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

Abstract

HF transfer reactions between organic substrates are potentially useful transformations. Such reactions require the development of catalytic systems that can promote both defluorination and fluorination steps in a single reaction sequence. Herein, we report a catalytic protocol in which an equivalent of HF is generated from a perfluoroarene | nucleophile pair and transferred directly to an alkyne. The reaction is catalyzed by [Au(IPr)N i Pr 2 ] (IPr = N , N ′-1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). HF transfer generates two useful products in the form of functionalized fluoroarenes and fluoroalkenes. Mechanistic studies (rate laws, KIEs, density functional theory (DFT) calculations, competition experiments) are consistent with the Au(I) catalyst facilitating a catalytic network involving both concerted S N Ar and hydrofluorination steps. The nature of the nucleophile impacts the turnover-limiting step. The cS N Ar step is turnover-limiting for phenol-based nucleophiles, while protodeuaration likely becomes turnover-limiting for aniline-based nucleophiles. The approach removes the need for direct handling of HF reagents in hydrofluorination and offers possibilities to manipulate the fluorine content of organic molecules through catalysis.

Synthesis of Carbene‐Metal‐Amido (CMA) Complexes and Their Use as Precatalysts for the Activator‐Free, Gold‐Catalyzed Addition of Carboxylic Acids to Alkynes

“…The application of CMAs in photo‐emissive materials and in medicinal chemistry have been documented but their use in the catalysis has been rarely discussed [47,52,53] . As previously mentioned, the use of Au I ‐NHC compounds as catalysts in the addition of carboxylic acids to alkynes has been reported as effective and affords enol‐esters with complete stereoselectivity.…”

“…We next investigated the scope of the protocol by diversifying the structure with NH‐containing heterocycles (Scheme 2). Our interest in this variant comes from recently reported Au‐based CMA complexes bearing various N‐heterocycles that have displayed anti‐proliferative properties superior to that of cis ‐platin [47,52] . Using [Au(BIAN‐IPr)Cl] as the model starting material, complexes ( 3 a – 3 d ) were obtained in good to excellent yields without modification of the optimized reaction conditions.…”

“…Our interest in this variant comes from recently reported Au-based CMA complexes bearing various N-heterocycles that have displayed anti-proliferative properties superior to that of cis-platin. [47,52] Using [Au(BIAN-IPr)Cl] as the model starting material, complexes (3 a-3 d) were obtained in good to excellent yields without modification of the optimized reaction conditions. X-ray diffraction studies on single crystals confirmed the atom connectivity in 3 b.…”

Hydrofluorination of Alkynes: From (E) to (Z)

“…In a different strategy, Crimmin and co-workers (Imperial College London) developed conditions using a gold-catalyzed polyfluoroarene functionalization reaction to perform the hydrofluorination of an alkyne (Scheme 13). [25] They demonstrated the reaction's efficacy with a variety of perfluoroarenes and nucleophiles and enabled the synthesis of various internal symmetrical and non-symmetrical fluoroalkenes in yields of 41 to 89 %. In this case, the HF molecule that was added to the alkyne came from S N Ar between the perfluoroarene (RÀ F) and the nucleophile (HÀ X).…”

Trendbericht Anorganische Chemie 2023: Nebengruppen, Bioanorganik und Koordinationschemie

“…Crimmin und Mitarbeiter verbanden die Hydrofluorierung von Alkinen mit der Funktionalisierung von hochfluorierten Aromaten mit Phenolen oder Aminen (Abbildung 9b). 28)…”