Synthesis and structural elucidation of diversely functionalized 5,10-diaza[5]helicenes

Article abstract of DOI:10.1021/jo301814m

Diversely functionalized diaza[5]helicenes have been synthesized starting from 6,9-dichloro-5,10-diaza[5]helicene, which was prepared from a readily available quinoline building block via Wittig reaction followed by photochemical electrocyclization. The helicene skeleton was substituted by a variety of O-, S-, N-, and C-centered nucleophiles using nucleophilic aromatic substitution reactions and palladium-catalyzed reactions like Suzuki coupling and Buchwald-Hartwig aminations. We have determined, using X-ray single-crystal diffraction, the crystal structures of the chloro- and methoxy-substituted diaza[5]helicenes. A resolution strategy based on diastereomeric separation by substitution of the dichloro derivative with a chiral amine has been shown.

Full text of DOI:10.1021/jo301814m

Article
pubs.acs.org/joc
Synthesis and Structural Elucidation of Diversely Functionalized
5,10-Diaza[5]Helicenes
Deepali Waghray,† Jing Zhang,† Jeroen Jacobs,‡ Wienand Nulens,† Nikola Basaric,§ Luc Van Meervelt,‡
́
and Wim Dehaen*,†
‡
†Molecular Design and Synthesis and Biomolecular Architecture, Department of Chemistry, Katholieke Universiteit Leuven,
Celestijnenlaan 200F, B-3001 Leuven, Belgium
§Department of Organic Chemistry and Biochemistry, Ruđer Bosk
ovic Institute, Bijenicka cesta 54, 10 000 Zagreb, Croatia
̌ ́ ̌
S
* Supporting Information
ABSTRACT: Diversely functionalized diaza[5]helicenes have been synthesized starting from 6,9-dichloro-5,10-diaza[5]helicene,
which was prepared from a readily available quinoline building block via Wittig reaction followed by photochemical
electrocyclization. The helicene skeleton was substituted by a variety of O-, S-, N-, and C-centered nucleophiles using
nucleophilic aromatic substitution reactions and palladium-catalyzed reactions like Suzuki coupling and Buchwald−Hartwig
aminations. We have determined, using X-ray single-crystal diffraction, the crystal structures of the chloro- and methoxy-
substituted diaza[5]helicenes. A resolution strategy based on diastereomeric separation by substitution of the dichloro derivative
with a chiral amine has been shown.
have gained interest because their complexes with transition-
metal ions show interesting properties in harvesting visible
light.11 Furthermore, if the helicene backbone has more than
one nitrogen atom, interesting supramolecular complexes can
be formed. These molecules have a tendency toward π−π*
stacking and the building of columnar systems, which can form
the basis of materials for optoelectronic applications.12
Applications of azahelicene derivatives have been reported in
the field of asymmetric catalysis,13,14 self-assembly,15 and metal
coordination complexes.16
In the past few years, various methods have been described
for the synthesis of aza[5]helicenes, methods that include the
classical photochemical procedure by Caronna et al.17 and its
expansion by Ben Hassine et al.,18,19 and a versatile synthetic
method based on Bu3SnH-mediated coupling was developed by
Harrowven and co-workers.20 Furthermore, the [2 + 2 + 2]
cycloisomerization of triynes,21−23 the Stille−Kelly reaction of
dihalogenated cis-stilbene type precursors,14 and palladium-
catalyzed arylations24 are a few reported metal-catalyzed
cyclizations. Examples of the synthesis of aza[5]helicenes and
diaza[5]helicenes are known in the literature, but to the best of
INTRODUCTION
■
Helicene chemistry has emerged to be a field of great interest
because of the fascinating properties of helicenes. These ortho-
annulated polycyclic aromatic or heteroaromatic compounds
are endowed with a inherently chiral π-conjugated system and
thus show intriguing interactions with circularly polarized light
while lacking a stereogenic center.1 The inherent chirality
originates from the steric repulsion between the ortho-
condensed aromatic rings, which locks the system in either
the P- or M-configuration.2 Helicenes have been extensively
studied due to their excellent self-assembly in the solid state,3
their ability to behave as organic conductors,4 and their use in
optical resolutions5 and molecular recognition.6 Furthermore,
enantiomerically pure helicenes form supramolecular architec-
tures and exhibit second-order nonlinear optical and chiroop-
tical properties,7 which allows for one of their potential
applications.8 To exploit these properties, helicene chemistry is
currently developing from fundamental science to applications.
Previous work has focused on the experimental and also
theoretical points of view.9
Azahelicenes constitute a subgroup of the heterahelicenes
and have been intensively studied due to their prospective
applications in fields such as light-emitting devices and
chemosensors.2,10 Indeed, nitrogen-containing heterahelicenes
Received: August 24, 2012
Published: October 24, 2012
© 2012 American Chemical Society
10176
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
Scheme 1. Synthesis of Phosphonium Salts 3c and 4c
our knowledge, diaza[5]helicenes with flexibility toward
functionalization, especially with SNAr reactions, are not very
well-known. Herein, we report the synthesis of symmetric and
asymmetric diaza[5]helicenes with chloro or methoxy groups at
the 6 and/or 9 position (numbering with respect to the parent
diazahelicenes) of the helicene skeleton, which provides an
opportunity for functionalization with a variety of oxygen-,
sulfur-, nitrogen-, and carbon-centered nucleophiles by SNAr
reactions,25 Suzuki coupling,26 and Buchwald−Hartwig amina-
tion.27
Scheme 2. Wittig Reaction and Photocyclization
RESULTS AND DISCUSSION
■
Our approach makes use of easily accessible 2-chloroquinoline-
3-carboxaldehyde28 1 as a versatile building block. We employ
the Wittig reaction and photochemical cyclization strategy. The
cooperative ortho effect20 of the halo and alkoxy groups
controls the stereochemical course of the Wittig reaction
leading to Z-selectivity, which in turn increases the yield of the
photocyclization reactions. 2-chloroquinoline-3-carboxaldehyde
1 was prepared from acetanilide according to a literature
procedure28 and was converted to 2 by refluxing with a solution
of KOH in MeOH to give 2-methoxyquinoline-3-carboxalde-
hyde in 89% yield. Aldehydes 1 and 2 were reduced to the
corresponding alcohols 3a and 4a using sodium borohydride in
THF/MeOH. The alcohols thus obtained were subsequently
converted via the Appel reaction to the bromo derivatives (3b
and 4b), which were converted to their phosphonium salts by
reaction with triphenylphosphine in refluxing toluene for 12 h
in 95% (3c) and 92% (4c) yield (Scheme 1).
(wavelength used is 350 nm) to obtain the diaza[5]helicenes
6a−c in good yields. These compounds were fully characterized
by NMR spectroscopy and HRMS and show good solubility in
a variety of medium-polarity solvents such as CH2Cl2, EtOAc,
and THF. A typical side product, diazabenzo[ghi]perylene, was
obtained each time during the photocyclization step, its yield
depending on the reaction time. We observed at most 8% of the
perylene (isolated only in the case of 6d) in each reaction run
for 10 h, sufficient for the complete conversion of the starting
material.
Increasing the reaction time also significantly increased the
amount of diazabenzo[ghi]perylene 6d formed. Nevertheless,
complete conversion of 5c to diazabenzo[ghi]perylene 6d was
not observed even after irradiation for 3 days. Each time, a
significant amount of diaza[5]helicene 6c remained unreacted
(∼25%). Complete spectroscopic characterization of
diazabenzo[ghi]perylene 6d was not possible due to its low
solubility in various organic solvents, and it was characterized
by HRMS.
