Enantioselective Syntheses of Strychnos and Chelidonium Alkaloids through Regio‐ and Stereocontrolled Cooperative Catalysis

Abstract

We describe enantioselective syntheses of strychnos and chelidonium alkaloids. In the first case, indole acetic acid esters were established as excellent partner nucleophiles for enantioselective cooperative isothiourea/Pd catalyzed α‐alkylation. This provides products containing indole‐bearing stereocenters in high yield and with excellent levels of enantioinduction in a manner that is notably independent of the N‐substituent. This led to concise syntheses of (−)‐akuammicine and (−)‐strychnine. In the second case, the poor performance of ortho‐substituted cinnamyl electrophiles in the enantioselective cooperative isothiourea/Ir catalyzed α‐alkylation was overcome by appropriate substituent choice, leading to enantioselective syntheses of (+)‐chelidonine, (+)‐norchelidonine, and (+)‐chelamine.

Recent progress in asymmetric synergistic catalysis – the judicious combination of selected chiral aminocatalysts with achiral metal catalysts

“…Specifically, C2/3 indole acetic acids were used to access Strychos alkaloids while Chelidonium alkaloids were accessed by the aforementioned branched selective allylation and Hofmann rearrangement. 50 …”

“…Specifically, C2/3 indole acetic acids were used to access Strychos alkaloids while Chelidonium alkaloids were accessed by the aforementioned branched selective allylation and Hofmann rearrangement. 50 Evidently, the use of an isothiourea-Pd catalyst system is a powerful solution to the parasitic coordination of NHCs to Pd. However, an alternative solution is the selection of an alternative metal catalyst.…”