Hydroarylation of Arenes via Reductive Radical-Polar Crossover

Abstract

A photocatalytic system for the dearomative hydroarylation of benzene derivatives has been developed. Using a combination of an organic photoredox catalyst and an amine reductant, this process operates through a reductive radical-polar crossover mechanism where aryl halide reduction triggers a regioselective radical cyclization event, followed by anion formation and quenching to produce a range of complex spirocyclic cyclohexadienes. This light-driven protocol functions at room temperature in a green solvent system (aq. MeCN) without the need for precious metal-based catalysts or reagents or the generation of stoichiometric metal byproducts.

Synthesis of Spirocyclic Piperidines by Radical Hydroarylation

“…Radical termination through HAT delivers the desired hydroarylation product 1. Evidence supporting this proposal includes a high observed rate of P1* luminescence quenching by the amine base (K SV ≈1700), 17 indicating that radical formation probably occurs through reductive quenching. 17 To probe the nature of radical termination in this process, we conducted a series of isotopic labeling studies.…”

“…Evidence supporting this proposal includes a high observed rate of P1* luminescence quenching by the amine base (K SV ≈1700), 17 indicating that radical formation probably occurs through reductive quenching. 17 To probe the nature of radical termination in this process, we conducted a series of isotopic labeling studies. We found that, when the amine reductant was replaced with triethylamine-d 15 , deuterium transfer occurred from the amine to product 1, albeit with moderate fidelity (~1:1 D/H).…”

Photoinduced Dearomatizing Three‐Component Coupling of Arylphosphines, Alkenes, and Water

“…Recently, photoredox‐catalyzed dearomatization reactions have been explored [5] . For example, Jui [5e] and Stephenson [5f] demonstrated that the well‐designed arene substrates were dearomatized through intramolecular carbocyclization. König [5c] and Miyake [5h] reported photoredox‐catalyzed Birch‐type reduction of arenes, which necessitated sacrificial reductants.…”

Recent Advances in the Construction of Spiro Compounds via Radical Dearomatization

“…In 2020, a photochemical approach for the dearomative functionalization of benzene derivatives was developed by Jui's group, which operated through a highly selective radical hydroarylation pathway (Scheme 28). [40k] This established method underwent a reductive radical‐polar crossover mechanism, in which aryl halide reduction triggered a regioselective 5‐ exo ‐trig radical cyclization. Then, the reduction of cyclohexa dienyl radical 132 would generate dienyl anion 133 , followed by protonation and finally producing spirocyclic cyclohexadienes 130 .…”