A new family of biisoquinoline chelates

Article abstract of DOI:10.1002/ejoc.200600796

Four 8,8′-diaryl-substituted 3,3′-biisoquinoline ligands have been synthesized and characterized. The key feature of this new family of chelates is their endotopic but sterically non-hindering nature. All four ligands were made from a common 8-bromoisoquinolin-3-ol precursor; between three and twelve synthetic steps were necessary to obtain the products. The reported synthetic procedures allow for gram-scale production of these biisoquinolines. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200600796

FULL PAPER
DOI: 10.1002/ejoc.200600796
A New Family of Biisoquinoline Chelates
Fabien Durola,[a] David Hanss,[a] Pirmin Roesel,[a] Jean-Pierre Sauvage,*[a] and
Oliver S. Wenger[a]
Keywords: Biisoquinolines / Chelates / Endotopicity / Steric hindrance / C–C coupling
Four 8,8Ј-diaryl-substituted 3,3Ј-biisoquinoline ligands have
been synthesized and characterized. The key feature of this
new family of chelates is their endotopic but sterically non-
hindering nature. All four ligands were made from a common
8-bromoisoquinolin-3-ol precursor; between three and
twelve synthetic steps were necessary to obtain the products.
The reported synthetic procedures allow for gram-scale pro-
duction of these biisoquinolines.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
nitrogen atoms and thus implies steric hindrance around
the coordination site.
Introduction
Bidentate chelates of the aromatic polyimine family are
among the most universally used ligands in coordination
chemistry, the two archetypical structures being 2,2Ј-bipyri-
dine (bipy) and 1,10-phenanthroline (phen).[1] These two li-
gands have also played a central role, and continue to do
so, in the field of coordination photochemistry[2] since the
observation that [Ru(bipy)3]2+ solutions are luminescent at
room temperature.[3] In particular, this complex and its de-
rivatives, as well as many related second- and third-row
transition-metal complexes displaying the d6 electronic con-
figuration, have been investigated extensively in relation to
light-induced electron and energy transfer processes as well
as light energy storage.[4]
Several examples of 2,2Ј-bipy- and phen-incorporating
macrocycles[6] have been reported previously. Many of them
share the key structural feature of being substituted at the
two positions α to the nitrogen atoms. This (and only this)
substitution pattern ensures an endocyclic coordination
mode. Substitution at other positions is significantly more
likely to yield exocyclic coordination modes as illustrated in
Scheme 1.
In this report, we would like to describe the efficient syn-
thesis of a novel series of compounds that display two ap-
parently contradictory structural features: i) Their coordi-
nation site is not or is only very slightly hindered by organic
substituents borne by the ligand since the ligands have no
chemical groups α to the nitrogen atoms and ii) neverthe-
less, the binding site is oriented towards the endo part of
the crescent-shaped ligand. In other words, if the chelate is
later on included in a ring, the coordination site will unam-
biguously be endocyclic.
A brief description of the geometrical principles that
govern the present family of compounds, namely 8,8Ј-di-
aryl-3,3Ј-biisoquinoline chelates, has been given in a re-
cently published communication.[5]
Note that, very generally speaking, the endotopic and
endocyclic nature of the bidentate chelates prepared until
now relies on the presence of substituents located α to the
Scheme 1. Illustration of 2,9-diphenyl-1,10-phenanthroline (dpp)
and 8,8Ј-diaryl-3,3Ј-biisoquinoline based macrocycles.
Our group has made a large number of catenanes and
rotaxanes that include the 2,9-diphenyl-1,10-phenanthroline
(dpp) motif because of its highly suitable geometry.[7] The
synthesis of these mechanically interlocked molecules is
based on a copper(I) template-assisted method. Thereby,
the dpp motif plays a key role: It ligates to copper(I) in an
endocyclic fashion yielding very stable [Cu(dpp)2]+ precate-
nate complexes.
The biisoquinoline-containing ligands described in this
paper are such that endocyclic coordination will be certain.
In addition, as shown in Scheme 1, the complexed metal
center will be remote from any organic group of the organic
backbone.
[a] Laboratoire de Chimie Organo-Minérale, UMR 7177, Uni-
versité Louis Pasteur, Institut Le Bel,
4, rue Blaise Pascal, 67070 Strasbourg, France
Fax: +33-3-90241368
E-mail: sauvage@chimie.u-strasbg.fr
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The “longer-legged” equivalent of ligand 1, chelate 2,
was obtained using a different strategy (Scheme 3, right) in
which the phenolic function of 8 was first treated with ben-
zoyl chloride to give the ester 8-bromoisoquinolin-3-yl ben-
zoate (12) in very high yields (95%). Attempts to use benzyl
ether protecting groups gave unsatisfactory results due to
competitive alkylation at both the nitrogen and oxygen he-
teroatoms of 8. Since the ester protecting group was incom-
patible with alkaline Suzuki coupling methodologies, we
turned our attention to Stille couplings that can be per-
formed under pH-neutral conditions.[12] 4-Tributylstannyl-
biphenyl 13 was made in two steps from commercially avail-
able 4-bromo-4Ј-hydroxy-1,1Ј-biphenyl (Ͼ85% overall
yield) and coupled to 12 (65% yield). This Stille coupling
required significantly more drastic reaction conditions (5 d
at reflux in a toluene/tetrahydrofuran mixture) than the Su-
zuki coupling reaction used to obtain the shorter-legged an-
alogue 11 (2 h at room temperature). The Stille coupling
product 14 was subsequently deprotected in tetra-
hydrofuran/aqueous potassium hydroxide, whereby essen-
tially quantitative conversion of the benzoyl group to the
Results and Discussion
The four ligands shown in Scheme 2 were all made from
one common precursor, 8-bromoisoquinolin-3-ol (8). This
molecule is made in two steps from commercially available
starting materials, as illustrated in Scheme 3. The key step
is the intramolecular cyclization reaction of N-(2-bro-
mobenzyl)-2,2-diethoxyacetamide (7) in concentrated sulfu-
ric acid, a so-called Pomeranz–Fritsch reaction. In our
hands this reaction led to considerably lower yields (50%)
than those reported in a previously published protocol,[8]
mainly because the product turned out to be contaminated
with an unidentified white side-product from which it had
to be purified by recrystallization from methanol. The sub-
sequent reaction steps, described in more detail below and
in the Exp. Sect., were developed as part of our research.
Hereafter we give an account of the syntheses of the four
ligands depicted in Scheme 2 starting with chelate 1.
8-Bromoisoquinolin-3-ol (8) was converted into the tri-
flate 9 with triflic anhydride in dry pyridine in 95% yield
following a procedure similar to the one reported by
Långström and co-workers.[9] The triflate was treated with hydroxy function was observed. Reaction of triflic anhy-
1 equiv. of commercially available 4-methoxyphenylboronic dride with 15 gave triflate 16 in excellent yield. The final
acid (10) in a palladium-catalyzed Suzuki coupling reac- step in the synthesis of 2 was the same homocoupling reac-
tion as used for 1; analogous reaction conditions were ap-
plied to obtain chelate 2 and yields of the order of 70%
were obtained.
tion. The key was to use the [Pd2(dba)3] (dba = dibenz-
ylideneacetone)/PtBu3 catalyst system which allows highly
selective and efficient C–C coupling at the isoquinoline 8-
bromo position,[10] whereas with other catalysts, for exam-
Whereas the 8,8Ј-substituents of biisoquinolines 1 and 2
ple, Pd(triphenylphosphane)4, competitive reactions at both were readily accessible (10 is commercially available, 13 is
the bromo and triflate functions were observed. Coupling made in two steps), more serious synthetic effort was re-
product 11 was treated in a palladium-catalyzed homo- quired to obtain the biphenyl substituents of ligands 3 and
4. The multistep syntheses of these substituents are illus-
trated in Scheme 4 and are described in the following two
paragraphs.
coupling reaction with elemental zinc as an electron source
to give 1 in 70% average yield (Scheme 3).[11] The use of
high triflate concentrations (Ͼ1 m) was of pivotal impor-
tance for bimolecular homocoupling to be favored over un-
1,4-Dichlorobenzene (17) was coupled to organomagnes-
desired triflate/hydrogen exchange. Furthermore, the use of ium compound 18 using a nickel catalyst following a pre-
dry N,N-dimethylformamide was imperative.
viously published synthetic protocol.[13] 1,4-Di-n-hexylben-
Scheme 2. The four new biisoquinoline chelates that were synthesized in this work.
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A New Family of Biisoquinoline Chelates
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Scheme 3. Synthesis of the chelates 1 and 2.
zene (19) was obtained in excellent yield (90%) and bromi- the benzyl alcohol with lithium aluminium hydride to give
nated in an electrophilic aromatic substitution reaction with 27, and benzyl alcohol protection with 3,4-dihydro-2H-py-
bromine. This reaction, when performed in the dark and ran to yield 28.[16] Each of these three reaction steps is es-
when using iodine as a reaction initiator and catalyst, gave sentially quantitative; tedious work up or chromatographic
1,4-dibromo-2,5-di-n-hexylbenzene (20) in high yield (90%) separation was unnecessary. Thus it is possible to generate
as previously reported by Rehan et al.[13] This molecule was large quantities (50 g) of 28 with relative ease. Boronic acid
coupled to 4-methoxyphenylboronic acid (10) using a palla- 29 was obtained in the same manner as 22: Treatment with
dium(0) catalyst. When using a threefold excess of 20, Su- n-butyllithium followed by trimethyl borate addition. Com-
zuki coupling product 21 was obtained in 65% yield and pound 29 was treated with one equivalent of commercially
only very small amounts (Ͻ5%) of the undesired double- available 1-bromo-4-iodobenzene (30) under standard Su-
Suzuki-coupled 4,4ЈЈ-dimethoxyterphenyl were obtained. zuki coupling conditions to afford biphenyl 31 in 90% yield.
