Construction of chiral α-tert-amine scaffolds via amine-catalyzed asymmetric Mannich reactions of alkyl-substituted ketimines

Stereoselective Mannich reactions of aldehydes with ketimines provide chiral beta-amino aldehydes that bear an alpha-tert-amine moiety. However, the structural variation of the ketimines is limited due to the formation of inseparable E/Z isomers, low reactivity, and other synthetic difficulties. In this study, a highly diastereodivergent synthesis of hitherto difficult-to-access beta-amino aldehydes that bear a chiral alpha-tert-amine moiety was achieved using the amine-catalyzed Mannich reactions of aldehydes with less-activated Z-ketimines that bear both alkyl and alkynyl groups.

Automated summary

This study demonstrated a highly diastereodivergent synthesis of beta-amino aldehydes with a chiral alpha-tert-amine moiety, utilizing less-activated Z-ketimines in amine-catalyzed Mannich reactions with aldehydes. This method overcame the limitations of structural variations in ketimines, achieving high diastereoselectivity.