Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira-Glaser cyclization sequence

Article abstract of DOI:10.3762/bjoc.10.60

2,5-Di(hetero)arylfurans are readily accessible in a pseudo five-component reaction via a Sonogashira-Glaser coupling sequence followed by a superbase-mediated (KOH/DMSO) cyclization in a consecutive one-pot fashion. Besides the straightforward synthesis of natural products and biologically active molecules all representatives are particularly interesting due to their bright blue luminescence with remarkably high quantum yields. The electronic structure of the title compounds is additionally studied with DFT computations.

Full text of DOI:10.3762/bjoc.10.60

Rapid pseudo five-component synthesis of
intensively blue luminescent 2,5-di(hetero)arylfurans
via a Sonogashira–Glaser cyclization sequence
Fabian Klukas, Alexander Grunwald, Franziska Menschel
and Thomas J. J. Müller*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 672–679.
Heinrich-Heine Universität Düsseldorf, Institut für Organische Chemie
und Makromolekulare Chemie, Universitätsstraße 1, D-40225
Düsseldorf, Germany
doi:10.3762/bjoc.10.60
Received: 13 December 2013
Accepted: 12 February 2014
Published: 18 March 2014
Email:
Thomas J. J. Müller* - ThomasJJ.Mueller@uni-duesseldorf.de
This article is part of the Thematic Series "Multicomponent reactions II"
and is dedicated to Prof. Dr. Rainer Weinkauf on the occasion of his 60th
birthday.
* Corresponding author
Keywords:
C–C coupling; copper; DFT; fluorescence; furans; mircowave-assisted
synthesis; multicomponent reactions; palladium
Associate Editor: J. P. Wolfe
© 2014 Klukas et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
2,5-Di(hetero)arylfurans are readily accessible in a pseudo five-component reaction via a Sonogashira–Glaser coupling sequence
followed by a superbase-mediated (KOH/DMSO) cyclization in a consecutive one-pot fashion. Besides the straightforward syn-
thesis of natural products and biologically active molecules all representatives are particularly interesting due to their bright blue
luminescence with remarkably high quantum yields. The electronic structure of the title compounds is additionally studied with
DFT computations.
Introduction
Multicomponent reactions (MCRs) [1-5] are conceptually diver- Interestingly, multicomponent syntheses of symmetrically
sity-oriented syntheses (DOS) [6,7] and have been developed to substituted furans have remained rare [12,13], although furans
powerful tools for exploring broad ranges of different structural are ubiquitous in nature [14]. In particular, 2,5-di(hetero)arylfu-
and functional characteristics. In addition, MCRs address the rans are structural units with pronounced biological activities
very fundamental principles of reaction efficiency and atom [15] and besides in natural products [16,17] they are also
economy. Besides lead finding in pharmaceutical and medic- present in potential pharmaceuticals for the treatment of human
inal chemistry [8-10] MCRs have also been recognized as a African trypanosomiasis [18-20], and against human renal
DOS tool for approaching functional π-systems [11] such as cancer cells [21-23]. Furthermore, 2,5-di(hetero)arylfurans have
luminescent chromophores [6].
been reported as photonic chromophores [24]. However, the
672

Beilstein J. Org. Chem. 2014, 10, 672–679.
electronic and photophysical properties of 2,5-di(hetero)aryl well (vide infra). In a set of experiments the reaction times
furans have only been occasionally studied [25-27].
under microwave heating (the temperature optimum of 130 °C
was quickly identified by screening experiments), the water/
The classical synthesis of symmetrical 2,5-disubstituted furans KOH ratio, and the concentrations were varied.
proceeds via Paal–Knorr synthesis [28]. Due to sophisticated
starting materials this very general pathway is often not suit-
Table 1: Evaluation of different reaction conditions.
