Tetrasubstituted olefinic xanthene dyes: Synthesis via Pd-catalyzed 6-exo-dig cyclization/C-H activation of 2-bromobenzyl-N-propargylamines and solid state fluorescence properties

Article abstract of DOI:10.1021/ol303326g

Tetrasubstituted olefin based new xanthene derivatives have been synthesized via palladium-catalyzed carbopalladation/C-H activation of 2-bromobenzyl-N-propargylamine derivatives. The synthesized compounds display a pronounced solid state fluorescence due to their restricted internal rotation of a C-Ar bond in the solid or aggregation state.

Full text of DOI:10.1021/ol303326g

ORGANIC
LETTERS
2013
Vol. 15, No. 2
382–385
Tetrasubstituted Olefinic Xanthene Dyes:
Synthesis via Pd-Catalyzed 6-exo-dig
Cyclization/CꢀH Activation of
2‑Bromobenzyl‑N‑propargylamines and
Solid State Fluorescence Properties
Avanashiappan Nandakumar and Paramasivan Thirumalai Perumal*
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar,
Chennai-600 020, India
ptperumal@gmail.com
Received December 6, 2012
ABSTRACT
Tetrasubstituted olefin based new xanthene derivatives have been synthesized via palladium-catalyzed carbopalladation/CꢀH activation of
2-bromobenzyl-N-propargylamine derivatives. The synthesized compounds display a pronounced solid state fluorescence due to their restricted
internal rotation of a CꢀAr bond in the solid or aggregation state.
Conjugated tetrasubstituted olefins have attracted much
attention from organic chemists due to their application in
photoresponsive organic materials, molecular devices, and
also in the field of biology.1 A number of different methods
have been developed to synthesize tetrasubstituted olefins,
including the McMurry reaction,2 Wittig reaction,3 and
transition metal catalyzed coupling reactions.4 Recent
approaches toward the synthesis of tetrasubstituted
olefins involve palladium catalyzed intramolecular carbo-
palladation of an in situ formed oxidative addition adduct
(ArꢀPdꢀX) to the internal alkyne followed by cross-
coupling with a organocopper5 or organostannane6 or
by direct CꢀH activation7 (Scheme 1). These approaches
enable chemists to construct tetrasubstituted olefins with
high stereo- and regioselectivity.
Solid state organic luminescence materials find several
applications in the field of optoelectronic devices including
light emitting diodes, electroluminescence, and molecular
sensors due to their phenomenal photophysical properties
and significant photostability.8 Several novel fluorescent
compounds are being designed based on the concept of
solid state luminescence.5,9 It poses a great challenge to
(1) (a) Flynn, A. B.; Ogilvie, W. W. Chem. Rev. 2007, 107, 4698. (b)
Feringa, B. L. J. Org. Chem. 2007, 72, 6635. (c) Cnossen, A.; Hou, L.;
Pollard, M. M.; Wesenhagen, P. V.; Browne, W. R.; Feringa, B. L.
J. Am. Chem. Soc. 2012, 134, 17613.
(5) (a) D’Souza, D. M.; Rominger, F.; Muller, T. J. J. Angew. Chem.,
Int. Ed. 2005, 44, 153. (b)D’Souza, D. M.; Muschelknautz, C.;Rominger,
F.; Muller, T. J. J. Org. Lett. 2010, 12, 3364. (c) Muschelknautz, C.;
Frank, W.; Muller, T. J. J. Org. Lett. 2011, 13, 2556.
(6) (a) Tietze, L. F.; Dufert, A.; Lotz, F.; Solter, L.; Oum, K.; Lenzer,
T.; Beck, T.; Herbst-lrmer, R. J. Am. Chem. Soc. 2009, 131, 17879.
(b) Tietze, L. F.; Dufert, M. A.; Hungerland, T.; Oum, K.; Lenzer, T.
Chem.;Eur. J. 2011, 17, 8452.
