Photoactivatable anthracenes

Article abstract of DOI:10.1021/jo5004482

Fifteen substituted maleimide cycloadducts of anthracene derivatives were synthesized in one or two steps from available precursors in yields ranging from 32 to 63%. They differ in the nature of the group on the maleimide nitrogen atom and of the substituents on the anthracene platform. In all instances, the introduction of a maleimide bridge across positions 9 and 10 of the anthracene skeleton isolates electronically its peripheral phenylene rings and suppresses its characteristic fluorescence. The cycloadducts with a 4-(dimethylamino)phenyl group on the maleimide nitrogen atom undergo retro-cycloaddition upon ultraviolet illumination with quantum yields ranging from 0.001 to 0.01. This structural transformation restores the aromatic character of the central ring of the oligoacene chromophore and activates its emission with fluorescence quantum yields ranging from 0.07 to 0.85. Thus, this particular choice of building blocks for the construction of photoresponsive compounds can translate into viable operating principles for fluorescence activation and, ultimately, lead to the realization of valuable photoactivatable fluorophores for imaging applications.

Full text of DOI:10.1021/jo5004482

Article
pubs.acs.org/joc
Photoactivatable Anthracenes
Ek Raj Thapaliya, Burjor Captain, and Franci̧ sco M. Raymo*
Laboratory for Molecular Photonics, Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida
33146-0431, United States
S
* Supporting Information
ABSTRACT: Fifteen substituted maleimide cycloadducts of anthra-
cene derivatives were synthesized in one or two steps from available
precursors in yields ranging from 32 to 63%. They differ in the nature
of the group on the maleimide nitrogen atom and of the substituents
on the anthracene platform. In all instances, the introduction of a
maleimide bridge across positions 9 and 10 of the anthracene
skeleton isolates electronically its peripheral phenylene rings and
suppresses its characteristic fluorescence. The cycloadducts with a 4-
(dimethylamino)phenyl group on the maleimide nitrogen atom
undergo retro-cycloaddition upon ultraviolet illumination with
quantum yields ranging from 0.001 to 0.01. This structural
transformation restores the aromatic character of the central ring of
the oligoacene chromophore and activates its emission with fluorescence quantum yields ranging from 0.07 to 0.85. Thus, this
particular choice of building blocks for the construction of photoresponsive compounds can translate into viable operating
principles for fluorescence activation and, ultimately, lead to the realization of valuable photoactivatable fluorophores for imaging
applications.
The anthracene skeleton is a convenient building block for
the construction of photoactivatable fluorophores. In fact, early
examples of fluorescence photoactivation were designed around
the structural and spectroscopic properties of this particular
chromophore.19,20 These seminal studies were aimed at the
development of photosensitive materials for photographic
applications and relied on the introduction of a photocleavable
anhydride bridge across positions 9 and 10 of the anthracene
platform. This particular bridging unit was designed to isolate
electronically the two peripheral phenylene rings of the
oligoacene skeleton and suppress its characteristic fluorescence.
Upon ultraviolet illumination, the anhydride bridge cleaves into
a molecule of carbon dioxide and one of carbon monoxide to
restore the aromatic character of the central benzene ring
together with the emission of the regenerated anthracene
fluorophore. Similarly, two carbon atoms within one of the
multiple rings on an oligoacene chromophore can also be
connected through an α-diketone bridge to interrupt electronic
delocalization across the aromatic platform.21−25 This particular
functional group cleaves into two molecules of carbon
monoxide upon excitation to restore the parent oligoacene
and its spectroscopic signature. In fact, these operating
principles have also been exploited to activate the fluorescence
of a few anthracene derivatives.24h,i,25
INTRODUCTION
■
The photochemical conversion of a nonemissive reactant into
an emissive product offers the opportunity to activate
fluorescence under the influence of optical stimulations.1−6
Specifically, a pair of independent irradiation sources, operating
at distinct wavelengths, can excite reactant and product
respectively to induce the photochemical transformation of
the former and the emission of the latter. Under these
conditions, the spatial overlap of the two illuminating beams
and their temporal interplay permits the activation of
fluorescence exclusively within a defined region of space at a
given interval of time. In turn, the sequential acquisition of
fluorescence images, after a single activation event, enables the
monitoring of the translocation of the activated emitters in real
time.7−12 Alternatively, the sequential localization of emitters,
activated at distinct intervals of time, with single-molecule
precision allows the reconstruction of images with spatial
resolution at the nanometer level.13−18 These ingenious
imaging schemes provide the possibility to track dynamic
events and visualize nanoscaled features respectively in a
diversity of specimens and, therefore, are becoming particularly
valuable in biological and materials sciences. Nonetheless, their
practical implementation is simply impossible with conven-
tional fluorophores and, instead, strictly demands the unique
combination of photochemical and photophysical properties
associated with their photoactivatable counterparts. Thus, the
identification of viable structural designs to photoactivate
fluorescence is essential to foster the further development of
such promising analytical techniques.
