Lithium Chloride Catalyzed Asymmetric Domino Aza-Michael Addition/[3+2] Cycloaddition Reactions for the Synthesis of Spiro- and Bicyclic alfa,beta,gamma-Triamino Acid Derivatives
2018
Abstract
Angularly and peri-fused tricyclic pyrrolidinopyrazolines are efficiently prepared by LiCl-catalyzed domino aza-Michael addition-1,3-dipolar cycloaddition reactions. The absolute stereochemistry is controlled in the aza-Michael addition step, nonaflyl azide serves as effective diazo transfer reagent to the formed enolate and the resulting diazo dipole engages in the 1,3-dipolar cycloaddition step.
The resulting tricyclic pyrrolidinopyrazolines can be easily transformed to enantiomerically enriched nonproteinogenic spirocyclic alfa,beta,gamma-triamino acids, angularly or peri-fused tricyclic beta-prolines or pyrimidines. The activity of the tricyclic amino acid derivatives against the hepatitis C virus was determined.