Solid-State Structural Elucidation. Crystals of 6c were
obtained by diffusing pentane into a chloroform solution of the
compound. The racemic compound crystallizes into the
centrosymmetric triclinic space group P-1 with one molecule
in the asymmetric unit (Figure 1). The distortion of the
molecular structure (65.22°), defined by the sum of the three
dihedral angles C17−C14−C4−C5, C14−C4−C5−C8, and
C4−C5−C8−C13, is comparable to the value of a non-
substituted diaza[5]helicene (61.34°).17,31 Viewed down the b-
axis, the molecules form columns of alternating opposite
enantiomers, held together with different kinds of weak
interactions (Figure 2). π−π stacking inside the columns
occurs between pyridine rings, with centroid−centroid
Wittig olefination29 of the phosphonium salts 3c and 4c with
2-chloroquinoline-3-carboxaldehyde 1 and 2-methoxyquino-
line-3-carboxaldehyde 2, respectively, using NaH as base in
CH2Cl2 gave the symmetric azastilbene derivatives 5a (85%,
cis/trans ∼5:1) and 5c (82%, cis/trans ∼3:1) (Scheme 2). The
alkenes were obtained with a high degree of Z selectivity. The
effect of halo and alkoxy substituents to control the
stereochemical outcome of the Wittig reaction is evident.
Similarly, the reaction of 2-chloroquinoline-3-carboxaldehyde 1
with phosphonium salt 4c gave the asymmetric diazastilbene
derivative 5b (cis/trans ∼10:1) in 66% yield. Compounds 5a−c
were fully characterized by 1H and 13C NMR spectroscopy and
HRMS. The ratio of the isomers was determined by integration
1
of the H NMR spectrum. Since E−Z isomerization occurs
during the irradiation process, no specific configuration of the
alkene precursor was required, but a high ratio of cis-isomer is
beneficial because of the increased solubility as compared to the
corresponding trans-isomer. The bis(quinolyl)ethene deriva-
tives 5a−c obtained were subjected to oxidative photo-
cyclization30 using a stoichiometric amount of iodine and
toluene as the solvent (1.0 mM). The reaction mixture was
irradiated at room temperature using a photochemical reactor
10177
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
ally, a C−H···π interaction occurs between the hydrogen on
C(12) and one of the pyridine rings (C12−H12···Cg1; with
Cg1 the centroid of the pyridine ring containing N2, C12···Cg1
= 3.448(2) Å).
Crystals of 6a were obtained by diffusing pentane into a
chloroform solution of the compound. In comparison to 6c, the
methoxy groups are exchanged with chlorine atoms. The
racemic compound crystallizes into the centrosymmetric
triclinic space group P-1 with two molecules in the asymmetric
unit (Figure 3). The distortion of the molecular structures
(60.52° and 61.23°), defined by the sum of the three dihedral
angles, C20−C16−C1−C6, C16−C1−C6−C9, C1−C6−C9−
C13, C33−C29−C26−C21, C29−C26−C21−C36, and C26−
C21−C36−C40 is again comparable to the value of a
nonsubstituted diaza[5]helicene (61.34°).17,31
In comparison to the previous structure, the crystal structure
now forms layers inside the crystal packing that are easily visible
when looking down the a-axis (Figure 4). The layers are kept
together by the nonclassical hydrogen bonds C(17)−
H(17)···N(3) and C(30)−H(30)···N(2) with D···A distances
of respectively 3.511(2) and 3.508(2) Å. Several π−π
interactions are seen between the different layers, mainly
between the pyridine and outer benzene rings, with distances
ranging from 3.7100(10) to 4.0898(10) Å. Remarkably, none of
the chlorine atoms is involved in intermolecular (nonclassical)
hydrogen bonding. Cl(1), however, is involved in a halogen−π
interaction with the benzene ring C(15)−C(20) with a distance
to the centroid of this ring of 3.9885(9) Å.
Figure 1. ORTEP view of molecular structure of 6c, thermal ellipsoids
drawn at 50% probability.
Functionalization of the Diaza[5]helicenes. Helicenes
6a−c were obtained using the Wittig reaction-plus-photo-
cyclization strategy in good yield and opened a new area for
further functionalization. Though postcyclization functionaliza-
tion is known for carbohelicenes,32 it is an underexplored area
for diaza[5]helicenes. Here, we report the easy functionaliza-
tion via SNAr reactions and palladium-catalyzed coupling
reactions. In this way, a variety of O-, S-, N-, and C-centered
nucleophiles can be bound to the diazahelicene platform
(Scheme 3).
In the first set of reactions, some SNAr reactions with O-, S-,
and N-nucleophiles were tested (Scheme 3). Initially, 6,9-
dichloro-5,10-diaza[5]helicene 6a was reacted with NaSMe (2.5
equiv) in DMF, and the reaction mixture was stirred at 80 °C
for 12 h. After column chromatographic purification, the
desired diaza[5]helicene 7a was obtained in 58% yield. SNAr of
thiophenol (2.5 equiv) on 6a could be performed using K2CO3
Figure 2. Packing in the crystals structure of 6c, viewed along the b-
axis.
distances of 4.528(2) and 4.685(2) Å. The different columns
interlink with each other by several π−π interactions starting
from the benzene ring C(8)−C(13), with centroid−centroid
distances ranging from 4.4469(19) Å to 5.425(2) Å. Addition-
Figure 3. ORTEP view of the molecular structure of 6a, showing two molecules in the asymmetric unit. Thermal ellipsoids are drawn at 50%
propability.
10178
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
Figure 4. Packing in the crystal structure of 6a, viewed along the a-axis.
Scheme 3. Functionalized Diaza[5]helicene Synthesized via SNAr Reaction
Scheme 4. Functionalized Diaza[5]helicene Synthesized via Palladium-Catalyzed Suzuki Coupling and Buchwald−Hartwig
Amination Reactions
as base and DMF as solvent, and the reaction mixture was
stirred at 80 °C for 12 h to furnish product 7b in 62% yield
after column purification.
compounds obtained were characterized by NMR spectroscopy
and HRMS.
In the second set, we explored the Suzuki and Buchwald−
Hartwig amination reactions (Scheme 4). The substitution of
both chloro groups at the 6 and 9 positions of the
diaza[5]helicene were done by Suzuki cross-coupling reactions.
An aryl group was introduced on the helicene skeleton using p-
tolylboronic acid (2.5 equiv), Pd(PPh3)4, aqueous NaHCO3,
MeOH, and toluene. The reaction mixture was stirred for 12 h
in refluxing toluene, yielding 42% of the desired product 7e.
Next, we attempted to substitute with aniline via Buchwald
amination conditions, which we expected to be more efficient
than the previously attempted SNAr reaction. 6,9-Dichloro-
5,10-diaza[5]helicene was reacted with aniline using Cs2CO3, 5
We opted for phenol as an O-nucleophile. SNAr of phenolate
(2.5 equiv) on 6a could be performed using the conditions
optimized for thiophenol affording compound 7c in 67% yield.
The introduction of N-nucleophiles appeared to be more
challenging. Using different conditions with temperatures up to
100 °C, no satisfying results were obtained for the substitution
of aniline. Only at 150 °C was a reaction between helicene 6a
and aniline observed. When an excess (5 equiv) of aniline was
added to 6a in DMF, and the reaction was kept at 150 °C for
20 h, diaza[5]helicene 7d was obtained in 50% yield. All
10179
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
mol % of Pd(OAc)2, rac-BINAP, and toluene as the solvent.
The reaction was run at 80 °C for 12 h to furnish the desired
product 7d in 57% yield. We indeed observed a significant
decrease in the reaction time and an increase in yield with these
conditions.
