Pd-Catalyzed Sequential Electrophilic Cyclization/Selective C-H Annulation Cascade: Synthesis of Isoxazole-Phthalimide-Fused Poly-Heterocyclics.

Abstract

Harnessing the organo-palladium intermediates generated from electrophilic cyclizations for tandem C-C bond construction is a challenging task but constitutes an excellent tool for constructing complex motifs from simpler substrates. We realize herein such a cyclative annulation of alkynyl-oxime ethers with maleimides for the facile construction of isoxazole-phthalimide hybrid motifs through Pd(II) catalysis. This protocol features excellent regio-selectivity in C-H selection, a broad substrate scope, good functional group tolerance, and scalability. Necessary KIE & labeling studies give insight into the reaction mechanism.