**1. Introduction**

Since the seminal contributions of Wynberg [1], Dolling [2], and O'Donnell [3] in the 1970s and 1980s, in which chiral quaternary ammonium salts based on Cinchona alkaloids were used as catalysts for enantioselective epoxidations and α-alkylations of prochiral substrates, the use of chiral quaternary ammonium salts as phase-transfer catalysts (PTCs) has been successfully demonstrated in a multitude of asymmetric organic transformations and now represents an established fundamental catalysis principle in asymmetric organocatalysis [4–8]. In addition to Cinchona alkaloid-based PTCs, other chiral backbones have also been successfully used to access high-performance catalysts. A group of highly efficient binaphthyl-based ammonium salts was introduced by Maruoka (the so-called Maruoka catalysts) [9,10], which have since established themselves as the second most privileged class of chiral ammonium salt PTCs, alongside Cinchona alkaloids (Figure 1). Over the years, efficient chiral quaternary ammonium salts based on tartaric acid [11,12], α-amino acids [13,14], *trans*-cyclohexane-1,2-diamine [15], and others [16] have been developed. Many of the developed quaternary ammonium salts, especially catalysts based on Cinchona alkaloids and some Maruoka-type catalysts, possess a hydrogen-bonding donor in the form of a OH group, which leads to improved catalytic properties [17]. The incorporation of (thio)urea-containing hydrogen bond donors in catalysts based on Cinchona alkaloids, and, in particular, in catalysts based on amino acids and cyclohexane-1,2-diamine, contributed significantly to the diversification of the available catalysts and extended the scope of catalyzed asymmetric transformations [13,15,18,19].

**Citation:** Ciber, L.; Požgan, F.; Brodnik, H.; Štefane, B.; Svete, J.; Waser, M.; Grošelj, U. Synthesis and Catalytic Activity of Bifunctional Phase-Transfer Organocatalysts Based on Camphor. *Molecules* **2023**, *28*, 1515. https://doi.org/10.3390/ molecules28031515

Academic Editors: Alison Rinderspacher, Mircea Darabantu and Gloria Proni

Received: 19 January 2023 Revised: 30 January 2023 Accepted: 31 January 2023 Published: 3 February 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

**Figure 1.** Selected efficient chiral quaternary ammonium salt phase-transfer catalysts (PTCs) and novel bifunctional camphor-based PTCs reported herein [20].

Camphor is one of nature's most privileged scaffolds, readily available in both enantiomeric forms. In addition, camphor undergoes a variety of interesting chemical transformations that functionalize, at first sight, inactive positions [21,22], allowing the synthesis of structurally and functionally very different products [23–27], thus making camphor a desirable starting material. The first reports on the application of camphor-derived organocatalysts date back to 2001. Camphor-derived phase-transfer organocatalysts were employed to catalyze the α-alkylation of a glycine Schiff base with enantioselectivities up to 39% ee (Figure 1) [20]. Since then, several types of camphor-based organocatalysts have been reported, exhibiting covalent or noncovalent activation modes, both those with a camphor backbone as the sole chiral fragment and those in which the camphor backbone is covalently linked to a chiral amino acid, usually proline, via a suitable spacer [28].

As part of our ongoing study of camphor-based diamines as potential organocatalyst scaffolds [29], we reported the synthesis of 1,3-diamine-based bifunctional squaramide organocatalysts prepared from camphor and their application as efficient catalysts in Michael additions of 1,3-dicarbonyl compounds and pyrrolones as nucleophiles to *trans*β-nitrostyrene derivatives [30,31]. Extending this work, we report here the synthesis of a new type of 1,3-diamine-based bifunctional quaternary ammonium salt phase-transfer organocatalyst (Figure 1) and its evaluation in the electrophilic α-functionalization of β-keto ester and the alkylation of a glycine-derived Schiff base with methyl acrylate.