As an alternative to the introduction of photocleavable
carbonyl groups, the cycloaddition of appropriate dienophiles
to the central ring of anthracene derivatives can also isolate
Received: February 24, 2014
© XXXX American Chemical Society
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electronically the peripheral phenylene rings with photo-
responsive bridges.26−29 Specifically, a handful of alkenes and
a few acylnitroso compounds form photolabile cycloadducts
capable of undergoing retro-cycloadditions under illumination
to restore the aromatic character of the oligoacene platform.
The synthetic accessibility of these particular cycloadducts,
together with the opportunity to regulate the spectroscopic
signature of the anthracene chromophore with the manipu-
lation of its substituents, can translate into the realization of
versatile photoactivatable fluorophores. Nonetheless, the
potential of these photochemical transformations to activate
fluorescence remains essentially unexplored. These consider-
ations suggest the possibility of assembling a series of
anthracene cycloadducts differing in their substituents with
the ultimate goal of identifying an optimal structural design for
fluorescence photoactivation. Indeed, this paper reports the
synthesis of a family of N-arylmaleimide cycloadducts, their
structural characterization, as well as the investigation of their
photochemical and photophysical properties.
This compound is a valuable precursor for the generation of an
entire family of anthracene cycloadducts, differing in the nature
of the bridging unit. Specifically, treatment of 1 with primary
amines 2−11, in the presence of potassium carbonate, produces
imides 12−21 in yields ranging from 32 to 63%.31
In addition to varying the group on the maleimide bridge,
substituents can be introduced on either the two o-phenylene
rings or positions 9 and 10 of these anthracene cycloadducts.
Specifically, the cycloaddition of maleimide 22 (Figure 2) on
RESULTS AND DISCUSSION
■
Figure 2. Synthesis of 26−28.
Synthesis and Structural Characterization. The cyclo-
addition of maleic anhydride on the central ring of anthracene
introduces a bridge between positions 9 and 10 of the
oligoacene platform in the shape of cycloadduct 1 (Figure 1).30
the central ring of substituted anthracenes 23−25 generates
adducts 26−28 in yields ranging from 36 to 55%. Alternatively,
reaction of maleic anhydride (29 in Figure 3) with substituted
anthracenes 30 and 31 produces anhydrides 32 and 33,
respectively.31 Treatment of these compounds with 6, in the
presence of potassium carbonate, produces 34 and 35 in yields
of 55 and 45% respectively.
The structural identity of all compounds was confirmed by
electrospray ionization mass spectrometry as well as 1H and 13C
nuclear magnetic resonance (NMR) spectroscopies (Figures
S1−S12, Supporting Information). In addition, single crystals
suitable for X-ray diffraction analysis were obtained for 15, 16,
18−21, 28, 34, and 35. The resulting structures (Figure 4 and
Tables S1−S3, Supporting Information) clearly reveal the
maleimide bridge across positions 9 and 10 of the anthracene
platform in all instances. The sp3 hybridization of the two
bridgehead carbon atoms forces the peripheral o-phenylene
rings out of planarity and interrupts electronic delocalization, in
agreement with the rationale behind the design of these
compounds.
Photochemical and Photophysical Properties. The
absorption spectrum of anthracene (36 in Figure 5) in
acetonitrile shows the characteristic vibronic structure of this
oligoacene chromophore between 300 and 390 nm (Figure 5,
a). Excitation within this range of wavelengths results in intense
fluorescence (Figure 5, b). The introduction of a maleimide
bridge across positions 9 and 10 isolates electronically the two
peripheral phenylene rings, alters drastically the absorption
spectrum and suppresses fluorescence. For example, the
absorption and emission spectra (Figure 5, c and d) of adduct
12 do not reveal any bands at wavelengths longer than 300 nm,
under otherwise identical experimental conditions.
Ultraviolet illumination (254 nm, 0.4 mW cm−2) of adducts
12−21 in acetonitrile results in noticeable absorption and
emission changes only for 16 and 17. Specifically, comparison
of the absorption and emission spectra recorded before (Figure
6, a and b) to those measured after (Figure 6, c and d)
irradiation of 16 reveals the appearance of the characteristic
anthracene bands. Indeed, retro-cycloaddition of 16 occurs
upon excitation to form 22 and 36. A plot of the absorbance
Figure 1. Synthesis of 12−21.
