Unusual solid-state luminescent push-pull indolones: A general one-pot three-component approach

Article abstract of DOI:10.1021/ol101165m

(Equation Presented). In a consecutive three-component cyclocarbopalladation, Sonogashira coupling, Michael addition sequence 4-aminopropenylidene indolones, i.e., terminally fixed push-pull chromophores, are obtained in yields as high as 99%. Most remarkable, however, is the pronounced orange red solid state fluorescence displaying large Stokes shifts of these merocyanines, in particular, since all chromophores are nonfluorescent in solution.

Full text of DOI:10.1021/ol101165m

ORGANIC
LETTERS
2010
Vol. 12, No. 15
3364-3367
Unusual Solid-State Luminescent
Push-Pull Indolones: A General
One-Pot Three-component Approach
Daniel M. D’Souza,†,‡ Christian Muschelknautz,† Frank Rominger,‡ and
Thomas J. J. Mu¨ller*,†
Institut fu¨r Organische Chemie und Makromolekulare Chemie,
Heinrich-Heine-UniVersita¨t Du¨sseldorf, UniVersita¨tsstrasse 1,
D-40225 Du¨sseldorf, Germany, and Organisch-Chemisches Institut,
Ruprecht-Karls-UniVersita¨t Heidelberg, Im Neuenheimer Feld 270,
D-69120 Heidelberg, Germany
thomasjj.mueller@uni-duesseldorf.de
Received May 21, 2010
ABSTRACT
In a consecutive three-component cyclocarbopalladation, Sonogashira coupling, Michael addition sequence 4-aminopropenylidene indolones, i.e.,
terminally fixed push-pull chromophores, are obtained in yields as high as 99%. Most remarkable, however, is the pronounced orange red solid
state fluorescence displaying large Stokes shifts of these merocyanines, in particular, since all chromophores are nonfluorescent in solution.
In recent years the productive concepts of multicomponent
processes1,2 and domino reactions3,4 have considerably
stimulated the synthetic scientific community. In particular,
the combination of structural and functional diversity has
initiated the quest of diversity oriented syntheses5 with broad
application in pharmaceutical lead discovery and development.
However, with respect to functional π-electron systems, such
as chromophores, fluorophores, and electrophores, required in
molecule based electronics,6 molecular photonics,7 and bio-
physical analytics,8 this approach is still quite novel.9,10
However, in heterocyclic chemistry consecutive multicom-
(4) For reviews, see: (a) Tietze, L. F. Chem. ReV. 1996, 96, 115–136.
(b) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993, 32, 131–
163. (c) Tietze, L. F. J. Heterocycl. Chem. 1990, 27, 47–69.
(5) For reviews on diversity oriented syntheses, see: (a) Schreiber, S. L.; Burke,
M. D. Angew. Chem., Int. Ed. 2004, 43, 46–58. (b) Burke, M. D.; Berger,
E. M.; Schreiber, S. L. Science 2003, 302, 613–618. (c) Spring, D. R. Org.
Biomol. Chem. 2003, 1, 3867–3870. (d) Arya, P.; Chou, D. T. H.; Baek,
M. G. Angew. Chem., Int. Ed. 2001, 40, 339–346. (e) Cox, B.; Denyer, J. C.;
Binnie, A.; Donnelly, M. C.; Evans, B.; Green, D. V. S.; Lewis, J. A.;
Mander, T. H.; Merritt, A. T.; Valler, M. J.; Watson, S. P. Prog. Med.
Chem. 2000, 37, 83–133. (f) Schreiber, S. L. Science 2000, 287, 1964–1969.
(6) Electronic Materials: The Oligomer Approach; Mu¨llen, K., Wegner,
G., Eds.; Wiley-VCH: Weinheim, Germany, 1998.
† Heinrich-Heine-Universita¨t Du¨sseldorf.
‡ Ruprecht-Karls-Universita¨t Heidelberg.
