Photocatalyzed Benzylic Fluorination: Shedding “Light” on the Involvement of Electron Transfer

Abstract

The photocatalyzed oxidation of benzylic compounds by 1,2,4,5-tetracyanobenzene (TCB) in the presence of Selectfluor provides a synthetically efficient route to electron deficient, less substituted, and otherwise inaccessible benzylic fluorides. The virtue of this system is multifold: it is metal-free and mild, and the reagents are inexpensive. Mechanistically, the data suggest the intimate formation of intermediate radical cations in the key radical forming step, as opposed to a concerted hydrogen atom transfer process.

Application of Benzylic C-H Fluorination for the Formal Synthesis of syn-α, β-Difluoro-γ-amino Acid

“…4 Si (δ 0.0) as an internal standard. 13 C NMR chemical shifts were determined relative to CDCl 3 (δ 77.0). 19 F NMR chemical shifts were determined relative to PhCF 3 (δ -62.7) as an external standard.…”

“…In a parallel, the research groups of Chen, [11] Inoue [8] Lectka, [12,13] Kappe [14] group achieved benzylic C-H bonds fluorination with the aid of visible light in the presence of an organocatalyst such as diarylketones, N,N-dihydroxypyromellitimide and 1,2,4,5-tetracyanobenzene. Method without using transition-metal catalysts and organocatalysts has also been developed.…”

Site‐Selective Approach to β‐Fluorination: Photocatalyzed Ring Opening of Cyclopropanols

“…Our laboratory recently unveiled a photocatalyzed procedure for the monofluorination of aliphatic 1d and benzylic 1g substrates by using the inexpensive photosensitizer 1,2,4,5‐tetracyanobenzene (TCB) along with Selectfluor as a source of atomic fluorine 4. This work was accompanied by a number of alternative sp 3 CH fluorination methods by using photosensitizers, such as fluorenone, 2d acetophenone, 2f anthraquinone, 2h and decatungstate ions.…”

“…2k Preliminary mechanistic experiments on our benzylic substrates suggest that the reaction proceeds through the formation of a radical‐cation intermediate that is rapidly (if not simultaneously) deprotonated to the corresponding benzylic radical (subsequently fluorinated by Selectfluor). 1g With this in mind, we deduced that a similar photochemical system may be amendable to substituted cyclopropanol‐based starting materials, because: 1) these compounds are known to form radical cations under mild irradiation in the presence of photooxidants due to their high‐lying HOMOs5 (release of strain energy being the thermodynamic driving force); and 2) the ring opening of radicals generated from cyclopropanols followed by halogen‐atom transfer is a well‐documented process to access β‐halo ketones (or enones) 6. In the calculated structure of the representative radical cation shown in Figure 1, elongation (to 2.02 Å) of the weakest CC bond between the C(Me)(OH) and C(H)(Me) fragments is observed.…”

Mono‐ and Difluorination of Benz­ylic Carbon Atoms

“…[34] The reaction takes place under N 2 with the aid of light radiation, leading to benzylic monofluorinated products with yields ranging from 28-65 % (Scheme 26, a). TCB, upon photolysis, is responsible for abstracting electrons from aryl substrates of type 1, thus leading to cationic radical species of type 20a.…”