able for a DOS approach. In addition, some starting materials
are either not readily available or quite expensive. 2,5-dihalo-
genated furans can be in principle employed in cross-coupling
reactions, however, the poor stability of these dihalogenated
precursors renders this approach very tedious [29]. Recent
publications report gold-catalyzed syntheses of di(hetero)arylfu-
Entry
H2O
KOH
DMSO
Time
[h]
Yielda
[%]
rans starting from arylbutadiynes [30,31]. However, the major
drawback of this approach is the complex, time-consuming
preparation of the complicated gold catalyst and the separate
synthesis of the butadiyne substrates. In a similar study arylbu-
tadiynes prepared by Glaser homocoupling were converted into
symmetrical 2,5-di(hetero)arylfurans [32] employing the super-
base system DMSO/KOH/H2O in the terminal cyclization step
[33]. The same approach was applied to butadiynes that were
formed by oxidative dimerization of arylalkynes with a Cu/Fe
catalyst [34]. Apart from using reactive terminal alkynes as
starting materials the major drawbacks of this approach are
clearly the extended reaction times (3–6 d) and the removal of
the catalyst after the coupling step.
[equiv] [equiv] [mL/mmol]
1
2
2
2
2
2
4
4
1
3
1
1
1
1
1
6
1
1
1
1
1
53
24
25
34
36
50
40
43
58
64
13
84
79
3
10
2
2
4
4b
5c
6c
7d
8d,e
9
2
4
2
2
4
16
8
10
10
10
2
4
4
8
4
2
8
10
11
12
13
4
4
8
2
8
16
16
16
8
8
12
12
aIsolated yield after chromatography on silica gel. bIn the presence of
2 mol % PdCl2(PPh3)2. cIn the presence of 5 mol % CuI, 15 mol %
DMEDA. dIn the presence of 5 mol % CuI, 15 mol % 1,10-phenanthro-
line. eConductive heating (oilbath at 130 °C).
Recently, we became particularly interested in sequentially
Pd-catalyzed processes [35] starting from (hetero)aryl iodides
[36]. In particular, the Pd–Cu-catalyzed Sonogashira–Glaser
sequence represents a highly intriguing combination of a cross-
coupling and an oxidation reaction in a one-pot fashion [37]. By
this approach we can efficiently avoid the major disadvantage In the course of our studies a related work using copper cata-
of starting from terminal alkynes, which are occasionally lysts with the electronrich DMEDA (N,N’-dimethylethylenedi-
unstable and tend to undergo polymerization. Based upon the amine) or the electronpoor 1,10-phenanthroline as ligands was
Sonogashira–Glaser sequence we recently presented a straight- published [32], however, in our hands no favorable effect on the
forward one-pot sequence for the synthesis of 2,5- isolated yields of 2a was found (Table 1, entries 4–8). The
di(hetero)arylthiophenes [38]. Here, we report the methodolog- cyclization works equally well with conductive heating in an oil
ical development of a novel multicomponent synthesis of bath instead of microwave heating (Table 1, entry 8). At higher
symmetrical 2,5-(hetero)arylfurans in the sense of a consecu- concentrations we always observed the formation of byprod-
tive one-pot sequence. In addition, the photophysical and elec- ucts that were not detectable by GC, although 1a was
tronical properties are studied and the electronic structure is completely consumed. An isolated black solid with an
investigated by DFT calculations.
elemental analysis matching with the elemental composition of
2a was partially soluble in acetone and THF. The supernatant of
the THF extraction was analyzed by MALDI–TOF mass spec-
trometry indicating the formation of oligomers with m/z = 422
Results and Discussion
Synthesis
Prior to setting up the one-pot sequence we first optimized the to 1046. We could efficiently suppress this oligo- and polymer-
conditions of the terminal cyclization step for the formation of ization by increasing the amount of solvent, i.e. by dilution (Ta-
2,5-diphenylfuran (2a, Table 1) starting from 1,4-diphenylbu- ble 1, entries 9–13). Additionally increasing the concentration
tadiyne (1a) as a substrate. Just upon eyesight a remarkable of KOH and water also proved to be beneficial (Table 1, entries
luminescence of 2a caught our attention and we were encour- 10–13). The optimal conditions for this cyclization are marked
aged to perform photophysical studies with these products as in entry 12 of Table 1.
673

Beilstein J. Org. Chem. 2014, 10, 672–679.
