Hydroxy-directed fluorination of remote unactivated C(sp3)–H bonds: a new age of diastereoselective radical fluorination (original) (raw)
Chemical Reviews, 2015
ABSTRACT C-F activation of highly fluorinated molecules can be an inspiring tool to access unique fluorinated building blocks. The approach involves hydrodefluorination reactions; element-carbon bonds other than C-H bonds can also be generated. Transition-metal-mediated C-F bond activations which involve a cleavage of a C-F bond in polyfluorinated molecules and its transformation into carbon- element bonds, excluding hydrodefluorination or defluorination reactions. On the other hand, fluorido complexes can also be crucial to complete a catalytic process, because of the higher reactivity of a fluorido ligand at d8-complexes. The catalytic generation of C-Si and C-B bonds is noteworthy, because the products might be very useful starting compounds for further transformations. Although carbon-fluorine bond activation reactions of fluoroalkenes have been thoroughly studied earlier, their functionalization via hydrodefluorination reactions is by far more explored than any other C-F bond transformations.
Photoinduced Remote Functionalisations by Iminyl Radical Promoted C-C and C-H Bond Cleavage Cascades
Angewandte Chemie (International ed. in English), 2018
A photoinduced cascade strategy leading to a variety of differentially functionalised nitriles and ketones has been developed. These reactions rely on the oxidative generation of iminyl radicals from simple oximes. Radical transposition by C(sp)-(sp) and C(sp)-H bond cleavage gives access to distal carbon radicals that undergo S2 functionalisations. These mild, visible-light-mediated procedures can be used for remote fluorination, chlorination, and azidation, and were applied to the modification of bioactive and structurally complex molecules.
Radical Fluoroalkylation Reactions
ACS Catalysis
Recent protocols and reactions for catalytic radical perfluoroalkylations (R F = C n F 2n+1 , n ≥ 2) will be described. The production of R F radicals that effect both addition and substitution reactions on organic substrates can be realized through a range of diverse methods such as the well-established visible light transition metal-mediated photocatalysis, organic dye-photocatalyzed reactions, by Electron Donor Acceptor (EDA) complexes or more recently through Frustrated Lewis Pairs (FLP). Thus, perfluoroalkylation reactions of carboncarbon multiple bonds, isocyanides, nitrones, hydrazones, β-ketoesters, αcyano arylacetates, sulfides, and (hetero)arenes will be described. Specially emphasis will be made on examples published after 2015 where higher fluorinated series of fluoroalkylating reagents are studied.
Direct arene C–H fluorination with 18F− via organic photoredox catalysis
Science, 2019
Positron emission tomography (PET) plays key roles in drug discovery and development, as well as medical imaging. However, there is a dearth of efficient and simple radiolabeling methods for aromatic C–H bonds, which limits advancements in PET radiotracer development. Here, we disclose a mild method for the fluorine-18 (18F)–fluorination of aromatic C–H bonds by an [18F]F− salt via organic photoredox catalysis under blue light illumination. This strategy was applied to the synthesis of a wide range of 18F-labeled arenes and heteroaromatics, including pharmaceutical compounds. These products can serve as diagnostic agents or provide key information about the in vivo fate of the labeled substrates, as showcased in preliminary tracer studies in mice.
Practical and Selective sp 3 C−H Bond Chlorination via Aminium Radicals
Angewandte Chemie, 2021
The introduction of chlorine atoms into organic molecules is fundamental to the manufacture of industrial chemicals, the elaboration of advanced synthetic intermediates and also the finetuning of physicochemical and biological properties of drugs, agrochemicals and polymers. We report here a general and practical photochemical strategy enabling the site-selective chlorination of sp 3 C-H bonds. This process exploits the ability of protonated Nchloroamines to serve as aminium radical precursors and also radical chlorinating agents. Upon photochemical initiation, an efficient radical-chain propagation is established allowing the functionalization of a broad range of substrates due to the large number of compatible functionalities. The ability to synergistically maximize both polar and steric effects in the H-atom transfer transition state through appropriate selection of the aminium radical has provided the highest known selectivity in radical sp 3 C-H chlorination.
Photochemical & Photobiological Sciences, 2008
To further explore the nature of the photo-Favorskii rearrangement and its commitment to substrate photorelease from p-hydroxyphenacyl (pHP), an array of ten new fluorinated pHP c-aminobutyric acid (GABA) derivatives was synthesized and photolyzed. The effects of fluorine substitution on the chromophore and the photophysical and photochemical properties of these new chromophores were shown to be derived primarily from the changes in the ground state pK a of the phenolic groups. The quantum yields and rate constants for release are clustered around U dis = 0.20 ± 0.05 and k r = 8 ± 7 × 10 7 s −1 (H 2 O), respectively. The triplet lifetimes of the pHP GABA derivatives were concentrated in the range of 0.4-6.0 ns (H 2 O). The corresponding deprotonated conjugate bases displayed reduced efficiencies by 50% or more (one exception) and exhibited a weak fluorescence in pH 8.2 buffer. Pump-probe spectroscopy studies have further defined the rates of intersystem crossing and the lifetimes of the reactive triplet state of the fluoro pHP chromophore.