Co-Catalyzed Hydrofluorination of Alkenes: Photocatalytic Method Development and Electroanalytical Mechanistic Investigation

Abstract

The hydrofluorination of alkenes represents an attractive strategy for the synthesis of aliphatic fluorides. This approach provides a direct means to form C(sp 3 )−F bonds selectively from readily available alkenes. Nonetheless, conducting hydrofluorination using nucleophilic fluorine sources poses significant challenges due to the low acidity and high toxicity associated with HF and the poor nucleophilicity of fluoride. In this study, we present a new Co(salen)-catalyzed hydrofluorination of simple alkenes utilizing Et 3 N•3HF as the sole source of both hydrogen and fluorine. This process operates via a photoredoxmediated polar-radical-polar crossover mechanism. We also demonstrated the versatility of this method by effectively converting a diverse array of simple and activated alkenes with varying degrees of substitution into hydrofluorinated products. Furthermore, we successfully applied this methodology to 18 Fhydrofluorination reactions, enabling the introduction of 18 F into potential radiopharmaceuticals. Our mechanistic investigations, conducted using rotating disk electrode voltammetry and DFT calculations, unveiled the involvement of both carbocation and Co IV −alkyl species as viable intermediates during the fluorination step, and the contribution of each pathway depends on the structure of the starting alkene.

Cobalt Hydride-Catalyzed Hydroalkynylation of Alkenes with Alkynyl Trifluoroborates

“…Then, a cobalt­(III) hydride-mediated reversible HAT with alkenes 1 furnishes the alkylcobalt­(III) complex E through intermediate D . ,,,− , Subsequently, a single-electron oxidation occurs between the resulting alkylcobalt­(III) complex E and cobalt­(III) cationic species (path a and b) or oxidant NFSI (path c) in the system, as illustrated in Scheme f, to form the pivotal alkyl Co­(IV) intermediate F . In recent literature, the formation of Co­(IV)-alkyl complexes from the corresponding Co­(III)-alkyl has been interrogated by Shigehisa, Pronin, Zhu, Lin, Carreira, Holland, and ourselves to enable nucleophilic substitution. Definitive evidence for the alkylcobalt­(IV) complex has also been elucidated by Holland and co-workers through experiments and DFT calculations, shedding light on the electronic structure, energetics, and reactivity of Co­(IV) in radical-polar crossover MHAT catalysis .…”

“…Both the LCo(III)-N(SO 2 Ph) 2 species and alkynyl cobalt(III) species have been detected by high-resolution mass spectrometry (HRMS) (see Figure S1 in Supporting Information). Then, a cobalt(III) hydride-mediated reversible HAT with alkenes 1 furnishes the alkylcobalt(III) complex E through intermediate D . ,,,− , Subsequently, a single-electron oxidation occurs between the resulting alkylcobalt(III) complex E and cobalt(III) cationic species (path a and b) or oxidant NFSI (path c) in the system, as illustrated in Scheme f, to form the pivotal alkyl Co(IV) intermediate F . In recent literature, the formation of Co(IV)-alkyl complexes from the corresponding Co(III)-alkyl has been interrogated by Shigehisa, Pronin, Zhu, Lin, Carreira, Holland, and ourselves to enable nucleophilic substitution.…”

“…Based on the mechanistic investigations described above and previous literature, ,,,− a plausible reaction mechanism for the cobalt-catalyzed hydroalkynylation reaction of alkenes is proposed (Scheme ). Initially, Co­(III)-F intermediate A is produced by oxidation of the Co­(II) catalyst with NFSI. , This intermediate subsequently undergoes transmetalation with hydrosilane (e.g., TMDSO) to furnish the putative Co­(III)-H species B . ,, During this step, cobalt­(III)-N­(SO 2 Ph) 2 complex C and silyl fluoride are also generated.…”

“…The intermediate alkyl radicals generated from the MHAT of alkenes can reversibly bind to form alkylcobalt­(III) species and further undergo chemical or electrochemical oxidation to access the corresponding alkyl cobalt­(IV) complexes, which have been shown to demonstrate a high level of electrophilicity for reacting with nucleophiles via an S N 2-like process . Various nucleophilic partners, including alcohols, carboxylic acids, amides, sulfonamides, isoureas, and thiophenols among others, have been implemented in this cobalt-catalyzed alkene radical-polar crossover MHAT reaction. ,,− In sharp contrast, the application of this protocol with carbon-based nucleophiles for C–C bond formation is particularly rare. , This led us to consider the application of this MHAT strategy that mimics the hydrofunctionaliation of alkenes with nucleophilic alkynyl reagents to provide a mechanically innovative approach for olefin hydroalkynylation . In this work, we have realized this design and described a cobalt hydride HAT-enabled alkene hydroalkynylation platform that utilizes nucleophilic potassium alkynyl trifluoroborates as alkynyl transfer agents to promote C­(sp 3 )-C­(sp) bond formation (Scheme C).…”

γ-Amino C(sp3)–H Functionalization of Aliphatic Amines through a Light-Driven Triple Catalysis

“…There are two possible pathways: oxidation of a benzyl radical to an benzyl cation and oxidation of a benzyl cobalt­(III) to a benzyl cobalt­(IV). According to previous report, we compared the stability of a benzyl cobalt­(III) and a benzyl radical by use of DFT calculation (Figure D). The results indicated that a benzyl radical is more stable than a benzyl cobalt­(III), which supports the idea that oxidation of the benzyl radical is feasible.…”