Synthesis of an enantiocomplementary catalyst of β-isocupreidine (β-ICD) from quinine

Compound 20, a pseudoenantiomer of β-isocupreidine (β-ICD), was synthesized from quinine employing a Barton reaction of nitrosyl ester 13 and acid-catalyzed cyclization of carbinol 18 as key steps. The Baylis-Hillman reaction of benzaldehyde, p-nitrobenzaldehyde, and hydrocinnamaldehyde with 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) using 20 as a chiral amine catalyst was found to give the corresponding S-enriched adducts in high optical purity (> 91% ee) in contrast to the β-ICD-catalyzed reaction which affords R-enriched adducts. This result suggests that compound 20 can serve as an enantiocomplementary catalyst of β-ICD in the asymmetric Baylis-Hillman reaction of aldehydes with HFIPA.