Electrochemical Installation of CFH₂−, CF₂H−, CF₃−, and Perfluoroalkyl Groups into Small Organic Molecules

Abstract

Electrosynthesis can be considered a powerful and sustainable methodology for the synthesis of small organic molecules. Due to its intrinsic ability to generate highly reactive species under mild conditions by anodic oxidation or cathodic reduction, electrosynthesis is particularly interesting for otherwise challenging transformations. One such challenge is the installation of fluorinated alkyl groups, which has gained significant attention in medicinal chemistry and material science due to their unique physicochemical features. Unsurprisingly, several electrochemical fluoroalkylation methods have been established. In this review, we survey recent developments and established methods in the field of electrochemical mono‐, di‐, and trifluoromethylation, and perfluoroalkylation of small organic molecules.

Robust and Self‐Cleaning Electrochemical Production of Periodate

“…of para-periodate, respectively. The 2-iodoaniline (17) was tested and could be > 90, > 95, and > 99 % degraded using 0.171, 0.222, and 0.341 kilo equiv. of para-periodate.…”

“…For example, hazardous and stoichiometric chemical redox reagents can be substituted directly by electricity derived from regenerative energy sources. This increases atom economy and lowers waste production for the desired reaction [5,10,11,16,17] . Further advantages are the improvement of safety and milder reaction conditions.…”

“…This increases atom economy and lowers waste production for the desired reaction. [5,10,11,16,17] Further advantages are the improvement of safety and milder reaction conditions. In total, this sustainable approach can pay off.…”

State of knowledge in photoredox-catalysed direct difluoromethylation

“…Within recent decades, outstanding progress in difluoromethylation has been made using direct and indirect approaches through electrophilic, nucleophilic, or radical processes. 3 Seminal works on direct radical difluoromethylation of alkenes were reported using HCF 2 I as the difluoromethylating agent as early as 1975 by Tedder's group and by Chen's group in 1994. 4 To date, radical-based difluoromethylation remains an advantageous synthetic method for the preparation of CF 2 H-containing organic molecules.…”

Synthesis of Secondary Trifluoromethylated Alkyl Bromides Using 2-Bromo-3,3,3-trifluoropropene as a Radical Acceptor

“…Due to the special properties of the trifluoromethyl group, such as strong electron-withdrawing ability, high lipophilicity, and excellent metabolic stability, the incorporation of CF 3 into drug molecular candidates can significantly enhance their selectivity of molecule–protein binding, boost membrane permeability, and improve metabolic stability in vivo . Over the past decade, numerous efforts have been devoted to the direct installation of a CF 3 entity into organic molecules, utilizing a variety of trifluoromethylation reagents . Among those advancements, efficient and general methods for the preparation of trifluoromethylated aliphatic compounds were much more lagging behind compared to the intelligent strategies focusing on the synthesis of trifluoromethylated aromatic compounds .…”