Resolution via Diastereomeric Separation. Expanding
on the Buchwald−Hartwig amination, we envisaged that a
chiral amine upon substitution to the racemic helicene skeleton
would result in the formation of diastereomers of the helicene,
which then could easily be separated via column chromatog-
raphy. Thus, palladium-mediated amination of 6a with L-(−)-α-
methylbenzylamine using Cs2CO3, 5 mol % of Pd(OAc)2, rac-
BINAP, and toluene as the solvent furnished the desired
product 7f in 72% yield as a 1:1 mixture of diastereomers
(M,S,S/P,S,S = 1:1; the ratio of isomers was determined by
integration of the NMR spectra) (Scheme 5).
group is too far removed from the helicene to have an
influence.
CONCLUSION
■
In the present study, we have developed an efficient and flexible
method for functionalization of the helicene skeleton with a
variety of O-, S-, N-, and C-centered nucleophiles via
straightforward methods. This strategy has also opened an
opportunity for substitution of chiral groups leading to the
resolution of the racemic helicene and exploration of various
applications of azahelicenes. Though the rapid racemization at
room temperature of the diaza[5]helicene derivatives employed
in the present study is inevitable, the ease of elaboration of the
substitution pattern introduces a platform for exploring this
strategy in future work for synthesis and substitution of higher
helicenes, thus illustrating the wide and unprecedented scope of
the procedures.
Scheme 5. Resolution via Diastereomeric Separation
EXPERIMENTAL SECTION
■
General Experimental Methods. NMR spectra were acquired on
commercial instruments (300 and 400 MHz), and chemical shifts (δ)
are reported in parts per million (ppm) referenced to tetramethylsilane
(1H) or the internal (NMR) solvent signal (13C). Mass spectra were
acquired using EI (70 eV ionization energy). Exact mass measure-
ments were performed in the EI mode at a resolution of 10000 and
also on a quadrupole orthogonal acceleration time-of-flight mass
spectrometer. Samples were infused at 3 μL/min, and spectra were
obtained in positive (or negative) ionization mode with a resolution of
15000 (fwhm). For column chromatography, 70−230 mesh silica 60
was used as the stationary phase. Chemicals received from commercial
sources were used without further purification. K2CO3 (anhydrous,
granulated) was finely ground (with mortar and pestle) prior to use.
All solvents were used as received from commercial sources and not
explicitly dried prior to use (H2O ≤ 0.1%). All photochemical
reactions were performed in the photochemical reactor equipped with
interchangeable light sources (250 nm, 300 nm, 350 nm lamps).
Experimental and Characterization Data. Synthesis of 2-
Chloroquinoline-3-carboxaldehyde (1). This compound has been
prepared according to the literature procedure28 from acetanilide.
The diastereomers formed were readily separated by silica gel
column chromatography. It was interesting to see that the pure
diastereomeric forms separated by column chromatography
racemize/revert back to a 1:1 mixture at room temperature
(∼25 °C). HPLC of the diaza[5]helicenes at room temperature
shows the presence of two helical isomers, but the separation
was never up to the baseline, probably indicating their dynamic
behavior (see the Supporting Information). To confirm this,
flash column chromatography was performed at low temper-
atures (−10 to 0 °C) using a precooled solvent system, with the
fractions being stored at −10 °C as soon as they were collected
from the column. The solvent was removed under vacuum, the
flasks being kept cold during evaporation. The fractions were
kept at −10 °C before performing the racemization studies
using temperature-dependent 1H NMR spectroscopy. We
determined the t1/2 at 25 °C to be 26 min and the free energy
barrier for racemization to be 22.4 kcal mol−1. Analogously, we
obtained a t1/2 of 4.2 h at 10 °C (see the Supporting
Information). The results obtained could be compared with the
studies of Caronna et al.33 on the monoaza[5]helicenes, which
describe experimental and calculated CD measurements of a
series of monoaza[5]helicenes and their half-lives (t1/2) and
energy barriers. Comparing our own observations with these
literature values, it is clear that the insertion of one or more
nitrogen atom decreases the enantiomeric stability of the
helicene compared to the carbo[5]helicenes, which have a t1/2
of 62.7 min at 57 °C.33 Thus, the resolution strategy employed
was indeed useful for the separation of the racemic
diazahelicene, but due to a very low racemization barrier, the
chiral forms cannot be handled easily at room temperature.
From the 1:1 ratio that is the convergence point of the
isomerization, it can be concluded that there is no significant
energy difference between the two diastereomers, and the chiral
1
Material identity was confirmed by mp, MS, and H and 13C NMR.
Synthesis of 2-Methoxyquinoline-3-carboxaldehyde (2). 2-Chlor-
oquinoline-3-carboxaldehyde 1 (5.0 g, 26.1 mmol) was added to a
solution of KOH (2.12 g, 39.0 mmol) in MeOH (250 mL), and the
reaction mixture was refluxed for 10 h. The solution was then cooled
to room temperature and water (200 mL) was added to obtain a
precipitate which was filtered, washed with water and Et2O, and dried
under vacuum to obtain 2 (4.30 g, 89%) as an off-white solid: mp
112−113 °C; MS (EI) m/z = 188 [MH]+; HRMS (EI) calcd for
1
C11H9NO2 187.0633, found m/z = 187.0609; HNMR (300 MHz,
CDCl3, 25 °C, TMS) δ 10.45 (s, 1H; CHO), 8.56 (s, 1H; ArH), 7.87−
7.81 (m, 2H; ArH), 7.72 (t, 1H, J = 6.9 Hz; ArH), 7.42 (t, 1H, J = 6.9
Hz; ArH), 4.18 (s, 3H; OMe); 13C NMR (75 MHz, CDCl3, 25 °C,
TMS) δ 189.5 (CHO), 161.3, 149.1, 140.1, 132.7, 129.8, 127.4, 125.1
(C, CH), 53.9 (OCH3).
Synthesis of (2-Chloroquinolin-3-yl)methanol (3a). General
Procedure. To a stirred solution of aldehyde 1 (3.0 g, 15.6 mmol)
in THF (50 mL) and MeOH (50 mL) was added sodium borohydride
(0.888 g, 23.4 mmol), and the reaction mixture was stirred at 0 °C for
30 min. The reaction mixture was quenched with water and diluted
with Et2O, the organic layer was separated, washed with brine, dried
over anhydrous MgSO4, and evaporated to dryness to give 3a (2.76 g,
92%) as a white solid. The compound obtained was used without
further purification: mp 167−168 °C; MS (EI) m/z = 194 [MH]+;
HRMS (EI) calcd for C10H8NOCl 193.0294, found m/z 193.0290; 1H
NMR (300 MHz, DMSO-d6) δ 8.47 (s, 1H, ArH), 8.09 (d, 1H, J = 7.7
Hz, ArH), 7.96 (d, 1H, J = 8.4 Hz, ArH), 7.78 (t, 1H, J = 7.1 Hz, ArH),
7.65 (t, 1H, J = 7.5 Hz, ArH), 5.72 (s, 1H, OH), 4.70 (d, 2H, J = 4.6
Hz, CH2OH); 13C NMR (75 MHz, DMSO-d6, 25 °C, TMS) δ 148.4,
10180
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
146.0, 135.9, 133.9, 130.2, 127.9, 127.5, 127.3, 127.2 (C, CH), 59.9
(CH2OH).
130.1, 127.9, 126.8, 124.9, 124.5, 118.5, 117.4, 112.0, 111.9 (C, CH),
53.2 (OCH3), 25.5, 24.8 (CH2).
