A Convenient Photocatalytic Fluorination of Unactivated CH Bonds

Abstract

Fluorination reactions are essential to modern medicinal chemistry, thus providing a means to block site-selective metabolic degradation of drugs and access radiotracers for positron emission tomography imaging. Despite current sophistication in fluorination reagents and processes, the fluorination of unactivated CH bonds remains a significant challenge. Reported herein is a convenient and economic process for direct fluorination of unactivated CH bonds that exploits the hydrogen abstracting ability of a decatungstate photocatalyst in combination with the mild fluorine atom transfer reagent N-fluorobenzenesulfonimide. This operationally straightforward reaction provides direct access to a wide range of fluorinated organic molecules, including structurally complex natural products, acyl fluorides, and fluorinated amino acid derivatives.

Visible light-promoted metal-free sp3-C–H fluorination

“…The Inoue, 9 Tang, 10 and Hartwig 11 groups have also shown that N -oxyl radical and silver salts can catalyze or promote C–H fluorination. More recently, photolytic activation methods have also been reported by Britton, 12 Lectka, 8c and Tan 13 using decatungstate, 1,2,4,5-tetracyanobenzene (TCB), and anthraquinone (AQN) as the catalyst, respectively.…”

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

“…28) [55]. The reaction was designed on the basis of the documented ability of 10 to abstract hydrogen atoms from saturated organic fragments upon irradiation with light [56].…”

The Uranyl Cation as a Visible‐Light Photocatalyst for C(sp3)−H Fluorination

“…An example is sclareolide: acetophenone 9 (80%/16 turnovers), anthraquinone 10 (77%/39 turnovers), 1,2,4,5-tetracyanobenzene 7 (61%/6.1 turnovers), and TBADT 8 (68%/34 turnovers) all produced mixtures of monofluorinated products in moderate to high yields as compared to the low result observed for the uranium system (26%/26 turnovers, Table 3, Entry 11). Similarly, acetal and ether functional groups are incompatible with the uranyl system, with the dioxolane derived from condensing cyclopentanone with ethylene glycol providing even less reactivity than the parent ketone (Table 3, Entry 12) and tert -butyl methyl ether not producing any fluorinated product.…”

“…Indeed, the recent reports from Lectka, 7 Britton, 8 Chen, 9 and Tan 10 suggests that, despite progress, this transformation is not yet a solved problem. With some exceptions, 11,12,13 recent strategies for selectively fluorinating C sp3 –H bonds have largely recruited photo-hydrogen atom abstraction (HAT) catalysts (denoted [cat]), such as acetophenone, anthraquinone, 1,2,4,5-tetracyanobenzene, and tetra- n -butylammonium decatungstate (TBADT, Figure 1), to generate a carbon-centered radical.…”