Asymmetric cinchona-based primary amines

Asymmetric Cydoaddition Reactions Catalyzed by Cinchona-Based Primary Amines... 

Cinchona-based primary amine catalysis in the asymmetric functionalization of carbonyl compounds 12AG(E)9748. 

Cinchona-based primary amine catalysis in the asymmetric functionalization of carbonyl compounds has been reviewed and their modularly designed thioamide 0 derivatives have been applied successfully to direct cross-aldol reactions between aldehydes and ketones, reactions of activated carbonyl compounds (isatins) with acetylphosphonate as the enol precursor, and C( 1) functionalization of 1,3-dicarbonyl compounds by aldehydes and ketones. Cross-aldol addition to C(3) of isatins by the methyl group of 4-aryl-tra 5 -cf, -unsaturated methyl ketones has also been promoted... 

Deng and co-workers developed the first asymmetric Diels-Alder reactions of a,p-unsaturated ketones and 2-pyrones (Scheme 5.36) [65] with cinchona-based primary amine catalysts 38 or 39. The substrate scopes are substantial and in most cases excellent diastereoselectivity and enantioselectivity were obtained. 

Iminium catalysis has been quite successful for asymmetric epoxidation of a,P-unsaturated carbonyl compounds, particularly, enals. Enones have remained difficult substrates. Recently, List and coworkers reported an enantioselective epoxidation of cyclic enones with either cinchona-based primary amine 38 or a counter-anion catalytic systan 149 combining a chiral vicinal diamine and a chiral phosphoric acid [69], High enantioseleclivities could be achieved in a number of cyclic enones (Scheme 5.40). 

While asymmetric counteranion-directed catalysis (ACDC) has been estab-hshed as a powerful strategy in iminium catalysis, enamine-based asymmetric counteranion-directed catalysis has not yet been developed. Recently, Lu et al. [32] demonstrated that the combination of a cinchona alkaloid-derived primary amine and chiral camphorsuhnnic acid (CSA) results in an effective ion-pair catalyst for the directed asymmetric amination of a-branched aldehydes through enamine activation (Scheme 43.21). 

Chiral primary amines based on cinchona alkaloids are versatile primary amin-ocatalysts and have been attempted in the asymmetric Michael additions of aliphatic ketones to nitro-olefins with moderate to high yield and good stereoselectivity [40]. 

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