With these optimized conditions in hand we started to concate-
nate the one-pot sequence by generating the required 1,4-
butadiynes from (hetero)aryl iodides. First, the
Sonogashira–Glaser sequence had to be performed in DMSO as
a solvent and in the presence of atmospheric oxygen for the
Glaser step. Starting from iodobenzene (3a) and trimethylsily-
lacetylene (TMSA) the cross-coupling in DMSO proceeded
uneventfully and the yield of the Glaser product 1a was found
Scheme 1: Sonogashira–Glaser sequence in DMSO as a solvent.
to be 80%, i.e. approximately the same yield as for the sequence Finally, starting from (hetero)aryl iodides 3 and TMSA we
in THF as a solvent (Scheme 1) [37]. Most favorably no addi- combined the Sonogashira–Glaser sequence with the cycliza-
tional cosolvent was needed for increasing the solubility of the tion step into a one-pot sequence and studied the substrate scope
fluoride source [38]. For an optimal Glaser step vigorous stir- of this pseudo five-component synthesis of 2,5-di(hetero)arylfu-
ring is required to ensure an efficient air saturation of the rans 2 (Scheme 2). All reactions were performed on a 2 mmol
solvent.
scale.
Scheme 2: Pseudo five-component Sonogashira–Glaser cyclisation synthesis of 2,5-di(hetero)arylfurans 2 (aobtained from the THP-protected
precursor).
674

Beilstein J. Org. Chem. 2014, 10, 672–679.
The structural assignments of all furans 2 were unambiguously
supported by 1H and 13C NMR spectroscopy, mass spectrom-
etry, and combustion analysis (HRMS in case of 2j and 2m).
Due to the poor solubility of some compounds all spectra were
recorded in DMSO at room temperature, whereas the com-
pounds 2r and 2p were measured at 80 °C.
The yields of the obtained 2,5-di(hetero)arylfurans 2 are
moderate to good and the employed (hetero)aryl substituents
can be electroneutral (2a, 2i, 2j) and electronrich (2b–2h, 2k,
2l, 2m). Substituents in ortho- (2b, 2h), meta- (2c, 2e–2h, 2k)
and para-position (2d, 2g, 2o) are well tolerated. Polar
substituents like alcohols (2k) can also be employed in the
sequence. From the literature it is known that the naturally
occurring compound 2h [16,17] and 2,5-bis(3,4,5-
trimethoxyphenyl)furan (2g) are highly biological active [39].
Compound 2k is structurally related to small molecule inhibi-
tors of p53-HDM-2 [21-23].
Figure 1: Compounds 2d (solid and THF solution) and 2n (solid and
THF solution) (from left to right) under daylight (top) and under UV light
(bottom, λmax,exc = 366 nm).
Electronic properties and computational
studies
The most furans display intense, broad absorption bands
All title compounds 2 display strong fluorescence in solution between 321 and 358 nm with molar extinction coefficients
and in the solid state upon UV excitation (Figure 1). Therefore, between 21000 to 35000 L/mol cm−1. In addition redshifted
the absorption and emission spectra of all compounds 2 were shoulders appear between 336 and 377 nm. Likewise the emis-
recorded in dichloromethane and the fluorescence quantum sion maxima are found between 367 and 439 nm and
yields Φf were determined with coumarin 1 or p-terphenyl as blueshifted shoulders appear between 351 and 424 nm. The
references (Table 2).
Stokes shifts determined from the absorption and emission
Table 2: Selected absorption and emission data (recorded in dichloromethane at T = 293 K).