Excess dibromodihexylbenzene 20 was subsequently reco- The bromide was converted into the boronic acid 32 using
vered by column chromatography. The desired coupling the n-butyllithium/trimethyl borate route from above (yield:
product 21 was converted from the bromide to the boronic 90%). The characterization of this product by both NMR
acid 22 using n-butyllithium and trimethyl borate in a yield and mass spectrometry turned out to be problematic, pre-
of about 70%. Before describing the subsequent steps of sumably as a result of trimer and dimer formation. For this
the synthesis of ligand 3, we first turn our attention to the reason we decided to convert the boronic acid 32 into its
synthesis of biphenyl fragment 33 (Scheme 4, right) which pinacol ester 33. The desired product was obtained in quan-
was made for the synthesis of ligand 4.
titative yield by using toluene solvent and a Dean–Stark
3,5-Dihydroxybenzoic acid (23) was converted quantita- trap.
tively to 4-bromo-3,5-dihydroxybenzoic acid (24) following
The two biphenylylboronic acids 22 and 32 were then
a literature procedure.[14] The acid was transformed quanti- coupled to triisopropylsilyl-protected isoquinoline 34, see
tatively into the methyl ester 25 using thionyl chloride in Scheme 5. Isoquinoline 34 was obtained in nearly quantita-
methanol following another previously published proto- tive yield from 8-bromoisoquinolin-3-ol (8) in N,N-dimeth-
col.[15] A paper by Lüning et al. served as a valuable basis ylformamide and triisopropylsilyl chloride (TIPSCl).[17] In
for the three subsequent reactions steps, namely hydroxy- contrast to the benzoyl protecting group 12, the TIPS group
alkylation to 26 with 1-bromopropane, ester reduction to is compatible with alkaline Suzuki coupling conditions.
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F. Durola, D. Hanss, P. Roesel, J.-P. Sauvage, O. S. Wenger
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Scheme 4. Synthesis of the 8,8Ј-subsitutents of chelates 3 and 4.
Thus 34 was treated with the biphenylylboronic acids 22
and 32 as well as pinacol ester 33 in the presence of a palla-
dium(0) catalyst to give isoquinolines 35 and 38 with yields
in the order of 60%. We observed no difference in reactivity
between boronic acid 32 and pinacol ester 33. The silyl
ether protecting group was cleaved using tetrabutylammo-
nium fluoride with yields of around 75–80%, that is, TIPS
deprotection to give 36 and 39 occurs less efficiently than
benzoyl deprotection to 15. This is in line with previous
observations.[18] The phenols 36 and 39 were then converted
into the triflates 37 and 40 using trifluoromethanesulfonic
anhydride. The respective yields were 95 and 50%. Subse-
quent homocoupling of the triflates in a palladium-cata-
lyzed reaction using zinc powder as an electron source gave
ligands 3 (70% yield) and 4 (15% yield).
Our initial plan was to synthesize only ligands 1 and 2
but the latter turned out to be insoluble in a large variety
of solvents including N,N-dimethylformamide. Therefore
Scheme 5. Synthesis of the chelates 3 and 4.
we initiated the syntheses of biisoquinolines 3 and 4 which significantly greater synthetic effort. This is illustrated in
bear solubilizing n-hexyl and n-propyloxy groups on their Figure 1 which shows the number of synthetic steps re-
8,8Ј-biphenyl substituents. This renders these chelates quired to obtain ligands 1–4 from their common precursor,
highly soluble in solvents such as dichloromethane, tetra- 8-bromoisoquinolin-3-ol (8). Chelate 1 is readily available
hydrofuran, or ethanol, but this comes at the price of a from precursor 8 in three steps in 60% overall yield while
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A New Family of Biisoquinoline Chelates
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ligand 2 requires five steps and has an overall yield of 39%.
The 8,8Ј-biphenyl substituents of ligands
3 and 4
(Scheme 4) are both made in roughly 60% overall yield;
they are coupled equally well to the isoquinoline moiety.
Figure 2. Crystallographic structure of the [Fe(1)3]2+ cation 41.
Conclusions
In summary we have developed efficient multistep syn-
theses of four endotopic biisoquinoline ligands. These che-
lates are ideally suited for macrocycle formation around
transition-metal ions and are thus valuable new building
blocks for topological chemistry. In contrast to the vast ma-
Figure 1. (᭺) The number of reaction steps required to synthesize
the four biisoquinolines in Scheme 2 from their common precursor jority of previously reported endotopic α-diimine ligands,
8-bromoisoquinolin-3-ol (8) (Scheme 3). (ᮀ) The number of reac-
the 8,8Ј-diaryl-3,3Ј-biisoquinolines are sterically nonhinder-
tion steps needed to synthesize the 8,8Ј-aryl substituents. The grey
ing, as confirmed by the crystal structure analysis of an
bars represent the overall yields obtained for the syntheses of li-
homoleptic tris(biisoquinoline)iron(II) complex. This is ex-
pected to pave the way to the synthesis of molecules with
gands 1–4 from precursor 8.
highly unusual topologies.
Important efficiency differences in the syntheses of li-
gands 3 and 4 were observed in the last two steps, namely
Experimental Section
the conversion of the hydroxy function into the triflate (37
and 40) and the subsequent homocoupling reactions. For
chelate 3, these two reactions give yields comparable to
those observed for ligands 1 and 2, that is, a conversion of
the hydroxy group to the triflate that is very nearly quanti-
tative and a homocoupling yield of about 70%. By contrast,
for ligand 4 the triflate yield is about 50% and the homo-
coupling yield 15%. An important chemical difference be-
tween ligand 4 and chelates 1, 2, and 3 is of course the
presence of a tetrahydropyran (THP)-protected benzyl
alcohol in 4; ligands 1–3 contain methyl-protected phenols.
The methoxy groups are known to be chemically more ro-
bust than OTHP groups and thus it seems plausible that
the lower yields of the last two steps in the synthesis of
ligand 4 are due to THP deprotection and subsequent unde-
sired side-reactions.
The following chemicals were obtained commercially and used
without further purification: Ammonium chloride (Aldrich), bar-
ium hydroxide octahydrate (Aldrich), 1,3-bis(triphenylphosphanyl)-
propanenickel(II) chloride (Strem), benzoyl chloride (Aldrich),
1,1Ј-bis(diphenylphosphanyl)ferrocenedichloropalladium(II) (Ald-
rich), bromine (Aldrich), 2-bromobenzylamine (Alfa Aesar), 1-
bromohexane (Aldrich), 4-bromo-4Ј-hydroxy-1,1Ј-biphenyl (Ald-
rich), 1-bromo-4-iodobenzene (Acros), 1-bromopropane (Aldrich),
n-butyllithium in hexanes (1.6  solution) (Aldrich), 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU) (Aldrich), 1,4-dichlorobenzene (Alfa
Aesar), dichlorobis(triphenylphosphane)palladium(II) (Aldrich),
3,4-dihydro-2H-pyran (Aldrich), 3,5-dihydroxybenzoic acid
(Acros), 1,2-dimethoxyethane (Aldrich), ethyl diethoxyacetate (Al-
drich), imidazole (Acros), iron(II) tetrafluoroborate hexahydrate
(Aldrich), lithium aluminium hydride (Aldrich), lithium chloride
(Merck), magnesium as ribbons (Riedel-de Haën), 4-methoxyphen-
ylboronic acid (Aldrich), potassium carbonate (Prolabo), potas-
sium hydroxide (Riedel-de Haën), potassium iodide (Prolabo), tet-
rabutylammonium chloride hydrate (Acros), tetrabutylammonium
fluoride trihydrate (Acros), tetrabutylammonium iodide (Aldrich),
tetrakis(triphenylphosphane)palladium(0) (Aldrich), thionyl chlo-
ride (Prolabo), tri-tert-butylphosphonium tetrafluoroborate
(Strem), tri-n-butyltin chloride (Aldrich), triethylamine (Riedel-
de Haën), trifluoromethanesulfonic anhydride (Alfa Aesar) triiso-
propylsilyl chloride (Acros), trimethyl borate (Aldrich), tris(diben-
zylideneacetone)dipalladium(0) (Strem), pinacol (Aldrich), potas-
sium fluoride (Aldrich), potassium iodide (Prolabo), sulfuric acid
(Riedel-de Haën), p-toluenesulfonic acid monohydrate (Aldrich),
zinc powder (Fluka).
However, despite the relatively large number of steps re-
quired to make these four 8,8Ј-diaryl-substituted 3,3Ј-biiso-
quinolines, it is possible to produce gram quantities of each
of the four ligands in Scheme 2 with relative ease.
Addition of ligand 1 to a solution of iron(II) tetrafluo-
roborate at room temperature led to the rapid formation of
the red [Fe(1)3]2+ complex 41 in nearly quantitative yield.
An X-ray crystal structure of this complex is shown in Fig-
ure 2. The FeN6 first coordination sphere is very nearly oc-
tahedral: Fe–N distances in the 1.958–1.972 Å range were
determined and all N–Fe–N angles are between 86 and 94°.
This strongly supports our hypothesis that this family of
ligands coordinates transition-metal ions in an endotopic
but sterically nonhindering fashion.