(1) For a recent monograph, see: Multicomponent Reactions; Zhu, J.,
Bienayme´, H., Eds.; Wiley-VCH: Weinheim, Germany, 2005
.
(2) For reviews, see: (a) Sunderhaus, J. D.; Martin, S. F. Chem.sEur.
J. 2009, 15, 1300–1308. (b) Isambert, N.; Lavilla, R. Chem.sEur. J. 2008,
14, 8444–8454. (c) Do¨mling, A. Chem. ReV. 2006, 106, 17–89. (d) Orru,
R. V. A.; de Greef, M. Synthesis 2003, 1471–1499. (e) Bienayme´, H.;
Hulme, C.; Oddon, G.; Schmitt, P. Chem.sEur. J. 2000, 6, 3321–3329. (f)
Do¨mling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168–3210. (g) Ugi,
I.; Do¨mling, A.; Werner, B. J. Heterocycl. Chem. 2000, 37, 647–658. (h)
Weber, L.; Illgen, K.; Almstetter, M. Synlett 1999, 366–374. (i) Armstrong,
R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc.
Chem. Res. 1996, 29, 123–131. (j) Ugi, I.; Do¨mling, A.; Ho¨rl, W. EndeaVour
(7) For a recent monograph, see: Organic Light-Emitting Diodes -
Synthesis, Properties, and Applications; Mu¨llen, K., Scherf, U., Eds.; Wiley-
VCH: Weinheim, Germany, 2006.
1994, 18, 115–122. (k) Posner, G. H. Chem. ReV. 1986, 86, 831–844
.
(8) For recent reviews, see: (a) Kim, E.; Park, S. B. Chem. Asian J.
2009, 4, 1646–1658. (b) Cairo, C. W.; Key, J. A.; Sadek, C. M. Curr. Opin.
Chem. Biol. 2010, 14, 57–63. (c) Wagenknecht, H.-A. Ann. N.Y. Acad. Sci.
2008, 1130, 122–130.
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Tietze, L. F., Brasche, G., Gericke, K. M., Eds.; Wiley-VCH: Weinheim,
Germany, 2006
.
10.1021/ol101165m  2010 American Chemical Society
Published on Web 07/02/2010

ponent syntheses based upon transition metal catalysis,11 such as
the Pd/Cu-catalyzed generation of alkynones and alkenones, have
paved the way to manifold classes of heterocycles.12
of diethyamine to a 2-fold acceptor-substituted enyne,20 Michael-
type additions have remained unexplored. Here, we com-
municate our findings on the three-component synthesis of
push-pull butadienes on the basis of the indolone scaffold. Most
remarkably, all representatives display intense orange to red
luminescence in the solid state; however, surprisingly, in
solution the same chromophores are completely nonemissive.
