Concave annelated terpyridines

Article abstract of DOI:10.1002/ejoc.201101356

Bimacrocyclic concave annelated terpyridines were generated from a U-shaped nonmacrocyclic tetraalkene precursor by ring closing metathesis followed by hydrogenation. The U-shaped precursor was synthesized by condensing two aryl-tetrahydroquinolones with

Full text of DOI:10.1002/ejoc.201101356

FULL PAPER
DOI: 10.1002/ejoc.201101356
Concave Annelated Terpyridines[‡]
Ulrich Lüning*[a] and Timo Liebig[a]
Keywords: Fused-ring systems / Ligand design / Nitrogen heterocycles / Macrocycles / Ring closing metathesis
Bimacrocyclic concave annelated terpyridines were gener- olones themselves were accessible by coupling a 2-chloro-
ated from a U-shaped nonmacrocyclic tetraalkene precursor
by ring closing metathesis followed by hydrogenation. The
U-shaped precursor was synthesized by condensing two aryl-
tetrahydroquinolones with Eschenmoser’s salt. The quin-
quinolone with a bis-alkenyloxy-substituted boronic acid.
The concave terpyridine was tested for reactivity and stereo-
selectivity in a copper(I)-catalyzed cyclopropanation.
Introduction
N-Heterocyclic compounds play an important role as li-
gands for metal ions, especially transition metal species. The
resulting complexes serve in a multitude of ways, for exam-
ple as catalysts,[1,2] but also in supramolecular chemistry for
self assembly.[3–6] When more than one nitrogen atom is
suitably positioned, the ligands are even more powerful due
to the chelate effect. Thus 2,2Ј-bipyridine (1) and 1,10-
phenanthroline (3) are widely used two-site chelates, and
2,2Ј:6Ј,2"-terpyridine (2) is the most prominent chelating
ligand with three coordinating nitrogen atoms
(Scheme 1).[7–10] Whereas the pyridine–pyridine dihedral
angles may vary in bi- and ter-pyridines 1 and 2 – with the
anti orientation usually being favored – the two nitrogen
atoms of 1,10-phenanthroline (3) are fixed in a syn orienta-
tion due to the annelated benzene ring. Therefore, the 1,10-
phenanthroline unit has been used in concave bases,[11] rather
than the 2,2Ј-bipyridine moiety to ensure the concave posi-
tioning of the lone pairs of the nitrogen atoms (Figure 1).
It is therefore clear that the use of bridged terpyridines 4
as concave bases and ligands would also be suitable.[15] In
Scheme 1. Chelating N-heterocycles.
Figure 1. General structure for a concave 1,10-phenanthroline
5.[11–14] X and Y may be polymethylene or oligoethylene glycol
the 1980’s, Thummel and Jahng presented the synthesis of chains.
annelated 2,2Ј:6Ј,2"-terpyridines 4,[16] and Zimmerman et
al. developed a route to such terpyridines with additional
functionalities in the α-position relative to the outer nitro-
gen atoms, eventually leading to the construction of par-
tially shielded systems such as molecular pincers,[17] which
were also found to act as host systems for organic guests
and transition-metal ions.[18]
anthrolines starts from
a
2,9-dihalogeno-1,10-phen-
anthroline.[13] The halogen atoms are then exchanged by
aryl bridgeheads that carry alkenyloxy chains in their ortho
positions. Ring-closing metathesis then generates the con-
cave bimacrocycles. For a similar approach in the case of
terpyridines, the bis-α-disubstituted terpyridines described
above seemed suitable.
At present, the most effective way of synthesizing bi-
macrocyclic concave reagents such as concave 1,10-phen-
[‡] Concave Reagents, 61; Part 60: D. Stoltenberg, S. Lüthje, O.
Winkelmann, C. Näther, U. Lüning, Eur. J. Org. Chem. 2011,
5845–5859.
Results and Discussion
[a] Otto-Diels-Institut für Organische Chemie, Christian-
Albrechts-Universität zu Kiel
Suitably substituted terpyridines (12 and 13) were first
required. For their syntheses, a literature approach[17] was
adopted. In the central step, two tetrahydroquinolone units
Olshausenstraße 40, 24098 Kiel, Germany
Fax: +49-431-8801558
E-mail: luening@oc.uni-kiel.de
1346
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1346–1350

Concave Annelated Terpyridines
such as 8 were to be submitted to a condensation reaction
The aryl-substituted tetrahydroquinolones 10 were then
with a carbonyl compound (or an equivalent) in the pres- condensed with Eschenmoser’s salt 11. The U-shaped prod-
ence of a nitrogen source (see below). Therefore, suitable ucts were formed when the reaction was carried out under
tetrahydroquinolone compounds had to be synthesized suitable conditions involving the following steps: first, one
first. Chlorotetrahydroquinolone 8 (Scheme 2) was synthe- equivalent of the quinolone 10 was mixed with Eschenmo-
sized in a multistep reaction starting from acrylonitrile (6) ser’s salt 11, and, in parallel, a second equivalent of 10 was
and cyclohexanone (7), as described in the literature.[17,19,20] mixed with ammonium acetate. The two batches were
mixed, and the reaction proceeded with the desired regio-
chemistry; the methoxy derivative 13a (Scheme 5) was iso-
lated in 25% yield, and the tetraalkenyloxy derivative 13b
in 48% yield, both were obtained as U-isomers exclusively.
