Highly diastereo- and enantioselective 1,6-addition of β-keto amides to p-quinone methides catalyzed by N-heterocyclic carbenes via ion-pair interaction is developed.

An active acyl donor intermediate generated in situ from an aldehyde by oxidative N-heterocyclic carbene (NHC)-catalysis enables direct acylation of NH-sulfoximine, affording variousN -acylsulfoximinesi ne xcellent yields. The reaction was performed with an inexpensive carbene catalyst and easily accessible bisquinone oxidant. This straightforwardtransformation demonstrated abroad substrate scope with respectt os ulfoximines and aldehydes. Importantly,t he method alloweda midation of several unactivated aliphatic aldehydes in good-to-moderate yields. Preparatives ynthesis of N-acylsulfoximine (up to > 2g) was achieved with this simple method.

Catalysis with N‐heterocyclic carbenes (NHCs) via substrate activation through noncovalent interactions offers a great opportunity to perform organic transformations. Herein, we demonstrate an efficient catalytic method for the 1,6‐conjugate addition of 1,3‐dicarbonyl compounds to para‐quinone methides (p‐QMs) using NHCs as Brønsted‐base catalysts. The method is applicable to a wide range of functionalized substrates with respect to both 1,3‐diketones and p‐QMs. An initial study using chiral NHCs provides information on the feasibility of developing a catalytic enantioselective variant of this reaction.

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.

Enantioenriched acyclic a-substituted b-hydroxy amides are valuable compounds in chemical, material and medicinal sciences, but their enantioselective synthesis remains challenging. A catalytic kinetic resolution (KR) of such amides with selectivity factor(s) up to > 200 is developed via enantioselective acylation of primary alcohol with N-heterocyclic carbene. An enhanced selectivity for the catalytic KR process is realized using cyclic tertiary amine as base additive. Diastereomeric transition state models for the process are proposed to rationalize the origin of enantioselectivity. Scheme 1. Previously reported kinetic resolution of alcohol using oxidative NHC-catalysis and this study.