
easily be synthesized by N-arylation of 2-aminopyridine
13. Applying a Pd(0)/BINAP catalyst system in the cou-
pling of 13 with 6-halopyridines 6, 7, 8, 10 and 12 led to
2,20-dipyridylamines 14-18 in yields up to 86% [11].
For the synthesis of a C2-symmetric 2,20-dipyridyl-
amine with a secondary amino group in the bridge (com-
pound 21), 6-chloropyridine 8 was converted into its
6-amino analogue 20 by palladium-catalyzed amination
with a Pd(0)/BINAP catalyst and ammonia surrogates
19 [9,19] followed by acid hydrolysis of the intermediate
benzophenone imine derivative (not shown; 91% yield
over two steps). Palladium-catalyzed coupling of 8 and
20 afforded C2-symmetric 2,20-dipyridylamine 21 in
91% yield (Scheme 2).
N
N
23
22
Next, we focused our attention on the preparation of
C2-symmetric derivatives by the palladium-catalyzed
double N-arylation. Since previous studies [10] had
shown that this transformation required long reaction
times leading to low product yields, a screening of
Pd(0) catalysts prepared from Pd(dba)2 and various
phosphine ligands was performed first. As coupling
partners N-butylamine and readily available 6-bromo-
pyridine 6 were chosen (Scheme 3).
From this initial catalyst screening a palladium cata-
lyst with DPPP as ligand was identified as the most effi-
cient one for the direct double N-arylation, giving
mono- and diarylated amines 24 and 25, respectively, in
a ratio of 40:60. Since we had used a twofold excess with
respect to the amine, the lack of remaining starting mate-
rial indicated that 6 had either decomposed or that unde-
sired side-reactions had occurred under these reaction
conditions. Stimulated by Hartwigꢀs [20] results, who de-
scribed positive effects of bromide ions in aminations of
aryl chlorides, and with the goal to maximize the yield
of diarylated product 25 the catalysis was next performed
2.3. Synthesis of amino-bridged 2-20-dipyridylamines 4
with R1 „H
In order to investigate the applicability of the palladi-
um-catalyzed amination reaction in the formation of chi-
Pd(dba)2, BINAP,
NaOtBu, toluene, 80 ˚C
NH
Ph
2M HCl, THF
+
r.t., 0.5 h
N
Cl
Ph
N
NH2
19
20
8
H
N
Pd(dba)2, DPPP, NaOtBu
Bu4NBr, toluene, 100 ˚C
N
N
8
+
20
21
Scheme 2. Synthesis of C2-symmetric dipyridylamine 21.

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C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
nBu
N
nBuNH2 (0.5 eq.)
Pd(dba)2, ligand,
N
N
+
6
nBu
O
O
N
N
O
NaOtBu, toluene,
100 ˚C, 20 h
H
24
25
ligand
24 (%) 25 (%)
BINAP
85
45
40
20
15
55
60
80
DPEphos
DPPP
DPPP + Bu4NBr (1 eq.)
Scheme 3. Optimization of the conditions for the direct double N-arylation reaction.
in the presence of 1 equiv. of Bu4NBr. To our delight we
found that use of this additive increased the ratio of 24
and 25 to 20:80. Finally, with a slight excess of 6 (2.2
equiv.) the double arylation afforded 25 in 92% yield. Un-
der these optimized conditions other C2-symmetric 2,20-
dipyridylamines could also be obtained in high yield.
Thus, use of benzyl amine and 6-halopyridines 7 and 8
led to 26 and 27 in 94% and 92% yield, respectively.
2,20-Dipyridylamine 28 [21] was isolated in 96% yield
starting from 2-picolylamine and 2-bromopyridine 6.
These results were very promising, as they showed that
this strategy was also applicable to different substrates.
we envisaged that highly unsymmetrical chiral 2,20-di-
pyridylamines would become accessible by a subsequent
second coupling [22] with a different 6-halopyridine.
Such approach would allow the straightforward prepa-
ration of ligand libraries, which could prove useful in
asymmetric catalysis. In order to test this hypothesis,
amino pyridine 24 was first prepared using the Pd(0)/
BINAP catalyst system as described in Scheme 3. On a
25 mmol scale, the product was obtained in 96% yield
after 24 h at 100 ꢁC, using only 1 mol% of catalyst.
The arylation of 24 with 6-halopyridines 7 and 12 was
then performed using 4 mol% of the DPPP-based palla-
dium(0) catalyst (in toluene at 100 ꢁC) with NaOtBu as
base and Bu4NBr as additive. Under these reaction con-
ditions, unsymmetrically substituted 2,20-dipyridylam-
ines 29 and 30 were obtained in 76 and 94% yield,
respectively.
N
N
N
N
N
N
nBu
N
nBu
N
OH HO
26
27
N
N
N
N
O
O
N
O
HO
N
O
N
N
N
29
30
O
In the light of these very positive results, it was sur-
prising to note that the attempted coupling between 24
and sulfoximidoyl-substituted bromo-pyridine 10 did
not proceed at all. Both reagents were recovered almost
quantitatively. Also performing the reaction at higher
temperature, longer reaction times and the use of ent-
10 did not lead to the desired coupling reaction.
28
Another interesting point arose from this optimiza-
tion study since it showed that the use of BINAP as
ligand resulted in the predominant formation of
mono-arylated (secondary) amines. As a consequence,

C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
3771
2.4. X-ray crystal structure analysis of a copper(II)
complex bearing a chiral dipyridylamine
2.5. Applications of chiral 2,20-dipyridylamines in asym-
metric catalysis
Next, we wondered about the capability of the chiral
2,20-dipyridylamines to coordinate to metals. In order
to explore the limits we chose sterically crowded and
rigid C2-symmetric dipyridylamine 27 for this study
and treated (in analogy to a literature protocol [23]) a so-
lution of 27 in dichloromethane with a solution of anhy-
drous copper dichloride in ethanol. Crystals of 1:1
complex 31 (Fig. 1), which were suitable for X-ray crystal
structure analysis, were then obtained by slow diffusion
of diethyl ether into a CH2Cl2 solution of the 27/CuCl2
mixture.
