Synthesis of Five-Membered Ring Systems Bearing gem-Difluoroalkenyl and Monofluoroalkenyl Substituents via Radical β-Bromo Fragmentation

Abstract

Fluoroalkenes are useful scaffolds in several areas, including drug development, the design of functional materials, and crop protection. Considering the importance of these fluoroalkenes, significant effort has been devoted to their synthesis; however, fast access to structurally diverse fluoroalkenes still remains a challenge. Herein, we report a radical β-bromo fragmentation approach to fluoroalkene moieties from terminal alkynes and gem-dibromofluoroalkanes, applying a well-designed photoinduced sequential radical addition–translocation–cyclization–fragmentation process. A series of structurally diverse, highly substituted five-membered ring systems with gem-difluoroalkenyl and monofluoroalkenyl side chains were prepared using this approach. The reaction proceeds efficiently under an air atmosphere at room temperature and benefits from easily available starting materials, a broad scope, and a good functional group tolerance.

Recent advances in hydrogen atom transfer induced C(sp3)–H functionalizations initiated by radical addition to alkynes

“…In this context, the group of Studer discovered the synthesis of gem -difluoroalkenylated and monofluoroalkenylated five-membered rings via the radical addition–translocation–cyclization–fragmentation sequence (Scheme 7). 20 The ˙CFX radical, generated from the reduction of CFXBr 2 by the excited photocatalyst, added to the terminal alkyne, followed by 1,5-HAT and 5- exo-trig cyclization to give β-bromocyclopentylmethyl radical 7C . Radical β-bromo fragmentation then occurred to produce highly substituted five-membered rings 12 with gem -difluoroalkenyl and monofluoroalkenyl units.…”

Photoinduced C–H heteroarylation of enamines via quadruple cleavage of CF2Br2

“…On the other hand, CF 2 Br 2 , as a commercially available and versatile organic synthetic block, has attracted extensive interest from the synthetic community. [13][14][15][16] In 2015, Qing's group 13 realized the single C-Br bond cleavage of CF 2 Br 2 , offering a new strategy for the diverse synthesis of bromodifluoroalkyl compounds. Studer 14 and Du 15,16 disclosed double C-Br bond cleavage of CF 2 Br 2 for the direct construction of gem-difluoro molecules, respectively.…”

“…13–16 In 2015, Qing's group 13 realized the single C–Br bond cleavage of CF 2 Br 2 , offering a new strategy for the diverse synthesis of bromodifluoroalkyl compounds. Studer 14 and Du 15,16 disclosed double C–Br bond cleavage of CF 2 Br 2 for the direct construction of gem -difluoro molecules, respectively. Most recently, our group 17 reported an alternative approach to 3-fluoropyrazoles via the triple cleavage of CF 2 Br 2 .…”

Radical-Polar Crossover Enabled Triple Cleavage of CF2Br2: A Multicomponent Tandem Cyclization to 3-Fluoropyrazoles

“…On the basis of the above-mentioned results and literature, ,, a plausible mechanism is proposed in Scheme . Initially, CF 2 Br 2 ( 3 ) is reduced by the excited-state [Ir III ]* to generate radical species • CF 2 Br ( 3′ ) along with [Ir IV ].…”

“…For example, Qing and co-workers realized a photoinduced selective bromodifluoromethylation of alkenes with CF 2 Br 2 under mild conditions. Very recently, the pioneering examples toward sequential debromation of CF 2 Br 2 have also been reported. − In 2022, the Studer group reported a novel strategy for accessing diverse five-membered rings bearing gem -difluoroalkenyl from substituted alkynes and CF 2 Br 2 via a photoinduced radical addition-translocation-cyclization, in which CF 2 Br 2 suffered from the single-electron reduction/radical β-bromo fragmentation process. Later on, Du and co-workers achieved the NHC-catalyzed difluoroolefination of 1,3-enynes by using CF 2 Br 2 as a C1F2 synthon, offering a fruitful way to a new class of functionalized gem -difluorovinyl allenes.…”