Study On The Mannich-type Acetamidation And Redox Amination Of Aldehyde

Amination of aldehyde is not only a very important reaction in building C-N bond, but also an efficient method to synthesize many biologically active natural products and pharmaceutical compounds. In this research, based on reviewing the research development in Mannich reaction and redox isomerization, the acetamidation of aldehyde, redox amination of aldehyde with indoline and decarboxylative redox amination of aldehydes with 2-carboxyindoline have been developed. The details are listed as follows:1. Firstly, the Mannich-type three-component reaction involving aldehydes, acetamide, and enolizable ketones orβ-keto esters for the preparation ofβ-acetamido carbonyl compounds in the presence of TMSCl is described. A mechanism for this reaction is proposed on the basis of the results and previous related Mannich reaction mechanistic research. First, TMSCl acts as a Lewis acid to activate aldehyde by complexation with aldehyde oxygen. Direct condensation the complex with acetamide gives the reactive intermediate, which is followed by the nucleophilic attack of enolizable ketones and keto esters to afford the final product.2. Then, the Br(?)nsted acid-catalyzed redox amination of aldehyde with indoline has been developed for the preparation of N-alkylindoles. This firstly presented protocol, with excellent atom economy and redox economy, is unprecedented among those established protocols. Moreover, an interesting intramolecular hydrogen bond effect is observed when salicylaldehyde is employed in the reaction. According to the result of isotopic labeling reaction, this kind of reaction is indicated to proceed via intermolecular hydride transfer.3. At last, a novel mode of reactivity for azomethine ylides has been disclosed, which is produced from the decarboxylative condensations of aldehydes with 2-carboxyindoline and then transforms into N-alkylindoles by isomerization. A series of N-alkylindoles have been prepared by this established protocol from readily available aldehydes. Besides, an isotopic labeling reaction is also carried out to support our proposed mechanism.In summary, several novel types of amintion reaction of aldehyde have been developed for the preparation ofβ-acetamido carbonyl compounds and N-alkylindoles. These unique reactions may stimulate subsequent research in amination of aldehyde.