A general ligand design for gold catalysis allowing ligand-directed anti-nucleophilic attack of alkynes

Abstract

Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding.

Strong Electron-Donating Ligands Accelerate the Protodeauration Step in Gold(I)-Catalyzed Reactions: A Quantitative Understanding of the Ligand Effect

“…An additional notable example has been reported by Zhang et al with the introduction of a basic center in the ligand, in order to direct and promote the nucleophilic attack on the coordinated UHC. 22 In an exhaustive work by Wang et al, 23 the authors experimentally categorized gold-catalyzed reactions and they found that reactions for which the rate-determining step (RDS) is the nucleophile attack are favored by electron-withdrawing ligands which, in contrast, give lower catalytic activities when the protodeauration step is the RDS.…”

Highly Efficient One-Pot Synthesis of 2,4-Disubstituted Thiazoles Using Au(I) Catalyzed Oxidation System at Room Temperature

“…The synthetic and characterization procedures have been described in detail in previous reports [11,27]. …”

“…Several years later, R 3 PAuX (X = trifluoromethanesulphonate, OTf − ) or other weakly coordinating counter ions) demonstrated excellent catalytic performance in Conia-ene [19,20] and hydroarylation [21][22][23] reactions, as well as several carbon-heteroatom bond-forming reactions [24][25][26]. Recently, Zhang's group designed a new complex with the ligand (1,1 -biphenyl)-2-ylphosphine, which was found to be effective in the reaction of acid and alkynes with a turnover number up to 99,000 [27]. In previous articles, we also reported gold complexes with Mor-Dalphos ligands, which show excellent catalytic performance in the synthesis of 2,4-disubstituted thiazoles from terminal alkynes and thioamides [10,11].…”

Soft Propargylic Deprotonation: Designed Ligand Enables Au-Catalyzed Isomerization of Alkynes to 1,3-Dienes

“…13 On the other hand, these ligands have found extensive utility in homogeneous gold catalysis, 14 although Au(I) complexes typically assume a distinctively different linear structure. To this end, there exist enormous yet largely untapped opportunities 15 for the development of novel gold catalysis based on new biphenyl-2-ylphosphine ligands specifically tailored to accommodate the linear Au(I) complexes. Our simple structural modeling revealed, as shown in Figure 1D, that with bulky groups on phosphorus gearing the P–Au–alkyne centroid axis parallel to the pendant phenyl ring the C–C triple bond would lie roughly at the same level as the line defined by C3′ and C5′, suggesting that functionalization of these positions and C4′ would offer unique and potentially novel reactivities to gold chemistry.…”