Highly enantioselective catalytic synthesis of chiral pyridines.

General methods to prepare chiral pyridine derivatives are greatly sought after due to their significance in medicinal chemistry. Here, we report highly enantioselective catalytic transformations of poorly reactive ß-substituted alkenyl pyridines to access a wide range of alkylated chiral pyridines. The simple methodology involves reactivity enhancement via Lewis acid (LA) activation, the use of readily available and highly reactive Grignard reagents, and a copper-chiral diphosphine ligand catalyst. Apart from allowing the introduction of different linear, branched, cyclic, and functionalised alkyl chains at the ß-position of alkenyl pyridines, the catalytic system also shows high functional group tolerance.

Synthesis of Chiral Tertiary Alcohols by Cu(I) -Catalyzed Enantioselective Addition of Organomagnesium Reagents to Ketones.

Catalytic enantioselective addition of organometallic nucleophiles to ketones is among the most straightforward approaches to the synthesis of chiral tertiary alcohols. The first such catalytic methodologies using the highly reactive organomagnesium reagents, which are the preferred organometallic reagents in terms of cost, availability, atom efficiency, and structural diversity, were developed only during the last five years. This Concept article highlights the fundamental breakthrough that made the development of methodologies for highly enantioselective Cu(I) -catalyzed alkylation of ketones using organomagnesium reagents possible.