THIQs reaction with ketones

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... 

Scheme 2.10 Intermolecular asymmetric CDC reactions of THIQs with ketones reported by Wang.

Using a catalytic amount of I2 in the presence of H2O2, CDC reaction of THIQs was achieved by Itoh (Scheme 8.49). Nitroalkane, ketone, and dimethyl malonate can be introduced to produce 100 in good yields. The generation of HOI from the oxidation of I2 or HI by H2O2 is expected to play an important role in the formation of the iminium ion intermediate 101, which reacts with the nucleophiles. 

The highly enantioselective CDC reactions between the tertiary amines and ketones have not been realized until very recently. Wang and co orkers described a metal-free enantioselective CDC reaction of Af-aryl THIQs 23 and cyclic ketones 24 by taking advantage of L-phenylalanine (S )-C5 as a suitable catalyst to activate the ketone substrates via a chiral ion-pair catalysis strategy. This new method provides an efficient way to access diverse Cl-alkylated THIQ derivatives 25 in up to 81% yield with good stereocontrol (up to 13 1 dr and 94% ee) when anhydrous PrOH was added (Scheme 2.10). 

The Wang group also realized enantioselective oxidative cross-coupling reactions between tertiary amines and the activated olefins by merging Cu(OTf)2 with quinine as the best cooperative catalysts/ A Morita-Baylis-Hillman-type mechanism is in operation. It was notable that molecular oxygen was employed as the sole oxidant. As shown in Scheme 2.12, the reactions between Ai-aryl THIQs and the a,p-unsaturated aldehydes or ketones 30 proceeded smoothly to afford the a-functionalized products 31 in up to 81% yield and 99% ee. 

In addition to THIQs that could act as the typical substrates for the asymmetric CDC reactions, glycine derivatives were also well tolerated in this kind of transformation. Xie and Huang reported a facile approach to iV-aryl amino acid derivatives via the CDC reactions between Af-substituted glycine esters with unmodified ketones under the cooperative catalytic system consisting of Cu(0Ac)2 H20 and pyrrolidine. TBHP and DDQ were proved to... 

Scheme 7.4 Asymmetric CDC reaction of Af-aryl THIQs with ketones using L-phenylalanine and DDQ.

The simple aerobic CDC reaction between xanthene and various ketones or 1,3-dicarbonyl compounds was demonstrated by Klussmann (Scheme 8.52). A catalytic amount of methanesulfonic acid is essential for this reaction. Coupling of acridanes and THIQs with ketones is also possible under these conditions. 

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