Gold nanoparticles supported on TiO2 catalyse the cycloisomerisation/oxidative dimerisation of aryl propargyl ethers

Article abstract of DOI:10.1039/c0cc03353g

Gold nanoparticles supported on TiO₂ (～1%) catalyse in high yields the selective cycloisomerisation of aryl propargyl ethers into the corresponding 2H-chromenes, under heterogeneous conditions. 2H,2′H-3, 3′-Bichromenes resulting from a catalytic oxidative dimerization pathway are also formed as by-products. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c0cc03353g

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Gold nanoparticles supported on TiO2 catalyse the cycloisomerisation/
oxidative dimerisation of aryl propargyl ethersw
Christina Efe, Ioannis N. Lykakis and Manolis Stratakis*
Received 19th August 2010, Accepted 22nd October 2010
DOI: 10.1039/c0cc03353g
Gold nanoparticles supported on TiO2 (B1%) catalyse in high
yields the selective cycloisomerisation of aryl propargyl ethers
into the corresponding 2H-chromenes, under heterogeneous
conditions. 2H,20H-3,30-Bichromenes resulting from a catalytic
oxidative dimerization pathway are also formed as by-products.
rearrangement. Apart from the thermal process, many metal-
catalysed protocols were developed, including cationic Pd, Ru,
Ag, Ga, Pt and Hg.12 Recently, Au(I)-catalysed versions under
homogeneous conditions have been reported.13
We were pleased to find that a variety of aryl propargyl
ethers (substrates 1–11, Table 1) cycloisomerise, primarily to
the corresponding 2H-chromenes, upon heating (70 1C) a
slurry of Au/TiO2 in dry 1,2-dichloroethane (DCE) having
dissolved the aryl propargyl ethers. As by-products, dimeric
2H- chromenes (1b–5b, 10b–11b, 12c), which obviously arise
from a gold-catalysed oxidative dimerisation14 pathway, as
well as, benzofurans are formed (up to 5% relative yield). The
relative ratio of dimers varies from 0–18% depending on
the substrate. No dimers were detected during the
cycloisomerisation of substrates 7–9, apparently due to steric
reasons. In a typical example, 0.2 mmol of aryl propargyl
Gold nanoparticles supported on metal oxide surfaces have
emerged as powerful heterogeneous catalysts for various
transformations.1 Primarily, they catalyse the oxidation of
CO,2 alcohols and aldehydes,3 as well as, the epoxidation of
alkenes4 under aerobic conditions. The mechanism of these
oxidation processes is questionable and under debate.
Recently, we reported that gold nanoparticles supported on
titania (Au/TiO2) catalyse the selective isomerisation of
epoxides into allylic alcohols,5 a process that requires the
synergism of an acidic and a basic catalytic site. Apparently
the Lewis acidic sites are provided by Au cationic species (AuI
and/or AuIII) stabilised by titania. Such species, which have
been identified by XPS6 and can be titrated by FT-IR7 using
CO as a probe, are likely to play a pivotal role in catalytic
processes which involve supported Au nanoparticles.
15
ether, and 50 mg of Au/TiO2 (approximately 1.2–1.3%
loading level in Au) were heated to 70 1C without taking any
precautions to exclude air. The reaction was monitored by
TLC and GC. After disappearance of the starting material
(1–48 h) the slurry was passed through a short pad containing
celite and silica gel. The products were purified by column
chromatography if necessary.