Scheme 2. Synthetic route to chlorotetrahydroquinolone 8.
The last step of the reaction sequence was the oxidation
of an alcoholic precursor to ketone 8. Swern oxidation is
critical for larger amounts of substrate, but the reaction was
quick and smooth. Several batch reactions were carried out
in parallel, which allowed a larger scale (20 g) synthesis of
8.
Scheme 5. Synthesis of diaryl-substituted terpyridines 13. Reagents
and conditions: a) NH4OAc, DMSO.
At this stage in the route to concave terpyridines, the
bridgehead moieties were introduced. Suzuki–Miyaura
cross-coupling between chloride 8 and boronic acid 9b gave
the arylated tetrahydroquinolone 10b as the precursor to
the concave terpyridines 14 and 15. For comparison, a di-
methoxy derivative 10a was also synthesized. Both com-
pounds were isolated in acceptable yields of 72% for build-
ing block 10b and 59% for the methyoxy analogue 10a
(Scheme 3).
In tetraalkene 13b, four vinyl groups are suitably posi-
tioned for macrocyclization by ring-closing metathesis. It
is well-established in the synthesis of other bimacrocyclic
concave reagents[13,25] that a double macrocyclization can
be carried out in moderate dilution in dichloromethane
using Grubbs’ catalyst. The resulting concave terpyridine
14, as a diene, was found to form as a mixture of diastereo-
isomers (E,E; E,Z; Z,Z). As established for other concave
reagents,[13,25] the mixture could be simplified to only one
saturated product by hydrogenation. The double ring-clo-
sure gave 14 in 74% isolated yield, the hydrogenated prod-
uct 15 was isolated in 90% yield (Scheme 6).
Scheme 3. Synthesis of aryl-substituted quinolones 10. Reagents
and conditions: a) [Pd(PPh3)4], Ba(OH)2, dimethoxyethane, H2O.
The condensation of two tetrahydroquinolones with a C1
unit and a nitrogen source was tested first with chloride 8.
Whereas Knoevenagel reactions with, for instance, benzal-
dehyde, only yielded products that were difficult to purify,
a variant, described by Risch,[21–23] was more successful. In
a one-pot reaction, tetrahydroquinolone 8 was treated with
Eschenmoser’s salt (11; N,N-dimethylmethylene iminium
iodide). In principle, S- and U-shaped annealed terpyridines
may form in this reaction, however, suitable reaction condi-
tions and substitution can direct the reaction to give the U-
shaped products.[24] Indeed, U-shaped dichloroterpyridine
12 was formed exclusively in the test reaction (Scheme 4).
Scheme 6. Synthesis of concave terpyridines 14 and 15. Reagents
and conditions: a) Grubbs’ catalyst, dichloromethane; b) H2, Pd/
C, MeOH.
With compounds 14 and 15, the first two concave terpyr-
idines have been manufactured. As a first test to investigate
whether the active site in the bimacrocyclic system is still
sufficiently accessible to allow catalysis and to determine
the influence of the concave shielding, the copper(I)-cata-
lyzed cyclopropanation of alkenes with ethyl diazoacetate
(17) was studied. Indene (16) was chosen as the substrate
so that the results could be compared with those of other
(concave) ligands (Scheme 7).[26] The cyclopropanation
product 18 was formed as a mixture of endo- and exo-cyclo-
propanes. An analysis of the stereoselectivity of the reaction
was conducted using gas chromatography (Table 1).[26–28]
Scheme 4. Synthesis of rigid dichloroterpyridine 12. Reagents and
conditions: a) NH4OAc, DMSO.
