Highly selective gold-catalyzed arene synthesis [24]

Full text of DOI:10.1021/ja005570d

J. Am. Chem. Soc. 2000, 122, 11553-11554
Highly Selective Gold-Catalyzed Arene Synthesis
11553
A. Stephen K. Hashmi,* Tanja M. Frost, and J. W. Bats
Institut fu¨r Organische Chemie
Johann Wolfgang Goethe-UniVersita¨t, Marie-Curie-Strasse 11
60439 Frankfurt am Main, Germany
ReceiVed September 3, 2000
Figure 1. ORTEP plot of the solid-state structure of 4g.
The classic route to aromatic compounds with specific substitu-
tion patterns is the aromatic substitution which introduces or
exchanges substituents at an already existing arene.1 A different
mechanism but the same synthetic principle is applied in the
different transition-metal-catalyzed (cross-) coupling reactions2
or ortho-metalation and subsequent functionalization reactions.3
Other approaches assemble the arene, e.g. use cycloaddition
reactions such as the Diels-Alder reaction followed by a
subsequent oxidation of the unsaturated six-membered ring to an
arene.4 Some major achievements in this field of cycloadditions
or cycloisomerizations of the past years stem from transition metal
catalysis.5 For arene synthesis Vollhardt’s [2+2+2] cycloaddition6
and variations thereof7 as well as the Do¨tz reaction8 are among
the most prominent.
Since both allenyl and propargyl ketones are known to
isomerize to furans with the gold catalyst,12 we assumed that first
3 is formed from 1 and 2 and then 3 is transformed to 4 by the
gold catalyst in a separate step.
We now want to report our results concerning the synthesis of
highly substituted arenes, more specifical phenols, by gold
catalysis. Gold-catalyzed homogeneous organic reactions are quite
rare: the only examples that reached some importance are the
Ito-Hayashi aldol reaction9 and the addition of O- or N-
nucleophiles to unsaturated compounds first described by Utim-
oto10 and later improved by Teles.11 Recently we reported new
C-O- and C-C-bond formations catalyzed by gold; further
investigation of these reactions led to the completely new results
described here.12
Further experiments prove that assumption. AuCl3 in acetoni-
trile cleanly transformed 3 to 4. The structure of 4g was
unequivocally proven by X-ray crystal structure analyses.14 The
reactions proceeded at room temperature, neither air nor water
needed to be excluded: even when 2.7 equiv of water was added,
no addition of water to the alkyne was observed, only 4 was
formed. No paramagnetic species were formed and no gold
precipitates; the reactions could nicely be monitored by 1H NMR.
The spectra show that during the reaction no detectable concentra-
tions of any intermediates build up.
When we subjected a mixture13 of the allenyl ketone 2 and the
propargyl ketone 1 in acetonitrile to AuCl3, besides the expected
furan 3, a second product, the hydroxyarene 4, could be isolated.
(1) Electrophilic or nucleophilic: Olah, G. A. Acc. Chem. Res. 1971, 4,
240-248. Hartshorn, S. R. Chem. Soc. ReV. 1974, 3, 167-192. Pearson, D.
E.; Buehler, C. A. Synthesis 1971, 455-477.
(2) Negishi, E. Acc. Chem. Res. 1982, 15, 340-348. Brown, J. M.; Cooley,
N. A. Chem. ReV. 1988, 88, 1031-1046. Miyaura, N.; Suzuki, A. Chem. ReV.
1995, 95, 2457-2483. Mitchell, T. N. Synthesis 1992, 803-815.
(3) Chauder, B.; Green, L.; Snieckus, V. Pure Appl. Chem. 1999, 71, 1521-
1529. Snieckus, V. Pure Appl. Chem. 1990, 62, 2047-2056.
(4) Oppolzer, W. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, pp 315-399. Fu, P. P.;
Harvey, R. G. Chem. ReV. 1978, 78, 317-361.
(5) Wender, P. A.; Snapper, M. L. Tetrahedron Lett. 1987, 28, 2221-
2224. Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T. J. Am. Chem.
Soc. 1990, 112, 4965-4966. Baldenius, K.-U.; tom Dieck, H.; Ko¨nig, W. A.;
Icheln, D.; Runge, T. Angew. Chem., Int. Ed. Engl. 1992, 31, 305-307.
