Fluorescent donor-acceptor psoralen cruciforms by consecutive suzuki-suzuki and sonogashira-sonogashira one-pot syntheses

Article abstract of DOI:10.1021/acs.joc.0c01059

Two novel donor-acceptor cruciform topologies are efficiently synthesized by site-selective Suzuki-Suzuki and Sonogashira-Sonogashira multicomponent reactions starting from a bromo-triflato-functionalized psoralen scaffold. In addition to tunability of photophysical properties, such as absorption and emission, many derivatives possess partially high relative fluorescence quantum yields in solution and fluoresce strongly in the solid state. Additionally, the promising compounds show solvatochromism and acidochromic effects. In addition, 8-p-anisyl-5-p-cyanophenyl-substituted psoralen exhibits aggregation-induced emission properties. Experimentally (applying the Lippert-Mataga model) and computationally (TD-DFT calculations), the pronounced charge transfer character of the longest wavelength absorption band was confirmed.

Full text of DOI:10.1021/acs.joc.0c01059

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Article
Fluorescent Donor-Acceptor-Psoralen Cruciforms by Consecutive
Suzuki-Suzuki and Sonogashira-Sonogashira One-pot Syntheses
Sarah R. Geenen, Torben Schumann, and Thomas J. J. Mueller
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01059 • Publication Date (Web): 23 Jun 2020
Downloaded from pubs.acs.org on June 28, 2020
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Page 1 of 14
The Journal of Organic Chemistry
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Fluorescent Donor-Acceptor-Psoralen Cruciforms by Consec-
utive Suzuki-Suzuki and Sonogashira-Sonogashira One-pot
Syntheses
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Sarah R. Geenen, Torben Schumann, and Thomas J. J. Müller*
Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1,
D-40225 Düsseldorf, Germany
Supporting Information Placeholder
ABSTRACT: Two novel donor-acceptor cruciform topologies are efficiently synthesized by site-selective Suzuki-Suzuki and So-
nogashira-Sonogashira multicomponent reactions starting from a bromo-triflato functionalized psoralen scaffold. Besides tunability
of photophysical properties, such as absorption and emission, many derivatives possess partially high relative fluorescence quantum
yields in solution and fluoresce strongly in the solid state. Additionally, the promising compounds show solvatochromism and acido-
chromic effects. Besides, 8-p-anisyl-5-p-cyanophenyl substituted psoralen exhibits aggregation induced emission properties. Exper-
imentally (applying the Lippert-Mataga model) and computationally (TD-DFT calculations), the pronounced charge transfer charac-
ter of longest wavelength absorption band was confirmed.
Introduction
skin and the affected areas were exposed to sunlight, whereby a
7
a
pigmentation of the skin appears. Today the accepted mode of ac-
Functional -systems are particularly valuable in modern appli-
cations, such as molecular electronics and photonics. Especially,
in the field of life sciences certain representatives of such chromo-
phores are highly attractive for therapy and diagnostic applications
9
1
tion is based on the PUVA mechanism. A double [2+2]-cycload-
dition between the psoralen and the DNA bases is supposed to
1
0
cause apoptosis inducing crosslinks. Recent studies also suggest
that, depending on the psoralen derivative and directly adjacent
base pair in the DNA helix, a photo-induced electron transfer takes
2
(
theranostics) due to their electronic properties. X-shaped mole-
cules with frontier orbitals that are localized on orthogonally ar-
ranged branches, so called cruciforms, enable the design of func-
tional chromophores with interesting properties stemming from
significant changes of the transition dipole vector‘s orientation. As
a modern approach, we have disclosed modular syntheses of func-
tional chromophores with tunable electronic characteristics by con-
11
place as a competitive process.
Most research areas are focused on the synthesis of naturally oc-
3
12
curring psoralen derivatives, such as 8-methoxypsoralen or its re-
1
3
lated compounds. Recently, starting from 5-bromo-8-methox-
ypsoralen we successfully disclosed diversity-oriented cross-cou-
pling reactions to 5-arylated, 5-styrylated and 5-arylalkynylated 8-
methoxypsoralens with fine-tunable absorption and emission max-
4
secutive and diversity-oriented multicomponent reactions. In par-
ticular, novel systems showing distinctive properties, such as
strong emission solvatochromism and aggregation-induced behav-
ior, became accessible and structure-property relationships were
1
4
ima (Scheme 1). Due to the inherent donor-acceptor chromophore
structure of psoralen we reasoned that placing donor and acceptor
moieties in positions 5 and 8 could result in orthogonal bis(donor-
acceptor) cruciforms. These X-shaped chromophores presumably
5
established. Furthermore, the concept of sequentially palladium-
catalyzed processes has often adopted a pivotal role, several con-
secutive reactions are conducted in the same reaction vessel using
a sole, suitable catalyst.
will possess distinct spatially separated frontier molecular orbitals
6
3a,15
(FMO).
These features are particularly interesting beyond pso-
ralen-typical applications as absorbers or emitters in molecular
photonics.
Psoralen, furo[3,2-g]chromen-7-one, is a tricyclic donor-accep-
tor heterocycle with ligation of electron-rich furan and electron-
poor -pyrone to a central benzene core. It occurs naturally in Pso-
ralea corylifolia, which has already been used as a medicinal plant
for thousands of years, without exactly knowing its mode of ac-
1
5b,16
Here, we report consecutive three-component syntheses of pso-
ralen cruciforms based upon site-selective Suzuki arylation and So-
nogashira alkynylation giving rise to unsymmetrically functional-
ized donor-acceptor psoralens in a one-pot fashion. The electronic
structure is investigated by absorption and emission spectroscopy,
7
tion. Psoralen was mainly used to treat various skin diseases such
8
as vitiligo or psoriasis. Therefore, the substance is applied on the
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Page 2 of 14
unambiguously assigned by H, 19F, and 13C NMR spectroscopy as
well as mass spectrometry.
1
as well as by (TD)DFT calculations. In addition, attractive photonic
characteristics, such as emission solvatochromism, acidochrom-
ism, and aggregation-induced emission, can be identified.
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For coupling the triflate functionality with a donor boronic acid,
several conditions were tested. Suzuki coupling of triflate 5 with p-
methoxyphenyl boronic acid (6a) in the presence of Pd(PPh ) as a
3 4
catalyst and cesium carbonate as base in DMF was unsuccessful
and resulted in a cleavage of the triflate. Neither conditions applied
for the formation of educt 5 (Scheme 3), nor Pd(dppf)Cl
2
and dry
cesium acetate in tetrahydrofuran led to the targeted product.
However, using Pd(dba) and SPhos as a catalyst system and po-
22
2
tassium phosphate as a base in THF/water finally gave rise to the
formation of the donor-acceptor system 7a in 77% yield after flash
chromatography (Scheme 4).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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0
1
2
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5
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0
1
2
3
4
5
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0
1
2
3
4
5
6
7
8
9
0
Scheme 1. Suzuki, Heck and Sonogashira approach to 5-substi-
tuted 8-methoxypsoralens with conjugated aryl, styryl, and ar-
Scheme 4. Suzuki synthesis of 5-donor-8-acceptor psoralen 7a.
ylethynyl substituents (R = CN, NO
2 2
, CHO, NMe etc.).
Applying the conditions outlined in Scheme 4 to the coupling of
5-bromo-8-triflatopsoralen (3) with p-cyanophenyl boronic acid
(4a) to furnish intermediate 5 gave a yield of 59% after isolation.
Interestingly, performing consecutively both couplings with bo-
Results and Discussion
Synthesis. For envisioning twofold site-selective stepwise cross-
coupling in the sense of a sequentially Pd-catalyzed process17 two
different (pseudo)halogen functionalities are prerequisite. Starting
from 8-methoxypsoralen (1), convenient selective monobromina-
tion was performed in 5-position to give 5-bromo-8-methoxypso-
2
ronic acids 4a and 6a with Pd(dba) and SPhos as the initially em-
ployed catalyst system resulted in formation of the donor-acceptor
psoralen 7a, which was isolated after flash chromatography in 82%
yield. This is a significantly higher yield of the one-pot process in
comparison to the combined stepwise processes furnishing com-
pound 7a only in 52% yield after isolation. These conditions were
applied to illustrate the novel consecutive three-component synthe-
sis of donor-acceptor psoralens 7 in 8 examples with yields in a
range of 32-82% (Scheme 5, for experimental details see Table 1).
The structures of the compounds 7 were unambiguously assigned
1
4,18
ralen (2) in excellent yield (Scheme 2).
Then, after demethyla-
1
9
tion of compound 2 with boron tribromide followed by triflation
with trifluoromethanesulfonic acid anhydride the proposed 5-
2
0
bromo-8-triflatopsoralen (3) was obtained in 86% over two steps.
1
13
by H and C NMR spectroscopy as well as mass spectrometry.
Besides p-cyanophenyl boronic acid (4a) p-nitro- (4b), p-
formyl- (4c), and p-trifluoromethyl (4d) derivatives were employed
as acceptor substrates, whereas p-methoxyphenyl (6a) and p-dime-
thylaminophenyl (6b) boronic acids were chosen as donor reac-
tants. This one-pot synthesis specifically takes advantage of the
concept of sequentially Pd-catalyzed processes where a single cat-
alyst system is operating in a one-pot fashion without further addi-
Scheme 2. Synthesis of 5-bromo-8-triflatopsoralen (3). a) 3.00
equivs HBr, 3.00 equivs DMSO, EtOAc, 60 °C, 16 h. b) 4.00 equivs
BBr
3
(1.00 m in CH
2
Cl
2
), CH
2 2 2
Cl , 0 °C, 3 h. c) 2.00 equivs Tf O,
3
.60 equivs pyridine, CH
2
2
Cl , 0 °C, 2 h.
17
For selectively introducing acceptor and donor units, Suzuki
tion of catalyst.
2
1
coupling was performed according to Fu’s conditions. In the pres-
ence of Pd (dba) as a catalyst, potassium fluoride as a base, tri-
With this concise consecutive Suzuki-Suzuki three-component
synthesis of 5-donor substituted 8-acceptor psoralens in hand, we
reasoned that a similar process based of a consecutive Sonogashira-
Sonogashira sequence could lead to alkynyl-expanded 5-donor sub-
stituted 8-acceptor psoralens. However, site selective Sonogashira
coupling turned out to be more challenging and three optimization
studies were performed, where Pd-catalyst systems, bases, sol-
2
3
tert-butylphosphonium tetrafluoroborate was used as a ligand in
THF as a solvent at room temperature (Scheme 3).
vents, and reaction temperatures and times had to be identified (see
®
Supp. Inf., chpt 1.1.). First, Pd
as a catalyst system with NEt
2
(dba)
3
3
and cataCXium ABn · HBr
23
as a base in 1,4-dioxane at 75 °C
for 24 h were identified as best conditions for coupling an acceptor
substituted alkyne selectively at the 5-bromo position of 5-bromo-
8
-triflatopsoralen (3) (for details, see Supp. Inf., Table S1). Then,
Scheme 3. Suzuki synthesis of the 5-(p-cyanophenyl) substituted
8-psoralen triflate 5.
the site-selective coupling with a donor substituted alkyne at the 8-
triflato position of this intermediate was found to occur optimally
with Pd(PPh ) as a catalyst in DMSO at 90 °C for 20 h (for details,
3 4
Under these conditions, 5-bromo-8-triflatopsoralen (3) was se-
lectively coupled with p-cyanophenyl boronic acid (4a) to give the
see Supp. Inf., Table S2).