The X-ray crystal structure of complex 31 differs sig-
nificantly from that of known dichloro(di-2-pyridylam-
ine-N,N0)copper(II) [24], prepared from unsubstituted
2,20-dipyridylamine. Whereas the former complex is
characterized by an almost planar ligand and a distorted
tetrahedral coordination of the copper atom, the 2,20-di-
pyridylamine segment is significantly bent in 31 with the
After the development of the synthetic strategy and
the investigation of the solid state structure of 31, we
wondered about the potential of the new 2,20-dipyridyl-
amines to serve as ligands in metal-catalyzed asymmetric
processes. Bidentate pyridines are known to be effective
in copper catalyzed transformations [2–4,17], and we
therefore focussed our attention on the copper-catalyzed
asymmetric allylic oxidation of olefins [25]. As test sub-
strate cyclohexene (32) in combination with tert-but-
ylperoxybenzoate (33) as oxidant was chosen.
Following well-established routes, the catalytically ac-
tive metal species was formed in situ by treatment of
copper(II) triflate with phenylhydrazine in the presence
of the ligand (Scheme 4).
The results of this study are summarized in Table 1.
Unfortunately, use of 2,20-dipyridylamines 15 and 16
as well as amino-pyridine 18 (with one or two equiva-
lents relative to copper) led to inactive catalysts. On
the other hand, 2,2-dipyridylamine 17 bearing a sulfox-
imidoyl substituent proved applicable leading to
product 34 in good yield and with some enantioselectiv-
ity (15% ee; Table 1, entry 4). The most active cata-
lysts were obtained with the various pinene-derived
˚
Cu atom 1.39(1) A above the N1–N2–N3 plane. More-
over, the angle between the N1–Cu–N2 and the
Cl1–Cu–Cl2 planes is only 27.0(5)ꢁ in 31 but 61.3(1)ꢁ
in dichloro(di-2-pyridylamine-N,N0)copper(II) [24]. In
the former complex the N–Cu and Cl–Cu distances of
˚
2.009(10)/2.078(12) and 2.209(8)/2.245(9) A are slightly
longer and shorter than those in the latter one
˚
[1.948(6) and 2.250(3) A]. All of those data indicated
Cu(OTf )2/ligand
(5 mol% each)
that the steric crowding due to the annulated bicyclic
ring systems on the two pyridines had a major effect
on the coordination geometry at the metal. Further-
more, we realized that the originally C2-symmetric
2,20-dipyridylamine became part of a C1-symmetric met-
al complex, which was most likely to be relevant for the
use of such complexes in asymmetric catalysis.
PhCO3tBu
+
OCOPh
PhNHNH2(6 mol%),
acetone, r.t.
33
34
32
Scheme 4. Copper-catalyzed allylic oxidation of cyclohexene (32).
Table 1
Allylic oxidation of cyclohexene (32) to give 34 (Scheme 4) catalyzed
by copper complexes bearing chiral 2,2-dipyridylamines
Entry Ligand Copper
Solvent
Time Yield ee
(h)
(%)
(%)
1
2
14
15
16
17
18
21
23
25
27
28
18
18
18
18
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Acetone
8
76
0
–
Acetone 160
Acetone 160
n.r.a
n.r.a
89
3
–
4
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
8
3
15
17
11
9
5
91
84
6
8
7
6
76
65
8
8
0
9
3
36
92
45
0
10
11
12
13
14
0
(CuOTf)2 ÆPhH Acetone 120
88
91
17
17
11
15
CuPF6
Cu(OTf)2
Cu(OTf)2
Acetone
CH2Cl2
3
2
87
56
CH3CN 150
a
Fig. 1. ORTEP plot of complex 31; H atoms omitted for clarity.
n.r.=no reaction.

3772
C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
2,2-dipyridylamines. Although in these cases high yields
(84–91%) were reached, the enantioselectivities re-
mained low (<20% ee). The best result was achieved
with C1-symmetric dipyridylamine 18 which led to 34
with 17% ee in 91% yield. The bridging amine was also
found to influence the efficiency of the catalyst (Table 1,
entries 5–7 and 9). Thus the ones derived from 2,20-di-
pyridylamines possessing a secondary bridging amine
gave higher enantioselectivities than their N-alkylated
analogues. The solvent or the copper source did not sig-
nificantly influence the enantioselectivity of the catalyst
prepared from 18 and only the reaction times varied
(Table 1, entry 5 versus entries 11–14).
The data presented in Table 1 also show that use of
C2-symmetric 2,20-dipyridylamine 27 led to racemic 34
(entry 9). Taking into account the structural informa-
tion of the X-ray crystal structure of 31 this result is
not too surprising, since the catalysis appears to proceed
rather remote from the stereogenic centers of the ligand
system. Apparently, a better control of the stereochem-
ical reaction path can be achieved with less crowded lig-
ands in this particular case.
3.2. Syntheses of the starting materials
3.2.1. (S)-2-Bromo-6-(S-methyl-S-phenyl)-sulfoximi-
doyl-pyridine (10)
In a Schlenk tube flushed with argon were succes-
sively added Pd(dba)2 (0.08 mmol, 46 mg), rac-BINAP
(0.1 mmol, 62 mg), (S)-(S-phenyl-S-methyl)-sulfoximine
(2.0 mmol, 310 mg), 2,6-dibromo-pyridine (3.0 mmol,
711 mg) and sodium tert-butylate (3.0 mmol, 288 mg).