Synthesis of 1,2-bis(2′-Chloroquinolin-3-yl)ethene (5a). General
Procedure. A solution of 2-chloroquinoline-3-carboxaldehyde 1 (0.50
g, 2.6 mmol) was added dropwise to a stirred solution of phosphonium
salt 3c (1.6 g, 3.1 mmol) and sodium hydride (0.187 g, 7.8 mmol) in
dichloromethane at 0 °C, after which the reaction mixture was stirred
for 6 h. The crude product was purified by silica gel column
chromatography using EtOAc/petroleum ether (15:85) as eluent to
obtain compound 5a (0.780 g, 85%, Z/E ∼5:1) as a yellow solid: mp
216−217 °C; MS (ESI+) m/z = 351 [MH]+; HRMS (EI) calcd for
Synthesis of 3-(Bromomethyl)-2-chloroquinoline (3b). To a
solution of (2-chloroquinolin-3-yl)methanol 3a (2.50 g, 12.9 mmol)
in dichloromethane was added tetrabromomethane (6.46 g, 19.35
mmol) and the reaction mixture cooled to 0 °C. Then a solution of
triphenylphosphine (5.03 g, 19.35 mmol) in dichloromethane was
added dropwise. The reaction mixture was stirred at room temperature
for 5 h and then quenched with water. The organic layer was
separated, washed with brine, dried over anhydrous MgSO4, and
evaporated to dryness and purified by column chromatography using
EtOAc/petroleum ether (20:80) as eluent to furnish compound 3b
(2.34 g, 69%) as a white solid: mp 125−126 °C; MS (EI) m/z = 255
[MH]+; HRMS (EI) calcd for C10H7NBrCl 254.9450, found m/z
254.9469; 1H NMR (300 MHz, CDCl3) δ 8.24 (s, 1H, ArH), 8.02 (d,
1H, J = 8.1 Hz, ArH), 7.82 (d, 1H, J = 8.1 Hz, ArH), 7.75 (t, 1H, J =
7.5 Hz, ArH), 7.58 (t, 1H, J = 7.3 Hz, ArH), 4.72 (s, 2H, OH), 4.70 (d,
2H, CH2Br); 13C NMR (75 MHz,CDCl3, 25 °C, TMS) δ 150.1, 147.4,
139.4, 138.7, 131.2, 129.6, 128.5, 127.6, 127.2 (C, CH), 29.9 (CH2Br).
(2-Chloroquinolin-3-yl)methyltriphenylphosphonium Bromide
(3c). To a solution of compound 3b (2.0 g, 7.84 mmol) in toluene
was added triphenylphosphine (5.8 g, 23.5 mmol), the reaction
mixture was refluxed for 12 h and cooled to room temperature, and the
solid obtained was filtered, washed with pentane, and dried under
vacuum to furnish the phosphonium salt 3c (3.8 g, 95%) as a white
solid: mp 256−257 °C; MS (ESI+) m/z = 518 [MH]+ (observed 518
− Br = 438); HRMS (EI) calcd for C28H22NClP 438.1178 [M − Br],
1
C20H12N2Cl2 350.0378, found m/z 350.0385; H NMR (300 MHz,
CDCl3, mixture of cis and trans isomers) δ 8.50 (s, 2H, vinylic protons
of trans isomer), 8.05−7.91 (m, 4H, ArH), 7.80 (s, 4H, ArH), 7.80−
7.60 (m, 4H, ArH), 7.47- 7.38 (m, 4H, ArH), 7.06 (s, 2H, vinylic
protons of cis isomer); 13C NMR (75 MHz, CDCl3) δ 138.4, 130.8,
129.1, 128.3, 127.7, 127.3 (C, CH).
Synthesis of 2-Chloro-3-(2-(2-methoxyquinolin-3-yl)vinyl)-
quinoline (5b). Synthesis according to the general procedure leading
to 5a, 2-chloroquinoline-3-carboxaldehyde 1 (0.50 g, 2.6 mmol),
phosphonium salt 4c (1.6 g, 3.1 mmol), and sodium hydride (0.187 g,
7.8 mmol) in dichloromethane. Purified by column chromatography
using EtOAc/petroleum ether (20:80) to obtain 5b (0.625 g, 66%, Z/
E ∼10:1) as a yellow solid: mp 171−172 °C; MS (ESI+) m/z = 347
[MH]+; HRMS (EI) calcd for C21H15N2ClO 346.0873, found m/z
1
346.0874; H NMR (300 MHz, CDCl3, mixture of cis−trans isomers)
δ 8.47 (s, 1H, ArH), 8.28 (s, 1H, ArH), 8.00−7.97 (m, 2H, ArH), 7.89
(s, 2H, ArH), 7.80−7.77 (m, 2H, ArH), 7.70−7.66 (m, 2H, ArH),
7.63−7.62 (m, 2H, ArH), 7.57−7.54 (m, 2H, ArH), 7.48−7.45 (m,
2H, ArH), 7.40−7.36 (m, 2H, ArH), 7.23−7.21 (m, 2H, ArH), 7.01−
6.91 (m, 4H, ArH), 4.19 (s, 3H, CH3-trans isomer), 4.05 (s, 3H, CH3-
cis isomer); 13C NMR (75 MHz, CDCl3) δ 160.1, 150.6, 146.9, 146.1,
137.9, 137.7, 130.5, 129.9, 129.7, 128.3, 127.8, 127.6, 127.1, 127.0,
126.9, 124.9, 124.3, 120.7, (C,CH), 53.8 (CH3).
1
found m/z 438.1168 [M − Br]; H NMR (300 MHz, CDCl3) δ 8.70
(s, 1H, ArH), 7.91 (d, 1H, J = 8.1 Hz, ArH), 7.66−7.84 (m, 17H,
ArH), 7.54 (t, 1H, J = 7.1 Hz, ArH), 5.98 (d, 2H, J = 14 Hz, CH2P);
13C NMR (75 MHz, CDCl3, 25 °C, TMS) δ 150.9, 147.0, 147.9, 142.8,
142.7, 135.4, 134.3, 134.1, 131.4, 130.5, 130.3, 128.1, 127.6, 126.9,
120.1, 117.6, 116.4 (C, CH), 28.5, 27.84 (CH2).
Synthesis of (2-Methoxyquinolin-3-yl)methanol (4a). Synthesis
according to the general procedure leading to 3a; 2-methoxyquinoline-
3-carboxaldehyde 2 (3.0 g, 16.0 mmol), NaBH4 (1.03 g, 27.2 mmol),
THF/MeOH (1:1, 50 mL). Compound 4a (2.8 g, 93%) was obtained
as a white solid: mp 78−80 °C; MS (EI) m/z = 190 [MH]+; HRMS
Synthesis of 1,2-Bis(2′-methoxyquinolin-3-yl)ethene (5c). Syn-
thesis according to the general procedure leading to 5a, 2-
methoxyquinoline-3-carboxaldehyde 2 (0.50 g, 2.67 mmol), phospho-
nium salt 4c (1.69 g, 3.2 mmol), and sodium hydride (0.192 g, 8.0
mmol) in dichloromethane. Purified by column chromatography using
EtOAc/petroleum ether (20:80) to obtain 5c (0.750 g, 82%, Z/E
∼3:1) as a yellow solid: mp 149−150 °C; MS (ESI+) m/z = 343
[MH]+; HRMS (EI) calcd for C22H18N2O2 342.1368, found m/z
342.1355; 1H NMR (300 MHz, CDCl3) δ 8.25 (s, 2H, vinylic protons
of trans isomer), 7.81−7.75 (m, 4H, ArH), 7.61−7.51 (m, 4H, ArH),
7.40−7.37 (m, 4H, ArH), 7.25−7.20 (m, 4H, ArH), 6.88 (s, 2H,
vinylic protons of cis isomer), 4.18 (s, 6H, CH3 of trans isomer), 4.08
(s, 6H, CH3 of cis isomer); 13C NMR (75 MHz, CDCl3) δ 160.3,
145.9, 137.1, 134.1, 129.5, 127.6, 127.5, 127.0, 126.9, 126.5, 125.4,
125.0, 124.4, 124.1, 121.7 (C, CH), 53.88, 53.83 (CH3).
