Selective and Scalable Perfluoroarylation of Nitroalkanes

Abstract

Functionalized per- and poly-fluoroarenes are important building blocks, with many industrially and medicinally important molecules containing them. Nucleophilic aromatic substitution can be employed as a quick and straightforward way to synthesize these building blocks. While many methods to derivatize fluoroarenes exist which use heteroatom centered nucleophiles, there are fewer methods that use carbon centered nucleophiles, and of those many are poorly defined. This work presents the SNAr reaction of nucleophiles generated from nitroalkanes with a variety of fluorinated arenes. Given that the products are versatile, accessing polyfluorinated arene building blocks in substantial scale is important. This method is highly regioselective, and produces good to moderate yields on a large scale, sans chromatography, and thus fulfills this need. In addition, the regioselectivity of the addition was probed using both DFT calculations and experimentally via halogen exchange.

Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control

“…39 We were pleased to see that the benzoyl protected amino acids ( 9a and 9b ) underwent smooth photo-HDF, and that the HDF products were isolated in good yields. The ethyl ester derivative was isolated in high yield ( 9c’ ) 27 .…”

Organic Superbases in Recent Synthetic Methodology Research

“…In addition to perfluorinated pronucleophile activation, superbases have also been used to address challenges in perfluorinated electrophile functionalization. In 2017, Weaver reported examples of TMG‐promoted nucleophilic aromatic substitution reactions (S N Ar) of perfluoroarenes with oxazolone [48a] and nitroalkane [48b] pronucleophiles (Figure 10). For oxazolone substrates, TMG is more reactive than N , N ‐diisopropylamine and enables access to perfluoroarylated α‐amino ester and acid products following acidic workup.…”

Mass spectrometrical and quantum‐chemical study of pentafluorophenylhydrazones

“…Poly/perfluorinated aromatics are very frequently used substrates for numerous nucleophiles like azides, 5,[13][14][15] nitromethane, [16][17][18] cyanide anion, 19 or other nucleophiles. 20 They are employed as a principal step in the building of selective substituted (hetero)aromatics.…”