Wender, P. A.; Jenkins, T. E.; Suzuki, S. J. Am. Chem. Soc. 1995, 117, 1843-
1844. Wender, P. A.; Takahashi, H.; Witulski, B. J. Am. Chem. Soc. 1995,
117, 4720-4721. Saito, S.; Salter, M. M.; Gevorgyan, V.; Tsuboya, N.; Tando,
K.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 3970-3971. Saito, S.;
Uchiyama, N.; Gevorgyan, V.; Yamamoto, Y. J. Org. Chem. 2000, 65, 4338-
4341.
(6) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539-556.
(7) Reppe, W.; von Kutepow, N.; Magin, A. Angew. Chem., Int. Ed. Engl.
1969, 8, 727-733. Mu¨ller, E. Synthesis 1974, 761-774. Grigg, R.; Scott, R.;
Stevenson, P. Tetrahedron Lett. 1982, 23, 2691-2692. Schore, N. E. Chem.
ReV. 1988, 88, 1081-1119. Schore, N. E. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5,
pp 1129-1162. McDonald, F. E.; Zhu, H. Y. H.; Holmquist, C. R. J. Am.
Chem. Soc. 1995, 117, 6605-6606. Witulski, B.; Stengel, T. Angew. Chem.,
Int. Ed. Engl. 1999, 38, 2426-2430.
Analysis of the spectra shows that the catalyst suffers deactiva-
tion. In the reaction of 1 and 2 with AuCl3 the deactivation of
the catalyst seems to be even faster, therefore the further
conversion of 3 to 4 is not complete when starting from these
substrates. On the other hand, only a small amount (2 mol %) of
catalyst is necessary for a complete reaction, which strongly
suggests that if the deactivation can be prevented by modification
(8) Do¨tz, K. H. Angew. Chem., Int. Ed. Engl. 1984, 23, 587-608.
(9) Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108, 6405-
6406.
(10) Fukuda, Y.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 2013-2015.
(11) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem., Int. Ed. Engl.
1998, 370, 1415-1418.
(12) Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew. Chem.,
Int. Ed. Engl. 2000, 39, 2285-2288.
10.1021/ja005570d CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/03/2000

11554 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Communications to the Editor
of the catalyst (at the moment a simple gold salt) an even smaller
amount of catalyst might be sufficient.
or external water may serve as nucleophiles, and possible
intermediates are 13 and 14. They finally lead to the product 4.
Such an isomerization of oxanorbornadienes to phenols usually
requires very strong acids.19 If the opening of the oxygen bridge
would occur in the other direction, the nucleophile could not attack
at the position where the OH group is attached in the product.
The local symmetry of the intermediates 13 or 14 for R ) H
would explain the formation of a mixture of 6 and 7 from 5.
This proposal cannot explain the highly regioselective formation
of 4 (no 9 or other isomers were observed), which could be
evidence for a completely different mechanism. The necessity of
a terminal alkyne might be evidence for an acetylide or even
vinylidene complex as intermediate, then the hydroxyl group
would end up at the position where the metal is attached in the
intermediates.
Due to their good accessibility, the use of furans 3 instead of
ketones 1 and 2 is synthetically appealing. Even if the furan
possesses only one substituent as in 5, the catalysis works but
two products, 6 and 7, were formed. 6 corresponds to 4, while 7
is an isomer without 1,2-transposition of the oxygen (vide infra).
With a disubstituted alkyne like 8 instead of a terminal one,
no reaction was observed.15 With tetrahydrothiophenegold(I)
chloride or a mixture of triethylphosphanegold(I) chloride and
silver tetrafluoroborate the reaction also proceeded but was much
slower. No reaction was observed with AgNO3, Hg(ClO4)2, Pd2-
dba3‚CHCl3, Pd(PPh3)4, Rh(PPh3)3Cl, ZnI2, AlCl3, FeCl3, InCl3,
and p-TsOH (all in MeCN), heating up to 170 °C in mesitylene
for several hours, and at 8 kbar in MeCN for 4 h. TfOH caused
an unspecific decomposition, with Cl2(PCy)2RudCHPh at room
temperature no reaction occurred, and at 80 °C a complex mixture
of products was formed. Only with PdCl2(MeCN)2 were traces
of 4 visible after several days at room temperature. The latter
observation is in accordance with our earlier results on the
synthesis of substrates of type 3 by PdII-catalyzed isomerizations
of allenyl ketones without further conversion to 4.16 First
experiments with 3h show that an anellation of a six-membered
ring with the benzene is also possible, but again ring closure
competes with catalyst deactivation and thus the 3-fold amount
of catalyst (6 mol %) was needed for a complete conversion to
4h.
