Recent Advances in C-F Bond Cleavage Enabled by Visible Light Photoredox Catalysis

Abstract

The creation of new bonds via C-F bond cleavage of readily available per- or oligofluorinated compounds has received growing interest. Using such a strategy, a myriad of valuable partially fluorinated products can be prepared, which otherwise are difficult to make by the conventional C-F bond formation methods. Visible light photoredox catalysis has been proven as an important and powerful tool for defluorinative reactions due to its mild, easy to handle, and environmentally benign characteristics. Compared to the classical C-F activation that proceeds via two-electron processes, radicals are the key intermediates using visible light photoredox catalysis, providing new modes for the cleavage of C-F bonds. In this review, a summary of the visible light-promoted C-F bond cleavage since 2018 was presented. The contents were classified by the fluorosubstrates, including polyfluorinated arenes, gem-difluoroalkenes, trifluoromethyl arenes, and trifluoromethyl alkenes. An emphasis is placed on the discussion of the mechanisms and limitations of these reactions. Finally, my personal perspective on the future development of this rapidly emerging field was provided.

Reduction of SF5CF3viairidium catalysis: radical trifluoromethylation of aromatics

“…This step is followed by the SET from the reduced [Ir(dtbbpy)(ppy) 2 ] (E pc = À1.51 V vs. SCE) 23,24 to SF 5 CF 3 . Alternatively, [Ir(dtbbpy)(ppy) 2 ] + * (E pc = À0.96 V vs. SCE) 23,24 reduces SF 5 CF 3 and the generated [Ir(dtbbpy)(ppy) 2 ] 2+ is then reduced by NEt 3 in an oxidative quenching cycle. Note that photocatalytic conversions of [Ir(dtbbpy)(ppy) 2 ] + have a tendency to proceed via a reductive quenching cycle.…”

Visible-Light-Induced Monofluoroalkenylation and gem-Difluoroallylation of Inactivated C(sp3)–H Bonds via 1,5-Hydrogen Atom Transfer (HAT)

“…Both isomers: 19 F NMR (377 MHz, CDCl 3 ) δ −99.76 (d, J = 26.9 Hz, 0.58F), −111.28 (d, J = 38.2 Hz, 0.42F). Both isomers: 13 7,4,. Pale-yellow oil obtained by column chromatography (PE/EA = 3:1−1:1); 85% yield; 50.2 mg. TLC R f = 0.40 (PE/EA = 1:1, v/v).…”

“…Both isomers (E/Z = 75:25): 1 H NMR (400 MHz, CDCl 3 ) δ 7.62−7.52 (m, 2H), 7.46− 7.17 (m, 2H), 6.30 (d, J = 26.3 Hz, 0.75H), 5.61 (two brs, 1H), 5.55 (d, J = 39.6 Hz, 0.25H), 2.78 (d, J = 4.9 Hz, 2.25H), 2.76 (d, J = 4.9 Hz, 0.75H), 2.18−2.11 (m, 2H), 1.90−1.85 (m, 0.50H), 1.79−1.75 (m, 1.50H), 1.20 (s, 1.50H), 0.96 (s, 4.50H). Both isomers: 19 4,phenyl]hex-5-enamide (3n). Colorless oil obtained by column chromatography (EA); 61% yield; 40.4 mg.…”

“…Synthesis of 7,4,15d To a 10 mL oven-dried sealed tube, 5b (107.2 mg, 0.3 mmol) and Selectfluor BF 4 (138.2 mg, 0.39 mmol) were added, followed by addition of CH 3 CN (3.0 mL) and H 2 O (43.2 mg, 2.4 mmol) under a nitrogen atmosphere. The reaction mixture was allowed to stir at 40 °C for 20 h. Then, the solvent was removed under vacuum, and the crude mixtures were purified by flash column chromatography to afford product 7 (103.8 mg, 88%).…”

“…It is highly ideal to realize the direct monofluoroalkenylation of C−H bonds with easily accessible gem-difluoroalkenes which will be an atom-and step-economic and practical approach. 4 However, the existing methods have mainly focused on monofluoroalkenylation with C(sp 2 )−H bonds, such as the S N V reaction 5 with activated C(sp 2 )−H bonds and transitionmetal (Rh, Ru, Mn, and Co)-catalyzed C(sp 2 )−H bond monofluoroalkenylation with the assistance of the directing group (DG) 6 (Scheme 1b). However, the methods for monofluoroalkenylation of C(sp 3 )−H bonds are quite challenging and limited to activated C(sp 3 )-H bonds.…”