Generation of an Aromatic Amide‐Derived Phosphane (Aphos) Library by Self‐Assisted Molecular Editing and Applications of Aphos in Room‐Temperature Suzuki–Miyaura Reactions

Abstract

Aromatic amide-derived phosphanes (Aphos) are hemilabile P,O-coordinating ligands, which, when combined with a Pd precursor, yield a promising precatalyst system for Suzuki-Miyaura cross-coupling reactions. A focused library of Aphos ligands has been constructed for structural optimization, with the target of improving catalytic efficacy. By using microwave irradiation at accurately regulated temperature, an expeditious and reproducible one-pot synthesis and screening protocol was designed and experimentally validated. The success is based on a unique self-assisted molecular editing (SAME) process in which both the substrate and the product molecules catalyze formation of the product. Thus, starting from a 4-chlorobenzamide-derived Aphos as the substrate, parallel reactions with a selected set of arylboronic acids, in the absence of an added external phosphane ligand to Pd, produced a family of structurally edited Aphos ligands. The resultant reaction mixture containing the new Aphos, the Pd species, and the base could be used for in situ screening of the Aphos efficacy in a reference Suzuki-Miyaura coupling reaction. The structures of all Aphos ligands were characterized by 31P NMR spectroscopy and their catalytic profiles in the reference reaction were evaluated by HPLC analysis. These data allowed the identification of an efficient Aphos ligand, capable of promoting room-temperature Suzuki-Miyaura coupling of unactivated and sterically hindered aryl chlorides with arylboronic acids under mildly basic conditions.

Phosphines and related C–P bonded compounds

“…25 Directed lithiation at a site near to an appropriate donor atom has also been widely utilised in the synthesis of new phosphines. Among new systems prepared in this way are the P-chirogenic phenoxaphosphine (19), 26 various 2,6-bis(phosphino)thiophenol derivatives 27 and 1,4bis(phosphino)-2,5-difluoro-3,6-dihydroxybenzenes, 28 a series of modular phosphine-aminophosphine ligands (20) based on a chiral 1,2,3,4-tetrahydro-1-naphthylamine backbone, 29 families of tunable indolylphosphine- (21), 30 t-butylsulfinylphosphine- (22), 31 and o-phosphinoarylamide-(23) 32 ligands and the chiral phosphinoaryl imidazole (24). 33 Donor group-directed metallation has also been used to prepare planar chiral ruthenocenebased phosphino-oxazoline ligands (25) 34 and in a four-step synthesis of the chiral tetraphosphinoferrocene (26).…”

“…39 Attempts to prepare polymeric alkylphosphines by treating (30, R ¼ Me or Ph) with lithiophosphide reagents by inducing nucleophilic ring-opening at carbon failed, the preferred route being attack at phosphorus to form a diphosphide anion, e.g., (31), and an alkene. 40 On the other hand, the established nucleophilic ring opening of epoxides by attack of phosphide anions at carbon has received further application in the synthesis of new sulfur-containing phosphine ligands, e.g., (32), from sugars 41 and a series of modular P-O-P ligands (phosphine-phosphites and phosphine-phosphinites), e.g., (33). 42 Borane-protected lithiophosphide reagents have also been used routinely in the synthesis of the heterocycle-functionalised chiral phosphines (34), 43 (35), 44 (36), 45 and (37).…”

Synthesis of a new palladium salt using N‐benzyl DABCO chloride and its application in Suzuki reaction

“…Over the past two decades, efforts have been made to develop efficient catalytic systems for the Suzuki–Miyaura coupling reaction. In this regard, palladium–phosphine complexes are among the most commonly employed catalysts of choice . However, some of the phosphorous ligands are sensitive to air and moisture and economically and environmentally undesirable due to difficulties with their recovery and the formation of toxic phosphines as byproducts in the reaction .…”

A novel ionic liquid-supported Schiff base ligand applied in the Pd-catalyzed Suzuki–Miyaura coupling reaction

“…[1][2][3][4] In the past few years, many attempts have been made to develop effective palladium complexes, which can act as highly active catalysts for this homogeneous reaction. Among them, various forms of ligands such as phosphorous ligands, 5-8 P, O-based ligands, [9][10] bis(thiourea) ligands, of organic, inorganic, and organometallic compounds favoring the formation of a homogeneous catalytic system. However, many palladium (II)-catalyzed coupling reactions are carried out in ILs in the presence of bulky phosphine ligands, [16][17][18] which are sensitive to both oxygen and moisture, and lead to catalyst decomposition.…”