Pentafluoroethylation of Carbonyl Compounds by HFC-125 via the Encapsulation of the K Cation with Glymes

Abstract

A simple protocol to overcome the explosive pentafluoroethylation of carbonyl compounds by HFC-125 is described. The use of potassium (K) bases with triglyme or tetraglyme as a solvent safely yields the pentafluoroethylation products in good to high yields. The experimental results suggest that an encapsulation of the K cation by glymes as K­(glyme)2 inhibits the contact between the K cation and the reactive anionic pentafluoroethyl counterion, preventing their transformation into KF and explosive tetrafluoroethylene (TFE). The generation of sterically demanding [K­(G3)2]+ and [K­(G4)2]+ is an effective way as an unstable pentafluoroethyl anion reservoir.

Pentafluoroethylation of Carbonyl Compounds Using HFC-125 in a Flow Microreactor System

“…As expected, the use of a micro-flow system allowed for a highly efficient pentafluoroethylation protocol, which did not require glyme as a stabilization solvent or low-temperature conditions ordinarily employed in batch systems. Besides, this micro-flow protocol enables the reaction within minutes, while the batch system requires more than hours . Thus, this continuous flow microreactor protocol for pentafluoroethylation would be advantageous for large-scale industrial preparation …”

“…The flow pentafluoroethylation of chalcone 5a was examined next (Table ). In this case, KHMDS was used based on the reported batch system . The desired 1,2-addition product 6a was obtained in 45% yield (entry 1).…”

“…Besides, this micro-flow protocol enables the reaction within minutes, while the batch system requires more than hours. 14 Thus, this continuous flow microreactor protocol for pentafluoroethylation would be advantageous for large-scale industrial preparation. 17…”

“…We have recently disclosed a novel protocol for the direct nucleophilic pentafluoroethylation of carbonyl compounds using pentafluoroethane (HC 2 F 5 , HFC-125) in the presence of potassium bases in glyme (Figure d) . The key to this transformation is the generation of glyme-encapsulated K + , resulting in the stabilization of C 2 F 5 – derived from HFC-125 by ion separation.…”

Repurposing of F-gases: challenges and opportunities in fluorine chemistry

“…The pentafluoroethyl moiety could then be transferred to a wide range of carbonyl substrates ( Scheme 7a ). 234 A recent report demonstrated flow-conditions for the pentafluoroethylation of a wide range of ketones, aldehydes and chalcones. 235 There has also been work on the cupration of C 2 F 5 H and the use of “CuCF 2 CF 3 ” as a pentafluoroethylation reagent.…”