One of the most fascinating fields in modern organic
chemistry is alkyne activation by Au(I) and Au(III), with an
explosive growth during the last decade. The CꢀC triple bond
is highly aurophilic allowing thus the achievement of
transformations that do not occur using conventional metal-
based catalysts.8 Despite the extensive development of Au-
catalysed addition reaction in alkynes under homogeneous
The reactivity of the substrates is in accordance to the
electronic nature of the substituents. Electron-withdrawing
groups retard the reaction rate, whereas, electron-donating
groups accelerate it (Friedel–Crafts type reactivity). We
observed that on prolonged reaction times, isomeric 4H-
chromenes start to form in up to 10–15% relative yield, and
obviously arise from the isomerization of the initially formed
2H-chromenes. The 4H-chromenes can be easily identified in
the crude reaction mixture by GC-MS and by comparing their
characteristic 1H NMR absorptions to those of known
compounds.13a,16 Indeed, pure 2H-chromene 2a was treated
with Au/TiO2 for 4 h under the reaction conditions and partly
converted (B20–25%) to its isomeric 4H-chromene (see ESIw)
without, however, forming any dimer. Notably the gold
conditions,
a
few examples7,9 appear in the literature
regarding heterogeneous protocols (e.g., hydrosilylation,
hydroboronylation), and use of gold nanoparticles on
various supports. Notably gold nanoparticles supported on
CeO2 have been reported to be inactive against 1,6-enyne
cyclization,10 yet active in the case of furan-ynes.7
We envisioned gold cationic species6,7 present in Au/TiO2 as
catalytic sites to activate alkynes for attack by carbon-based
nucleophiles under heterogeneous conditions, and provide a
novel application to this material. The chosen key-reaction was
the cycloisomerisation of aryl propargyl ethers to form 2H-
chromenes or benzofurans (Scheme 1).11 This reaction is
known to proceed under extreme thermal conditions (e.g.
boiling PhNMe2), and has been proposed to form an
nanoparticles-catalysed cyclization tolerates
a variety of
substituents on the propargyl chain. For instance, gem-
dimethyl substituted 10 has been reported to be unreactive
under homogeneous Au(III)-catalysis.14a Moreover, we
intermediate o-allenyl phenol via
a
[3,3]-sigmatropic
Department of Chemistry, University of Crete, Voutes 71003 Iraklion,
Greece. E-mail: stratakis@chemistry.uoc.gr; Fax: +30 2810 545001;
Tel: +30 2810 545087
w Electronic supplementary information (ESI) available: Experimental
details for the synthesis of substrates; 1H and 13C NMR of all
compounds; MS and HRMS spectra of new compounds. See DOI:
10.1039/c0cc03353g
Scheme 1 The cycloisomerisation of aryl propargyl ethers into 2H-
chromenes and benzofurans.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 803–805 803

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Table 1 Cyclization of aryl propargyl ethers catalysed by Au/TiO2
performed several blank experiments which support the
heterogeneous nature of the reaction. Thus, the aryl
propargyl ethers are unreactive either on refluxing DCE or in
a refluxing slurry of DCE with TiO2. Additionally, after
heating a slurry of Au/TiO2 in DCE for several hours, we
observed that the supernatant solution is totally inefficient in
promoting cyclisation. Indeed, ICP analysis17 revealed that the
gold content in the supernatant is extremely low (B0.4 ppb).
The efficiency of the method allowed the use of Au/TiO2 as a
catalyst to synthesise the naturally occurring pyranocoumarins
seselin (12a) and xanthyletin (12b), compounds with
surprisingly rich biological activities,18 from a simple aryl
propargyl ether precursor (Table 1). The Au/TiO2-catalysed
cycloisomerisation of umbelliferyl propargyl ether 12 yielded
after 25 h a mixture of seselin and xanthyletin in 65/35 relative
ratio (92% isolated yield).18b,19 Additionally, the symmetrical
dimer of xanthyletin 12c was also isolated in 4% relative yield.
As the mechanism for the formation of monomeric 2H-
chromenes 1a–11a under Au-catalysis is straightforward,13a we
will focus on the origins for the formation of dimeric products
(Scheme 2). While 2H-chromenes can be formed by either
cationic Au(I) or Au(III) species present in Au/TiO2, the
dimers apparently are formed by oxidative Au(III)-catalysis.
Thus, in the proposed mechanism shown in Scheme 2, we
concentrate on Au(III)-catalysis. In several entries (e.g.,
substrates 1–5) the amount of the isolated dimeric product
exceeds substantially the overall loading (Au0, AuI, AuIII) of
the catalyst in gold (B1.2%), therefore, the dimerisation
process is catalytic without any doubt. In recent years there
are several examples in the literature describing oxidative
dimerisation reactions under Au(III)14 conditions, yet in
catalytic versions, an external added oxidant (e.g. t-
BuOOH,20 PhI(OAc)2, Selectfluor) is always necessary to re-
oxidise Au(I) to Au(III). Thus, we postulate that the initially
formed auric-monocyclic I (Scheme 2) acts as an electrophilic
center to cyclise a second propargyl ether. The diorganogold II
undergoes intermolecular C–C coupling to form the dimeric
products with elimination of Au(I)-species. In the absence of an
Yield/
time
Substrate
Product
82%/
15 h
83%/
7 h
74%/
3 h
88%/
23 h
80%/
18 h
94%/
1 ha
—
—
85%/
24 hb
91%/
48 hb
—
—
96%/
2 hb
94%/
26 h
90%/
15 h
92%/
25 h
a
For substrate 6, the dimer was formed in ca. 2% yield (crude 1H
Scheme 2 Proposed mechanism for the formation of monomeric and
dimeric 2H-chromenes through Au(III)-catalysis.