Toluene (40 mL) was added and the solution was heated
at 80 ꢁC for 8 h. The reaction mixture was evaporated to
dryness, and the oily residue redissolved in diethyl ether
and filtered onto celite. The solvent was removed, and
the yellow residue recrystallized from toluene/hexanes.
White solid, 84% yield; m.p. 158–160 ꢁC [a]D =+77.4.
1H NMR (300 MHz): d=8.08 (m, 2H), 7.72–7.56 (m,
3H), 7.32 (d, J=7.9, 7.7 Hz, 1H), 6.95 (d, J=7.7 Hz,
1H), 6.79 (d, J=7.9 Hz, 1H), 3.46 (s, 3H). 13C NMR
(75 MHz): d=158.9, 139.6, 139.2, 133.3, 129.5, 127.8,
119.8, 114.9, 45.2. IR: 1426, 1389, 1302, 1201, 1154,
1123, 1123, 1095, 1068, 1021. MS (EI, 70 eV): m/z=
312.0, 310.0 (M+). Calc. for C12H11BrN2OS: C,
46.31; H, 3.56; N, 9.00. Found: C, 46.35; H, 3.74; N,
8.93.
2.5.1. Conclusion and outlook
New chiral 2,20-dipyridylamines have been synthe-
sized by palladium-catalyzed cross coupling reactions
and their applicability in copper-catalyzed allylic oxida-
tions has been demonstrated. The information obtained
by the X-ray crystal structure analysis of copper com-
plex 31 proved useful for the understanding of the
stereochemical requirements of the ligands. Our current
efforts are devoted to the synthesis of other chiral 2,20-
dipyridylamines that will allow to improve the so far
rather limited enantioselectivity in this synthetically
highly useful oxidative C–O-bond formation.
3.2.2. (4S)-2-Bromo-6-(4-isopropyl-4,5-dihydro-oxazol-
2-yl)pyridine (12)
To a solution of oxalyl chloride (7.5 mmol, 635 lL) in
THF (10 mL) were added 2-bromo-pyridine-6-carboxy-
lic acid (5.0 mmol, 1.01 g), and the reaction mixture was
stirred for 30 min at room temperature. The excess
oxalyl chloride and the solvent were removed under re-
duced pressure, and the solid residue was dissolved in
CH2Cl2 (20 mL). This solution was added dropwise to
a cooled solution of (S)-valinol (6.0 mmol, 618 mg)
and triethylamine (9.0 mmol, 1.2 mL) in CH2Cl2 (20
mL). The solution was stirred for 4 h, and then
quenched with 1 M NaOH (50 mL). The organic layer
was separated, washed with saturated NaHCO3, brine
and dried over MgSO4. The resulting amido alcohol
(with a purity of 95% as determined by NMR spectros-
copy) was directly used for the next step. A solution of
the amido alcohol in CH2Cl2 was cooled to 0 ꢁC and
SOCl2 (6.0 mmol) was added. The mixture was stirred
over night at room temperature and then quenched with
1 M NaOH. The aqueous phase was extracted twice
with CH2Cl2, and the combined organic phases were
dried with MgSO4. The product was purified by column
chromatography on silica gel. White solid, 74% yield;
3. Experimental
3.1. General
All reactions were performed under an inert atmos-
phere of argon using Schlenk techniques. All glasses
were flame dried prior to use and then flushed with ar-
1
gon. H NMR and 13C NMR were recorded in CDCl3
using TMS as an internal standard on an Inova 400
spectrometer or Gemini 300. Chemical shifts are given
in ppm relative to TMS. IR spectra were recorded on
a Perkin–Elmer FTIR as KBr pellets. MS spectra were
measured on a Varian MAT 212 and HRMS spectra
on a Finnigan MAT 95 mass spectrometer. Optical rota-
tion was measured on a polarimeter Perkin–Elmer PE-
241 in CHCl3 with c=1 unless otherwise stated. Melting
1
m.p. 105–107 ꢁC. [a]D =ꢀ67.1. H NMR (400 MHz):
d=8.05 (dd, J=7.4, 1.4 Hz, 1H), 7.62 (dd, J=7.9, 7.4
Hz, 1H), 7.59 (dd, J=7.9 Hz, 1H), 4.51 (dd, J=9.6,
9.3 Hz, 1H), 4.19 (m, 2H), 1.89 (m, 1H), 1.04 (d,
J=6.9 Hz, 3H), 0.94 (d, J=6.9 Hz, 3H). 13C NMR
(100 MHz): d=161.1, 147.6, 141.7, 138.5, 130.0, 122.7,
72.8, 70.9, 32.7, 19.0, 18.1. IR: 2984, 2961, 2870, 1640,
points were measured on a Buchi B-540. Elemental anal-
¨
yses were measured on a Heraeus CHNO-Rapid.

C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
3773
1550, 1442, 1357, 1120. MS (EI, 70 eV): m/z=270.2,
268.2 (M+). Calc. for C11H13BrN2O: C, 49.09; H, 4.87;
N, 10.41. Found: C, 48.76; H, 4.84; N, 10.31.
s, 1H), 7.55–7.50 (m, 3H), 7.03 (d, J=8.2 Hz, 1H),
6.78 (dd, J=7.2, 5.8 Hz, 1H), 4.41 (dd, J=9.1, 8.8 Hz,
1H), 4.11 (m, 2H), 1.92 (m, 1H), 1.06 (d, J=6.9 Hz,
3H), 0.96 (d, J=6.9 Hz, 3H). 13C NMR (100 MHz):
d=162.7, 154.0, 153.7, 147.8, 144.9, 138.5, 138.0,
117.1, 116.7, 114.2, 111.8, 73.1, 70.9, 33.1, 19.6, 18.5.
