Studies on the Synthesis of Perfluoroaryl Sulfides and their Application in Desulfurative Nickel-Catalyzed Reductive Cross-Coupling

Abstract

The C−S activation and sulfur removal from native thiols is challenging and limits the application of thiols as typical feedstock materials in organic synthesis despite their natural abundance. Herein, we describe a simple procedure to introduce a per-/polyfluoroaryl moiety, which serves as a redox-active scaffold, into alkyl/aryl thiols using nucleophilic aromatic substitution (SNAr) chemistry to activate the C−S bond. The per-/polyfluoroaryl group acts as an electron acceptor in single electron transfer events to generate radical intermediates through cleavage of the C−S bond of mercaptans and utilize them in nickel-catalyzed reductive cross-coupling reactions. In addition, using computational methods, we shed light on the mechanism of this class of SNAr reaction and show that the preference for a concerted or stepwise mechanistic pathway can be easily rationalized through a Marcus-type argument, as well as consideration of the relative stability of the potential energy surfaces.

Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers

“…On the basis of our previous experiences and the literature on mechanochemical realizations of S N Ar reactions, − and as part of our general policy to search for green methodologies, we conducted a routine experiment under mechanochemical conditions (Table S1, entry 1) in a one-pot fashion, starting from the same substrate 1e . To our content, the evident presence of the target product in the reaction mixture was demonstrated by TLC and confirmed after separation (12% yield).…”