Quaternary Ammonium Trifluoromethoxide Salts as Stable Sources of Nucleophilic OCF₃

Abstract

The reaction of nucleophilic tertiary amines with trifluoromethyl and pentafluoroethyl methyl ethers provides quaternary ammonium trifluoromethoxide (NR4OCF3) and pentafluoroethoxide (NR4OCF2CF3) salts, respectively, in good yields. The new trifluoromethoxide salts disclosed herein are uniquely stable for extended periods of time in both the solid state and in solution, which complements contemporary reagents. Here we describe the preparation of a range of NR4OCF3 salts, their long-term stability, and utility in substitution reactions.

Trifluoromethyl Nonaflate: A Practical Trifluoromethoxylating Reagent and its Application to the Regio‐ and Stereoselective Synthesis of Trifluoromethoxylated Alkenes

“…Additives played a key role: The reaction yield decreased dramatically without them. Various quaternary ammonium salt additives improved the AgF solubility and helped to stabilize the CF 3 O − [13g, 17] . The reaction yield was further improved when 0.2 mmol of chloroalkyne 4 was employed, due to scale merit (entry 17).…”

“…Despite their effectiveness in straightforward trifluoromethoxylation reactions,D NTFB showed low reactivity and very limited scope;T FMS and TFBO were prepared with Tognisr eagent, whose suspected explosiveness raises safety concerns in large-scale synthesis;a nd the synthesis of TFBz required stringent reaction conditions because of the hygroscopic nature of the reagents required for its preparation as well as the generation of toxic fluorophosgene during the reaction. Recently,i tw as reported that R 4 NOCF 3 [17] was prepared by the reaction of CF 3 OCH 3 with tertiary amines. But CF 3 OCH 3 is ag as and the resulting hygroscopic CF 3 O À ammonium salts showed low reactivity.A lso,A gOCF 3 generated from triphosgene and AgF, [22] was reported, but triphosgene is hazardous;the reaction scope was narrow too.…”

Direct Trifluoromethoxylation without OCF3‐Carrier through In Situ Generation of Fluorophosgene

“…[23] All these reagents release F 3 CO À upon activation by fluoride anions. Very recently, trifluoromethyl methyl ether, a gas of comparable price with regard to TFMT, was used as trifluoromethoxide source by treatment with tertiary amine nucleophiles, [25] and O-trifluoromethyl benzaldoximes (TFBO) were shown to liberate F 3 CO À in the presence of cesium carbonate as Brønsted base (Figure 1). [26] However, using a trifluoromethoxylating reagent, besides adding at least one step to the global procedure, leads upon generation of the F 3 CO À anion to the presence of a side-product in the reaction mixture (sulfonyl-, aryl-or acyl fluoride for example).…”

“…All these reagents release F 3 CO − upon activation by fluoride anions. Very recently, trifluoromethyl methyl ether, a gas of comparable price with regard to TFMT, was used as trifluoromethoxide source by treatment with tertiary amine nucleophiles, [25] and O ‐trifluoromethyl benzaldoximes (TFBO) were shown to liberate F 3 CO − in the presence of cesium carbonate as Brønsted base (Figure 1). [26] …”

Trifluoromethyl Nonaflate: A Practical Trifluoromethoxylating Reagent and its Application to the Regio‐ and Stereoselective Synthesis of Trifluoromethoxylated Alkenes

“…Despite their effectiveness in straightforward trifluoromethoxylation reactions, DNTFB showed low reactivity and very limited scope; TFMS and TFBO were prepared with Togni's reagent, whose suspected explosiveness raises safety concerns in large‐scale synthesis; and the synthesis of TFBz required stringent reaction conditions because of the hygroscopic nature of the reagents required for its preparation as well as the generation of toxic fluorophosgene during the reaction. Recently, it was reported that R 4 NOCF 3 [17] was prepared by the reaction of CF 3 OCH 3 with tertiary amines. But CF 3 OCH 3 is a gas and the resulting hygroscopic CF 3 O − ammonium salts showed low reactivity.…”