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Date: 24-09-12 17:00:20
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Gold-Catalyzed Rearrangement of 1-Alkynyloxiranes
knowledged. R. V. is a Ramón y Cajal Fellow. We thank Prof.
Dr. J. M. González for his support.
Finally, according to this mechanistic proposal and con-
sidering the oxophilic character of gold(III) complexes,[17]
we decided to evaluate whether or not the presence of the
alkyne is required to perform an epoxide rearrangement.
Interestingly, we found that AuCl3 (5.0 mol-%, DCE, r.t.)
proved capable to catalyze the Meinwald-type rearrange-
ment of representative epoxides 4 to ketones 5 in moderate
to good yields (Scheme 5). This result clearly reveals the
ability of gold(III) catalysts to act efficiently not only as a
π-Lewis acid but also as a σ-oxophilic Lewis acid.[18,19]
[1] a) E. N. Jacobsen, M. H. Wu in Comprehensive Asymmetric
Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),
Springer, New York, 1999, vol. 3, pp. 1309–1326; b) A. K. Yu-
din, Aziridines and Epoxides in Organic Synthesis 1st ed.,
Wiley-VCH, Weinheim, 2008.
[2] a) D. Miller, J. Chem. Soc. C 1969, 12; b) H. Berbalk, K. Eich-
inger, R. Schuster, Synthesis 1981, 613; c) H. Berbalk, K. Eich-
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F. E. McDonald, C. C. Schlutz, J. Am. Chem. Soc. 1994, 116,
9363; g) C.-Y. Lo, H. Guo, J.-J. Lian, F.-M. Shen, R.-S. Liu, J.
Org. Chem. 2002, 67, 3930.
[3] Reviews on gold catalysis: a) Z. Li, C. Brouwer, C. He, Chem.
Rev. 2008, 108, 3239; b) A. Arcadi, Chem. Rev. 2008, 108, 3266;
c) E. Jiménez-Núñez, A. M. Echavarren, Chem. Rev. 2008, 108,
3326; d) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev.
2008, 108, 3351; e) A. S. K. Hashmi, Chem. Rev. 2007, 107,
3180; f) A. Fürstner, P. W. Davies, Angew. Chem. 2007, 119,
3478; Angew. Chem. Int. Ed. 2007, 46, 3410; g) A. S. K.
Hashmi, G. J. Hutchings, Angew. Chem. 2006, 118, 8064; An-
gew. Chem. Int. Ed. 2006, 45, 7896.
[4] A. S. K. Hashmi, P. Sinha, Adv. Synth. Catal. 2004, 346, 432.
[5] a) M. Yoshida, M. Al-Amin, K. Matsuda, K. Shishido, Tetra-
hedron Lett. 2008, 49, 5021; b) M. Yoshida, M. Al-Amin, K.
Shishido, Synthesis 2009, 2454.
[6] a) A. Blanc, K. Tenbrink, J.-M. Weibel, P. Pale, J. Org. Chem.
2009, 74, 4360; b) A. Blanc, K. Tenbrink, J.-M. Weibel, P. Pale,
J. Org. Chem. 2009, 74, 5342; c) A. Blanc, A. Alix, J.-M. Wei-
bel, P. Pale, Eur. J. Org. Chem. 2010, 1644.
[7] For an indium-catalyzed reaction, which is proposed to occur
through a distinct mechanism, see: J. Y. Kang, B. T. Connell,
J. Org. Chem. 2011, 76, 2379.
[8] For reactions using aziridines, see: a) P. W. Davies, N. Martin,
N. Spencer, Beilstein J. Org. Chem. 2011, 7, 839; b) N. Kern,
A. Blanc, J.-M. Weibel, P. Pale, Chem. Commun. 2011, 47, 6665;
c) P. W. Davies, N. Martin, J. Organomet. Chem. 2011, 696,
159. See also ref.[5b]
[9] A single exception: C. Gronnier, S. Kramer, Y. Odabachian, F.
