## 2 Topical Research Areas Related to Ionic Liquids and the Contribution of Spiroammonium Compounds
### The Use of Metal-Free Small Organic Molecules as Phase-Transfer Catalysts
#### 2.5.2 Azoniaspiro Compounds as Phase-Transfer Catalysts  
Chiral PTCs are employed in various asymmetric syntheses like the enantioselective alkylation, epoxidation and Darzens condensation, Michael addition, asymmetric 1,6-conjugate addition, and others [162]. * _Catalytic asymmetric alkylation reaction_ C2-symmetric chiral quaternary ammonium salt (S)-1 serves as a chiral phase-transfer catalyst in the catalytic enantioselective alkylation of tert-butyl glycinate-benzophenone Schiff base under mild phase-transfer conditions (Scheme 10) [163]. (S)-1 catalysts type can be readily assembled in the same manner; starting from either (R)- or (S)-binapthol, a wide variety of natural and unnatural \(\alpha\)-amino acids can be synthesized in an enantiomerically pure form via phase-transfer catalytic alkylation. * _The Darzen reaction and epoxy condensation_  
Figure 9: The most popular phase transfer catalyst of the chiral quaternary ammonium salt type [161]. The synthesis of new phase-transfer catalysts (PTCs) has been described. These catalysts were synthesized from proline with competitive yields. They were designed and synthesized in such a way that out of the four sides, three sides of quaternary nitrogen are blocked with cyclic groups and one aromatic group at \(\alpha\)- or \(\beta\)-position to the nitrogen, whereas only one side is available for ion pairing with an anion [164]. These PTCs ((R)-1-((R)-hydroxy(phenyl)methyl)-5-azaspiro-[4.4]-nonan-5-ium bromide (**a**) and (R)-1-((R)-hydroxy(phenyl)methyl)-5-azaspiro-[4,5]-decan-5-ium bromide (**b**)) have the OH group at the \(\beta\)-position to the quaternary nitrogen, which can help lead to hydrogen bonding or attractive van der Waals interaction, which are advantageous for enhancing enantioselectivity (Figure 10). The effectiveness of these novel chiral cyclic phase-transfer catalysts has been evaluated by applying them in the enantioselective epoxide synthesis from \(\alpha\),\(\beta\)-unsaturated ketone (chalcone) and Darzens condensation (Schemes 11 and 12). \begin{tabular}{c c c c c c} \hline \hline Entry & PTC & Loading PTC, & Reaction & & & \\  & & mol \% & time, h & Yield, \% & ee, \% \\ \hline
1 & **a** & 5 & 11 & 87 & 78.30 \\
2 & **a** & 10 & 7 & 88 & 78.62 \\
3 & **b** & 5 & 10 & 88 & 79.65 \\
4 & **b** & 10 & 6 & 90 & 79.99 \\ \hline \hline \end{tabular}   
**Scheme 11. ** Epoxidation of chalcone to get a chiral epoxide by using the novel chiral PTCs (**a**, **b**). Reproduced from [164]. Copyright 2019 SNCSC. **Scheme 12. ** The Darzen condensation to get a chiral epoxide by using the novel chiral PTCs (**a**, **b**). Reproduced from [164]. Copyright 2019 SNCSC. **Scheme 13. ** The Darzen condensation to get a chiral epoxide by using the novel chiral PTCs (**a**, **b**). Reproduced from [164]. Copyright 2019 SNCSC. **Scheme 14. ** The Darzen condensation to get a chiral epoxide by using the novel chiral PTCs (**a**, **b**). Reproduced from [164]. Copyright 2019 SNCSC. In the first case, the reaction was carried out in a two-phase system consisting of a 10% solution of NaOCl and toluene at a temperature close to r.t. (Scheme 11); in the second case, mild synthesis conditions were also used in a two-phase system consisting of an aqueous solution of LiOH\(\cdot\)H\({}_{2}\)O (2.0 mol. eq) and methyl tert-butyl ether (MTBE) at a temperature close to r.t. (20\(-\)30 \({}^{\circ}\)C) (Scheme 12). The obtained results show that the synthesized derivatives of proline are as effective as PTCs since the reaction products have been obtained with high yields (87-90% and 82-85%) and excellent enantioselectivity (78.30-79.99 and 77.34-79.35%), respectively. * _The Michael addition_ (A) A Michael addition reaction with the formation of a carbon-carbon bond through the use of a catalytical methodology can provide enantiomerically pure Michael adducts. An example of Michael addition is the enantioselective addition of malonic esters to \(\alpha\),\(\beta\)-unsaturated carbonyls, which results in optically active tricarbonyl Michael adducts.