Gold Catalysis
FULL PAPER
Conclusion
The gold-catalyzed phenol reaction is well-suited to be one
of the key steps in the synthesis of tetrahydroisoquinoline
alkaloids even with sterically demanding group in the 7-po-
sition of that heterocyclic framework. The related dihydroi-
soindoles were also synthesized by gold catalysis in good
yield. Even very bulky substituents, such as 2,6-dichloro-
phenyl or the adamantyl group, could be converted to the
phenols by the gold catalysts in good yields. The influence
of these sterically demanding substituents seems to be stron-
ger in the previous steps, the substrate synthesis, in the gold-
catalyzed step the effect is less pronounced. Probably, the
following can be applied in general: if one can make the
substrate, one can also successfully cyclize it with the gold
catalyst. A methoxy donor in the 2-position of the phenyl
substituents had, unlike the
Figure 4. Solid-state structure of 28e.
Reduction with LiAlH4 and subsequent tosylation gave
the sulfonamide 37 in yields between 39–49%.[23] Compound
37 was alkylated with propargyl bromide to deliver 38 in
yields between 39 and 80% (Scheme 9).
same group in the 4-position, a
strongly accelerating effect on
the reaction. Further details of
the mechanism and rate-limit-
ing step are under investiga-
tion.
Experimental Section
Detailed reaction and catalysis condi-
tions, as well as full characterization
of all unknown compounds are given
in the Supporting Information.
Scheme 9. Reaction sequence to w-alkynyl furans 38. a) CH3NO2, KOH, MeOH, 08C; b) LiAlH4, Et2O, 35 8C;
ꢀ
c) TsCl, CH2Cl2, RT; d) HC CCH2Br, Cs2CO3 acetone, RT.
Acknowledgements
We thank Johnson Mattey for the
donation of gold complexes, the
Reactions of 38a, 38b, and 38c with 5 mol% of complex
30 in chloroform as solvent afforded the 8-hydroxytetrahy-
droisoquinoline 39a in three days and 40% yield, 39b in
five days and 62% yield, and 39c in 2 h and 53% yield
(Scheme 10). Again the o-methoxy substituent influenced
the rate of reaction dramatically. The conversion was moni-
tored by 1H NMR spectroscopy and the reaction mixtures
were worked up when no further conversion was observed.
Fonds der Chemischen Industrie, the Deutsche Forschungsgemeinschaft
(HA 1932/9–1), and the AURICAT EU-RTN (HPRN-CT-2002–00174).
[1] For reviews, see: a) A. S. K. Hashmi, Gold Bull. 2003, 36, 3–9;
b) A. S. K. Hashmi, Gold. Bull. 2004, 37, 51–65; c) N. Krause, A.
Hoffmann-Rçder, Org. Biomol. Chem. 2005, 3, 387–391; d) A. S. K.
Hashmi, Angew. Chem. 2005, 117, 7150–7154; Angew. Chem. Int.
Ed. 2005, 44, 6990–6993.
[2] a) A. S. K. Hashmi, T. M. Frost, J. W. Bats, J. Am. Chem. Soc. 2000,
122, 11553–11554; b) A. S. K. Hashmi, T. M. Frost, J. W. Bats, Org.
Lett. 2001, 3, 3769–3771; c) A. S. K. Hashmi, L. Grundl, Tetrahedron
2005, 61, 6231–6236; d) A. S. K. Hashmi, M. C. Blanco, E. Kurpe-
jovic, W. Frey, J. W. Bats, Adv. Synth. Catal. 2006, 348, 709–713.
[3] A. Pictet, T. Spengler, Chem. Ber. 1911, 44, 2030–2036.
[4] A. Bischler, B. Napieralski, Chem. Ber. 1893, 26, 1903–1908.
[5] a) C. Pomeranz, Monatsh. Chem. 1893, 14, 116–119; b) P. Fritsch,
Chem. Ber. 1893, 26, 419–422.
[6] Even a recent example of a gold-catalyzed Pictet–Spengler reaction
only showed the selectivity known for other Lewis acids and Brønst-
ed acids: S. W. Youn, J. Org. Chem. 2006, 71, 2521–2523.
[7] a) A. S. K. Hashmi, L. Ding, J. W. Bats, P. Fischer, W. Frey, Chem.
Eur. J. 2003, 9, 4339–4345; b) A. S. K. Hashmi, J. P. Weyrauch, M.
Rudolph, E. Kurpejovic, Angew. Chem. 2004, 116, 6707–6709;
Scheme 10. Gold-catalyzed tetrahydroisoquinoline synthesis. [a] Con-
version monitored by H NMR spectroscopy.
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Chem. Eur. J. 2006, 12, 6991 – 6996
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