b
NMR, GC-MS) No dimers were detected.
c
804 Chem. Commun., 2011, 47, 803–805
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external oxidant added into the reaction mixture, we propose
that the Au(I) to Au(III) re-oxidation occurs by reactive oxygen
species (ROS),21 the proposed transient oxidants in the aerobic
oxidation of alcohols to carbonyl compounds by gold nano-
particles on titania or ceria. Indeed, by excluding air from the
reaction medium (argon atmosphere), the amount of dimer for
the case of substrate 2 was drastically reduced to 3–4% (com-
pared to 18% if the reaction takes place in open air). Moreover,
by occasionally blowing air into the reaction mixture, the relative
amount of dimer 2b increased to 25%, which indicates that
under those partly-aerated conditions, approximately 40% of
the reacting molecules of 2 follow the dimerisation pathway.
In conclusion, we report the first application of Au/TiO2 as a
heterogeneous gold-based catalyst to activate CꢀC triple bonds
and effectively cyclise arenynes. This is likely to open a new
window to the applications of gold nanoparticles in alkyne
activation and C–C bond formation reactions,9a,22 a topic
with scarce examples from the heterogeneous point of view.
Further work to delineate the mechanism for the formation of
dimeric products, as well as, new applications in alkyne
activation involving supported gold nanoparticles is in progress.
9 (a) C. Gonzalez-Arellano, A. Abad, A. Corma, H. Garcia, M. Iglesias
and F. Sanchez, Angew. Chem., Int. Ed., 2007, 46, 1536–1538;
(b) A. Abad, A. Corma and H. Garcia, Top. Catal., 2007, 44,
237–243; (c) A. Corma, C. Gonzalez-Arellano, M. Iglesias and
F. Sanchez, Angew. Chem., Int. Ed., 2007, 46, 7820–7822;
(d) A. M. Caporusso, L. A. Aronica, E. Schiavi, G. Martra, G. Vitulli
and P. Salvadori, J. Organomet. Chem., 2005, 690, 1063–1066.
10 M. Garcia-Mota, N. Cabello, F. Maseras, A. M. Echavarren,
J. Perez-Ramirez and N. Lopez, ChemPhysChem, 2008, 9,
1624–1629.
11 R. P. Lutz, Chem. Rev., 1984, 84, 205–247.
12 (a) C. Jia, W. Lu, J. Oyamada, T. Kitamura, K. Matsuda, M. Irie and
Y. Fujiwara, J. Am. Chem. Soc., 2000, 122, 7252–7263;
(b) S. J. Pastine, S. W. Youn and D. Sames, Org. Lett., 2003, 5,
1055–1058; (c) A. Furstner and V. Mamane, Chem. Commun., 2003,
2112–2113; (d) N. Chatani, H. Inoue, T. Ikeda and S. Murai, J. Org.
Chem., 2000, 65, 4913–4918; (e) J. S. Yadav, B. S. V. Reddy,
B. Padmavani and M. K. Gupta, Tetrahedron Lett., 2004, 45,
7577–7579; (f) M. Nishizawa, H. Takao, V. K. Yadav,
H. Imagawa and T. Sugihara, Org. Lett., 2003, 5, 4563–4565;
(g) M. Bandini, E. Emer, S. Tommasi and A. Umani-Ronchi, Eur.
J. Org. Chem., 2006, 3527–3544; (h) U. Koch-Pomeranz,
H.-J. Hansen and H. Schmid, Helv. Chim. Acta, 1973, 56, 2981–3004.
13 (a) C. Nevado and A. M. Echavarren, Chem.–Eur. J., 2005, 11,
3155–3164; (b) N. Mezailles, L. Ricard and F. Gagosz, Org. Lett.,
2005, 7, 4133–4136; (c) R. S. Menon, A. D. Findlay, A. C. Bissember
and M. G. Banwell, J. Org. Chem., 2009, 74, 8901–8903.
