Quinoline-Derived Two-Photon-Sensitive Octupolar Probes

Article abstract of DOI:10.1002/open.201700097

A systematic study on quinoline-derived light sensitive probes, having third-order rotational symmetry is presented. The electronically linked octupolar structures show considerably improved linear and nonlinear photophysical properties under one- and two-photon irradiation conditions compared to the corresponding monomers. Photolysis of the three acetate derivatives shows strong structure dependency: whereas irradiation of the 6- and 7-aminoquinoline derivatives resulted in fast intramolecular cyclization and only trace amounts of fragmentation products, the 8-aminoquinoline derivative afforded clean and selective photolysis, with a sequential release of their acetate groups (δ_u ^[730]=0.67 GM).

Full text of DOI:10.1002/open.201700097

DOI: 10.1002/open.201700097
Quinoline-Derived Two-Photon-Sensitive Octupolar Probes
Petra Dunkel,[a] Morgane Petit,[a] Hamid Dhimane,[a] Mireille Blanchard-Desce,[b]
David Ogden,[c] and Peter I. Dalko*[a]
A systematic study on quinoline-derived light sensitive probes,
having third-order rotational symmetry is presented. The elec-
tronically linked octupolar structures show considerably im-
proved linear and nonlinear photophysical properties under
one- and two-photon irradiation conditions compared to the
corresponding monomers. Photolysis of the three acetate de-
rivatives shows strong structure dependency: whereas irradia-
tion of the 6- and 7-aminoquinoline derivatives resulted in fast
intramolecular cyclization and only trace amounts of fragmen-
tation products, the 8-aminoquinoline derivative afforded
clean and selective photolysis, with a sequential release of
their acetate groups (du[730] =0.67 GM).
1. Introduction
The combined use of two-photon (TP)-sensitive probes
(switches, actuators and “caged” compounds) with high-
energy pulsed laser-light excitation enables higher spatiotem-
poral resolution at greater depth within biological tissues than
conventional one-photon excitation.[1,2] This is a significant im-
provement that enables optical imaging and photoactivation
at depth in tissues in vivo or in vitro. This field of interest
spans from cell biology to targeted therapeutic applications.[3]
The availability of tunable ultrashort-pulse lasers at near-IR
wavelengths and progress in our understanding of TP chromo-
phore design[4] have contributed to a rapid emergence of TP
techniques in biological applications. In the context of caged
compounds, although many TP chromophores have been de-
veloped, none satisfy the stringent conditions of TP activation
of high water solubility and low pharmacological interference
in the target tissues.[1r,5] We showed recently a simple algo-
rithm to improve probe design rationally by 1) the optimiza-
tion of the substitution pattern of the dipole; 2) the increase
of the conjugation length, and 3) the incorporation of allowed
symmetry elements in the chromophore, allowing access to
improved nonlinear properties (third-order rotational symme-
try, C3, opens for allowed TP transitions, whereas third-order
central symmetry, S3, leads to TP-forbidden transitions).[6] Al-
though the combination of these elements is promising, the
scope for tunability is narrow and limited by biological require-
ments. The fact that the probe should ideally be soluble at
a concentration of at least 10 mm in physiological solutions
sets narrow limits for the extension of the conjugation length.
In this study, we investigated the incorporation of third-
order rotational symmetry that might further improve absorp-
tion parameters by resonance, enhancing the corresponding
transition dipole moments and the magnitude of TP absorp-
tion and uncaging cross sections (s2 and du, respectively). Two
important parameters that permit cooperativity between
branches to increase TP absorption are: 1) the density of the
TP-absorbing units per molecule; 2) their synergic interaction
through electronic interactions by conjugation or through
space by their close proximity, with alternating donor–acceptor
or donor–p-acceptor elements. In these structures, the sym-
metric charge transfer, as well as the change in quadrupole
moment, appear to be important for molecules with small
ground-state mesomeric quadrupole moments. The symmetric
charge transfer, from the ends of a conjugated system to the
middle, or vice versa, upon excitation is expected to enhance
TP absorption cross-section values (s2). The question of wheth-
er these s2 values can be translated into optimized du values,
as is the case with fluorescent probes for df, remained to be
addressed.
[a] Dr. P. Dunkel, Dr. M. Petit, Prof. H. Dhimane, Dr. P. I. Dalko
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques
Universitꢀ Paris Descartes
45, rue des Saints-Pꢁres, 75270, Paris Cedex 06 (France)
E-mail: peter.dalko@parisdescartes.fr
[b] Dr. M. Blanchard-Desce
Universitꢀ de Bordeaux, ISM (CNRS UMR5255)
Bꢂtiment A12, 351, Cours de la Libꢀration, 33405 Talence Cedex (France)
We present here a study on aminoquinoline-derived octupo-
lar probes having third-order rotational symmetry. Quinolines
have been successfully used for the photochemical liberation
of phenols, carboxylates, phosphates and diols with examples
of the physiologically relevant signaling molecules serotonin,
tyrosine, glutamate or kainate.[7] Recent structure–activity stud-
ies showed significant effects of substituents on TP uncaging
and, furthermore, extension of p-conjugation yielded a 5-ben-
zoyl-8-(dimethylamino)quinoline acetate derivative having an
enhanced TP uncaging of 2.0 GM (1 GM=10ꢀ50 cm4 s per pho-
ton).[6b,c] Concerning previous symmetry-related studies of the
[c] Dr. D. Ogden
Laboratoire de Physiologie Cꢀrꢀbrale
Universitꢀ Paris Descartes
45, rue des Saints-Pꢁres, 75270, Paris Cedex 06 (France)
Supporting Information and the ORCID identification number(s) for the
author(s) of this article can be found under https://doi.org/10.1002/
open.201700097.
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This is an open access article under the terms of the Creative Commons
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any medium, provided the original work is properly cited.
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quinoline platform, in the case of directly linked dimers,
modest one-photon and TP uncaging was detected, resulting
presumably more from a substitution by the heteroaryl groups
than quadrupolar coupling.[6a,d] A modest TPA response was
observed for quadrupolar derivatives having (dimethylamino)-
quinoline moieties directly linked to a fluorene core.[6a] Further-
more, these probes showed high two-photon sensitivity (s2Qu,
typically around 2 GM at 730 nm), whereas they were inert
under femtosecond irradiation conditions. Fast and selective
photolysis was observed, however, by using picosecond irradi-
ation conditions with a remarkably high TP uncaging cross sec-
tion (du =2.3 GM at 730 nm). At opposite, no photolysis was
observed with analogous derivatives having an ethylene
spacer in between the fluorene and (dimethylamino)quinoline
end-groups.[6a,8] Octupolar constructs having triphenylamine
cores attached through an ethylene spacer at position C6 or
C8 of the quinoline were found to have enhanced TP absorp-
tion with low (practically zero) uncaging cross sections[8] [both
the dipolar (monomer) and quadrupolar analogues showed
very low uncaging quantum yields]. Remarkably, the octupolar
derivatives showed much lower levels of fluorescence than
their dipolar counterparts, indicating that nonradiative relaxa-
tion processes are enhanced in the branched molecules.