Compound
λmax, abs [nm]a
([L·mol·cm−1])
λmax, em [nm]
Φf
Δ
[cm−1]b
2a
2b
2c
2d
2e
2f
327 (35000), 342 sh
314 (23000), 342 sh
329 (33000), 344 sh
331 (33000), 348 sh
331 (28000), 347 sh
331 (29000), 347 sh
340 (33000), 356 sh
347 (33000), 364 sh
347 (29000)
358 sh, 373
359 sh, 375
360 sh ,376
360 sh, 379
362 sh, 379
362 sh, 381
378 sh, 391
377 sh, 395
424 sh, 436
393 sh, 411
362 sh, 377
389 sh, 407
351 sh, 367
439
3800
5200
3800
3800
3800
4000
3800
3500
5900
3600
3900
3800
3900
6400
3800
83%c
59%c
72%c
64%c
55%c
95%c
80%c
47%c
75%d
100%d
80%c
42%c,e
29%c
69%d
76%c
2g
2h
2i
2j
358 (26000), 377 sh
329 (32000), 345 sh
353 (24000), 371 sh
321 (23000), 336 sh
343 (23000)
2k
2l
2m
2n
2o
323 (21000), 338 sh
353 sh, 368
ash = shoulder. bThe boldfaced absorption and emission maxima were used to calculate the Stokes shifts. cp-Terphenyl (Φf = 93% in cyclohexane) as
a reference [40]. dCoumarin 1 (Φf = 73% in EtOH) as a reference [41]. eRef. [26]: Φf = 33% in acetonitrile.
675

Beilstein J. Org. Chem. 2014, 10, 672–679.
maxima range from 3500 to 6400 cm−1 and the quantum yields studied representatives are potentially interesting singlet blue-
are quite large in a range from Φf = 29 to 100%. The com- light emitters.
pounds 2b, 2i and 2n display unstructured broad absorption and
emission bands and possess the largest Stokes shifts.
In addition, the electronic properties of the furans 2 have been
studied by cyclic voltammetry (Table 3). Most cyclovoltammo-
This peculiar effect could arise from considerable geometrical grams display reversible Nernstian one-electron oxidations in
differences between the electronic ground state and the vibra- the anodic region between 1.06 and 1.25 V (vs Ag/AgCl) (Ta-
tionally relaxed excited state caused by significant distortion of ble 3). Expectedly, with increasing electron density the oxida-
the aryl substituents from coplanarity in the ground state [42]. tive potential diminishes. The compounds 2f, 2g, 2l, and 2n
Therefore, the geometries of the ground state structures of the could not be measured by cyclic voltammetry due to precipita-
compounds 2a,2b,2i,2j, and 2n were optimized on the DFT tion on the electrode. The determined oxidation potentials
level of theory (B3LYP functional [43-46] and the Pople E1/20/+1 vs Ag/AgCl were recalculated vs the normal hydrogen
6-311G(d,p) basis set [47]) as implemented in Gaussian09 [48]. electrode (NHE) and then transformed into eV [50]. The reduc-
The computations applied the Polarizable Continuum Model tion potentials were calculated by subtraction of the S1–S0
(PCM) using dichloromethane as solvent [49]. All minima were energy gap (in eV) from the first oxidation potential E1/20/+1.
confirmed by analytical frequency analyses. In conclusion, the This gap was estimated by the cross-section of the absorption
computations clearly reveal that the ortho-aryl substituted com- and emission spectra. For the missing oxidation potentials of 2f,
pounds 2b, 2h, 2i and 2n are twisted from coplanarity while the 2g, 2m, and 2l the HOMO and LUMO energies were deter-
other compounds are coplanar (Figure 2).
mined by DFT calculations [48]. For validation of the experi-
mental and computational data the oxidation and reduction
In the UV–vis spectra the similar planar structures 2a and 2c are potentials were converted into the corresponding experimental
bathochromically shifted in comparison to the twisted structure HOMO and LUMO energies (for details see Supporting Infor-
2b. The twisting from coplanarity also results in a lower fluo- mation File 1). The plot of measured and calculated HOMO
rescence quantum yield Φf. The same holds true for the com- energies gives a reasonable linear correlation (r2 = 0.815, omit-
parison of the constitutional isomers 2i and 2j. Therefore, the ting the twisted compounds 2b, 2h, 2i and 2n) with a mean
twisted structure of 2j causes a larger Stokes shift and a much deviation of 0.05 eV (see Supporting Information File 1).
lower fluorescence quantum yield Φf. The huge Stokes shift Roughly a similar trend can be found for the HOMO–LUMO
originates from a considerable planarization in the excited state gap.
