Triazoliptycenes: A Twist on Iptycene Chemistry for Regioselective Cross-Coupling to Build Nonstacking Fluorophores

Article abstract of DOI:10.1021/acs.orglett.7b03239

Triazoliptycene fluorophores have been designed and synthesized, in which a three-dimensional propeller-like iptycene motif is employed to suppress intermolecular π-π stacking in the solid state. Key to the success of this modular synthesis is a stereoelectronic bias imposed by the iptycene scaffold, which assists the desired regioselectivity in the C-N cross-coupling step as the last-stage structure diversification from a common precursor.

Full text of DOI:10.1021/acs.orglett.7b03239

Letter
pubs.acs.org/OrgLett
Triazoliptycenes: A Twist on Iptycene Chemistry for Regioselective
Cross-Coupling To Build Nonstacking Fluorophores
Taewon Kang, Hongsik Kim, and Dongwhan Lee*
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea
S
* Supporting Information
ABSTRACT: Triazoliptycene fluorophores have been de-
signed and synthesized, in which a three-dimensional
propeller-like iptycene motif is employed to suppress
intermolecular π−π stacking in the solid state. Key to the
success of this modular synthesis is a stereoelectronic bias
imposed by the iptycene scaffold, which assists the desired
regioselectivity in the C−N cross-coupling step as the last-
stage structure diversification from a common precursor.
uminescent molecules are finding wide applications as light-
propeller-shaped architecture have subsequently been exploited
in various applications including crystal engineering, host−guest
chemistry, conformationally rigid ligands, and polymers having
internal free volume.2,10
L
emitting diodes,1 vapor sensors,2 and encryption materials.3
Flat and rigid organic molecules developed for such a purpose,
however, tend to engage in extensive intermolecular π−π
interactions upon solidification.4 This structural property often
perturbs intrinsic molecular photophysical properties in the solid
state.5,6 An intuitive solution to this problem is building steric
shields to isolate fluorogenic molecular motifs.2,7,8
Toward this objective, we have devised and implemented a
last-stage cross-coupling strategy to construct a new class of
organic solid-state fluorophores, N-aryl triazoliptycenes (1)
(Figure 1). Formally considered as a hybrid between a flat N-aryl
As the fluorophores to be fused with the iptycene system, we
chose N-aryl functionalized triazoles (Figure 1, in red). This
decision was made for the following reasons. First, the electron-
deficient triazole ring could function as an acceptor in charge-
transfer (CT) type transitions, which respond sensitively to
changes in the local environment.6 Second, without close orbital
overlap between neighboring arene units, the intrinsic photo-
physical properties of the fluorophore would be maintained even
after being fused with the iptycene scaffold. Third, the iptycene
scaffold offers a rather unconventional yet viable solution for
regioselective C−N cross-coupling reactions, as discussed below.
Transition metal-catalyzed C−N cross-coupling reactions
have widely been employed to construct structurally elaborate
molecules from nitrogen-containing precursors.11 When such
precursor has multiple nitrogen atoms to react, however, the
problem of isomerism could arise. For N-arylation reactions of
1,2,3-triazoles via direct C−N coupling (Scheme 1),12,13
a
mixture of nonfluorescent N1- (2) and fluorescent N2-arylated
(3) products are typically obtained with poor to moderate
selectivity (1:1−4.3).13a−c
Figure 1. Chemical structure of N2-aryl triazoliptycene (1), and a
schematic representation of the design concept to suppress close and
contiguous π−π contacts of the N-aryl triazole fluorophores (in red) in
the solid state.
Since the photophysical properties of 3 can be tuned by
varying the N-aryl substituent,13c,e,14 diversity-oriented synthesis
by late-stage C−N bond-making should significantly expand the
scope of this chemistry. This strategy, however, requires a high
N2-selectivity in cross-coupling, which is difficult to achieve.
Previous efforts to realize this goal have focused on triazoles
having special substituents,13d or bulky and electron-rich ligands
for the metal catalyst.13a
triazole fluorophore and iptycene-based three-dimensional
scaffold, these molecules are designed specifically to avoid
close and contiguous π−π contacts upon aggregation.