After reaction between alkynoyl o-iodo anilides 1 and
terminal alkynes 3 at room temperature under Sonogashira
conditions, the anticipated enyne indolones 4 (the reaction
was monitored by TLC to ensure complete conversion) were
not isolated but subsequently treated with ethanolic solutions
of primary or secondary amines 7 at reflux to give 4-ami-
noprop-3-enylidene indolones 8 in good to excellent yields
as crystalline solids with a bright orange red hue (Scheme
2, Table 1).21 The structures of the 4-aminoprop-3-enylidene
As early as 2000, we had developed a multicomponent
method for the synthesis of chromophores13 and fluoro-
phores.14 This was recently further extended by a domino
insertion-coupling sequence of alkynoyl o-iodo anilides 1,15
or phenolates 2, with p-anisyl acetylene (3a) or propargyl
allyl ethers 5, to give an enyne indolone 4 or highly
fluorescent structurally rigidified butadienes 6 in a spirocyclic
framework in good to excellent yields, displaying extraor-
dinary large Stokes shifts and fluorescence quantum yields
Φf as high as 62% (Scheme 1).16 The latter spirocyclic
Scheme 1. Coupling of Alkynoyl o-Iodo Anilides 1 or
Phenolates 2 with Terminal Alkynes 3 and Propargyl Allyl
Ethers 5 Giving Rise to the Formation of Various Heterocycles
in a Domino Fashion
Scheme 2. Three-Component Insertion-Coupling-Addition
Synthesis of 4-Aminoprop-3-enylidene Indolones 8 and
Mechanistic Rationale
lumophores 6 are formed in the sense of an insertion-coupling
isomerization-Diels-Alder domino sequence, a quite gen-
eral route to complex polycyclic frameworks that has recently
found application in various domino sequences with other
concluding pericyclic steps.17
Most interestingly the Z-configured enyne indolone 418
represents a vinyl expanded ynamide and, therefore, Michael-
type reactions can be conceived, eventually in a one-pot fashion
as already successfully demonstrated with the three-component
coupling-amine addition sequence to give enaminones.19 Al-
though Michael additions to ynones have been extensively
studied, with the exception of a single example of an addition
indolones 8 were unambiguously assigned by spectroscopic
characterization and combustion analysis, and later cor-
roborated by X-ray crystal structure analyses for compounds
8a, 8k (see the Supporting Information), and 8n (Figure 1).22
This protocol shows a broad scope with respect to the
electronic nature of the aryl substituents R2 and R3 and the
(9) For reviews, see: (a) Mu¨ller, T. J. J.; D’Souza, D. M. Pure Appl.
Chem. 2008, 80, 609–620. (b) Mu¨ller, T. J. J. In Functional Organic
Materials. Syntheses, Strategies, and Applications; Wiley-VCH: Weinheim,
Germany, 2007; pp 179-223.
(13) (a) Karpov, A. S.; Rominger, F.; Mu¨ller, T. J. J. J. Org. Chem.
2003, 68, 1503–1511. (b) Mu¨ller, T. J. J.; Robert, J. P.; Schma¨lzlin, E.;
Bra¨uchle, C.; Meerholz, K. Org. Lett. 2000, 2, 2419–2422.
(10) For a review on combinatorial syntheses of π-systems, see: Briehn,
C. A.; Ba¨uerle, P. Chem. Commun. 2002, 1015–1023.
(11) (a) D’Souza, D. M.; Mu¨ller, T. J. J. Chem. Soc. ReV. 2007, 36,
1095–1108. (b) Balme, G.; Bossharth, E.; Monteiro, N. Eur. J. Org. Chem.
2003, 4101–4111. (c) Battistuzzi, G.; Cacchi, S.; Fabrizi, G. Eur. J. Org.
Chem. 2002, 2671–2681.
(14) (a) Willy, B.; Mu¨ller, T. J. J. Eur. J. Org. Chem. 2008, 4157–
4168. (b) Willy, B.; Dallos, T.; Rominger, F.; Scho¨nhaber, J.; Mu¨ller, T. J. J.
Eur. J. Org. Chem. 2008, 4796–4805. (c) Schramm ne´e Dediu, O. G.; Oeser,
T.; Mu¨ller, T. J. J. J. Org. Chem. 2006, 71, 3494–3500. (d) Rotaru, A. V.;
Druta, I. D.; Oeser, T.; Mu¨ller, T. J. J. HelV. Chim. Acta 2005, 88, 1798–
1812. (e) Braun, R. U.; Mu¨ller, T. J. J. Synthesis 2004, 2391–2406. (f)
Braun, R. U.; Zeitler, K.; Mu¨ller, T. J. J. Org. Lett. 2001, 3, 3297–3300.
(12) (a) Willy, B.; Mu¨ller, T. J. J. Curr. Org. Chem. 2009, 13, 1777–
1790. (b) Willy, B.; Mu¨ller, T. J. J. ARKIVOC 2008, Part I, 195–208. (c)
Mu¨ller, T. J. J. Targets Heterocycl. Syst. 2006, 10, 54–65.