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Figure 3. Synthesis of 34 and 35.
Figure 4. ORTEP representations of the geometries adopted by 15, 16, 18−21, 28, 34, and 35 in single crystals, showing 30% (15, 34), 40% (19,
20, 21), and 50% (16, 18, 28, 35) thermal ellipsoid probability.
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Table 1. Quantum Yield (ϕP) for the Photochemical Retro-
cycloadditions and Fluorescence Quantum Yield (ϕF) of the
a
Resulting Anthracenes
ϕP
ϕF
16 → 36
28 → 25
34 → 30
35 → 31
0.001
0.01
0.27
0.07
0.43
0.85
0.001
0.002
a
All measurements were performed in aerated MeCN at 25 °C.
Samples were illuminated at 254 nm. The irradiation power per unit
area (0.4 mW cm−2) was measured with a potassium ferrioxalate
actinometer, and this value was used to determine ϕP from the
corresponding absorbance evolution during photolysis, according to an
established procedure (ref 33). The values of ϕF listed for 25, 30, and
36 are literature data (ref 35), and that of 31 was determined against
an EtOH solution of 9,10-diphenylanthracene. The value of ϕF for this
standard is 0.95 (ref 34).
Figure 5. Absorption and emission spectra (MeCN, 25 °C, λEx = 350
nm) of 36 (30 μM, a and b) and 12 (0.1 mM, c and d).
estimated wavelength (λCal) and oscillator strength (f Cal) of
259 nm and 0.179 respectively (Table S3, Supporting
Information). Instead, λCal for the S0 → S1 transition is 321
nm with a fCal of only 0.004, in agreement with the presence of
a relatively weak band in the experimental spectrum (Figure 7,
b) at this wavelength. Visualization of the main orbital pair
responsible for this electronic transition reveals that the
highest-occupied molecular orbital (HOMO in Figure 7) is
mostly localized on the 4-(dimethylamino)phenyl ring, while
the lowest unoccupied molecular orbital (LUMO in Figure 7)
is predominantly on the imide group. In fact, the orthogonal
arrangement of one relative to the other, evident also in the
crystal structure (Figure 4), isolates electronically the two
groups in the ground state. Thus, the population of S1 results
essentially in the formal transfer of one electron from the 4-
(dimethylamino)phenyl ring to the imide group.
The dissociation of adduct 16 into diene 36 and dienophile
22 can be simulated by elongating stepwise one of the two [C−
C] bonds joining the anthracene and maleimide fragments. The
energies for S0, S1, and T1 of the optimized geometries at each
step can then be plotted against the bond length to build the
reaction profiles illustrated in Figure 8. In S0, the energy
increases monotonically and dramatically with bond length in
full agreement with experiments, which did not reveal any
thermal dissociation of the cycloadduct into its constituent
components even after heating for prolonged time.32 In fact,
frequency calculations indicate the free energy of the transition
state, found along this reaction path, to be 33.94 kcal mol−1
greater than that of 16 (Figure 9). Instead, the free energy of
the two separate products is only 3.67 kcal mol−1 higher than
that of the cycloadduct.
In contrast to the reaction profile in S0 (Figure 8), the energy
remains almost constant in S1 (ΔE < 0.2 eV) and, after a
modest initial increase (ΔE = 0.6 eV), decreases significantly in
T1. Thus, the retro-cycloaddition of 16 into 22 and 36 can,
indeed, proceed photochemically, and it can evolve along the
potential energy surface of either one of these two excited
states. Presumably, ultraviolet illumination of 16 results
predominantly in the population of S6 (Figure 7). Then, 16
can decay to S1, after internal conversion, and either dissociate
along the relatively flat potential energy surface of this state or
undergo intersystem crossing and dissociate in T1.
Figure 6. Absorption and emission spectra of 16 (20 μM, MeCN, 25
°C, λEx = 350 nm) before (a and b) and after (c and d) ultraviolet
(UV) irradiation (254 nm, 0.4 mW cm−2, 40 min) and the
corresponding absorbance evolution at 355 nm during photolysis.
evolution at 355 nm during photolysis indicates the quantum
yield (ϕP in Table 1) for this photochemical transformation to
be 0.001.32 In contrast to the behavior of 16, illumination of 17
does not result in the formation of 36. Instead of the
anthracene bands, an absorption centered at 359 nm together
with a weak and broad emission appear in the spectra recorded
after relatively short irradiation times (a−d in Figure S13,
Supporting Information).