Eur. J. Org. Chem. 2012, 1346–1350
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1347

U. Lüning, T. Liebig
FULL PAPER
enium (Fluka), cyclohexanone (Merck), cyclohexylamine (Aldrich),
1,2-dimethoxyethane (Acros), dimethyl sulfoxide (Merck), Eschen-
moser’s salt (N,N-dimethylmethyleneiminium iodide; Acros), gla-
cial acetic acid (Merck), hydrogen peroxide (30%; Merck), 4-meth-
oxyphenol (Aldrich), oxalyl chloride (Fluka), Pd/C (10%) (Merck),
phosphoroxy chloride (Merck), sulfuric acid (96%) (Riedel-de
Haën), tetrakis(triphenylphosphane)palladium(0) (Aldrich), trieth-
ylamine (Merck). [2,6-Bis(hex-5-enyloxy)phenyl]boronic acid[14]
and (2,6-dimethoxyphenyl)boronic acid[14] were prepared according
to literature procedures. Anhydrous solvents were obtained by
using suitable desiccants: ethyl acetate, cyclohexane, and chloro-
form were distilled from calcium chloride, and dichloromethane
was distilled from calcium hydride. Column chromatography was
carried out on silica gel (Macherey–Nagel, activity I) and neutral
alumina (Merck, activity II). Preparative, centrifugally accelerated,
thin-layer chromatograph (Chromatotron) was performed with a
model 7924 T instrument from Harrison Research. 1H and 13C
NMR spectra were recorded with Bruker AC 200 (200 MHz or
50 MHz), ARX 300 (300 MHz or 75 MHz), DRX 500 (500 MHz
or 125 MHz), or Avance 600 (600 MHz or 150 MHz) spectrome-
ters. Assignments are supported by COSY, HSQC, HMBC, and
NOESY experiments; the type of 13C NMR signal is always listed
(singlet, doublet, etc). All chemical shifts are referenced to either
TMS or to the residual proton or carbon signal of the solvent. If
not stated otherwise, coupling constants are 3J. Mass spectra (MS)
and high-resolution mass spectra (HRMS) were recorded with Fin-
Scheme 7. Copper(I)-catalyzed cyclopropanation of indene (16)
with ethyl diazoacetate (17). For the nature of ligands L, see
Table 1.
Table 1. Stereoselectivity of the copper(I)-catalyzed cycloprop-
anation of indene (16) with ethyl diazoacetate (17) in the presence
(and absence) of ligands.
Ligand (L)
endo-18/exo-18
None
31:69
29:71
32:68
32:68
12:88
2,9-Dimethyl-1,10-phenanthroline
12
13a
15
In all reactions, the expected cyclopropanes 18 were
formed, and, in all cases, the exo-product (exo-18) predomi- nigan MAT 8200 or 8230 spectrometers, or with an ESI mass spec-
trometer Mariner (Applied Biosystems, using methanol/dichloro-
methane, 1:1, as solvent). IR spectra were measured with a Perkin–
Elmer 1600 Series spectrometer. Elemental analyses were carried
out with an Euro EA3000 CHNS instrument (HEKAtech). Gas
chromatography was performed with an 6890 N instrument
(Agilent; split/splitless injector, split ratio 11:1; injector temp.
250 °C; FID detector temp. 300 °C).
nated. The nonmacrocyclic ligands 12 and 13a showed no
influence on the stereochemistry when compared to neocu-
proine (2,9-dimethyl-1,10-phenanthroline) or copper(I) ca-
talysis in the absence of ligands. When bimacrocycle 15 was
employed, a shift of the selectivity towards the exo-product
was found.
General Procedure for the Synthesis of Substituted U-Shaped Ter-
pyridines:[24] A solution of 2-substituted 5,6,7,8-tetrahydroquinoli-
none and ammonium acetate (1.1 equiv.) in anhydrous DMSO was
heated at 85 °C for 5 min. In a second flask, 2-substituted 5,6,7,8-
tetrahydroquinolinone and Eschenmoser’s salt (N,N-dimethylmeth-
yleneiminium iodide, 1.1 equiv.) were dissolved in anhydrous
DMSO. The homogeneous solution of the iminium salt and 2-sub-
stituted 5,6,7,8-tetrahydroquinolinone was added to the mixture of
warm (85 °C) 2-substituted 5,6,7,8-tetrahydroquinolinone and am-
monium acetate in DMSO. The combined mixture was heated for
an additional 16–48 h at 130 °C. The reaction mixture was cooled
to room temp., water (50 mL) and dichloromethane (50 mL) were
added, the layers were separated, and the aqueous layer was ex-
Conclusions
As a new class of concave bases and concave ligands,
terpyridines 14 and 15 have been synthesized. The saturated
bimacrocycle 15 has been used as a ligand for copper(I)
ions and the resulting complex has successfully been used
in a cyclopropanation reaction. The stereoselectivity of the
cyclopropanation of indene 16 was studied and the results
were compared to those obtain with analogous terpyridine
ligands 12, 13a, and with 2,9-dimethyl-1,10-phenanthroline.
The concave shielding enhances the endo/exo selectivity
from ca. 30:70 to 12:88 in favor of the exo form. Thus, tracted with dichloromethane (4–6ϫ40 mL). The combined or-
ganic layer was washed with water (3ϫ20 mL) and brine
(3ϫ20 mL) and dried with magnesium sulfate. After removal of
the solvent in vacuo, the residue was purified as detailed below.
concave terpyridine 15 is indeed a promising concave li-
gand. The catalytic center remained active, and the concave
part of the ligand enhances selectivity. In this test reaction,
however, 15 did not reach the results[27] achieved by tailored 2-(2,6-Dimethoxyphenyl)-5,6,7,8-tetrahydro-8-quinolone (10a): (2,6-
Dimethoxyphenyl)boronic acid[14] (9a; 5.64 g, 31.1 mmol), tetrakis-
concave 1,10-phenanthrolines (up to 1:99) but its potential
has nevertheless been demonstrated.
