Dual C–F, C–H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls

Abstract

Multifluorinated biaryls are challenging to synthesize and yet an important class of molecules. Owing to the difficulty associated with selective fluorination, this class of molecules represent a formidable synthetic challenge. An alternative approach to selective fluorination of biaryls is to couple an arene which already possess C–F bonds in the desired location. This strategy has been regularly utilized, relying heavily on traditional cross-coupling strategies which employ organometallics and halides (or pseudohalides) in order to achieve the coupling. Herein, we report conditions for the photocatalytic coupling via the direct functionalization of the C–F bond of a perfluoroarene and C–H bond of the other arene to provide an expedient route to multifluorinated biaryls. The mild conditions and good functional group tolerance enable a broad scope-including access to the anti-Minisci product of basic heterocycles. Finally, we demonstrate the value of the C–F functionalization approach by utilizing the high fluorine content to systematically build complex biaryls that contain between 2–5 Caryl–F bonds via synergistic use of photocatalysis and SNAr chemistry.

Room‐Temperature Arylation of Thiols: Breakthrough with Aryl Chlorides

“…The overlap in the potential range of the oxidation signal of Ir III /Ir II (from −1.55 to −0.78 V) and the reduction signal of PhCl/Ph .− Cl (from −1.27 to −2.22 V) indicates that the process is thermodynamically feasible. The similar reduction of Ar−Cl to the radical anion Ar .− Cl by Ir II in the presence of diisopropylethylamine (DIPEA) was reported by Senaweera and Weaver . The Ar 2 S − anion reacts with II to give the sulfur‐centered radical anion III , and single‐electron transfer from III to Ar 2 S .…”

Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic Compounds

“…7, 9, 12 Although many of the spectra match experiment, two of the structures had large errors (Chart 3, red). Based on the correction described above, revised structures were tested and these match the experimental values within the error expected for our scaling factors.…”

Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control

“…Returning to the problem of multifluorinated arenes, we have previously demonstrated that the perfluoroaryl radical is a powerful intermediate for the functionalization of perfluoroarenes, which can elicit C–F alkylation, 16 arylation, 17 and alkenylation. 18 While the perfluoroaryl radical has proven competent for cross-coupling, the inherent limitation is the regioselectivity of the C–F fragmentation event.…”