The chemistry of iptycenes has evolved from the parent
triptycene system (Figure 1), which was invented originally to
study the exceptional stability of bridgehead C−X bonds in
substitution reactions.9 The unique structural properties of such
Received: October 17, 2017
Published: November 16, 2017
© 2017 American Chemical Society
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DOI: 10.1021/acs.orglett.7b03239
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Organic Letters
Letter
Scheme 1. Tautomeric Triazoles To Produce Isomeric N-Aryl
Triazoles by Metal-Catalyzed C−N Cross-Coupling Reactions
Scheme 2. Synthetic Route to Triazoliptycene
In order to assess the effects of iptycene scaffold on the
chemistry outlined in Scheme 1, we first investigated the
tautomer equilibrium by DFT computational studies (Figure 2).
removal of the temporarily installed N-aryl appendage to unveil
the desired triazoliptycene 5 as the newest addition to
heterocycle-fused iptycenes (Scheme 2). A simplified 1H NMR
spectral pattern of 5 (Figure S2), in particular, a single resonance
of the bridgehead C−H protons at δ = 5.55 ppm, is consistent
with the presence of a mirror plane that bisects the molecule. The
dominance of the 2H-tautomer 5, as predicted by DFT
computational studies (Figure 2), has thus been confirmed
experimentally.
Starting from 5 as a common synthetic precursor, various aryl-
substituted triazoliptycenes 1-H, 1-CN, 1-NMe2, 1-NPh2, and 1-
NaphNMe2 were readily prepared by straightforward C−N
cross-coupling reactions with the corresponding aryl bromides or
iodides (Scheme 3, Route A).
Figure 2. Thermodynamic preference between the 2H- and 1H-
tautomer of the parent triazole (4 and 4′), and the corresponding
triazoliptycene system (5 and 5′) probed by DFT computational studies
(B3LYP/6-31G(d) level; in DMSO solvent at t = 120 °C to simulate the
reaction conditions for C−N cross-coupling). Shown next to the
Scheme 3. Synthesis of N-Aryl Triazoliptycenes
chemical structure of 5′ is an NBO representation of the nN → πCC
donor−acceptor interaction plotted with an isovalue of 0.05.
*
For the simple triazole, both isomers are essentially
isoenergetic (
Gcalc = 0.67 kcal mol−1), with 4 slightly favored
Δ
(K = [4′]/[4] = 4.26 × 10−1). Once integrated into the iptycene
scaffold, however, a dramatic change is observed in the
thermodynamic preference. For triazoliptycene, the 1H-isomer
(5′) becomes significantly destabilized over the 2H-isomer (5)
by as much as
Δ
Gcalc = 3.06 kcal mol−1. Our NBO analysis
(Figure 2) based on the Wiberg bond index (Figure S1) revealed
that the C−C double bond character of the iptycene-fused
triazole fragment is significantly diminished for the triazolipty-
cene. With strong nN → πCC* donor−acceptor type orbital
interaction (Figure 2, bottom right), the electron density at the
N1 position (and thus its affinity toward proton) is reduced,
which promotes tautomerization of 5′ to 5.
It still remained an open question whether such electronically
driven thermodynamic bias (Figure 2) would somehow translate
to the desired regiochemical preference, thereby producing the
desired N2-aryl product 3 (Scheme 1). We were intrigued by
such possibility, and proceeded to carry out experimental studies.
The first step was making the hitherto unknown triazoliptycene
5.
