It Is Not All about the Ligands: Exploring the Hidden Potentials of tBu₃P through Its Oxidative Addition Complex as the Precatalyst

Abstract

A series of oxidative addition complexes with a general formula (tBu3P)Pd(Ar)X, as a class of precatalysts, were synthesized for challenging Suzuki–Miyaura coupling involving coupling partners, such as (i) sensitive polyfluorinated arylboronic acids or their corresponding boronic esters, (ii) sterically hindered electrophiles, and (iii) sterically hindered nucleophiles. A total of 89 examples are reported, of which 39 examples are in the Supporting Information. These precatalysts, in particular (tBu3P)Pd(4-CF3Ph)Br, were demonstrated to be powerful catalytic systems in general for cross coupling reactions in comparison to the in situ systems created by mixing tBu3P ligand with a palladium precursor. The precatalysts are also superior to the other monoligated systems, such as Buchwald’s biaryl based G3 or G4 palladacycles. In addition, the (tBu3P)Pd(4-CF3Ph)Br precatalyst is also highly effective for the second most popular coupling reaction, namely the Buchwald–Hartwig coupling. In this study, hindered and electron-deficient amines were coupled with hindered (hetero)aryl bromides and chlorides with 34 examples, of which 8 are in the Supporting Information. Interestingly, the results obtained for both C–C and C–N couplings were on par with or superior to that of the “state-of-the-art” catalysts containing Ad3P and Np3P ligands for the same or similar substrates, suggesting that it is not all about the ligands.

Alkene-Coordinated Palladium(0) Cross-Coupling Precatalysts: Comparing Oxidative Addition and Catalytic Reactivity for Dimethyl Fumarate and Maleic Anhydride Stabilizing Ligands

“…In particular, we wanted to be able to access Pd(II) oxidative addition complexes directly from phosphine-ligated Pd(0) alkene complexes. Isolable oxidative addition complexes are “on-cycle” precatalysts and are also useful in late-stage modification of pharmaceuticals and biomolecules. − Often, these complexes are made from homoleptic Pd(PR 3 ) n precursors (for simple phosphines), − or from in situ combinations of phosphine ligands and Pd 2 dba 3 or (COD)PdR 2 species. ,,,, …”

Palladium-Catalyzed Sequential Cross-Coupling/Annulation of ortho-Vinyl Bromobenzene with Aryl Bromide: Bimetallic Pathway versus Pd(II)–Pd(IV) Pathway: A DFT Investigation

“…Due to the facile oxidation of Pd(0) species in air, more stable Pd­(II) species are commonly used as precatalysts in experiments to generate the active Pd(0)-L species − in situ through ligand exchange. Accordingly, the catalyst precursor Pd­(OAc) 2 initially undergoes ligand exchange with the DPEphos ligand to form the active Pd(0)-L species (L = DPEphos, CAT in Scheme S1) and concurrently releasing ∼27.1 kcal·mol –1 of free energies.…”

A Thermally Stable, Alkene-Free Palladium Source for Oxidative Addition Complex Formation and High-Turnover Catalysis

“…62 Importantly, our synthesis of 3 combines the advantages of the two reported synthetic pathways: high yield, short reaction time, operational convenience, and readily removable byproducts. Complex 6 was first reported by Carrow and co-workers, prepared from the Buchwald G3 mesylate dimer as a Pd source; 20 more recently, Colacot and co-workers reported its synthesis from Caḿpora and Palma's palladacycle E. 19 In addition to solution-phase characterization, we obtained solid-state molecular structures for all three new OACs. Complexes 3 and 4 are isostructural, mononuclear pseudosquare-planar complexes, with the fourth coordination site occupied by the second pyrazole ring through its π-system; this is analogous to one of the aforementioned tBuBippyPhos OACs.…”

“…Palladium-catalyzed cross-coupling reactions continue to be among the most important methods for C–C and C–heteroatom bond formation. − The canonical catalytic mechanism consists of three general stepsoxidative addition, (trans)metalation, and reductive eliminationwhere oxidative addition is often the rate- and/or selectivity-determining step. − Palladium oxidative addition complexes (OACs), generated by R–X addition to Pd 0 , play a significant role in cross-coupling catalysis (Figure ). ,− In addition to their importance in mechanistic studies of cross-coupling reactions, these complexes are now being exploited as robust and superior (pre)catalysts in specific cases. − Notably, Buchwald and co-workers have incorporated sterically demanding biarylphosphine ligands in OACs (referred to Buchwald G6 precatalysts) and demonstrated their use for various cross-couplings ( A ). ,,, OACs can also be used for late-stage functionalization of complex molecules, offering substantial advantages in drug discovery efforts ( B ) …”