Mechanisms of Metal-Catalyzed Electrophilic F/CF3/SCF3 Transfer Reactions from Quantum Chemical Calculations
Electrophilic F/CF3/SCF3 transfer reactions have recently emerged as a promising strategy to introduce fluorine substituents to organic compounds at mild conditions with high reactivity and selectivity. Several safe and stable electrophilic reagents have
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Mechanisms of Metal-Catalyzed Electrophilic F/CF3/SCF3 Transfer Reactions from Quantum Chemical Calculations Binh Khanh Mai and Fahmi Himo
Contents 1 2 3 4
Introduction Technical Details Zinc-Catalyzed Aminofluorination of Alkenes Rhodium-Catalyzed Oxyfluorination and Trifluoromethylation of Diazocarbonyl Compounds 5 Reactions with N–F and N–SCF3 Reagents 6 Conclusions References
Abstract Electrophilic F/CF3/SCF3 transfer reactions have recently emerged as a promising strategy to introduce fluorine substituents to organic compounds at mild conditions with high reactivity and selectivity. Several safe and stable electrophilic reagents have been introduced and have found interesting applications in synthetic chemistry. To control the reactivity and selectivity of these reactions, metal catalysts are typically used in combination with the reagents. Herein, we describe our recent efforts to elucidate the detailed mechanisms and origins of selectivity for a number of metal-catalyzed electrophilic F/CF3/SCF3 transfer reactions using density functional theory calculations. Focus is on reactions employing hypervalent fluoroiodine and nitrogen-based reagents, with zinc or rhodium as the metal catalysts. The roles of the metal ions are discussed, and some novel mechanistic ideas have emerged from these calculations that can have bearing on other reactions for introducing fluorinecontaining groups.
B. K. Mai and F. Himo (*) Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden e-mail: [email protected]
B. K. Mai and F. Himo
Keywords Density functional theory (DFT) · Fluorination · Hypervalent iodine · Metal catalyst · Reaction mechanism
1 Introduction Introduction of fluorine substituents can dramatically change the physical and chemical properties of organic compounds, such as their metabolic stability, lipophilicity, and membrane permeability [1, 2]. Accordingly, organofluorine compounds have found numerous applications in, e.g., the pharmaceutical and agrochemical industries [3–7]. In addition, 18F-labelled organic compounds are increasingly applied in medical diagnostics as radiotracers in positron-emission tomography, due to the special radionuclear properties of this isotope [8–10]. The increasing demand for synthetic fluorine-containing organic compounds has led to the emergence of new strategies to introduce fluorine to diverse substrates [11– 17]. Depending on the form of fluorine atom transferred, the introduction of fluorine substituents to organic compounds can be classified as being either nucleophilic, electrophilic, or radical [17–19]. While all three strategies have some advantages and disadvantages in terms of reactivity and selectivity, the use of electrophilic fluorination reagents in combination with metal catalysts constitutes an important trend in fluorination chemistry in recent years and has led to significant breakthroughs [15, 17–27]. A number of stable, safe, and easy-to-handle electrophilic reagents have been developed, such as the ones shown in Scheme 1: (X)–I–F/CF3
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