Asymmetric Cycloaddition Catalyzed by Cinchona-Based Phase-Transfer Catalysts

Asymmetric Cycloaddition Catalyzed by Cinchona-Based Phase-Transfer Catalysts 

A key to the reaction is the use of the stereochemically well-defined a,P-dihalo-genated acrylate ester as the electrophile in the substitution process. Under the control of a chiral phase-transfer catalyst, enantioselective C—C bond formation by the stereospecific substitution of the chlorine atom, with retention of configuration, 

This protocol was subsequently optimized and developed for high enantioselective variants using the dihydrocinchonine-derived phase-transfer catalyst It or lu. En-antiopure products 23 were easily obtained after recrystallization with high yields (Table 10.10). 

The iodo-substituted products were obtained as single enantiomers in 63-73% yield by recrystallization of the crude reaction mixture. The chloro-substituted product was unfortunately not crystalline, but was isolated in 90% yield and with 85% ee after column chromatography. It is worth to note that the overall process is very practical, scalable, and chromatography-free. 

As discussed above, the vast synthetic potential of cinchona alkaloids and their derivatives in the asymmetric cycloadditions has been well demonstrated over the past few years. Cinchona-based organocatalysts possess diverse chiral skeletons and are multifunctional. There is no doubt that the further development of cinchona-based organocatalysts and their catalyzed cycloaddition reactions will continue to provide exciting results in the near future. 

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