Copper-Catalyzed Direct Asymmetric Vinylogous Mannich Reaction between ß,γ-Alkynyl-α-ketimino Esters and ß,γ-Unsaturated N-Acylpyrazoles.

ABSTRACT

We report a Cu(I)-Ph-BPE-catalyzed asymmetric vinylogous Mannich reaction of ß,γ-alkynyl-α-ketimino esters with ß,γ-unsaturated N-acylpyrazoles. In this process, the Cu(I)-Ph-BPE catalyst activates the ß,γ-alkynyl-α-ketimino ester through N,O-coordination, enabling the subsequent nucleophilic addition of a dienolate generated from the ß,γ-unsaturated N-acylpyrazole via α-position deprotonation with a catalytic amount of tertiary amine. The reactions gave useful products with very high enantioselectivities. A broad range of substrates with various substituents are tolerated in this reaction. The versatility of this method was demonstrated by a gram-scale reaction, and subsequent elaboration of the Mannich adducts was also provided.