A typical entry point for the iptycene chemistry is direct [4 +
2]-cycloaddition reactions between anthracenes and appropriate
dienophiles, such as benzynes, to construct the three-bladed
architecture.15 For triazoles, however, no such heteroaryne
equivalent is available. We thus devised a synthetic detour that
commenced with the known dione 6 (Scheme 2).16
With standard protocols using a combination of a copper(I)
precatalyst and proline ligand,13c−e the reactions proceeded
cleanly to produce the desired N2-arylated triazoliptycenes. The
cross-coupling reaction of 5 with 1,4-dibromobenzene to
produce 1-Br, however, suffered from decomposition of the
substrate under the reaction conditions. For the reaction of 5
with 4-iodonitrobenzene to produce 1-NO2, we had difficulty in
separating the N-aryl triazoliptycene product from the
dehalogenative homocoupling byproduct. Preparatory-scale
synthesis of 1-Br and 1-NO2 thus resorted to stepwise functional
group transformations from 6 (Scheme 3, Route B). Compound
1-NH2 was prepared by reduction of 1-NO2 with SnCl2. The
1
Sequential condensation reactions of 6 with 4-methoxy-
phenylhydrazine and hydroxylamine, followed by dehydration,
produced 1-OMe. Oxidation with CAN at rt cleanly effected
products were fully characterized by a combination of H/13C
NMR spectroscopic and X-ray crystallographic analysis (Figure
3; Figures S4−S22).
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Letter
Figure 3. ORTEP diagrams of (a) 1-H (prepared by Route A in Scheme
3) and (b) 1-NO2 (prepared by Route B in Scheme 3) with thermal
ellipsoids at 50% probability.
One salient feature of the triazole-based fluorophores is the
tunability of their photophysical properties by the N2-aryl
substituent.13c,e,14 Indeed, the emission of triazoliptycenes in
MeCN spans a wide spectral window (λmax,em = 340−495 nm;
Figure 4a) with visually discernible purple (for 1-H, 1-Br, 1-CN,
Figure 5. (a) Normalized fluorescence spectra of (a) 1-H, (b) 1-CN, (c)
1-Br, and (d) 7 in MeCN solution, powder, drop-cast film, and spin-cast
film samples (t = 298 K; λexc = 280 nm). See the figure legend (top) for
sample designations.
shifts are observed upon going from solution to solid state
(Figures 5b and 5c), but their solid-state fluorescence spectra
also overlap nicely. Donor−acceptor (D−A) type triazolipty-
cenes also display similar longer-wavelength CT-type emissions
across differently prepared solid samples (Figure S26).18
In stark contrast to the context-insensitive emission properties
of triazoliptycenes, the simple triazole 7 (Figure 5d), used as a
reference system prone to π−π stacking, suffers from large red
shifts and spectral broadenings in the condensed phase.
Moreover, different sample preparation methods (i.e., powder,
drop-cast film, or spin-cast film) produced widely different
spectra with varying and unpredictable degrees of energy shifts
and spectral broadening, as shown in Figure 5d.
According to our empirical observations described above,
triazoliptycene aggregates behave as if they were discrete
molecules in solution, as far as the emission energy windows
and spectral line shapes are concerned. What structural features
are responsible for the apparent lack of strong interchromophore
interactions in the condensed phase? As shown in Figures 6 and
S27, triazoliptycenes adopt either (i) slipped face-to-face dimeric
pairs (Figures 6a and 6b; Figure S27; two N-aryl triazole units
pointing in opposite directions to minimize dipole moment) or
(ii) edge-to-face interaction between the N-aryl triazole units
(Figure 6c). The latter spatial arrangement is reinforced by an
electrostatic attraction between one end of the molecule and the
aryl ring of the neighboring molecule. The crystallographic 4-fold
rotational symmetry maximizes such edge-to-face interactions by
establishing a cyclic array.
While their positioning varies depending on the electronic and
steric demand of the aryl group, the distance between two
adjacent π-faces of N-aryl triazole fluorophore ranges as 3.9−5.9
Å (Table S2). These metric parameters are significantly longer
than the ∼3.4 Å spacing anticipated for typical π−π contacts.4
Moreover, the steric shield afforded by the iptycene scaffold does
not allow parallel stacking of π-faces beyond the simple dimer
stage (Figure 6; Figure S27). Without intimately spaced π-faces
to form a continuous array for exciton delocalization or hopping,
as typically observed for flat rigid aromatics, triazoliptycene
aggregates seem to behave as discrete molecules in solution as far
as light-emitting properties are concerned (Figure 5).