Dry solvents were obtained with suitable desiccants. Diethyl ether
and tetrahydrofuran were distilled from sodium, triethylamine and
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pyridine from potassium hydroxide. N,N-Dimethylformamide was
distilled from anhydrous aluminium oxide.
8-(p-Anisyl)isoquinolin-3-yl Trifluoromethanesulfonate (11): Because
of the very air-sensitive phosphane, the subsequently described ma-
nipulations must be carried out under argon. 4-Methoxyphenylbo-
ronic acid (10) (3.01 g, 19.8 mmol), potassium fluoride (3.45 g,
59.4 mmol), and tris(dibenzylideneacetone)dipalladium(0) (825 mg,
0.9 mmol) were added to a dry two-necked flask equipped with
a stirring bar. A solution of 8-bromoisoquinolin-3-yl trifluoro-
methanesulfonate (9) (6.41 g, 18 mmol) in dry and degassed
tetrahydrofuran (20 mL) was first added through a cannula. A
mixture of tri-tert-butylphosphonium tetrafluoroborate (627 mg,
2.16 mmol) and DBU (about 0.35 mL, 2.3 mmol) in dry and de-
gassed tetrahydrofuran (20 mL) was then added through a cannula.
The reaction mixture was stirred at room temperature (25 °C) for
2 h and subjected to thin-layer chromatography [silica; dichloro-
methane/pentane 3:2 (v/v)]. In case the reaction had not finished,
it was then stirred for two more hours at room temperature. Finally,
the reaction mixture was diluted with diethyl ether and filtered
through a pad of silica gel with copious washings. The solvent was
evaporated and the residue purified by chromatography on silica
gel using dichloromethane/pentane (3:7, 4:6, and 5:5) as the eluent
to give pure 11 as colorless crystals (6.18 g, 90%). 1H NMR
(CD2Cl2): δ = 9.12 (s, 1 H, 1-H), 7.90 (d, J = 8.2 Hz, 1 H), 7.82
(dd, J = 7.1, 8.2 Hz, 1 H, 7-H), 7.63 (s, 1 H, 4-H), 7.59 (d, J =
7.1 Hz, 1 H), 7.44 (d, J = 8.8 Hz, 2 H), 7.06 (d, J = 8.8 Hz, 2 H),
3.89 (s, 3 H, OCH3) ppm. ES-MS: calcd. for C17H12F3NO4S + Li+
390.0594; found 390.0575.
All silica column chromatography was performed using Merck sil-
ica gel 60 (0.063–0.200 mm). Fluka aluminium oxide 17994 was
used in alumina columns and for filtrations.
1H and 13C NMR spectra were recorded with a Bruker AVANCE
300 [300 MHz (1H); 75 MHz (13C)] spectrometer using deuteriated
solvent as the lock. The spectra were collected at 25 °C and the
chemical shifts were referenced to residual solvent protons as in-
ternal standards. 1H: CDCl3 7.27 ppm, CD2Cl2 5.32 ppm, [D6]ace-
tone, 2.05 ppm, [D6]DMSO 2.50 ppm; 13C: CD3Cl 77 ppm, CD2Cl2
53.7 ppm, [D6]acetone 30.6 ppm.[19] Mass spectra were obtained
with a VG ZAB-HF spectrometer (FAB) and a VG-BIOQ triple
quadrupole in positive or negative mode (ES-MS).
Single-crystal X-ray diffraction experiments were carried out with
a Kappa CCD diffractometer using graphite-monochromated Mo-
Kα radiation (λ = 0.71073 Å). The SHELX-97[20] program was used
for structure solution and refinement.
N-(2-Bromobenzyl)-2,2-diethoxyacetamide (7): Sodium diethoxy-
acetate (22.95 g, 135 mmol) was dissolved in dry diethyl ether
(110 mL) and to this mixture was added thionyl chloride (10.0 mL,
16.2 g, 136 mmol) with stirring for 10 min at 10 °C. The reaction
mixture was refluxed for 30 min and then cooled. A solution of 2-
bromobenzylamine (25 g, 13.4 mmol) in dry toluene (70 mL) and
freshly distilled pyridine (41 mL) was added to this reaction mix-
ture through a cannula with vigorous stirring. The resulting mix-
ture was refluxed for 30 min and then cooled to room temperature.
Then the mixture was poured into ice–water (ca. 200 mL) and ex-
tracted with toluene (3ϫ100 mL). The organic extracts were com-
bined and washed with a solution of hydrochloric acid (2%,
100 mL) and water. The organic solvents were evaporated and the
residue purified by chromatography [silica; pentane/ethyl acetate
9:1 (v/v)]. Thereby pure 7 was obtained as a yellow oil (23.6 g,
8,8-Di-p-anisyl-3,3Ј-biisoquinoline (1): Zinc powder (20 g) was acti-
vated in acetic acid (100 mL) for 1 h. After filtration, the powder
was washed three times with distilled water and dried under vac-
uum for 6 h at 120 °C. Dichloro[1,1Ј-bis(diphenylphosphanyl)ferro-
cene]palladium(II) dichloromethane adduct (800 mg, 1.09 mmol),
zinc powder (10.2 g, 156 mmol), potassium iodide (10.3 g,
62 mmol), and 8-(p-anisyl)isoquinolin-3-yl trifluoromethanesulfon-
ate (11) (6.02 g, 15.7 mmol) were stirred in the smallest possible
volume of dry and degassed N,N-dimethylformamide (about
10 mL) for 2 h at 90 °C. Then the solvent was evaporated and the
residue dissolved in dichloromethane (100 mL), distilled water
(100 mL), and a 32% ammonium hydroxide solution (10 mL). The
organic phase was separated and the aqueous phase extracted twice
with dichloromethane. The combined organic phases were washed
once with distilled water and then evaporated. Dichloromethane
(20 mL) was added to the crude product and the mixture was fil-
tered through a glass frit with porosity 4. The solid was washed
with acetone and diethyl ether to give pure 1 as a white powder
1
60%). H NMR (CDCl3): δ = 7.34 (m, 2 H), 7.23 (m, 2 H), 7.04
(br. s, 1 H), 4.82 (s, 1 H), 4.55 (d, 2 H, J = 6.2 Hz), 3.63 (m, 4 H),
1.23 (t, 6 H, J = 7.1 Hz) ppm.
8-Bromoisoquinolin-3-ol (8): N-(2-Bromobenzyl)-2,2-diethoxyacet-
amide (7) (23.6 g, 74.6 mmol) was added carefully to concentrated
sulfuric acid (120 mL) with stirring under ice cooling. The reaction
mixture was stirred at room temperature for 16 h, poured into ice–
water, and filtered. The filtrate was slowly neutralized with 33%
aqueous ammonium hydroxide and the resulting precipitate was
filtered, dried, and then recrystallized from methanol to give 10.7 g
(47.8 mmol, 64%) of pure 8 as yellow needles. 1H NMR (CD2Cl2):
δ = 9.13 (s, 1 H, 1-H), 7.66 (d, J = 8.7 Hz, 1 H, 7-H), 7.60 (d, J =
7.2 Hz, 1 H, 5-H), 7.42 (dd, J = 8.7, 7.2 Hz, 1 H, 6-H), 7.03 (s, 1
H, 4-H) ppm. ES-MS: calcd. for C9H6BrNO + H+ 223.9711; found
223.9694. C9H6BrNO: C 48.25, H 2.70, N 6.25; found C 47.99, H
3.06, N 6.46.
1
(2.47 g, 67%). H NMR (CDCl3): δ = 9.48 (s, 2 H, 1-H), 8.92 (s, 2
H, 4-H), 7.94 (d, J = 8.2 Hz, 2 H), 7.72 (dd, J = 7.1, 8.2 Hz, 2 H),
7.52 (d, J = 8.8 Hz, 4 H), 7.51 (d, J = 7.1 Hz, 2 H), 7.08 (d, J =
8.8 Hz, 4 H), 3.93 (s, 6 H, OCH3) ppm. ES-MS: calcd. for
C32H24N2O2 + H+ 469.1911; found 469.1907.
8-Bromoisoquinolin-3-yl Benzoate (12): Benzoyl chloride (0.62 mL,
5.36 mmol) was added dropwise to a solution of 8-bromoisoquino-
lin-3-ol (1.0 g, 4.47 mmol) in freshly distilled pyridine (15 mL) at
0 °C under argon. The resulting mixture was stirred for 2 h at room
temperature. After evaporation of the pyridine solvent, the crude
product was dissolved in dichloromethane and filtered through alu-
8-Bromoisoquinolin-3-yl Trifluoromethanesulfonate (9): A solution
of 8-bromoisoquinolin-3-ol (4.0 g, 17.9 mmol) in dry pyridine
(125 mL) was cooled to 0 °C and carefully treated with trifluorome-
thanesulfonic anhydride (4.0 mL, 6.8 g, 23 mmol). The mixture was
warmed to room temperature and stirred overnight. Then the sol-
vent was removed under reduced pressure. The crude product was
purified by chromatography on silica gel using pentane/diethyl
ether (1:4) as eluent to afford pure 9 as colorless crystals (6.06 g,
95%). 1H NMR (CD2Cl2): δ = 9.43 (s, 1 H, 1-H), 7.95 (d, J =
7.5 Hz, 1 H), 7.91 (d, J = 7.9 Hz, 1 H), 7.65 (dd, J = 7.9, 7.5 Hz,
1
mina to yield 1.42 g (4.36 mmol; 97%) of pure compound 12. H
NMR (CD2Cl2): δ = 9.47 (s, 1 H, 1-H), 8.27 (d, J = 7.7 Hz, 2 H,
Ha), 7.85 (d, J = 7.7 Hz, 2 H, Hb), 7.70 (ddd, J = 7.4, 7.4 Hz, 1 H,
6-H), 7.59–7.54 (m, 4 H) ppm. ES-MS: calcd. for C16H10BrNO2
329.995; found 329.999. C16H10BrNO2: C 58.56, H 3.07, N 4.27;
found C 58.81, H 3.41, N 4.02.