The absorption spectrum (Figure 7, a) of 12 indicates the
molar extinction coefficient (ε) to be less than 1 mM−1 cm−1
between 240 and 300 nm. The introduction of a 4-
(dimethylamino)phenyl chromophore on the maleimide
bridge, in the shape of 16, translates into the appearance of
an intense band within this range of wavelengths with a ε of 21
mM−1 cm−1 at 264 nm (Figure 7, b). These observations
indicate that this particular chromophoric fragment is mainly
responsible for absorbing the exciting photons and initiating the
photochemical transformation of 16 into 22 and 36.
Adducts 12−21 differ exclusively in the nature of their
maleimide bridge. Their spectroscopic analysis, together with
the DFT calculations on 16, indicate that a 4-(dimethylamino)-
Density functional theory (DFT) calculations assign the
main band of 16 to a S0 → S6 transition (Figure 7) with
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Figure 7. Experimental absorption spectra (MeCN, 25 °C) of 12 (a) and 16 (b) together with calculated [B3LYP/6-311+G(d,p), IEFPCM for
MeCN] singlet excited states of 16 and isosurfaces for the main orbital pair associated with the S0 → S1 transition.
Figure 9. Relative free energies [B3LYP/6-311+G(d,p), IEFPCM for
MeCN] of adduct 16, products 22 and 36, and the corresponding
transition state.
Figure 8. Relative energies [B3LYP/6-311+G(d,p), IEFPCM for
MeCN] of 16 in S0, S1, and T1 against the length of one of the two
[C−C] bonds joining the anthracene and maleimide fragments.
In contrast to the behavior of 26 and 27, cycloadducts 28, 34,
and 35 undergo photoinduced retro-cycloaddition. In all
instances, the characteristic absorption and emission bands
(Figures S16−S18, Supporting Information) of the correspond-
ing anthracene derivatives develop under illumination. Plots of
the absorbance evolution during photolysis indicates ϕP to
range from 0.001 up to 0.01 (Table 1). Interestingly, ϕP of 28 is
1 order of magnitude greater than those of 16, 34, and 35.
Presumably, the steric hindrance associated with the two
bromine substituents on the bridgehead carbon atoms of 28
facilitates the dissociation of this particular adduct into the
corresponding diene and dienophile. By contrast, the
introduction of a pair of methoxy or phenylethynyl substituents
on the two o-phenylene rings, in the shape of 34 or 35,
respectively, has negligible influence on ϕP, which remains
almost identical to that of 16. Nonetheless, the two
phenylethynyl groups have a pronounced influence on the
fluorescence quantum yield (ϕF in Table 1) of the photo-
chemical product. Indeed, 31 has the greatest ϕF out of the four
photoactivatable anthracenes investigated and, therefore, is the
phenyl group is essential on the bridging unit for the
photochemical dissociation of these adducts to occur. Adducts
26−28, 34, and 35 all have this particular group on their
maleimide bridge and differ instead in the substituents on the
anthracene fragment. In all instances, ultraviolet illumination
results in significant changes in absorption and emission. The
spectra (Figures S14 and S15, Supporting Information) of 26
and 27, however, do not reveal the characteristic band of the
corresponding anthracene drivatives after irradiation. Instead,
an absorption at ca. 355 nm together with a broad and weak
emission appear for both compounds. These bands resemble
the ones detected for 17 (Figure S13, Supporting Information).
All three cycloadducts have iodide substituents and such heavy
atoms are known to encourage intersystem crossing.35
Presumably, a photochemical pathway in competition with
the expected retro-cycloaddition is promoted for all three
compounds via the efficient population on the corresponding
triplet states.
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46.3, 47.3, 112.8, 120.1, 124.7, 125.6, 127.2, 127.4, 127.5, 139.2, 141.8,
150.9, 177.2.
best candidate for possible imaging applications based on this
family of photoactivatable fluorophores.36
17: AcOEt/hexanes (1:4, v/v); yellow solid (80 mg, 32%); ESIMS
m/z = 478.0296 [M + H]+ (m/z calcd for C24H17INO2 = 478.0305);
1H NMR (CDCl3) δ = 3.38 (2H, s), 4.89 (2H, s), 6.29 (2H, d, 8 Hz),
7.19−7.24 (4H, m), 7.32−7.36 (2H, m), 7.41−7.45 (2H, m), 7.64
(2H, d, 8 Hz); 13C NMR (CDCl3) δ = 46.3, 47.5, 80.0, 94.8, 117.7,
124.8, 125.5, 127.3, 127.6, 128.5, 131.4, 138.3, 138.7, 139.1, 141.5,
146.5, 176.2.