(2) Ephritikhine, M. Chem. Commun. 1998, 2549.
(3) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(4) (a) Zhou, C. X.; Larock, R. C. J. Org. Chem. 2005, 70, 3765. (b)
Zhou, C.; Larock, R. C. J. Org. Chem. 2006, 71, 3184–91. (c) Negishi,
E. I.; Huang, Z. H.; Wang, G. W.; Mohan, S.; Wang, C. Acc. Chem.
Res. 2008, 41, 1474. (d) Ni, Y.; Kassab, R. M.; Chevliakov, M. V.;
Montgomery, J. J. Am. Chem. Soc. 2009, 131, 17714. (e) Kwon, K.-H.;
Lee, D. W.; Yi, C. S. Angew. Chem., Int. Ed. 2011, 50, 1692.
(7) Tietze, L. F.; Hungerland, T.; Dufert, A.; Objartel, I.; Stalke, D.
Chem.;Eur. J. 2012, 18, 3286.
r
10.1021/ol303326g
Published on Web 01/10/2013
2013 American Chemical Society

organic chemists to design a new core structure for fluoro-
phores with tunable solid state emission despite the plethora
of examples available for such molecules. Recently we
reported an efficient stereo- and regioselective palladium-
catalyzed protocol for the synthesis of trisubstituted
olefins.10 In this paper, we describe a convenient method
for the synthesis of tetrasubstituted olefinic xanthene
derivatives via palladium catalyzed intramolecular carbo-
palladation followed by CꢀH activation of substituted
2-bromobenzyl-N-propargylamines and their photophysi-
cal properties in both solid and aggregation states.
Scheme 1. Concept for Synthesis of Tetrasubstituted Olefins
The requisite starting materials (4aꢀh) were synthesized
using our previous A3 coupling protocol,10a and the reac-
tion yields are tabulated (Table 1). We studied the scope of
the reaction by varying the aldehyde substrates. Generally
the reaction proceeded smoothly and led to the desired
products in good yields (Table 1, entries 1ꢀ8) of which
1,3,5-trioxane and naphthaldehyde displayed high reactiv-
ity (Table 1, entries 3 and 5). It is noteworthy to mention
that aldehydes possessing heteroaromatic motifs provided
the products in good yields (Table 1, entries 7 and 8).
Then we initiated our palladium catalyzed carbocycliza-
tion using N-benzyl-N-(2-bromo-4,5-dimethoxybenzyl)-
3-(2-phenoxyphenyl)-1-p-tolylprop-2-yn-1-amine (4a).
The reaction was carried out in the presence of Pd(OAc)2
(5 mol %), PPh3 (20 mol %), and Cs2CO3 (5 equiv) at
100 °C in DMF under a N2 atmosphere (Table 2, entry 1).
The desired cyclization product 5a was obtained in 65%
yield. This low yield prompted us to improve the reaction
conditions to obtain better yields, for which bases and
other solvents were investigated (Table 2, entries 2ꢀ6).
Other Pd sources such as PdCl2, Pd(CH3CN)2Cl2,
Pd(PPh3)4, and Pd2(dba)3 did not significantly affect the
Table 1. Scope of A3 Coupling Reaction for Synthesis of
Propargylamine (4aꢀh)
entry
substrate (2)
product
yielda,b
1
2
3
4
5
6
7
4-methylbenzaldehyde (2a)
4-methoxybenzaldehyde (2b)
1-naphthaldehyde (2c)
1-pyrenecaboxaldehyde (2d)
1,3,5-trioxane (2e)
4a
4b
4c
4d
4e
4f
87
89
90
75
90
86
77
ferrocenecarboxaldehyde (2f)
9-ethyl-9H-carbazole-3-
carbaldehyde (2g)
4g
8
1,3-diphenyl-1H-pyrazole-4-
carbaldehyde (2h)
4h
75
a The reactions were performed with amine 1 (0.5 mmol), aldehyde
2aꢀh (0.55 mmol), and alkyne 3 (0.75 mmol). b Isolated yields.
reaction yield (Table 2, entries 7ꢀ10). On increasing the
stoichiometry of the Pd(OAc)2 catalyst from 5 to 10 mol %,
the yield of the product improved to 86% (Table 2, entry 11).