Gagosz, J. Am. Chem. Soc. 2012, 134, 828.
[10] Under otherwise identical conditions, PtCl2 or [(PPh3)AuCl]
did not promote this reaction. Trifluoromethanesulfonic acid
(TfOH) proved active, albeit in lower yield and reproducibility
(40–50%). For analogous reactivity of gold and TfOH, see for
example: T. Jin, Y. Yamamoto, Org. Lett. 2007, 9, 5259.
[11] For examples of the beneficial use of AuCl3 and silver salts as
a catalytic system over simple AuCl3, see: a) Z. Shi, C. He, J.
Am. Chem. Soc. 2004, 126, 5964; b) Z. Shi, C. He, J. Org.
Chem. 2004, 69, 3669.
[12] Control experiments revealed that Ag(BF4) (5–15 mol-%) was
able to promote the formation of 2a, albeit in lower yield
(51%). In contrast, it proved incompetent for the preparation
of compounds 2h–j.
Scheme 5. Gold-catalyzed rearrangement of epoxides
ketones 5.
4 into
Conclusions
In summary, we have disclosed that the reactivity of 1-
alkynyloxiranes in the presence of gold(III) catalysts is
strongly affected by the substituents. Thus, whereas pre-
vious studies involving di- and trisubstituted epoxides af-
forded furan derivatives, the use of the corresponding tetra-
substituted analogues selectively gives rise to synthetically
relevant tertiary α-alkynylketones 2[20] by Meinwald-type re-
arrangement. The chemo- and regioselective formation of
alkynols 3 when the reaction is conducted by using alcohols
as solvent suggests the participation of a propargyl carbo-
cation as the intermediate. Finally, the capability of
gold(III) to act as a σ-oxophilic Lewis acid catalyst was
illustrated in the rearrangement of simple epoxides 4. This
unusual reactivity trend could be further exploited to de-
velop catalytic processes in which gold catalysts activate dif-
ferent functionalities.
Experimental Section
Preparation of 2-Phenyl-2-(phenylethynyl)cyclohexanone (2a) as a
Representative Procedure: To a stirred solution of AuCl3 (4.5 mg,
5.0 mol-%) in 1,2-dichloroethane (ca. 0.1 m) at 20 °C was added
alkynylepoxide 1a (82 mg, 1.0 equiv., 0.3 mmol) in one portion.
The resulting mixture was stirred at this temperature until 1a was
completely consumed (TLC analysis, reaction time = 1 h). Then,
the solvent was removed under vacuum, and the resulting residue
was purified by flash column chromatography (SiO2) to yield 2a as
a white solid (69 mg, 84%).
[13] a) M. Georgy, V. Boucard, J.-M. Campagne, J. Am. Chem. Soc.
2005, 127, 14180; b) M. Georgy, V. Boucard, O. Debleds, C.
Dal Zotto, J.-M. Campagne, Tetrahedron 2009, 65, 1758; c) O.
Debleds, E. Gayon, E. Vranken, J.-M. Campagne, Beilstein J.
Org. Chem. 2011, 7, 866.
Supporting Information (see footnote on the first page of this arti-
1
cle): Experimental procedures and copies of the H NMR and 13C
[14]
A similar reactivity trend was described in some alkynyl azirid-
ines, see: a) P. W. Davies, N. Martin, Org. Lett. 2009, 11, 2293;
b) M. Yoshida, Y. Maeyama, M. Al-Amin, K. Shishido, J. Org.
Chem. 2011, 76, 5813; for a review on gold-promoted 1,2-alkyl
migrations, see: c) B. Crone, S. F. Kirsch, Chem. Eur. J. 2008,
14, 3514; for a review on gold-catalyzed ring expansion, see: d)
D. Garayalde, C. Nevado, Beilstein J. Org. Chem. 2011, 7, 767
and references cited therein.
NMR spectra.
Acknowledgments
Funding from the Ministerio de Economía y Competitividad (MI-
NECO), Spain (Project CQT-201020517-C02) is gratefully ac-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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