RESUMEN
Herein, we describe a method for the catalytic enantioselective α-amination of α-substituted acyclic 1,3-ketoamides and 1,3-amidoesters that affords the products possessing N-substituted quaternary stereocenters with a chiral N-heterocyclic carbene (NHC). The reaction is based on the utilization of an intrinsic Brønsted base characteristic of NHC that enables the catalytic formation of a chiral ion pair comprising the enolate and the azolium ion. A series of challenging open-chain α-substituted 1,3-dicarbonyls are aminated via this method with ee's of ≤99%.
RESUMEN
A simple yet highly effective approach toward enantioselective synthesis of trans-3,4-disubstituted glutarimides from readily available starting materials is developed using oxidative N-heterocyclic carbene catalysis. The catalytic reaction involves a formal [3 + 3] annulation between enals and substituted malonamides enabling the production of glutarimide derivatives in a single chemical operation via concomitant formation of C-C and C-N bonds. The reaction offers easy access to a broad range of functionalized glutarimides with excellent enantioselectivity and good yield. Synthetic application of the method is demonstrated via formal synthesis of (-)-paroxetine and other bioactive molecules.
RESUMEN
Highly diastereo- and enantioselective 1,6-addition of 1,3-ketoamides to p-quinone methides (p-QMs) using chiral NHCs as Brønsted base catalysts is developed. The reaction is based on the utilization of a 1,3-ketoamide having acidic N-H that forms a chiral ion-pair consisting of the enolate and the azolium ion. Different ß-ketoamides and functionalized p-QMs are applicable to the reaction. Synthetic application of the method is demonstrated via the preparation of highly enantioenriched ß and γ-lactam derivatives.