5
-(p-cyanophenyl) substituted 8-psoralen triflate 5 in a good yield
Finally, the complete one-pot sequence with two consecutive So-
nogashira alkynylations, starting 5-bromo-8-triflatopsoralen (3)
of 67% after flash chromatography. The structure of product 5 was
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proceeds optimally, indeed, with two different catalyst systems in
each step. The first alkynylation takes place with Pd (dba) and cat-
aCXium ABn · HBr as a catalyst system in 1,4-dioxane at 75 °C
for 24 h, followed by addition of Pd(PPh and DMSO for the sec-
ond alkynylation at 90 °C for 18 h (for details, see Supp. Inf., Table
S3). These conditions were then applied to 5-bromo-8-triflatopso-
ralen (3), p-(acceptor)phenylacetylenes 8, (8a: p-Acc = CN; 8b: p-
Acc = CHO), and p-(donor)phenylacetylenes 9 (9a: p-Do = OMe;
9b: p-Do = NMe ). This novel consecutive three-component syn-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
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3
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4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
3
2
®
thesis of alkynyl-expanded 5-donor substituted 8-acceptor psora-
lens 10 is illustrated in nine examples with yields in a range of 31-
77% (Scheme 6, , for experimental details see Table 2). The struc-
3 4
)
1
tures of the compounds 10 were unambiguously assigned by H and
13
C NMR spectroscopy as well as mass spectrometry.
2 3 6 4
Acc = NO ; 8c: p-Acc = CF ; 8d: p-(Acc)C H = 4-pyridyl; 8e: p-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 5. Selective consecutive sequentially Pd-catalyzed Suzuki-Suzuki three-component synthesis of 5-donor substituted 8-acceptor pso-
ralens 7.
Table 1. Experimental details of the selective Suzuki-Suzuki three-component synthesis of 5-acceptor-8-donor psoralens 7.
5
-Bromo-8-tri-
Pd(dba)
SPhos [mg]
([mmol])
2
/
KF
[mg]
([mmol])
214
(3.69)
106
(1.82)
63.2
(1.09)
106
(1.82)
63.2
(1.09)
106
(1.82)
84.4
(1.45)
106
K
[mg]
3
PO
4
p-(Acc)C
6
H
4
B(OH)
2
THF p-(Do)C
6
H
4
B(OH)
2
Product 7 (yield)
flatopsoralen (3)
4 [mg] ([mmol])
198 (1.35) of 4a
103 (0.700) of 4a
66.7 (0.400) of 4b
111 (0.666) of 4b
61.2 (0.408) of 4c
100 (0.666) of 4c
106 (0.558) of 4d
133 (0.668) of 4d
[mL]
5.00
2.50
1.75
2.50
1.75
2.50
2.00
2.50
6 [mg] ([mmol])
205 (1.35) of 6a
116 (0.700) of 6b
[mg] (%)
[
mg] ([mmol])
510 (1.23)
([mmol])
1040
(4.92)
513
(2.42)
308
(1.45)
513
(2.42)
308
(1.45)
513
(2.42)
411
(1.94)
513
(2.42)
1
42 (0.247) /
386 (80) of 7a
98.4 (40) of 7b
120 (80) of 7c
82.1 (32) of 7d
137 (76) of 7e
86.7 (32) of 7f
143 (68) of 7g
130 (44) of 7h
1
21 (0.295)
6
9.6 (0.121) /
2
1
2
1
2
50 (0.605)
50 (0.363)
50 (0.605)
50 (0.363)
50 (0.605)
6
7.1 (0.163)
4
1.7 (0.0726) /
62.0 (0.408) of 6a
116 (0.700) of 6b
62.0 (0.408) of 6a
110 (0.666) of 6b
80.9 (0.532) of 6a
110 (0.666) of 6b
40.2 (0.0980)
69.6 (0.121) /
67.1 (0.163)
1.7 (0.0726) /
0.2 (0.0980)
4
4
6
9.6 (0.121) /
6
7.1 (0.163)
5.7 (0.0968) /
7.7 (0.116)
9.6 (0.121) /
7.1 (0.163)
5
200 (0.484)
50 (0.605)
4
6
2
6
(1.82)
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
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2
2
2
2
2
2
2
2
2
3
3
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3
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4
4
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4
4
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5
5
5
5
5
5
5
5
6
0
1
2
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4
5
6
7
8
9
0
1
2
3
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 6. Selective consecutive Sonogashira-Sonogashira three-component synthesis of alkynyl-expanded 5-donor substituted 8-acceptor
psoralens 10.
Table 2. Experimental details of the selective Sonogashira coupling of alkynyl expanded 5-donor substituted 8-acceptor psoralens 10.
Pd
2
(dba)
3
/ cat-
p-Do-
CCH
9 [mg]
5-Bromo-8-tri-
flatopsoralen (3)
p-Acc-
BCCH 8
[mg] ([mmol])
1,4-di-
oxane
[mL]
4
Pd(PPh) / DMSO
[mg] ([µmol]) /
[mL]
aCXium
NEt
[mg] ([mmol])
3
/ CuI
C
6
H
4
Product 10
(%) [mg]
C
6
H
4
®
.
ABn HBr
mg] ([µmol])
6.08 (6.65) /
11.4 (24.1)
2.21 (2.42) /
4.58 (9.68)
1.90 (2.08) /
3.55 (7.51)
1.90 (2.08) /
3.55 (7.51)
2.29 (2.50) /
4.73 (10.0)
2.29 (2.50) /
4.73 (10.0)
2.29 (2.50) /
4.73 (10.0)
9.70 (10.6) /
20.0 (42.4)
2.29 (2.50) /
4.73 (10.0)
2.29 (2.50) /
4.73 (10.0)
[
mg] ([mmol])
[
([mmol])
96.6 (0.732)
of 9a
38.1 (0.266)
of 9b
30.3 (0.229)
of 9a
33.2 (0.229)
of 9b
36.3 (0.275)
of 9a
40.0 (0.275)
of 9b
9
3.1 (0.732) of
202 (2.00) /
10.1 (0.0531)
73.5 (0.726) /
3.69 (0.0194)
63.1 (0.624) /
3.16 (0.0166)
63.1 (0.624) /
3.16 (0.0166)
75.9 (0.75) /
3.80 (2.00)
75.9 (0.75) /
3.80 (2.00)
75.9 (0.75) /
3.80 (2.00)
322 (3.18) /
16.1 (8.48)
75.9 (0.75) /
3.80 (0.0200)
75.9 (0.75) /
3.80 (2.00)
196 (77) of
10a
40.1 (34)
of 10b
40.0 (43)
of 10c
59.2 (60)
of 10d
84.1 (70)
of 10e
64.0 (52)
of 10f
45.0 (43)
of 10g
177 (40) of
10g
2
1
74 (0.664)
00 (0.242)
3.00
1.50
1.00
1.00
1.00
1.00
1.00
4.00
1.00
1.00
14.4 (12.5) / 3.00
5.60 (4.84) / 1.50
4.80 (4.16) / 1.00
4.80 (4.16) / 1.00
5.78 (5.00) / 1.00
5.78 (5.00) / 1.00
5.78 (5.00) / 1.00
24.5 (21.2) / 4.00
5.78 (5.00) / 1.00
5.78 (5.00) / 1.00
8
a
33.8 (0.266) of
8a
33.7 (0.229) of
8
8
5.9 (0.208)
5.9 (0.208)
8
b
3
4
4
3
3.7 (0.229) of
8
b
6.8 (0.275) of
103 (0.250)
103 (0.250)
8
c
6.8 (0.275) of
8
c
8.4 (0.275) of
36.3 (0.
1
03 (0.250)
8
d
275) of 9a
158 (1.20)
of 9a
40.0 (0.275)
of 9b
4
36 (1.06)
03 (0.250)
03 (0.250)
124 (1.20) of 8d
38.4 (0.275) of
53.8 (50)
of 10h
34.0 (31)
of 10i
1
1
8
d
3
5.7 (0.275) of
36.3 (0.
275) of 9a
8
a
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Photophysical properties. All cruciforms 7 and 10 are colorless
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9
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1
1
1
1
1
1
1
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2
2
2
2
2
2
3
3
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3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
to red solids, depending on the substitution pattern. Moreover, with
exception of the nitro derivatives 7c,d and 10c,d, all dyes are emis-
sive in solution and in the solid state upon excitation with the hand-
held UV lamp (Figures 1 and 2). Therefore, a comprehensive quan-
titative photophysical characterization by measuring absorption
and emission spectra, and determining relative fluorescence quan-
24
F
tum yields  with Coumarin 30 as a standard was conducted for
all cruciforms 7 and 10 (Tables 3 and 4).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 2. Psoralen derivatives 10 in solid state in daylight (top row)
and in UV-light (center row), and in dichloromethane (bottom row,
-
7
c(10) = 10 M, hand-held UV-Lamp, exc = 365 nm).
Table 4. Selected photophysical properties of alkynyl expanded 5-
acceptor-8-donor psoralens 10.
[a]
max,em [nm][b]
compound

max,abs [nm]

Stokes shift
-
1
-1
-1 [c]
( [M cm ])
304 (20300)
365 (29200)
93 (22300)
273 (26200)
31 (36000)
32 (27200)
308 (30000)
372 (35300)
404 (34700)
280 (29800)
(
F
[a.u.])

̃
[cm ]
10a
Figure 1. Psoralen derivatives 7 in solid state in daylight (top row)
492 (0.38)
620 (0.32)
-
5100
and in UV-light (center row), and in dichloromethane (bottom row,
3
-
7
c(7) = 10 M, hand-held UV-lamp, exc = 365 nm).
1
0b
3
4
7000
-
Table 3. Selected photophysical properties of 5-substituted 5-ac-
ceptor-8-donor psoralens 7.
1
0c
[
a]
max,em [nm][b]
compound

(
max,abs [nm]

Stokes shift
-
1
-1
-1 [c]
 [M cm ])
(
F
[a.u.])

