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

Abstract

In this review, we provide a comprehensive and critical perspective on the synthesis and application of 1,1,2,2‐tetrafluoroethyl‐ and tetrafluoroethylene‐containing compounds. These structures have been the focus of increasing attention as witnessed by a spectrum of new synthetic approaches, which have recently appeared in the literature. Likewise, applications of molecules containing the CF2CF2 fragment as pharmaceuticals, agrochemicals, pesticides, and advanced materials are described. It is expected that the number of successful applications of these compounds will increase in the future as a result of availability of the synthetic methods outlined here.

Systematic Investigation of Lipophilicity Modulation by Aliphatic Fluorination Motifs

“…The efficiency of fluorine introduction for property optimization is exemplified by statistics on the proportion of commercial drugs, or drugs currently in clinical trials, that are fluorinated. [6][7][8] The vast advances that are continuing to be made in synthetic organofluorine chemistry [9][10][11][12][13][14][15][16][17] have accelerated its use and, with the emergence of late stage fluorination methodologies, 18,19 this is set to continue. The increased understanding of the stability of fluorinated motifs, especially when heteroatoms are involved, [20][21][22] will further enhance its successful application.…”

Nickel‐Catalyzed Three‐Component Coupling Reaction of Tetrafluoroethylene and Aldehydes with Silanes via Oxa‐Nickelacycles

“…Moreover, the transient fluoroalkyl lithium species formed upon deprotonation of 2b by LDA can be trapped with Me 3 SiCl to produce Me 3 SiCF 2 CF 2 CH(OSiEt 3 )( p ‐C 6 H 4 CH 3 ) ( 9b ) in 90 % yield. [3b], Although tetrafluoroethylene‐containing alcohols are expected to be physiologically active, studies on the subject remain scarce due to the lack of efficient synthetic methods . These applications demonstrate the synthetic utility of the present catalytic reaction.…”

Regioselective Markovnikov hydrodifluoroalkylation of alkenes using difluoroenoxysilanes

“…The resulting ketone 3 is a versatile difluoro synthon capable of undergoing a variety of diversifying reactions. For instance, upon treatment with tert -BuOK or diethylaminosulfur trifluoride, the α,α-difluorinated benzoyl moiety of 3a could be converted to a CF 2 H or CF 2 CF 2 Ph moiety, which has important applications in drugs, agrochemicals, and advanced materials 15 , 66 . Furthermore, the ketone moiety of 3 could be transformed into an ester or an alcohol via oxidation, reduction, or a nucleophilic addition reaction, as demonstrated by the synthesis of ester 19 , secondary alcohol 20 , and tertiary alcohol 21 bearing an ethynyl group.…”