IR: 3201, 2865, 1646, 1576, 1533, 1459, 1331. MS (EI,
70 eV): m/z=282.3 (M+). Calc. for C16H18N4O: C,
68.06; H, 6.43; N, 19.84. Found: C, 68.02; H, 6.34; N,
19.48.
3.3. N-Arylation of primary amino pyridines (GP1)
In a Schlenk tube flushed with argon were succes-
sively added Pd(dba)2 (0.04 mmol, 23 mg), rac-BINAP
(0.05 mmol, 31 mg), 2-halo-6-substituted-pyridine (1.0
mmol), 2-amino-pyridine (13, 1.1 mmol, 103 mg) and
sodium tert-butylate (1.5 mmol, 144 mg). The Schlenk
tube was flushed with argon, toluene (20 mL) was added,
and the reaction mixture was heated at 80 ꢁC until the
reaction was complete (monitored by TLC or GC).
The mixture was cooled to room temperature, diluted
with diethyl ether and filtered through celite. Solvents
were removed on a rotary evaporator and the product
purified by column chromatography on silica gel.
3.3.4. (S)-[6-(S-Methyl-S-phenyl)-sulfoximidoyl-pyri-
din-2-yl]-pyridin-2-yl-amine (17)
Synthesized according to GP1. White solid, 84%
yield; m.p. 81–83 ꢁC. [a]D =+314.9. 1H NMR (300
MHz): d=8.11 (d, J=4.9 Hz, 1H), 7.99 (d, J=1.0 Hz,
1H), 7.97 (d, J=1.5 Hz, 1H), 7.61 (d, J=8.4 Hz, 1H),
7.53–7.43 (m, 4H), 7.35 (t, J=7.9 Hz, 1H), 7.05 (br s,
1H), 6.72 (dd, J=5.9, 1.0 Hz, 1H), 6.63 (d, J=8.2 Hz,
1H), 6.41 (d, J=7.9 Hz, 1H), 3.28 (s, 3H). 13C NMR
(75 MHz): d=158.6, 153.8, 152.3, 147.6, 140.5, 139.4,
137.6, 133.1, 129.5, 128.0, 116.1, 111.9, 108.4, 103.3,
46.0. IR: 3191, 1601, 1433, 1336, 1151. MS (EI, 70
eV): 324.1 (M+). Calc. for C17H16N4OS: C, 62.94; H,
4.97; N, 17.27. Found: C, 63.32; H, 5.20; N, 16.86.
3.3.1. (1S,2R,5S)-(+)-[6-(2-Isopropyl-5-methyl-cyclo-
hexyloxy)-pyridin-2-yl]-pyridin-2-yl-amine (14)
Synthesized according to GP1. White solid, 78%
yield; m.p. 118–120 ꢁC. [a]D =+99.3. 1H NMR (400
MHz): d=8.27 (d, J=4.1 Hz, 1H), 7.83 (d, J=8.5 Hz,
1H), 7.71 (br s, 1H), 7.57 (td, J=7.1, 1.6 Hz, 1H), 7.45
(t, J=8.0 Hz, 1H), 6.84 (dd, J=7.1 Hz, 1H), 6.72 (d,
J=7.7 Hz, 1H), 6.25 (d, J=8.0 Hz, 1H), 4.88 (ddd,
J=10.7, 10.7, 4.1 Hz, 1H), 2.31 (d, J=12.1 Hz, 1H),
2.11 (m, 1H), 1.74 (m, 2H), 1.54 (m, 2H), 1.20–0.96
(m, 9H), 0.95 (m, 6H), 0.76 (d, J=6.9 Hz, 3H). 13C
NMR (100 MHz): d=162.6, 153.9, 152.0, 147.6, 140.0,
137.2, 116.0, 111.4, 102.1, 75.0, 47.5, 40.9, 34.6, 31.8,
26.3, 24.0, 22.2, 20.7, 16.7. IR: 3268, 3191, 2958, 1624,
1578, 1536, 1438, 1339, 1293, 1225, 1145, 1040. HRMS
Calc. for C20H27N3O: 325.21541. Found: 325.21549.
Calc. for C20H27N3O: C, 73.81; H, 8.36; N, 12.91.
Found: C, 73.42; H, 8.35; N, 12.63.
3.3.5. (6R,8R)-(ꢀ)-(5,6,7,8-Tetrahydro-7,7-dimethyl-
6,8-methanoquinolin-2-yl)-pyridin-2-yl-amine (18)
Synthesized according to GP1. White solid, 86%
yield; m.p. 72–74 ꢁC. [a]D =ꢀ49.4. 1H NMR (300
MHz): d=8.16 (dq, J=4.9, 1.0 Hz, 1H), 7.47 (td,
J=8.6, 2.0 Hz, 1H), 7.36 (d, J=8.2 Hz, 1H), 7.30 (m,
2H), 6.70 (m, 1H), 2.76 (m, 3H), 2.61 (ddd, J=9.6,
5.7, 5.7 Hz, 1H), 2.24 (sept, J=2.9 Hz, 1H), 1.34 (s,
3H), 1.24 (d, J=9.4 Hz), 0.64 (s, 3H). 13C NMR (75
MHz): d=154.0, 150.4, 147.6, 137.7, 137.3, 122.2,
115.8, 111.3, 108.8, 50.1, 40.4, 39.3, 30.9, 30.6, 29.6,
26.2, 21.3. IR: 3309, 2934, 1597, 1509, 1434, 1311. MS
(EI, 70 eV): m/z=265.2 (M+). Calc. for C17H19N3: C,
76.95; H, 7.22; N, 15.84. Found: C, 77.16; H, 7.28; N,
15.52.