̃
[cm ]
1
0d
7
7
a
313 (21000)
-
-
3
32 (42200)
-
-
3
59 (6300sh)
443 (31200)
318 (28100)
360 (40700)
b
308 (25300)
10e
3
45 (14300sh)
586 (0.10)
8700
480 (0.08)
602 (0.06)
478 (0.08)
618 (0.05)
487 (0.08)
4900
7700
4800
7100
4700
3
88 (7300sh)
325 (16000)
376 (8100sh)
305 (24900)
402 (7200sh)
317 (17900)
3
88 (27400)
7
c
-
-
-
-
1
0f
275 (21100)
3
4
31 (35000)
12 (19900)
7d
1
0g
0h
315 (28500)
7
e
4
55 (0.05)
5300
3
3
60 (40800)
89 (29600)
3
67 (5400sh)
302 (29000)
43 (16700sh)
7
f
1
275 (24600)
31 (39000)
3
600 (0.17)
452 (0.01)
573 (0.07)
8900
5600
8600
3
3
93 (8800sh)
429 (27500)
310 (24400)
367 (33300)
397 (27221)
7
7
g
287 (27700)
10i
3
14 (23200sh)
3
60 (6100sh)
304 (25800)
340 (14400sh)
384 (5600sh)
h
[
a]
Recorded in CH
2
Cl2, c(10) = 10 M at T = 293 K. [b] Recorded
-5
-
7
2 2
in CH Cl , c(10) = 10 M at T = 293 K, relative quantum yields
were determined with Coumarin 30 as a standard in acetonitrile (
F
[
a]
Recorded in CH
2
Cl2, c(7) = 10 M at T = 293 K. [b] Recorded
-5
1
1
2
4
[c]
, c(7) = 10- M at T = 293 K, relative quantum yields were
7
= 0.67 ). 
̃
=
−
.
in CH Cl
2 2
휆푚푎푥,푎푏푠
휆푚푎푥,푒푚
determined with Coumarin 30 as a standard in acetonitrile (
F
=
For all (hetero)aryl substituted compounds 7 the longest wave-
length absorption band in dichloromethane is just discernible as a
shoulder (Figure 3). These psoralen derivatives exhibit relatively
1
1
2
4
[c]
0
.67 ). 
̃
=
−
.
휆푚푎푥,푎푏푠
휆푚푎푥,푒푚
-
1
-
low molar absorption coefficients  between 5600 and 8800 M cm
1
(Table 3). Changing the donor substituent from p-methoxy to p-
dimethylamino for the same acceptor moiety causes a significant
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bathochromic shift of the longest wavelength absorption maxima
bottom). At a water/acetonitrile ratio of 50% a significant increase
-
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
between 1720 and 2082 cm . Even more pronounced is the redshift
of the emission maxima upon changing from p-methoxy (7e: 455
nm) to p-dimethylamino substitution (7f: 600 nm). This reflects
also in the Stokes shifts, which appear for p-dimethylamino deriv-
of fluorescence intensity with a concomitant solvatochromic effect
occurs up to 70%. At higher water content the color shifts to sky
blue (for further details, see Supp. Inf. Figure S15).
-
1
atives 7b, 7f, and 7h between 8600 and 8900 cm and for p-meth-
-1
oxy derivatives 7e and 7g between 5300 and 5600 cm . The fluo-
F
rescence quantum yields  of the cruciforms 7 range between 1
and 17% and are mainly related to the donor strength of the substit-
uents. Thus, directly linked p-dimethylaminophenyl-substituted
psoralens tend to show higher relative fluorescence quantum yields,
while anisyl-functionalized psoralens 7 show no or only low rela-
tive fluorescence quantum yields of up to 5 %. As mentioned above
the nitro derivatives 7c-d do not fluoresce as a consequence of a
common competitive deactivation of the excited state by predisso-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
5
ciation. With exception of compound 7d all (hetero)aryl psoralen
cruciforms 7 fluoresce in the solid state with tunable emission color
from blue over green to yellow and orange (Figure 1, center).
Figure 4. Normalized UV/Vis absorption (recorded in CH
2
Cl
293 K, c(10) = 10 M, bold lines) and emission bands (recorded in
CH Cl
, T = 293 K, c(10) = 10-7 M, dashed lines) of compounds 10.
2
, T =
-
5
2
2
Figure 3. Normalized UV/Vis absorption (recorded in CH
2
Cl
2
, T =
-5
2
93 K, c(7) = 10 M, bold lines) and emission bands (recorded in
2 2
CH Cl
, T = 293 K, c(7) = 10- M, dashed lines) of compounds 7.
7
Compared to 5-donor substituted 8-acceptor psoralens 7 their al-
kynyl-expanded congeners 10 in dichloromethane solutions clearly
exhibit pronounced maxima of the longest wavelength absorption
bands, as a consequence of the extended -conjugation, in a range
between 388 and 443 nm with intense molar absorption coefficients
-
1
-1
between 22300 and 34700 Lmol cm (Figure 4, Table 4). The
emission maxima of cruciforms 10 with similar substituent patterns
are redshifted as well and appear between 480 and 620 nm with
Figure 5. Top: Cruciform 7a in different MeCN/H
(from left to right the ratio of H O increases) (hand-held UV-Lamp,
exc = 365 nm). Bottom: Aggregation induced emission of 7a in so-
2
O mixtures
2
-
1
Stokes shifts of 4700 to 5100 cm for p-methoxy derivatives and
000 to 7700 for p-dimethylamino systems. Furthermore, their flu-
orescence quantum yields  (between 5 and 38%) are signifi-

7
lution measured in MeCN/H
2
O (recorded at T = 293 K, c(7a) = 2.41
.
-4
F
10 M , exc = 359 nm).
cantly higher than the corresponding (hetero)aryl substituted cruci-
forms 7, being no longer dependent on the donor strength of the
aryl acetylene in position 8. Here, the acceptor strength seems to
have a more significant effect, since especially the strongly elec-
tron-withdrawing cyano group leads to a very high relative fluores-
cence quantum yield. Again, the nitro derivatives 10c-d do not flu-
oresce in solution due to deactivation (Figure 2, bottom).
The combination of large Stokes shifts and donor-acceptor sub-
stitution pattern accounts for significant excited state polarity.
Therefore, we performed solvatochromism studies with selected
cruciforms 7 and 10. First, absorption and emission spectra of 5-(p-
dimethylaminophenyl)-8-(p-trifluoromethylphenyl)psoralen (7h)
were recorded in solvents of different polarity, indicating a pro-
nounced positive emission solvatochromism (Figure 6, top),
whereas the absorption maxima essentially remained unchanged
(for details, see Supp. Inf., Table S4). The emission color shifts
from blue in cyclohexane to orange in dichloromethane (Figure 6).
The positive emission solvatochromicity accounts for a large dipole
The weak fluorescence of compound 7a in solution and its in-
tense emission in the solid state (Figure 1, center and bottom)
26
caught our interest to study its aggregation induced emission be-
havior in water/acetonitrile mixtures (Figure 5, top). While a pure
acetonitrile solution of compound 7a is essentially nonluminescent,
increasing water/acetonitrile ratios at constant cruciform concen-
tration causes a constant increase in emission intensity (Figure 5,
1
moment of the vibrationally relaxed S state, which is stabilized by
2
7
increasing solvent polarity.
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 6. Top: Fluorescence of compound 7h in solvents of differ-
ent polarity (from left to right: cyclohexane, toluene, chloroform,
ethyl acetate, tetrahydrofuran, dichloromethane; exc = 365 nm).
Bottom: UV/Vis absorption (bold lines) and emission (dashed
lines) spectra of compound 7h measured in six solvents of different
polarity recorded at T = 293 K.
Figure 7. UV/Vis absorption (bold lines) and emission (dashed
lines) spectra of compound 10a (top) and 10b (bottom) measured
in solvents of different polarity recorded at T = 293 K.
Dimethylamino substituted cruciforms will change the donor ef-
29
Applying the Lippert-Mataga model28 the change of dipole mo-
fect to an inductive acceptor upon protonation and should cause
for psoralen cruciforms significant changes of their photophysical
properties. Upon adding trifluoroacetic acid to dichloromethane so-
lutions of the dimethylamino-substituted cruciforms 7b and 10b,
the apparent fluorescence disappeared (compound 7b) or decreased
ment from ground to vibrationally relaxed excited state for com-
pound 7h is calculated by plotting the Stokes shifts of the solvent
against the corresponding orientation polarizability f to give  =
-
29
13 D (4.20  10 Cm), indicating a significant charge transfer char-
(compound 10b) (Figure 8). Upon addition of triethylamine as a
acter (for details, see Supp. Inf., Table S4 and Figure S2).
base, the acidochromicity can be reversed.
Likewise, the solvatochromism of two ethynyl-expanded cruci-
forms 10a-b was studied in detail. Expectedly, the weaker donor
methoxy in cruciform 10a results in considerably lower absorption
and emission solvatochromicity (Figure 7, top) than the stronger
donor dimethylamine in cruciform 10b (Figure 7, bottom). How-
ever, the effect of the stronger donor on the polarity of the excited
state becomes apparent by magnitude of the corresponding Stokes
-
1
shift in the same solvent, e.g. ethyl acetate (10a: 4300 cm ; 10b:
-
1
7
300 cm ). This is also supported by the ensuing values for the
2
8
change of dipole moments applying the Lippert-Mataga model
giving  = 11 D (3.57  10 Cm) for compound 10a and  = 17
-
29
-
29
D (5.50  10 Cm) for compound 10b (for details, see Supp. Inf.,
Table S5 and S6, and Figures S4 and S6). From the three studied
cruciforms 7h, 10a and 10b it becomes apparent that the charge
transfer character of the excited state is governed by the donor-ac-
ceptor substitution at positions 5 and 8, where the longest chromo-
phore axes are embedded.
Figure 8. Cruciforms 7b (top) and 10b (bottom) in dichloro-
methane and by addition of trifluoroacetic acid (TFA) and subse-
quently by addition of triethylamine under the hand-held UV lamp
-5
(
c = 10 M, exc = 365 nm).
The acidochromicity can be monitored by absorption and emis-
sion spectroscopy as shown for cruciform 10b (Figure 9). Upon
addition of aliquots of trifluoroacetic acid the longest wavelength
absorption maximum at 432 nm steadily decreases to a shoulder
while the absorption band at 331 nm redshifts to 363 nm by the
occurrence of isosbestic points. Upon plotting the spectral changes
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+
311G(d,p)34 basis set. For comparison with the experimental data,
the pK
a
value of 10b+H is determined to 2.78 (for experimental
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
details, see Supp. Inf., Figure S10). Likewise, a pK
is determined for 7b+H .
a
value of 3.65
the polarizable continuum model (PCM) with dichloromethane as
solvent was chosen. For comparing the general tendency, the
+
35
methoxy (7a and 10a) and dimethylamino (7b and 10b) donor sys-
tems bearing a cyano substituent as an acceptor are briefly dis-
cussed. Starting from the geometry-optimized structures the lowest
energy Franck-Condon singlet configurations of cruciforms 7a-b
and 10a-b were computed on the level of TD-DFT theory using the
3
6
Pople 6-3-11G(d,p) basis set (Table 5). As the experimental spec-
tra reveal broad shoulders (compounds 7) and broad maxima (com-
pounds 10) for the longest wavelength absorption maxima, devia-
tions to the calculated maxima of the lowest energy Franck-Condon
singlet configurations to longer wavelengths are often found. Nev-
ertheless, the significant oscillatory strengths indicate that they rep-
resent dominant, allowed transitions. In all cases, the longest wave-
length absorption maxima can be interpreted as HOMO-LUMO
transitions.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
As can be seen from the Kohn-Sham frontier molecular orbitals
the coefficient densities of the HOMOs of the methoxy-substituted
cruciforms 7a and 10a are located on the p-methoxy-p-cyano do-
nor-acceptor axes and the benzofuran moiety of the psoralen core
Figure 9. Absorption and emission spectra of 10b in the presence
2
of increasing amounts of trifluoroacetic acid (recorded in CH Cl ,
(
Figure 10). The electronic structure of the dimethylamino-substi-
2
-
5
.
