Calcium(II)-Catalyzed Reductive Amination of Biomass-Derived Keto Acids to Functionalized Lactams under Solvent-Free
Haoran Li1, Fangting Huang1, Hui Gao1
1Key Laboratory of Molecular Target & Clinical Pharmacology and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Abstract:
Direct access to the polyfluorinated lactams through Ca(NTf2)2 catalyzed by either the reductive amination of biomass-derived keto acids with amines or the reductive amination of amino acids with carbonyl derivatives under solvent-free conditions is realized. The two versatile protocols display chemospecificity and good substrate tolerance to deliver five- to eight-membered lactams with diverse functionality and substitution patterns. The robustness of the methodology is further demonstrated by subsequent application in the late-stage functionalization of drug molecules.
Related Concept Videos
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
Amides to Amines: LiAlH4 Reduction
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
Preparation of Aldehydes and Ketones from Nitriles and Carboxylic Acids
Reducing carboxylic acid derivatives like acyl chlorides (RCOCl), esters (RCO2R′), and nitriles (RCN) using milder aluminum hydride agents like lithium tri-tert-butoxyaluminum hydride [LiAlH(O-t-Bu)3] and diisobutylaluminum hydride [DIBAL-H]...
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
Aldol Condensation with β-Diesters: Knoevenagel Condensation


