Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination

Abstract

The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98% yield and 99% ee.

Catalytic Asymmetric Dearomatization by Transition-Metal Catalysis: A Method for Transformations of Aromatic Compounds

“…As an extension of our previous works on Ir-catalyzed asymmetric allylic substitution reactions with nitrogen-containing aromatic rings, we recently disclosed a highly regio-and enantioselective synthesis of chiral N-substituted 2-pyridones via Ir-catalyzed intermolecular asymmetric allylic amination (Scheme 14). 47 The designed reaction involved 2-hydroxypyridine 57 as the nucleophile. Tautomeric equilibrium of 57 between its 2-hydroxypyridine form and 2-pyridone form allows facile N-attack on the p-allyliridium electrophile.…”

“…Ir-Catalyzed Asymmetric N-allylation of 2-HydroxypyridineOriginally reported by the You group 47. Scheme 15.…”

Rhodium‐Catalyzed Dynamic Kinetic Asymmetric Allylation of Phenols and 2‐Hydroxypyridines

“…Electron‐neutral pyridone could also react smoothly to give the corresponding N‐allylated product with high ee ( 11 ad ). The absolute configuration was assigned to be S by comparison with literature data . Then we examined the scope of racemic allylic carbonates, especially those with small alkyl substituents, which are not easily available for the corresponding allene counterparts.…”

A Novel Synthesis of Highly Functionalized Pyridines by a One-Pot, Three-Component Tandem Reaction of Aldehydes, Malononitrile and N-Alkyl-2-cyanoacetamides under Microwave Irradiation

“…Accordingly, methods for the efficient synthesis of new derivatives of these compounds have thus attracted the great interest of synthetic and medicinal chemists. However, a literature survey showed that efficient, direct approaches to the selective synthesis of N -alkylated 2-pyridone derivatives are much less well explored, as known methods generally suffer from certain drawbacks such as the lack of generality or selectivity, poor yields, the use of expensive transition-metal catalysts and/or a competitive process between N - and O -alkylation (poor chemoselectivity) [ 34 , 35 ]. Therefore, the development of novel straightforward approaches to densely substituted N -alkylated 2-pyridones still remains as a hot research topic.…”