[42]. The absorption maximum of 2h is considerably shifted
bathochromically in comparison to those of 2c, 2e, and 2f. The The inspection of the coefficient densities in the Kohn–Sham
DFT calculation on structure 2h reveals a twisted ground state frontier molecular orbitals of the compounds 2i, 2j, and 2n
structure. In the whole series compound 2j shows the most underlines that the HOMO and the LUMO are delocalized over
redshifted absorption maximum and the highest fluorescence the whole molecule (Figure 3), which plausibly rationalizes the
quantum yield Φf. This finding correlates well with the planar high extinction coefficient of the longest wavelength absorp-
ground state structure and an associated low Stokes shift. All tions bands.
Figure 2: Selected computed minimum conformations of the 2,5-diarylfurans 2i, 2j, and 2n.
676

Beilstein J. Org. Chem. 2014, 10, 672–679.
Table 3: Selected cyclovoltammetrica (recorded in dichloromethane at 293 K) and computationalb data.
Compound E00/+1 [V]c
E1/20/+1 [V] vs NHEc
E1/20/-1 [V] vs NHEd
HOMO [eV]
LUMO [eV]
ΔEHOMO−LUMO
exp.e calcd.d exp.f calcd.b exp. calcd.b
2a
2b
2c
2d
2e
2f
1.25
1.19
1.19
1.09
1.06
−
1.45
1.39
1.39
1.29
1.26
−
−2.11
−2.18
−2.15
−2.22
−2.24
−
−5.60 −5.57 −2.04 −1.60
−5.54 −5.59 −1.97 −1.51
−5.54 −5.50 −2.00 −1.57
−5.44 −5.41 −1.93 −1.49
−5.41 −5.46 −1.91 −1.51
3.56
3.57
3.54
3.51
3.50
−
3.97
4.08
3.93
3.92
3.95
3.98
3.86
4.25
3.73
3.53
3.97
3.67
4.06
3.78
3.97
−
−
−5.55
−5.44
−
−
−1.57
−1.58
2g
2h
2i
−
−
−
−
1.24
1.15
1.10
1.16
−
1.44
1.35
1.30
1.36
−
−2.22
−1.81
−1.94
−2.17
−
−5.59 −5.41 −1.93 −1.16
−5.50 −5.54 −2.34 −1.81
−5.45 −5.46 −2.21 −1.93
−5.51 −5.53 −1.98 −1.56
3.66
3.16
3.24
3.53
−
2j
2k
2l
−
−
−5.37
−5.44
−
−
−1.70
−1.38
2m
2n
2o
−
−
−
−
1.14
1.24
1.34
1.44
−1.82
−2.17
−5.49 −5.59 −2.33 −1.81
−5.59 −5.57 −1.98 −1.60
3.16
3.61
a 0.1 M electrolyte: [Bu4N][PF6] (120 mg in 3 mL dichloromethane), Pt working electrode, Pt counter electrode, Ag/AgCl (in KCl) reference electrode.
bCalculated with Gaussian09, B3LYP/6-311G(d,p). c
(with NHE (3 M KCl Ag/Ag+) = 0.198 V).
.
d
(with cross-section of absorption and emission spectra).
e
. f
Figure 3: Kohn–Sham HOMOs (bottom) and LUMOs (top) of the compounds 2i, 2j, and 2n (calculated on the DFT level of theory (B3LYP/6-
311G(d,p)).
677

Beilstein J. Org. Chem. 2014, 10, 672–679.
Conclusion
Supporting Information
In summary we have disclosed a concise and efficient
microwave-assisted pseudo five-component synthesis of
symmetrical 2,5-di(hetero)arylfurans in a one-pot fashion,
which opens a ready access to biologically active furan deriva-
tives. In addition the investigation of the photophysical prop-
erties of these compounds reveals an intense blue luminescence
in solution approaching unity for the fluorescence quantum
yield Φf of distinct derivatives. Computations account for
significant distortions from coplanarity in the electronic ground
state and the computed HOMO energies correlate with the first
reversible oxidation potentials determined by cyclic voltam-
metry.
For experimental details of the optimization studies of the
cyclization step (compound 2a), of general procedure of the
Sonogashira–Glaser cyclization synthesis of the
2,5-di(hetero)arylfurans 2, for UV–vis, fluorescence, and
NMR spectra and cyclovoltammograms of the compounds
2, and for computational data of the DFT calculations on
the structures 2 of see Supporting Information.
