Cinchona quincoridine

The catalytic efficiency of the diamines, 24 and 25, derived from the truncated cinchona alkaloids, quincorine and quincoridine, respectively, for the desymmetrization of meso- 1,4-diols was also investigated by Kiindig and coworkers [31a, b[. Both pseudoenantiomers 24 and 25 efficiently catalyzed the desymmetrization of the meso-complex 26 with benzoyl chloride, giving the enantiopure monobenzoylated Cr (CO)3 complexes, 27 and ent-27, respectively, with up to 99% ee (Scheme 11.17). This process will provide easy access to new planar chiral complexes. 

Preparation ofQuincorineand Quincoridine Discovery of a Novel Cleavage Reaction of Cinchona Alkaloids... 

Scheme 12.4 Invention and innovation in natural product chemistry quincorine and quincoridine from cinchona alkaloids (H.M.R. Hoffmann, 1996).

Pyridine is an aromatic 6n electron heterocycle, which is isoelectronic with benzene, but electron deficient. Nucleophiles thus add almost invariably to carbon C2 of the imine-like C=N double bond. Perhaps the best known nucleophilic addition is the Chichibabin reaction with sodium amide in liquid ammonia, giving 2-aminopyr-idine. Reactions of the quinoline moiety of cinchona alkaloids can be more complex. Although expected 2 -addition can be achieved easily with organolithium reagents to yield 13 (Scheme 12.6) [9], LiAlH4, for example, has been shown to attack C4 en route to quincorine and quincoridine (Schemes 12.4 and 12.5). C4 selectivity is due to chelation of aluminum by the C9 OH oxygen. 

Scheme 12.39 First cinchona cage expansion of quincorine and quincoridine. Distinct bridgehead iminium ions 109 + and 110+ and their stereospecific capture by nucleophiles.

Cinchona alkaloids comprising quinine, quinidine, cinchonidine, and cinchonine as the major members constitute a unique class of quinoline alkaloids with tremendous impact on human civilization. The odyssey of Cinchona alkaloids began with the discovery of their antimalarial properties followed by the very successful application in stereochemistry and in asymmetric synthesis. Currently, the portfolio of applications of Cinchona alkaloids is much broader, involving chiral stationary phases for enantioselective chromatography, novel biological activities, and several useful transformation converting them into other modular and chiral building blocks, such as, for example, quincorine or quincoridine. Current pressure on a more intense exploration of sustainable products and easy access to diverse molecular architectures make Cinchona alkaloids of primary importance for synthetic catalytic and medicinal chemistry. 

Conversion of the vinyl group in cinchona alkaloids into an acetylene, followed by Sonogashira and Heck chemistry, has led to the synthesis of a series of dimeric quinine quinidine, quincorine, and quincoridine derivatives. The role of bystander Lctionality on these reactions was investigated. ... 

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