Palladium‐Catalyzed Intramolecular Self‐Alkylation of Polyfluoroarene via Heck and Decarboxylation Process

Abstract

An efficient palladium‐catalyzed cyclization and polyfluorophenylation of γ,δ‐unsaturated polyfluorobenzoyl oxime ester via iminopalladation/polyfluorobenzoyloxy decarboxylation cascade reaction is developed. The protocol provides a practical and atom‐economical access to a broad scope of various polyfluorophenylated dihydropyrrole derivatives. The reaction effectively utilizes the polyfluorobenzoyloxy leaving group as polyfluorophenylated source for the first time, precluding the need of additional polyfluoroarene. This is the first example of the introduction of electron‐deficient arenes in the further transformation of Narasaka‐Heck‐type reaction. Additionally, the reaction is conducted in a short time.

Activation of N−O σ Bonds with Transition Metals: A Versatile Platform for Organic Synthesis and C−N Bonds Formation**

“…Most reactions also lack atom economy since a sacrificial O‐ substituent (benzoate, electron‐poor aromatic ring, pivalate…) is most of the time required. In only a few cases, the nitrogen and oxygen moieties are incorporated in the final molecule either through amino‐oxygenation pathways with alkenes [73–74,92] or in alkylation reactions upon decarboxylation of the carboxylate moiety [100,105] . One can expect that understanding the critical features of the catalytic mechanistic pathways will offer more possibilities.…”

“…In only a few cases, the nitrogen and oxygen moieties are incorporated in the final molecule either through amino-oxygenation pathways with alkenes [73][74]92] or in alkylation reactions upon decarboxylation of the carboxylate moiety. [100,105] One can expect that understanding the critical features of the catalytic mechanistic pathways will offer more possibilities. Intermolecular reactions and the use of more available transition metals will be thus accessible.…”

Activation of N–O σ Bonds with Transition Metals: a Versatile Platform for Organic Synthesis and C–N Bonds Formation

“…Most reactions also lack atom-economy since a sacrificial O-substituent (benzoate, electron-poor aromatic ring, pivalate…) is most of the time required. In only few cases both nitrogen and oxygenated moieties are incorporated in the final molecule either through amino-oxygenation pathways with alkenes, [86,98] or, upon decarboxylation of the carboxylate moiety, in alkylation reactions. [93] One can expect that understanding the key features of the catalytic mechanistic pathways will offer more possibilities, such as intermolecular reactions, using more available transition metals, and improving the atom-economy by using more systematically both parts of the molecule like in the case of the recently emerged photoexcited energy transfer reactions.…”

Regioselective synthesis of spirocyclic pyrrolines via a palladium-catalyzed Narasaka–Heck/C–H activation/[4 + 2] annulation cascade reaction

“…In addition, our group reported the synthesis of polyfluorophenylated pyrrolines by using the C 6 F 5 CO 2 − leaving group as the C 6 F 5 − source via its decarboxylation. 76 Altogether, previous reports about the Narasaka–Heck reaction mainly focused on σ-alkyl-Pd( ii ) intermediate nucleophile trapping and β-hydrogen elimination. Recently, our group made a significant breakthrough, synthesizing a series of highly strained spirocyclobutane-pyrrolines through a Narasaka–Heck/C–H activation cascade reaction ( Scheme 1a ), which is the first case of using the σ-alkyl-Pd( ii ) intermediate from Narasaka–Heck cyclization for intramolecular C–H activation.…”