1
(EI) calcd for C11H11NO2 189.0790, found m/z 189.0793; H NMR
(300 MHz, CDCl3) δ 7.95 (s, 1H, ArH), 7.84 (d, 1H, J = 8.2 Hz,
ArH), 7.71 (d, 1H, J = 7.5 Hz, ArH), 7.62 (t, 1H, J = 7.1 Hz, ArH),
7.32 (t, 1H, J = 7.8 Hz, ArH), 4.76 (d, 2H, J = 5.8 Hz, CH2), 4.11 (s,
3H, OCH3), 2.43 (t, 1H, J = 6.2 Hz, OH); 13C NMR (75 MHz,
CDCl3, 25 °C, TMS) δ 160.3, 146.0, 135.7, 129.3, 127.5, 125.3, 124.9,
124.3(C, CH), 61.4 (CH2OH), 53.6 (OCH3).
Synthesis of 3-(Bromomethyl)-2-methoxyquinoline (4b). Syn-
thesis according to the general procedure leading to 3b, (2-
methoxyquinolin-3-yl)methanol 4a (2.8 g, 14.7 mmol), tetrabromo-
methane (4.9 g, 14.7 mmol), triphenylphosphine (3.8 g, 14.7 mmol),
and dichloromethane. Compound 4b (2.5 g, 68%) was obtained as a
white solid: mp 105−107 °C; MS (EI) m/z = 251 [MH]+; HRMS
(EI) calcd for C11H10NBrO 250.9946, found m/z 250.9948; 1H NMR
(300 MHz, CDCl3) δ 8.02 (s, 1H, ArH), 7.84 (d, 1H, J = 8.2 Hz,
ArH), 7.70 (d, 1H, J = 7.9 Hz, ArH), 7.62 (t, 1H, J = 8.1 Hz, ArH),
7.38 (t, 1H, J = 7.7 Hz, ArH), 4.61 (s, 2H, CH2Br), 4.14 (s, 1H,
OCH3); 13C NMR (75 MHz, CDCl3, 25 °C, TMS) δ 159.9, 146.7,
138.8, 130.1, 127.6, 127.1, 124.5 (C, CH), 53.9 (OCH3), 28.3
(CH2Br).
Synthesis of (2-Methoxyquinolin-3-yl)methyltriphenyl-
phosphonium Bromide (4c). Synthesis according to the general
procedure leading to 3c, 3-(bromomethyl)-2-methoxyquinoline 4b
(2.0 g, 7.9 mmol), triphenylphosphine (6.1 g, 23.8 mmol), and
toluene. Phosphonium salt 4c (3.7 g, 92%) was obtained as a white
solid: mp 202−204 °C; MS (ESI+) m/z = 514 [MH]+(obsd 514 − Br
= 434); HRMS (EI) calcd for C29H25NOP 434.1674 [M − Br], found
m/z 434.1667 [M − Br]; 1H NMR (300 MHz, CDCl3) δ 8.42 (s, 1H,
ArH), 7.83−7.56 (m, 18H, ArH), 7.33 (t, 1H, J = 7.7 Hz, ArH), 5.63
(d, 2H, J = 14.4 Hz, CH2P), 3.45 (s, 3H, OCH3); 13C NMR (75 MHz,
CDCl3, 25 °C, TMS): δ 159.4, 146.2, 142.3, 135.0, 134.3, 134.1, 130.2,
Synthesis of 6,9-Dichloro-5,10-diaza[5]helicene (6a). General
Procedure. To a solution of compound 5a (0.15 g, 0.42 mmol, mixture
of two isomers) in toluene (425 mL) was added iodine (0.108 g, 0.42
mmol). Argon was bubbled through the solution for 30 min, and then
excess propylene oxide was added to the solution. The reaction
mixture was irradiated using a Rayonet photochemical reactor
(wavelength used is 350 nm) for 10 h, after which it was washed
with aqueous Na2S2O3, water, and brine, dried over anhydrous MgSO4,
and evaporated to afford a dark yellow residue. Purification by column
chromatography using EtOAc/petroleum ether (10:90) as eluent gave
the racemic diaza[5]helicene 6a (0.085 g, 57%) as a light yellow solid:
mp 247−249 °C; MS (ESI+) m/z = 349 [MH]+; HRMS (EI) calcd for
1
C20H10N2Cl2 348.0221, found m/z 348.0227; H NMR (300 MHz,
CDCl3) δ 8.57 (s, 2H, ArH), 8.42 (d, 2H, J = 8.4 Hz, ArH), 8.16 (d,
2H, J = 8.1 Hz, ArH), 7.73 (t, 2H, J = 7.3, ArH), 7.37 (t, 2H, J = 8.1
Hz, ArH); 13C NMR (75 MHz, CDCl3, 25 °C, TMS) δ 150.9, 144.5,
131.9, 130.4, 128.9, 127.6, 127.1, 126.5, 126.1, 124.0 (C, CH).
Synthesis of 6-Chloro,9-methoxy-5,10-diaza[5]helicene (6b).
Synthesis according to the general procedure leading to 6a, compound
5b (0.15 g, 0.43 mmol), and I2 (0.109 g, 0.43 mmol) in toluene.
Purification by column chromatography using EtOAc/petroleum ether
10181
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
(20:80) as eluent gave the racemic diaza[5]helicene 6b (0.069 g, 46%)
as a light yellow solid: mp 217−219 °C; MS (ESI+) m/z = 345
[MH]+; HRMS (EI) calcd for C21H13N2ClO 344.0716, found m/z
Synthesis of 6,9-Bis(phenoxy)-5,10-diaza[5]helicene (7c). To a
solution of 6a (20 mg, 0.057 mmol) in DMF (10 mL) were added
K2CO3 (19.8 mg, 0.14 mmol) and phenol (13.4 mg, 0.14 mmol), and
the reaction was stirred at 80 °C for 12 h. Subsequently, the mixture
was diluted with ethyl acetate (20 mL) and washed with distilled water
(3 × 20 mL). The organic fraction was dried over MgSO4 and filtered,
and the solvent was removed under vacuum. After column
chromatographic purification using EtOAc/petroleum ether (20:80)
as eluent the substituted diaza[5]helicene 7d (18 mg, 67%) was
obtained as a yellow solid: mp 256−258 °C; MS (ESI+) m/z = 465
[MH]+; HRMS (EI) calcd for C32H20N2O2 464.1525, found m/z
464.1525; 1H NMR (300 MHz, CDCl3) δ 8.68 (s, 2H, ArH), 8.54 (d,
2H, J = 8.1 Hz, ArH), 7.83 (d, 2H, J = 8.2 Hz, ArH), 7.58−7.49 (m,
6H, ArH), 7.43−7.41 (m, 4H, ArH), 7.32 (t, 2H, J = 7.1 Hz, ArH),
7.21 (t, 2H, J = 6.9 Hz, ArH); 13C NMR (75 MHz, CDCl3, 25 °C,
TMS) δ158.7, 153.8, 143.7, 132.6, 129.6, 129.4, 128.1, 127.7, 125.1,
123.7, 123.5, 123.2, 122.6, 122.1 (C, CH).