3.3.2. (1S)-(+)-2,2-Dimethyl-1-[6-(pyridin-2-ylamino)-
pyridin-2-yl]-propan-1-ol (15)
Synthesized according to GP1. Colorless viscous oil,
1
78% yield. [a]D =+44.2. H NMR (400 MHz): d=8.37
(br s, 1H), 8.26 (d, J=4.1 Hz, 1H), 7.62–7.46 (m, 3H),
7.34 (d, J=8.2 Hz, 1H), 6.83 (td, J=6.6, 1.1 Hz, 1H),
6.72 (d, J=7.4 Hz, 1H), 4.30 (s, 2H), 0.95 (s, 9H). 13C
NMR (100 MHz): d=158.3, 154.2, 152.8, 138.0, 137.6,
116.6, 115.5, 112.0, 110.3, 80.7, 36.6, 26.4. IR: 3600–
2820 (m), 1607, 1533, 1454, 1152, 1059, 1015. HRMS
Calc. for C15H19N3O: 257.15281. Found: 257.15263.
3.3.6. (6R,60R,8R,80R)-(+)-bis-(5,6,7,8-Tetrahydro-7,7-
dimethyl-6,8-methanoquinolin-2-yl)-amine (21)
Synthesized according to GP1 using 20 instead of 2-
amino-pyridine (13). White solid, 84% yield; m.p. 179–
1
181 ꢁC. [a]D =+120.4 (c=0.735). H NMR (400 MHz):
d=7.23 (m, 4H), 7.02 (br.s, 1H), 2.84-2.72 (m, 6H),
2.61 (m, 2H), 2.24 (sept, J=3.2 Hz, 2H) 1.33 (s, 6H),
1.25 (d, J=9.6 Hz, 2H), 0.63 (s, 6H). 13C NMR (100
MHz): d=164.3, 150.8, 137.0, 121.4, 108.1, 50.2, 40.5,
39.4, 31.0, 30.7, 26.3, 21.4. IR: 3406, 2937, 1582, 1510,
1444, 1344, 1265. MS (EI 70 eV): m/z=359.3 (M+). Calc.
for C24H29N3: C, 80.18; H, 8.13; N, 11.68. Found: C,
80.23; H, 7.83; N, 11.85.
3.3.3. (4S)-(ꢀ)-[6-(4-Isopropyl-4, 5-dihydro-oxazol-2-
yl)-pyridin-2-yl]-pyridin-2-yl-amine (16)
Synthesized according to GP1. White solid, 78%
yield; m.p. 101–103 ꢁC. [a]D =ꢀ65.2. 1H NMR (400
MHz): d=8.20 (dd, J=4.9, 1.1 Hz, 1H), 8.09 (d,
J=8.2 Hz, 1H), 7.63 (dd, J=7.4, 5.3 Hz, 1H), 7.56 (br

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C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
3.4. Direct bis-N-arylation reaction (GP2)
0.59 (s, 6H). 13C NMR (75 MHz):d=164.6, 154.1,
140.4, 136.4, 128.1, 128.0, 126.3, 122.2, 111.7, 51.2,
50.2, 40.4, 39.2, 30.9, 30.7, 26.2, 21.3. IR: 2911, 1582,
1448, 1244, 1222. MS (EI, 70 eV): m/z=449.5 (M+).
Calc. for C31H35N3: C, 82.81; H, 7.85; N, 9.35. Found:
C, 82.53; H, 7.69; N, 9.23.
In a Schlenk tube flushed with argon were successively
added Pd(dba)2 (0.04 mmol, 46 mg), DPPP (0.05 mmol,
42 mg) in toluene (2 mL) and the solution was stirred 15
min at room temperature. Then, the 2-halo-6-substituted-
pyridine (2.2 mmol), tetrabutylammonium bromide (2.0
mmol, 644 mg), amine (1.0 mmol) and sodium tert-buty-
late (3.0 mmol, 288 mg) were added under inert atmos-
phere. The reaction mixture was treated with toluene
(18 mL), and then heated at 100 ꢁC until the reaction
was complete (monitored by TLC or GC). The mixture
was cooled to room temperature, diluted with ethyl ace-
tate and filtered through celite. Solvents were removed
on a rotary evaporator and the product was purified
by column chromatography on silica gel.
