Asymmetric Cross-Dehydrogenative Coupling

Recently, Chi and co-workers reported a highly enantioselective oxidative coupling reaction of aldehydes 14 with tertiary amines 13 under cooperative 

Compared with aldehydes, the asymmetric CDC reactions of THIQs with ketones are much more challenging due to the diminished reactivity of the carbonyl group of ketones. Since 2000, the chiral amine catalysts including secondary amines and primary amines have witnessed rapid development as a significant category of organocatalysts, providing versatile reactivities 

In 2011, Rueping and eo orkers realized asymmetric CDC reactions between THIQs and aeetone by utilizing a dual catal3 ic system eontaining photoredox catalyst Ru(bpy)3(PFg)2 and L-proline under the irradiation of 5 W fluorescent bulb. The interplay between the photoredox catalytie eyele and the effective addition of ketones to the photocatalytically generated iminium 

DDQ was proved to be the optimal stoichiometric oxidant, and the copper salts were not necessary. A chiral organic contact ion-pair interaction was proposed for the reaction. The enamine intermediate is generated from the ketone and the primary amine moiety of the L-phenylalanine. The interae-tion between the carboxylate-bearing enamine intermediate and the imin-ium cation from the oxidation probably contributes to the diastereomerie discrimination, which furnishes this asymmetric CDC process. 

In addition, Wang and cowvorkers developed an intramoleeular CDC reaction between tertiary amines and ketones mediated by DDQ (Seheme 2.11). Preliminary attempts towards asymmetric reaction were carried out. Screening of various chiral organocatalysts revealed the simple chiral phosphoric acid (S)-C6 as the most stereoselective eatalyst, giving the cyclization produet 29 with 14% ee. 

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