1
344.0694; H NMR (300 MHz, CDCl3) δ 8.54 (d, 1H, J = 8.4 Hz,
ArH), 8.47 (s, 1H, ArH), 8.35 (d, 1H, J = 8.2 Hz, ArH), 8.12 (d, 1H, J
= 8.2 Hz, ArH), 7.95 (d, 1H, J = 8.1 Hz, ArH), 7.69 (t, 1H, J = 8.1 Hz,
ArH), 7.60 (t, 1H, J = 8.1 Hz, ArH), 7.35 (t, 1H, J = 8.1 Hz, ArH),
7.18 (t, 1H, J = 8.1 Hz, ArH), 4.32 (s, 3H, OCH3); 13C NMR (75
MHz, CDCl3, 25 °C, TMS) δ 159.0, 151.2, 144.4, 144.2, 131.9, 129.9,
129.7, 128.7, 127.8, 127.6, 127.0, 125.7, 125.6, 124.4, 124.3, 123.0,
122.7, 122.4 (C,CH), 54.3 (OCH3).
Synthesis of 6,9-Dimethoxy-5,10-diaza[5]helicene (6c). Synthesis
according to the general procedure leading to 6a, compound 5c (0.20
g, 0.58 mmol), and I2 (0.148 g, 0.58 mmol) in toluene. Purification by
column chromatography using EtOAc/petroleum ether (20:80) as
eluent gave the racemic diaza[5]helicene 6c (0.125 g, 63%) as a light
yellow solid: mp 198−202 °C; MS (ESI+) m/z = 341 [MH]+; HRMS
1
(EI) calcd for C22H16N2O2 340.1212, found m/z 340.1185; H NMR
Synthesis of 6,9-Bis(phenylamino)-5,10-diaza[5]helicene (7d). To
a solution 6a (20 mg, 0.057 mmol) in DMF (10 mL) was added
aniline (26 μL, 0.28 mmol, 5 equiv), and the reaction mixture was
stirred at 150 °C for 20 h. Subsequently, the mixture was diluted with
ethyl acetate (20 mL) and washed with distilled water (3 × 20 mL).
The organic fraction was dried over MgSO4 and filtered, and the
solvent was removed under vacuum. After column chromatographic
purification using EtOAc/petroleum ether (40:60) as eluent, the
substituted diaza[5]helicene 7d (13 mg, 50%) was obtained as a yellow
solid: mp 288−290 °C; MS (ESI+) m/z = 463 [MH]+; HRMS (EI)
(300 MHz, CDCl3) δ 8.48 (d, 2H, J = 8.4 Hz, ArH), 8.39 (s, 2H,
ArH), 7.93 (d, 2H, J = 8.1 Hz, ArH), 7.57 (t, 2H, J = 7.7 Hz, ArH),
7.17 (t, 2H, J = 7.7 Hz, ArH), 4.29 (s, 3H, OCH3); 13C NMR (75
MHz, CDCl3, 25 °C, TMS) δ 159.3, 144.1, 131.9, 129.2, 127.9, 127.4,
123.3, 122.7, 122.5 (C,CH), 54.2 (OCH3). During the synthesis of
diaza[5]helicene, the typical side product diazabenzo[ghi]perylene was
formed in low yield.
Synthesis of 5,8-Dimethoxy-4,9-diazabenzoperylene (6d). Syn-
thesis according to the general procedure leading to 6a, compound 5c
(0.05 g, 0.146 mmol), and I2 (0.074 g, 0.292 mmol) in toluene. The
reaction mixture was irradiated for 3 days. Purification by column
chromatography using EtOAc/petroleum ether (20:80) to CH2Cl2/
toluene (50:50) as eluent gave first the racemic diaza[5]helicene 6c
(0.012 g, 25%) as a light yellow solid and 6d (0.031 g, 63%) as a silver-
white solid. Material identity of the first fraction was confirmed by mp,
1
calcd for C32H22N4 462.1844, found m/z 462.1840; H NMR (300
MHz, DMSO-d6) δ 9.54 (s, 2H, NH), 8.73 (s, 2H, ArH), 8.27 (d, 2H,
J = 8.4 Hz, ArH), 8.10−8.07 (m, 4H, ArH), 7.75 (d, 2H, J = 8.1 Hz,
ArH), 7.55 (t, 2H, J = 7.7 Hz, ArH), 7.45−7.40 (m, 4H, ArH), 7.14−
7.07 (m, 4H, ArH); 13C NMR (75 MHz, DMSO-d6, 25 °C, TMS) δ
150.9, 144.5, 141.2, 131.1, 129.5, 128.5, 127.3, 126.8, 122.7, 122.3,
121.8, 121.7, 121.4, 120.8.
1
MS, and H and 13C NMR of 6c. For 6d: mp 305−310 °C; MS (EI)
m/z = 338 [MH]+; HRMS (EI) calcd for C22H14N2O2 338.1055,
found m/z 338.1051.
Palladium-Catalyzed Reactions. Suzuki Coupling. Synthesis of
6,9-Bis(4-methylphenyl)-5,10-diaza[5]helicene (7e). To a solution of
6a (20 mg, 0.057 mmol) in toluene (20 mL) was added Pd(PPh3)4 (3
mg, 5 mol %), and to this a solution of p-tolylboronic acid (24 mg,
0.171 mmol) in aqueous NaHCO3 (19 mg, 0.228 mmol) and MeOH
(0.5 mL) was added. The reaction mixture was refluxed for 12 h.
Subsequently, the mixture was washed with distilled water (3 × 20
mL). The organic fraction was dried over MgSO4 and filtered, and the
solvent was removed under vacuum. After column chromatographic
purification using EtOAc/petroleum ether (20:80) as eluent the
substituted diaza[5]helicene 7e (11.2 mg, 42%) was obtained as an off-
white solid: mp 286−287 °C; MS (ESI+) m/z = 461 [MH]+; HRMS
Nucleophilic Substitution Reactions. Synthesis of 6,9-Bis-
(thiomethoxy)-5,10-diaza[5]helicene (7a). To a solution of 6a (20
mg, 0.05 mmol) in DMF (10 mL) was added sodium thiomethoxide
(10 mg, 0.14 mmol),d and the reaction was stirred at 80 °C for 12 h.
Subsequently, the mixture was diluted with EtOAc (20 mL) and
washed with distilled water (3 × 20 mL). The organic fraction was
dried over MgSO4 and filtered, and the solvent was removed under
vacuum. After column chromatographic purification using EtOAc/
petroleum ether (20:80) as eluent, the substituted diaza[5]helicene 7a
(12.5 mg, 58%) was obtained as a light yellow solid: mp 250−253 °C;
MS (ESI+) m/z = 373 [MH]+; HRMS (EI) calcd for C22H16N2S2
1
(EI) calcd for C34H24N2 460.1939, found m/z 460.1926; H NMR
1
372.0755, found m/z 372.0766; H NMR (300 MHz, CDCl3) δ 8.41
(300 MHz, CDCl3) δ 8.63 (d, 2H, J = 8.2 Hz, ArH), 8.30 (d, 2H, J =
8.1 Hz, ArH), 8.05 (s, 2H, ArH), 7.76−7.68 (m, 6H, ArH), 7.42−7.36
(m, 6H, ArH), 2.48 (s, 6H, PhCH3); 13C NMR (75 MHz, CDCl3, 25
°C, TMS) δ 160.1, 145.0, 139.2, 136.7, 131.0, 130.4, 129.8, 129.4,
129.3, 127.4, 126.7, 126.6, 125.4, 124.5 (C, CH), 21.5 (CH3).