Finally it must be mentioned that with related starting materials,
namely 15, under strongly basic conditions at 85 °C via an allenic
intermediate a Kanematsu furan ring transfer reaction20 to 16 can
be achieved. In these reactions the oxygen atom always remains
attached to the same carbon atom.
For the mechanism of the reaction, we can only offer a simple
proposal that falls back on steps known from classical organic
chemistry. One could assume that the gold coordinates and thus
increases the electrophilicity of the triple bond. This would be
quite similar to the activiation of C-C multiple bonds for
nucleophilic addition mentioned above.10,11 Now an intramolecular
Diels-Alder reaction could provide 10. Usually furans are
notorious unreactive diene partners in Diels-Alder reactions that
even in intramolecular cases17 react only if the dienophile is
activated by at least one electron withdrawing group or high
pressure is applied for strain-activated olefins.18
So our reaction not only represents a new access to arenes from
easily available furans but also nicely complements the synthetic
potential of substrates such as 4. In addition, the phenolic hydroxyl
group opens several possibilities for a further fuctionalization of
the substrate and it should easily be possible to incorporate
stereogenic centers from compounds of the chiral pool.
Acknowledgment. This work was generously supported by the
Deutsche Forschungsgemeinschaft (Ha 1932/5-1, Ha 1932/6-1), the Fonds
der Chemischen Industrie, and the Dr. Otto Ro¨hm Memorial Fond. Noble
metals were donated by Degussa-Hu¨ls AG. We are indebted to Prof. Dr.
M. Go¨bel for laboratory space.
In the next step the oxygen bridge must be broken, and this
could either be induced by gold(III) acting as a Lewis acid
(forming 12) or by Au(I) which forms a Au(III)-stabilized
pentadienyl cation 11. Then either the nucleophilic oxygen atom
Supporting Information Available: Characerization data of com-
pounds 4a-4h, 6, and 7 and X-ray crystal analysis data for 4g (PDF).
This material is available free of charge via the Internet at http://pubs.acs.org.
(13) During workup 2 does not completely isomerize to 1, this behavior
differs from the one of terminal propargyl ketones: Hashmi, A. S. K.; Bats,
J. W.; Choi, J.-H.; Schwarz, L. Tetrahedron Lett. 1998, 39, 7491-7494.
(14) Crystal data for 4g: monoclinic, space group P21/c, colorless crystal,
a ) 7.8560(12) Å, b ) 10.758(2) Å, c ) 15.490(3) Å, b ) 101.504(14)°,
154(2) K, Z ) 4, GOF ) 1.342, R1 ) 0.0664.
JA005570D
(15) Even in the presence of another terminal alkyne.
(19) Batt, D. G.; Jones, D. G.; La Greca, S. J. Org. Chem. 1991, 56, 6704-
6708. Epsztajn, J.; Jo´z´wiak, A.; Szczes´niak, A. K. J. Chem. Soc., Perkin Trans.
1 1998, 2563-2567.
(16) Hashmi, A. S. K.; Schwarz, L. Chem. Ber./Recl. 1997, 130, 1449-
1456.
(17) Brieger, G.; Bennett, J. N. Chem. ReV. 1980, 80, 63-97 (specifically
p 81). Roush, W. R. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, pp 513-550.
(18) Buback, M.; Heiner, T.; Hermans, B.; Kowollik, C.; Kozhushkov, S.
I.; de Meijere, A. Eur. J. Org. Chem. 1998, 107-112.
(20) Yamaguchi, Y.; Tatsuta, N.; Hayakawa, K.; Kanematsu, K. J. Chem.
Soc., Chem. Commun. 1989, 470-472. Kanematsu, K.; Nishizaki, A.; Sato,
Y.; Shiro, M. Tetrahedron Lett. 1992, 33, 4967-4970. For related results,
see: Wu, H.-J.; Yen, C.-H.; Chuang, C.-T. J. Org. Chem. 1998, 63, 5064-
5070.