1
H, 7-H), 7.60 (s,
1
H, 4-H) ppm. ES-MS: calcd. for
4-Methoxy-4Ј-tri-n-butylstannyl-1,1Ј-biphenyl (13): This compound
was obtained in two steps: commercially available 4-bromo-4Ј-hy-
C10H5BrF3NO3S + Li+ 361.9280; found 361.9404.
130
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A New Family of Biisoquinoline Chelates
FULL PAPER
droxy-1,1Ј-biphenyl (10.0 g, 40.14 mmol) was treated with methyl
iodide (17.1 g, 120.42 mmol) and tetrabutylammonium iodide
(0.74 g, 2.00 mmol) in a biphasic system consisting of 1  aqueous
potassium carbonate (50 mL) and acetonitrile (100 mL). After re-
fluxing for 16 h the reaction mixture was evaporated to dryness and
the solids were taken up in water (100 mL) and dichloromethane
(300 mL). Filtration of the organic phase through silica gel and
solvent evaporation yielded 9.38 g (35.65 mmol; 89%) of pure 4-
bromo-4Ј-methoxy-1,1Ј-biphenyl as a white powder. The latter was
dissolved in freshly distilled tetrahydrofuran (125 mL) and dry tolu-
ene (125 mL) and cooled to –78 °C. After dropwise addition of
1.6  n-butyllithium (24.5 mL) in hexanes solution, the reaction
mixture was stirred for 2 h at –78 °C under argon before tri-n-bu-
tyltin chloride (10.7 mL, 39.45 mmol) was slowly added. The solu-
tion was subsequently warmed to room temperature and stirred for
another 4 h. The solvents were evaporated and the remaining oil
was dissolved in pentane and filtered through neutral alumina. Pen-
tane evaporation yielded 16.2 g (34.23 mmol; 96%) of pure com-
(CD2Cl2): δ = 9.19 (s, 1 H, 1-H), 7.99 (d, J = 8.4 Hz, 1 H, 7-H),
7.87 (dd, J = 8.4, 6.9 Hz, 1 H, 6-H), 7.77–7.57 (m, 8 H), 7.04 (d, J
= 8.7 Hz, 2 H) 6.97 (s, 1 H, 4-H), 3.87 (s, 3 H, OCH3) ppm. ES-
MS: calcd. for C22H17NO4F3S + H+ 460.082; found 460.081.
C22H17NO4F3S: C 60.13, H 3.51, N 3.05; found C 60.10, H 3.86,
N 2.74.
8,8Ј-Bis(p-anisyl-p-phenyl)-3,3Ј-biisoquinoline (2): Triflate 16
(6.50 g, 14.15 mmol) and 1,1Ј-bis(diphenylphosphanyl)ferrocene-
dichloropalladium(II) (1.17 g, 1.28 mmol) were dissolved in freshly
distilled N,N-dimethylformamide (19 mL). After addition of freshly
activated zinc powder (9.26 g, 141.6 mmol) (for activation pro-
cedure, see 1) and dry potassium iodide (9.39 g, 56.56 mmol), the
reaction mixture was heated to 90 °C for 8 h. Then the mixture was
filtered through a glass frit (porosity 4) and the residue taken up in
dichloromethane (100 mL) and a 10% aqueous ammonia solution
(100 mL). Filtration of the organic phase and repeated washings of
the filtered residue with dichloromethane and diethyl ether yielded
3.19 g of biisoquinoline 2 (5.14 mmol; 73%) as a white powder. 1H
NMR (CDCl3, 5% TFA): δ = 9.72 (s, 2 H, 1-H), 9.07 (s, 2 H, 4-
H), 8.36–8.34 (m, 4 H, 5-H, 7-H), 8.12 (dd, J = 5.0, 3.4 Hz, 2 H,
6-H) 7.83 (d, J = 8.8 Hz, 4 H), 7.66 (d, J = 8.8 Hz, 4 H), 7.61 (d,
J = 8.8 Hz, 4 H), 7.08 (d, J = 8.8 Hz, 4 H), 3.93 (s, 6 H,
OCH3) ppm. ES-MS: calcd. for C44H32N2O2 + H+ 621.2537; found
621.2529.
1
pound 13 as a colorless oil. H NMR (CD2Cl2): δ = 7.56 [d, J =
8.8 Hz, 2 H, -C6(-m)H2(o-)H2OCH3], 7.53 (s, 2 H, -SnC6H4–), 6.99
[d, J = 8.8 Hz, 2 H, -C6(-m)H2(o-)H2OCH3], 3.85 (s, 3 H, OCH3),
1.64–1.54 (m, 6 H, -CH2CH2CH2CH3), 1.37 (tt, J = 7.5, 7.5 Hz, 6
H, -CH2CH2CH2CH3), 1.13–1.08 (m,
6
H, -CH2CH2-
CH2CH3), 0.92 (t, J = 7.3 Hz, 9 H, -CH2CH2CH2CH3) ppm.
8-(p-Anisyl-p-phenyl)isoquinolin-3-yl Benzoate (14): 8-Bromoisoqui-
nolin-3-yl benzoate (12) (8.20 g, 25.0 mmol) and 4-methoxy-4Ј-tri-
n-butylstannyl-1,1Ј-biphenyl (13) (13.3 g, 28.1 mmol), and dichlo-
robis(triphenylphosphane)palladium(II) (0.95 g, 1.4 mmol) were
dissolved in a mixture of tetrahydrofuran and toluene (200 mL, 1:1,
v/v). After addition of dry lithium chloride (5.3 g, 125 mmol), the
reaction mixture was placed under argon and refluxed for 5 d and
the reaction progress was monitored by thin-layer chromatography
[silica; pentane/ethyl acetate 4:1 (v/v)]. Then the solvents were evap-
orated, the residue taken up in dichloromethane (200 mL) and
washed with water (200 mL). Evaporation of the dichloromethane
yielded a yellow solid which was subjected to column chromatog-
raphy [silica; pentane/ethyl acetate 4:1 (v/v)]. This procedure
yielded 5.26 g (12.19 mmol; 49%) of the coupling product 14 as a
1,4-Di-n-hexylbenzene (19): 1-Hexyl bromide (70 mL, 500 mmol) in
dry diethyl ether (50 mL) was added dropwise, over 30 min, to a
suspension of magnesium ribbons (13.4 g, 550 mmol) in dry diethyl
ether (100 mL) maintained at slight reflux. After complete ad-
dition, the solution was refluxed for an additional 30 min. When
cooled to room temperature, the n-hexylmagnesium bromide was
transferred, over 30 min, to an ice-cooled and stirred solution of
1,4-dichlorobenzene (29.4 g, 200 mmol) and 1,3-bis(triphenylphos-
phanyl)propanenickel(II) chloride (108 mg, 200 µmol) in dry di-
ethyl ether (200 mL). Then the cooling bath was removed and the
solvent began to boil after an induction period of about 1 h. The
mixture was refluxed overnight, cooled to 0 °C, and quenched care-
fully with water (10 mL), followed by 2  hydrochloric acid
(100 mL). After phase separation, the aqueous phase was extracted
with diethyl ether (2ϫ50 mL) and the combined organic phases
were washed with water (50 mL) and dried (anhydrous magnesium
sulfate). The solvent was removed to yield the crude but analyti-
cally pure 19 (48.2 g, 98%) as a slightly yellow oil. 1H NMR
(CDCl3): δ = 7.09 (s, 4 H, aryl-H), 2.57 [t, J = 7.7 Hz, 4 H, CH2(α)],
1.65–1.52 [m, 4 H, CH2(β)], 1.37–1.26 (m, 12 H), 0.89 (t, J =
7.1 Hz, 6 H, CH3) ppm.
1
white solid. H NMR (CD2Cl2): δ = 9.23 (s, 1 H, 1-H), 8.27 (d, J
= 6.9 Hz, 2 H, Ha), 7.90–7.55 (m, 13 H), 7.03 (d, J = 9.0 Hz, 2 H),
3.86 (s, 3 H, OCH3) ppm. ES-MS: calcd. for C28H22NO3 + H+
432.1594; found 432.1541.
8-(p-Anisyl-p-phenyl)isoquinolin-3-ol (15): Benzoate-protected iso-
quinoline 14 (5.26 g (12.19 mmol) was dissolved in tetrahydrofuran
(150 mL). After addition of 2  aqueous potassium hydroxide
(150 mL) the resulting biphasic solution was stirred vigorously for
2 h at room temperature during which time it turned yellow. After
neutralizing it with 1  hydrochloric acid under ice cooling, the
solution was filtered through a glass frit (porosity 3) and the yellow
solid was vacuum-dried overnight to yield 3.87 g (11.83 mmol;
97%) of pure compound 15. ES-MS: calcd. for C22H18NO2
328.1332; found 328.1342. C22H18NO2: C 80.71, H 5.23, N 4.28;
found C 82.46, H 5.14, N 4.16.
