Silver/ThioClickFerrophos-Catalyzed 1,3-Dipolar Cycloaddition and Tandem Addition-Elimination Reaction of Morita-Baylis-Hillman Adducts

The asymmetric 1,3-dipolar cycloaddition of glycine imino esters to Morita-Baylis-Hillman (MBH) adducts or acetylated MBH adducts is described. The reaction was efficiently catalyzed by AgOAc/(R,S-p)-ThioClickFerrophos at room temperature to afford pyrrolidine derivatives bearing a quaternary carbon as a single diastereomer with excellent enantioselectivity. When a cyclic pyrroline ester was used as the nucleophile instead of a glycine imino ester, the enantioselective tandem addition-elimination reaction with an acetylated MBH adduct proceeded with an excellent yield and enantioselectivity, resulting in the formation of an exo-olefin. The wide substrate scope of these reactions and the transformability of the products enable expeditious access to divergent multifunctionalized pyrrolidines in an optically pure fashion.

Automated summary

The asymmetric 1,3-dipolar cycloaddition of glycine imino esters to Morita-Baylis-Hillman (MBH) adducts or acetylated MBH adducts was efficiently catalyzed by AgOAc/(R,S-p)-ThioClickFerrophos to provide pyrrolidine derivatives with a quaternary carbon center as a single diastereomer with excellent enantioselectivity. Additionally, utilizing a cyclic pyrroline ester as the nucleophile in the tandem addition-elimination reaction with an acetylated MBH adduct resulted in the formation of an exo-olefin with high yield and enantioselectivity. The broad substrate scope and transformability of the products allow for rapid access to diverse multifunctionalized pyrrolidines in an optically pure manner.