Supporting Information File 1
Experimental procedures, spectroscopic and analytical data
of all compounds 2.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-60-S1.pdf]
Experimental
Pseudo five-component synthesis of 2a [51] in a manner
similar to [38]): A mixture of iodobenzene (3a, 408 mg,
2.00 mmol), PdCl2(PPh3)2 (28.1 mg, 0.04 mmol, 2 mol %), and Acknowledgements
CuCl (7.92 mg, 0.08 mmol, 4 mol %) was dissolved in DMSO The support of this work by the Fonds der Chemischen Indus-
(2.00 mL) in a 80 mL microwave vessel equipped with a stir- trie is gratefully acknowledged.
ring bar and a septum and was degassed with N2 for 5 min.
References
1. Müller, T. J. J., Ed. Multicomponent Reactions; Science of Synthesis
After addition of trimethylsilylacetylene (0.42 mL, 3.00 mmol)
and dry triethylamine (0.55 mL, 4.00 mmol) the solution was
Series; Georg Thieme Verlag KG: Stuttgart, 2014.
stirred at room temperature for 1 h. Then, KF (232 mg,
2. Sunderhaus, J. D.; Martin, S. F. Chem.–Eur. J. 2009, 15, 1300–1308.
4.00 mmol) was added and the reaction mixture was vigorously
doi:10.1002/chem.200802140
stirred under air in the open reaction vessel at room tempera-
3. Isambert, N.; Lavilla, R. Chem.–Eur. J. 2008, 14, 8444–8454.
ture for 16 h. After the addition of H2O (144 mg, 8.00 mmol),
doi:10.1002/chem.200800473
potassium hydroxide (449 mg, 16 mmol), and DMSO (14.0 mL)
the mixture was heated in the microwave cavity at 130 °C for
1 h. After cooling to room temperature the mixture was
extracted with methylene chloride (300 mL) and brine
(500 mL). The organic phase was dried with anhydrous Na2SO4
and the solvents were removed under reduced pressure. The
residue was absorbed on Celite® and purified by column chro-
matography on silica gel with n-hexane as an eluent to give
96.0 mg (0.44 mmol, 44%) of the desired product as colorless
crystals. Rf: = 0.31 (n-hexane). Mp 84 °C (66–68 °C [51]). 1H
NMR (DMSO-d6, 600 MHz) δ 7.08 (s, 2H), 7.31 (t, 3J = 7.4
Hz, 2H), 7.46 (t, 3J = 7.8 Hz, 4H), 7.82 (d, 3J = 7.3 Hz, 4H);
13C NMR (DMSO, 150 MHz) δ 108.2 (CH), 123.4 (CH), 127.5
(CH), 128.9 (CH), 130.0 (Cquat), 152.6 (Cquat). GC–MS (m/z
(%)): 220 (M+, 100), 191 (13), 115 ((M-C7H5O)+, 41), 105
((C7H5O)+, 22), 89 (14), 77 ((C6H5)+, 51), 63 (13), 51 (22); IR
(KBr): = 1479 (w) cm−1, 1446 (w), 1155 (w), 1022 (m), 925
(w), 910 (w), 794 (m), 756 (s), 689 (s), 671 (m). Anal. calcd for
C16H12O (220.3): C 87.25, H 5.49; Found: C 87.09, H 5.42;
UV–vis (CH2Cl2): λmax(ε): 327 nm (35000 L·mol−1·cm−1), 342
(22000). Fluorescence (CH2Cl2): λmax: 358 nm. Stokes shift
4. Orru, R. V. A.; de Greef, M. Synthesis 2003, 1471–1499.
doi:10.1055/s-2003-40507
5. Bonne, D.; Coquerel, Y.; Constantieux, T.; Rodriguez, J.
Tetrahedron: Asymmetry 2010, 21, 1085–1109.