1,4-Dibromo-2,5-di-n-hexylbenzene
(20):
Bromine
(67.1 g,
420 mmol) was added dropwise, over 30 min, to a stirred and ice-
cooled solution of 1,4-dihexylbenzene (19) (49.3 g, 200 mmol) and
iodine (≈500 mg, 0.01 equiv.) under rigorous exclusion of light. Af-
ter 1 d at room temperature, 20% aqueous potassium hydroxide
solution (100 mL) was added and the mixture was shaken under
slight warming until the color disappeared. The mixture was then
cooled to room temperature, the aqueous solution decanted, and
the remaining residue was recrystallized from ethanol to give 20
8-(p-Anisyl-p-phenyl)isoquinolin-3-yl
(16): 8-(p-Anisyl-p-phenyl)isoquinolin-3-ol
Trifluoromethanesulfonate
(15) (3.87 g,
1
(65.9 g, 82%) as colorless crystals. H NMR (CDCl3): δ = 7.35 (s,
2 H, aryl-H), 2.64 [t, J = 7.7 Hz, 4 H, CH2(α)], 1.60–1.49 [m, 4 H,
CH2(β)], 1.41–1.24 (m, 12 H), 0.90 (t, J = 7.1 Hz, 6 H, CH3) ppm.
11.83 mmol) was dissolved in freshly distilled pyridine (250 mL).
Triflic anhydride (3.29 mL, 19.56 mmol) was added dropwise under
argon at 0 °C; thereby the solution turned red-brown. After stirring
for 16 h at room temperature the pyridine solvent was removed and
the remaining dark brown solid was subjected to column
chromatography (silica; dichloromethane). This yielded 4.51 g
(9.82 mmol; 83%) of pure triflate 16 as a white solid. 1H NMR
4-Bromo-2,5-di-n-hexyl-4Ј-methoxy-1,1Ј-biphenyl
(21): 1,4-Di-
bromo-2,5-dihexylbenzene (20) (23.9 g, 59.2 mmol), 4-methoxy-
phenylboronic acid (10) (4.50 g, 29.6 mmol), and sodium carbonate
(5.02 g, 47.4 mmol) were dissolved in toluene (800 mL), ethanol
(150 mL), and water (50 mL). The solution was degassed with ar-
Eur. J. Org. Chem. 2007, 125–135
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131

F. Durola, D. Hanss, P. Roesel, J.-P. Sauvage, O. S. Wenger
FULL PAPER
gon (30 min) before addition of tetrakis(triphenylphosphane)palla-
dium(0) (867 mg, 750 µmol). The reaction mixture was refluxed for
16 h, extracted twice with water (200 mL), and purified by column
chromatography [silica; 0.4% ethyl acetate in pentane (v/v)] to yield
21 (10.1 g, 79%) as a colorless oil. H NMR (CDCl3): δ = 7.41 (s,
1 H, aryl-H), 7.19 (d, J = 8.8 Hz, 2 H, aryl-H), 7.01 (s, 1 H, aryl-
partially during the reaction. In order to complete the deprotection
process, the reaction mixture was then evaporated to dryness, dis-
solved in tetrahydrofuran (100 mL), and tetrabutylammonium
fluoride trihydrate (6.18 g, 19.6 mmol) was added. This reaction
mixture was stirred for a period of 30 min. Then the solvent was
evaporated and the residue filtered through silica [washings with
1
H), 6.93 (d, J = 8.8 Hz, 2 H, aryl-H), 3.85 (s, 3 H, OCH3), 2.68 [t, dichloromethane and a 9:1 (v/v) mixture of dichloromethane and
J = 7.7 Hz, 2 H, CH2(α)], 2.49 [t, J = 7.7 Hz, 2 H, CH2(αЈ)], 1.65– methanol] in order to remove less polar impurities. Finally, the
1.52 (m, 2 H), 1.46–1.11 (m, 14 H), 0.88–0.75 (m, 6 H, CH3) ppm.
crude phenol was dissolved in anhydrous dichloromethane
(250 mL)andanhydroustriethylamine(40 mL).Thesolutionwascooledto
13C NMR (CDCl3): δ = 158.6, 140.7, 140.0, 139.1, 133.5, 133.0,
131.8, 130.2, 123.0, 113.5, 55.3 (OCH3), 35.8, 32.4, 31.7, 31.5, 31.1, –10 °C and trifluoromethanesulfonic anhydride (4.5 mL,
30.0, 20.2, 20.1, 22.6, 22.5, 14.1 (CH3) ppm. ES-MS: calcd. for
C25H35BrO 432.1849; found 432.1855.
26.7 mmol) was added slowly. The reaction mixture was stirred for
16 h at room temperature, washed with saturated ammonium chlo-
ride solution, and purified by column chromatography [silica; pen-
tane/diethyl ether 20:1 (v/v)] to yield triflate 37 (7.22 g, 65% with
Boronic Acid 22: Bromide 21 (4.28 g, 9.92 mmol) was dissolved in
anhydrous tetrahydrofuran (500 mL) and cooled to –78 °C. N-Bu-
tyllithium (12.4 mL, 1.6  solution in hexanes, 19.8 mmol) was
added dropwise to this solution. The reaction mixture was stirred
over a period of 2 h at this temperature whereby a slight yellow
coloring was observed. Trimethyl borate (2.2 mL, 19.8 mmol) was
added and the reaction mixture (now colorless) was stirred at room
temperature overnight. Hydrochloric acid (200 mL, 4 ) was added
and the solvents removed in vacuo. The white precipitate was dis-
solved in diethyl ether (150 mL) and water (150 mL). The organic
phase was separated and the solvent removed to yield a white solid
(4.06 g, quantitative) which was used without further purification
1
respect to 34) as a pale yellow oil. H NMR (CDCl3): δ = 8.81 (t,
J = 0.8 Hz, 1 H, 1-H), 7.93–7.81 (m, 2 H), 7.62–7.56 (m, 2 H), 7.32
[d, J = 8.8 Hz, 2 H(10)], 7.19 (s, 1 H), 7.10 (s, 1 H), 7.00 (d, J =
9.0 Hz, 2 H), 3.89 (s, 3 H, OCH3), 2.58–2.55 [m, 2 H, CH2(α)],
2.42–2.28 [m, 2 H, CH2(αЈ)], 1.40–0.91 (m, 16 H), 0.80 (t, J =
6.8 Hz, 3 H, CH3), 0.73 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR
(CDCl3): δ = 158.6, 152.4, 151.7, 141.7, 141.2, 138.6, 138.4, 137.9,
135.4, 134.0, 131.4, 131.2, 131.0, 130.3, 129.3, 127.8, 126.0, 113.5,
110.6, 76.6 (CF3), 55.3 (OCH3), 32.8, 32.6, 31.5, 31.3, 31.1, 29.7,
29.2, 28.9, 22.5, 22.3, 14.0, 13.9 ppm. 19F NMR (CDCl3): δ =
–73.4 (s) ppm. ES-MS: calcd. for C35H40F3NO4S + H+ 628.2703;
found 628.2727.
1
in the next step. H NMR ([D6]acetone/D2O ≈ 6:1): δ = 7.47 (s, 1
H, aryl-H), 7.17 (d, J = 8.8 Hz, 2 H, aryl-H), 6.94 (d, J = 8.8 Hz,
2 H, aryl-H), 6.87 (s, 1 H, aryl-H), 3.79 (s, 3 H, OCH3), 2.79 [t, J
= 7.7 Hz, 2 H, CH2(α)], 2.49 [t, J = 7.7 Hz, 2 H, CH2(αЈ)], 1.58–
8,8Ј-Diaryl-3,3Ј-biisoquinoline 3: Triflate 37 (1.68 g, 2.68 mmol),
freshly activated zinc powder (1.75 g, 10 equiv., for activation pro-
cedure, see 1), dry potassium iodide (1.78 g, 10.7 mmol), and 1,1Ј-
bis(diphenylphosphanyl)ferrocenedichloropalladium(II) (218 mg,
268 µmol) were dissolved in dry N,N-dimethylformamide (1.8 mL)
and stirred for 16 h at 90 °C. The mixture was hydrolyzed with
10% aqueous hydrochloric acid (40 mL) and extracted with diethyl
ether. The red solution was filtered three times through alumina
before purification by column chromatography [silica; pentane/di-
ethyl ether 20:1 (v/v)] to yield 3 (950 mg, 74%) as a white solid. 1H
NMR (CDCl3): δ = 9.12 (s, 2 H, 1-H), 8.94 (s, 2 H, 4-H), 7.98 (d,
J = 8.1 Hz, 2 H, 6-H), 7.76 (t, J = 7.5 Hz, 2 H, 7-H), 7.52 (d, J =
7.6 Hz, 2 H, 8-H), 7.36 (d, J = 7.7 Hz, 4 H, anisyl-H), 7.23 (s, 2
H, aryl-H), 7.20 (s, 2 H, aryl-H), 7.02 (d, J = 7.7 Hz, 4 H, anisyl-
H), 3.91 (s, 6 H, OCH3), 2.65–2.55 [m, 4 H, CH2(α)], 2.49–2.37 [m,
2 H, CH2(αЈ)], 2.36–2.22 [m, 2 H, CH2(αЈЈ)], 1.52–0.93 (m, 32 H),
0.82 (t, J = 7.2 Hz, 6 H, CH3), 0.71 (t, J = 7.2 Hz, 6 H, CH3Ј) ppm.