3.4.4. (1S,10S,2R,20R,5S,50S)-(+)-Bis-[6-(2-isopropyl-
5-methyl-cyclohexyloxy)-pyridin-2-yl]-pyridin-2-ylmeth-
yl-amine (28)
Synthesized according to GP2. White solid, 96%
yield; m.p. 93–95 ꢁC. [a]D =+160.0. 1H NMR (300
MHz): d=8.45 (dq, J=4.0, 1.0 Hz, 1H), 7.41 (td,
J=7.9, 2.0 Hz, 1H), 7.34 (t, J=7.9 Hz, 2H), 7.15 (d,
J=7.9 Hz, 1H), 6.99 (m, 1H), 6.82 (d, J=7.7 Hz, 2H),
6.16 (d, J=7.7 Hz, 2H), 5.53 (d, J=17.3 Hz, 1H), 5.33
(d, J=17.3 Hz, 1H), 4.60 (ddd, J=10.6, 10.6, 4.2 Hz,
2H), 1.98–1.78 (m, 4H), 1.59–1.49 (m, 6H), 1.19–1.0
(m, 2H), 0.98 (m, 18H), 0.52 (d, J=6.9 Hz, 6H). 13C
NMR (75 MHz): d=162.8, 160.7, 154.7, 148.8, 139.6,
136.1, 121.1, 120.7, 105.0, 103.3, 74.5, 53.7, 47.4, 40.9,
34.5, 31.2, 26.3, 23.8, 22.2, 20.7, 16.6. IR: 2953, 2922,
1572, 1434, 1328, 1263, 1216, 1151. MS (EI, 70 eV):
m/z=570.6 (100). Calc. for C36H50N4O2: C, 75.75; H,
8.83; N, 9.82. Found: C, 75.59; H, 9.05; N, 9.75
3.4.1. (1S,10S,2R,20R,5S,50S)-(+)-Butyl-bis-[6-(2-iso-
propyl-5-ethyl-cyclohexyloxy)-pyridin-2-yl]-amine (25)
Synthesized according to GP2. Colorless oil, 92%
1
yield. [a]D =+207.8. H NMR (400 MHz): d=7.35 (t,
J=8.0 Hz, 2H), 6.70 (d, J=8.0 Hz, 2H), 6.20 (d,
J=8.0 Hz, 2H), 4.96 (ddd, J=10.7, 10.7, 4.1 Hz, 2H),
4.12 (m, 2H), 2.22 (m, 2H), 2.10 (septd, J=4.4, 7.1
Hz, 2H), 1.71 (m, 4H), 1.58–1.31 (m, 6H), 1.16-0.88
(m, 20H), 0.77 (d, J=6.9 Hz, 3H). 13C NMR (100
MHz): d=163.0, 155.5, 139.5, 105.8, 102.7, 74.6, 48.0,
47.4, 41.0, 34.6, 31.6, 30.7, 26.3, 23.9, 22.2, 20.7, 20.6,
16.6, 14.1. IR: 2956, 2868, 1592, 1454, 1372, 1329,
1251, 1215, 1155, 1049, 1013. HRMS Calc. for
C34H53N3O2: 535.41377. Found: 535.41384.
3.5. Syntheses of 2-aminopyridines
3.5.1. (6R,8R)-(ꢀ)-(5,6,7,8-Tetrahydro-7,7-dimethyl-
6,8-methaquinolin-2-yl)-amine (20)
In a Schlenk tube flushed with argon were successively
added Pd(dba)2 (0.04 mmol, 23 mg), DPPP (0.05 mmol,
21 mg), 2-chloro-6-pinenyl-pyridine (8, 1.0 mmol), ben-
zophenone imine (19, 1.2 mmol, 217 mg) and sodium
tert-butylate (1.5 mmol, 144 mg). The Schlenk tube
was again degassed (three times) and flushed with argon.
Toluene (20 mL) was added, and the reaction mixture
heated at 80 ꢁC until the reaction was complete (moni-
tored by TLC or GC). The mixture was cooled to room
temperature, diluted with diethyl ether and filtered
through celite. Solvents were removed using a rotary
evaporator and the crude product redissolved in THF
(5 mL). A 2 M HCl solution (5 mL) was added, and
the solution stirred 30 min at room temperature. The so-
lution was diluted with 0.5 M HCl (5 mL), the aqueous
phase extracted twice with ether and finally rendered al-
kaline. The aqueous layer was extracted with diethyl
ether, the combined organic phases dried on Na2SO4
and the solvent evaporated. The brown solid was recrys-
tallized from ether/pentane to give a white solid, 91%
yield; m.p. 101–103 ꢁC. [a]D =ꢀ6.7. 1H NMR (400
MHz): d=7.11 (d, J=8.0 Hz, 1H), 6.24 (d, J=8.0 Hz,
1H), 4.2 (br s, 2H), 2.71 (dd, J=3.6, 3.3 Hz, 2H), 2.66
(dd, J=5.8, 5.4 Hz, 1H), 2.56 (m, 1H), 2.21 (sept,
J=3.0 Hz, 1H), 1.31 (s, 3H), 1.21 (d, J=13.4 Hz, 1H),
0.61 (s, 3H). 13C NMR (100 MHz): d=164.4, 155.2,
3.4.2. (1S)-(+)1-(6-{Benzyl-[6-(1-hydroxy-2,2-dimeth-
yl-propyl)-pyridin-2-yl]-amino}-pyridin-2-yl)-2,2-di-
methyl-propan-1-ol (26)
Synthesized according to GP2. White solid, 94%
yield; m.p. 96–98 ꢁC. [a]D =+99.6. 1H NMR (300
MHz): d=7.39 (dd, J=8.2, 7.6 Hz, 2H), 7.24–7.03 (m,
7H), 7.00 (d, J=8.2 Hz, 2H), 6.66 (d, J=7.6 Hz, 2H),
5.47 (d, J=16.3 Hz, 1H), 5.20 (d, J=16.3 Hz, 1H),
4.15 (d, J=6.9 Hz, 2H), 3.94 (d, J=6.9 Hz, 2H), 0.77
(s, 18H). 13C NMR (75 MHz): d=158.6, 155.5, 139.5,
137.1, 128.5, 126.7, 126.5, 116.3, 112.8, 80.2, 52.0,
36.3, 26.0. IR: 3433, 2956, 2865, 1595, 1574, 1464,
1399, 1231, 1060. MS (EI, 70 eV): m/z= 433.3 (M+).
Calc. for C27H35N3O2: C, 74.79; H, 8.14; N, 9.69.
Found: C, 74.47; H, 7.89; N, 9.57.
