Amines as Activating Ligands for Phosphine Palladium(II) Precatalysts: Effect of Amine Ligand Identity on the Catalyst Efficiency

Abstract

Palladium-catalyzed cross-coupling reactions between C–X/C–H bonds and nucleophilic reagents remain a staple in organic synthesis. These reactions rely on the in situ generation of an active LPd0 species. Air-stable palladium(II) precatalysts that readily form the LPd0 species under catalytic conditions have been identified as effective precatalysts. The alkyl amine ligand can serve as potential reducing ligands for palladium(II) complexes in the presence of a base through a sequence of β-hydrogen elimination and base-promoted reductive elimination of the resulting palladium hydride. A series of air-stable ( t Bu2PNp)Pd(amine)Cl2 (Np = neopentyl) complexes were synthesized with a range of structurally different primary and secondary amine ligands. These complexes allowed the effect of the amine ligand structure on the catalyst performance in cross-coupling of aryl halides and aniline derivatives to be analyzed. The identity of the amine ligand has a significant effect on catalyst activity and lifetime. Precatalysts with primary n-alkylamine ligands afford the most active catalysts. Reactions using ( t Bu2PNp)Pd(n-butylamine)Cl2 as the precatalyst provide excellent yields at room temperature under 1 h. Moreover, (Np3P)Pd(n-butylamine)Cl2 was synthesized and exhibited promising activity for sterically demanding aniline derivatives and aryl chlorides. Preliminary mechanistic studies show that the structure of the amine ligand has a significant effect on the selectivity for palladium(0) formation that correlates with the activity of the precatalysts.

Synthesis, characterization, and reactivity of [Pd(phosphine)(py)Cl2] (PEPPSI) and [Pd(phosphine)Cl2]2complexes

“…In the course of preparation of this manuscript, two new reports on mixed phosphine/amine complexes were published by Nicasio and Shaughnessy groups. 20,21 One of the most utilized classes of Pd-NHC pre-catalysts is represented by the Pd-PEPPSI family. These air-and moisturestable pre-catalysts have been utilized in various cross-coupling reactions such as the Negishi, 22 Suzuki-Miyaura, 2,23 Buchwald-Hartwig, 24 Stille-Migita, 25 and Kumada-Tamao-Corriu.…”

“…In the course of preparation of this manuscript, two new reports on mixed phosphine/amine complexes were published by Nicasio and Shaughnessy groups. 20,21…”