Copper‐Catalyzed Reaction of Trifluoromethylketones with Aldehydes via a Copper Difluoroenolate

Abstract

A copper‐catalyzed reaction of easily accessible α,α,α‐trifluoromethylketones with various aldehydes affords difluoro‐methylene compounds in the presence of diboron and NaOtBu. The key process of the reaction is the formation of a copper difluoroenolate by 1,2‐addition of a borylcopper intermediate to α,α,α‐trifluoromethylketones and subsequent β‐fluoride elimination. Mechanistic studies including the isolation and characterization of a possible anionic copper alkoxide intermediate are also described.

Indium-Mediated Reformatsky Reaction of Iododifluoro Ketones with Aldehydes: Preparation of α,α-Difluoro-β-hydroxyketone Derivatives in Water

“…16 17 18 19 In 2016, Ogoshi and co-workers reported the β-F elimination of trifluoroacetophenone to obtain α-metalated alkoxides and aldehydes to give the corresponding α,α-difluoro-β-hydroxyketones. 20…”

Synthesis and Reactivity of Fluoroalkyl Copper Complexes by the Oxycupration of Tetrafluoroethylene

“…Based on the fact that the reaction of CuI with 2equivalents of NaOtBu in the presence of phen yielded [Cu-(OtBu) 2 ][(phen)Na], [22] the result of entry 2 ( Table 3) indicated that [Cu(OPh) 2 ]s hould be sufficiently reactive to facilitate the oxycupration to TFE without the need of phen as an auxiliary ligand for the copper center.I ndeed, when aD MF solution of a1 :2 mixture of CuCl and NaOPh was exposed to TFE at room temperature for 8hours in the absence of phen, the 19 Fa nalysis clearly demonstrated that two types of fluoroalkylcopper species,t hat is, [CuCF 2 CF 2 OPh] (12 neutral )a nd [(DMF) 2 Na]-[Cu(CF 2 CF 2 OPh) 2 ]( 12 ionic )w ere generated in 82 %a nd 12 %, respectively (Scheme 5). [23] Considering that an eutral copper(I) phenoxide did not show any reactivity toward the oxycupration of TFE (Scheme 2) and that the treatment of CuCl with 2equivalents of NaOtBu in DMF afforded [(DMF) 2 Na][Cu(OtBu) 2 ], [17,24] [(DMF) 2 Na][Cu(OPh) 2 ] should be the active species towards the oxycupration of TFE in the absence of phen to yield 12 ionic .H owever, 12 ionic might be unstable and undergo partial decomposition to give 12 neutral .F urther treatment of aD MF solution of 12 neutral and 12 ionic with 4b at 100 8 8Ca fforded 5ab in 92 %y ield upon isolation.…”

Photoredox Catalyzed Single C−F Bond Activation of Trifluoromethyl Ketones: A Solvent Controlled Divergent Access ofgem‐Difluoromethylene Containing Scaffolds

“…It is noteworthy to mention the contribution from Portella (Scheme 2a), Uneyama (Scheme 2b) and Ogoshi et al. (Scheme 2c and 2d)) in terms of C−F bond cleavage of aryltrifluoromethyl ketones following an enolate chemistry [16a–d] . Recently, an electrochemical approach (Scheme 2f) for the mono‐selective hydrodefluorination of trifluoromethyl ketones was reported by Lennox et al [16e] .…”