Org. Lett., Vol. 12, No. 15, 2010
3365

Table 1. Three-Component Synthesis of 4-Aminoprop-3-enylidene Indolones 8
4-aminoprop-3-enylidene
entry
o-iodo alkynylanilide 1
alkyne 3
amine 7
indolones 8 (isolated yield)a
1
2
3
4
5
6
7
8
R1 ) Ac, R2 ) H (1a)
R3 ) OMe (3a)
R4, R5 ) (CH2)4 (7a)
8a (89%)b
8b (60%)b
8c (97%)b
8d (95%)b
8e (97%)
8f (92%)
8g (86%)
8h (88%)
8i (99%)
8j (88%)
8k (94%)
8l (92%)
8m (98%)
8n (83%)
8o (87%)
8p (80%)
8q (95%)
8r (93%)
1a
3a
R4, R5 ) (CH2CH2)2O (7b)
t
t
R1 ) Ac, R2 ) Bu (1b)
R3 ) Bu (3b)
7a
7b
1b
1a
3b
R3 ) CN (3c)
R4 ) nhexyl, R5 ) p-anisyl (7c)
R1 ) Me, R2 ) H (1c)
3a
7a
7a
7b
7b
7a
7c
1c
1c
1c
R3 ) Cl (3d)
3a
3d
3d
3c
9
10
11
12
13
14
15
16
17
18
R1 ) SO2Me, R2 ) OMe (1d)
1d
1d
i
3a
R4 ) H, R5 ) propyl (7d)
R1 ) SO2Me, R2 ) Cl (1e)
R3 ) NO2 (3e)
7a
7b
7a
7b
7c
7d
1e
3a
3d
3a
3c
3a
R1 ) SO2Tol, R2 ) H (1f)
1f
1f
1f
a Reaction conditions: 1.00 equiv of alkynoyl o-iodo anilides 1 (0.1 M in THF), 1.10 equiv of terminal alkynes 3, 0.05 equiv of PdCl2(PPh3)2, 0.05 equiv
of CuI, and 10.0 equiv of diisopropylethylamine; after stirring for 16-24 h at rt addition of 20.0 equiv of amine 7 (4 M in ethanol), heating to reflux
b
temperature for 24 h in a sealed tube. The acetyl group is cleaved, R1 ) H.
of single sets of signals in all 13C NMR spectra. Interestingly, when
R1 ) Ac, this substituent is cleaved in the amine addition step,
furnishing the 1H indolones 8a-d (entries 1-4).
The 4-aminoprop-3-enylidene indolones 8 can be regarded
as merocyanines or push-pull chromophores.23 The longest
wavelength absorption maxima are found between 446 and 488
nm (acetonitrile) and between 438 and 484 nm (THF) with
significant extinction coefficients (Table 2 and Table SI-2 in
the Supporting Information). A closer inspection reveals that
the positive absorption solvochromicity is modest, indicating a
relatively low polarity of the electronic ground state and a small
charge transfer of S0-S1-transition character.24 The electronic
fine-tuning of the absorption maxima is achieved by the
indolone N-substituent and by the terminal amino moiety.
Most interestingly, all merocyanines 8 are essentially
nonfluorescent in solution. However, slightly red-shifted absorp-
tion maxima (492-502 nm) in the solid state spectra indicate
J-aggregation25 of the push-pull chromophores. Most remark-
Figure 1. ORTEP plot of compound 8n (hydrogen atoms are
omitted for clarity).
ably the dyes 8 display intense orange red fluorescence with
large Stokes shifts (∆V ≈ 2600 cm-1) and sharp emission
maxima between 622 and 644 nm (Table 2, Figures 2 and 3).
This effect is peculiar and apparently caused by packing and
aggregation in the solid state. X-ray structure analyses reveal
cyclic, acyclic, primary, or secondary amine component.
