Cinchonidine-derived ammonium salt

As (—)-cinchonidine-derived ammonium salts have been mainly used as chiral PTCs in monomeric cinchona-PTCs via the asymmetric alkylation of 1, and have generally shown better results than those of others [e.g., derived from (+)-cinchonine, (—(-quinine, and (+)-quinidine], the Park-Jew group primarily prepared (—) -cinchonidine derivatives to identify both the optimal linker and best relationship of attachment for the two cinchona units, and to compare catalytic efficiency with that of monomeric cinchona-PTCs. 

Recently, Lamaty and coworkers [70] demonstrated asymmetric phase-transfer catalyzed alkylation of fert-butyl glycinate-benzophenone Schiff base under solvent-free ball milling conditions (Scheme 21.33). The reaction proceeds with different alkylating agents in the presence of the cinchonidine-derived ammonium salt (10mol%) with very high yields (91-97%). This protocol reduces the reaction time however, the enantioselectivity (36-75% ee) is lower compared to conventional method with solvents (>90% ee) [71]. 

Making use of the stereochemically matched combination of a chiral auxiliary and a chiral ammonium catalyst, Minakata and coworkers succeeded in developing a highly diastereoselective aziridination of electron-deficient alkenes with iV-carbamate chloramine salts [60]. For example, in the presence of a cinchonidine-derived ammonium salt as an organocatalyst, the reaction of the enone that has L-mentho-pyrazole moiety as an auxiliary with iV-Boc chloramine salt gave diastereochemicaUy pure aziridine in 77% yield (Scheme 2.39). 

Dimeric phase-transfer catalysts were also reported by Najera et al., who used cinchonidine- and cinchonine-derived ammonium salts bearing a dimethyl-anthracenyl bridge as a spacer [32]. In the presence of these catalysts high enantioselectivity of up to 90% ee was obtained. 

Epoxidation is another important area which has been actively investigated on asymmetric phase transfer catalysis. Especially, the epoxidation of various (i.)-a,p-unsaturated ketones 68 has been investigated in detail utilizing the ammonium salts derived from cinchonine and cinchonidine, and highly enantioselective and diastereoselective epoxidation has now been attained. When 30 % aqueons H202 was utilized in the epoxidation of various a, 3-unsaturated ketones 68, use of the 4-iodobenzyl cin-choninium bromide 7 (R=I, X=Br) together with LiOH in Bu20 afforded the a,p-epoxy ketones 88 up to 92% ee,1641 as shown in Table 5. The O-substituted... 

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],... 

BQC is derived from quinine, which is a member of the cinchona family of alkaloids. Ammonium salts derived from quinidine, a diastereomer of (1) at the hydroxyl substituent, have been used less frequently in catalysis than BQC. Quini-dinium salts often give rise to products with enantioselectivity opposite to that from (1). Other related compounds, such as those derived from cinchonine and cinchonidine (which lack the methoxy substituent on the quinoline nucleus), have found application in organic synthesis. The cinchona alkaloids, as well as salt derivatives in which the benzyl group bears various substituents, have also been studied. Results from polymer-bound catalysts have not been promising. ... 

Asymmetric Michael additions can also be performed under phase-transfer conditions with an achiral base in the presence of a chiral quaternary ammonium salt as a phase-transfer agent. Conn and coworkers conducted the Michael addition of 2-propyl-l-indanone (13) to methyl vinyl ketone under biphasic conditions (aq 50% NaOH/toluene) using the cinchonine/cinchonidine-derived chiral phase-transfer catalysts (PTCs), 14a and 14b, as a catalyst (Scheme 9.5). However, only low to... 

Wang M, Gao LX, Mai WP, Xia AX, Wang F, Zhang SB. Enantioselective iodolactonization catalyzed hy chiral quaternary ammonium salts derived from cinchonidine. J. Org. Chem. 2004 69(8) 2874-2876. 

Figure 12.3 Cinchonine- and cinchonidine-derived quaternary ammonium salt phase-transfer catalysts.

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