13C NMR (CDCl3): δ = 158.6, 151.4, 149.8, 141.2, 140.6, 138.6,
137.7, 136.9, 136.4, 134.4, 131.4, 130.9, 130.4, 130.0, 128.4, 127.6,
126.9, 117.5, 113.5, 55.3, 32.9, 32.7, 31.5, 31.4, 31.3, 31.1, 29.2,
28.9, 22.5, 22.3, 14.0, 13.9 ppm. ES-MS: calcd. for C68H80N2O2 +
H+ 957.6298; found 957.6266.
1.46 (m, 2 H), 1.42–1.03 (m, 14 H), 0.83–0.72 (m, 6 H, CH3) ppm.
–
ES-MS: calcd. for C25H37BO3
509.2658.
+
CF3SO2 509.2696; found
8-Bromoisoquinolin-3-yl Triisopropylsilyl Ether (34): 8-Bromoiso-
quinolin-3-ol (8) (10.03 g, 44.8 mmol) and imidazole (7.62 g,
112 mmol) were dissolved in N,N-dimethylformamide (250 mL).
After dropwise addition of triisopropylsilyl chloride (11.4 mL) at
0 °C the reaction mixture was stirred for 12 h at room temperature.
Then the N,N-dimethylformamide was evaporated and the residue
was taken up in dichloromethane (200 mL) and water (200 mL).
After phase separation, the water phase was extracted once with
dichloromethane (100 mL). The combined organic phases were
evaporated and the residue subjected to column chromatography
(silica; dichloromethane). This procedure yielded 16.01 g
(42.1 mmol; 94%) of pure 34 as a slightly yellow oil which crys-
tallized within several hours upon standing at room temperature.
1H NMR (CDCl3): δ = 9.20 (s, 1 H, 1-H), 7.61–7.57 (m, 2 H, 6,7-
H), 7.34 (dd, J = 8.4, 7.3 Hz, 1 H, 5-H), 6.97 (s, 1 H, 4-H), 1.45
[hept, J = 7.9 Hz, 3 H, CH(CH3)3], 1.13 [d, J = 7.9 Hz, 18 H,
CH(CH3)3] ppm. 13C NMR (CDCl3): δ = 160.10 (C-3), 150.40 (C-
1), 141.12 (C-10), 130.29, 128.02, 125.50, 123.28, 122.58, 103.97,
18.07 [CH(CH3)3], 12.70 [CH(CH3)3] ppm. ES-MS: calcd. for
4-Bromo-3,5-dihydroxybenzoic Acid (24): 3,5-Dihydroxybenzoic
acid (23) (100 g, 649 mmol) and bromine (103.6 g, 649 mmol) were
refluxed in 20% hydrochloric acid (1.1 L) for 2 h. The initially in-
homogeneous reaction mixture temporarily became a homogen-
eous solution before the reappearance of a white precipitate
towards the end of the reaction time. Then the reaction mixture
was extracted with diethyl ether (3ϫ500 mL). The combined or-
ganic phases were dried with anhydrous sodium sulfate. Evapora-
tion of the solvent yielded 151.2 g (649 mmol; 100%) of pure 4-
bromo-3,5-dihydroxybenzoic acid (24) as a sticky white solid. 1H
NMR ([D6]acetone): δ = 7.19 (s, 2 H, aryl-H) ppm. ES-MS: calcd.
for C7H5BrO4 + Na+ 254.9460; found 254.9263.
C18H26BrNOSi
+
H+ 382.1021; found 382.1014; calcd. for
C18H26BrNOSi + Na+ 404.0841; found 404.0820.
8-(1,1Ј-Biphenyl-4-yl)isoquinolin-3-yl Trifluoromethanesulfonate 37:
Three synthetic steps were performed without isolation of the inter-
mediates 35 and 36: First, triisopropylsilyl ether 34 (6.77 g,
17.8 mmol) and boronic acid 22 (8.72 g, 22.0 mmol) were dissolved
in 1,2-dimethoxyethane (90 mL) and water (15 mL). The solution
was degassed with argon (30 min) before addition of tetrakis(tri-
phenylphosphane)palladium(0) (825 mg, 712 µmol) and barium hy-
droxide octahydrate (7.30 g, 23.2 mmol). The mixture was refluxed
overnight. The triisopropylsilyl ether protecting group was removed
Methyl 4-Bromo-3,5-dihydroxybenzoate (25): 4-Bromo-3,5-dihy-
droxybenzoic acid (24) (151.2 g, 649 mmol) was dissolved in dry
132
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A New Family of Biisoquinoline Chelates
FULL PAPER
methanol (750 mL). After dropwise addition of thionyl chloride
(52.1 mL, 714 mmol) at 0 °C under argon the reaction mixture was
refluxed for 6 h. Evaporation of the solvent and vacuum drying of
the white residue yielded 150.12 g (608 mmol; 94%) of methyl 4-
bromo-3,5-dihydroxybenzoate (25) as a white powder. 1H NMR
([D6]acetone): δ = 9.16 (s, 2 H, OH), 7.15 (s, 2 H, aryl-H), 3.83 (s,
3 H, OCH3) ppm. 13C NMR ([D6]acetone): δ = 165.76 (COO),
155.29 (C-2), 130.24 (C-4), 107.66 (C-3), 51.57 (OCH3) ppm. ES-
MS: calcd. for C8H7BrO4 + H+ 246.9606; found 246.9792.
(CH3) ppm. ES-MS: calcd. for C18H27BrO4 + Na+ 409.0985; found
409.1046.
Phenylboronic Acid 29: Compound 28 (34.4 g, 88.9 mmol) was dis-
solved in freshly distilled tetrahydrofuran (450 mL). After cooling
to –78 °C a 1.6  n-butyllithium solution in hexanes (61 mL) was
added dropwise and the reaction mixture was stirred at –78 °C for
2 h under argon. After addition of trimethyl borate (11 mL,
98.7 mmol), the solution was warmed to room temperature and
stirred for another 12 h. Diethyl ether (150 mL) and water
(200 mL) were then added. The aqueous phase was discarded and
the ether phase evaporated to dryness. A 1 g portion of crude prod-
Methyl 4-Bromo-3,5-bis(n-propyloxy)benzoate (26): Methyl 4-
bromo-3,5-dihydroxybenzoate (25) (50 g, 202 mmol) was dissolved
in acetone (800 mL) along with 1-bromopropane (52 mL, uct 29 was subjected to column chromatography (silica; diethyl
606 mmol) and tetrabutylammonium iodide (14.8 g, 40 mmol). Af-
ter addition of potassium carbonate (84 g, 518 mmol) the reaction
mixture was refluxed for 16 h under argon. Then the acetone was
evaporated and the residue taken up in as much diethyl ether and
water as was needed to obtain two homogeneous phases. The aque-
ous phase was extracted diethyl ether (2ϫ150 mL). The combined
organic phases were dried with anhydrous sodium sulfate, filtered,
and the ether evaporated. This procedure yielded 64.67 g
(195 mmol; 96%) of a slightly brown oil that crystallized within 4 h
upon standing at room temperature. This product turned out to
ether) yielding 0.746 g (2.12 mmol; 82%) of pure 29 as a white so-
lid. H NMR (CDCl3): δ = 7.34 (s, 2 H, OH), 6.61 (s, 2 H, aryl-
1
H), 4.75 (d, J = 12.8 Hz, 1 H, Hα), 4.73 (m, 1 H), 4.49 (d, J =
12.8 Hz, 1 H, Hα), 4.04 (t, J = 6.4 Hz, 4 H, OCH2CH2CH3), 3.96–
3.85 (m, 1 H), 3.62–3.52 (m, 1 H), 1.87 (tq, J = 7.5, 6.4 Hz, 4 H,
OCH2CH2CH3), 1.80–1.53 (m, 6 H, pyran-H), 1.07 (t, J = 7.5 Hz,
6 H, CH3) ppm. 13C NMR (CDCl3): δ = 165.09, 143.91, 104.17,
97.88, 70.61 (OCH2CH2CH3), 68.53, 62.38, 30.56, 25.40, 22.49
(OCH2CH2CH3), 19.42, 10.55 (CH3) ppm. ES-MS: calcd. for
C18H29O6B 352.2057; found 352.2449.
1
be NMR-pure methyl 4-bromo-3,5-di-n-propoxybenzoate (26). H
1,1Ј-Biphenyl-4-yl Bromide 31: Crude 29 (i.e. the non-column-
chromatography purified portion from above) (27.5 g) was dis-
solved in tetrahydrofuran (350 mL) along with 1-bromo-4-iodo-
benzene (25.0 g, 88.4 mmol) and tetrakis(triphenylphosphane)pal-
ladium(0) (2.57 g, 2.22 mmol). After addition of 2  aqueous po-
tassium carbonate (350 mL) the resulting biphasic mixture was re-
acted for 20 h at 70 °C under argon. Then the organic phase was
evaporated to yield 47.4 g of a brown oil which was purified by
column chromatography [silica; pentane/diethyl ether 1:1 (v/v)].
This yielded 39.5 g (88.3 mmol; 98%) of 31 as a slightly orange oil.