(triphenylphosphane)palladium(0) (1.43 g, 1.24 mmol), barium hy-
droxide (3.12 g, 18.2 mmol), and water (30.0 mL) were added to a
solution of 2-chloro-5,6,7,8-tetrahydro-8-quinolone (8; 4.51 g,
24.8 mmol) in 1,2-dimethoxyethane (300 mL). The reaction mix-
ture was heated to reflux temperature for 45 h. After the addition
Experimental Section
General Remarks: The following chemicals were obtained commer-
cially and used without further purification: acetic anhydride (Ald-
rich), acrylonitrile (Acros), ammonia solution (25%) (Riedel-de
Haën), ammonium acetate (Merck), barium hydroxide octahydrate
of water (50 mL) and chloroform (50 mL), the aqueous layer was
extracted with chloroform (3ϫ50 mL) and the combined organic
layer was washed with brine (20 mL). The solvent was removed in
vacuo and the residue was purified by chromatography (silica gel;
cyclohexane/ethyl acetate, 1:1), yielding 10a (4.10 g, 59%). IR
(Merck),
benzylidenebis(tricyclohexylphosphane)dichlororuth-
1348
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1346–1350

Concave Annelated Terpyridines
(KBr): ν = 2934, 1697, 1598, 1471, 1241, 1090 cm–1. 1H NMR C19H13Cl2N3 (354.23): calcd.
C
64.42, H 3.70, N 11.86;
˜
(300 MHz, CDCl3): δ = 7.67 (d, J = 8.0 Hz, 1 H, 4-H), 7.38 (d, J C19H13Cl2N3·0.2 CH2Cl2: calcd. C 62.12, H 3.64, N 11.32; found
= 8.0 Hz, 1 H, 3-H), 7.29 (t, J = 8.4 Hz, 1 H, 4Ј-H), 6.61 (mc, 2 H, C 62.11, H 3.77, N 11.25.
3Ј-H, 5Ј-H), 3.69 (s, 6 H, OCH3), 3.06 (t, J = 6.1 Hz, 2 H, 7-H),
2,12-Bis(2,6-dimethoxyphenyl)-5,6,8,9-tetrahydroquino[8,7-b]-1,10-
2.81 (t, J = 6.1 Hz, 2 H, 5-H), 2.21 (quint, J = 6.4 Hz, 2 H, 6-
phenanthroline (13a): Synthesized according to the general pro-
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 196.6 (s, C-8), 158.3
cedure: 2-(2,6-dimethoxyphenyl)-5,6,7,8-tetrahydro-8-quinolone
(10a; 0.48 g, 1.66 mmol), ammonium acetate (64.0 mg, 0.83 mmol),
Eschenmoser’s salt (155 mg, 0.83 mmol), DMSO (25 mL). Purified
by column chromatography on neutral alumina (activity II–III)
(s, C-2Ј, C-6Ј), 154.3 (s, C-2), 148.1 (s, C-1Ј), 138.9 (s, C-8a), 137.2
(d, C-4), 129.8 (d, C-3, C-4Ј), 118.8 (s, C-4a), 104.2 (d, C-3Ј, C-5Ј),
55.9 (q, CH3), 39.9 (t, C-7), 29.2 (t, C-5), 22.7 (t, C-6) ppm. MS
(ESI): m/z (%) = 306 (100) [M + Na+]. HRMS: calcd. for
eluting with dichloromethane/ethyl acetate (4:1); yield 139 mg
C17H17NO3 283.12085; found 283.12304 (7.7 ppm); calcd. for
1
(25%). IR (KBr): ν = 2928, 1601, 1473, 1430, 1251, 1109 cm–1. H
˜
C1613CH17NO3 284.12421; found 284.12462 (1.4 ppm). C17H17NO3
NMR (500 MHz, CDCl3): δ = 7.55 (d, J = 7.7 Hz, 2 H, 4-H, 10-
H), 7.40 (s, 1 H, 7-H), 7.27 (t, J = 8.3 Hz, 2 H, 4Ј-H, 4ЈЈ-H), 7.22
(d, J = 7.7 Hz, 2 H, 3-H, 11-H), 6.59 (d, J = 8.3 Hz, 4 H, 3Ј-H,
(283.32): calcd. C 72.07, H 6.05, N 4.94; found C 71.90, H 6.23, N
4.94.
2-[2,6-Bis(hex-5-enyloxy)phenyl]-5,6,7,8-tetrahydro-8-quinolone (10b):
[2,6-Bis(hex-5-enyloxy)phenyl]boronic (9b; 1.25 g,
acid[14]
3ЈЈ-H, 5Ј-H, 5ЈЈ-H), 3.66 (s, 12 H, OCH3), 2.99 (m, 8 H, 5-H, 6-H,
8-H, 9-H) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.5 (s, C-2Ј,
C-2ЈЈ, C-6Ј, C-6ЈЈ), 153.3 (s, C-2, C-12), 151.8 (s, C-13a, C-14b),
151.1 (s, C-13b, C-14a), 135.3 (d, C-4, C-10), 135.0 (d, C-7), 133.8
(s, C-6a, C-7a), 131.6 (s, C-4a, C-9a), 129.3 (d, C-4Ј, C-4ЈЈ), 125.9
(d, C-3, C-11), 119.6 (s, C-1Ј, C-1ЈЈ), 104.6 (d, C-3Ј, C-3ЈЈ, C-5Ј, C-
5ЈЈ), 56.3 (q, OCH3), 27.7 (t, C-6, C-8), 27.6 (t, C-5, C-9) ppm. MS
(ESI): m/z (%) = 1115 (4) [2M+], 558 (100) [M + H+]. C35H31N3O4
(557.64): calcd. C 75.38, H 5.60, N 7.54; found C 75.24, H 5.51, N
7.35.
