Dnchona alkaloids

In the presence of cinchona derivatives as catalysts, peroxides or hypochlorites as Michael donors react with electron-deficient olefins to give epoxides via conjugate addition-intramolecular cyclization sequence reactions. Two complementary methodologies have been developed for the asymmetric epoxidation of electron-poor olefins, in which either cinchona-based phase-transfer catalysts or 9-amino-9(deoxy)-epi-dnchona alkaloids are used as organocatalysts. Mechanistically, in these two... 

The introduction of a 1,3-benzodithiol group in a stereoselective fashion can be used to generate an anionic or cationic equivalent and could be easy removed by Raney nickel. This procedure was applied to the synthesis arundic acid [34], which is currently undergoing phase 11 development for the treatment of acute ischemic stroke, and to the bisabolane skeleton (P. Canestrari, E. Emer, A. Gualandi, and P.G. Cozzi, unpubUshed results). The procedure was recently extended to the formation of quaternary stereogenic centers, in particular the alkylation of a-branched aldehydes with the benzodithiolyUum ion can be catalyzed by the use of 9-amino-9-deoxy-epi-dnchona alkaloid primary amines [35]. The use of primary... 

Substituents at C9 play a key role in determining the conformation of cinchona alkaloids. For example, esters are present in the anti-dosed form in solution, while C9 methyl ethers prefer an anti-open conformation. Recently, the conformations of cinchona alkaloids with a CF3 and a hydroxyl group at the C9 position were examined with F NMR spectroscopy [16]. The CF3 group was observed to act as a conformational stabilizer by decreasing the rate of rotation around the C4 -C9, thus allowing the syn and anti conformers to be differentiated at room temperature. The anti conformer was observed to be stabilized by polar solvents with the exception of D2O, in which the syn conformer appeared to be preferred. As found for natural dnchona alkaloids, the syn conformer dominates in apolar solvents. 

In terms of substrate choice, C9 amino derivatives of the dnchona alkaloids have proven to be suitable for stericaUy hindered a-branched aldehydes, a-branched unsaturated aldehydes, as well as simple unsaturated ketones and a-branched enones. In general terms, catalysis with the C9 amino derivatives can involve... 

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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