Halogen Bond Activation in Gold Catalysis

Abstract

Gold catalysis has, over the past decades, provided innovative organic transformations under mild conditions with high chemoselectivities. It receives steadily growing attention thanks to its wide synthetic applicability. The catalytically active form, [L n -Au] + , of ligated gold complexes, [L n -Au-Cl], is formed via halide abstraction. This is typically achieved by anion exchange upon the addition of an appropriate silver salt to the reaction mixture. Herein, an alternative silver-free route for gold activation is presented, making use of halogen bonding to promote halide abstraction. We demonstrate that a catalytic amount of a strong halogen bond donor efficiently activates both gold(I) and gold(III) catalysts. Following the reaction, both the catalyst and the activator are easily recovered. Importantly, this not only reduces the metal waste in a gold-catalyzed process but also enables its upscaling, possibly opening new avenues for its use in industrial settings. Gold is an expensive and limited resource, and its recyclability is of supreme importance. Based on systematic reaction kinetics, NMR spectroscopic, and computational investigations, we describe the mechanism of halogen bond-activated gold(I/III) catalysis using cyclopropanation as a model reaction. Our discovery paves the way for the development of gold-mediated transformations that allow recycling of the precious gold catalyst and that may thereby become useful also for the large-scale generation of complex molecules.

Cooperativity between the Silver(I) and Iodine(III) Centers in Electrophilic Activation of Organic Substrates

“…Previous works of other authors, 25,50,51 as well as our observations indicate that utilization of a noble metal halides or their other halogen-containing species results in abstraction of the halide ligand by the iodolium cation, which suppresses the electrophilicity of the latter and typically results in precipitation of the organic residues almost insoluble in many organic solvents. Thus, it was found by us that Cat4 OTf reacts with K2[PtCl4] in H2O to give insoluble in H2O, EtOH, Me2CO, and CHCl3 platinum-containing residue and Cat4 Cl (which also almost insoluble in these solvents).…”

“…Thus, tetratopic noncharged iodine(I)-based XB-donors were utilized as a template for ruthenium(II)-catalyzed macrocyclization of olefines, 49 whereas cationic iodine(I)-and iodine(III)-based XB-donors were utilized as a chloride-abstracting agents for in situ activation of gold(I)-containing catalysts. 25,50,51 These two examples represent an application of XB donors in the systems involving noble metal catalysis but none of them utilize the XB donor for the electrophilic activation of a reaction substrate.…”

Silver-Free Gold-Catalyzed Heterocyclizations through Intermolecular H-Bonding Activation

“…Typically, silver salts have played the role of chloride scavengers, although their light instability, hygroscopic nature, and the “silver effect” in catalysis often represent major drawbacks . Several approaches have been developed to overcome these practical issues, including the use of alternative alkali metal borates and copper salts, self-activation of gold­(I) chloride complexes bearing specially designed ancillary ligands, and, more recently, H-bonding activation by certain solvents such as hexafluoroisopropanol (HFIP) as well as via halogen-bonding catalysis . Great efforts have been focused on the design and synthesis of [L–Au-Cl] complexes possessing multifunctional phosphine or NHC ligands bearing H-bond donor (HBD) groups (Figure , top), such as trifluoroacetamido ( A ), p -tolyl-sulfonamido ( B ), and bidentate HBD groups ( C ) .…”

“… 2 Several approaches have been developed to overcome these practical issues, 3 including the use of alternative alkali metal borates and copper salts, 4 self-activation of gold(I) chloride complexes bearing specially designed ancillary ligands, 3 and, more recently, H-bonding activation by certain solvents such as hexafluoroisopropanol (HFIP) 5 as well as via halogen-bonding catalysis. 6 Great efforts have been focused on the design and synthesis of [L–Au-Cl] complexes possessing multifunctional phosphine or NHC ligands bearing H-bond donor (HBD) groups ( Figure 1 , top), such as trifluoroacetamido ( A ), 7 p -tolyl-sulfonamido ( B ), 8 and bidentate HBD groups ( C ). 9 These reports constitute an excellent proof of concept of a synergistic Au(I)/ion-pairing strategy based on chloride abstraction from an electrophilic metal center by classical H-bond donors.…”

Activation of metal-involved halogen bonds and classical halogen bonds in gold(i) catalysis

“…Gold catalysis has undergone rapid development in the past two decades. [1][2][3][4][5][6] In gold(I) catalysis, a cationic LAu + (L = phosphine, phosphite, NHC, and other) complex is usually the catalytically active species, and the counteranions affect the catalytic activity. [7][8][9][10][11] Currently, the activation of the gold(I) chloride catalyst [LAuCl] to obtain the LAu + complex is generally performed by chloride abstraction.…”