3.93 mmol), tetrakis(triphenylphosphane)palladium(0) (186 mg,
161 μmol), barium hydroxide (390 mg, 2.28 mmol), and water
(15 mL) were added to a solution of 2-chloro-5,6,7,8-tetrahydro-8-
quinolone (8; 584 mg, 3.22 mmol) in 1,2-dimethoxyethane (90 mL).
The reaction mixture was heated to reflux temperature for 48 h.
After addition of water (50 mL) and chloroform (50 mL), the aque-
ous layer was extracted with chloroform (3ϫ50 mL) and the com-
bined organic layer was washed with brine (20 mL). The solvent
was removed in vacuo and the residue was purified by chromatog-
raphy (silica gel; cyclohexane/ethyl acetate, 1:1), yielding 10b
2,12-Bis[2,6-bis(hex-5-enyloxy)phenyl]-5,6,8,9-tetrahydroquino[8,7-
b]-1,10-phenanthroline (13b): Synthesized according to the general
procedure: 2-[2,6-Bis(hex-5-enyloxy)phenyl]-5,6,7,8-tetrahydro-8-
quinolone (10b; 2.02 g, 4.76 mmol), ammonium acetate (185 mg,
2.40 mmol), Eschenmoser’s salt (450 mg, 2.43 mmol), DMSO
(30 mL). Purified by column chromatography on neutral alumina
(activity II–III) eluting with dichloromethane/ethyl acetate (4:1)
and chromatotron on neutral alumina eluting with dichlorometh-
(973 mg, 72%). IR (KBr): ν = 2934, 1697, 1639, 1598, 1471, 1241,
˜
1
1090 cm–1. H NMR (200 MHz, CDCl3): δ = 7.61 (d, J = 8.0 Hz,
1 H, 4-H), 7.37 (d, J = 8.0 Hz, 1 H, 3-H), 7.22 (t, J = 8.3 Hz, 1 H,
4Ј-H), 6.57 (d, J = 8.3 Hz, 2 H, 3Ј-H, 5Ј-H), 5.69 (tdd, J = 6.8,
10.9, 17.8 Hz, 2 H, CH=), 4.96–4.82 (m, 4 H, =CH2), 3.90 (t, J =
6.2 Hz, 4 H, OCH2), 3.04 (t, J = 6.1 Hz, 2 H, 7-H), 2.80 (t, J =
6.1 Hz, 2 H, 5-H), 2.21 (quint, J = 6.4 Hz, 2 H, 6-H), 1.98–1.84 (m,
4 H, =CHCH2), 1.66–1.48 (m, 4 H, OCH2CH2), 1.38–1.22 (m, 4
H, OCH2CH2CH2) ppm. 13C NMR (50 MHz, CDCl3): δ = 196.3
(s, C-8), 157.9 (s, C-2Ј, C-6Ј), 154.4 (s, C-2), 147.8 (s, C-1Ј), 138.8
(d, CH2CH=CH2), 138.5 (s, C-8a), 136.7 (d, C-4), 129.9 (d, C-3),
129.6 (d, C-4Ј), 119.8 (s, C-4a), 114.3 (t, CH2CH=CH2), 105.6 (d,
C-3Ј, C-5Ј), 68.7 (t, OCH2CH2), 39.9 (t, C-7), 33.2 (t,
CH2CH=CH2), 29.2 (t, C-5), 28.8 (t, OCH2CH2), 28.5 (t,
CH2CH2CH2), 22.8 (t, C-6) ppm. MS (ESI): m/z (%) = 861 (17)
[2M + Na+], 442 (16) [M + Na+], 420 (100) [M + H+]. C27H33NO3
(419.56): calcd. C 77.29, H 7.93, N 3.34; found C 77.54, H 8.05, N
3.35.
