Phase transfer catalysis cinchona-based catalysts

Enantioselective synthesis of a-amino acids by phase-transfer catalysis with achiral Schiff base esters using Cinchona alkaloids as phase-transfer catalysts 04ACS506. 

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... 

Asymmetric phase-transfer catalysis is a method that has for almost three decades proven its high utility. Although its typical application is for (non-natural) amino acid synthesis, over the years other types of applications have been reported. The unique capability of quaternary ammonium salts to form chiral ion pairs with anionic intermediates gives access to stereoselective transformations that are otherwise very difficult to conduct using metal catalysts or other organocatalysts. Thus, this catalytic principle has created its own very powerful niche within the field of asymmetric catalysis. As can be seen in Table 5 below, the privileged catalyst structures are mostly Cinchona alkaloid-based, whereas the highly potent Maruoka-type catalysts have so far not been applied routinely to complex natural product total synthesis. 

The versatile nature of cinchona alkaloid ammonium salts for phase-transfer catalysis can be illustrated by recent reports on conjugate additions [118] and a nitro-Mannich reachon [119]. Dimeric catalysts derived from quinine and quini-dine were applied in the conjugate addition of cyclic (l-ketoesters to a, 3-unsaturated carbonyl compounds. The reaction proceeded in the presence of a tertiary amine as base and afforded the products in moderate to high yield and enantioselectivity (Scheme 6.56). 

Phase-Transfer Catalysis Phase-transfer catalysis is an interesting alternative approach that can induce high to very high enantioselectivities. For this purpose, quaternary ammonium salts derived from cinchona alkaloids are good catalysts for the fluorination of C H acidic substrates such as (3-keto esters. Treatment of (3-keto esters with NFSI in the presence of 10 mol% of chiral phase-transfer catalyst and 6 equivalents of base afforded the a-fluoro- 3-keto esters in excellent yields and moderate enantioselectivities (Scheme 44.27). With a-cyano esters,... 

After the first successful application of Cinchona alkaloid-based quaternary amo-nium salts as chiral phase-transfer catalysts in 1984 [187], the use of chiral quaternary ammonium salts in asymmetric catalysis has experienced a notable growth [177a, 188]. In particular, the asymmetric alkylation of glycine-derived Schiff bases by means of phase-transfer organocatalysis, pioneered by O Donnell et al. [ 189] and further improved by Lygo and Wainwright [190] and by Maruoka and co-workers [191], among others, has become one of the most reliable procedures for... 

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