# A Squaramide-Based Organocatalyst as a Novel Versatile Chiral Solvating Agent for Carboxylic Acids

## TL;DR

A new squaramide-based organocatalyst was found to effectively differentiate enantiomers of various carboxylic acids through unique interactions.

## Contribution

The study introduces a novel squaramide-based organocatalyst as a versatile chiral solvating agent for carboxylic acids.

## Key findings

- High enantiodifferentiations were observed at multiple nuclei for various carboxylic acids.
- The organocatalyst interacts via proton transfer to tertiary amine sites, enabling solubilization.
- DOSY and ROESY experiments confirmed the formation of a tight ionic adduct and the role of the squaramide unit.

## Abstract

A squaramide-based organocatalyst for asymmetric Michael reactions has been tested as a chiral solvating agent (CSA) for 26 carboxylic acids and camphorsulfonic acid, encompassing amino acid derivatives, mandelic acid, as well as some of its analogs, propionic acids like profens (ketoprofen and ibuprofen), butanoic acids and others. In many cases remarkably high enantiodifferentiations at 1H, 13C and 19F nuclei were observed. The interaction likely involves a proton transfer from the acidic substrates to the tertiary amine sites of the organocatalyst, thus allowing for pre-solubilization of the organocatalyst (when a chloroform solution of the substrate is employed) or the simultaneous solubilization of both the catalyst and the substrate. DOSY experiments were employed to evaluate whether the catalyst–substrate ionic adduct was a tight one or not. ROESY experiments were employed to investigate the role of the squaramide unit in the adduct formation. A mechanism of interaction was proposed in accordance with the literature data.