Showing papers by "Georgios C. Vougioukalakis published in 2023"
TL;DR: In this paper , hexafluoroisopropanol (HFIP) is shown to be a uniquely simple tool for gold-catalyzed cycloisomerization, rendering the use of external activators obsolete and leading to highly active catalytic systems with ppm levels of catalyst loading in certain cases.
Abstract: Despite the unique position of gold catalysis in contemporary organic synthesis, this area of research is notorious for requiring activators and/or additives that enable catalysis by generating cationic forms of gold catalysts. Cycloisomerization reactions occupy a significant portion of the gold-catalyzed reaction space, while they represent a diverse family of reactions that are frequently utilized in synthesis. Herein, hexafluoroisopropanol (HFIP) is shown to be a uniquely simple tool for gold-catalyzed cycloisomerizations, rendering the use of external activators obsolete and leading to highly active catalytic systems with ppm levels of catalyst loading in certain cases. HFIP assumes a dual role as a solvent and an activator, operating via the dynamic activation of the Au–Cl bond through hydrogen bonding, which initiates the catalytic cycle. This special mode of catalysis can enable efficient and scalable cyclization reactions of propargylamides and ynoic acids with simple [AuCl(L)] complexes. A thorough screening of ancillary ligands and counter anions has been performed, establishing this methodology as an alternative to elaborate ligand/catalyst design and to the use of activators. Additionally, this concept is applied in C–C bond-forming cycloisomerization reactions leading to 2H-chromenes and to the design of catalytic systems for sequential or one-pot transformations leading to activated ketoesters, a functionalized N-heterocyclic carbene (NHC) precursor salt, and a compound bearing the bioactive indole core, among others. Importantly, through mechanistic investigations, including a “snapshot” of the species of interest in the solid state, we were able to unambiguously detect the key H-bonding interaction between HFIP and the gold catalyst, shedding light on the intermolecular mode of activation that enables catalysis. In the cases examined herein, HFIP is not only an excellent solvent but also a potent activator and a valuable synthetic handle when incorporated into functional groups of products.
TL;DR: In this article , the authors describe the synthesis and characterization of N-heterocyclic carbene (NHC)-based Au(I) complexes, with and without pendant coordinating groups, and their reactivity in the presence of different oxidants.
Abstract: The Lewis-acidic character and robustness of NHC-Au(I) complexes enable them to catalyze a large number of reactions, and they are enthroned as the catalysts of choice for many transformations among polyunsaturated substrates. More recently, Au(I)/Au(III) catalysis has been explored either by utilizing external oxidants or by seeking oxidative addition processes with catalysts featuring pendant coordinating groups. Herein, we describe the synthesis and characterization of N-heterocyclic carbene (NHC)-based Au(I) complexes, with and without pendant coordinating groups, and their reactivity in the presence of different oxidants. We demonstrate that when using iodosylbenzene-type oxidants, the NHC ligand undergoes oxidation to afford the corresponding NHC=O azolone products concomitantly with quantitative gold recovery in the form of Au(0) nuggets ~0.5 mm in size. The latter were characterized by SEM and EDX-SEM showing purities above 90%. This study shows that NHC-Au complexes can follow decomposition pathways under certain experimental conditions, thus challenging the believed robustness of the NHC-Au bond and providing a novel methodology to produce Au(0) nuggets.
TL;DR: In this paper , the three-component coupling of aldehydes or ketones with amines and alkynes, commonly known as A3 or KA2 coupling, is a convenient, highly efficient strategy for the synthesis of propargylamines, a family of compounds with multifaceted chemical behavior.
TL;DR: The 4-RN-1,3-Ar2-imidazolium salt was metalated by AuI at the C2-, C5- and 4RN positions depending on the reactants and conditions employed as discussed by the authors .
Abstract: The 4-RN-1,3-Ar2-imidazolium salt, R = iPr, tBu, Ar = Mes, Dipp, Mes = mesityl, Dipp = 2,6-bis-diisopropyl-phenyl was metalated by AuI at the C2-, C5- and 4-RN positions depending on the reactants and conditions employed; a rare direct rearrangement of a AuI aminide to an abnormal imidazol-5-ylidene AuI complex was also observed and based on a DFT study it may involve TfO- facilitated H+ transfer.