Pd-Catalyzed Domino Narasaka-Heck/C-H Activation/Amination Reactions: Synthesis of Bis-heterocyclic Spirocycles

Org Lett. 2023 Jul 21;25(28):5361-5365. doi: 10.1021/acs.orglett.3c01941. Epub 2023 Jul 12.

Abstract

The palladium-catalyzed synthesis of bis-heterocyclic spirocycles containing both pyrroline and indoline motifs is reported. Di-tert-butyldiaziridinone is used to functionalize palladacycles generated in situ via domino Narasaka-Heck/C-H activation reactions. The reaction is readily scalable, and the spirocyclic products can undergo deprotection, reduction, and (3 + 2) cycloadditions, highlighting their synthetic utility. Additionally, kinetic isotope effect experiments support a turnover-limiting C-H functionalization step in the catalytic cycle.