A further increase in the amount of catalyst did not alter
the yield (Table 2, entry 12). The effect of temperature on
the reaction rate was also studied (Table 2, entry 13). Thus
the desired carbocyclization product 5a was obtained in
maximum yield (86%), when the reaction was carried out
with10mol % ofPd(OAc)2, 20 mol % of PPh3, and 5 equiv
of K2CO3 at 100 °C in DMF (Table 2).
Product 5a was isolated on completion of the reaction as
indicated by TLC and characterized using spectroscopic
techniques. The product 5a did not show any characteristic
property on the TLC plate under a UV lamp as soon as it
was withheld from the solvent pool. But upon evaporation
of solvent, the spot of 5a on the TLC plate developed
strong emission. We inferred that compound 5a on the
TLC plate exhibits a nonemissive property when it is
exposed in organic solvents but becomes an intense green
solid emitter under dry conditions. The PL spectrum of 5a
in dilute acetonitrile exhibits a flat line parallel to the
abscissa confirming that it is nonemissive in the solution
state. The solid state PL spectrum of 5a shows an emission
maximum at 523 nm. This anomalous behavior of 5a is
due to the phenomenon of aggregation induced emission
(8) (a) Yang, J. S.; Swager, T. M. J. Am. Chem. Soc. 1998, 120, 11864.
(b) Liu, Y.; Nishiura, M.; Wang, Y.; Hou, Z. M. J. Am. Chem. Soc. 2006,
128, 5592. (c) Tonzola, C. J.; Alam, M. M.; Kaminsky, W.; Jenekhe,
S. A. J. Am. Chem. Soc. 2003, 125, 13548. (d) Sreejith, S.; Divya, K. P.;
Ajayaghosh, A. Chem. Commun. 2008, 2903. (e) Chan, C. Y. K.; Zhao,
Z. J.; Lam, J. W. Y.; Liu, J. Z.; Chen, S. M.; Lu, P.; Mahtab, F.; Chen,
X. J.; Sung, H. H. Y.; Kwok, H. S.; Ma, Y. G.; Williams, I. D.; Wong,
K. S.; Tang, B. Z. Adv. Funct. Mater. 2012, 22, 378. (f) Yuan, W. Z.;
Gong, Y. Y.; Chen, S. M.; Shen, X. Y.; Lam, J. W. Y.; Lu, P.; Lu, Y. W.;
Wan, Z. M.; Hu, R. R.; Xie, N.; Kwok, H. S.; Zhang, Y. M.; Sun, J. Z.;
Tang, B. Z. Chem. Mater. 2012, 24, 1518. (g) Shimizu, M.; Hiyama, T.
Chem.;Asian. J. 2010, 5, 1516.
(9) (a) Shultz, D. A.; Fox, M. A. J. Am. Chem. Soc. 1989, 111, 6311.
(b) Oelkrug, D.; Tompert, A.; Gierschner, J.; Egelhaaf, H. J.; Hanack,
M.; Hohloch, M.; Steinhuber, E. J. Phys. Chem. B 1998, 102, 1902. (c)
Wurthner, F.; Sens, R.; Etzbach, K. H.; Seybold, G. Angew. Chem., Int.
