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DOI: 10.1055/s-2007-968755
Asymmetric α-Arylation of Aldehydes
Contributor(s):Benjamin List, Sebastian HoffmannAarhus University, Denmark
Asymmetric Organocatalytic α-Arylation of Aldehydes
Angew. Chem. Int. Ed. 2007, 46: 5520-5523
Publication History
Publication Date:
24 July 2007 (online)
Key words
α-arylation - aldehydes - enamine catalysis - quinones
Significance
The first amine-catalyzed enantioselective α-arylation of aldehydes is reported. These products are assumed to be formed via the Michael reaction of an aldehyde 2 derived enamine intermediate with a quinone 1 and subsequent proton transfers (aromatization). Aldehydes 3 are in equilibrium with hemiacetals 4 which could be isolated as single diastereomers. In order to obtain good conversions of the starting materials, the presence of an excess of water was crucial, due to its possible involvement in the proton-transfer reactions. Furthermore, the authors presented transformations of hemiacetals 4 leading to optically active quinones and to doubly acetylated products without loss of enantiopurity.
Comment
Enantioselective transition-metal-catalyzed α-arylations of activated carbonyl compounds are well known. Nevertheless, aldehydes are still challenging substrates for direct enantioselective α-arylations. After having reported numerous organocatalytic α-, β-, and γ-functionalizations, Jørgensen and co-workers could now show that a covalent catalysis approach leads to stereoselective C(sp3)-C(sp2) bond formations between aldehydes and quinones using chiral secondary amines. This represents the first highly enantioselective direct organocatalytic α-arylation of aldehydes. The system’s inherent aromatic substitution pattern limits this approach.