CONCLUSIONS
■
The reaction of the maleic anhydride cycloadduct of anthracene
with substituted anilines offers convenient synthetic access to
the corresponding maleimide cycloadducts in good yields. In
the resulting compounds, the maleimide bridge, across
positions 9 and 10 of the oligoacene platform, isolates the
peripheral o-phenylene rings and suppresses the characteristic
absorption and emission bands of the anthracene chromophore.
When a 4-dimethylamino group is attached to the nitrogen
atom of the maleimide bridge, ultraviolet illumination results in
retro-cycloaddition with a quantum yield of 0.001 to regenerate
anthracene and its spectroscopic signature. The 4-dimethyla-
mino appendage collects the exciting photons effectively and
encourages the population of the excited state responsible for
the photochemical regeneration of anthracene. The introduc-
tion of substituents, in the form of a pair of bromine atoms, on
the bridgehead carbon atoms of the N-4-(dimethylamino)-
maleimide cycloadduct facilitates the photochemical trans-
formation and brings the corresponding quantum yield up to
0.01. Instead, the presence of substituents on the peripheral o-
phenylene rings of the cycloadduct has negligible influence on
the quantum efficiency of the photochemical process. These
groups, however, can be exploited to regulate the photophysical
properties of the photochemical product. When a pair of
phenylethynyl groups are attached to positions 2 and 8 of the
anthracene chromophore the fluorescence quantum yields
raises up to 0.85. Thus, these particular operating principles
provide the possibility to convert photochemically a non-
fluorescent reactant into a fluorescent product and, hence to
activate fluorescence efficiently under the influence of optical
stimulations. As a result, this structural design can evolve into
the realization of valuable molecular probes for imaging
applications based on fluorescence photoactivation.
18: AcOEt/hexanes (3:2, v/v); white solid (130 mg, 63%); ESIMS
m/z = 434.1375 [M + Na]+ (m/z calcd for C26H21NO4Na =
1
434.1368); H NMR (CDCl3) δ = 3.38 (2H, s), 3.72 (3H, s), 3.82
(3H, s), 4.90 (2H, s), 5.73 (1H, s), 6.14 (1H, d, 9 Hz), 6.76 (1H, d, 9
Hz), 7.19−7.24 (4H, m), 7.33−7.39 (2H, m), 7.40−7.46 (2H, m); 13C
NMR (CDCl3) δ = 46.3, 47.4, 56.4, 110.1, 111.4, 119.5, 124.4, 124.8,
125.6, 127.3, 127.4, 139.4, 141.6, 149.6, 149.7, 176.9.
19: AcOEt/hexanes (1:4, v/v); white solid (92 mg, 46%); ESIMS
m/z = 424.1302 [M + Na]+ (m/z calcd for C28H19NO2Na =
1
424.1313); H NMR (CD3CN) δ = 3.56 (2H, s), 4.95 (2H, s), 5.32
(1H, d, 8 Hz), 7.16−7.31 (4H, m), 7.40−7.56 (8H, m), 7.88−7.90
(1H, m), 7.94 (1H, d, 8 Hz); 13C NMR (CDCl3) δ = 45.9, 46.4, 47.8,
47.9, 122.3, 124.7, 124.8, 125.6, 125.7, 126.2, 126.3, 126.8, 127.3,
127.4, 127.7, 127.9, 128.5, 128.9, 129.5, 130.2, 130.4, 134.5, 139.4,
139.9, 141.7, 142.2, 176.7, 176.8.
20: AcOEt/CH2Cl2 (1:4, v/v); white solid (82 mg, 38%); ESIMS
m/z = 434.1376 [M + H]+ (m/z calcd for C28H20NO4 = 434.1394);
1H NMR (CDCl3) δ = 2.40 (3H, s), 3.43 (2H, s), 4.91 (2H, s), 6.29
(1H, s), 6.58 (1H, s), 7.21−7.26 (4H, m), 7.33−7.39 (2H, m), 7.42−
7.47 (2H, m), 7.54 (2H, d, 8 Hz); 13C NMR (CDCl3) δ = 19.0, 30.1,
46.3, 47.5, 115.6, 116.1, 120.4, 122.5, 124.8, 125.5, 127.4, 127.8, 134.5,
139.0, 141.4, 151.9, 153.8, 160.5, 175.9.