14 (a) H. A. Wegner, S. Ahles and M. Neuburger, Chem.–Eur. J.,
2008, 14, 11310–11313; (b) G. Zhang, Y. Peng, L. Cui and
L. Zhang, Angew. Chem., Int. Ed., 2009, 48, 3112–3115;
(c) L. Cui, G. Zhang and L. Zhang, Bioorg. Med. Chem. Lett.,
2009, 19, 3884–3887; (d) M. N. Hopkinson, A. Tessier,
A. Salisbury, G. T. Giuffredi, L. E. Combettes, A. D. Gee and
V. Gouverneur, Chem.–Eur. J., 2010, 16, 4739–4743;
(e) H. A. Wegner, Chimia, 2009, 63, 44–48; (f) A. Kar,
N. Mangu, H. M. Kaiser and M. K. Tse, J. Organomet. Chem.,
2009, 694, 524–537; (g) H. Harkat, A. Y. Dembele, J.-M. Weibel,
A. Blanc and P. Pale, Tetrahedron, 2009, 65, 1871–1879; (h) A. Kar,
N. Mangu, H. M. Kaiser, M. Beller and M. K. Tse, Chem.
Commun., 2008, 386–388; (i) A. S. K. Hashmi, M. C. Blanco,
D. Fischer and J. W. Bats, Eur. J. Org. Chem., 2006, 1387–1389;
(j) F. Zamora, P. Amo-Ochoa, B. Fischer, A. Schimanski and
B. Lippert, Angew. Chem., Int. Ed., 1999, 38, 2274–2275; (k) A. S.
K. Hashmi, T. D. Ramamurthi and F. Rominger, J. Organomet.
Chem., 2009, 694, 592–597; (l) P. Garcia, M. Malacria, C. Aubert,
V. Gandon and L. Fensterbank, ChemCatChem, 2010, 2, 493–497.
15 The catalyst containing B1% w/w in Au is commercially available
from Strem Chemicals. A catalyst with B1.5% w/w in Au (World
Gold Council), used in the initial experiments, is no longer
available.
16 S. J. Pastine, S. W. Youn and D. Sames, Tetrahedron, 2003, 59,
8859–8868.
17 We thank professor S. Pergantis (Univ. of Crete) for carrying out
the ICP analysis.
18 (a) P. Magiatis, E. Melliou, A.-L. Skaltsounis, S. Mitaku,
S. Leonce, P. Renard, A. Pierre and G. Atassi, J. Nat. Prod.,
1998, 61, 982–986; (b) R. S. Mali, P. P. Joshi, P. K. Sandhu and
A. Manekar-Tilve, J. Chem. Soc., Perkin Trans. 1, 2002, 371–376.
19 Syntheses of seselin and xanthyletin using alternative approaches:
(a) K. C. Nicolaou, J. A. Pfefferkorn and G.-Q. Cao, Angew.
Chem., Int. Ed., 2000, 39, 734–739; (b) P. C. Bulman Page,
L. F. Appleby, D. Day, Y. Chan, B. R. Buckley, S. M. Allin and
M. J. McKenzie, Org. Lett., 2009, 11, 1991–1993.
Notes and references
1 (a) A. Corma and H. Garcia, Chem. Soc. Rev., 2008, 37, 2096–2126;
(b) R. Coquet, K. L. Howard and D. J. Willock, Chem. Soc. Rev.,
2008, 37, 2046–2076; (c) M. Chen and D. W. Goodman, Chem. Soc.
Rev., 2008, 37, 1860–1870; (d) M.-C. Daniel and D. Astruc, Chem.
Rev., 2004, 104, 293–346.
2 (a) M. Haruta, N. Yamada, T. Kobayashi and S. Iijima, J. Catal.,
1989, 115, 301–309; (b) M. Valden, X. Lai and D. W. Goodman,
Science, 1998, 281, 1647–1650; (c) C.-J. Jia, Y. Liu, H. Bongard and
F. Schuth, J. Am. Chem. Soc., 2010, 132, 1520–1522; (d) J. Guzman
and B. C. Gates, J. Am. Chem. Soc., 2004, 126, 2672–2673;
(e) M. F. Camellone and S. Fabris, J. Am. Chem. Soc., 2009, 131,
10473–10483.