Moreover, the E,E-configured butadiene products 8 are formed
with excellent diastereoselectivity. Interestingly, the insertion-
coupling step occurs with stereomutation18 and the Michael-type
addition concludes in a stereoconvergent fashion as indicated by
structural assignments from the crystallography and the occurrence
(17) (a) D’Souza, D. M.; Rominger, F.; Mu¨ller, T. J. J. Chem. Commun.
2006, 4096–4098. (b) D’Souza, D. M.; Liao, W.-W.; Rominger, F.; Mu¨ller,
T. J. J. Org. Biomol. Chem. 2008, 6, 532–539. (c) Shen, R.; Huang, X.;
Chen, L. AdV. Synth. Catal. 2008, 350, 2865–2870. (d) Shen, R.; Huang,
X. Org. Lett. 2008, 10, 3283–3286. (e) Shen, R.; Zhu, S.; Huang, X. J.
Org. Chem. 2009, 74, 4118–4123. (f) Huang, X.; Zhu, S.; Shen, R. AdV.
Synth. Catal. 2009, 351, 3118–3122.
(15) For related insertion-coupling sequences starting from alkynoyl
o-iodo anilides, see e.g.: (a) Cheung, W. S.; Patch, R. J.; Player, M. R. J.
Org. Chem. 2005, 70, 3741–3744. (b) Yanada, R.; Obika, S.; Inokuma, T.;
Yanada, K.; Yamashita, M.; Ohta, S.; Takemoto, Y. J. Org. Chem. 2005,
70, 6972–6975.
(18) The observed stereomutation deviates from the expected Pd-
mediated syn-insertion of triple bonds, but the geometry has now unam-
bigously been assigned by NOESY and the occurrence of a single set of
signals in the 13C NMR spectrum of compound 4.
(19) Karpov, A. S.; Mu¨ller, T. J. J. Synthesis 2003, 2815–2826.
(20) Krasnaya, Z. A.; Stytsenko, T. S.; Yufit, S. S.; Prokofev, E. P.;
Kucherov, V. F. IzV. Akad. Nauk SSSR Ser. Khim. 1969, 416–420.
(16) (a) D’Souza, D. M.; Kiel, A.; Herten, D.-P.; Mu¨ller, T. J. J.
Chem.sEur. J. 2008, 14, 529–547. (b) D’Souza, D. M.; Rominger, F.;
Mu¨ller, T. J. J. Angew. Chem., Int. Ed. 2005, 44, 153–158.
3366
Org. Lett., Vol. 12, No. 15, 2010

Table 2. Electronic Spectral Data of Selected 4-Aminoprop-3-enylidene Indolones 8a
entry 4-aminoprop-3-enylidene indolones 8 λmax,abs [nm] (ε) in CH3CN λmax,abs [nm] (ε) in THF λmax,abs [nm] film λmax,em [nm] film
1
2
3
4
5
8a
8j
456 (23200)
474 (21800 sh)
458 (38900)
482 (47700)
480 (27800)
452 (12400)
472 sh
498
473 sh
496
494
470
476 sh
502
492
643
622
639
644
630
464 (27500)
482 (28800)
476 (14800)
8m
8n
8r
486 (34000)
482 (45100)
474 (28600)
478 (40100)
a Absorption Maxima in Solution and in the Solid State, and Emission Maxima in the Solid State.
Figure 3. Photographs of solid-state fluorescent single crystals of
the 4-aminoprop-3-enylidene indolones 8a (left), 8m (center), and
8n (right) (λexcitation ) 460 nm).
In conclusion we have disclosed a consecutive three-
component insertion-coupling-addition sequence giving
4-aminoprop-3-enylidene indolones with a flexible substitu-
tion pattern in yields as high as 99%. Most remarkably, all
representatives of these novel push-pull chromophores
display intense solid-state fluorescence with large Stokes
shifts, yet they are completely nonemissive in solution.