21: AcOEt/hexanes (2:3, v/v); white solid (85 mg, 36%); ESIMS
m/z = 491.1724 [M + Na]+ (m/z calcd for C32H24N2O2Na =
1
491.1735); H NMR (CD3CN) δ = 1.34 (3H, t, 6 Hz), 3.43 (2H, s),
4.38 (2H, q, 6 Hz), 4.89 (2H, s), 6.48 (1H, d, 9 Hz), 7.03 (1H, s),
7.20−7.27 (3H, m), 7.31−7.45 (5H, m), 7.47−7.56 (4H, m), 8.00
(1H, d, 9 Hz); 13C NMR (CDCl3) δ = 13.8, 37.6, 46.0, 47.1, 50.9,
108.7, 108.9, 119.0, 119.2, 120.6, 122.4, 123.3, 123.7, 124.4,
125.3,126.2, 126.9, 127.2, 139.0, 139.6, 140.3, 141.4, 177.1.
General Procedure for Synthesis of 26−28. An equimolar
solution of 22 (108 mg, 0.5 mmol) and the corresponding anthracene
derivative (23−25) in m-xylene (5 mL) was heated under reflux for 16
h. After the solution was cooled to ambient temperature, the solvent
was distilled off under reduced pressure and the residue was purified
by column chromatography (SiO2).
26: AcOEt/hexanes (1:4 v/v); yellow solid (116 mg, 36%); ESIMS
m/z = 646.9717 [M + H]+ (m/z calcd for C26H21I2N2O2 = 646.9694);
1H NMR (CD3CN) δ = 2.92 (6H, s), 3.35 (2H, s), 4.79 (2H, s), 6.29
(2H, d, 8 Hz), 6.65 (2H, d, 8 Hz), 7.11 (1H, d, 8 Hz), 7.27 (1H, d, 8
Hz), 7.61 (2H, t, 8 Hz), 7.70 (1H, s), 7.86 (1H, s); 13C NMR
(CDCl3) δ = 40.9, 45.3, 45.4, 46.6, 46.9, 92.4, 92.7, 112.9, 126.6, 127.3,
127.4, 133.8, 134.3, 136.4, 136.7, 138.3, 140.8, 141.1, 143.6, 151.0,
151.2, 176.4.
27: AcOEt/hexanes (2:3 v/v); yellow solid (178 mg, 55%); ESIMS
m/z = 646.9692 [M + H]+ (m/z calcd for C26H21I2N2O2 = 646.9694);
1H NMR (CD3CN) δ = 2.90 (6H, s), 3.36 (2H, s), 4.86 (1H, s), 5.48
(1H, s), 6.30 (2H, d, 6 Hz), 6.63 (2H, d, 6 Hz), 6.99 (2H, t, 6 Hz),
7.33 (1H, d, 6 Hz), 7.48 (1H, d, 9 Hz), 7.68−7.77 (2H, m); 13C NMR
(CDCl3) δ = 40.8, 46.1, 46.6, 47.9, 53.6, 95.3, 96.3, 112.8, 120.0, 124.6,
125.6, 127.3, 129.2, 129.3, 137.5, 137.8, 143.0, 143.5, 144.9, 150.9,
175.4, 176.6.
EXPERIMENTAL SECTION
■
Materials and Methods. Chemicals were purchased from
commercial sources and used as received with the exception of
MeCN, which was distilled over CaH2. Compounds 1, 12−15, 22, and
30−32 were prepared according to literature procedures.30−39
Electrospray ionization mass spectra (ESIMS) were recorded with a
TOF-Q spectrometer. NMR spectra were recorded with 300 and 400
MHz spectrometers. Absorption spectra were recorded in quartz cells
with a path length of 1.0 cm. Emission spectra were recorded in
aerated solutions. The value of ϕF for 31 was determined with a 9,10-
diphenylanthracene standard, following a literature protocol.40
Solutions were irradiated either at 254 nm (0.4 mW cm−2) or at
350 nm (2.5 mW cm−2). The values of ϕP were determined with a
potassium ferrioxalate actinometer, according to an established
procedure.33
General Procedure for the Synthesis of 16−21. An equimolar
solution of 1 (138 mg, 0.5 mmol) and the corresponding amine (2−
11) in MeCN (5 mL) was heated under reflux for 16 h over K2CO3
(112 mg, 0.8 mmol). After being cooled to ambient temperature, the
mixture was diluted with CH2Cl2 (30 mL) and washed with H2O (20
mL). The combined organic layers were dried over Na2SO4, the
solvent was distilled off under reduced pressure, and the residue was
purified by column chromatography (SiO2).