3 (a) A. S. K. Hashmi and G. J. Hutchings, Angew. Chem., Int. Ed.,
2006, 45, 7896–7936; (b) A. S. K. Hashmi, Chem. Rev., 2007, 107,
3180–3211; (c) C. Della Pina, E. Falletta, L. Prati and M. Rossi, Chem.
Soc. Rev., 2008, 37, 2077–2095; (d) A. Abad, A. Corma and H. Garcia,
Chem.–Eur. J., 2008, 14, 212–222; (e) P. Fristrup, L. B. Johansen and
C. H. Christensen, Chem. Commun., 2008, 2750–2752.
4 (a) M. Turner, V. B. Golovko, O. P. H. Vaughan, P. Abdulkin,
A. Berenguer-Murcia, M. S. Tikhov, B. F. G. Johnson and
R. M. Lambert, Nature, 2008, 454, 981–983; (b) A. K. Sinha,
S. Seelan, T. Akita, S. Tsubota and M. Haruta, Catal. Lett.,
2003, 85, 223–228; (c) A. K. Sinha, S. Seelan, S. Tsubota and
M. Haruta, Angew. Chem., Int. Ed., 2004, 43, 1546–1548;
(d) B. Taylor, J. Lauterbach and W. N. Delgass, Appl. Catal., A,
2005, 291, 188–198; (e) E. E. Stangland, K. B. Stavens,
R. P. Andres and W. N. Delgass, J. Catal., 2000, 191, 332–347.
5 C. Raptis, H. Garcia and M. Stratakis, Angew. Chem., Int. Ed.,
2009, 48, 3133–3136.
6 J. C. Fierro-Gonzaleza and B. C. Gates, Chem. Soc. Rev., 2008, 37,
2127–2134.
7 S. Carrettin, M. C. Blanco, A. Corma and A. S. K. Hashmi, Adv.
Synth. Catal., 2006, 348, 1283–1288.
8 Recent selected examples: (a) E. Jimenez-Nunez and
A. M. Echavarren, Chem. Rev., 2008, 108, 3326–3350;
(b) D. J. Gorin, B. D. Sherry and F. D. Toste, Chem. Rev., 2008,
108, 3351–3378; (c) Z. Li, C. Brouwer and C. He, Chem. Rev., 2008,
108, 3239–3265; (d) N. D. Shapiro and F. D. Toste, Synlett, 2010,
675–691; (e) H. C. Shen, Tetrahedron, 2008, 64, 3885–3903;
(f) A. Furstner and P. W. Davies, Angew. Chem., Int. Ed., 2007,
46, 3410–3449; (g) A. Furstner, Chem. Soc. Rev., 2009, 38,
3208–3221; (h) A. S. K. Hashmi, Chem. Rev., 2007, 107,
3180–3211; (i) A. S. K. Hashmi, Angew. Chem., Int. Ed., 2010,
49, 5232–5241; (j) V. Lopez-Carrillo and A. M. Echavarren, J. Am.
Chem. Soc., 2010, 132, 9292–9294.
20 A. S. K. Hashmi, C. Lothschuetz, M. Ackermann, R. Doepp,
S. Anantharaman, B. Marchetti, H. Bertagnolli and F. Rominger,
Chem.–Eur. J., 2010, 16, 8012–8019.
21 (a) J. Guzman, S. Carrettin and A. Corma, Angew. Chem., Int. Ed.,
2005, 44, 4778–4781; (b) J. Guzman, S. Carrettin and A. Corma,
J. Am. Chem. Soc., 2005, 127, 3286–3287; (c) J. Jiang, S. M. Oxford,
B. Fu, M. C. Kung, H. H. Kung and J. Ma, Chem. Commun., 2010,
46, 3791–3793.
22 (a) V. K. Kanuru, G. Kyriakou, S. K. Beaumont,
A. C. Papageorgiou, D. J. Watson and R. M. Lambert, J. Am.
Chem. Soc., 2010, 132, 8081–8086; (b) J. Han, J. Y. Liu and R. Guo,
J. Am. Chem. Soc., 2009, 131, 2060–2061.
c
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Chem. Commun., 2011, 47, 803–805 805