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DOI: 10.1055/s-2007-968405
Organocatalytic Asymmetric Friedel-Crafts Alkylation of Indoles with Enones
Contributor(s):Benjamin List, Nolwenn J. A. MartinUniversità di Bologna, Italy
Organocatalytic Asymmetric Friedel-Crafts Alkylation of Indoles with Simple α,β-Unsaturated Ketones
Org. Lett. 2007, 9: 1403-1405
Publication History
Publication Date:
24 April 2007 (online)
Key words
asymmetric counterion-directed catalysis (ACDC) - Friedel-Crafts alkylation - β-indolyl ketones
Significance
Melchiorre and co-workers reported an efficient asymmetric organocatalytic alkylation of indoles 1 with simple α,β-unsaturated ketones 2, giving access to a broad range of highly enantioenriched β-indolyl ketones 3. The reaction is catalyzed by amine salt 4, in which both the cation and anion are chiral, through iminium ion catalysis, and tolerates steric and electronic demands of the β-olefin substitutent as well as aromatic ketones. The methodology can also be applied to substituted indoles without affecting the efficiency of the system. However, substitution on the indolic nitrogen leads to a strong decrease of the reactivity and has a detrimental effect on the selectivity.
Comment
The synthesis of indolyl-containing compounds bearing a stereocenter adjacent to the heteroaromatic ring is of high chemical and biochemical importance. Bandini, Umani-Ronchi, and co-workers recently reported the first efficient, asymmetric metal-catalyzed Friedel-Crafts reactions of indoles to monochelating ketones, however, with important restriction in substrate scope (M. Bandini et al. J. Org. Chem. 2004, 69, 7511-7518). In this paper, Melchiorre and co-workers described a general and efficient organocatalytic variant, using a new amine salt made of a chiral cation and a chiral anion as catalyst.