Catalytic Asymmetric Mannich Reaction of α-Fluoronitriles with Ketimines: Enantioselective and Diastereodivergent Construction of Vicinal Tetrasubstituted Stereocenters

2019/02/06 by Ransheng Ding, Zeus A. De los Santos, Christian Wolf · 2 citations
Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Fluorine in Organic Chemistry #Asymmetric Synthesis and Catalysis #Cyclopropane Reaction Mechanisms

paper · doi:10.1021/acscatal.8b05164

openalex publication_date 2019/02/06 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

Diastereodivergent and enantioselective conversion of isatin ketimines to α-fluoro-β-aminonitriles with vicinal tetrasubstituted stereocenters is achieved by a chiral copper complex/guanidine base catalyzed Mannich reaction with proper choice of the bisphosphine ligand. The reaction is broad in scope, scalable, and provides efficient access to a series of 3-aminoindolinones exhibiting a quaternary carbon-fluorine stereocenter with high yields and stereoselectivities. Selective transformations of the Mannich reaction products into multifunctional 3-aminooxindoles without erosion of enantiomeric and diastereomeric purity highlight the synthetic utility.

Citations

• Highly Diastereo‐ and Enantioselective Mannich Reactions of Synthetically Flexible Ketimines with Secondary Amine Organocatalysts
• Construction of Vicinal Quaternary Stereogenic Centers by Enantioselective Direct Mannich‐Type Reaction Using a Chiral Bis(guanidino)iminophosphorane Catalyst

Cited by

• Construction of chiral α- tert -amine scaffolds via amine-catalyzed asymmetric Mannich reactions of alkyl-substituted ketimines
• Ketimine Mannich reaction [wikipedia]

Related

• Catalytic Enantioselective Decarboxylative Mannich-Type Reaction ofN-Unprotected Isatin-Derived Ketimines
• Highly Diastereo‐ and Enantioselective Mannich Reactions of Synthetically Flexible Ketimines with Secondary Amine Organocatalysts
• Construction of Vicinal Quaternary Stereogenic Centers by Enantioselective Direct Mannich‐Type Reaction Using a Chiral Bis(guanidino)iminophosphorane Catalyst
• BINOL Phosphoric Acid‐Catalyzed Asymmetric Mannich Reaction of Cyclic N‐Acyl Ketimines with Cyclic Enones
• Direct Catalytic Asymmetric Vinylogous Additions of α,β‐ and β,γ‐Butenolides to Polyfluorinated Alkynyl Ketimines