doi:10.1016/j.tetasy.2010.04.045
6. Müller, T. J. J.; D’Souza, D. M. Pure Appl. Chem. 2008, 80, 609–620.
doi:10.1351/pac200880030609
7. Burke, M. D.; Schreiber, S. L. Angew. Chem., Int. Ed. 2004, 43, 46–58.
doi:10.1002/anie.200300626
8. Dömling, A. Chem. Rev. 2006, 106, 17–89. doi:10.1021/cr0505728
9. Weber, L. Curr. Med. Chem. 2002, 9, 2085–2093.
doi:10.2174/0929867023368719
10.Shaw, A. Y.; Denning, C. R.; Hulme, C. Synthesis 2013, 45, 459–462.
doi:10.1055/s-0032-1317983
11.Müller, T. J. J. In Functional Organic Materials. Syntheses, Strategies,
and Applications; Müller, T. J. J.; Bunz, U. H. F., Eds.; Wiley-VCH
Verlag GmbH & Co. KGaA: Weinheim, 2007; pp 179–223.
12.Karpov, A. S.; Merkul, E.; Oeser, T.; Müller, T. J. J. Chem. Commun.
2005, 2581–2583. doi:10.1039/B502324F
13.Willy, B.; Müller, T. J. J. ARKIVOC 2008, i, 195–208.
14.Keayand, B. A.; Dibble, P. W. In Comprehensive Heterocyclic
Chemistry II, 2nd ed.; Katritzky, A. R.; Reesand, C. W.;
Scriven, E. F. V., Eds.; Elsevier: Oxford, 1997; pp 395–436.
15.Das, B. P.; Boykin, D. W. J. Med. Chem. 1977, 20, 531–536.
doi:10.1021/jm00214a014
Δ
= 3800 cm−1. Quantum yield: Φf = 83% (Ref.: p-terphenyl
16.Majumder, P.; Saha, S. Phytochemistry 1978, 17, 1439–1440.
doi:10.1016/S0031-9422(00)94610-7
(Φf = 93% in cyclohexane)). Cyclic voltammetry (CH2Cl2):
E1/20/+1 = 1.25 V.
678

Beilstein J. Org. Chem. 2014, 10, 672–679.
17.Masood, M.; Tiwari, K. P. Phytochemistry 1981, 20, 295–296.
doi:10.1016/0031-9422(81)85110-2
44.Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
doi:10.1063/1.464913
18.Thuita, J. K.; Karanja, S. M.; Wenzler, T.; Mdachi, R. E.; Ngotho, J. M.;
Kagira, J. M.; Tidwell, R.; Brun, R. Acta Trop. 2008, 108, 6–10.
doi:10.1016/j.actatropica.2008.07.006
45.Kim, K.; Jordan, K. D. J. Phys. Chem. 1994, 98, 10089–10094.
doi:10.1021/j100091a024
46.Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J.
J. Phys. Chem. 1994, 98, 11623–11627. doi:10.1021/j100096a001
47.Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys.
1980, 72, 650–654. doi:10.1063/1.438955
19.Wenzler, T.; Boykin, D. W.; Ismail, M. A.; Hall, J. E.; Tidwell, R. R.;
Brun, R. Antimicrob. Agents Chemother. 2009, 53, 4185–4192.
doi:10.1128/AAC.00225-09
20.Barrett, M. P.; Croft, S. L. Br. Med. Bull. 2012, 104, 175–196.
doi:10.1093/bmb/lds031
48.Gaussian 09, Revision A.02; Gaussian, Inc.: Wallingford CT, 2009.
49.Scalmani, G.; Frisch, M. J. J. Chem. Phys. 2010, 132, 114110–114124.
doi:10.1063/1.3359469
21.Nieves-Neira, W.; Rivera, M. I.; Kohlhagen, G.; Hursey, M.;
Pourquier, P.; Sausville, E. A.; Pommier, Y. Mol. Pharmacol. 1999, 56,
478–484.
50.Pommerehne, J.; Vestweber, H.; Guss, W.; Mahrt, R. F.; Bässler, H.;
Porsch, M.; Daub, J. Adv. Mater. 1995, 7.
22.Chène, P. Nat. Rev. Cancer 2003, 3, 102–109. doi:10.1038/nrc991
23.Issaeva, N.; Bozko, P.; Enge, M.; Protopopova, M.;
Verhoef, L. G. G. C.; Masucci, M.; Pramanik, A.; Selivanova, G.
