Cinchona alkaloid derived quaternary ammonium salts

O Donnell (1989), Corey/Lygo (1997) cinchona alkaloid-derived quaternary ammonium salts Lewis Base Cataiysis... 

Alkylation of Schiff bases, derived from amino acid and non-optically active aromatic aldehydes by phase-transfer catalysis in the presence of cinchona alkaloid derived quaternary ammonium salts, gave ce values of up to 50% l42. 

Currently, the chiral phase-transfer catalyst category remains dominated by cinchona alkaloid-derived quaternary ammonium salts that provide impressive enantioselec-tivity for a range of asymmetric reactions (see Chapter 1 to 4). In addition, Maruoka s binaphthyl-derived spiro ammonium salt provides the best results for a variety of asymmetric reactions (see Chapters 5 and 6). Recently, some other quaternary ammonium salts, including Shibasaki s two-center catalyst, have demonstrated promising results in asymmetric syntheses (see Chapter 6), while chiral crown ethers and other organocatalysts, including TADDOL or NOBIN, have also found important places within the chiral phase-transfer catalyst list (see Chapter 8). 

Non-cinchona alkaloid-derived quaternary ammonium salts 1 [10] and 2 [11] were each shown to promote asymmetric alkylation reactions, with enantioselectivity of up to 48% and 94% ee, respectively (Scheme 7.1). 

ASYMMETRIC PHASE-TRANSFER CATALYSED ALKYLATION OF GLYCINE IMINES USING CINCHONA ALKALOID DERIVED QUATERNARY AMMONIUM SALTS... 

The use of inorganic bases and cinchona alkaloids derived quaternary ammonium salts under phase-transfer conditions resulted in lower enantioselectivities [28,29]. 

Cinchona Alkaloid-Derived Quaternary Ammonium Salts The first successful application of cinchona-based quaternary ammonium salts as chiral phase-transfer catalysts was conducted by the Merck research group in 1984 [16]. Dolling and coworkers reported the N-p-trifluoromethylbenzylcinchoninium bromide 11a for the highly enantioselective alkylation of indanone derivatives imder phase-transfer conditions (Figure 12.3). 

Five years later, a similar cinchona alkaloid-derived quaternary ammonium salt was applied for the alkylation of N-(diphenylmethylene) glycine tert-butyl ester by O Donnell et al. [17]. By using either 11b or 12a, both enantiomers of the alkylated products, which could be hydrolyzed to afford the chiral a-amino acids, were obtained in high yield with a maximum of 66% ee. Further optimization indicated that, with the corresponding 9-OH-protected catalyst 11c, the enantioselectivity could be enhanced to 81% ee [6bj. 

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]. 

Cinchona alkaloids now occupy the central position in designing the chiral non-racemic phase transfer catalysts because they have various functional groups easily derivatized and are commercially available with cheap price. The quaternary ammonium salts derived from cinchona alkaloids as well as some other phase transfer catalysts are... 

Very successful results have been obtained with functionalized quaternary ammonium salts derived from cinchona alkaloids. An example... 

In 1989, O Donnell and coworkers successfully utilized cinchona alkaloid-derived chiral quaternary ammonium salts for the asymmetric synthesis of a-amino acids using tert-butyl glycinate benzophenone Schiff base 1 as a key substrate [5]. The asymmetric alkylation of 1 proceeded smoothly under mild phase-transfer... 

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 wide variety of catalytic asymmetric transformations have been achieved in the above investigations, which clearly indicates that quaternary ammonium salts derived from cinchona alkaloids are still powerful reagents, despite their limited structural diversity. Moreover, as PTC chemistry has been recognized as a highly practical approach, further progress should be expected in this area of research. 

Cinchona alkaloids, of course, have occupied the central position in the design of chiral PTCs. By employing a simple chemical transformation of the tertiary amine ofthe natural cinchona alkaloids to the corresponding quaternary ammonium salts, using active halides (e.g., aryl-methyl halides), a basic series of PTCs can be readily prepared. Cinchona alkaloid-derived PTCs have proved their real value in many types of catalytic asymmetric synthesis, including a-alkylation of modified a-amino acids for the synthesis of higher-ordered a-amino acids [2], a-alkylation of... 

It is generally considered that a quaternary ammonium salt derived from cinchona alkaloids has an imaginary tetrahedron composed of four carbon atoms adjacent to the bridgehead nitrogen. As shown in Figure 4.2, in order to serve as an efficient... 

Both experimental and theoretical studies have been reported of fluoro-denitration and fluoro-dechlorination reactions using anhydrous tetrabutylammonium fluoride in DMSO. The absences of ion pairing and strong solvation are critical in contributing to the reactivity of the fluorinating agent24 Quaternary ammonium salts derived from cinchona alkaloids have been shown to be effective catalysts in an improved asymmetric substitution reaction of /1-dicarbonyl compounds with activated fluoroarenes. The products may be functionalized to yield spiro-oxindoles.25... 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

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],... 

Hodge, P., Khoshdel, E. and Waterhouse, J. Michael reactions catalyzed by polymer-supported quaternary ammonium-salts derived from cinchona and ephedra alkaloids, J. Chem. Soc., Perkin Trans. 1, 1983, 2205-2209. 

As mentioned above, quaternary ammonium salts derived from cinchona alkaloids have occupied the central position as efficient PTCs in various organic transformations, especially in the asymmetric a-substitution reaction of carbonyl derivatives. A cinchona alkaloidal quaternary ammonium salt, which acts as a PTC in various organic reactions, is prepared by a simple and easy chemical transformation of the bridgehead tertiary nitrogen with a variety of active halides, mainly arylmethyl halides. Other moieties of cinchona alkaloids (the 9-hydroxy, the 6 -methoxy, or the 10,11-vinyl) are occasionally modified for the enhancement of both chemical and optical yields (Figure 6.4). 

Figure 6.4 Quaternary ammonium salts derived from cinchona alkaloids.

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. 

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