Ed. 1999, 38, 1649. (d) Deans, R.; Kim, J.; Machacek, M. R.; Swager,
T. M. J. Am. Chem. Soc. 2000, 122, 8565. (e) Luo, J. D.; Xie, Z. L.; Lam,
J. W. Y.; Cheng, L.; Chen, H. Y.; Qiu, C. F.; Kwok, H. S.; Zhan, X. W.;
Liu, Y. Q.; Zhu, D. B.; Tang, B. Z. Chem. Commun. 2001, 1740. (f) An,
B. K.; Kwon, S. K.; Jung, S. D.; Park, S. Y. J. Am. Chem. Soc. 2002, 124,
14410. (g) Jayanty, S.; Radhakrishnan, T. P. Chem.;Eur. J. 2004, 10,
791. (h) Willy, B.; Dallos, T.; Rominger, F.; Schonhaber, J.; Muller,
T. J. J. Eur. J. Org. Chem. 2008, 4796. (i) D’Souza, D. M.; Kiel, A.;
Herten, D. P.; Rominger, F.; Muller, T. J. J. Chem.;Eur. J. 2008, 14,
529. (j) Shimizu, M.; Takeda, Y.; Higashi, M.; Hiyama, T. Angew.
Chem., Int. Ed. 2009, 48, 3653. (k) Anthony, S. P.; Varughese, S.; Draper,
S. M. J. Phys. Org. Chem. 2010, 23, 1074. (l) Ikejiri, M.; Tsuchino, M.;
Chihara, Y.; Yamaguchi, T.; Imanishi, T.; Obika, S.; Miyashita, K. Org.
Lett. 2012, 14, 4406. (m) Kubota, Y.; Tanaka, S.; Funabiki, K.; Matsui,
M. Org. Lett. 2012, 14, 4682.
(10) (a) Nandakumar, A.; Muralidharan, D.; Perumal, P. T. Tetrahedron
Lett. 2011, 52, 1644. (b) Nandakumar, A.; Balakrishnan, K.; Perumal, P. T.
Synlett 2011, 2733.
Org. Lett., Vol. 15, No. 2, 2013
383

Scheme 2. Tetrasubstituted Olefinic Xanthene Derivatives(5aꢀh)a
Table 2. Optimization of Palladium Catalyzed Carbocyclization
catalyst (mol %) þ
time yield
solvent (h) (%)a
entry
ligand
base
1
2
3
4
5
6
7
8
9
Pd(OAc)2(5) þ PPh3
Pd(OAc)2(5) þ PPh3
Pd(OAc)2(5) þ PPh3
Pd(OAc)2(5) þ PPh3
Pd(OAc)2(5) þ PPh3
Pd(OAc)2(5) þ PPh3
PdCl2(5) þ PPh3
Cs2CO3 DMF
K2CO3 DMF
5
5
5
5
5
5
5
8
5
5
2
2
2
65
70
NEt3
DMF
55
K2CO3 dioxane
K2CO3 toluene
K2CO3 CH3CN
K2CO3 DMF
30
45
60
55
PdCl2(CH3CN)2(5) þ PPh3 K2CO3 DMF
trace
50
a Isolated yields.
Pd(PPh3)4(5) þ PPh3
K2CO3 DMF
K2CO3 DMF
K2CO3 DMF
K2CO3 DMF
K2CO3 DMF
10 Pd2(dba)3(5) þ DPPFb
11 Pd(OAc)2(10) þ PPh3
12 Pd(OAc)2(15) þ PPh3
13 Pd(OAc)2(10) þ PPh3
45
86
85
86c
Scheme 3. Plausible Mechanism for Formation of 5
a The reactions were carried out with propargylamine 4a (0.3 mmol)
in the presence of a Pd source and base (5 equiv) at 100 °C under a N2
atmosphere. b DPPF-1,10-bis(diphenylphosphino)ferrocene. c The reac-
tion was carried out at 120 °C.
(AIE),9e and this is observed only in the solid or aggrega-
tion state.
Having the optimal conditions in hand, we synthesized
analogues of tetrasubstituted olefin based xanthenes
(5aꢀh) in good yields (Scheme 2) and studied their photo-
physical properties in both solid and solution states (Table 3).