3.4.3. (6R,60R,8R,80R)-(+)-Benzyl-bis-(5,6,7,8-tetra-
hydro-7,7-dimethyl-6,8-methanoquinolin-2-yl)-amine (27)
Synthesized according to GP2. White solid, 92%
yield; m.p. 94–96 ꢁC. [a]D =+45.9. 1H NMR (300
MHz): d=7.28 (d, J=8.3 Hz, 2H), 7.16–7.02 (m, 5H),
6.78 (d, J=8.3 Hz, 2H), 5.39 (dt, J=15.6, 8.3 Hz, 2H),
2.84–2.71 (m, 6H), 2.57 (ddd, J=9.4, 6.9, 6.9 Hz, 2H),
2.20 (m, 2H), 1.31 (s, 6H), 1.23 (d, J=9.4 Hz, 2H),

C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
3775
137.2, 119.2, 105.5, 53.2, 50.1, 40.5, 39.3, 30.9, 30.5, 26.3,
21.3, 20.7, 14.0. IR: 3291, 3173, 2921, 1631, 1599, 1473,
1421.MS (EI, 70 eV): 188.1 (M+). Calc. for C12H16N2: C,
76.55; H, 8.57; N, 14.88. Found: C, 76.77; H, 8.90; N,
14.48.
4.6 Hz, 2H), 4.26–4.0 (m, 2H), 2.26–2.0 (m, 2H), 1.80-
1.65 (m, 4H), 1.60-1.25 (m, 4H), 1.20–0.80 (m, 21H),
0.76 (d, J=6.9 Hz, 3H). 13C NMR (75 MHz):
d=162.9, 158.0, 155.9, 155.2, 139.6, 136.3, 115.2,
113.2, 105.3, 103.4, 80.0, 74.6, 48.2, 47.4, 41.0, 36.3,
34.6, 31.6, 30.7, 26.4, 26.0, 23.9, 22.2, 20.7, 20.5, 16.7,
14.1. IR: 3464, 2956, 2927, 2864, 1572, 1439, 1249,
1214, 1152. HRMS Calc. for C29H45N3O2: 467.351178.
Found: 467.351115.
3.5.2. (1S,2R,5S)-(+)-Butyl-[6-(2-isopropyl-5-methyl-
cyclohexyloxy)-pyridin-2-yl]-amine (24)
In a Schlenk tube flushed with argon were successively
added Pd(dba)2 (0.2 mmol, 115 mg), BINAP (0.2 mmol,
125 mg), 6-bromopyridine 6 (20.0 mmol, 6.22 g), N-bu-
tylamine (30.0 mmol, 2.19 g) and sodium tert-butylate
(30.0 mmol, 2.88 g). Toluene (100 mL) was added, and
the reaction mixture was heated for 24 h at 80 ꢁC. After
the reaction was complete, the mixture was cooled to
room temperature, diluted with ethyl acetate and filtered
through celite. Solvents were removed using a rotary
evaporator, and the product purified by column chroma-
tography on silica gel using pentane/ether (100:1) as elu-
ent. Colorless oil, 96% yield. [a]D =+72.8. 1H NMR (300
MHz): d=7.30 (dd, J=7.9, 7.7 Hz, 1H), 5.95 (d, J=7.9
Hz, 1H), 5.87 (d, J=7.7 Hz, 1H), 4.83 (td, J=10.6, 4.8
Hz, 1H), 3.21(m, 1H), 2.36 (m, 2H), 2.2–2.04 (m, 2H),
1.77–1.35 (m, 8H), 1.15–0.86 (m, 12 H), 0.77 (d, J=6.9
Hz, 3H). 13C NMR (75 MHz): d=163.2, 157.9, 139.9,
97.8, 96.9, 74.1, 47.7, 42.1, 41.0, 34.6, 31.8, 31.6, 26.2,
23.7, 22.2, 20.8, 20.3, 16.6, 13.9. IR: 3420, 2955, 2868,
1592, 1499, 1371, 1328, 1314, 1255, 1144. HRMS Calc.
for C19H32N2O: 304.25124. Found: 304.25146
3.6.2. Butyl-[6-(4-isopropyl-4,5-dihydro-oxazol-2-yl)-py-
ridin-2-yl]-[6-(2-isopropyl-5-methyl-cyclohexyloxy)-py-
ridin-2-yl]-amine (30)
Synthesized according to GP3. Colorless viscous oil,
1
76% yield. [a]D =+42.5. H NMR (400 MHz): d=7.63
(d, J=6.9 Hz, 1H), 7.54 (t, J=8.2, 6.9 Hz, 1H), 7.38
(t, J=8.0, 7.7 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 6.58
(d, J=8.0 Hz, 1H), 6.21 (d, J=7.7 Hz, 1H), 4.91 (ddd,
J=10.7, 10.7, 4.1 Hz, 1H), 4.49 (dd, J=9.3, 8.0 Hz,
1H), 4.19 (m, 4H), 2.21–2.05 (m, 2H), 1.89 (sext,
J=6.6 Hz, 1H), 1.77–1.64 (m, 4H), 1.55–1.32 (m, 4H),
1.07 (d, J=6.9 Hz, 3H), 0.97–0.87 (m, 12H), 0.74 (d,
J=6.9 Hz, 3H). 13C NMR (100 MHz): d=162.4,
156.9, 155.0, 145.3, 139.5, 136.7, 118.2, 117.1, 103.8,
102.7, 74.2, 72.7, 70.6, 48.2, 47.3, 40.9, 34.5, 32.9, 31.6,
30.6, 26.3, 23.9, 22.2, 20.6, 20.4, 19.1, 18.2, 16.6, 14.0.
IR: 2956, 1645, 1569, 1439, 1253. MS (EI, 70 eV):
m/z=492.6 (M+). Calc. for C30H44N4O2: C, 73.13; H,
9.00; N, 11.37. Found: C, 73.03; H, 9.40; N, 11.65.