ane/ethyl acetate (10:1 to 4:1); yield 946 mg (48%). IR (Film): ν =
˜
2928, 1639, 1600, 1244, 1099 cm–1. 1H NMR (500 MHz, CDCl3):
δ = 7.51 (d, J = 7.7 Hz, 2 H, 4-H, 10-H), 7.40 (s, 1 H, 7-H), 7.22
(t, J = 8.3 Hz, 2 H, 4Ј-H, 4ЈЈ-H), 7.19 (d, J = 7.7 Hz, 2 H, 3-H, 11-
H), 6.57 (d, J = 8.3 Hz, 4 H, 3Ј-H, 5Ј-H, 3ЈЈ-H, 5ЈЈ-H), 5.58 (tdd,
J = 6.6, J = 10.3, J = 16.9 Hz, 4 H, CH=), 4.84–4.76 (m, 8 H,
=CH2), 3.87 (t, J = 6.3 Hz, 8 H, OCH2), 2.98 (br. s, 8 H, 5-H, 6-
H, 8-H, 9-H), 1.85–1.79 (m, 8 H, =CHCH2), 1.53–1.45 (m, 8 H,
OCH2CH2), 1.28–1.21 (m, 8 H, OCH2CH2CH2) ppm. 13C NMR
(125 MHz, CDCl3): δ = 157.9 (s, C-2Ј, C-2ЈЈ, C-6Ј, C-6ЈЈ), 153.5 (s,
C-2, C-12), 151.6 (s, C-13a, C-14b), 151.1 (s, C-13b, C-14a), 139.1
(d, CH=), 134.9 (d, C-4, C-7, C-10), 133.8 (s, C-6a, C-7a), 131.6
(s, C-4a, C-9a), 129.2 (d, C-4Ј, C-4ЈЈ), 126.0 (d, C-3, C-11), 120.4
(s, C-1Ј, C-1ЈЈ), 113.9 (t, =CH2), 105.9 (d, C-3Ј, C-3ЈЈ, C-5Ј, C-5ЈЈ),
68.8 (t, OCH2), 33.4 (t, CH2CH=), 28.6 (t, OCH2CH2), 27.9 (t, C-
6, C-8), 27.7 (t, C-5, C-9), 25.2 (t, CH2) ppm. MS (ESI): m/z (%)
= 830 (100) [M + H+]. C55H63N3O4 (830.11): calcd. C 79.58, H
7.65, N 5.06; found C 79.38, H 7.60, N 5.10.
2,12-Dichloro-5,6,8,9-tetrahydroquino[8,7-b]-1,10-phenanthroline (12):
Synthesized according to the general procedure: 2-chloro-5,6,7,8-
tetrahydro-8-quinolone (8; 1.22 g, 6.60 mmol), ammonium acetate
(255 mg, 3.30 mmol), Eschenmoser’s salt (648 mg, 3.50 mmol),
DMSO (50 mL). Purified by column chromatography on neutral
alumina (activity II–III) eluting with dichloromethane/ethyl acetate
(4:1); yield 322 mg (26%). IR (KBr): ν = 2927, 1654, 1543, 1457,
˜
1403 cm–1. H NMR (300 MHz, CDCl3): δ = 7.95 (d, J = 7.9 Hz, 275,276,278,279-Tetrahydro-2,13,15,26-tetraoxa-1,14(1,3,2)-dibenz-
1
2 H, 4-H, 10-H), 7.46 (s, 1 H, 7-H), 7.23 (d, J = 7.9 Hz, 2 H, 3- ena-27(2,12)-{quino[8,7-b]-1,10-phenanthrolina}bicyclo[12.12.1]-
1
H, 11-H), 3.06–2.92 (m, 8 H, 5-H, 6-H, 8-H, 9-H) ppm. H NMR
heptacosaphane-7,20-diene (14): 2,12-Bis-[2,6-bis(hex-5-enyloxy)-
(200 MHz, CD2Cl2): δ = 7.56 (d, J = 7.9 Hz, 2 H, 4-H, 10-H), 7.46 phenyl]-5,6,8,9-tetrahydroquino[8,7-b]-1,10-phenanthroline (13b;
(s, 1 H, 7-H), 7.27 (d, J = 7.9 Hz, 2 H, 3-H, 11-H), 3.03–2.96 (m,
950 mg, 1.14 mmol) was dissolved in dichloromethane (600 mL)
and benzylidenebis(tricyclohexylphosphane)dichlororuthenium
8 H, 5-H, 6-H, 8-H, 9-H) ppm. 13C NMR (50 MHz, CD2Cl2): δ =
152.7 (s, C-2, C-12), 150.5 (s, C-13a, C-14b), 150.1 (s, C-13b, C- (84.0 mg, 102 μmol, 9 mol-%) was added. After stirring for 19 h at
14a), 139.1 (d, C-4, C-10), 136.1 (d, C-7), 135.5 (s, C-6a, C-7a), room temp., the solvent was removed in vacuo and the residue was
133.2 (s, C-4a, C-9a), 124.2 (d, C-3, C-11), 27.6 (t, C-6, C-8), 27.1 filtered two times through neutral alumina (activity II–III) eluting
(t, C-5, C-9) ppm. MS (ESI): m/z (%) = 731 (45) [2M + Na+], 376
(100) [M + Na+]. MS (EI, 70 eV): m/z (%) = 355 (13), 353 (21)
[M+]. MS (CI, isobutane): m/z (%) = 356 (26), 354 (31) [M + H+].
