Radical Perfluoroalkylation of Aliphatic Substrates

Abstract

A selection of perfluoroalkylation reactions of aliphatic substrates that display methodological and synthetic amplitude will be studied, giving examples of their applications and mechanistic details. An array of synthetic approaches for fluoroalkylation reactions are documented; in particular, radical protocols are prominent among perfluoroalkylation methods. To that effect, addition reactions of perfluoroalkyl radicals R F (R F =C n F 2n+1 , n > 1) to unsaturated organic substrates serve as one of the most direct and efficacious ways to access fluoroalkylated scaffolds. The syntheses of perfluoroalkyl-substituted vinyl, alkynyl, and allylic compounds; the syntheses of perfluoroalkyl-substituted hydro-, iodo-, and oxy-perfluoroalkylated alkanes and olefins; the syntheses of perfluoroalkyl-substituted carbonyl compounds; the syntheses of perfluoroalkyl-substituted enamides, amides, thioamides, and hydrazones; and multicomponent perfluoroalkylation reactions will be studied. While there are a number of accomplished reports on organofluorination, we aim to provide an overview of radical-involved perfluoroalkylation reactions of aliphatic substrates, covering examples from 2018 to early 2023, as summarized in Tables 1−4.

Radical Reactions in Organic Synthesis: Exploring in-, on-, and with-Water Methods

“…Radical additions to carbon-carbon multiple bonds are very useful synthetic transformations, especially for producing medium-molecular-weight scaffolds from smaller molecules [135]. In this subsection, representative examples of radical alkylation [136], arylation [137], acylation [138], and fluoroalkylation [139], including atom transfer radical addition (ATRA) reactions [140] on carbon-carbon multiple bonds, will be presented.…”

Metal free regio – and stereoselective semireduction of CF3-substituted N-allenamides

“…3 In particular, unsaturated nitrogen containing fluorinated compounds are of ongoing interest in synthetic methodologies. 4 Nonetheless, the semireduction of allenes is confronted with significant challenges such as the control of chemo-, regio-, and stereo-selectivities. Both π-bonds can be reduced to the corresponding alkane, and the differentiation of 1,2- vs. 2,3-semireduction becomes complicated.…”

4-Pyridyl perfluoroalkyl sulfide as a practical nucleophilic perfluoroalkylation reagent

“…In fluoroalkylation reactions, perfluoroalkylation reagent is a key to introduce a perfluoroalkyl group into the substrate molecule. Various organic perfluoroalkylation reagents featuring electrophilic, 7 radical, 8 and https://doi.org/10.26434/chemrxiv-2023-l3lhp ORCID: https://orcid.org/0000-0002-8465-1358 Content not peer-reviewed by ChemRxiv. License: CC BY-NC 4.0 2 nucleophilic 9 characters have been invented to meet the demands of perfluoroalkylation for different substrate types (Fig.…”