Borazine‐CF₃⁻ Adducts for Rapid, Room Temperature, and Broad Scope Trifluoromethylation

Abstract

A fluoroform-derived borazine CF transfer reagent is used to effect rapid nucleophilic reactions in the absence of additives, within minutes at 25 °C. Inorganic electrophiles spanning seven groups of the periodic table can be trifluoromethylated in high yield, including transition metals used for catalytic trifluoromethylation. Organic electrophiles included (hetero)arenes, enabling C-H and C-X trifluoromethylation reactions. Mechanistic analysis supports a dissociative mechanism for CF transfer, and cation modification afforded a reagent with enhanced stability.

[3,3]‐Sigmatropic Rearrangement of Cyclopropenylcarbinyl Cyanates: Access to Alkylidene(aminocyclopropane) Derivatives

“…The above‐mentioned mechanism shares some similarities with the reaction of in situ generated ketenes (from enolizable acid chlorides and pyridine) with trifluoroacetic anhydride, which constitutes a powerful entry to trifluoromethyl ketones . It is also worth pointing out that the conversion of isocyanates into trifluoroacetamides has been previously accomplished by treatment of acyl azide precursors (by Curtius rearrangement) with trifluoroacetic acid, or addition of a nucleophilic trifluoromethyl group generated from bromotrifluoromethane in the presence of zinc, (trifluoromethyl)trimethylsilane or a (trifluoromethyl)borazine . Hence, reaction with trifluoroacetic anhydride in the presence of a nucleophilic promotor such as pyridine provides an interesting alternative, which was applied to other isocyanates.…”

“…[43] It is also worth pointing out that the conversion of isocyanatesi nto trifluoroacetamidesh as been previously accomplished by treatment of acyl azide precursors (by Curtius rearrangement) with trifluoroacetic acid, [44] or addition of an ucleophilic trifluoromethyl group generated from bromotrifluoromethane in the presence of zinc, [45] (trifluoromethyl)trimethylsilane [46] or a( trifluoromethyl)borazine. [47] Hence, reaction with trifluoroacetic anhydride in the presence of an ucleophilic promotor such as pyridine provides an interesting alternative, which was applied to other isocyanates. Carbamates 3a, 3d, 3j and 3k were subjected to the dehydration/[3,3]-sigmatropic rearrangements equence [TFAA (1.2 equiv), Et 3 N (3 equiv), CH 2 Cl 2 , À78 8C],a nd when the transformation into the correspondingi socyanates 5a, 5d, 5j and 5k was complete, TFAA (1.5 equiv)a nd pyridine (1.5 equiv) were added to the reaction mixture (RT,1 6h).…”

Nucleophilic Trifluoromethylation Reactions Involving Copper(I) Species: From Organometallic Insights to Scope

“…In 2018, Szymczak and co-workers presented an interesting strategy for the introduction of a CF 3 group into different inorganic electrophiles using a fluoroform-derived borazine (Scheme 17). 41 In particular, the reaction of CuI and borazine-CF 3 in dimethyl sulfoxide (DMSO) gives rise a mixture of (DMSO)CuCF 3 (19%) and [Cu(CF 3 )I] -(63%) that reacts with 4-iodobiphenyl at 80 °C during 12 hours, forming the trifluoromethyl organic molecule in 66% yield.…”

“…Scheme 17 (a) Transmetalation reaction from borazine to copper and the trifluoromethylation reaction of 4-iodobiphenyl (see the original publication 41 for further details).…”

Counterintuitive deshielding on the 13C NMR chemical shift for the trifluoromethyl anion

“…The trifluoromethyl (CF 3 ) group is one of the most important fluorinated substituents applied in organic synthesis to increase the bioavailability and metabolic stability of drugs . Trifluoromethylation reactions may be performed through three mechanistic strategies: electrophilic (CF 3 + ), radical (CF 3 .…”