Visible-Light-Mediated Tandem Difluoromethylation/Cyclization of Alkenyl Aldehydes toward CF₂H-Substituted Chroman-4-one Derivatives

Abstract

An efficient and facile visible-light-mediated tandem difluoromethylation/cyclization of alkenyl aldehydes, with easily accessible and air-stable [Ph3PCF2H]+Br– as the difluoromethylation reagent, has been established. A range of CF2H-substituted chroman-4-one skeletons and their derivatives, such as 2,3-dihydroquinolin-4­(1H)-ones, chroman, 3,4-dihydronaphthalen-1­(2H)-one, 2,3-dihydrobenzofuran, and 2,3-dihydro-1H-inden-1-one, are efficiently produced in moderate to good yields with excellent chemoselectivity under mild reaction conditions.

Recent Advances in Visible Light‐Mediated Radical Fluoro‐alkylation, ‐alkoxylation, ‐alkylthiolation, ‐alkylselenolation, and ‐alkylamination

“…In 2022, Yang and coworkers showcased the visible light-mediated synthesis of difluoromethyl chroman-4-one derivatives utilizing 5 and Ir(ppy) 3 . [70] With this protocol, the authors also demonstrated the synthesis of difluoromethylated 2,3-hydroquinolin-4(1H)-one, 3,4-dihydronapthalen-1(2H)-one, chroman, 2,3-dihydrobenzofuran, and 2,3-dihydro-1H-inden-1-one utilizing the reported conditions. Wu and coworkers detailed the synthesis of difluoromethylated quinazolinones also utilizing 5 and Ir-(ppy) 3 .…”

“…Triphenyldifluoromethylphosphonium bromide ( 5 ) has also been utilized in many difluoromethyl addition‐cyclization protocols (Scheme 18). In 2022, Yang and coworkers showcased the visible light‐mediated synthesis of difluoromethyl chroman‐4‐one derivatives utilizing 5 and Ir(ppy) 3 [70] . With this protocol, the authors also demonstrated the synthesis of difluoromethylated 2,3‐hydroquinolin‐4(1 H )‐one, 3,4‐dihydronapthalen‐1(2 H )‐one, chroman, 2,3‐dihydrobenzofuran, and 2,3‐dihydro‐1 H ‐inden‐1‐one utilizing the reported conditions.…”

Catalyst-free intramolecular radical cyclization cascades initiated by the direct homolysis of Csp3–Br under visible light

“…The bromides that can undergo ground-state transition under visible light are designed, which allows direct homolysis of C sp 3 –Br (BDE = 68 kcal mol −1 ) without a photosensitizer. Furthermore, as important scaffolds of natural products and biologically active molecules, chroman-4-one derivatives exhibit a broad range of biological effects, such as anti-inflammatory, 13 antibiotic, 14 anti-aging, 15 anti-HIV, 16 and especially anti-tumor activities. 17 Therefore, the chroman-4-one framework was determined as one of the target fragments for the cyclization strategy.…”

Visible-Light Photocatalytic Synthesis of Difluoromethylated Selenides from Selenosulfonates through a Radical Process

“…By means of developing new reagents, including BnSeCF 2 H, ClSeCF 2 H, TsSeCF 2 H, and BT-SeCF 2 H, the direct introduction of SeCF 2 H group has shown wide applications in modifying the organic molecules, but a multistep synthesis was required and a key precursor, BnSeCF 2 H, was obtained in low yields (10–36%). In the past few years, bench-stable and easily accessible difluoromethyltriphenylphosphonium salts have emerged as attractive tools for difluoromethylation reactions . In 2017, Studer described one example about radical difluoromethylation of benzylic selenol with [Ph 3 PCF 2 H]Br under UV irradiation .…”