ORGANIC LETTERS
Direct Carbocyclization of Aldehydes with Alkynes: Combining Gold Catalysis with Aminocatalysis
2008 Vol. 10, No. 5 1025-1028
Jo1 rg T. Binder, Benedikt Crone, Timm T. Haug, Helge Menz, and Stefan F. Kirsch* Department Chemie, Technische UniVersita¨t Mu¨nchen, Lichtenbergstrasse 4, 85747 Garching, Germany
[email protected] Received January 15, 2008
ABSTRACT
A combination of gold(I) complexes and amine bases catalyzes the 5-exo-dig cyclization of formyl alkynes. This direct r-functionalization of aldehydes with unactivated alkynes does not involve the use of preformed enol equivalents.
Cyclization reactions involving homogeneous gold catalysts as carbophilic Lewis acids have emerged as a powerful strategy to construct complex carbocyles.1 Among the many different C-C bond formations that proceed through a gold(I)-catalyzed activation of alkynes toward nucleophilic attack, the addition of activated methylene compounds such as malonates and β-ketoesters to an unactivated alkyne (Scheme 1) has been particularly well-studied.2 However, less enolizable carbonyls lack the required nucleophilicity to react directly with gold(I)-complexed alkynes under C-C bondforming R-functionalization, instead suffering an initial C-O bond formation.3,4 As an alternative strategy, a variety of (1) (a) Hashmi, A. S. K. Chem. ReV. 2007, 107, 2180. (b) Jime´nez-Nunez, E.; Echavarren, A. M. Chem. Commun. 2007, 333. (c) Fu¨rstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410. (d) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395. (e) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817. (f) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896. (g) Hoffmann-Ro¨der, A.; Krause, N. Org. Biomol. Chem. 2005, 3, 387. (2) (a) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem., Int. Ed. 2004, 43, 5350. (b) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526. 10.1021/ol800092p CCC: $40.75 Published on Web 01/31/2008
© 2008 American Chemical Society
enol equivalents derived from ketones and aldehydes were employed in gold(I)-catalyzed cyclization reactions. For instance, electron-rich alkyl enol ethers,5 silyl enol ethers,6 silyl ketene amides,7 and enamines8 efficiently attack gold(I)-alkyne complexes, although their synthetic utility is Scheme 1.
Combining Gold Catalysis with Enamine Catalysis
Table 1. Effect of Catalysts on the Cyclization of 1a
entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
catalyst A (mol %)
catalyst B (mol %)
conditions
yield [%]a 1a:2a:3a
HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)(c-Hex) (20) H2N(i-Pr) (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20) HN(i-Pr)2 (20)
120 °C, toluene, 24 h 70 °C, CDCl3, 6 h 70 °C, CDCl3, 6 h 70 °C, CDCl3, 6 h 70 °C, CDCl3, 6 h 70 °C, CDCl3, 10 h 70 °C, CH3NO2, 6 h 70 °C, CDCl3, 3 h 70 °C, CDCl3, 3 h 70 °C, CDCl3, 3 h 70 °C, CDCl3, 6 h 70 °C, CDCl3, 2 h 70 °C, CDCl3, 24 h 70 °C, CDCl3, 2 h 120 °C, toluene, 24 h
100:0:0b 0:0:0b 82:0:0 100:0:0b 0:0:82 0:0:75 0:0:80 0:0:86 0:0:83 0:0:74 0:0:74 0:0:13 0:0:16 0:0:59 0:0:50
(Ph3P)AuSbF6 (10) [(Ph3PAu)3O]BF4 (10) (Ph3P)AuSbF6 (10) (Ph3P)AuSbF6 (2) (Ph3P)AuSbF6 (10) [(Ph3PAu)3O]BF4 (10) [(Ph3PAu)3O]BF4 (10) [(Ph3PAu)3O]BF4 (10) LAuSbF6 (10)c (Ph3P)AuNTf2 (10) AgSbF6 (10) AgOTf (10) PtCl2 (10)
a Yield of pure product after column chromatography unless otherwise indicated. b The ratios were determined by 1H NMR spectroscopy. c L ) 2-(biphenyl)ditert-butylphosphine. d Traces of 3a (
