Palladium-Catalyzed Allylic Alkylation Reactions of Nucleophilic Allenones: Asymmetric Allylic Alkylation, Z/E Divergent Allylic Alkylation, and [5 + 2] Annulation

Metal-catalyzed allenylic substitution reactions where allenes serve as electrophilic precursors have been recognized as a rapid way for novel allene construction. On the contrary, the chemistry in which allenes act as nucleophiles has been far less investigated, especially in a powerful platform such as metal-catalyzed allylic alkylation reactions. We herein describe two unprecedented palladium-catalyzed allylic alkylation reactions of an allene nucleophile. In the first reaction, using vinyloxazolidinones as the allyl precursor, the palladium-catalyzed asymmetric allylation of trisubstituted allenones worked well to prepare an array of axially chiral tetrasubstituted allenes. Mechanistic studies and density functional theory (DFT) calculations indicated that weak hydrogen-bonding interaction between the acidic C(sp2)–H of allenone and the nitrogen anion of chiral π-azaallyl-Pd species is key to the success of stereocontrol. This reaction revealed the intriguing reactivity of nucleophilic allenones in a metal-catalyzed asymmetric allylation reaction for the first time. In the second reaction, with the use of allenylethylene carbonates as π-oxyallyl-Pd precursors, the palladium-catalyzed allylic alkylation reaction of allenone presented unique reactivity under different reaction conditions to provide divergent synthetic access to (E)- and (Z)-allenyl diene products. Interestingly, the subsequent sequential intramolecular cyclization/isomerization reaction of the (Z)-product delivered dihydrooxepine derivatives as [5 + 2] annulation products.