Cinchona novel transformations

Selected Novel Transformations of the Quinuclidine Moiety of Cinchona Alkaloids... 

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

Finally, the Tu group reported a novel transfer fluorination/semipinacol rearrangement of allylic alcohols that generated enantioenriched fluorinated products containing a chiral quaternary carbon center (Scheme 13.4) [12]. Quinine was identified as the optimal Cinchona alkaloid for this transformation. While the majority of substrates examined contained cyclohexenes, resembling the one shown in Scheme 13.4, substrates containing a cycloheptene and an acyclic allylic alcohol were also suitable for this transformation. 

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. 

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