-9
tuted chromophores 7b and 10b are exclusively located on the p-
dimethylamino-p-cyano donor-acceptor axes without any contribu-
tion of the benzofuran part. Therefore, the HOMO energy differ-
ences roughly amount to 0.5 to 0.6 eV in the corresponding con-
sanguineous pair. In contrast, the LUMO structures reveal that co-
efficient density is distributed over p-cyanophenyl(ethynyl) accep-
tor part and the complete psoralen, -pyrone and benzofuran. The
remote donor substituent affects neither the electronic structure nor
the LUMO energies, which only deviate by 0.06 eV within the con-
sanguineous pairs.
c(10b) = 9.46 · 10 M (absorption), c(10b) = 9.24 10 M (emis-
sion; the decrease of the fluorescence signal at 618 nm (exc = 432
nm) was monitored); T = 293 K).
a
In addition, the pK value can also be determined by emission
quenching using the Stern-Volmer model.30 In this case, the Stern-
Volmer constant upon protonation with trifluoroacetic acid corre-
sponds to the pK
a
values (for experimental details, see Supp. Inf.,
values of 2.62
10b+H ) and 3.90 (7b+H ) are in good agreement with the values
chpts. 5.2.3 and 5.2.4). The corresponding pK
a
+
+
(
determined by absorption measurements.
The electronic structure of the HOMO-LUMO contributed long-
est wavelength absorption band clearly reveals a charge transfer
character from the remote p-(donor)phenyl moiety to the T-shaped
p-(acceptor)phenyl-substituted psoralen, i.e. a deviation from the
main p-(donor)phenyl(ethynyl)-p-(acceptor)phenyl axis to a more
diffuse transfer in the psoralen-acceptor part. The charge transfer
character is in good agreement with the experimental findings of
emission solvatochromicity of these novel psoralen cruciforms.
Calculated electronic structure. For assigning the nature of the
longest wavelength absorption bands of these novel cruciforms,
TD-DFT calculations were performed for all psoralen chromo-
phores 7 and 10 (for details, see Supp. Inf., chpt. 7). The geometry
of the electronic ground state structures was optimized by Gaussian
3
1
32
0
9, with the PBE1PBE functional, taking into account signifi-
3
3
cant contributions of charge transfer character, and the Pople 6-
Table 5. Selected photophysical properties of alkynyl expanded 5-acceptor-8-donor psoralens 10. TD-DFT calculations (PBE1PBE/6-
311G(d,p) of the UV/Vis absorption maxima of 7a-b, 10a-b using PCM with dichloromethane as solvent.
-1
-1
compound

max,abs [nm][a] ( [M cm ])
max,calcd [nm]
dominant contributions
HOMOLUMO (96%)
oscillator strength
0.3226
7
a
359 (6300sh)
371
3
3
444
22
14
HOMO-1LUMO (44%), HOMOLUMO+1 (45%)
HOMO-1LUMO (48%)
HOMOLUMO (97%)
0.2018
0.1254
0.2613
313 (21000)
388 (7300sh)
7
b
3
3
68
34
HOMOLUMO+1 (94%)
HOMO-1LUMO (93%)
HOMOLUMO+2 (83%)
HOMOLUMO (98%)
HOMO-1LUMO (58%)
HOMO-2LUMO (41%)
HOMOLUMO (99%)
0.1252
0.1029
0.3384
1.4820
0.1704
0.4030
1.2437
3
45 (14300sh)
308 (25300)
393 (22300)
312
460
361
10a
3
65 (29200)
3
47
530
80
347
35
Cl2, c(7), c(10) = 10-5 M at T = 293 K.
2
1
0b
432 (27200)
3
HOMO-1LUMO (48%)
HOMO-2LUMO (76%)
HOMOLUMO+2 (79%)
0.7760
0.3515
0.2726
3
31 (36000)
3
[a]
Recorded in CH
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2
2
2
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2
2
2
2
2
3
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6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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8
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0
1
2
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 10. Selected Kohn-Sham frontier molecule orbitals (FMOs) of psoralens 7a-b and 10a-b (with PBE1PBE/6-311G(d,p) and PCM
with dichloromethane as solvent).
®
Conclusion
purification by adsorption of the crude products on Celite . The
reaction progress was observed qualitatively using TLC silica
gel 60 F254 aluminum sheets. The spots were detected with UV
light at 254 and 365 nm and with iodine vapor. Chemical shifts 
In summary, two site-selective and efficient one-pot syntheses
combining Suzuki-Suzuki and Sonogashira-Sonogashira sequen-
tially Pd-catalyzed processes have been disclosed employing 5-
bromo-8-triflatopsoralen as a versatile substrate. By implementing
donor- and acceptor-substituted coupling partners as substrates
novel orthogonally oriented cruciforms were formed, with the
newly installed donor-acceptor axis and psoralen, a donor-acceptor
composite by its own virtue. The title compounds reveal interesting
tunable photophysical properties, such as bright emission colors in
a range from sky-blue to deep orange, large Stokes shifts and par-
tially high fluorescence quantum yields of up to 38%. Particularly
promising are also aggregation induced emission of a solution
nonemissive derivative, solvatochromism and acidochromism of
several cruciforms. The experimentally determined change of di-
1
13
1
in the H and C{ H} NMR spectra are reported in ppm relative to
the signal of the remaining proton resonances of the deuterated sol-
vent. The assignments of Cquat, CH, CH , and CH signals were
2 3
made by using DEPT spectra. Melting points (uncorrected values)
were measured using a Büchi Melting Point B-535 apparatus.
5
-Bromo-8-triflatopsoralen (3). In a two-necked 100 mL round-
bottom flask with magnetic stir bar 5-bromo-8-methoxypsoralen
2) (1.59 g, 5.39 mmol) was solved in dichloromethane (19 mL)
14
(
and cooled down to 0 °C. Boron tribromide (1.00 M in dichloro-
methane, 21.6 mL, 21.6 mmol) was added to the reaction solution
and stirred at 0 °C for 3 h. Then, ice water was added and the pre-
cipitated intermediate product was dried in vacuo. The resulting
solid (1.51 g, 5.37 mmol) was dissolved in dichloromethane (25
mL) and pyridine (1.56 mL, 19.28 mmol) and cooled to 0 °C. After
addition of trifluoromethanesulfonic anhydride (1.79 mL, 10.62
mmol) the solution was stirred for at 0 °C for 2 h. The reaction was
then terminated by adding ice water (20 mL) and extracted with
dichloromethane (3 × 20 mL). The organic phases were combined,
a
pole moments and pK values additionally indicate that these novel
chromophores also have a potential as molecular sensors. Finally,
accompanying TD-DFT calculations assign and rationalize the
electronic structure of the longest wavelength absorption bands.
This novel type of psoralen derivatives tunable in their electronic
properties can as well be considered for PUVA therapy, since they
1
4
absorb efficiently in the range of visible light. As for other cruci-
3
a
forms sensory applications and responsive materials lie at hand.
Further studies directed to an extension of the synthetic concept to
other orthogonally attached chromophore branches, their electronic
properties and applications are currently underway.
®
dried (anhydrous sodium sulfate) and absorbed on Celite before
purification by column chromatography (petroleum ether/ethyl ac-
etate 1:1). Yield: 1.91 g (4.62 mmol, 86%), colorless crystals, R =
f
.47 (petroleum ether/ethyl acetate, 3:1), Mp 135 °C. H NMR:
1
0
Experimental Section
(300 MHz, CDCl )  = 8.13 (d, J = 10.0 Hz, 1 H), 7.83 (d, J = 2.3
3
Hz, 1 H), 6.97 (d, J = 2.2 Hz, 1 H), 6.51 (d, J = 10.0 Hz, 1 H).
General Considerations. Reactions were carried out in nitrogen
atmosphere by in heat-gun dried Schlenk glassware. Oil baths were
used as heating source for all thermal reactions. Dry solvents were
obtained from a solvent drying system. Commercially available re-
agents, catalysts and ligands were purchased and employed without
13
1
C{ H} NMR: (75 MHz, CDCl
3
)  = 157.6 (Cquat), 148.3 (CH),
1
46.5 (Cquat), 144.4 (Cquat), 141.9 (CH), 128.3 (Cquat), 120.6 (Cquat),
1
118.6 (Cquat, q, JCF = 320.8 Hz), 116.6 (CH), 115.9 (Cquat), 113.4
+
(Cquat), 107.9 (CH). MS (EI) (m/z (%)): 412 ([C12
H
4
79BrF
] , 100). IR: ṽ [cm ] 3170 (w), 3115 (w),
1734 (vs), 1636 (w), 1581 (m), 1460 (m), 1422 (s), 1391 (m), 1263
w), 1321 (m), 1298 (m), 1238 (m), 1209 (vs), 1186 (m), 1132 (s),
067 (s), 1026 (m), 989 (m), 887 (s), 797 (vs), 756 (s), 727 (w), 689
w), 652 (w), 631 (m). Anal. calcd. for C12 BrF S [411.89]: C
34.89, H 0.98, S 7.76. Found: C 34.87, H 0.81, S 7.77.
3 6
O S] ,
7
9
+
-1
1
4
4 4
20), 279 ([C11H BrO
further purification. 5-Bromo-8-methoxy-psoralen (2) and termi-
3
7
38
nal alkynes 8 and 9 were synthesized according to literature.
