The unique fluorine effects in organic reactions: recent facts and insights into fluoroalkylations

Abstract

Fluoroalkylation reaction, featuring the transfer of a fluoroalkyl group to a substrate, is a straightforward and efficient method for the synthesis of organofluorine compounds. In fluoroalkylation reactions, fluorine substitution can dramatically influence the chemical outcome. On the one hand, the chemistry of alkylation with non-fluorinated reagents may not be applicable to fluoroalkylations, so it is necessary to tackle the fluorine effects to achieve efficient fluoroalkylation reactions. On the other hand, fluorine substitution may bring about new reactivities and transformations that cannot be realized in alkylation with non-fluorinated reagents; thus, fluorine substitution can be used to explore new synthetic methods. This tutorial review provides a brief overview of the unique fluorine effects in recently developed nucleophilic, electrophilic, radical, and transition metal-mediated fluoroalkylation reactions by comparing with either their non-fluorinated counterparts or fluorinated counterparts with different numbers of fluorine substituents.

Taming Metal/Fluorine Carbenoids

“…Hence, applications are extremelyl imited, mostly to fluoroalkylation reactions with in situ generated a-fluorocarbanions, as was reported by Olah and co-workers, Hu, and others. [9,10] However,t he handling of these compounds and the choice of the right reaction conditions to controld ecomposition and to allow for selective transformations remainsachallenge. This has been expressed by the so-called "negativef luorine effect" (NFE), which distinguishes fluorine carbenoids from their chlorine or bromine congeners.…”

Visible‐Light‐Promoted Synthesis of Fluoroalkylated Oximes

“…An additional experiment using non‐fluoroalkylated alkenes proved that the presence of fluorine atoms changes the reactivity of the molecule significantly. While the reaction of 1 a with 2 a provided the oxime product 3 aa , the reaction with the non‐fluoroalkyl analogue 1‐octene 4 did not produce the corresponding oxime product 5 at all under the same conditions [Scheme ] . It is likely that the radical intermediate ( C in Scheme ) is stable enough to undergo further reactions with a longer life time when the radical center is present next to a fluoroalkyl group.…”

Advances in the Synthesis and Application of Tetrafluoroethylene‐ and 1,1,2,2‐Tetrafluoroethyl‐Containing Compounds

“…The importance of fluorinated pharmaceuticals has been well documented . Some biological studies involving the CF 2 CF 2 ‐contatining compounds have already been mentioned in the context of fluorinated sugars (Chapter 4.2), such as novel antituberculosis agents (Figure ), or antiviral candidates (Scheme ) …”