Umpolung Asymmetric 1,5‐Conjugate Addition via Palladium Hydride Catalysis.

Electronically matched nucleophilic 1,6‐conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5‐conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5‐conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5‐conjugate reaction, followed by inter‐ or intramolecular [3+2] cyclization. A migratory 1,5‐addition protocol is established to corroborate the feasibility of this umpolung concept. The 1,5‐addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis. [ABSTRACT FROM AUTHOR]