Direct Catalytic Asymmetric Vinylogous Additions of α,β‐ and β,γ‐Butenolides to Polyfluorinated Alkynyl Ketimines

2018/07/02 by Barry M. Trost, Chao‐I Hung, Manuel J. Scharf · 4 citations
Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Fluorine in Organic Chemistry #Asymmetric Synthesis and Catalysis #Carbohydrate Chemistry and Synthesis

paper · doi:10.1002/anie.201806249

openalex publication_date 2018/07/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

We report a Zn-ProPhenol catalyzed asymmetric Mannich reaction between butenolides and polyfluorinated alkynyl ketimines to obtain vinylogous products featuring two contiguous tetrasubstituted stereogenic centers. Notably, this is the first successful use of ketimines in the ProPhenol Mannich process, and the reaction offers a new approach for the preparation of pharmaceutically relevant products possessing trifluoromethylated tetrasubstituted alkylamines. The reaction can be performed on large scale with reduced catalyst loading without impacting its efficiency. Moreover, the acetylene moiety can be further elaborated using various methods.

Citations

• Understanding organofluorine chemistry. An introduction to the C–F bond
• Direct Access to N‐Unprotected α‐ and/or β‐Tetrasubstituted Amino Acid Esters via Direct Catalytic Mannich‐Type Reactions Using N‐Unprotected Trifluoromethyl Ketimines
• Asymmetric Synthesis of Less Accessible α‐Tertiary Amines from Alkynyl Z‐Ketimines

Cited by

• Construction of chiral α- tert -amine scaffolds via amine-catalyzed asymmetric Mannich reactions of alkyl-substituted ketimines
• Enantiodivergence by minimal modification of an acyclic chiral secondary aminocatalyst
• Zn-ProPhenol Catalyzed Enantioselective Mannich Reaction of 2H-Azirines with Alkynyl Ketones
• Ketimine Mannich reaction [wikipedia]

Related

• A Decade of Advance in the Asymmetric Vinylogous Mannich Reaction
• Direct Catalytic Asymmetric Mannich‐type Reaction of α,β‐Unsaturated γ‐Butyrolactam with Ketimines
• Catalytic Asymmetric Mannich Reaction of α-Fluoronitriles with Ketimines: Enantioselective and Diastereodivergent Construction of Vicinal Tetrasubstituted Stereocenters
• Highly Diastereo‐ and Enantioselective Mannich Reactions of Synthetically Flexible Ketimines with Secondary Amine Organocatalysts
• Zn-ProPhenol Catalyzed Enantioselective Mannich Reaction of 2H-Azirines with Alkynyl Ketones