with dichloromethane/ethyl acetate (4:1). Finally, the residue was
purified with a chromatotron (neutral alumina) eluting with dichlo-
romethane/ethyl acetate (10:1 to 4:1); yield 670 mg (74 %). IR
Eur. J. Org. Chem. 2012, 1346–1350
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1349

U. Lüning, T. Liebig
FULL PAPER
(Film): ν = 2929, 1599, 1458, 1245, 1099 cm–1. 1H NMR (500 MHz, opment of gas was frequently noted. After filtration of the mixture
˜
CDCl3): δ = 7.51, 7.50 (3d, J = 7.7 Hz, 2 H, 274-H, 2710-H), 7.38, through silica gel with diethyl ether as eluent, most of the solvent
7.37, 7.36 (3ϫ s, 1 H, 277-H), 7.31, 7.29, 7.27 (3ϫ d, J = 7.7 Hz, mixture was evaporated in vacuo until ca. 5 mL remained. 1,2-
2 H, 273-H, 2711-H), 7.24, 7.23, 7.22 (3ϫ t, J = 8.3 Hz, 2 H, 14-H, Dichloromethane was then added to give ca. 10 mL of solution.
144-H), 6.66, 6.65, 6.50 (3ϫ d, J = 8.3 Hz, 4 H, 13-H, 15-H, 143- After addition of n-hexadecane [ca. 25 mg (Ϯ0.01 mg)] as GC stan-
H, 145-H), 4.95–4.79 (m, 2 H, CH=), 4.25–4.04, 3.84–3.69 (m, 8 H,
dard, the products were analyzed by GC (HP-5/30 m; 80 °C for
OCH2), 3.00, 2.99 (2ϫ s, 8 H, 275-H, 276-H, 278-H, 279-H), 1.64– 5 min, 2 °C/min until 140 °C, 1 min, 1 °C/min until 160 °C, 1 min,
0.88 (m, 32 H, CH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 158.4, 20 °C/min until 240 °C, 20 min).
158. 3, 158.2 (3ϫ s, C-12, C-16, C-142, C-146), 153.2, 153.1 (2ϫ s,
C-272, C-2712), 151.4, 151.3 (4ϫ s, C-2713a, C-2713b, C-2714a, C-
[1] See, for instance: D. Steinborn, Grundlagen der metallor-
2714b), 134.6 (2ϫ d, C-274, C-2710), 134.4 (2ϫ d, C-277), 133.2,
ganischen Komplexchemie, Teubner, Wiesbaden, Germany,
132.9 (2ϫ s, C-276a, C-277a), 131.0, 130.7 (2ϫ s, C-274a, C-279a),
2007.
130.3, 129.8, 128.9 (3ϫ d, C-14, C-144), 125.9, 125.7 (2ϫ d, C-273, [2] C. Elschenbroich, Organometallchemie, 6th ed., Teubner, Wies-
C-2711), 124.2, 123.4 (2ϫ s, C-11, C-141), 109.1, 108.7, 108.4 (3ϫ
d, C-13, C-15, C-143, C-145), 70.9, 70.7, 70.3 (3ϫ t, OCH2), 31.8,
31.7, 28.7, 28.3, 28.0, 27.9, 27.8, 27.6, 25.9, 25.7, 25.3, 24.5, 24.3
(13ϫ t, C-275, C-276, C-278, C-279, CH2) ppm. MS (ESI): m/z (%)
= 774 (100) [M + H+]. C51H57N3O4 (776.02): calcd. C 78.93, H
7.40, N 5.41; found C 78.67, H 7.51, N 5.25.
baden, Germany, 2008.
[3] See, for instance: J. W. Steed, J. L. Atwood, Supramolecular
Chemistry, Wiley, New York, 2nd ed., 2009.
[4] U. S. Schubert, C. Eschbaumer, Angew. Chem. 2002, 114, 3016–
3050; Angew. Chem. Int. Ed. 2002, 41, 2892–2926.
[5] D. S. Lawrence, T. Jiang, M. Levett, Chem. Rev. 1995, 95,
2229–2260.
[6] L. Flamigni, J.-P. Collin, J.-P. Sauvage, Acc. Chem. Res. 2008,
2,13,15,26-Tetraoxa-1,14(1,3,2)-dibenzena-27(2,12)-{quino[8,7-b]-
1,10-phenanthrolina}bicyclo[12.12.1]heptacosaphane (15): Palladium
on charcoal (10%, 210 mg) was mixed with methanol (140 mL) and
hydrogen was bubbled through the mixture for 30 min. This acti-
vated mixture was then mixed with a solution of 14 (510 mg,
659 μmol) in chloroform (10 mL), and hydrogen was bubbled
through the solution for 3 h, while stirring at room temp. The solu-
tion was stirred under a hydrogen atmosphere for 18 h at room
temp., then the solvent was evaporated in vacuo and the residue
was purified by chromatography on neutral alumina (activity II–
III) eluting with dichloromethane/ethyl acetate (4:1) and by using
a chromatotron (neutral alumina) eluting with dichloromethane/
41, 857–871.
[7] I. Eryazici, C. N. Moorefield, G. R. Newkome, Chem. Rev.
2008, 108, 1834–1895.
