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

Abstract

The protocol of micro-flow nucleophilic pentafluoroethylation using pentafluoroethane (HC 2 F 5 , HFC-125), a nontoxic, inexpensive, and commercially available greenhouse gas, is described. The micro-flow pentafluoroethylation by HFC-125 proceeded smoothly at room temperature or at −10 °C in DMF or toluene in the presence of a potassium base, namely, t-BuOK or KHMDS. A broad range of ketones, aldehydes, and chalcones with various substituted benzene rings were successfully converted to the corresponding pentafluoroethyl carbinols instantly with good to high yields.

Synthesis and Properties of the Perfluoroethyl Martin Silicate: Reactivity in Solution and Solid‐State Mechanochemistry

“…However, addition of cesium fluoride (CsF) allowed the formation of the fluorinated secondary alcohol 8 with an NMR yield of 57 % (Scheme 4, reaction 1). [14,15] During the optimization of the process, we observed that the reaction seems to occur on the surface of the CsF, and we also observed the formation of HC 2 F 5 presumably occurring via the decoordination of the ligand. This observation drove us to study the possible reactivity in solid state by mechanochemistry (Scheme 4, reaction 2).…”

“…To limit the potential hazard (violent decomposition/explosion), [11][12][13] the batch generation of the required organolithium reagent has recently evolved to a safer microflow method (Figure 1.b). [14,15] As an alternative, stabilization of the organolithium in the form of a stannate reagent reservoir has proven to be a more reliable solution for safer handling of this chemical (Figure 1.c). [16] Other stabilizations of HFC-125 as pentafluoroethyl -cuprates, [17,18] -gallanes, [19,20] -bismuthanes [21a] or very recently -indates salts [21b] have also been developed.…”

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

“…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. 236,237 Tsui and co-workers reported ''CuCF 2 CF 3 '' as a source of the CF 2 CF 3 radical for pentafluoroethylation of unactivated alkenes.…”

Ex-situ generation and synthetic utilization of bare trifluoromethyl anion in flow via rapid biphasic mixing

“…1b ) 12 . Nevertheless, this in situ quenching method approaches could not be completely evitable even in the use of additional reagents for stabilization of CF 3 − 9 , 21 , 26 and/or the utilization of flow reaction setup for easy handling the gas with high pressure to prevent gas volatilization 27 – 31 . This method, however, has fatal problems of not only narrowing down the scope of reaction and the selectivity when the reaction partner is irreconcilable with reaction condition for generating the desired intermediate but also completely depriving the opportunity to explore the nature of a given intermediate for fully understanding a synthetic pathway because the intermediate cannot be solely existed (Fig.…”