The purification of the crude products was carried out by column
chromatography with silica gel 60 (particle size 0.04-0.063 mm)
from Macherey and Nagel. A chromatograph apparatus used for
(
1
(
H
4
3 6
O
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 14
(d, J = 9.9 Hz, 1 H), 3.91 (s, 3 H). 13C{ H} NMR: (151 MHz,
1
General procedure GP1 of the selective consecutive Suzuki-
Suzuki three-component synthesis of 5-donor substituted 8-ac-
ceptor psoralens 7. 5-Bromo-8-triflatopsoralen (3, 1.00 equivs)
was placed in dry THF (4.50 mL/mmol) under nitrogen atmosphere
in a screw-cap Schlenk tube with magnetic stir bar (for experi-
mental details, see Table 1). The p-(acceptor)phenyl boronic acid 4
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CDCl ) δ = 160.2 (Cquat), 159.9 (Cquat), 153.7 (Cquat), 149.0 (Cquat),
3
147.9 (Cquat), 147.6 (CH), 142.6 (Cquat), 141.4 (CH), 131.8 (CH),
131.3 (CH), 128.9 (Cquat), 124.4 (Cquat), 124.1 (CH), 121.7 (Cquat),
115.1 (CH), 114.8 (Cquat), 114.1 (CH), 113.7 (Cquat), 105.7 (CH),
-
1
3
55.4 (CH ). IR: ṽ [cm ] = 1724 (s), 1581 (m), 1541 (w), 1510 (vs),
(
1.10 equivs), bis(dibenzylidene-acetone)palladium(0) (0.20
1456 (w), 1410 (w), 1342 (s), 1305 (w), 1251 (m), 1219 (w), 1184
(m), 1146 (s), 1130 (s), 1028 (s), 1011 (w), 924 (w), 903 (w), 870
(w), 852 (m), 831 (vs), 785 (m), 760 (s), 750 (s), 721 (m), 700 (m).
equivs), SPhos (0.24 equivs) and potassium fluoride (3.00 equivs)
were added and the solution was then degassed with nitrogen for 5
min. The reaction mixture was stirred at room temp for 24 h. Sub-
sequently, the p-(donor)phenyl boronic acid 6 (1.10 equivs), potas-
sium phosphate (4.00 equivs) and water (1 mL) were added and
stirred at 80 °C for further 24 h. After cooling, water was added (10
mL) and the aqueous phase extracted with dichloromethane (3 x 30
mL). The organic layers were combined and dried (anhydrous so-
dium sulfate). The mixture was adsorbed on Celite® and purified
by column chromatography (petroleum ether/ethyl acetate or petro-
leum ether/acetone). 4-(9-(4-Methoxyphenyl)-7-oxo-7H-furo[3,2-
g]chromen-4-yl)benzonitrile (7a). According to GP1 and after pu-
rification by flash chromatography on silica gel (petroleum
ether/acetone 3:1) and after crystallization from ethanol/dichloro-
methane (4:1) compound 7a (395 mg, 82%) was obtained as a yel-
+
MS (EI) (m/z (%)): 414 (25), 413 ([M] , 100). HR-MS (ESI) (m/z)
+
calcd. for (C24
H16NO
6
+H) : 414.0972; Found: 414.0976. HPLC
(acetonitrile): 99% (RT = 7.3 min).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
9
-(4-(Dimethylamino)phenyl)-4-(4-nitrophenyl)-7H-furo[3,2-
g]chromen-7-one (7d). According to GP1 and after purification by
flash chromatography on silica gel (petroleum ether/acetone 1:1)
and after crystallization from acetone compound 7d (82.1 mg,
3
2%) was obtained as a red solid, R
f
= 0.15 (petroleum ether/ethyl
acetate, 3:1). Mp 225 °C (dec). H NMR: (500 MHz, CD Cl ) δ =
8.48 – 8.37 (m, 2 H), 7.80 – 7.72 (m, 2 H), 7.73 – 7.63 (m, 4 H),
1
2
2
7
3
1
1
1
.01 (s, 2 H), 6.67 (d, J = 2.3 Hz, 1 H), 6.32 (d, J = 9.9 Hz, 1 H),
.08 (s, 6 H). C{ H} NMR: (126 MHz, CD Cl ) δ = 160.7 (Cquat),
2 2
54.5 (Cquat), 149.8 (Cquat), 148.6 (Cquat), 148.1 (CH), 143.4 (Cquat),
42.1 (CH), 132.1 (CH), 132.1 (CH), 129.3 (Cquat), 125.0 (Cquat),
13
1
lowish solid, R
f
= 0.25 (petroleum ether/ethyl acetate, 3:1). Mp 289
°C. H NMR: (300 MHz, CDCl ) δ = 7.91 – 7.86 (m, 2 H), 7.77 –
.69 (m, 4 H), 7.62 – 7.57 (m, 2 H), 7.14 – 7.07 (m, 2 H), 6.63 (d,
1
3
24.6 (CH), 117.8 (Cquat), 113.4 (Cquat), 115.4 (CH), 115.7 (Cquat),
7
-1
113.4 (Cquat), 106.4 (CH), 41.3 (CH
3
). IR: ṽ [cm ] = 1719 (s), 1609
1
3
1
J = 2.3 Hz, 1 H), 6.36 (d, J = 9.9 Hz, 1 H), 3.90 (s, 3 H). C{ H}
NMR: (75 MHz, CDCl ) δ = 160.4 (Cquat), 160.0 (Cquat), 153.8
quat), 149.1 (Cquat), 147.6 (CH), 141.6 (CH), 140.8 (Cquat), 132.8
CH), 132.0 (CH), 131.2 (CH), 129.5 (Cquat), 124.5 (Cquat), 121.9
quat), 118.4 (Cquat), 115.1 (CH), 114.8 (Cquat), 114.2 (CH), 113.7
(m), 1570 (m), 1508 (s), 1449 (w), 1408 (w), 1368 (w), 1340 (m),
300 (m), 1233 (w), 1200 (m), 1144 (s), 1107 (m), 1067 (w), 1040
s), 1015 (w), 989 (m), 951 (w), 923 (w), 851 (w), 829 (m), 818 (s),
91 (w), 768 (s), 748 (w), 700 (w), 615 (w). MS (EI) (m/z (%)): 427
3
1
(
(
(
(
C
7
C
+
(35), 426 ([M] ,100). HR-MS (ESI) (m/z) calcd. for
-
1
(Cquat), 112.7 (Cquat), 105.9 (CH), 55.5 (CH
3
). IR: ṽ [cm ] = 2901
+
25 18 2 5
(C H N O +H) : 427.1288; Found: 427.1289. HPLC (acetoni-
(w), 2228 (w), 1724 (s), 1605 (w), 1582 (m), 1516 (m), 1458 (w),
trile): 98% (RT = 7.4 min).
1
429 (w), 1408 (w), 1356 (w), 1290 (m), 1254 (s), 1179 (m), 1136
4
-(9-(4-Methoxyphenyl)-7-oxo-7H-furo[3,2-g]chromen-4-
(s), 1109 (m), 1028 (s), 926 (w), 901 (w), 868 (m), 826 (s), 802 (m),
+
yl)benzaldehyde (7e). According to GP1 and after purification by
flash chromatography on silica gel (petroleum ether/acetone 3:1)
and after crystallization from acetone compound 7e (137 mg, 76%)
7
54 (m), 719 (w). ESI-MS (m/z): 394.5 ([M+H] , 100%). HR-MS
+
(ESI) (m/z) calcd. for (C25
H
15NO
4
+H) : 394.1074; Found:
94.1073. HPLC (acetonitrile/acetone): 99% (RT = 4.7 min).
-(9-(4-(Dimethylamino)phenyl)-7-oxo-7H-furo[3,2-
3
was obtained as a yellow solid, R
f
= 0.38 (petroleum ether/ethyl
acetate, 3:1). Mp 257 °C (dec). H NMR: (600 MHz, CDCl ) δ =
0.16 (s, 1 H), 8.15 – 8.02 (m, 2 H), 7.80 (d, J = 9.9 Hz, 1 H), 7.75
7.72 (m, 2 H), 7.70 (d, J = 2.3 Hz, 1 H), 7.67 – 7.63 (m, 2 H),
4
1
3
g]chromen-4-yl)benzonitrile (7b). According to GP1 and after pu-
rification by flash chromatography on silica gel (petroleum
ether/acetone 3:1) and after crystallization from dichloromethane
compound 7b (98.4 mg, 40%) was obtained as an orange solid, R
=
1
–
7.15 – 7.05 (m, 2 H), 6.66 (d, J = 2.3 Hz, 1 H), 6.35 (d, J = 9.9 Hz,
f
13
1
1 H), 3.90 (s, 3 H). C{ H} NMR: (151 MHz, CDCl
3
) δ = 191.6
1
0.25 (petroleum ether/ethyl acetate, 3:1). Mp 295 °C (dec). H
(
(
(
(
(
(
CH), 160.4 (Cquat), 159.8 (Cquat), 153.7 (Cquat), 149.0 (Cquat), 147.3
CH), 142.0 (Cquat), 141.9 (CH), 136.1 (Cquat), 131.8 (CH), 131.0
CH), 130.2 (Cquat), 130.1 (CH), 124.4 (Cquat), 121.9 (Cquat), 114.7
NMR: (500 MHz, CDCl
3
) δ = 7.93 – 7.82 (m, 2 H), 7.78 – 7.68 (m,
H), 7.03 (s, H), 6.61
d, J = 2.2 Hz, 1 H), 6.35 (d, J = 9.8 Hz, 1 H), 3.08 (s, 6 H). C{ H}
NMR: (126 MHz CDCl ) δ = 160.6 (Cquat), 154.1 (Cquat), 149.4
(Cquat), 147.8 (CH), 141.8 (CH), 141.2 (Cquat), 133.0 (CH), 132.0
4
(
H), 7.62
–
7.55 (m,
2
2
13
1
CH), 114.4 (Cquat), 114.1 (CH), 113.7 (Cquat), 106.0 (CH), 55.4
3
-1
CH
3
). IR: ṽ [cm ] = 1719 (vs), 1692 (vs), 1603 (m), 1582 (s), 1541
w), 1514 (m), 1460 (w), 1410 (w), 1358 (w), 1304 (m), 1250 (m),
(
(
(
CH), 132.0 (Cquat), 131.5 (CH), 129.2 (Cquat), 124.7 (Cquat), 118.6
1204 (w), 1173 (m), 1144 (vs), 1113 (s), 1096 (w), 1031 (s),
C
quat), 115.3 (CH), 114.0 (Cquat), 112.9 (Cquat), 112.9 (Cquat), 106.1
993 (m), 925 (w), 903 (m), 867 (m), 825 (s), 794 (m), 763 (s), 731
-
1
CH) 44.0 (CH
3
). IR: ṽ [cm ] = 2226 (w), 1720 (vs), 1603 (m),
+
(
w), 675 (w), 615 (m). ESI-MS (m/z): 397.3 ([M+H] , 100%). HR-
1
578 (m), 1526 (m), 1449 (w), 1410 (m), 1360 (m), 1302 (m), 1229
+
MS (ESI) (m/z) calcd. for (C25
97.1069. HPLC (acetonitrile): 98% (RT = 7.0 min).
-(9-(4-(Dimethylamino)phenyl)-7-oxo-7H-furo[3,2-
16 5
H O +H) : 397.1071; Found:
(w), 1202 (w), 1144 (vs), 1111 (m), 1092 (w), 1065 (w), 1040 (s),
3
1020 (w), 991 (m), 949 (w), 924 (w), 903 (w), 868 (m), 833 (m),
820 (s), 793 (m), 770 (m), 750 (w), 725 (s). ESI-MS (m/z): 407.5
4
+
+
g]chromen-4-yl)benzaldehyde (7f). According to GP1 and after pu-
rification by flash chromatography on silica gel (petroleum
ether/acetone 2:1) and after crystallization from dichloromethane
([M] , 100%). HR-MS (ESI) (m/z) calcd. for (C26
H
18
N
2
O
3
+H) :
4
07.1390; Found: 407.1384. HPLC (acetonitrile): 98% (RT = 6.9
min).