All the derivatives showed an AIE phenomenon except
compounds 5e and 5f. This further explains that the presence
of a phenyl or fused aromatic or heteroaromatic group at
the C-3 position in products (5aꢀd, 5g, and 5h) prompts the
molecule to be AIE active. In solution, the intramolecular
rotation of the C3ꢀAr bond is active which causes non-
radiative deactivation from its excited state, whereas in the
solid state the intramolecular rotation is restricted and hence
this activates the radiative decay pathway causing the mole-
cule to exhibit an AIE phenomenon.
Mechanistically, the formation of product 5 consists of
the following sequential steps. First, aryl bromide 4 under-
goes oxidative addition to the in situ generated Pd(0) leads
to aryl palladium complex 6 (ArꢀPdꢀBr). Insertion of an
internal alkyne to aryl palladium complex 6 affords the
carbopalladation complex 8, and subsequent intramolecu-
lar CꢀH activation leads to seven-membered palladium
ring 9. Reductive elimination of 9 affords the tetrasubsti-
tuted olefin 5 with concomitant regeneration of the Pd(0)
species (Scheme 3).
visually emissive, and the solution consisting of a large
fraction of water showed an enhancement in its emissive
property. The PL spectrum of compound 5h in an aqueous
mixture initially starts to display emission intensity at 512 nm
when the water content was a 65% volume fraction and
reaches maximum at 75%. The intensity started to decrease
as the water content was altered from 75 to 80% (Figure 1a
and 1b). The plausible reason for this behavior could be due
to the change in the packing order of the molecules in the
aggregates. Low water content in the solution mixture may
cause the molecules to arrange in an ordered fashion to form
a more emissive crystalline aggregate, whereas at high water
content the solubility of the molecules decreases which
enforce the molecules to form lower emission agglomerated
amorphous aggregates.11 This confirms that, upon addition
of water, the compound starts to exhibit a PL property
due to formation of aggregation in aqueous mixtures. The
normalized absorption and emission spectra of compound
5h are shown in Figure 1c. The structure and optimized
Further, to confirm the AIE property of these com-
pounds, we analyzed the PL spectra of compound 5h.
Compound 5h at a 10 μM solution in acetonitrile did not
show any variation of intensity with wavelength. The slower
addition of a nonsolvent, e.g. water, made the solution
(11) Tong, H.; Hong, Y. N.; Dong, Y. Q.; Ren, Y.; Haussler, M.;
Lam, J. W. Y.; Wong, K. S.; Tang, B. Z. J. Phys. Chem. B 2007, 111,
2000–2007.
384
Org. Lett., Vol. 15, No. 2, 2013

Table 3. Optical Properties of Compounds (5aꢀd, 5g, and 5h)
λ
,
max ab, nm
λmax,em, nm
Stokes shift,e cmꢀ1
solid state fluorescent lifetimef
compd
solid
solutiona (ε cmꢀ1 b
)
solidc
solutiona,d
solid
solutiona
τ1 (ns)
τ2 (ns)
τ3 (ns)
A1/A2/A3
5a
5b
5c
5d
5g
5h
400
348
386
401
352
348
349 (10691)
350 (12007)
350 (9727)
357 (26230)
346 (12914)
355 (16521)
523
522
532
534
518
526
516
519
532
533
510
517
5879
9578
7110
6211
9104
9724
9273
9303
9774
9249
9294
8826
1.50
1.12
1.72
1.81
1.27
1.98
ꢀ
4.37
4.04
4.61
4.38
3.80
4.77
0.32/0/0.68
1.32
ꢀ
0.11/0.33/0.56
0.36/0/0.64
2.31
2.45
ꢀ
0.32/0.06/0.62
0.37/0.14/0.49
0.30/0/0.70
a In CH3CN/H2O (1:99) mixture at 10 μM. b Recorded at 1 ꢁ 10ꢀ5 M. c Excitation wavelengh: 400 nm. d Excitation wavelength: 350 nm. e Stokes shift =
λmax,abs ꢀ λmax,em (cmꢀ1). f A and τ are the fractional amount and fluorescent lifetime of the shorter (1), medium (2), and longer (3) species.
