A general overview of the organocatalytic intramolecular aza-Michael reaction

Abstract

The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the implementation of numerous tandem processes, as well as the total synthesis of several natural products.

Lipase‐catalyzed aza‐Michael addition of amines to acrylates in supercritical carbon dioxide

“…[7][8][9] In general, this reaction can be catalyzed by acid, base, or metal catalysts. 10,11 However, the competition of aminolysis is a major drawback in aza-Michael additions when amines are used as nucleophiles, and the low chemoselectivity of aza-Michael additions limit its utility in organic synthesis. Considering the wide application of chemoselective aza-Michael addition, it remains a fascinating topic for researchers in organic chemistry.…”

Crystal structure of ethyl (E)-3-(cyclopropylamino)-2-(2,4-dichloro-5-fluorobenzoyl) acrylate, C15H14Cl2FNO3

“…Since the introduction of the first quinolone as a therapeutic agent of urinary tract infections [6], quinolones have become one of the main drugs to treat bacterial infections, widely used in the treatment of diseases including sexually transmitted diseases, urinary tract infections, chronic bronchitis, community acquired pneumonia, respiratory infections and so on [7]. Among these, the most notable ones are 4-quinolones [8][9][10][11][12], which form the core backbone of several quinolone-based and commerciallyavailable antibiotics. For these reasons, it is necessary to develop simple and efficient approaches for the synthesis of 4-quinolones.…”

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

“…Oxa-, [3][4][5] aza-, [6][7][8] thia-, [9][10][11] and phospha- [12] Michael addition reactions are the conceptual extension to heteroatom-centered anions. Utility of the Michael additions for the constructiono f CÀCb ond employing carbon nucleophiles are very well developed.…”