As earlier studies indicated a strong influence of the photol-
ysis efficiency on the position of the donor amino group, the
synthesis of C6, C7 and C8 isomers 1b, 2b and 3b, respective-
ly, was achieved (Figure 1).
Scheme 1. Synthesis of 1b. Reagents and conditions: i) SeO2 (1.3 equiv), di-
oxane, 808C, 3 h (97%); ii) NaBH4 (1.1 equiv), EtOH, RT, 1 h (85%); iii) TBSCl
(1.1 equiv), imidazole (1.1 equiv), DMF, RT, 3 h (80%); iv) CuI (0.2 equiv), l-
proline (0.4 equiv), K2CO3 (3.0 equiv), NH4OH (aq. 28%, 10 equiv), DMSO,
808C, 18 h (58%); v) 7 (2.2 equiv), [Pd2(dba)3] (0.1 equiv), tBu3P (1m in tolu-
ene, 0.2 equiv), tBuONa (2.4 equiv), toluene, 1108C, 18 h (79%); vi) HF–pyri-
dine (7.5 equiv), MeCN, RT, 1 h (70%); vii) Ac2O (4.5 equiv), Et3N (4.5 equiv),
DMAP (cat), CH2Cl2, RT, 2 h (89%).
was obtained by an oxidation–reduction–protection sequence
using standard conditions (67% overall yield for three steps).
Amination of part of the bromoquinoline, 7, was realized in
the presence of ammonia (28%aq) by using copper(I) iodide/
l-proline catalyst and potassium carbonate, as base.[9] Amino-
quinoline 8 was subjected to bidirectional Buchwald–Hartwig-
type coupling in the presence of 2.2 equivalents of bromoqui-
naldine with [Pd2(dba)3]/tBu3P as the catalyst and tBuONa as
a base in toluene at 1108C (79% yield). The sequence was
completed by deprotection of the alcohol by using HF–pyri-
dine followed by acetylation under standard conditions (62%
overall yield for two steps).
The synthesis of compound 2b followed a similar strategy,
as shown in Scheme 2. The desired aminoquinoline 15, ob-
tained from 11 by CuI-catalyzed amination of the protected al-
cohol 14[10] was subjected to a two-directional Buchwald–Hart-
wig coupling in the presence of 2.2 equiv of 7-bromoquinoline
14, in the presence of [Pd2(dba)3]/tBu3P catalyst and tBuONa as
Figure 1. Quinoline-derived dipolar (1a–3a) and octupolar probes (1b–3b).
2. Results and Discussion
Two-directional Buchwald–Hartwig-type coupling between hal-
oquinolines and the aminoquinoline appeared to be a straight-
forward strategy for the preparation of compounds 1b–3b. Al-
though the choice of the general strategy was almost trivial,
the timing of the functional group transformations (i.e. before
or after the coupling) to allow the introduction of the frag-
menting side chain was revealed to be a key issue in terms of
stability and solubility problems of the intermediates. The opti-
mized reaction sequence is shown in Scheme 1 (for alternative
pathways, see the Supporting Information).
Scheme 2. Synthesis of 2b. Reagents and conditions: i) SeO2 (1.3 equiv), di-
oxane, 808C, 3 h (95%); ii) NaBH4 (1.1 equiv), EtOH, RT, 1 h (78%); iii) TBSCl
(1.2 equiv), imidazole (1.2 equiv), DMF, RT, 3 h (64%); iv) CuI (0.2 equiv), l-
proline (0.4 equiv), K2CO3 (3.0 equiv), aq NH4OH (28%, 10 equiv), DMSO,
808C, 18 h (35%); v) 14 (2.2 equiv), [Pd2(dba)3] (0.2 equiv), tBuONa
(2.2 equiv), tBu3P (1m in toluene, 0.8 equiv), toluene, 1108C, 18 h (83%);
vi) HF–pyridine (7.5 equiv), MeCN, RT, 1 h (85%); vii) Ac2O (4.5 equiv), Et3N
(4.5 equiv), DMAP (cat), CH2Cl2, RT, 2 h (88%).
Compound 1b was prepared from the advanced intermedi-
ate 4.[6c] The tert-butyldimethylsilyl (TBS)-protected alcohol 7
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a base in toluene (83% yield). The desired triacetate 2b was
isolated upon HF–pyridine deprotection and acylation (75%
overall yield for two steps).
If the analogous Buchwald–Hartwig strategy was attempted
in the synthesis of the C8 isomer 3b, the reaction formed ex-
clusively the dimer (for further details see the Supporting Infor-
mation). Therefore, a threefold Doebner–Miller strategy starting
from
2,2’,2’’-triamino-triphenylamine[11]
was
devised
(Scheme 3). Under standard conditions (6m HCl, toluene,
Figure 2. MM2 conformational analysis of compounds 1b–3b.
tion maximum of compound 3b was slightly redshifted com-
pared to the 8-(dimethylamino)quinoline monomer, whereas
the absorption band in the near-UV region of all three trimers
was characterized by significantly higher molar extinction coef-
l =
max =369 nm, emax
Scheme 3. Reagents and conditions: i) crotonaldehyde (9.0 equiv), HCl (6m),
toluene, 1208C, 3 h (41%); ii) SeO2 (3.3 equiv), dioxane, 808C, 3 h (95%), iii)
NaBH4 (4.5 equiv), EtOH, RT, 1 h (47%); iv) Ac2O (4.5 equiv), Et3N (4.5 equiv),
DMAP (cat), CH2Cl2, RT, 2 h (54%).