Buchwald−Hartwig Amination. Synthesis of 6,9-Bis-
(phenylamino)-5,10-diaza[5]helicene (7d). To a solution 6a (20
mg, 0.057 mmol) in toluene (10 mL) were added aniline (13.3 mg,
0.143 mmol), Cs2CO3 (370 mg, 1.14 mmol), rac-BINAP (1.7 mg,
0.0028 mmol), and Pd(OAc)2 (1.2 mg, 0.0057 mmol), and the
reaction mixture was stirred at 80 °C for 12 h. Subsequently, the
mixture was diluted with ethyl acetate (20 mL) and washed with
distilled water (3 × 20 mL). The organic fraction was dried over
MgSO4 and filtered and the solvent was removed under vacuum. After
column chromatographic purification using EtOAc/petroleum ether
(40:60) as eluent the substituted diaza[5]helicene 7d (15.2 mg, 57%)
was obtained as a yellow solid. The material’s identity was compared
with 7d prepared via SNAr reaction and confirmed by mp, MS, and 1H
and 13C NMR.
(d, 2H, J = 8.0 Hz, ArH), 8.35 (s, 2H, ArH), 8.05 (d, 2H, J = 8.2 Hz,
ArH), 7.61(t, 2H, J = 8.1 Hz, ArH), 7.22 (t, 2H, J = 8.3 Hz, ArH), 2.86
(s, 6H, SCH3); 13C NMR (75 MHz, CDCl3, 25 °C, TMS): δ 159.7,
145.3, 129.6, 129.4, 128.1, 127.6, 124.0, 123.7, 123.2(C, CH), 13.5
(SCH3).
Synthesis of 6,9-Bis(thiophenoxy)-5,10-diaza[5]helicene(7b). To
a solution of 6a (20 mg, 0.05 mmol) in DMF (10 mL) were added
K2CO3 (19.8 mg, 0.14 mmol) and thiophenol (14 μL, 0.14 mmol),
and the reaction was stirred at 80 °C for 12 h. Subsequently, the
mixture was diluted with ethyl acetate (20 mL) and washed with
distilled water (3 × 20 mL). The organic fraction was dried over
MgSO4 and filtered, and the solvent was removed under vacuum. After
column chromatographic purification using EtOAc/petroleum ether
(30:70) as eluent the substituted diaza[5]helicene 7b (18 mg, 62%)
was obtained as a light yellow solid: mp 227−229 °C; MS (ESI+) m/z
= 497 [MH]+; HRMS (EI) calcd for C32H20N2S2 496.1068, found m/z
496.1071; 1H NMR (300 MHz, CDCl3) δ 8.53 (s, 2H, ArH), 8.39 (d,
2H, J = 8.1 Hz, ArH), 7.84 (d, 2H, J = 8.1 Hz, ArH), 7.82−7.69 (m,
4H, ArH), 7.53 (t, 2H, J = 6.9 Hz, ArH), 7.49−7.45 (m, 6H, ArH),
7.23 (t, 2H, J = 7.1 Hz, ArH); 13C NMR (75 MHz, CDCl3, 25 °C,
TMS) δ158.8, 145.1, 135.0, 130.3, 129.4, 129.2, 128.8, 128.7, 127.6,
127.4, 124.6, 124.4, 123.7 (C, CH).
Synthesis of 6,9-Bis[(S)-α-(methylbenzylamino)]-5,10-diaza[5]-
helicene (7f). To a solution of 6a (50 mg, 0.143 mmol) in toluene
(20 mL) were added (S)-α-methyl benzylamine (43 μL, 0.358 mmol),
Cs2CO3 (931 mg, 2.86 mmol), rac-BINAP (4.4 mg, 5 mol %), and
10182
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183

The Journal of Organic Chemistry
Article
Pd(OAc)2 (3.2 mg, 10 mol %), and the reaction mixture was stirred at
80 °C for 12 h. Subsequently, the mixture was diluted with ethyl
acetate (20 mL) and washed with distilled water (3 × 20 mL). The
organic fraction was dried over MgSO4 and filtered, and the solvent
was removed under vacuum. After column chromatographic
purification using EtOAc/petroleum ether (20:80) as eluent, the
diaza[5]helicene 7f (54 mg, 72% 1:1 mixture of diastereomers) was
obtained as a yellow solid: mp 205−207 °C; MS (ESI+) m/z = 519
[MH]+; HRMS (EI) calcd for C36H30N4 519.2549 [M + H]+, found
Tahara, H.; Xu, Y.; Kawase, T.; Bando, T.; Sugiyama, H. J. Am. Chem.
Soc. 2010, 132, 3778−82. (c) Xu, Y.; Zhang, Y.; Sugiyama, H.; Umano,
T.; Osuga, H.; Tanaka, K. J. Am. Chem. Soc. 2004, 126, 6566−67.
(d) Honzawa, S.; Okubo, H.; Anzai, S.; Yamaguchi, M.; Tsumoto, K.;
Kumagai, I. Bioorg. Med. Chem. 2002, 10, 3213−8.
(7) Kaseyama, T.; Furumi, S.; Zhang, X.; Tanaka, K.; Takeuchi, M.
Angew. Chem., Int. Ed 2011, 50, 3684−3687.
(8) Verbiest, T.; Van Elshocht, S.; Kauranen, M.; Hellemans, L.;
Snauwaert, J.; Nuckolls, C.; Katz, T. J.; Persoons, A. Science 1998, 282,
913−915.
1
m/z 519.2552; H NMR (300 MHz, CDCl3) δ 8.33−8.29 (m, 4H,
ArH), 7.83 (s, 2H, ArH), 7.81 (s, 2H, ArH), 7.77 (d, 2H, J = 7.6 Hz,
ArH), 7.72 (d, 2H, J = 8.2 Hz, ArH), 7.58−7.55 (m, 8H, ArH), 7.47−
7.42 (m, 4H, ArH), 7.39−7.36 (m, 8H, ArH), 7.29−7.25 (m, 4H,
ArH), 6.99−6.96 (m, 8H, ArH), 5.80−5.78 (m, 2H, CH of one
diastereomer), 5.75−5.73 (m, 2H, CH of second diastereomers),
5.51−5.48 (m, 4H, NH), 1.78−1.74 (m, 12H, CH3); 13C NMR (75
MHz, CDCl3, 25 °C, TMS): δ 152.1, 152.0, 145.7, 145.0, 144.8, 132.2,
132.1, 129.3, 128.8, 128.6, 128.0, 127.3, 127.2, 126.9, 126.8, 126.7 (C,
CH), 50.8, 50.4 (CHNH), 22.4, 22.3 (CH3).
(9) Grimme, S.; Peyerimhoff, S. D. Chem. Phys. 1996, 204, 411−417.
(10) Bell, J. W.; Hext, N. M. Chem. Soc. Rev. 2004, 33, 589−598.
(11) Rodriguezubis, J. C.; Alpha, B.; Plancherel, D.; Lehn, J. M. Helv.
Chim. Acta 1984, 67, 2264−2269.
(12) Phillips, K. E. S.; Katz, T. J.; Jockusch, S.; Lovinger, A. J.; Turro,
N. J. J. Am. Chem. Soc. 2001, 123, 11899−11907.
(13) Crittall, M. R.; Rzepa, H. S.; Carbery, D. R. Org. Lett. 2011, 13,
1250−1253.
(14) Takenaka, N.; Sarangthem, R. S.; Captain, B. Angew. Chem., Int.