On the basis of the results obtained, compounds 5aꢀd,
5g, and 5h were essentially nonluminescent in CH3CN
solution and displayed intense green to yellow fluorescence
with a large Stokes shift in both the solid and aggregation
states. Therefore, they prove to be promising candidates
for a new class of AIE based dye materials with a rigid
structure. The absorption maxima of all of the above com-
pounds were measured in the solid state and 99% H2O/
CH3CN solution mixture. All the compounds showed an
intense absorption maximum in the range of 348ꢀ401 and
346ꢀ357 nm for solid and solution states respectively. The
solid state photoluminescence study of 5aꢀd, 5g, and 5h
were carried out at rt. Introducing a fused aromatic group
(naphthyl 5c or pyrene 5d) at the C3 carbon center caused
the emission maximum to show a red shift. Moreover, the
presence of the pyrazole 5g moiety in the C3 position
displayed a blue shift in emission spectra. The same results
were obtained in 99% H2O/CH3CN solutions. All the
Figure 1. (a) PL spectra of 5h in CH3CN/H2O mixtures with
varying water fraction (fw): concentration (μM), 10; excitation
compounds in the solid and aggregation states showed
large Stokes shift values which occur in the range
wavelength (nm), 350. (b) Plot of PL peak intensity vs water
5879ꢀ9774 cmꢀ1. The solid state fluorescent lifetimes of
fractions in CH3CN/H2O mixtures of 5h. I0 was the PL intensity in
pure CH3CN solution. The inset in panel b: Photos of 5h in
5aꢀd, 5g, and 5h were also analyzed (Table 3).
UV luminescence. (c) Normalized absorption (dash line) and
CH3CN/H2O mixtures (fw = 0, 75, and 99%) taken under
In summary, we have developed a palladium-catalyzed
domino reaction involving a carbopalladation/CꢀH
PL (solid line) spectra of compound 5h in solid (blue) and
aggregated solution (CH3CN/H2O (1:99) mixture) state (red).
(d) Ortep of 5h.
activation process that enables a new foundation for the
synthesis of AIE materials. These novel AIE compounds
are distinguishably featured by their intense solid state
fluorescence with large Stoke shifts. Further studies to
delineate this methodology are underway.
geometry of 5h were studied using X-ray single crystal
analysis (Figure 1d).12 Molecular packing in the crystal state
elucidates that the crystal geometry of 5h is stabilized by the
Acknowledgment. One of the authors, A.N., thanks
the Council of Scientific and Industrial Research (CSIR),
New Delhi, India for a research fellowship. The authors
thank Dr. P. Ramamurthy, Director, National Centre for
Ultrafast Processes, University of Madras, Chennai for
providing photoluminescence and lifetime studies and also
the Department of Chemistry, IITM, Chennai for single
crystal XRD analysis.
intermolecular CꢀH O hydrogen bond with a distance of
3 3 3
˚
2.529 A, causing the structure to be rigid in the crystalline
state (see Supporting Information). The presence of
N-benzyl and carbazole at the C2 and C3 carbons
respectively makes the molecule even more rigid. These
collective effects rigidify the molecule in the crystal
lattice and lock the molecular motion, thereby inducing
emission in the visible region.
Supporting Information Available. Experimental sec-
tion, 1H and 13C NMR spectra, and UVꢀvisible and PL
spectra of all compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
(12) Crystallographic data of compound 5h in this paper have
been deposited with the Cambridge Crystallographic Data Centre
as supplemental publication no. CCDC 899105. Copies of the data
can be obtained, free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: þ44 01223 336033 or email:
deposit@ccdc.cam.ac.uk).
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 2, 2013
385