compound 7f (86.7 mg, 32%) was obtained as an orange solid, R
f
9
-(4-Methoxyphenyl)-4-(4-nitrophenyl)-7H-furo[3,2-
1
= 0.38 (petroleum ether/ethyl acetate, 3:1). Mp 269 °C. H NMR:
g]chromen-7-one (7c). According to GP1 and after purification by
flash chromatography on silica gel (petroleum ether/acetone 3:1)
and after crystallization from ethanol (3:1) compound 7c (120 mg,
(
(
7
(
500 MHz, CDCl
d, J = 9.8 Hz, 1 H), 8.04 – 8.00 (m, 2 H), 7.99 (d, J = 2.3 Hz, 1 H),
.95 – 7.92 (m, 2 H), 7.25 (s, 2 H), 6.93 (d, J = 2.3 Hz, 1 H), 6.63
d,
J = 9.8 Hz, 1 H), 3.35 (s, 6 H). C{ H} NMR: (126 MHz, CDCl
3
) δ = 10.44 (s, 1 H), 8.39 – 8.35 (m, 2 H), 8.07
80%) was obtained as a yellow solid, R
f
= 0.25 (petroleum
ether/ethyl acetate, 3:1). Mp 304 °C dec. H NMR: (600 MHz,
CDCl ) δ = 8.52 – 8.36 (m, 2 H), 7.77 – 7.72 (m, 4 H), 7.67 (d, J =
.6 Hz, 2 H), 7.13 – 7.08 (m, 2 H), 6.64 (d, J = 2.2 Hz, 1 H), 6.38
1
13
1
3
)
3
δ = 191.8 (CH), 160.8 (Cquat), 154.2 (Cquat), 149.4 (Cquat), 147.5
(CH), 142.6 (Cquat), 142.2 (CH), 136.5 (Cquat), 131.9 (CH), 131.4
8
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Page 11 of 14
The Journal of Organic Chemistry
(
CH), 130.4 (CH), 130.4 (Cquat), 130.4 (Cquat), 124.7 (Cquat), 124.7
organic layers were combined and dried (anhydrous sodium sul-
fate). The mixture was adsorbed on Celite and purified by column
chromatography (petroleum ether/ethyl acetate).
®
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(Cquat), 115.1 (CH), 114.1 (Cquat), 106.3 (CH), 77.6 (Cquat), 53.7
(
-
1
CH
3
). IR: ṽ [cm ] = 1717 (m), 1690 (m), 1601 (m), 1577 (m),
1
558 (s), 1526 (w), 1452 (w), 1410 (w), 1368 (w), 1304 (w), 1202
4-((9-((4-Methoxyphenyl)ethynyl)-7-oxo-7H-furo[3,2-
(
(
(
(
w), 1179 (w), 1038 (m), 991 (m), 951 (w), 924 (w), 903 (w), 868
w), 839 (m), 820 (s), 795 (w), 767 (m), 675 (w). MS (EI) (m/z
%)): 410 (30), 409 ([M] , 100). HR-MS (ESI) (m/z) calcd. for
26 4
C H19NO +H) : 410.1387; Found: 410.1386 (100%). HPLC (ac-
g]chromen-4-yl)ethynyl) benzonitrile (10a). According to GP2 and
after purification by flash chromatography on silica gel (petroleum
ether/ethyl acetate 3:1) and after crystallization from ethanol com-
+
+
pound 10a (196 mg, 77%) was obtained as a yellow solid, R
f
= 0.31
petroleum ether/ethyl acetate, 3:1). Mp 254 °C (dec). H NMR:
(500 MHz, CD Cl ) δ = 8.20 (d, J = 9.8 Hz, 1 H), 7.78 (d, J = 2.2
etonitrile): 97% (RT = 7.0 min).
1
(
9
-(4-Methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)-7H-
2
2
furo[3,2-g]chromen-7-one (7g). According to GP1 and after puri-
fication by flash chromatography on silica gel (petroleum
ether/ethyl acetate 3:1) and after crystallization from ethanol/di-
chloromethane (4:1) compound 7g (143 mg, 68%) was obtained as
Hz, 1 H), 7.70 – 7.63 (m, 4 H), 7.58 – 7.51 (m, 2 H), 7.01 (d, J =
2.3 Hz, 1 H), 6.91 – 6.85 (m, 2 H), 6.41 (d, J = 9.7 Hz, 1 H), 3.78
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1
2 2
(s, 3 H). C{ H} NMR: (126 MHz, CD Cl ) δ = 161.5 (Cquat), 160.3
(Cquat), 156.1 (Cquat), 152.8 (Cquat), 148.6 (CH), 142.3 (CH), 134.3
(CH), 133.1 (CH), 133.0 (CH), 127.6 (Cquat), 127.5 (Cquat),
118.9 (Cquat), 117.5 (Cquat), 116.4 (CH), 115.0 (CH), 113.5 (Cquat),
a colorless solid, R
f
= 0.68 (petroleum ether/ethyl acetate, 2:1). Mp
80 °C (dec). H NMR: (300 MHz, CDCl ) δ = 7.87 – 7.68 (m, 6
H), 7.62 – 7.56 (m, 2 H), 7.14 – 7.07 (m, 2 H), 6.65 (d, J = 2.3 Hz,
1
2
3
112.5 (Cquat), 107.4 (CH), 102.9 (Cquat), 99.8 (Cquat), 99.0 (Cquat),
1
3
1
-1
1 H), 6.35 (d, J = 9.9 Hz, 1 H), 3.91 (s, 3 H). C{ H} NMR: (75
MHz, CDCl ) δ = 160.5 (Cquat), 159.8 (Cquat), 153.7 (Cquat), 148.9
quat), 147.3 (CH), 141.8 (CH), 139.5 (Cquat), 131.8 (CH), 130.7
87.7 (Cquat), 77.3 (Cquat), 56.2 (CH
3
). IR: ṽ [cm ] = 2961 (w), 2226
3
(w), 1747 (s), 1728 (s), 1601 (m), 1581 (m), 1508 (s), 1464 (m),
1375 (m), 1294 (m), 1250 (s), 1169 (m), 1140 (m), 1123 (m), 1090
(m), 1022 (s), 980 (m), 793 (s), 756 (m), 691 (w), 615 (w). MALDI
(
(
C
3
CH), 130.0 (Cquat), 125.9 (q, JCF = 3.95 Hz, CH), 124.5 (Cquat),
+
1
1
21.9 (Cquat), 114.7 (CH), 114.3 (Cquat), 114.1 (CH), 113.8 (Cquat),
(m/z (%)): 441.029 ([M ]). HR-MS (ESI) m/z calcd. for
-1
+
06.0 (CH), 77.2 (Cquat), 55.4 (CH
3
). IR: ṽ [cm ] = 1740 (s), 1724
(C29
H15NO
4
+H) : 442.1074 ; Found: 442.1067. HPLC (acetone):
(s), 1589 (m), 1545 (w), 1512 (m), 1460 (w), 1431 (w), 1406 (w),
98% (RT = 6.0 min).
1323 (s), 1287 (w), 1250 (m), 1167 (m), 1144 (m), 1109 (s), 1065
(s), 1018 (s), 993 (m), 926 (w), 903(w), 870 (m), 833 (s), 810 (w),
7
HR-MS (ESI) (m/z) calcd. for (C25
4
4
-((9-((4-(Dimethylamino)phenyl)ethynyl)-7-oxo-7H-furo[3,2-
g]chromen-4-yl) ethynyl)benzonitrile (10b). According to GP2 and
after purification by flash chromatography on silica gel (petroleum
ether/ethyl acetate 3:1) and after crystallization from dichloro-
methane compound 10b (40.1 mg, 34%) was obtained as an orange
+
68 (m), 754 (m).MS (EI) (m/z (%)): 438 (27), 437 ([M+H] , 100).
+
H
15
F
3
O
4
+H) : 437.0995; Found:
37.0995. HPLC (acetonitrile): 98% (RT = 7.8 min).
-(4-(Dimethylamino)phenyl)-4-(4-(trifluoromethyl)phenyl)-
H-furo[3,2-g] chromen-7-one (7h). According to GP1 and after
9
solid, R
f
= 0.27 (petroleum ether/ethyl acetate, 3:1). Mp 246 °C
1
7
(dec). H NMR: (500 MHz, DMSO-d ) δ = 8.48 (d, J = 9.8 Hz, 1
6
purification by flash chromatography on silica gel (petroleum
ether/ethyl acetate 2:1) and after crystallization from ethanol/di-
chloromethane (4:1) compound 7h (130 mg, 44%) was obtained as
H), 8.32 (d, J = 2.2 Hz, 1 H), 8.04 – 7.94 (m, 4 H), 7.45 (d, J = 8.8
Hz, 2 H), 7.40 (d, J = 2.2 Hz, 1 H), 6.80 – 6.74 (m, 2 H), 6.60 (d, J
1
3
1
= 9.7 Hz, 1 H), 3.00 (s, 6 H). C{ H} NMR: (126 MHz, DMSO-
) δ = 159.6 (Cquat), 154.6 (Cquat), 151.5 (Cquat), 151.2 (Cquat), 149.5
a yellow solid, R
f
= 0.38 (petroleum ether/ethyl acetate, 3:1). Mp
96 °C (dec.). H NMR: (300 MHz, CDCl ) δ = 7.88 – 7.66 (m, 6
H), 7.59 (m, 2 H), 6.97 (s, 2 H), 6.64 (d, J = 2.3 Hz, 1 H), 6.34 (d,
d
6
1
2
3
(CH), 142.5 (CH), 133.1 (CH), 133.0 (CH), 132.9 (CH), 126.9
(Cquat), 126.7 (Cquat), 118.7 (Cquat), 117.0 (Cquat), 116.1 (CH), 112.3
(CH), 112.1 (Cquat), 111.0 (Cquat), 107.7 (Cquat), 107.2 (CH), 103.9
1
3
1
J = 9.9 Hz, 1 H), 3.07 (s, 6 H). C{ H} NMR: (75 MHz, CDCl
160.6 (Cquat), 158.8 (Cquat), 153.7 (Cquat), 153.3 (Cquat), 148.9
quat), 147.9 (Cquat), 147.1 (CH), 141.9 (CH), 139.7 (Cquat), 137.8
3
) δ
=
(Cquat), 99.8 (Cquat), 98.9 (Cquat), 98.7 (Cquat), 87.3 (Cquat), 76.7
-1
(
C
(Cquat), 40.6 (CH
3
). IR: ṽ [cm ] = 2195 (w), 1719 (s), 1599 (m),
3
(Cquat), 131.5 (CH), 130.7 (CH), 125.8 (q, JCF = 3.90 Hz CH),
124.4 (Cquat), 114.6 (CH), 113.8 (Cquat), 105.9 (CH), 77.2 (Cquat),
4
1
1578 (s), 1522 (s), 1445 (w), 1364 (m), 1254 (w), 1225 (w), 1184
(w), 1140 (s), 1078 (w), 1030 (m), 989 (w), 941 (w), 835 (s), 816
(s), 787 (w), 762 (m).ESI-MS (m/z (%)): 440.3 (55%), 455.2
-
1
0.8 (CH
3
). IR: ṽ [cm ] = 1735 (s), 1608 (m), 1585 (m), 1525 (m),
+
+
449 (s), 1408 (m), 1357 (m), 1321 (s), 1227 (w), 1194 (w), 1163
18 2 3
([M+H] , 100%). HR-MS (ESI) m/z calcd. for (C30H N O +H) :
(
(
s), 1142 (s), 1123 (s), 1109 (s), 1065 (s), 1036 (m), 1016 (s), 993
m), 949 (w), 924 (w), 903 (w), 867 (w), 837 (m), 822 (s), 795 (w),
455.1390; Found: 455.1383. HPLC (acetonitrile): 99% (RT = 8.3
min).