28: AcOEt/hexanes (2:3 v/v); yellow solid (105 mg, 38%); ESIMS
m/z = 552.9945 [M + H]+ (m/z calcd for C26H21Br2N2O2
=
1
552.9949); H NMR (CD3CN) δ = 2.91 (6H, s), 3.64 (2H, s), 6.40
(2H, d, 8 Hz), 6.57 (2H, d, 8 Hz), 7.35−7.43 (4H, m), 7.79−7.83
(2H, m), 7.98−8.03 (2H, m); 13C NMR (CDCl3) δ = 40.8, 55.4, 64.3,
112.5, 119.9, 125.9, 125.9, 127.2, 128.7, 129.0, 137.2, 140.1, 150.9,
171.8.
16: AcOEt/hexanes (1.5:3.5, v/v); white solid (120 mg, 60%);
ESIMS m/z = 395.1758 [M + H]+ (m/z calcd for C26H23N2O2 =
1
395.1761); H NMR (CD3CN) δ = 2.88 (6H, s), 3.23 (2H, s), 4.82
(2H, s), 6.23 (2H, d, 9 Hz), 6.59 (2H, d, 9 Hz), 7.18−7.26 (4H, m),
7.28−7.33 (2H, m), 7.44−7.51 (2H, m); 13C NMR (CDCl3) δ = 40.8,
F
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Synthesis of 33. A solution of 29 (40 mg, 0.4 mmol) and 31 (150
mg, 0.4 mmol) in m-xylene (5 mL) was heated under reflux for 16 h.
After being cooled to ambient temperature, the mixture was cooled
further with an ice bath and the resulting precipitate was filtered off.
The solid residue was washed with hexane and then crystallized with
m-xylene to give 33 (80 mg, 42%) as a white solid: ESIMS m/z =
molecule of MeCN cocrystallized with 35. The solvent molecule was
included in the analysis and refined with anisotropic thermal
parameters. Compound 18 crystallized in the orthorhombic crystal
system. The systematic absences in the intensity data identified the
unique space group P212121. Compounds 19 and 28 crystallized in the
monoclinic crystal system. The systematic absences in the intensity
data identified the unique space group P21/n.
1
499.1293 [M + Na]+ (m/z calcd for C34H20O3Na = 499.1310); H
Computational Methods. Density-functional theory43 (DFT)
calculations were performed with the 6-311+G(d,p) basis set and the
restricted B3LYP44,45 functional implemented in Gaussian 09.46
Geometry optimizations, frequencies, molecular orbitals, and excited
states were computed with the polarizable continuum model (PCM)
for acetonitrile using the integral equation formalism (IEF) variant.47
The geometry adopted by 16 in single crystals (Figure 4) was
optimized. No imaginary frequencies were found for the optimized
structure. Molecular orbitals and the first 10 singlet excited states were
computed for this geometry (HOMO, LUMO and S1−S6 in Figure 7).
The [C−C] bond between one of the two bridgehead carbon atoms
and the corresponding maleimide carbon atom was elongated in 20
consecutive steps of 0.1 Å each. The remaining coordinates were
optimized at each step and the first 5 singlet and 5 triplet excited states
of each optimized geometry were computed.48,49 The energies of S0,
S1, and T1 of each optimized geometry were plotted against the
corresponding [C−C] distances (Figure 8). The geometry with
highest S0 energy (step 12) was optimized to a transition state with no
distance constraint. One imaginary frequency (video S1, Supporting
Information) was found. The last geometry of the distance scan (step
20) shows the two separate products (22 and 36) was optimized
further with no distance constraint. No imaginary frequencies were
found. The free energies of transition state and products were
computed relative to that of the very first geometry of the distance
scan (Figure 8).
NMR (CD3CN) δ = 3.68−3.74 (1H, m), 3.77−3.83 (1H, m), 5.00
(1H, s), 5.96 (1H, s), 7.19−7.32 (6H, m), 7.34−7.54 (10H, m); 13C
NMR (CDCl3) δ = 41.5, 46.1, 47.5, 48.1, 86.0, 86.1, 94.2, 94.3, 120.4,
121.3, 122.9, 123.3, 124.6, 125.5, 127.4, 127.9, 128.7, 128.8, 128.9,
131.0, 131.5, 132.2, 132.3, 138.9, 139.5, 141.4, 141.9, 144.7, 169.8,
170.8.
General Procedure for the Synthesis of 34 and 35. An
equimolar solution of 6 (0.2 mmol) and the corresponding anthracene
derivative (32 or 33) in MeCN (5 mL) was heated under reflux for 16
h over K2CO3 (42 mg, 0.3 mmol). After being cooled to ambient
temperature, the mixture was diluted with CH2Cl2 (30 mL) and
washed with H2O (20 mL). The combined organic layers were dried
over Na2SO4, the solvent as distilled off under reduced pressure, and
the residue was purified by column chromatography [SiO2, AcOEt/
hexanes (2:3, v/v)] to give the product.