ficients versus the monomers (1a:
3400mꢀ1 cmꢀ1; 2a: lmax =371 nm, emax =4800mꢀ1 cmꢀ1; 3a:
max =347 nm, emax =4800mꢀ1 cmꢀ1). Importantly, trimers 1b–
l
3b exhibited modest fluorescence in the visible region (1b:
lemmax =489 nm, Stokes shift=6.6ꢂ103 cmꢀ1, Ff =0.20; 2b:
lemmax =501 nm, Stokes shift=7.2ꢂ103 cmꢀ1, Ff =0.21; 3b:
lem max =535 nm, Stokes shift=7.6ꢂ103 cmꢀ1, Ff =0.02). The
TP absorption cross sections (s2) of 1b–3b were measured ex-
perimentally in the 700–900 nm range by TP-induced fluores-
cence in MeCN or acetone (see Ref. [19] in the Supporting In-
formation). Chromophores 1b–3b show TP absorption cross
section (s2max) values of 42 GM, for the tripod 2b with an ab-
sorption maxima at 705 nm, 22 GM (740 nm) for 3b, and
24 GM for 1b, with an absorption maxima at 720 nm, which
are one order of magnitude larger than for the corresponding
monomers (1a: lTPAmax =740 nm, s2max =3.0 GM s2[730] =2.0 GM;
2a: lTPAmax =760 nm, s2max =2.8 GM, s2[730] =2.2 GM). In con-
trast, 3b has a comparatively lower TP absorption enhance-
ment (s2max =22 GM at 740 nm) with respect to the monomer
3a (lTPAmax =700 nm, s2max =10 GM, s2[730] =3.0 GM). Differences
between the TP absorption cross sections of the tripods might
be attributed to the conformational bias that reduces the elec-
tronic coupling between the branches.
808C), in the presence of excess crotonaldehyde, a mixture of
singly (19a) and doubly (19b) cyclized products were ob-
tained. The desired triquinaldine 19c was obtained at a higher
temperature (1208C) albeit in modest yield (41%). The usual
sequence of oxidation (SeO2, 95%), reduction (NaBH4, 47%)
and acetylation (54%) yielded 3b.
MM2 conformational analysis of 1b–3b (Figure 2) showed
helix-like arrangements around the central nitrogen atom with
dihedral angles of 408 (1b), 318 (2b), and 348 (3b). Notably,
this conformation facilitates partial overlap between the nitro-
gen doublet and the heteroaromatic rings, resulting in reduced
communication between the quinoline monomers. The central
nitrogen atom appeared considerably sp2-hybridized—almost
planar for 1b with bond angles of 119.68, and somewhat more
pyramidal for 2b (118.58) and 3b (117.78). The closest intramo-
lecular distance between the quinoline carbons was 3.2 ꢁ in
1b, 3.3 ꢁ in 2b, and somewhat larger in 3b at 3.7 ꢁ.
The photophysical characteristics of the products are sum-
marized in Table 1. The absorption spectra of 1b–3b were re-
corded in a 1:1 mixture of MeCN/Tris (pH 7.4) at 293 K in the
250–600 nm wavelength range (for details see the Supporting
Information). The first absorption maxima were found to be
In order to evaluate the photofragmentation of the trimers,
aliquot samples of 1b–3b (0.1 mm) were irradiated in MeCN/
Tris (1:1) at 366 nm. The time course of the UV photolysis was
monitored by LC–MS, plotting the consumption of the starting
material versus time (see the Supporting Information). No
quantitative analysis of the photoreleased acetic acid was
370, 368 and 380 nm, with molar extinction coefficients (emax
)
of 13900, 13900 and 12900 mꢀ1 cmꢀ1, respectively. The absorp-
Table 1. Photophysical properties of probes 1b–3b.
[a,b]
[b,c]
[b]
[730] [c]
max
max [d]
[730]
lmax[a]
emax[a]
[mꢀ1 cmꢀ1
e[366]
Qu
e
[366]Qu
du
lTPA
s2
s2
s2Qu
[GM]
[nm]
]
[mꢀ1 cmꢀ1
]
[%]
[mꢀ1 cmꢀ1
]
[GM]
[nm]
[GM]
[GM]
1b
2b
3b
370
368
380
13926
13923
12853
13546
13705
11693
N.A.
N.A.
1.5
N.A.
N.A.
173
–
–
0.67
720[d]
705[d]
740[e]
24[d]
42[d]
22[e]
22[d]
28[d]
20[e]
–
–
0.30
[a] Measured in MeCN/Tris buffer (20 mm) 1:1 at 293 K. [b] Measured at 366 nm. [c] Samples (0.1 mm) were prepared in MeCN/Tris buffer (1:1, pH 7.4).
[d] Measured in acetone by two-photon-induced fluorescence. [e] Measured in acetonitrile. For a full experimental protocol, see the Supporting Informa-
tion. N.A.=not applicable.
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made. A rapid photolysis of 1b was observed, although in-
stead of liberation of the acid, a carbazole product resulted
from intramolecular cyclization. A similar cyclization product
was observed from the principal photochemical path for the
C7 isomer 2b. The photolysis of the C8 isomer 3b showed
a different reaction course, however, with a sequential libera-
tion of acetate, similar to the previously disclosed fluorene-de-
rived quadrupolar and triphenylamine-derived octupolar con-
structs.[6a,b,12] The TP uncaging cross section du of compound
3b was measured experimentally at 730 nm from the conver-
sion of the acetate 3b to the free carbinol 21. A 45 mL sample
from a 0.1 mm solution in MeCN/Tris (1:1) was irradiated in
a 3 mm path length quartz cuvette by the beam of a Ti–sap-
phire mode-locked laser at a wavelength of 730 nm with
150 fs pulses at 80 MHz. The expanded beam was focused
with a 32 mm lens so that the whole of the excitation volume
was contained in the cuvette. Samples were irradiated for 2–
4 h at an average power of 100 mW. The loss of the cage was
quantified by HPLC, and the photolysis cross section was calcu-
lated from the rate of reduction of the fractional cage concen-
tration at the laser beam parameters given above: compound
3b had a TP uncaging cross section of du[730] =0.67 GM, identi-
cal to the corresponding monomer (3a: du[730] =0.67 GM). This
result is consistent with previous observations on substituted
pyridyl radicals,[13] in which the fragmentation rate was dimin-
ished by increased delocalization. The delocalization results
lowering of the p* orbital energy, and also in a decrease of s*
character, thus increasing the thermodynamic stability of the
overall system. Analogously, the increased thermodynamic sta-
bility might result in less productive kinetic excited states for
photolysis, as well. The stabilization effect in the present case
appears comparable in magnitude to the gain of the sensitivity
that results from increased TP absorption.
Experimental Section
Materials and Methods
Thin layer chromatography was performed on aluminum-backed
Merck Kieselgel 60F 254 pre-coated plates.
