Palladium-meta-Terarylphosphine Catalyst for the Mizoroki–Heck Reaction of (Hetero)Aryl Bromides and Functional Olefins

Abstract

The evolutionary meta-terarylphosphine ligand architecture of Cy*Phine was recently shown to be a key feature that imposed outstanding performance in palladium-catalyzed copper-free Sonogashira applications. Herein, the Pd-Cy*Phine combination has similarly proven to be a powerful catalyst system for the Mizoroki-Heck reaction. Using high-throughput screening (HTS) methodology, DMF and NaHCO3 were rapidly identified as the most effective solvent and base pair for the cross-coupling catalysis of challenging and industrially valuable substrates including highly electron-rich heteroaryl bromides and unactivated olefins. Unprotected functional groups were well tolerated using low catalyst loadings, and the simple protocol produced excellent yields (up to 99%) with unprecedented substrate diversity. The Pd-Cy*Phine system broadly outperformed many state-of-the-art commercial alternatives, which demonstrated its potential as a next-generation cross-coupling catalyst.

Empirical and Computational Insights into N‐Arylation Reactions Catalyzed by Palladium meta‐Terarylphosphine Catalyst

“…Recently, the monodentate meta ‐terarylphosphine architecture has proven to be an excellent promoter of palladium‐catalyzed C−C, C−B, and C−F cross‐coupling reactions, exhibiting a significant advantage over their respective biarylphosphine analogues . Reactions such as copper‐free Sonogashira coupling, the Mizoroki–Heck reaction, decarboxylative coupling, and borylation/Suzuki–Miyaura sequences have recently been reported with the Cy*Phine ligand (Figure ). Advancements in nucleophilic aryl fluorination have been demonstrated by using the HGPhos and AlPhos ligands .…”

“…Advancements in nucleophilic aryl fluorination have been demonstrated by using the HGPhos and AlPhos ligands . Encouraged by the excellent performance and broad applicability of Pd–Cy*Phine in various C−C bond‐forming reactions (Scheme ), we envisaged that this system might also achieve enhanced performance for N‐arylation.…”

One‐Pot Palladium‐Catalyzed Cross‐Coupling Treble of Borylation, the Suzuki Reaction and Amination

“…Previously, our group reported the use of a meta ‐terarylphosphine‐based catalyst, Pd‐Cy*Phine, that is capable of coupling aryl halides with terminal olefins and alkynes with notable substrate tolerability and low catalyst loads. Here, we describe our developments for the Pd(Cy*Phine) 2 Cl 2 precatalyst used in one‐pot multi‐step reactions including two‐step borylation–Suzuki coupling and three‐step borylation–Suzuki–amination (BSA) sequences.…”

Silica‐coated nano‐Fe3O4‐supported iminopyridine palladium complex as an active, phosphine‐free and magnetically separable catalyst for Heck reactions

“…And the substituted olefins are versatile and valuable building blocks in the fields of pharmaceuticals, natural products and functional materials . Usually, the reaction is catalyzed by palladium salts associated with ligands, such as phosphines, which stabilize the palladium species and prevent the appearance of inactive palladium black. However, homogeneous catalytic processes suffer from the tedious separation of the catalyst in order to avoid contamination of residual metals in the final products, especially for pharmaceuticals .…”