7
56 (s), 721 (w), 619 (m). MS (EI) (m/z (%)): 451 (28), 450
9
-((4-Methoxyphenyl)ethynyl)-4-((4-nitrophenyl)ethynyl)-7H-
+
+
18 3 3
([M+H] , 100). HR-MS (ESI) (m/z) calcd. for (C26H F NO +H) :
furo[3,2-g]chromen-7-one (10c). According to GP2 and after puri-
fication by flash chromatography on silica gel (petroleum
ether/ethyl acetate 3:1) and after crystallization from acetone/etha-
nol (1:1) compound 10c (40 mg, 42%) was obtained as a yellow
450.1312; Found: 450.1305. HPLC (acetonitrile): 98% (RT = 8.0
min).
General procedure GP2 of the one-pot synthesis of alkynyl
expanded 5-donor substituted 8-acceptor psoralens 10. 5-
Bromo-8-triflatopsoralen (3, 1.00 equivs) was placed in dry 1,4-
dioxane (4.00 mL/mmol) under nitrogen atmosphere in a screw-cap
Schlenk tube with a magnetic stir bar (for experimental details, see
Table 2). p-(Acceptor)arylalkyne 8 (1.10 equivs), tris(dibenzyli-
solid, R
f
= 0.63 (petroleum ether/ethyl acetate, 3:1). Mp 281 °C
1
(dec). H NMR: (300 MHz, CDCl ) δ = 8.37 – 8.22 (m, 3 H), 7.87
3
– 7.73 (m, 3 H), 7.70 – 7.59 (m, 2 H), 7.06 (d, J = 2.3 Hz, 1 H),
6.96 – 6.88 (m, 2 H), 6.54 (d, J = 9.7 Hz, 1 H), 3.87 (s, 3 H).
13
1
3
C{ H} NMR (75 MHz, CDCl ) δ = 192.1 (Cquat), 167.9 (Cquat),
®
deneacetone)dipalladium(0) (0.01 equivs), cataCXium ABn (0.04
165.1 (Cquat), 163.8 (Cquat), 160.5 (Cquat), 159.9 (Cquat), 147.8 (CH),
147.7 (Cquat), 133.8 (CH), 132.5 (CH), 132.0 (Cquat), 128.8 (Cquat),
126.9 (Cquat), 123.9 (CH), 116.7 (Cquat), 115.9 (CH), 114.1 (CH),
111.1 (Cquat), 107.8 (Cquat), 106.7 (CH), 88.1 (Cquat), 77.4 (CH),
equivs), copper iodide (0.08 equivs), and triethylamine (3.00
equivs) were added and the solution was then degassed with nitro-
gen for 5 min. The reaction mixture was stirred at 75 °C for 48 h.
Subsequently, p-(donor)arylalkyne 9 (1.10 equivs), tetrakis(tri-
phenylphosphane)palladium(0) (0.02 equivs), and dimethyl sulfox-
ide (4.00 mL/mmol) were added and stirred at 90 °C for further
-
1
3
37.7 (CH ). IR: ṽ [cm ] = 1728 (s), 1593 (w), 1578 (m), 1509 (s),
1441 (w), 1377 (w), 1341 (s), 1310 (w), 1292 (m), 1248 (s), 1175
(m), 1143 (s), 1130 (s), 1105 (s), 1022 (m), 986 (m), 885 (w), 854
(s), 835 (s), 812 (w), 756 (s), 746 (s), 723 (w), 687 (m), 662 (m).
2
4 h. After cooling to room temp, water was added (10 mL) and the
+
aqueous phase extracted with dichloromethane (3 x 30 mL). The
MALDI (m/z (%)): 461.256 ([M] , 100%). HR-MS (ESI m/z calcd.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 14
+
for (C28
H15NO
6
+H) : 462.0972; Found: 462.0973. HPLC (acetoni-
9-((4-Methoxyphenyl)ethynyl)-4-(pyridin-4-ylethynyl)-7H-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
trile): 98% (RT = 8.5 min).
furo[3,2-g]chromen-7-one (10g). According to GP2 and after puri-
fication by flash chromatography on silica gel (petroleum
ether/ethyl acetate 1:2) and after crystallization from ethanol com-
9-((4-(Dimethylamino)phenyl)ethynyl)-4-((4-nitrophenyl)-
ethynyl)-7H-furo[3,2-g] chromen-7-one (10d). According to GP2
and after trituration with hot dichloromethane compound 10d (59.2
pound 10g (45 mg, 43%) was obtained as a yellowish solid, R
f
1
=
0
.63 (petroleum ether/ethyl acetate, 1:2). Mp 267 °C (dec). H
f
mg, 60%) was obtained as a red solid, R = 0.50 (petroleum
1
NMR: (300 MHz, CD
9.7 Hz, 1 H), 7.88 (d, J = 2.3 Hz, 1 H), 7.66 – 7.60 (m, 2 H), 7.57
– 7.48 (m, 2 H), 7.10 (d, J = 2.3 Hz, 1 H), 6.98 – 6.94 (m, 2 H),
2 2
Cl ) δ = 8.68 (d, J = 5.5 Hz, 2 H), 8.30 (d, J
ether/ethyl acetate, 3:1). Mp 301 °C (dec). H NMR: (600 MHz,
DMF-d ) δ = 8.61 (d, J = 9.7 Hz, 1 H), 8.41 – 8.37 (m, 2 H), 8.30
d, J = 2.2 Hz, 1 H), 8.18 – 8.13 (m, 2 H), 7.57 – 7.52 (m, 2 H),
=
7
(
1
3
1
6.51 (d, J = 9.7 Hz, 1 H), 3.87 (s, 3 H). C{ H} NMR: (75 MHz,
CD Cl ) δ = 161.0 (Cquat), 160.0 (Cquat), 155.7 (Cquat), 152.4 (Cquat),
7
.43 (d, J = 2.2 Hz, 1 H), 6.89 – 6.82 (m, 2 H), 6.64 (d, J = 9.7 Hz,
1
3
1
2
2
1 H), 3.07 (s, 6 H). C{ H} NMR: (151 MHz, DMF-d
7
) δ = 159.3
1
1
1
9
50.3 (CH), 148.3 (CH), 142.0 (CH), 133.9 (CH), 130.6 (Cquat),
27.8 (Cquat), 125.8 (CH), 117.2 (Cquat), 116.1 (CH), 114.6 (CH),
14.5 (Cquat), 111.9 (Cquat), 107.0 (CH), 102.5 (Cquat), 99.5 (Cquat),
(
(
(
(
(
C
C
C
C
C
quat), 155.0 (Cquat), 151.9 (Cquat), 151.5 (Cquat), 149.1 (CH), 148.1
quat), 142.1 (CH), 133.2 (CH), 133.0 (CH), 128.9 (Cquat), 127.0
quat), 123.9 (CH), 117.2 (Cquat), 115.9 (CH), 112.2 (CH), 111.0
quat), 108.4 (Cquat), 106.9 (CH), 104.1 (Cquat), 98.3 (Cquat), 87.9
quat), 76.3 (Cquat), 39.4 (CH
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-1
3
7.4 (Cquat), 87.6 (Cquat), 76.9 (Cquat), 55.9 (CH ). IR: ṽ [cm ] =
-1
1728 (s), 1595 (m), 1582 (m), 1558 (w), 1508 (m), 1441 (w), 1373
(w), 1292 (w), 1256 (s), 1225 (w), 1167 (m), 1130 (s), 1105 (w),
3
). IR: ṽ [cm ] = 1717 (s), 1605 (m),
1
578 (s), 1512 (s), 1443 (w), 1364 (s), 1339 (s), 1310 (w), 1287
1
026 (m), 988 (m), 881 (w), 822 (s), 791 (w), 750 (w), 637 (m).
(w), 1253 (w), 1224 (w), 1180 (w), 1138 (s), 1076 (w), 1028 (s),
984 (m), 941 (w), 853 (s), 831 (s), 814 (s), 758 (s), 750 (s), 725 (w),
+
ESI-MS (m/z (%)): 418.4 ([M+H] , 100%). HR-MS (ESI) m/z
calcd. for (C27H15NO +H) : 418.1074; Found: 418.1080. HPLC
4
+
+
6
87 (w). ESI-MS (m/z (%)): 475.4 ([M+H] , 100%). HR-MS (ESI)
+
(acetonitrile): 99% (RT = 7.4 min).
m/z calcd. for (C29
HPLC (acetonitrile/DMF): 98% (RT = 7.8 min).
-((4-Methoxyphenyl)ethynyl)-4-((4-(trifluoromethyl)phenyl)-
18 2 5
H N O +H) : 475.1288; Found: 475.1287.