1H and 13C NMR spectra were recorded on a Bruker 250 spectrome-
ter (250 and 63 MHz, respectively) and on a Bruker AV-500 spec-
trometer (500 and 125 MHz, respectively). Chemical shifts for pro-
tons are reported in parts per million (ppm) downfield from tetra-
methylsilane and are referenced to residual proton in the NMR sol-
vent (CDCl3: d=7.26, [D6]acetone: d=2.05, [D6]DMSO: d=2.50,
[D4]MeOH: d=4.78 and 3.31 ppm). Chemical shifts for carbon are
reported in ppm downfield from tetramethylsilane and are refer-
enced to the carbon resonances of the solvent (CDCl3: d=77.16,
[D6]acetone: d=29.84, [D6]DMSO: d=39.52, [D4]MeOH: d=
49.15 ppm). Data are represented as follows: chemical shift, multi-
plicity (s=singlet, d=doublet, dd=double doublet, t=triplet, m=
multiplet), coupling constants [Hz], integration. All solvents and in-
organic reagents were obtained from commercial sources and
used without purification unless otherwise noted.
HPLC analyses were performed on a Waters instrument using a 515
pump with a reverse-phase X-Terra MS C18 column (length:
75 mm, diameter: 4.6 mm, stationary phase: 2.5 mm) using
a Waters 2487 dual absorbance detector (260–360 nm) and an iso-
cratic system of elution [MeOH/MeCN/H2O 7:2:1 or H2O/NH4OAc
(10 mm, pH 4.6)]. The volume of injection was 10 mL. The mass ana-
lyzer was an Agilent (model 6100). The capillary tension was 3.5 kV.
The cone tension was 24 V. The temperature of the source was
1308C and the temperature of desolvation was 3508C. Data were
analyzed with ThermoQuest.
UV Photolysis
Samples (0.1 mm) were irradiated for 1–2 h in MeCN/Tris buffer
mixture (1:1, pH 7.4). An aliquot (1 mL) of this solution was irradiat-
ed at approximately 366 nm by using an 8 W Carl Roth lamp. One-
photon quantum yields were determined by using Equation (1):
3. Conclusions
The first systematic study on the effect of third-order rotational
symmetry on the one-photon and two-photon fragmentation
propensity of quinoline-derived caged compounds was pre-
sented. A short synthetic path was developed allowing access
to three highly congested structures, 1b–3b, having the donor
nitrogen as the linchpin between the three branches. Octupo-
lar structures showed enhanced extinction coefficients and TP
absorption cross-section values compared to the correspond-
ing monomers.[7] Photolysis of 1b–3b was strongly dependent
on structure: whereas irradiation of 1b and 2b resulted in fast
intramolecular cyclization and only in trace amounts of frag-
mentation products, compound 3b afforded clean and selec-
tive photolysis under one-photon and TP irradiation condi-
tions, with a sequential release of their acetate groups, with
photolysis quantum yield and uncaging cross sections close to
the parent dipolar derivative 3a. This observation is in accord-
ance with the earlier observed trend that probes having
higher-order symmetry behave more like coupled dipoles, pro-
viding sequential release of the desired molecule, than a reso-
nant system allowing the “one-shot” release upon light excita-
tion. A study on alternative octupolar constructs is underway.
Qu ¼ ½103 e
I0ðlexcÞ t90 %ꢁꢀ1
ð1Þ
ðlexcÞ
where e(lexc) is the molar extinction coefficient of the compound at
the excitation wavelength [mꢀ1 cmꢀ1]; t90% is the time at which
90% of the product was converted [s] as determined by HPLC
(from the fit of the kinetic data), and I0(lexc) is the light intensity at
the excitation wavelength [einsteincmꢀ2 sꢀ1]. Small aliquots (20 mL)
of the solution were removed at fixed intervals for analysis by re-
verse-phase HPLC using dual absorbance detection at 254 and
360 nm. Dark hydrolysis rates were measured similarly except with-
out illumination.
Two-Photon Photolysis
Near-IR irradiation experiments were performed by irradiating a so-
lution (0.1 mm in MeCN/Tris buffer, 1:1, pH 7.4) for 1–4 h. TP uncag-
ing cross-sections (du) were calculated according to the method of
Kiskin and Ogden[14] from the fractional conversion of the cage
after exposure for approximately 4 h in a 45 mL cuvette of 3 mm
pathlength. Irradiation experiments were performed in a way to
minimize the thermal effect: no appreciable temperature change
of the samples was observed. Photolysis was achieved in a closed
cuvette and the sample was recovered integrally at the end. Two-
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photon excitation was calibrated from the fluorescence emission
of 1 mM fluorescein (aq) solution in the same apparatus. The ex-
panded output of a MaiTai BB (Spectra-Physics) pulsed laser was fo-
cused with a 30 mm focal length lens into the cuvette. The TP exci-
tation volume was entirely contained within the cuvette volume to
obviate the need to measure the beam waist. Beam parameters
were 730 nm with 150 fs pulse width at 80 MHz and 100 mW aver-
age power after the cuvette. Samples were centrifuged if necessary
to remove particles if apparent in the transmitted beam. For refer-
ence, the TP uncaging cross section for l-glutamate release from
the widely used 4-methoxy-7-nitroindolinyl-caged glutamate deter-
mined in this way was 0.05 GM. The conversion of the product was
assessed by HPLC by monitoring the remaining caged compound.
The two-photon uncaging cross section du was calculated as fol-
lows [Eq. (2)]:
6-Bromo-2-{[(tert-butyldimethylsilyl)oxy]methyl}quinoline (7)
A solution of alcohol 6 (2.00 g, 8.00 mmol, 1.0 equiv), TBSCl (1.40 g,
9.00 mmol, 1.1 equiv) and imidazole (623 mg, 9.00 mmol, 1.1 equiv)
in DMF (20 mL) was stirred at RT overnight, and then the solvent
was removed under reduced pressure. CH2Cl2 was added and the
organic phase was washed with water and brine, dried over
Na2SO4, filtered and concentrated under reduced pressure. The
crude product was purified by column chromatography on silica
gel (cyclohexane/EtOAc 9:1) to afford the corresponding protected
1
alcohol 7 as a white solid (2.30 g, 80%). H NMR (250 MHz, CDCl3):
d=7.98 (d, J=8.5 Hz, 1H), 7.88–7.78 m, 2H), 7.67 (d, J=8.0 Hz,
2H), 4.95 (s, 2H), 0.96 (s, 9H), 0.13 ppm (s, 6H); 13C NMR (63 MHz,
CDCl3): d=162.3, 145.8, 135.5, 132.8, 130.4, 129.6, 128.4, 119.6,
119.2, 66.6, 25.9, 18.3, ꢀ5.3 ppm; MS (ESI): m/z: 351.9, 353.9
[M+H]+; HRMS (ESI): m/z: calcd for C16H23BrNOSi: 352.0732,
354.0712 [M+H]+; found: 352.0743, 354.0726.
