Direct nucleophilic trifluoromethylation of carbonyl compounds by potent greenhouse gas, fluoroform: Improving the reactivity of anionoid trifluoromethyl species in glymes

Abstract

A simple protocol to overcome the problematic trifluoromethylation of carbonyl compounds by the potent greenhouse gas “HFC-23, fluoroform” with a potassium base is described. Simply the use of glymes as a solvent or an additive dramatically improves the yields of this transformation. Experimental results and DFT calculations suggest that the beneficial effect deals with glyme coordination to the K+ to produce [K(polyether)n]+ whose diminished Lewis acidity renders the reactive anionoid CF3 counterion species more ‘naked’, thereby slowing down its undesirable decomposition to CF2 and F− and simultaneously increasing its reactivity towards the organic substrate.

Generation and Applications of the Hydroxide Trihydrate Anion, [OH(OH2)3]−, Stabilized by a Weakly Coordinating Cation

“…Shibata et al. recently presented the possibility to lower the fluorophilicity of the potassium cation of trifluoromethyl potassium by the use of glyme as a coordinating solvent . Weakly coordinating phosphazenium cations also prevent the difluorocarbene elimination (Scheme ) as presented by Shibata et al.…”

“…[26] Therefore the preparative trifluoromethylation reaction is accomplished via the detour of Me 3 SiCF 3. [27] Weakly coordinating phosphazenium cations also prevent the difluorocarbene elimination (Scheme 5) as presented by Shibata et al and Zhang et al for the trifluoromethylation of electrophilic carbonyl compounds [28] and sulfonyl fluorides, [29] as well as for different epoxides,carbon dioxide, and esters [30] in good to excellent yields using 2 and fluoroform. [22] Shibata et al recently presented the possibility to lower the fluorophilicity of the potassium cation of trifluoromethyl potassium by the use of glyme as ac oordinating solvent.…”

Generierung und Anwendung des Hydroxid‐Trihydrat‐Anions, [OH(OH2)3]−, stabilisiert durch ein schwach koordinierendes Kation

“…Shibata et al. stellten kürzlich die Möglichkeit vor, die Fluorophilie des Kaliumkations von Trifluormethylkalium durch die Verwendung von Glyme als koordinierendem Lösungsmittel zu senken . Schwach koordinierende Phosphazenium‐Kationen verhindern ebenfalls die Difluorcarben‐Eliminierung (Schema ), wie von Shibata et al.…”

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

“…Rather than decomposing CF 3 compounds, it would be better to maximize the efficiency of their use [16][17][18]. However, taming HCF 3 as a trifluoromethylation agent is a challenge in organic chemistry [19][20][21][22][23][24][25][26][27][28], although recent rapid progress in the chemistry of HCF 3 by Grushin (for CuCF 3 ) [29][30][31][32][33][34][35][36][37], Prakash (for KCF 3 ) [38], and others [39][40][41][42][43][44], including our group [45][46][47][48][49][50], has dramatically improved the prospects. One of the problems facing the treatment of HCF 3 for nucleophilic trifluoromethylation reactions is the low stability of the directly generated CF 3 anion (CF 3 − ) for decomposing to difluorocarbene (:CF 2 ) and fluoride (F − ) (Scheme 1a).…”

“…One of the problems facing the treatment of HCF 3 for nucleophilic trifluoromethylation reactions is the low stability of the directly generated CF 3 anion (CF 3 − ) for decomposing to difluorocarbene (:CF 2 ) and fluoride (F − ) (Scheme 1a). Due to the formation of highly stable fluoride salts (MF), the breakdown of CF Although the reaction has a broad substrate scope of embracing ketones, chalcones and aldehydes, the transformation of esters to trifluoromethyl ketones by this protocol was never examined [46].…”