Figure 4. Fluorescence spectra of N-aryl triazoliptycenes in MeCN (t =
298 K; λexc = 280 nm). The emission intensities were rescaled by
dividing with the absorbance at λ = 280 nm, so that they are proportional
to the fluorescence quantum yields (ΦF). (b) Emission energy (in cm−1)
of 1-H (light blue), 1-NPh2 (red), 1-NMe2 (orange), and 1-NaphNMe2
(green) plotted vs solvent polarity (ET(30) parameter). Overlaid linear
lines are obtained by least-squares fitting.
1-OMe), blue (for 1-NH2, 1-NMe2, 1-NPh2), and green (for 1-
NaphNMe2) colors. The fluorescence quantum yield also
changes as the N-aryl substituent is varied (Table S1). Notably,
a large red shift in fluorescence is observed for compounds
having electron-donating N-aryl groups (Figure 4a), implicating
the involvement of charge-transfer (CT) type emission; the
electron-deficient triazole group promotes the evolution of
charge-separated excited states upon photoexcitation. In support
of this notion, 1-NMe2, 1-NPh2, and 1-NaphNMe2 show
systematic red shifts in the emission wavelength with increasing
solvent polarity (Figure S25). A good linear relationship (R2 =
0.94−1.00) is observed between the emission energy (in cm−1)
and the ET(30) value (Figure 4b);17 such an effect is less
pronounced for 1-H having an unsubstituted phenyl group,
which serves as a control (Figure 4b).
Due to intermolecular electronic coupling, light-emitting
properties of molecular aggregates often deviate significantly
from those of solution samples. To demonstrate that the three-
blade shaped iptycene scaffold could be a viable solution to this
problem, we prepared three different types of solid samples of
triazoliptycenes (powder, drop-cast film, and spin-cast film) and
compared their emission spectra (Figure 5).
For the iptycene-appended fluorophores 1-H, 1-CN, and 1-Br,
both the energy (λmax,em) and spectral width (fwhm) remain
largely invariant upon changing from solution to solid environ-
ments. Notably, the normalized emission spectra of 1-H are
essentially superimposable (Figure 5a), regardless of whether the
molecule is in solution or solidified as a powder, drop-cast film, or
spin-cast film. For 1-CN and 1-Br, slight (Δλ = 6−11 nm) red
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Organic Letters
Letter
ACKNOWLEDGMENTS
■
This work was supported by the Basic Research Grant
(2017R1A2B2006605), Creative Materials Discovery Program
(2017M3D1A1039558), and NRF-2016-Global Ph.D. Fellow-
ship Program (2016H1A2A1906550 to T.K.) through the
National Research Foundation of Korea (NRF).
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b03239.
Synthesis and characterization; additional spectroscopic
data (PDF)
Accession Codes
CCDC 1579227−1579231 and 1579233−1579234 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.uk,
or by contacting The Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
336033.
(16) Mondal, R.; Shah, B. K.; Neckers, D. C. J. Am. Chem. Soc. 2006,
AUTHOR INFORMATION
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(18) Apparently, solidified triazoliptycene experiences essentially the
identical local dielectric, regardless of whether the sample is prepared as
powder, drop-cast, or spin-cast film.
■
Corresponding Author
*E-mail: dongwhan@snu.ac.kr.
ORCID
(19) Saragi, T. P. I.; Spehr, T.; Siebert, A.; Fuhrmann-Lieker, T.;
Salbeck, J. Chem. Rev. 2007, 107, 1011−1065.
(20) Mei, J.; Leung, N. L. C.; Kwok, R. T. K.; Lam, J. W. Y.; Tang, B. Z.
Chem. Rev. 2015, 115, 11718−11940.
Dongwhan Lee: 0000-0001-6683-9296
Notes
The authors declare no competing financial interest.
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DOI: 10.1021/acs.orglett.7b03239
Org. Lett. 2017, 19, 6380−6383