ꢀ
ꢁ
2
VtPf hc
ð2Þ
du ¼ 3:41 ꢂ conversion ꢂ
P
pnlt
where du is the TP uncaging cross-section [cm4 s per photon], V is
the sample volume (45ꢂ10ꢀ3 cm3), tP is the pulse width, f=80ꢂ
106 Hz; n=1.3, l is the wavelength [cm], t is the exposure time [s],
h=6.6ꢂ10ꢀ34 Js, c=3ꢂ1010 cmsꢀ1, and P is the average power
[W].
2-{[(tert-Butyldimethylsilyl)oxy]methyl}quinolin-6-amine (8)
The protected bromoquinoline 7 (600 mg, 1.70 mmol, 1.0 equiv),
copper iodide (65 mg, 0.30 mmol, 20 mol%), l-proline (78 mg,
0.70 mmol, 40 mol%) and K2CO3 (705 mg, 5.0 mmol, 3.0 equiv)
were dissolved in DMSO (20 mL). Aqueous ammonia (28%, 1.6 mL,
45.4 mmol, 25 equiv) was then introduced and the mixture was
heated at 808C for 18 h. After cooling to RT, CH2Cl2 was added fol-
lowed by saturated NH4Cl solution. The aqueous layer was extract-
ed twice with CH2Cl2, and the combined organic layers were
washed again with a saturated NH4Cl solution. The product was
purified by column chromatography on silica gel (cyclohexane/
EtOAc 1:1) to afford 8 as a white solid (284 mg, 58%). 1H NMR
(250 MHz, CDCl3): d=7.91 (d, J=8.5 Hz, 1H), 7.83 (d, J=8.8 Hz,
1H), 7.57 (d, J=8.5 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 6.86 (brs, 1H),
4.96 (s, 2H), 3.99 (brs, 2H), 0.98 (s, 9H), 0.14 ppm (s, 6H); 13C NMR
(63 MHz, CDCl3): d=157.9, 144.3, 142.3, 134.5, 129.7, 128.8, 121.6,
118.9, 107.6, 66.8, 26.0, 18.4, ꢀ5.2 ppm; MS (ESI): m/z: 289.2
[M+H]+; HRMS (ESI): m/z: calcd for C16H25N2OSi: 289.1736 [M+H]+;
found: 289.1732.
Synthesis of 1b
6-Bromoquinoline-2-carbaldehyde (5)
A mixture of selenium dioxide (1.30 g, 12.0 mmol, 1.3 equiv) in di-
oxane (50 mL) was heated at 808C for 30 min, then quinaldine 4
(2.0 g, 9.0 mmol, 1.0 equiv) was introduced and the mixture was
stirred 3 h at 808C. After cooling to RT, the mixture was filtered
through Celite and eluted with CH2Cl2 to give 5 as a crude a white
solid (2.10 g, 97%), which was used without further purification for
the next step. 1H NMR (250 MHz, CDCl3): d=9.94 (s, 1H), 7.96 (d,
J=8.5 Hz, 1H), 7.84 (d, J=9.0 Hz, 1H), 7.82–7.75 (m, 2H), 7.62 ppm
(dd, J=9.0, 2.0 Hz, 1H); 13C NMR (63 MHz, CDCl3): d=193.3, 152.8,
146.5, 136.5, 134.2, 132.1, 131.0, 130.0, 123.7, 118.3 ppm; MS (ESI):
m/z: 236.1, 238.1 [M+H]+, 268.0. 270.0 (hemiacetal), 282.2, 284.1
(acetal); HRMS (ESI): m/z: calcd for C10H879BrNO+H+: 235.9771
[M+H]+; found: 235.9781.
Tris(2-{[(tert-butyldimethylsilyl)oxy]methyl}quinolin-6-yl)amine
(9)
In a glove box, the amino derivative 8 (100 mg, 0.30 mmol,
1.0 equiv), the bromo derivative 7 (269 mg, 0.80 mmol, 2.2 equiv),
[Pd2(dba)3] (70 mg, 0.07 mmol, 20 mol%) and tBuONa (73 mg,
0.80 mmol, 2.2 equiv) were introduced into a sealed tube. Tri-tert-
butylphosphine (1m in toluene, 64 mL, 0.30 mmol, 80 mol%) and
distilled toluene (1.7 mL) were added and the tube was sealed. The
mixture was heated at 1108C for 18 h. After cooling to RT, CH2Cl2
was added and the organic layer was washed twice with water
and brine, dried over Na2SO4, and concentrated under reduced
pressure. The crude product was purified by column chromatogra-
phy on silica gel (cyclohexane/EtOAc 9:1) to afford 9 as a yellow
(6-Bromoquinolin-2-yl)methanol (6)
NaBH4 (28 mg, 0.75 mmol, 1.0 equiv) was added to a mixture of
carbaldehyde 5 (177 mg, 0.75 mmol, 1.0 equiv) and EtOH (5 mL) at
08C. The mixture was stirred at RT for 30 min before being
quenched with HCl (1m). The EtOH was evaporated and CH2Cl2
was added to the residue. The organic layer was washed with
water (twice) and brine, dried over Na2SO4, filtered and concentrat-
ed under reduced pressure to afford 7 as a white solid (152 mg,
1
1
85%). H NMR (500 MHz, CDCl3): d=8.03 (d, J=8.5 Hz, 1H), 7.97 (d,
powder (197 mg, 79%). H NMR (250 MHz, CDCl3): d=8.18 (s, 1H),
J=2.0 Hz, 1H), 7.92 (d, J=9.0 Hz, 1H), 7.77 (dd, J=9.0, 2.0 Hz, 1H),
7.31 (d, J=8.5 Hz, 1H), 4.90 (s, 2H), 4.36 ppm (brs, 1H); 13C NMR
(125 MHz, CDCl3): d=159.8, 145.5, 135.9, 133.4, 130.5, 129.9, 128.8,
120.3, 119.4, 64.4 ppm; MS (ESI): m/z: 238.0, 240.0 [M+H]+; HRMS
(ESI): m/z: calcd for C10H9BrNO: 237.9868, 239.9847 [M+H]+; found:
237.9872, 239.9852.
8.11 (d, J=8.5 Hz, 1H), 7.69 (d, J=8.5 Hz, 1H), 7.63 (d, J=8.5 Hz,
1H), 7.55 (d, J=8.5 Hz, 1H), 4.98 (s, 2H), 0.97 (s, 9H), 0.14 ppm (s,
6H); 13C NMR (63 MHz, CDCl3): d=160.9, 145.0, 144.7, 135.7, 130.2,
128.4, 128.0, 120.4, 119.1, 66.8, 26.0, 18.5, ꢀ5.2 ppm; MS (ESI): m/z:
831.3 [M+H]+; HRMS (ESI): m/z: calcd for C48H67N4O3Si3: 831.4521
[M+H]+; found: 831.4560.
