Pd‐Catalyzed Diastereoselective Intramolecular Amide α‐C−H Arylation in Sterically Hindered Monospirooxindole Motifs

Abstract

This paper reveals the diastereoselective Pd‐catalyzed intramolecular α‐C(sp3)−H arylation in amides. The intermolecular and intramolecular α‐arylation of tertiary C(sp3)−H bond of carbonyl compounds have been well documented in the literature. Nevertheless, the diastereoselective intramolecular α‐arylation of tertiary C(sp3)−H bond involving sterically hindered spirocyclic carbonyl substrates, especially amides remains a less explored task. Accordingly, we have demonstrated the diastereoselective Pd‐catalyzed intramolecular amide α‐arylation of tertiary C(sp3)−H bond using monospirooxindole‐based carboxamide substrates and construction of various sterically hindered 1,2‐bisspirooxindolopyrrolidines possessing contiguous vicinal quaternary stereocenters with high diastereoselectivity. Monospirooxindole‐based carboxamide substrates suitably positioned with an aryl halide unit and tertiary α‐C−H bond, which were required for investigating the intramolecular α‐C(sp3)−H arylation were assembled via the stereoselective [3+2] cycloaddition of azomethine ylides with acrylamides. The stereochemistry of monospirooxindoles and 1,2‐bisspirooxindolopyrrolidines possessing contiguous vicinal quaternary stereocenters was assigned based on the X‐ray structure analyses of representative compounds.