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

Abstract

Modulable monosulfonyl squaramides have been shown to exert activation of gold(I) chloride complexes through H-bonding in an intermolecular way. Combinations of (PPh3)AuCl or IPrAuCl complexes and an optimal sulfonyl squaramide cocatalyst bearing two 3,5-bis(trifluoromethyl)phenyl groups efficiently catalyzed diverse heterocyclizations and a cyclopropanation reaction, avoiding in all cases undesired side reactions. Computational studies indicate that the Au–Cl bond breaks by transligation to the triple bond in a ternary complex formed by the actual AuCl···HBD catalyst and the substrate.

Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

“…Τhe transformation of 14a into oxazoline 15a is the most widely studied gold-catalyzed reaction exploring novel Au–Cl activation manifolds. − To thoroughly compare our simple system to others of similar nature, representative propargylic amides were subjected to these conditions (Scheme ). Although many of these innovative catalytic systems employ 2 mol % [Au] or higher, − , we purposefully do not exceed 1 mol % loading throughout our studies since the circumvention of expensive additives and activators should not come at the cost of additional quantities of precious gold complexes in order to perform efficient catalysis. Thus, our system is competitive with the state-of-the-art catalytic systems, already having the advantage of lower-than-average catalyst loading .…”

“…We recently contributed to the area by carrying out ligand and counter-anion screening in gold-catalyzed reactions in hexafluoroisopropanol (HFIP), exploiting this solvent’s exceptional hydrogen bond-donor character to develop the first intermolecular H-bonding activation regime . More recently, during the preparation of this manuscript, a report using specially designed squaramides as intermolecular H-bonding activators has appeared …”

Hexafluoroisopropanol (HFIP) as a multifunctional agent in gold-catalyzed cycloisomerizations and sequential transfor-mations

“…[19][20][21][22][23][24][25][26][27] To thoroughly compare our simple system to others of similar nature, representative propargylic amides were subjected to these conditions (Scheme 1). Although many of these innovative catalytic systems employ 2 mol% [Au] or higher, [19][20][21][22][23][24][25]28 we purposefully do not exceed 1 mol% loading throughout our studies, since the circumvention of expensive additives and activators should not come at the cost of additional quantities of precious gold complexes in order to perform efficient catalysis. Thus, our system is competitive with the state-ofthe-art catalytic systems, already having the advantage of lower than average catalyst loading.…”

“…These are slight changes pointing towards the formation of species which are more "cationic" in nature; 8,14 however, combined with the complete picture of the spectra, which involves a significantly different aromatic region in the case of JohnPhos and differences in the relative chemical shifts of the diisopropyl groups of IPr, there is evidence of a different environment in the close vicinity of the ancillary ligands, attributed to HFIP (see the Supplementary Information for spectra). Up to this point there was no clear evidence of hydrogen bonding, and combined with the lack of hard evidence in most cases of intermolecular, dynamic activation of Au-Cl bonds, be it through halogen bonding or a case of intermolecular hydrogen bonding that appeared after our first report on HFIP and during the preparation of this manuscript, 28 the probability of obtaining such evidence seemed low. 82 However, inspired by the work of Gabbaï and co-workers on Au---H-O hydrogen bonds and their data on intermolecular Au-Cl---H-O hydrogen bonding between two molecules of their hydroxyl group-containing complex, 83 we attempted to cocrystallize 1 and 10 with HFIP.…”

“…27 More recently, during the preparation of this manuscript, a report using specially designed squaramides as intermolecular H-bonding activators has appeared. 28 Being aware of the effects of hydrogen bonding on gold catalysis, 29,30 as well as the cases in which Au-Cl containing complexes have been used in catalysis owing to their ligand design rendering them highly electrophilic or enabling their interactions with water or deep eutectic solvents, 19,[31][32][33][34][35][36][37][38][39] we extensively studied the HFIP-based activation mode in order to uncover its underlying mechanism and its true potential. 40,41 HFIP is a solvent that has received significant attention by the chemical community in recent years, because of its recyclability, and H-bonding donor property in combination with its low nucleophilicity, high acidity, and cationstabilizing ability.…”