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butylphosphine (1m in toluene, 64 mL, 0.30 mmol, 80 mol%) and
toluene (1.7 mL) were added and the tube was sealed. The mixture
was heated at 1108C for 18 h. After cooling to RT, CH2Cl2 was
added and the organic layer was washed twice with water and
brine, dried over Na2SO4, and concentrated under reduced pres-
sure. The crude product was purified by column chromatography
on silica gel (cyclohexane/EtOAc 9:1) to afford 16 as a yellow
[Nitrilotris(quinoline-6,2-diyl)]trimethanol (10)
HF–pyridine (16 mL, 0.27 mmol, 7.5 equiv) was added to the TBS-
protected alcohol 9 (35 mg, 0.04 mmol, 1.0 equiv) in MeCN (1 mL)
at 08C, and the mixture was stirred at RT for 2 h in the dark. After
completion of the reaction, saturated NaHCO3 solution was added
and the mixture was concentrated under reduced pressure. A 1:1
mixture of CH2Cl2 and water (30 mL) was added to the residue and
the organic phase was washed with water and brine, dried over
Na2SO4, filtered and concentrated under reduced pressure to afford
1
powder (350 mg, 83%). H NMR (250 MHz, CDCl3): d=8.06 (d, J=
8.3 Hz, 1H), 7.63 (d, J=9.3 Hz, 1H), 7.60 (s, 1H), 7.55 (d, J=8.3 Hz,
1H), 7.27 (dd, J=8.8, 2.3 Hz, 1H), 4.97 (s, 2H), 0.98 (s, 9H),
0.15 ppm (s, 6H); 13C NMR (63 MHz, CDCl3): d=162.5, 148.7, 148.4,
136.3, 128.9, 124.6, 124.5, 122.3, 117.5, 66.9, 26.1, 18.5, ꢀ5.2 ppm;
MS (ESI): m/z: 831.2 [M+H]+; HRMS (ESI): m/z: calcd for
C48H67N4O3Si3: 831.4521 [M+H]+; found: 831.4517.
1
10 as a yellow oil (14 mg, 70%). H NMR (500 MHz, [D4]MeOH): d=
8.90 (d, J=2.5 Hz, 1H), 8.46 (d, J=6.5 Hz, 1H), 8.11 (s, 1H), 8.08 (d,
J=6.5 Hz, 1H), 7.99 (d, J=3.5 Hz, 1H), 5.22 ppm (s, 2H); 13C NMR
(125 MHz, [D4]MeOH): d=161.3, 148.0, 146.8, 136.7, 133.6, 131.1,
123.9, 123.5, 121.7, 62.0 ppm; MS (ESI): m/z: 489.1 [M+H]+; HRMS
(ESI): m/z: calcd for C30H25N4O3: 489.1927 [M+H]+; found: 489.1916.
[7,7’,7’’-Nitrilotris(quinoline-7,2-diyl)]trimethanol (17)
[Nitrilotris(quinoline-6,2-diyl)]tris(methylene) Triacetate (1b)
HF–pyridine (16 mL, 0.27 mmol, 7.5 equiv) was added to the TBS-
protected alcohol 16 (30 mg, 0.04 mmol, 1.0 equiv) in MeCN (1 mL)
at 08C, and the mixture was stirred at RT for 2 h in the dark. After
completion of the reaction, saturated NaHCO3 solution was added
and the mixture was concentrated under reduced pressure. A mix-
ture of CH2Cl2 and water (1:1, 30 mL) was added to the residue
and the organic phase was washed with water and brine, dried
over Na2SO4, filtered and concentrated under reduced pressure.
The crude product was purified by column chromatography on
silica gel (CH2Cl2/MeOH 95:5) to afford 17 as a yellow oil (15 mg,
85%). 1H NMR (250 MHz, [D6]DMSO): d=7.82 (d, J=8.3 Hz, 1H),
7.45 (d, J=8.5 Hz, 1H), 7.06 (d, J=8.5 Hz, 1H), 7.03 (s, 1H), 6.93 (d,
J=8.8 Hz, 1H), 5.00 (t, J=5.5 Hz, 1H), 4.14 ppm (d, J=5.5 Hz, 2H);
13C NMR (125 MHz, [D6]DMSO): d=163.1, 147.9, 147.5, 136.1, 129.3,
124.1, 123.9, 121.0, 118.0, 64.7 ppm; MS (ESI): m/z: 489.2 [M+H]+;
HRMS (ESI): m/z: calcd for C30H25N4O3: 489.1927 [M+H]+; found:
489.1952.
Triol 10 (11 mg, 0.02 mmol, 1.0 equiv), triethylamine (14 mL,
0.10 mmol, 4.5 equiv), acetic anhydride (10 mL, 0.10 mmol,
4.5 equiv) and a catalytic amount of DMAP were dissolved in
CH2Cl2 (100 mL) and the mixture was stirred at RT for 2 h in the
dark. The crude product was purified by column chromatography
on silica gel (CH2Cl2/MeOH 95:5) to afford 1b as a yellow oil
1
(11 mg, 89%). H NMR (500 MHz, CDCl3): d=8.10 (d, J=8.0 Hz, 1H),
7.74 (s, 1H), 7.74 (d, J=9.0 Hz, 1H), 7.46 (dd, J=9.0, 2.0 Hz, 1H),
7.37 (d, J=9.0 Hz, 1H), 5.29 (s, 2H), 2.16 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): d=170.8, 155.3, 145.5, 145.1, 136.1, 130.8, 128.7,
128.3, 120.4, 120.4, 67.4, 27.2 ppm; MS (ESI): m/z: 615.3 [M+H]+;
HRMS (ESI): m/z: calcd for C36H31N4O6: 615.2244 [M+H]+; found:
615.2233.