Ed 2008, 47, 9708−9710.
ASSOCIATED CONTENT
* Supporting Information
(15) Murguly, E.; McDonald, R.; Branda, N. R. Org. Lett. 2000, 2,
3169−3172.
■
S
(16) Graule, S.; Rudolph, M.; Vanthuyne, N.; Autschbach, J.; Roussel,
C.; Crassous, J.; Reau, R. J. Am. Chem. Soc. 2009, 131, 3183−85.
(17) (a) Caronna, T.; Gabbiadini, S.; Mele, A.; Recupero, F. Helv.
Chim. Acta 2002, 85, 1−8. (b) Bazzini, C.; Brovelli, S.; Caronna, T.;
Gambarotti, C.; Giannone, M.; Macchi, P.; Meinardi, F.; Mele, A.;
Panzeri, W.; Recupero, F.; Sironi, A.; Tubino, R. Eur. J. Org. Chem.
2005, 1247−1257.
1H and 13C NMR spectra of the novel precursors and
diaza[5]helicenes 6a−c and substituted derivatives. Temper-
ature-dependent 1HNMR spectra and racemization studies
related analysis and HPLC of compound 7f. UV−vis and CD
spectra of compound 7f. X-ray data for compounds 6a and 6c.
This material is available free of charge via the Internet at
http://pubs.acs.org
(18) Aloui, F.; El Abed, R.; Ben Hassine, B. Tetrahedron. Lett 2008,
49, 1455−1457.
(19) Aloui, F.; El Abed, R.; Marinetti, A.; Hassine, B. Tetrahedron.
Lett 2008, 49, 4092−4095.
AUTHOR INFORMATION
Corresponding Author
*E-mail: wim.dehaen@chem.kuleuven.be.
■
(20) Harrowven, D. C.; Guy, I. L.; Nanson, L. Angew. Chem., Int. Ed.
2006, 45, 2242−2245.
Notes
(21) Misek, J.; Teply, F.; Stara, I. G.; Tichy, M.; Saman, D.; Cisarova,
I.; Vojtisek, P.; Stary, I. Angew. Chem., Int. Ed. 2008, 47, 3188−3191.
(22) Andronova, A.; Szydlo, F.; Teply, F.; Tobrmanova, M.; Volot,
A.; Stara, I. G.; Stary, I.; Rulisek, L.; Saman, D.; Cvacka, J.; Fiedler, P.;
Vojtisek, P. Collect. Czech. Chem. C 2009, 74, 189−215.
(23) Stara, I. G.; Andronova, A.; Kollarovic, A.; Vyskocil, S.; Juge, S.;
Lloyd-Jones, G. C.; Guiry, P. J.; Stary, I. Collect. Czech. Chem. C 2011,
76, 2005−2022.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the FWO (Fund for Scientific Research - Flanders),
the K.U. Leuven, and the Ministerie voor Wetenschapsbeleid
(IAP-IV-27) for continuing financial support, the Hercules
Foundation of the Flemish Government (Grant No. 20100225-
7) for mass spectrometry, and the Ministry of Science
Education and Sports of the Republic of Croatia (Grant No.
098-0982933-2911).
(24) Kelgtermans, H.; Dobrzanska, L.; Van Meervelt, L.; Dehaen, W.
Org. Lett. 2012, 14, 1500−1503.
(25) Van Rossom, W.; Maes, W.; Kishore, L.; Ovaere, M.; Van
Meervelt, L.; Dehaen, W. Org. Lett. 2008, 10, 585−588.
(26) Mamane, V.; Louerat, F.; Lehl, J.; Abboud, M.; Fort, Y.
Tetrahedron 2008, 64, 10699−10705.
(27) Masters, K. S.; Rauws, T. R. M.; Yadav, A. K.; Herrebout, W. A.;
Van der Veken, B.; Maes, B. U. W. Chem.Eur. J. 2011, 17, 6315−
6320.
(28) (a) Meth-Cohn, O.; Narine, B.; Tarnowski, B. J. Chem. Soc.,
Perkin Trans. 1 1981, 1520. (b) Baruah, B.; Bhuyan, P. J. Tetrahedron
2009, 65, 7099−7104.
(29) Hu, L. X.; Li, Z. R.; Wang, Y. M.; Wu, Y. B.; Jiang, J. D.; Boykin,
D. W. Bioorg. Med. Chem. Lett. 2007, 17, 1193−1196.
(30) (a) Abbate, S.; Bazzini, C.; Caronna, T.; Fontana, F.;
Gambarotti, C.; Gangemi, F.; Longhi, G.; Mele, A.; Natali Sora, I.;
Panzeri, W. Tetrahedron 2006, 62, 139−148. (b) Waghray, D.; Nulens,
W.; Dehaen, W. Org. Lett. 2011, 13, 5516−5519.
(31) Bazzini, C.; Caronna, T.; Fontana, F.; Macchi, P.; Mele, A.;
Natali Sora, I.; Panzeri, W.; Sironi, A. New. J. Chem. 2008, 32, 1710−
1717.
REFERENCES
■
(1) (a) Rajca, A.; Miyasaka, M. Synthesis and Characterization of
Novel Chiral Conjugated Materials. Functional Organic Materials:
Syntheses and Strategies; Mueller, T. J. J., Bunz, U. H. F., Eds.; Wiley-
VCH: Germany, 2007; pp 543−577. (b) Shen, Y.; Chen, C.-F. Chem.
Rev. 2012, 112, 1463−1535. (c) Stara, I. G.; Stary, I. Sci. Synth. 2010,
́
45b, 885−953. (d) Rajca, A.; Rajca, S.; Pink, M.; Miyasaka, M. Synlett
2007, 14, 2007. (e) Collins, S. K.; Vachon, M. P. Org. Biomol. Chem
2006, 4, 2518−2524. (f) Urbano, A. Angew. Chem., Int. Ed 2003, 42,
3986−3989.
(2) Dumitrascu, F.; Dumitrescu, D. G.; Aron, I. Arkivoc 2010, 1−32.
(3) Rybacek, J.; Huerta-Angeles, G.; Kollarovic, A.; Stara, I. G.; Stary,
I.; Rahe, P.; Nimmrich, M.; Kuhnle, A. Eur. J. Org. Chem. 2011, 853−
860.
(4) Kim, C.; Marks, T. J.; Facchetti, A.; Schiavo, M.; Bossi, A.;
Maiorana, S.; Licandro, E.; Todescato, F.; Toffanin, S.; Muccini, M.;
Graiff, C.; Tiripicchio, A. Org. Electronic 2009, 10, 1511−1520.
(5) Ichinose, W.; Miyagawa, M.; An, Z. J.; Yamaguchi, M. Org. Lett.
2012, 14, 3123−3125.
(32) Songis, O.; Misek, J.; Schmid, M. B.; Kollarovie, A.; Stara, I. G.;
Saman, D.; Cisarova, I.; Stary, I. J. Org. Chem. 2010, 75, 6889−6899.
(33) Abbate, S.; Bazzini, C.; Caronna, T.; Fontana, F.; Gangemi, F.;
Lebon, F.; Longhi, G.; Mele, A.; Natali Sora, I. Inorg. Chim. Acta 2007,
360, 908−912.
(6) (a) An, Z.; Yamaguchi, M. Chem. Commun 2012, 48, 7383−7385.
(b) Shinohara, K.-I.; Sannohe, Y.; Kaieda, S.; Tanaka, K.-I.; Osuga, H.;
10183
dx.doi.org/10.1021/jo301814m | J. Org. Chem. 2012, 77, 10176−10183