9-((4-(Dimethylamino)phenyl)ethynyl)-4-(pyridin-4-ylethynyl)-
7
H-furo[3,2-g] chromen-7-one (10h). According to GP2 and after
9
purification by flash chromatography on silica gel (petroleum
ether/ethyl acetate 1:2) and after crystallization from acetone com-
ethynyl)-7H-furo[3,2-g]chromen-7-one (10e). According to GP2
and after purification by flash chromatography on silica gel (petro-
leum ether/ethyl acetate 5:1) and after crystallization from ethanol
pound 10h (53.8 mg, 50%) was obtained as a red solid. R
f
= 0.45
1
(petroleum ether/ethyl acetate, 1:2). Mp 221 °C (dec). H NMR:
compound 10e (84.1 mg, 70%) was obtained as a yellow solid, R
f
1
3
(300 MHz, CDCl ) δ = 8.72 (s, 2 H), 8.25 (dd, J = 9.7, 1.0 Hz, 1
= 0.25 (petroleum ether/ethyl acetate, 3:1). Mp 213 °C. H NMR:
300 MHz, CDCl ) δ = 8.28 (d, J = 9.7 Hz, 1 H), 7.82 (d, J = 2.3
Hz, 1 H), 7.79 – 7.51 (m, 7 H), 7.04 (d, J = 2.2 Hz, 1 H), 6.92 (d, J
H), 7.82 (d, J = 2.1 Hz, 1 H), 7.61 – 7.53 (m, 2 H), 7.49 (s, 2 H),
.03 (d, J = 2.1 Hz, 1 H), 6.68 (d, J = 8.6 Hz, 2 H), 6.52 (dd, J =
(
3
7
13
1
1
3
1
9.7, 1.0 Hz, 1 H), 3.03 (d, J = 1.1 Hz, 6 H). C{ H} NMR: (75
MHz, CDCl ) δ = 160.1 (Cquat), 155.1 (Cquat), 151.6 (Cquat), 150.7
(Cquat), 150.0 (CH), 147.6 (CH), 141.6 (CH), 136.0 (Cquat), 133.5
CH), 126.8 (Cquat), 116.8 (Cquat), 115.8 (CH), 111.6 (CH), 110.3
(Cquat), 108.8 (Cquat), 106.6 (CH), 104.7 (Cquat), 100.4 (Cquat), 96.6
=
8.9 Hz, 1 H), 6.51 (d, J = 9.8 Hz, 1 H), 3.86 (s, 3 H). C{ H}
NMR: (75 MHz, CDCl ) δ = 160.4 (Cquat), 160.0 (Cquat), 155.3
quat), 152.0 (Cquat), 147.5 (CH), 141.7 (CH), 133.7 (CH), 132.0
3
3
(
C
(
(CH), 131.2 (Cquat), 130.8 (Cquat), 126.7 (Cquat), 125.6 (Cquat), 125.6
3
(q, JCF = 3.91 Hz, CH), 116.6 (Cquat), 115.6 (CH), 114.5 (Cquat),
-
1
(
C
quat), 87.6 (Cquat), 76.1 (Cquat), 40.2 (CH
1605 (m), 1522 (m), 1489 (w), 1445 (w), 1404 (m), 1364 (m), 1327
w), 1256 (w), 1182 (w), 1138 (s), 1080 (w), 1028 (m), 988 (m),
39 (w), 881 (w), 858 (w), 837 (m), 816 (s), 787 (w), 760 (s), 727
3
). IR: ṽ [cm ] = 1720 (s),
1
9
1
14.1 (CH), 111.8 (Cquat), 106.7 (CH), 102.4 (Cquat), 99.2 (Cquat),
8.4 (Cquat), 85.4 (Cquat), 77.3 (Cquat), 55.4 (CH
724 (s), 1604 (w), 1582 (m), 1510 (m), 1406 (w), 1375 (w), 1321
-
1
3
). IR: ṽ [cm ] =
(
9
(
1
s), 1295 (m), 1250 (m), 1190 (m), 1144 (s), 1123 (s), 1105 (s),
080 (w), 1063 (s), 1030 (s), 986 (m), 883 (w), 856 (s), 787 (w),
756 (s), 745 (m), 721 (w), 640 (w). ESI-MS (m/z): 986.1
+
(w), 698 (w), 635 (m). ESI-MS (m/z (%)): 431.4 ([M+H] ,100%).
HR-MS (ESI) m/z calcd. for (C28H N O +H) : 431.1390; Found:
18 2 3
+
+
+
431.1399. HPLC (acetonitrile): 98% (RT = 8.0 min).
([M
85.0995; Found: 485.0996. HPLC (acetonitrile): 99% (RT = 8.7
min).
2 2 15 3 4
+H O] ). HR-MS (ESI) m/z calcd. for (C29H F O +H) :
4
4-((9-((4-Methoxyphenyl)ethynyl)-7-oxo-7H-furo[3,2-
g]chromen-4-yl)ethynyl) benzaldehyde (10i). According to GP2
and after purification by flash chromatography on silica gel (petro-
leum ether/ethyl acetate 3:1) and after crystallization from ace-
tone/dichloromethane/ethanol (4:1:1) compound 10i (34 mg, 31%)
9
-((4-(Dimethylamino)phenyl)ethynyl)-4-((4-(trifluoromethyl)-
phenyl)ethynyl)-7H-furo[3,2-g]chromen-7-one (10f). According to
GP2 and after purification by flash chromatography on silica gel
was obtained as a yellow solid, R
acetate, 3:1). Mp 225 °C (dec). H NMR: (300 MHz, CDCl ) δ =
f
= 0.31 (petroleum ether/ethyl
(
petroleum ether/ethyl acetate 5:1) and after crystallization from di-
chloromethane/ethanol compound 10f (64 mg, 52%) was obtained
as a yellow solid, R = 0.33 (petroleum ether/ethyl acetate, 5:1). Mp
202 °C (dec). H NMR: (300 MHz, CDCl ) δ = 8.29 (d, J = 9.8 Hz,
H), 7.82 (d, J = 2.2 Hz, 1 H), 7.79 – 7.56 (m, 6 H), 7.04 (d, J =
.3 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 2 H), 6.52 (d, J = 9.7 Hz, 1 H),
1
3
10.07 (s, 1 H), 8.30 (d, J = 9.7 Hz, 1 H), 8.00 – 7.91 (m, 2 H), 7.86
– 7.74 (m, 3 H), 7.72 – 7.58 (m, 2 H), 7.06 (d, J = 2.3 Hz, 1 H),
f
1
3
6
.98 – 6.87 (m, 2 H), 6.53 (d, J = 9.7 Hz, 1 H), 3.86 (s, 3 H).
1
2
3
1
1
1
1
3
1
C{ H} NMR: (75 MHz, CDCl
160.0 (Cquat), 155.3 (Cquat), 152.0 (Cquat), 147.6 (CH), 141.7 (CH),
36.2 (Cquat), 133.7 (CH), 132.3 (CH), 129.8 (CH), 128.1 (Cquat),
3
) δ = 191.2 (CH), 160.4 (Cquat),
1
3
1
3
.05 (s, 6 H). C{ H} NMR: (75 MHz, CDCl ) δ = 160.2 (Cquat),
1
55.1 (Cquat), 151.7 (Cquat), 150.7 (Cquat), 147.4 (CH), 146.3 (Cquat),
41.8 (CH), 133.4 (CH), 132.0 (CH), 128.2 (CH), 127.3 (Cquat),
126.8 (Cquat), 116.7 (Cquat) , 115.7 (CH), 114.5 (Cquat), 114.1 (CH),
111.7 (Cquat), 106.7 (CH), 102.6 (Cquat), 99.4 (Cquat), 98.9 (Cquat),
3
26.7 (Cquat), 125.6 (q,
JCF = 3.85 Hz, CH), 116.6 (Cquat),
-
1
8
(
6.9 (Cquat), 77.2 (Cquat), 55.4 (CH
s), 1597 (m), 1578 (m), 1503 (s), 1375 (w), 1292 (m), 1247 (m),
1207 (m), 1169 (m), 1144 (s), 1126 (m), 1101 (w), 1070 (w), 1022
m), 984 (w), 883 (w), 820 (s), 795 (m), 752 (m), 752 (w), 621 (m).
3
). IR: ṽ [cm ] = 2922 (m), 1719
115.6 (CH), 111.6 (CH), 110.0 (Cquat), 108.9 (Cquat), 106.7 (CH),
104.4 (Cquat), 100.0 (Cquat), 98.1 (Cquat), 85.6 (Cquat), 77.2 (Cquat),
-
1
4
1
1
3
0.2 (CH ). IR: ṽ [cm ] = 1728 (s), 1607 (s), 1582 (m), 1526 (s),
(
447 (w), 1361 (s), 1319 (s), 1227 (w), 1180 (w), 1163 (m),
140 (s), 1124 (s), 1105 (m), 1020 (m), 1063 (m), 1030 (m), 989
+
+
ESI-MS (m/z (%)): 445.3 ([M+H] , 15%), 889.6 ([M
2
+H] , 100%).
+H) : 445.1071; Found:
445.1074. HPLC (acetonitrile): 99% (RT = 4.7 min).
+
16 5
HR-MS (ESI) m/z calcd. for (C29H O
(w), 943 (w), 883 (w), 841 (m), 916 (s), 760 (m), 743 (w), 723 (w).
+
ESI-MS (m/z (%)): 498.5 ([M+H] , 100%). HR-MS (ESI) m/z
+
calcd. for (C30
18 3 3
H F NO +H) : 498.1312; Found: 498.1313. HPLC
(acetonitrile): 99% (RT = 8.7 min).
ACS Paragon Plus Environment

Page 13 of 14
Supporting Information
The Journal of Organic Chemistry
Characteristics. Sci. China Chem. 2018, 61, 909924. (c) Merkt, F.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
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3
3
4
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5
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5
5
5
5
5
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K.; Höwedes, S. P.; Gers-Panther, C. F.; Gruber, I.; Janiak, C.;
Müller, T. J. J. Three-component Activation−Alkynylation−Cy-
clocondensation (AACC) Synthesis of Enhanced Emission Solva-
tochromic 3-Ethynyl Quinoxalines. Chem. Eur. J. 2018, 24,
81148125. (d) Gers-Panther, C. F.; Fischer, H.; Nordmann, J.;
Seiler, T.; Behnke, T.; Würth, C.; Frank, W.; Resch-Genger, U.;
Müller, T. J. J. Four- and Five-component Syntheses and Photo-
physical Properties of Emission Solvatochromic 3-Aminovinyl-
quinoxalines. J. Org. Chem. 2017, 82, 567578. (e) Denißen, M.;
Nirmalananthan, N.; Behnke, T.; Hoffmann, K.; Resch-Genger, U.;
Müller, T. J. J. 3-Piperazinyl propenylidene indolone merocyanines
The Supporting Information is available free of charge on the ACS
Publications website at DOI:
Optimization studies of the selective consecutive Sonogashira-
Sonogashira three-component synthesis, HPLC of compounds 7
1
13
and 10, and all H and C NMR spectra of compounds 3, 7 and 10,
absorption and emission spectra, aggregation induced emission en-
hancement, solvatochromicity and acidochromicity studies as well
as TD-DFT calculations are compiled in the Supporting Infor-
mation.
0
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9
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0
AUTHOR INFORMATION
Corresponding Author
–
consecutive three-component synthesis and electronic properties
of solid state luminophores with AIE properties. Mater. Chem.
Front. 2017, 1, 20132026. (f) Gers, C. F.; Nordmann, J.; Kumru,
C.; Frank, W.; Müller, T. J. J. Highly Solvatochromic Fluorescent
*
ThomasJJ.Mueller@hhu.de
ORCID
2
-Substituted 3-Ethynyl Quinoxalines – Four-component Synthe-
Thomas J. J. Müller: 0000-0001-9809-724X
sis, Photophysical Properties, and Electronic Structure. J. Org.
Chem. 2014, 79, 32963310.
Notes
The authors declare no competing financial interests.
(
6) (a) Lessing, T.; Müller, T. J. J. Sequentially Palladium-Cat-
alyzed Processes in One-pot Syntheses of Heterocycles. Appl. Sci.
015, 5, 18031836. (b) D'Souza, D. M.; Müller, T. J. J. Multi-
ACKNOWLEDGMENT
2
Component Syntheses of Heterocycles by Transition Metal Catal-
ysis. Chem. Soc. Rev. 2007, 36, 10951108.
(7) (a) Gupta, A. K.; Anderson, T. F. Psoralen photochemo-
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Seeds. Evid.-Based Complementary Altern. Med. 2011, Article ID
We are grateful to Deutsche Forschungsgemeinschaft (Mu
088/14-1, Mu 1088/9-1) and Fonds der Chemischen Industrie for
1
financial support. Computational support and infrastructure were
provided by the “Center for Information and Media Technology”
(ZIM) at the University of Düsseldorf (Germany). We cordially
thank M. Sc. Tobias Wilcke (Heinrich-Heine-Universität Düssel-
dorf) for taking the photographs.
3
63052.
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