Gold N‐Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates

Abstract

An efficient and chemoselective methodology deploying gold-N-heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Brønsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailordesigned gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine-and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.

Au(I) Fluorido Phosphine Complexes: Tools for the Hydrofluorination of Alkynes

“…However, no distinct anion influence was observed, [23] on using AgSbF 6 and AgOTf instead of AgBF 4 with [Au(Cl)(SIPr)] as well as [Au(I)(SPhos)] ( 19 ) as catalytic precursors (entries 9–12). The observed yields were mostly lower when compared the literature, [3a,5b,d,e,6b] but higher than reported for [Au(Cl)(PPh 3 )]/AgBF 4 , which showed only a stoichiometric conversion [5a] …”

“…After formation of the vinyl species, the protodeauration should provide the hydrofluorinated compound and the catalytic cycle is completed (Scheme 5). In a recent paper regarding the Au(I) catalyzed hydrofluorination of terminal alkynes with aqueous HF, cationic complexes have also been postulated as intermediates [6b] . In addition to mononuclear intermediates, binuclear species involving Au(I) alkynyl complexes, were proposed.…”

“…characterized the alkyne complex [Au(3‐hexyne)(SIPr)][BF 4 ] (SIPr=1,3‐bis(2,6‐diisopropylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene) as well as the vinyl compounds [Au(R 1 C=C(F)R 2 )(SIPr)] (R 1 =Ph, R 2 =CH 3 as well as R 1 =R 2 =C 2 H 5 ) [5a] . In a recent contribution towards the hydrofluorination of terminal alkynes, the compound [{Au(SIPr)} 2 μ‐OH][FHF] as well as mono‐ and binuclear alkynyl species were identified as potential intermediates [6b] …”

Au(I) Catalyzed HF Transfer: Tandem Alkyne Hydrofluorination and Perfluoroarene Functionalization

“…NBO analysis reveals partial C–H bond formation and C–Au bond breaking in the transition state, while IRC calculations are consistent with the association of the resulting charged fragments {Au(IPr)} + and X – occurring afterward. 59 − 64 The overall transformation is calculated to be exergonic (Δ G ° rxn = −22.6 kcal mol –1 ), with the S N Ar step being turnover-limiting.…”

Vessel effects in organic chemical reactions; a century-old, overlooked phenomenon

“…Furthermore, it has been reported that attempted crystal growth of a gold bifluoride complex in a glass vessel led to the formation of an undesired complex bearing a pentafluorosilicate counterion. 38 The desired bifluoride complex was successfully obtained by instead growing the crystals in a plastic vessel.…”