Nat. Med. 2004, 10, 1321–1328. doi:10.1038/nm1146
24.Liu, C.-Y.; Luh, T. Org. Lett. 2002, 4, 4305–4307.
doi:10.1021/ol026941t
doi:10.1002/adma.19950070608
51.Zhang, M.; Jiang, H.-F.; Neumann, H.; Beller, M.; Dixneuf, P. H.
Angew. Chem., Int. Ed. 2009, 48, 1681–1684.
doi:10.1002/anie.200805531
25.Altınok, E.; Friedle, S.; Thomas, S. W., III. Macromolecules 2013, 46,
756–762. doi:10.1021/ma3025656
License and Terms
26.Seixas de Melo, J.; Elisei, F.; Becker, R. S. J. Chem. Phys. 2002, 117,
4428–4435. doi:10.1063/1.1498115
This is an Open Access article under the terms of the
Creative Commons Attribution License
27.Kutsyna, L. M.; Sidorova, R. P.; Voevoda, L. V.; Ishchenko, I.;
Demchenko, N. P. Bull. Acad. Sci. USSR, Phys. Ser. (Engl. Transl.)
1962, 26, 1304–1322.
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
28.Amarnath, V.; Amarnath, K. J. Org. Chem. 1995, 60, 301–307.
doi:10.1021/jo00107a006
29.Rao, M. L. N.; Awasthi, D. K.; Talode, J. B. Synlett 2012, 23,
1907–1912. doi:10.1055/s-0032-1316567
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
30.Nun, P.; Dupuy, S.; Gaillard, S.; Poater, A.; Cavallo, L.; Nolan, S. P.
Catal. Sci. Technol. 2011, 1, 58–61. doi:10.1039/C0CY00055H
31.Kramer, S.; Madsen, J. L. H.; Rottländer, M.; Skrydstrup, T. Org. Lett.
2010, 12, 2758–2761. doi:10.1021/ol1008685
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
32.Jiang, H.; Zeng, W.; Li, Y.; Wu, W.; Huang, L.; Fu, W. J. Org. Chem.
2012, 77, 5179–5183. doi:10.1021/jo300692d
33.Fillmore, F.; Hengyao, L.; Qingbei, Z. J. Org. Chem. 1994, 59,
4350–4354. doi:10.1021/jo00094a062
doi:10.3762/bjoc.10.60
34.Pérez, M.; Cano, R.; Yus, M.; Ramón, D. J. Synthesis 2013, 45,
1373–1379. doi:10.1055/s-0032-1316872
35.Müller, T. J. J. Top. Organomet. Chem. 2006, 19, 149–205.
doi:10.1007/3418_012
36.Merkul, E.; Klukas, F.; Dorsch, D.; Grädler, U.; Greiner, H. E.;
Müller, T. J. J. Org. Biomol. Chem. 2011, 9, 5129–5136.
doi:10.1039/C1OB05586K
37.Merkul, E.; Urselmann, D.; Müller, T. J. J. Eur. J. Org. Chem. 2011,
238–242. doi:10.1002/ejoc.201001472
38.Urselmann, D.; Antovic, D.; Müller, T. J. J. Beilstein J. Org. Chem.
2011, 7, 1499–1503. doi:10.3762/bjoc.7.174
39.De Oliveira, R. B.; De Souza-Fagundes, E. M.; Siqueira, H. A. J.;
Leite, R. S.; Domici, C. L.; Zani, C. L. Eur. J. Med. Chem. 2006, 41,
756–760. doi:10.1016/j.ejmech.2006.03.010
40.Pavlopoulos, T. G.; Hammond, P. R. J. Am. Chem. Soc. 1974, 96,
6568–6579. doi:10.1021/ja00828a005
41.Jones, G., II; Jackson, W. R.; Choi, C.; Bergmark, W. R.
J. Phys. Chem. 1985, 89, 294–300. doi:10.1021/j100248a024
42.Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.;
Springer: Berlin/Heidelberg, 2006; chapter 1.9.
43.Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785–789.
doi:10.1103/PhysRevB.37.785
679