1H NMR (CDCl3): δ = 7.46 (d, J = 8.8 Hz, 2 H), 7.24 (d, J =
8.8 Hz, 2 H), 6.62 (s, 2 H, 3-H), 4.77 (d, J = 12.1 Hz, 1 H, Hα),
4.74 (m, 1 H), 4.50 (d, J = 12.1 Hz, 1 H, α-H), 4.01–3.91 (m, 1 H),
3.86 (t, J = 6.4 Hz, 4 H, OCH2CH2CH3), 3.60–3.55 (m, 1 H), 1.92–
1.53 (m, 6 H), 1.63 (tq, J = 7.3, 6.4 Hz, 4 H, OCH2CH2CH3), 0.87
(t, J = 7.3 Hz, 6 H, CH3) ppm. 13C NMR (CDCl3): δ = 156.93 (C-
2), 139.33 (C-4), 132.96, 130.28, 120.26, 117.95, 104.77 (C-3), 97.79,
70.14 (OCH2CH2CH3), 69.07, 62.35, 30.63, 25.47, 22.49, 19.48,
10.60 (CH3) ppm. ES-MS: calcd. for C24H31BrO4 + Na+ 487.1281;
found 487.1119.
NMR (CDCl3): δ = 7.20 (s, 2 H, aryl-H), 4.04 (t, J = 6.6 Hz, 4
H, OCH2), 3.93 (s, 3 H, OCH3), 1.88 (tq, J = 7.5, 6.6 Hz, 4 H,
OCH2CH2CH3), 1.09 (t, J = 7.5 Hz, 6 H, CH3) ppm. 13C NMR
(CDCl3): δ = 166.63 (COO), 156.58 (C-2), 129.87 (C-4), 107.79 (C-
1), 106.05 (C-3), 70.99 (OCH2), 52.36 (OCH3), 22.48
(OCH2CH2CH3), 10.55 (CH3) ppm. ES-MS: calcd. for C14H19BrO4
+ H+ 331.0539; found 331.0511.
4-Bromo-3,5-bis(n-propyloxy)benzyl Alcohol (27): Ester 26 (34.4 g,
104 mmol) was dissolved in freshly distilled diethyl ether (300 mL)
and added dropwise to lithium aluminium hydride (7.89 g,
208 mmol) in dry diethyl ether (200 mL) at 0 °C under argon. After
addition was completed, the reaction mixture was stirred for 2 h at
room temperature. Excess lithium aluminium hydride was de-
stroyed by slow sequential addition of ethyl acetate, water, and con-
centrated hydrochloric acid. The organic phase was separated from
the aqueous phase and the latter was extracted diethyl ether
(2ϫ150 mL). The combined organic phases were dried with anhy-
drous sodium sulfate, filtered, and the solvents evaporated to dry-
ness. Thereby 30.0 g (98.9 mmol; 95%) of pure 27 were isolated as
a pale yellow oil. 1H NMR (CDCl3): δ = 6.55 (s, 2 H, aryl-H), 4.63
(s, 2 H, CH2OH), 3.99 (t, J = 6.6 Hz, 4 H, OCH2), 1.85 (tq, J =
7.5, 6.6 Hz, 4 H, OCH2CH2CH3), 1.07 (t, J = 7.5 Hz, 6 H,
CH3) ppm. 13C NMR (CDCl3): δ = 156.73 (C-2), 141.36 (C-4),
104.04 (C-3), 70.83 (OCH2), 65.21 (CH2OH), 22.53
(OCH2CH2CH3), 10.53 (CH3) ppm. ES-MS: calcd. for C13H19BrO3
+ H+ 303.0590; found 303.0594.
1,1Ј-Biphenyl-4-ylboronic Acid 32: Bromide 31 (27.76 g, 60 mmol)
was dissolved in freshly distilled tetrahydrofuran (300 mL) and co-
oled to –78 °C before a 1.6  n-butyllithium in hexanes solution
(52.4 mL) was added dropwise under argon. After stirring for 2 h
at –78 °C trimethyl borate (8.0 mL, 71.8 mmol) was slowly added.
Then the reaction mixture was warmed to room temperature and
stirred for another 20 h. Then dichloromethane (100 mL) and water
2-[4-Bromo-3,5-bis(n-propyloxy)]benzyloxytetrahydro-2H-pyran (300 mL) were added to the reaction mixture. The water phase was
(28): Alcohol 27 (28.0 g, 92.4 mmol), 3,4-dihydro-2H-pyran (18.0 g,
214 mmol), and p-toluenesulfonic acid (0.32 g, 1.7 mmol) were dis-
solved in tetrahydrofuran (250 mL) and stirred for 16 h. Filtration
through silica and solvent evaporation yielded 34.4 g (88.9 mmol;
extracted once each with dichloromethane and diethyl ether. The
combined organic phases were dried with anhydrous sodium sul-
fate, filtered, and evaporated to yield 24.38 g (56.9 mmol; 95%) of
pure boronic acid 32 (white solid). 1H NMR ([D6]acetone/D2O
3:1): δ = 7.78 (d, J = 8.2 Hz, 2 H), 7.24 (d, J = 8.8 Hz, 2 H), 6.66
(s, 2 H, 3-H), 4.67 (m, 1 H), 4.66 (d, J = 12.2 Hz, 1 H, Hα), 4.44
(d, J = 12.2 Hz, 1 H, Hα), 3.85–3.75 (m, 1 H), 3.80 (t, J = 6.6 Hz,
4 H, OCH2CH2CH3), 3.57–3.45 (m, 1 H), 1.80–1.40 (m, 10 H),
0.77 (t, J = 7.2 Hz, 6 H, CH3) ppm. 13C NMR ([D6]acetone/D2O
1
96%) of pure 28 as a colorless oil. H NMR (CDCl3): δ = 6.55 (s,
2 H, aryl-H), 4.70 (d, J = 12.4 Hz, 1 H, Hα), 4.66 (m, 1 H, OCHO),
4.45 (d, J = 12.4 Hz, 1 H, Hα), 3.99 (t, J = 6.6 Hz, 4 H,
OCH2CH2CH3), 3.96–3.86 (m, 1 H), 3.55–3.50 (m, 1 H), 1.85 [tq,
J = 7.5, 6.6 Hz, 4 H, (OCH2CH2CH3)], 1.80–1.48 (m, 6 H), 1.07
(t, J = 7.5 Hz, 6 H, CH3) ppm. 13C NMR (CDCl3): δ = 156.61 (C- 3:1): δ = 156.87 (C-2), 139.51, 136.59, 133.02, 130.30, 118.97,
2), 138.67 (C-4), 105.19 (C-3), 97.64, 70.79 (OCH2CH2CH3), 68.63,
62.35, 30.58, 25.42, 22.54 (OCH2CH2CH3), 19.44, 10.56
104.83 (C-3), 97.61, 69.86, 68.56, 65.42, 61.79, 25.13, 22.21, 19.04,
10.02 (CH3) ppm. ES-MS: calcd. for C24H31O2B(OCH3)2 479.2581;
Eur. J. Org. Chem. 2007, 125–135
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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133

F. Durola, D. Hanss, P. Roesel, J.-P. Sauvage, O. S. Wenger
FULL PAPER
found 479.2655; calcd. for C24H31O2B(OCH3)H 479.2581; found
465.2497.
fluoride trihydrate (2.15 g, 6.8 mmol) was slowly added to the iso-
quinoline solution and the yellow reaction mixture was stirred for
12 h at room temperature. Then the solution was washed with water
(100 mL) and the dichloromethane phase was dried with anhydrous
sodium sulfate, filtered, and the solvents evaporated to dryness. The
yellow residue was then dissolved in dry dichloromethane (150 mL)
and freshly distilled triethylamine (50 mL). Trifluoromethanesul-
fonic anhydride (2.29 mL, 13.6 mmol) was added dropwise to this
solution at 0 °C under argon. This solution was stirred at room
temperature for 12 h before the solvents were evaporated. The red-
brown residue was subjected to column chromatography [silica;
pentane/diethyl ether 1:1 (v/v)] giving 1.14 g [1.7 mmol; 38% (two
steps)] of pure 40 as a pale yellow oil that crystallized within several
Pinacol (1,1Ј-Biphenyl-4-yl)boronate 33: Boronic acid 32 (11.91 g,
27.8 mmol) and pinacol (5.19 g, 43.9 mmol) were dissolved in tolu-
ene (250 mL) and refluxed for 4 h using a Dean–Stark trap. After
toluene evaporation the residue was taken up in diethyl ether and
filtered through silica. Ether evaporation yielded 13.83 g
(27.1 mmol; 97%) of pinacol ester 33 as a pale yellow oil. 1H NMR
(CDCl3): δ = 7.79 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.4 Hz, 2 H),
6.62 (s, 2 H), 4.78 (d, J = 12.1 Hz, 1 H, Hα), 4.73 (m, 1 H), 4.50
(d, J = 12.1 Hz, 1 H, Hα), 4.04–3.96 (m, 1 H), 3.85 (t, J = 6.4 Hz,
3 H, OCH2CH2CH3), 3.62–3.55 (m, 1 H), 1.95–1.55 (m, 10 H),
1.38 [s, 12 H, CH(CH3)2], 0.87 (t,
J = 7.3 Hz, 6 H,
1
hours upon standing at room temperature. H NMR (CDCl3): δ =
OCH2CH2CH3) ppm. 13C NMR (CDCl3): δ = 157.11 (C-2), 139.23,
134.56, 130.84, 119.36, 105.00, 97.76, 70.27, 69.12, 62.35, 30.66,
25.50, 22.53, 19.50, 14.04, 10.61 ppm. ES-MS: calcd. for
C30H43O6B + H+ 511.3231; found 511.3177; calcd. for C30H43O6B
+ Na+ 533.3050; found 533.2996.