34: white solid (50 mg, 55%); ESIMS m/z = 455.1975 [M + H]+
1
(m/z calcd for C28H27N2O4 = 455.1973); H NMR (CD3CN) δ =
2.90 (6H, s), 3.29 (2H, s), 3.76 (3H, s), 3.78 (3H, s), 4.71 (2H, s),
6.30 (2H, d, 8 Hz), 6.63 (2H, d, 8 Hz), 6.74 (2H, t, 8 Hz), 6.89 (1H,
s), 7.07 (1H, s), 7.19 (1H, d, 8 Hz), 7.35 (1H, d, 8 Hz); 13C NMR
(CDCl3) δ = 40.8, 45.8, 47.4, 47.6, 55.9, 56.0, 111.2, 111.4, 112.6,
112.8, 120.2, 120.3, 125.4, 126.3, 127.4, 131.1, 133.8, 141.1, 143.8,
150.9, 158.9, 159.3, 177.1, 177.3.
+
35: white solid (40 mg, 45%); ESIMS m/z = 595.2409 [M + H]
1
(m/z calcd for C42H31N2O2 = 595.2387); H NMR [(CD3)2CO] δ =
2.90 (6H, s), 3.47−3.51 (1H, m), 3.53−3.57 (1H, m), 5.01 (1H, s),
6.03 (1H, s), 6.42 (2H, d, 8 Hz), 6.60 (2H, d, 8 Hz), 7.16−7.20 (2H,
m), 7.26−7.35 (5H, m), 7.37−7.48 (6H, m), 7.55−7.63 (3H, m); 13C
NMR (CDCl3) δ = 29.7, 40.4, 41.6, 46.0, 46.2, 46.6, 86.1, 86.3, 112.5,
119.9, 120.7, 122.7, 123.2, 124.2, 125.1, 126.6, 126.8, 127.0, 128.2,
128.3, 130.3, 130.4, 131.8, 132.0, 139.2, 140.0, 141.8, 142.3, 150.5,
175.5, 176.5.
ASSOCIATED CONTENT
* Supporting Information
■
S
1H and 13C NMR spectra of 16−21, 26−28, and 33−35;
crystallographic data for 15, 16, 18−21, 28, 34, and 35;
absorption and emission spectra of 17, 26−28, 34, and 35;
computed coordinates of 16, 22, 36, and the corresponding
transition state; animation of the vibration associated with the
imaginary frequency of the transition state. This material is
available free of charge via the Internet at http://pubs.acs.org.
Crystallographic Analysis. Single crystals of 15, 18, and 21 were
obtained after diffusion of Et2O vapors into a CH2Cl2 solution of the
corresponding compound. Single crystals of 16 were obtained after
diffusion of hexane vapors into a CHCl3 solution of the compound.
Single crystals of 19 and 28 were obtained after diffusion of Et2O
vapors into a CHCl3 solution of the corresponding compound. Single
crystals of 20 were obtained after diffusion of hexane/Et2O (2:1, v/v)
vapors into a CHCl3 solution of the compound. Single crystals of 34
were obtained after diffusion of Et2O vapors into an EtOAc solution of
the compound. Single crystals of 35 were obtained after diffusion of
hexane vapors into a MeCN solution of the compound. The data
crystal of 15, 16, 18−21, and 34 was glued onto the end of a thin glass
fiber. The data crystals of 28 and 35 were mounted onto the end of a
thin glass fiber using Paratone-N for data collection at 100 K under
flow of N2. X-ray intensity data were measured with a CCD-based
diffractometer, using Mo Kα radiation (λ = 0.71073 Å).41 The raw
data frames were integrated with a narrow-frame integration algorithm.
Corrections for Lorentz and polarization effects were applied. An
empirical absorption correction based on the multiple measurement of
equivalent reflections was applied. The structures were solved by a
combination of direct methods and difference Fourier syntheses and
refined by full-matrix least-squares on F2.42 All non-hydrogen atoms
were refined with anisotropic displacement parameters. Hydrogen
atoms were placed in geometrically idealized positions and included as
standard riding atoms during the least-squares refinements. Crystal
data, data collection parameters, and results of the analyses are listed in
Tables S1−S3 (Supporting Information).
AUTHOR INFORMATION
Corresponding Author
*E-mail: fraymo@miami.edu.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The National Science Foundation (CAREER Award CHE-
0237578, CHE-0749840, and CHE-1049860) is acknowledged
for financial support.
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I
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