Lithium Chloride Catalyzed Asymmetric Domino Aza‐Michael Addition/[3 + 2] Cycloaddition Reactions for the Synthesis of Spiro‐ and Bicyclic α,β,γ‐Triamino Acid Derivatives

• Published in: European journal of organic chemistry Vol. 2018; no. 37; pp. 5213 - 5221
• Main Authors: Just, David, Hernandez‐Guerra, Daniel, Kritsch, Susanne, Pohl, Radek, Císařová, Ivana, Jones, Peter G., Mackman, Richard, Bahador, Gina, Jahn, Ullrich
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 09.10.2018
• Subjects: 1,3 Dipolar cycloaddition; Cascade chemical reactions; Chemical reactions; Chemical synthesis; Cycloaddition; Derivatives; Diazo transfer; Hepatitis C; Lithium; Lithium chloride; Michael addition; Nitrogen heterocycles; Non‐natural amino acids; Pyrimidines; Reagents; Stereochemistry; Tandem reactions; Viruses; β‐Prolines
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201800585

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 α,β,γ‐triamino acids, angularly or peri‐fused tricyclic β‐prolines or pyrimidines. The activity of the tricyclic amino acid derivatives against the hepatitis C virus was determined. Angularly and peri‐fused tricyclic pyrrolidinopyrazolines are efficiently prepared by LiCl catalyzed domino aza‐Michael addition‐1,3‐dipolar cycloaddition. The resulting tricyclic pyrrolidinopyrazolines can be easily transformed to spirocyclic or condensed bicyclic α,β,γ‐triamino acid derivatives.