Chiral ammonium salts, catalysis

Enantioselective phase-transfer catalysis (PTC) has been extensively applied for the alkylation, epoxidation, conjugate addition and related process, with the use of chiral ammonium salts being the typical transfer agent [293]. However, the related aldol... 

Although the term phase-transfer catalysis was introduced in 1971 by Starks [104], this field has received particular attention in recent decades. The use of chiral ammonium salts as catalysts (Figure 44.11) has been recognized as an effective tool for organic synthesis and much time has been spent in both industrial and academic sectors, making possible the development of munerous highly enanti-oselective processes [105]. The appHcabUity of phase-transfer catalysis (PTC) has... 

As reviewed in this chapter, cinchona alkaloids have played a crucial role in the development of asymmetric phase-transfer catalysis since its advent, and today constitute a privileged structural motif that may be widely utilized for the design of new chiral quaternary ammonium salts. These benefits are due not only to the... 

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

A biphenyl and ct-methylnaphthylamine-derived chiral quaternary ammonium salt 23d, which was shown by Lygo to be effective for the asymmetric alkylation of Schiffs base 20, was also effective in the Michael reaction (Scheme 7.12) [43]. Notably, the enantioselectivity was highly dependent on the reaction conditions and substrates used. The Michael reaction of imine esters such as benzhydryl and benzyl esters with a,p-unsaturated ketones under solid-liquid phase-transfer catalysis conditions afforded the Michael adduct in up to 94% ee and 91% ee, respectively, while the tert-butyl ester showed moderate enantioselectivity (Scheme 7.12). Interestingly, in contrast to earlier reports, acrylate [42] and acrylamides failed to undergo the Michael reaction under these optimized conditions. 

Phase-transfer catalysis has been widely been used for asymmetric epoxidation of enones [100]. This catalytic reaction was pioneered by Wynberg et al., who used mainly the chiral and pseudo-enantiomeric quaternary ammonium salts 66 and 67, derived from the cinchona alkaloids quinine and quinidine, respectively [101-105],... 

Lygo, B. and Andrews, B.I. (2004) Asymmetric phase-transfer catalysis utilizing chiral quaternary ammonium salts asymmetric alkylation of glycine imines. Ace. Chem. Res., 37, 518. 

Ooi, T., Uematsu, Y. and Maruoka, K. (2006) Asymmetric Strecker reaction of aldimines using aqueous potassium cyanide by phase-transfer catalysis of chiral quaternary ammonium salts with a tetranaphthyl backbone. J. Am. Chem. Soc., 128, 2548. 

Another interesting feature of polymer-supported catalysts containing quaternary ammonium salts involves the development of enantioselective catalysis using salts derived from cinchonia or ephedra alkaloids.11341 The first application of such chiral supported catalysts in the Michael reaction between methyl 1-oxoindan-2-carboxylate and methyl vinyl ketone revealed a high chemical yield in condensation product (60-100 %) although the enantioselectivities were only moderate (ee <27 %). 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

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. 

Reaction with alkaline peroxide (or hypochlorite) and a chiral catalyst allows the asymmetric epoxidation of enones. Excellent asymmetric induction has been achieved using metal-chiral ligand complexes, such as those derived from lanthanides and (/ )- or (5)-BlNOL. Alternatively, phase-transfer catalysis using ammonium salt derivatives of Cinchona alkaloids, or the use of polyanuno acid... 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

The use of ot,p-unsaturated aldehydes as Michael acceptors always represents a challenging situation because of the tendency of enals to undergo 1,2- rather than the desired 1,4- addition reaction. Moreover, working under phase-transfer catalysis conditions incorporates an additional element of difficulty, because of the propensity of enolizable enals to undergo self-condensation side reactions. For this reason, there are only a few examples reporting enantioselective Michael reactions with ot,p-unsaturated aldehydes as Michael acceptors under PTC conditions, both coming from the Maruoka research team and also both making use of chiral tV-spiro quaternary ammonium salts as 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... 

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