Diversity‐Oriented Synthesis of Aliphatic Fluorides via Reductive C(sp³)−C(sp³) Cross‐Coupling Fluoroalkylation

Abstract

Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel‐catalyzed monofluoromethylation of unactivated alkyl halides using a low‐cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross‐coupling of two alkyl halides. Results with 1‐bromo‐1‐fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3)‐C(sp3) cross‐coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first‐order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate‐determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides.

Noble metal-free bis-tridentate benzimidazole zinc(ii) and iron(ii) complexes for selective CO2photoreduction

“…40–42 In similarity to 2,2′:6′,2′′-tripyridine, 2,6-bis(2-benzimidazole)pyridine has both strong σ-donor (benzimidazole unit) and π-acceptor (pyridine ring) properties, which allows them to form various metal complexes that might be also used for CO 2 photoreduction like terpyridine-based metal complexes. 43,44 Those benzimidazole-based tridentate metal complexes have been studied in numerous research fields such as sensing, 45 spin crossover, 46–48 and anticancer agents. 49 However, to our knowledge, their applications in CO 2 photoreduction have yet to be reported.…”

Transition‐Metal‐Catalyzed Monofluoroalkylation: Strategies for the Synthesis of Alkyl Fluorides by C−C Bond Formation

“…In 2021, Wang and co-workers developed the sp 3 -sp 3 reductive coupling of alkyl bromides with a-fluoro alkyl bromides. [27] In this case,the terminal reductant was bis(neopentyl glycolato)diboron and the products were aliphatic fluorides,not benzylic fluorides (Scheme 13).…”

The synthetic versatility of fluoroiodomethane: recent applications as monofluoromethylation platform

“…Recently, CH 2 FBr has been adopted for the generation of FCH 2 • radical species. 78,79 In this context, very recently, Gouverneur 80 and Gaunt 81 independently proposed the use of fluoroiodomethane (CH 2 FI) as a convenient platform for the generation of monofluoromethyl radical through silyl radical-mediated transformations under blue LED activation. 82 Both protocols adopted tris Gouverneur et al described the hydrofluoromethylation of several electron-deficient alkenes including biologically active unsaturated acceptors through a blue LED irradiation for 16 hours in acetonitrile.…”

“…Recently, CH 2 FBr has been adopted for the generation of FCH 2 ˙ radical species. 78,79 In this context, very recently, Gouverneur 80 and Gaunt 81 independently proposed the use of fluoroiodomethane (CH 2 FI) as a convenient platform for the generation of monofluoromethyl radical through silyl radical-mediated transformations under blue LED activation. 82 Both protocols adopted tris(trimethylsilyl)silane (TTMSS, (Me 3 Si) 3 Si-H) as a precursor of the supersilyl radical (TMS) 3 Si˙ which can release CH 2 F radical from fluoroiodomethane through halogen-atom transfer (XAT), simultaneously producing (TMS) 3 SiI.…”