C2-Symmetric Chiral Squaramide, Recyclable Organocatalyst for Asymmetric Michael Reactions

J Org Chem. 2019 Apr 5;84(7):4304-4311. doi: 10.1021/acs.joc.9b00252. Epub 2019 Mar 13.

Abstract

A very simple and highly efficient C2-symmetric tertiary amine-squaramide organocatalyst for asymmetric Michael reactions has been elaborated. In the presence of only 1 mol % of this catalyst, kojic acid derivatives and β-dicarbonyl compounds reacted with nitroolefins, affording the corresponding adducts in a nearly quantitative yield with an enantioselectivity up to 99% ee. The kojic acid-derived adducts could be efficiently produced under "green" conditions (in 96% EtOH or pure water). Moreover, due to the very low solubility in organic solvents, the developed nonsupported catalyst could be readily recovered and reused in catalytic reactions up to 7 times. Utmost availability (one-step synthesis without chromatographic purification), high level of stereoinduction, low efficient loading, and recyclability make it attractive for industrial application in the pharmaceutical industry.

Publication types

  • Research Support, Non-U.S. Gov't