Synthesis of Biaryl Phosphine Palladium(0) Precatalysts

Abstract

Well-defined palladium precatalysts have become increasingly important in cross-coupling chemistry. Despite the wide choice of complexes available today, palladium(0) compounds bearing Buchwald’s biaryl phosphines are still under-represented. We present here an efficient and facile synthesis of biaryl phosphine palladium(0) complexes supported by a divinyltetramethyldisiloxane (dvtms) ligand. Starting from commercially available [Pd­(allyl)­Cl]2, a variety of [Pd­(L)­(dvtms)] complexes can be accessed in high yields under mild reaction conditions. Their catalytic activity was tested in Buchwald–Hartwig couplings and found to be very good for both (hetero)­aryl bromides and chlorides.

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

“…37,40 Con-temporaneously, Fantasia and co-workers reported a series of phosphine−Pd−DVDS complexes (DVDS = 1,3-divinyl-1,1,3,3-tetramethyldisiloxane), and demonstrated their efficiency as single-component precatalysts. 41 Herein we report our studies of diazabutadiene (DAB) and phosphine Pd(0) dimethylfumarate (DMFU) complexes in the context of cross-coupling catalysis and high-throughput experimentation. Our hypothesis was that the less stabilizing DMFU ligand would lead to increased catalytic activity compared to MAH-based precatalysts.…”

“…In 2021 we reported DMP DAB–Pd–MAH ( 1 ) as a convenient and active Pd(0) source designed specifically to enable HTE studies ( DMP DAB = N , N ′-bis(2,6- d i m ethyl p henyl) d i a za- b utadiene; MAH = maleic anhydride) . A key strength of this complex is its rapid and quantitative ligand substitution chemistry, enabling reliable in situ formation of phosphine–Pd–MAH species for a wide range of phosphine ligands during catalysis. , We further isolated and characterized several of these phosphine–Pd–MAH complexes and used them as active single-component precatalysts (Figure C). , Contemporaneously, Fantasia and co-workers reported a series of phosphine–Pd–DVDS complexes (DVDS = 1,3-divinyl-1,1,3,3-tetramethyldisiloxane), and demonstrated their efficiency as single-component precatalysts …”

Convenient One-Pot Synthesis of L2Pd(0) Complexes for Cross-Coupling Catalysis

“…Fantasia and co-workers developed a method using allylpalladium chloride dimer to synthesize several Pd(0) precatalysts bearing Buchwald's ligands which could likely be utilized for the synthesis of (tBu 3 P) 2 Pd(0). 48 While some of these procedures could produce (tBu 3 P) 2 Pd(0) in very good yield, the synthesis of this precursor based on our experience requires tedious work up (including recrystallization) with the use of chlorinated solvents. In addition, the synthesis of the complex utilizes CO gas in a reported procedure and the complex turns to green or black if not stored properly.…”

“…Other recent methods for the preparation of ( t Bu 3 P) 2 Pd­(0) were developed using Pd­(II) sources, such as Pd (cod)­bis­[(trimethylsilyl)­methyl]­palladium, Pd­(η 5 -C 5 H 5 )­(η 3 -1-PhC 3 H 4 ), and allylpalladium chloride dimer. , However, syntheses of these precursors are time-consuming and involve loss of precious metal. Although ( t Bu 3 P) 2 Pd­(0) can be made from Pd (cod)­bis­[(trimethylsilyl)­methyl]palladium within 5 min, the process requires cryogenic recrystallizations; in addition, the synthesis and scale-up of (cod)­bis­[(trimethylsilyl)­methyl]­palladium is very tedious with the formation of Pd black during scale-up.…”

Cu Oxamate-Promoted Cross-Coupling of α-Branched Amines and Complex Aryl Halides: Investigating Ligand Function through Data Science

“…The incorporation of α-branched aryl amine (αBAA) substructures in pharmaceutically active molecules can impart beneficial changes in lipophilicity, solubility, conformation, selectivity, and activity compared to nonbranched structures. − As such, a range of methods for the preparation of αBAAs have been developed. − For drug discovery applications, the C–N cross-coupling of aryl halides and branched amines is particularly useful for preparing diverse αBAAs due to the commercial availability of large pools of building blocks . In its modern form, C–N cross-coupling has a broad scope and is operationally simple, − but relatively few examples of C–N cross-coupling using α-branched amines have been reported, − particularly with complex, medicinally relevant substrates. While several studies have focused on Ni- and Pd-catalyzed cross-coupling of primary − and secondary − α-branched amines and aryl halides, this transformation remains under-developed for pharmaceutical applications (Figure A).…”