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1763–1782.
[9] D. J. Mercer, S. J. Loeb, Dalton Trans. 2011, 40, 6385–6387.
[10] A. Wild, A. Winter, F. Schlütter, U. S. Schubert, Chem. Soc.
Rev. 2011, 40, 1459–1511.
[11] For the first example of a concave 1,10-phenanthroline with
aryl bridgeheads, see: U. Lüning, M. Müller, Chem. Ber. 1990,
123, 643–645.
[12] U. Lüning, F. Fahrenkrug, Eur. J. Org. Chem. 2004, 3119–3127.
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3294–3303.
[15] For a recent review on concave reagents, see: U. Lüning, in:
Molecular Encapsulation (Eds.: U. H. Bringer, J.-L. Mieusset),
John Wiley & Sons, Chichester, UK, 2010, pp. 175–199.
[16] R. P. Thummel, Y. Jahng, J. Org. Chem. 1985, 50, 2407–2412.
[17] S. C. Zimmerman, Z. Zeng, W. Wu, D. E. Reichert, J. Am.
Chem. Soc. 1991, 113, 183–196.
ethyl acetate (10:1 to 4:1); yield 460 mg (90%). IR (Film): ν = 2929,
˜
1599, 1458, 1245, 1099 cm–1. 1H NMR (500 MHz, CDCl3): δ =
7.51 (d, J = 7.7 Hz, 2 H, 274-H, 2710-H), 7.38 (s, 1 H, 277-H), 7.29
(d, J = 7.7 Hz, 2 H, 273-H, 2711-H), 7.20 (t, J = 8.3 Hz, 2 H, 14-H,
144-H), 6.63 (d, J = 8.3 Hz, 4 H, 13-H, 15-H, 143-H, 145-H), 3.99–
3.96, 3.92–3.87 (m, 8 H, OCH2), 2.97 (s, 8 H, 275-H, 276-H, 278-H,
279-H), 1.54–1.46, 1.40–1.32, 1.15–1.04, 0.99–0.91, 0.88–0.72 (m,
32 H, CH2) ppm. 13C NMR (150 MHz, CDCl3): δ = 158.1 (s, C-
[18] J. D. Crowley, I. M. Steele, B. Bosnich, Eur. J. Inorg. Chem.
2005, 3907–3917.
12, C-16, C-142, C-146), 153.1 (s, C-272, C-2712), 151.6 (s, C-2713a
,
C-2714b), 151.5 (s, C-2713b, C-2714a), 134.6 (d, C-274, C-2710), 134.4
(d, C-277), 133.5 (s, C-276a, C-277a), 131.2 (s, C-274a, C-279a), 129.1
(d, C-14, C-144), 126.3 (d, C-273, C-2711), 122.1 (s, C-11, C-141),
107.8 (d, C-13, C-15, C-143, C-145), 69.7 (t, OCH2), 28.6, 28.2, 28.0,
27.6, 27.1, 24.7 (6t, C-275, C-276, C-278, C-279, CH2) ppm. MS
(ESI): m/z (%) = 678 (100) [M + H+]. HRMS: calcd. for
C51H59N3O4 777.45056; found 777.45012 (0.6 ppm); calcd. for
C5013CH59N3O4 778.45392; found 778.45483 (–1.2 ppm).
[19] L. Cotarca, P. Delogu, P. Maggioni, A. Nardelli, R. Bianchini,
S. Sguassero, Synthesis 1997, 328–332.
[20] A. I. Meyers, G. Garcia-Munoz, J. Org. Chem. 1964, 29, 1435–
1438.
[21] U. Westerwelle, A. Esser, N. Risch, Chem. Ber. 1991, 124, 571–
576.
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1996, 5, 705–715.
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Chem. 2004, 2, 863–868.
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2007, 981–987.
[26] F. Löffler, M. Hagen, U. Lüning, Synlett 1999, 1826–1828.
[27] F. Löffler, Dissertation, Christian-Albrechts-Universität zu
Kiel, Germany, 2001.
[28] M. Hagen, Dissertation, Christian-Albrechts-Universität zu
Kiel, Germany, 1999.
C51H59N3O4 (778.03): calcd.
C
78.73,
H
7.64,
N 5.40,
C51H59N3O4·H2O: calcd. C 76.95, H 7.72, N 5.28; found C 76.93,
H 7.89, N 5.25.
Cyclopropanation: Under argon, copper(I) triflate hemi-benzene
complex [Aldrich; 4.0–12.0 mg (Ϯ0.01 mg)] was placed in a vial,
and indene 16 [350 equiv. based on copper(I)] and ligands 2,9-di-
methyl-1,10-phenanthroline 12, 13a, or 15 (1.2–2.4 equiv.) dis-
solved in 1,2-dichloroethane (c = 0.01 molL–1), were added. After
addition of diazoacetate 17 (50 equiv.), the mixture was stirred at
room temp. for 24 h. At the beginning of the reaction, rapid devel-
Received: September 16, 2011
Published Online: January 11, 2012
1350
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1346–1350