Synthesis of 2b
2-{[(tert-Butyldimethylsilyl)oxy]methyl}quinolin-7-amine (15)
[7,7’,7’’-Nitrilotris(quinoline-7,2-diyl)]tris(methylene) Triacetate
The protected bromoquinoline 14 (1.00 g, 2.84 mmol, 1.0 equiv),
copper iodide (109 mg, 0.57 mmol, 20 mol%), l-proline (116 mg,
1.14 mmol, 40 mol%) and K2CO3 (1.2 g, 8.52 mmol, 3.0 equiv) were
dissolved in DMSO (4 mL). Aqueous ammonia (28%) (1 mL,
28.4 mmol, 10 equiv) was then introduced and the mixture was
heated at 808C for 18 h. After cooling to RT, CH2Cl2 was added fol-
lowed by saturated NH4Cl solution. The aqueous layer was extract-
ed twice with CH2Cl2, and the combined organic layers were
washed again with a saturated NH4Cl solution. The product was
purified by column chromatography on silica gel (cyclohexane/
EtOAc 3:1) to afford 15 as a white solid (200 mg, 35%). 1H NMR
(500 MHz, CDCl3): d=7.99 (d, J=9.0 Hz, 1H), 7.57 (d, J=8.0 Hz,
1H), 7.42 (d, J=9.0 Hz, 1H), 7.14 (d, J=2.0 Hz, 1H), 6.92 (dd, J=
9.0, 2.0 Hz, 1H), 4.95 (s, 2H), 4.09 (brs, 2H), 0.96 (s, 9H), 0.13 ppm
(d, 6H); 13C NMR (63 MHz, CDCl3): d=162.1, 149.2, 147.9, 136.3,
128.8, 121.4, 118.1, 115.0, 108.8, 66.9, 26.0, 18.4, ꢀ5.2 ppm; MS
(ESI): m/z: 289.2 [M+H]+; HRMS (ESI): m/z: calcd for C16H25N2OSi:
289.1736 [M+H]+; found: 289.1742.
(2b)
Triol 17 (15 mg, 0.03 mmol, 1.0 equiv), triethylamine (19 mL,
0.1 mmol, 4.5 equiv), acetic anhydride (13 mL, 0.1 mmol, 4.5 equiv)
and a catalytic amount of DMAP were dissolved in CH2Cl2 (100 mL)
and the mixture was stirred at RT for 2 h in the dark. The crude
product was purified by column chromatography on silica gel
(CH2Cl2/MeOH 95:5) to afford 2b as a yellow oil (16 mg, 88%).
1H NMR (500 MHz, CDCl3): d=8.11 (d, J=8.5 Hz, 1H), 7.75 (d, J=
8.5 Hz, 1H), 7.75 (d, J=2.5 Hz, 1H), 7.47 (dd, J=8.5, 2.0 Hz, 1H),
7.38 (d, J=8.5 Hz, 1H), 5.30 (s, 2H), 2.17 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): d=170.8, 156.9, 149.1, 148.4, 136.6, 129.0, 125.2,
124.9, 122.6, 118.7, 67.5, 21.1 ppm; MS (ESI): m/z: 615.1 [M+H]+;
HRMS (ESI): m/z: calcd for C36H31N4O6: 615.2244 [M+H]+; found:
615.2221.
Synthesis of 3b
N1,N1-Bis(2-aminophenyl)benzene-1,2-diamine[11]
(18,
822 mg,
2.83 mmol, 1.0 equiv) was dissolved in a solution of HCl (6m,
20 mL). After addition of crotonaldehyde (1.40 mL, 16.90 mmol,
6.0 equiv) the mixture was stirred for 1 h at RT. Then, toluene
(5 mL) was added and the reaction was heated at 808C for 3 h.
After cooling to RT the organic layer was removed. The aqueous
layer was neutralized with NaOH pellets and the solution was ex-
tracted with CH2Cl2. Then the organic layer was washed with water
Tris(2-{[(tert-butyldimethylsilyl)oxy]methyl}quinolin-7-yl)amine
(16)
In a glove box, the amino derivative 15 (100 mg, 0.30 mmol,
1.0 equiv), the bromo derivative 14 (269 mg, 0.80 mmol, 2.2 equiv),
[Pd2(dba)3] (70 mg, 0.07 mmol, 20 mol%) and tBuONa (73 mg,
0.80 mmol, 2.2 equiv) were introduced into a sealed tube. Tri-tert-
&
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and brine, dried over Na2SO4, filtered and concentrated under re-
duced pressure. The crude product was purified by column chro-
matography on silica gel (cyclohexane/EtOAc 2:1), to afford the
single (19a, 140 mg, 14%) and double (19b, 150 mg, 12%) cycliza-
tion products.
[8,8’,8’’-Nitrilotris(quinoline-8,2-diyl)]trimethanol (21)
NaBH4 (22 mg, 0.59 mmol, 4.5 equiv) was added to trisaldehyde 20
(63 mg, 0.13 mmol, 1.0 equiv) in EtOH (0.5 mL) at 08C and the mix-
ture was stirred at RT for 1 h before being quenched with aq HCl
(1m). After removing the EtOH under reduced pressure, water was
added to the residue, then the mixture was extracted with CH2Cl2.
The combined organic phases were washed twice with water and
brine, dried over Na2SO4, filtered and evaporated to dryness. The
product 21 was obtained as a beige solid (30 mg, 47%) and was
used without further purification. 1H NMR (250 MHz, CDCl3): d=
8.08 (d, J=8.5 Hz, 3H), 7.58 (dd, J=5.3, 4.3 Hz, 3H), 7.43–7.35 (m,
6H), 7.04 (d, J=8.5 Hz, 3H), 4.42 (s, 6H), 3.27 ppm (brs, 3H);
13C NMR (63 MHz, CDCl3): d=157.3, 147.5, 141.7, 137.2, 129.1,
126.7, 125.5, 123.1, 118.2, 63.4 ppm; MS (ESI): m/z: 489.3 [M+H]+;
HRMS (ESI): m/z: calcd for C30H24N4O3Na: 511.1741 [M+Na]+; found:
511.1766.
Reacting the bisquinoline product 19b (200 mg, 0.51 mmol,
1.0 equiv) in the cyclization with crotonaldehyde (0.13 mL,
1.53 mmol, 3.0 equiv) at 1208C for 3 h yielded, after work-up and
purification as described above, the threefold cyclization product
19c (92 mg, 41%).
N1-(2-Aminophenyl)-N1-(2-methylquinolin-8-yl)benzene-1,2-di-
amine (19a)
Yellow oil. 1H NMR (250 MHz, CDCl3): d=7.95 (d, J=8.3 Hz, 1H),
7.48 (dd, J=8.3, 1.5 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 7.22 (dd, J=
7.5, 1.5 Hz, 1H), 7.17 (d, J=8.3 Hz, 1H), 6.97 (td, J=7.3, 1.5 Hz, 2H),
6.90 (dd, J=7.8, 1.5 Hz, 2H), 6.75 (dd, J=7.8, 1.5 Hz, 2H), 6.64 (td,
J=7.3, 1.5 Hz, 2H), 3.96 (brs, 4H), 2.47 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): d=157.5, 144.6, 143.1, 142.6, 136.1, 135.1, 128.0,
126.9, 125.7, 125.5, 123.0, 122.8, 122.1, 118.5, 116.3, 25.5 ppm; MS
(ESI): m/z: 341.6 [M+H]+; HRMS (ESI): m/z: calcd for C22H21N4:
341.1761 [M+H]+; found: 341.1748.