3.6. N-Arylation of secondary amino pyridines (GP3)
3.6.3. (6R,8R)-(+)-Benzyl-(5,6,7,8-tetrahydro-7,7-di-
methyl-6, 8-methanoquinolin-2-yl)-pyridin-2-yl-amine (23)
In a Schlenk tube flushed with argon were succes-
sively added Pd(dba)2 (0.04 mmol, 23 mg) and DPPP
(0.05 mmol, 21 mg) in toluene (2 mL), and the solution
was stirred 15 min at room temperature. Benzyl-2-py-
ridinyl amine 9 (1.2 mmol), tetrabutylammonium bro-
mide (1.0 mmol, 322 mg), N-benzyl-2-amino-pyridine
(1.0 mmol) and sodium tert-butylate (1.5 mmol, 144
mg) were then added under argon. The reaction mixture
was then treated with toluene (18 mL) and subsequently
heated at 100 ꢁC until the reaction was complete (mon-
itored by TLC or GC). The mixture was cooled to room
temperature, diluted with ethyl acetate and filtered
through celite. Solvents were removed using a rotary
evaporator and the product purified by column chroma-
tography on silica gel. White solid, 81% yield; m.p. 70–
In a Schlenk tube flushed with argon were successively
added Pd(dba)2 (0.04 mmol, 23 mg) and DPPP (0.05
mmol, 21 mg) in toluene (2 mL) and the solution was
stirred 15 min at room temperature. The 2-bromo-6-sub-
stituted-pyridine (1.2 mmol), tetrabutylammonium bro-
mide (1.0 mmol, 322 mg), amino pyridine 24 (1 mmol)
and sodium tert-butylate (1.5 mmol, 144 mg) were then
added under argon. The reaction mixture was then treated
with toluene (18 mL) and subsequently heated at 100 ꢁC
until the reaction was complete (monitored by TLC
or GC). The mixture was cooled to room temperature,
diluted with ethyl acetate and filtered through celite.
The solvents were removed using a rotary evaporator,
and the product purified by column chromatography
on silica gel.
1
3.6.1. (+)-1-(6-{Butyl-[6-(2-isopropyl-5-methyl-cyclo-
hexyloxy)-pyridin-2-yl]-amino}-pyridin-2-yl)-2,2-dimeth-
yl-propan-1-ol (29)
Synthesized according to GP3. Colorless viscous oil,
1
94% yield. [a]D =+139.6. H NMR (300 MHz): d=7.41
(m, 2H), 7.08 (d, J=8.4 Hz, 1H), 6.68 (d, J=7.4 Hz,
1H), 6.61 (d, J=7.9 Hz, 1H), 6.26 (d, J=7.9 Hz, 1H),
4.90 (ddd, J=10.6, 10.6, 4.2 Hz, 1H), 4.31 (dd, J=7.4,
72 ꢁC. [a]D =+23.8. H NMR (400 MHz): d=8.23 (dd,
J=4.9, 1.1 Hz, 1H), 7.40 (dt, J=4.9, 1.1 Hz, 1H), 7.33
(d, J=7.4 Hz, 1H), 7.29–7.20 (m, 4H), 7.18–7.12 (m,
1H), 7.02 (d, J=8.5 Hz, 1H), 6.95 (d, J=7.9 Hz, 1H),
6.72 (ddd, J=7.1, 4.9, 0.8 Hz, 1H), 5.46 (dd, J=16.2,
14.2 Hz, 2H), 2.91–2.83 (m, 3H), 2.67 (ddd, J=9.7,
5.8, 5.8 Hz, 1H), 2.30 (sept, J=2.8 Hz, 1H), 1.40 (s,
3H), 1.31 (d, J=9.6 Hz, 1H), 0.67 (s, 3H). 13C NMR

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C. Bolm et al. / Journal of Organometallic Chemistry 689 (2004) 3767–3777
(100 MHz): d=165.2, 157.4, 153.6, 147.9, 139.8, 136.7,
136.7, 128.2, 127.4, 126.4, 124.3, 115.4, 114.1, 112.3,
51.4, 50.3, 40.4, 39.3, 30.9, 26.2, 21.4. IR: 2921, 2864,
1589, 1434, 1244, 1222, 1101, 1088. MS (EI, 70 eV):
m/z=355.6 (M+). Calc. for C24H25N3: C, 81.09; H,
7.09; N, 11.82. Found: C, 81.47; H, 6.91; N, 11.85.
4. Supplementary material
The crystallographic data for the structural analysis
have been deposited at the Cambridge Crystallographic
Data Centre, CCDC No. 230412. Copies of this infor-
mation may be obtained free of charge from The Direc-
tor, CCDC, 12 Union Road, Cambridge CB2 1EZ (fax:
+44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk or
http://www.ccdc.cam.ac.uk).
3.7. Synthesis of the copper(II) complex
3.7.1. (6R,60R,8R,80R)-(+)-Benzyl-bis-(5,6,7,8-tetra-
hydro-7,7-dimethyl-6,8-methanoquinolin-2-yl)-amine cop-
per dichloride (31)
Acknowledgements
To a solution of anhydrous CuCl2 (0.5 mmol, 67 mg)
in absolute ethanol (10 mL) was added under vigorous
stirring 2,20-dipridylamine 27 (0.5 mmol, 225 mg) in
CH2Cl2 (2 mL). Immediately, a green solid precipitated
and stirring was continued for 15 min. The solvent was
partially evaporated under reduced pressure, and the so-
lution let to stand at 4 ꢁC over night. The green solid
was collected by filtration to afford 31 in 93% yield.
Crystals suitable for X-ray analysis were grown by slow
diffusion of diethyl ether into a CH2Cl2 solution of the
complex, which was obtained as the CH2Cl2 adduct.
M.p. >250 ꢁC. Calc. for C31H35Cl2CuN3OÆCH2Cl2: C,
57.45; H, 5.57; N, 6.28. Found: C, 57.60; H, 5.78; N,
6.25.
We gratefully acknowledge the Deutsche Fors-
chungsgemeinschaft, the Fonds der Chemischen Indust-
rie, and the Alexander von Humboldt-Stiftung (J.L.P.)
for financial support.
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