Further studies addressing this unusual luminescence behavior by
more detailed photophysical and computational investigations are
currently underway.
Figure 2. Normalized solid-state absorption (solid line) and
emission spectra (dashed line) of compound 8r.
that the coplanarity of the push-pull chromophore is stabilized
by the parallel alignment of the aryl substituents (Figure 1) and
short intermolecular distances between 3.96 to 5.08 Å in the
crystal lattice (see the Supporting Information). The narrow red-
shifted emission band (Figure 2) also accounts for aggregation
induced emission26 in the solid state and can be additionally
rationlized by Davydov splitting.27
Acknowledgment. This work was supported by the DFG
(Graduate College 850, stipend for D.M.D.) and the Fonds der
Chemischen Industrie.
Supporting Information Available: Experimental details,
NMR and selected solid state absorption and emission spectra
of compounds 8, and CIF files of compounds 8a, 8k, and 8n.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(21) Typical procedure (8o): In a flame-dried and nitrogen-flushed
screw cap vessel, iodo phenylanilide 1e (501 mg, 1.00 mmol) and alkyne
3d (150 mg, 1.10 mmol) were dissolved in dry THF (10 mL). After
degassing with a canula for 5 min diisopropylethylamine (1.7 mL, 10.0
mmol), PdCl2(PPh3)2 (35.0 mg, 0.05 mmol), and CuI (10.0 mg, 0.05 mmol)
were added to the reaction mixture. After stirring at rt for 16 h amine 7a
(1.6 mL, 20.0 mmol) dissolved in ethanol (5 mL) was added to the reaction
mixture. Then the sealed reaction vessel was placed in a thermostat oil
bath and heated to reflux temperature for 24 h. After cooling to rt the
solvents were removed in vacuo and the residue was chromatographed on
silica gel (hexanes/acetone 2:1) and crystallized from chloroform/pentane
to give 506 mg (87%) of 8o as a deep bright red solid: mp 248 °C; 1H
NMR (300 MHz, CDCl3) δ 1.80 (br, 2 H), 2.04 (br, 2 H), 2.40 (s, 3 H),
2.89 (br, 2 H), 3.71 (br, 2 H), 5.18 (d, J ) 7.7 Hz, 1 H), 6.50 (dt, J ) 8.1
Hz, J ) 0.9 Hz, 1 H), 6.70 (m, 4 H), 6.86-6.92 (m, 3 H), 6.97 (m, 2 H),
7.10 (m, 1 H), 7.29 (d, J ) 8.0 Hz, 2 H), 7.62 (s, 1 H), 7.87 (d, J ) 8.1 Hz,
1 H), 8.03 (d, J ) 8.3 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ 21.6 (CH3),
25.2 (CH2), 25.2 (CH2), 49.9 (CH2), 50.1 (CH2), 104.5 (CH), 108.1 (Cquat),
112.3 (CH), 120.5 (CH), 122.7 (CH), 124.1 (CH), 126.7 (Cquat), 127.2 (CH),
127.6 (CH), 127.9 (CH), 128.2 (CH), 129.1 (CH), 129.5 (CH), 130.2 (CH),
133.9 (Cquat), 134.6 (Cquat), 134.9 (Cquat), 136.9 (Cquat), 139.5 (Cquat), 144.3
(Cquat), 160.5 (Cquat); HRMS calcd for C34H29ClN2O3S 580.1587, found
580.1577. Anal. Calcd for C34H29ClN2O3S (581.1): C 70.27, H 5.03, N 4.82,
S 5.52, Cl 6.10. Found: C 70.02, H 4.99, N 4.97, S 5.64, Cl 6.27.
OL101165M
(22) Crystallographic data (excluding structure factors) for the structures reported
in this paper have been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication nos. CCDC 778168 (8a), CCDC 778169 (8k), and
CCDC 778170 (8n). Copies of the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: + 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk).
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3367