[8,8’,8’’-Nitrilotris(quinoline-8,2-diyl)]tris(methylene) Triacetate
(3b)
Triol 21 (30 mg, 0.06 mmol, 1.0 equiv), triethylamine (38 mL,
0.27 mmol, 4.5 equiv), acetic anhydride (26 mL, 0.27 mmol,
4.5 equiv) and a catalytic amount of DMAP were dissolved in
CH2Cl2 (500 mL) and the mixture was stirred at RT for 2 h in the
dark. The crude product was then purified by column chromatog-
raphy on silica gel (CH2Cl2/MeOH 95:5) to afford 3b as a yellow oil
N1,N1-Bis(2-methylquinolin-8-yl)benzene-1,2-diamine (19b)
1
(20 mg, 54%). H NMR (250 MHz, CDCl3): d=8.10 (d, J=8.5 Hz, 3H),
Yellow oil. 1H NMR (250 MHz, CDCl3): d=7.92 (d, J=8.3 Hz, 2H),
7.40 (dd, J=8.3, 1.3 Hz, 2H), 7.26 (dd, J=8.1, 7.5 Hz, 2H), 7.13–7.01
(m, 6H), 6.83 (dd, J=8.0, 1.5 Hz, 1H), 6.67 (td, J=7.3, 1.5 Hz, 1H),
4.55 (brs, 2H), 2.17 ppm (s, 3H); 13C NMR (63 MHz, CDCl3): d=
156.0, 146.5, 145.2, 142.8, 135.9, 135.7, 129.3, 127.7, 126.5, 125.7,
122.1, 121.6, 121.3, 118.3, 116.5, 25.1 ppm; MS (ESI): m/z: 391.7
[M+H]+; HRMS (ESI): m/z: calcd for C26H23N4: 391.1917 [M+H]+;
found: 391.1907.
7.49 (dd, J=7.5, 1.5 Hz, 3H), 7.31 (d, J=7.5 Hz, 3H), 7.27–7.21 (m,
6H), 4.67 (s, 6H), 1.97 ppm (s, 9H); 13C NMR (63 MHz, CDCl3): d=
170.6, 153.7, 147.7, 142.5, 136.8, 128.8, 126.7, 125.2, 122.4, 118.6,
67.6, 20.9 ppm; MS (ESI): m/z: 615.5 [M+H]+, 637.5 [M+Na]+;
HRMS (ESI): m/z: calcd for C36H31N4O6: 615.2238 [M+H]+; found:
615.2224.
Acknowledgements
Tris(2-methylquinolin-8-yl)amine (19c)
This research was supported by the Marie Curie Intra-European
Fellowship within the Seventh European Community Framework
Program (FP7-PEOPLE-2013-IEF: 629675) to P.D., and also by the
ANR-TP-Photolysis grants. M.B.-D. gratefully acknowledges Con-
seil Rꢀgional d’Aquitaine for financial support (Chaire d’Accueil
grant). Dr. Marina Charlot and Vincent Hugues are also acknowl-
edged for their contribution to two-photon absorption measure-
ments.
Yellow oil. 1H NMR (250 MHz, CDCl3): d=7.94 (d, J=8.5 Hz, 3H),
7.46 (dd, J=6.3, 3.0 Hz, 3H), 7.29–7.21 (m, 6H), 7.03 (d, J=8.5 Hz,
3H), 2.14 ppm (s, 9H); 13C NMR (63 MHz, CDCl3): d=156.2, 147.6,
142.7, 135.7, 127.6, 125.4, 124.8, 121.9, 121.1, 25.1 ppm; MS (ESI):
m/z: 441.4 [M+H]+; HRMS (ESI): m/z: calcd for C30H26N4: 441.2074
[M+H]+; found: 441.2082.
8,8’,8’’-Nitrilotris(quinoline-2-carbaldehyde) (20)
Conflict of Interest
A mixture of selenium dioxide (48 mg, 0.43 mmol, 3.3 equiv) and
dioxane (2.5 mL) was heated at 808C for 30 min. Trisquinaldine
19c (57 mg, 0.13 mmol, 1.0 equiv) was then introduced and the
mixture was stirred for 3 h at 808C. After cooling to RT, the mixture
was filtered through Celite, eluted with CH2Cl2 and the solvents
were evaporated under reduced pressure. The product 20 was ob-
tained as a beige solid (60 mg, 95%) and was used without further
The authors declare no conflict of interest.
Keywords: caged compounds · nonlinear optics · photolysis ·
protecting groups · reactive intermediates
1
purification. H NMR (250 MHz, CDCl3): d=9.03 (s, 1H), 8.26 (d, J=
[1] For selected reviews, see: a) A. S. Lubbe, W. Szymanski, B. L. Feringa,
Chem. Soc. Rev. 2017, 46, 1052–1079; b) D. Brinks, Y. Adam, S. Kheifets,
A. E. Cohen, Acc. Chem. Res. 2016, 49, 2518–2526; c) D. Blꢃger, S. Hecht,
Angew. Chem. Int. Ed. 2015, 54, 11338–11349; Angew. Chem. 2015, 127,
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8.5 Hz, 1H), 7.83 (d, J=8.5 Hz, 1H), 7.62 (dd, J=7.8, 1.8 Hz, 1H),
7.49 (t, J=7.8 Hz, 1H), 7.43 ppm (dd, J=7.8, 1.8 Hz, 1H); 13C NMR
(125 MHz, CDCl3): d=193.6, 150.7, 149.0, 142.9, 137.6, 131.5, 129.6,
125.8, 123.1, 117.0 ppm; MS (ESI): m/z: 505.3 [M+Na]+, 537.3 (hem-
iacetal), 569.4 (hemiacetal), 601.4 (hemiacetal); HRMS (ESI): m/z:
calcd for C30H18N4O3Na: 505.1271 [M+Na]+; found: 505.1293.
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Received: May 18, 2017
Version of record online && &&, 2017
&
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ꢀ 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

FULL PAPERS
Let out of the cage: The incorporation
of third-order rotational symmetry into
quinoline-derived light-sensitive probes
results in improved linear and nonlinear
photophysical properties compared to
the corresponding monomers. The two-
photon uncaging cross-section is un-
affected.
P. Dunkel, M. Petit, H. Dhimane,
M. Blanchard-Desce, D. Ogden,
P. I. Dalko*
&& – &&
Quinoline-Derived Two-Photon-
Sensitive Octupolar Probes
ChemistryOpen 2017, 00, 0 – 0
www.chemistryopen.org
9
ꢀ 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