9.27 (s, 1 H, 1-H), 7.91–7.80 (m, 2 H, 6,7-H), 7.68 (dd, J = 8.2,
1.4 Hz, 1 H, 5-H), 7.63 (s, 1 H, 4-H), 7.57 (d, J = 8.9 Hz, 2 H,
ArH2H2), 7.48 (d, J = 8.9 Hz, 2 H, ArH2H2), 6.70 [s, 2 H, Aryl-
(OC3H7)2H2], 4.83 (d, J = 12.1 Hz, 1 H, Hα), 4.78 (m, 1 H), 4.55
(d, J = 12.1 Hz, 1 H, Hα), 4.05–3.95 (m, 1 H), 3.94 (t, J = 6.4 Hz,
4 H, OCH2CH2CH3), 3.65–3.55 (m, 1 H), 1.97–1.55 (m, 10 H),
0.92 (t, J = 7.3 Hz, 6 H, OCH2CH2CH3) ppm. ES-MS: calcd. for
C34H36NO7F3S + H+ 660.2243; found 660.2161.
8-(1,1Ј-Biphenyl-4-yl)isoquinolin-3-yl Triisopropylsilyl Ether 38:
Protected bromoisoquinoline (34) (10.21 g, 26.8 mmol), boronic
acid pinacol ester 33 (15.46 g, 30.3 mmol), and tetrakis(triphenyl-
phosphane)palladium(0) (1.25 g, 1.1 mmol) were dissolved in tetra-
hydrofuran (400 mL). After addition of 1  aqueous potassium car-
bonate solution (200 mL), the reaction mixture was refluxed for
48 h under argon. Then the aqueous phase was discarded and the
organic phase evaporated to dryness. The residue was subjected to
column chromatography [silica; pentane/ethyl acetate 4:1 (v/v)] giv-
ing 10.4 g (15.2 mmol; 57%) of pure 38 as a colorless oil. 1H NMR
(CDCl3): δ = 9.02 (s, 1 H, 1-H), 7.66–7.55 (m, 2 H, 6,7-H), 7.51 (s,
4 H, Aryl-H), 7.32 (d, J = 6.8 Hz, 1 H, 5-H), 7.04 (s, 1 H, 4-H),
6.69 [s, 2 H, Aryl-(OC3H7)2H2], 4.81 (d, J = 12.1 Hz, 1 H, Hα),
4.77 (m, 1 H), 4.53 (d, J = 12.1 Hz, 1 H, Hα), 4.03–3.95 (m, 1 H),
3.93 (t, 4 H, OCH2CH2CH3), 3.61–3.57 (m, 1 H), 1.95–1.58 (m, 10
H), 1.14 [hept, J = 6.6 Hz, 3 H, CH(CH3)3],1.11 [d, J = 6.6 Hz, 18
H, CH(CH3)3], 0.92 (t, J = 7.5 Hz, 6 H, OCH2CH2CH3) ppm. 13C
NMR (CDCl3): δ = 159.14, 157.21, 149.73, 141.42, 140.17, 139.08,
136.97, 133.69, 131.23, 129.63, 128.86, 125.04, 123.43, 105.08,
104.13, 97.83, 70.28, 69.16, 62.35, 30.66, 25.50, 22.56, 19.50, 18.09,
12.72, 10.58 ppm. ES-MS: calcd. for C42H57N5OSi + H+ 684.4079;
found 684.3787.
8,8Ј-Diaryl-3,3Ј-biisoquinoline 4: Triflate 40 (873 mg, 1.32 mmol)
and dichloro[1,1Ј-bis(diphenylphosphanyl)ferrocene]palladium(0)
(108 mg, 0.15 mmol) were dissolved in freshly distilled N,N-dimeth-
ylformamide (4.5 mL). Freshly activated zinc powder (865 mg,
13.2 mmol) (for activation procedure, see 1) and anhydrous potas-
sium iodide (879 mg, 5.28 mmol) were added to this solution. The
resulting reaction mixture was heated at 90 °C for 16 h. Then water
(20 mL) and dichloromethane (20 mL) were added and the aqueous
phase was separated from the organic phase. The latter was evapo-
rated to dryness and the brown oily residue subjected to column
chromatography [silica; dichloromethane/methanol 50:1 (v/v)] to
yield 101 mg (0.1 mmol; 15%) of pure 4 as a white solid. 1H NMR
(CDCl3): δ = 9.61 (s, 2 H, 1-H), 8.95 (s, 2 H, 4-H), 8.01–7.96 (m,
2 H), 7.78–7.53 (m, 12 H), 6.70 [s, 4 H, Aryl-(OC3H7)2H2], 4.81 (d,
J = 12.0 Hz, 2 H, Hα), 4.78 (m, 2 H, Ha), 4.54 (d, J = 12.0 Hz, 2
H, Hα), 4.00–3.90 (m, 2 H, He), 3.95 (t, J = 6.6 Hz, 8 H,
OCH2CH2CH3), 3.64–3.55 (m, 2 H, He), 1.97–1.51 (m, 20 H), 0.94
(t, J = 7.2 Hz, 12 H, OCH2CH2CH3) ppm. MALDI-TOF MS:
calcd. for C66H72N2O8 + H+ 1021.5367; found 1021.546.
8-(1,1Ј-Biphenyl-4-yl)isoquinolin-3-ol 39: The triisopropylsilyl ether
protected isoquinoline (0.75 g, 1.1 mmol) was dissolved in dichloro-
methane (5 mL). A solution of tetrabutylammonium fluoride tri-
hydrate (0.52 g, 1.5 mmol) in dichloromethane (10 mL) was added
to this solution. The reaction mixture immediately turned yellow
and it was stirred at room temperature for 4 h. Then water (30 mL)
was added and the organic phase separated from the aqueous
phase. The latter was extracted once with dichloromethane
(10 mL). The combined organic phases were evaporated to yield
0.88 g of an orange oil which was subjected to column chromatog-
raphy [silica; dichloromethane/methanol 50:1 (v/v)] yielding 0.42 g
Tris(8,8Ј-di-p-anisyl-3,3Ј-biisoquinoline)iron(II)
Hexafluorophos-
phate (41): By stirring a dichloromethane solution of bis(tetrafluo-
roborate)iron(II) and ligand 1 for 2 h at room temperature and sub-
sequent anion exchange, 41 was obtained in quantitative yields. Sin-
gle crystals suitable for crystal structure determination were ob-
tained by slow diffusion of diisopropyl ether into acetone solutions
1
at room temperature. H NMR (CD2Cl2): δ = 8.89 (s, 6 H, 1-H),
8.10 (d, J = 8.4 Hz, 6 H), 7.87 (s, 6 H, 4-H), 7.84 (dd, J = 8.4,
7.2 Hz, 6 H, 6-H), 7.45 (d, J = 7.2 Hz, 6 H), 6.62 (d, J = 8.7 Hz,
12 H), 6.31 (d, J = 8.7 Hz, 12 H), 3.58 (s, 18 H, OCH3) ppm. ES-
MS: calcd. for C96H72N6O6Fe2+ 730.443; found 730.7444. Crystal
structure analysis: C96H72F12Fe1N6O6P2, M = 1751.39, monoclinic,
a = 15.4180(3), b = 34.4150(6), c = 17.0120(4) Å, β = 116.3621(8)°,
V = 8088.0(3) Å3, T = 173(2) K, space group P21/n, Z = 4, µ(Mo-
Kα) = 0.316 mm–1, 45635 collected reflections, 23640 independent
1
(0.8 mmol; 73%) of pure 39 as a yellow oil. H NMR (CDCl3): δ
= 9.12 (s, 1 H, 1-H), 8.66 (s, 1 H, OH), 7.59–7.51 (m, 2 H, 6,7-H),
7.43 (s, 4 H, Aryl-H), 7.38 (d, J = 7.0 Hz, 1 H, 5-H), 6.82 (s, 1 H,
4-H), 6.52 [s, 2 H, Aryl-(OC3H7)2H2], 4.85 (d, J = 12.1 Hz, 1 H,
Hα), 4.78 (m, 1 H), 4.54 (d, J = 12.1 Hz, 1 H, Hα), 4.05–3.82 (m,
5 H, pyran-H, OCH2CH2CH3), 3.67–3.55 (m, 1 H), 2.01–1.53 (m,
10 H), 0.87 (t, J = 7.5 Hz, 6 H, OCH2CH2CH3) ppm. ES-MS:
reflections [R(int) = 0.048], final R indices R1 = 0.052, wR2
0.1261.
=
–
calcd. for C33H37NO5 526.2584; found 526.2593.
CCDC-283554 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
8-(1,1Ј-Biphenyl-4-yl)isoquinolin-3-yl Trifluoromethanesulfonate 40:
The protected isoquinoline 38 (3.1 g, 4.5 mmol) was dissolved in
dichloromethane (120 mL). A solution of tetrabutylammonium
134
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 125–135

A New Family of Biisoquinoline Chelates
FULL PAPER
Lewis, P. R. Raithby, M. D. Vargas, J. Chem. Soc., Chem. Com-
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Acknowledgments
Funding from the following institutions is gratefully acknowledged:
the CNRS and the Région Alsace (fellowship to F. D.), the Euro-
pean Commission (MOLDYNLOGIC) (fellowship to D. H.), the
Stiftung Stipendien-Fonds der Chemischen Industrie e.V., Frank-
furt (fellowship to P. R.), and the Swiss National Science Founda-
tion (fellowship to O. S. W.). P. R. wishes to thank Prof. E. C. Con-
stable (University of Basel, Switzerland) for the opportunity to
work on this project. Dr. A. De Cian is acknowledged for the crys-
tal structure resolution.
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Received: September 13, 2006
Published Online: November 14, 2006
Eur. J. Org. Chem. 2007, 125–135
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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135