PTCs, alkaloid-based

General principles applied on the design of chiral cinchona alkaloid-based chiral ammonium salt PTC catalysts. 

Phase-transfer catalysis is one of the most practical synthetic methodologies because of its operational simplicity and mild reaction conditions, which enable applications in industrial syntheses as a sustainable green chemical process. As reviewed in this chapter, diverse Cinchona alkaloid-derived quaternaiy ammonium salts have been developed via the modification of Cinchona alkaloids based on steric or electronic factors as highly efficient chiral PTC catalysts and successfully applied in various asymmetric organic reactions. Despite the successful development and application of these catalysts, some problems remain to be addressed. Although Cinchona alkaloids have unique structural features, resulting in the availability of four... 

FIGURE 1 Representative examples for powerful Cinchona alkaloid-based PTCs. 

Cinchona alkaloids gained importance as chiral catalysts in various asymmetric reactions [32] and it was already mentimied above that Cinchona alkaloid-based PTCs are by far the most commonly used chiral anunonium salt catalysts. Accordingly, it also comes as no surprise that PTCs derived from Cinchona alkaloids have been systematically exploited in the syntheses of many (biologically active) natural products. 

The 1,2-addition of sulfone-containing nucleophiles to aldehydes is a highly valuable tool in synthetic chemistry. H owever, since the first addition of a-chlorophenyl-sulfone to aromatic aldehydes under PTC in 1998 [65], only one further approach has been reported. Hu et al. reported the enantioselective 1,2-addition of Me3SiCp2 S02Ph and PhS02Cp2H to aromatic aldehydes catalyzed by a chiral alkaloid-based quaternary ammonium salt (Scheme 29.30) [66]. Several chiral ammonium salts were screened and the best results were obtained with cinchonine and quinine... 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

Alkylations. Highly enantioselective alkylation of t-butyl 4,4-bis (p-dimethyl-aminophenyl)-3-butenoate and t-butyl A -diphenylmethyleneglycine in the presence of a quatemized cinchona alkaloid results. The salt plays a dual role in asymmetric induction and as a phase-transfer catalyst. The products from the former reaction can be cleaved at the double bond to furnish chiral malonaldehydic esters which have many obvious synthetic applications. A combination of PTC, LiCl, and an organic base (e.g., DBU) favors the enantioselective alkylation of a chiral A-acylimidazolidinone in which the acyl side chain is derived from glycine. ... 

The asymmetric alkylation of glycine derivatives is one of the most simple methods by which to obtain optically active a-amino acids [31]. The enantioselective alkylation of glycine Schiff base 52 under phase-transfer catalysis (PTC) conditions and catalyzed by a quaternary cinchona alkaloid, as pioneered by O Donnell [32], allowed impressive degrees of enantioselection to be achieved using only a very simple procedure. Some examples of polymer-supported cinchona alkaloids are shown in Scheme 3.14. Polymer-supported chiral quaternary ammonium salts 48 have been easily prepared from crosslinked chloromethylated polystyrene (Merrifield resin) with an excess of cinchona alkaloid in refluxing toluene [33]. The use of these polymer-supported quaternary ammonium salts allowed high enantioselectivities (up to 90% ee) to be obtained. 

Based on the successful introduction of solid-supported catalysts, a novel type of polymeric PTC catalysts derived from the Cinchona alkaloid was... 

Other Quaternary Ammonium Salts In order to understand the role of the quinoline nucleus on the dnchona alkaloid-derived quaternary ammonium salts in asymmetric PTC, Dehmlow and coworkers replaced the quinoline residue with various sterically bulky aromatic groups. It is interesting that, in the asymmetric epoxidation reaction, the monodea2acinchona alkaloid derivative 56 could provide a higher enantioselectivity than the corresponding cinchona-based catalyst (Figure 12.13) [89]. 

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