New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

Abstract

The preparation of new organocatalysts for asymmetric syntheses has become a key stage of enantioselective catalysis. In particular, the development of new cyclodextrin (CD)-based organocatalysts allowed to perform enantioselective reactions in water and to recycle catalysts. However, only a limited number of organocatalytic moieties and functional groups have been attached to CD scaffolds so far. Cinchona alkaloids are commonly used to catalyze a wide range of enantioselective reactions. Thus, in this study, we report the preparation of new α- and β-CD derivatives monosubstituted with cinchona alkaloids (cinchonine, cinchonidine, quinine and quinidine) on the primary rim through a CuAAC click reaction. Subsequently, permethylated analogs of these cinchona alkaloid–CD derivatives also were synthesized and the catalytic activity of all derivatives was evaluated in several enantioselective reactions, specifically in the asymmetric allylic amination (AAA), which showed a promising enantiomeric excess of up to 75% ee. Furthermore, a new disubstituted α-CD catalyst was prepared as a pure AD regioisomer and also tested in the AAA. Our results indicate that (i) the cinchona alkaloid moiety can be successfully attached to CD scaffolds through a CuAAC reaction, (ii) the permethylated cinchona alkaloid–CD catalysts showed better results than the non-methylated CDs analogues in the AAA reaction, (iii) promising enantiomeric excesses are achieved, and (iv) the disubstituted CD derivatives performed similarly to monosubstituted CDs. Therefore, these new CD derivatives with cinchona alkaloids effectively catalyze asymmetric allylic aminations and have the potential to be successfully applied in other enantioselective reactions.

Evolution of a Biocatalysis CURE for Organic Chemistry Students

“…The teams each worked on their own synthesis of a “clickable” cyclodextrin, but the teams with the same type of cyclodextrin were encouraged to collaborate and compare results (Table S2). , We note that while all teams made considerable progress over the course of the semester, some ran out of time to complete their projects. For example, some teams struggled to purify and characterize their click reaction products.…”

Beyond L-proline: Investigation of the properties of other natural amino acids in an organocatalytic warfarin synthesis

“…Organocatalytic approaches to the synthesis of warfarin have been known for quite some time [5,6]. Some of these approaches have both high yields and enantioselectivities (DPEN catalysts, Cinchona alkaloids), while others have high yields but low enantioselectivities (L-proline) [7,8]. Organocatalytic applications of L-proline are widespread throughout the chemical literature, with particular utility in the catalysis of carbon-carbon bond forming reactions such as Aldol additions, Michael additions, Knoevenagel condensation, and Robinson Annulation [9].…”

Beyond L-proline: Investigation of the properties of other natural amino acids in an organocatalytic warfarin synthesis

“…Organocatalytic approaches to the synthesis of warfarin have been known for quite some time [5,6]. Some of these approaches have both high yields and enantioselectivities (Diphenylethylenediamine (DPEN) catalysts, Cinchona alkaloids), while others have high yields but low enantioselectivities (L-proline) [7,8].…”