Synthesis of key intermediates to 20(R)-and 20(S)-trifluoromethyl-23,24-dinor-25-hydroxy-cholesterol and VD3 analogs

Synthesis of 20(R)-and 20(S)-trifluoromethyl substituted steroids as the key intermediates (1a, 1b) to 23,24-dinor-20-trifluoromethyl-25-hydroxy-cholesterol and VD3 analogs, using trifluoromethyltrimethylsilane (CF₃SiMe₃) as a trifluoromethylating agent, was described.     

Electrophilic trifluoromethylation of simple inorganic salts: a one step route to trifluoromethylnitromethane, CF3NO2

Trifluoromethylnitromethane is readily synthesized in high yield from the electrophilic trifluoromethylation of NaNO₂.     

Remote asymmetric trifluoromethylation induced by chiral sulfinyl group: synthesis of enantiomerically pure 1-(2-naphthyl)-2,2,2-trifluoroethanol

The reaction of 1-[(2,4,6-triisopropylphenyl)sulfinyl]-2-naphthaldehyde with (trifluoromethyl)trimethylsilane using tetramethylammonium fluoride gave trifluoromethylated compounds in high yield with high diastereoselectivity. Desilylation and subsequent recrystallization yielded the enantiomerically and diastereomerically pure trifluoroethanol, which afforded chiral 1-(2-naphthyl)-2,2,2-trifluoroethanol after removal of the sulfinyl group.     

Continuous-Flow Photocatalysis for the Direct C-H Trifluoromethylation of Heterocycles with an Organic Photoredox Catalyst

Photocatalysis for direct C−H trifluoromethylation represents an ideal way to synthesize trifluoromethyl-containing chemical compounds, but the conventional batch processes are inefficient with limited light penetration and indispensably irradiated for a long while. Herein, we report a continuous-flow protocol for photocatalytic direct C−H trifluoromethylation of heterocycles in the presence of an organic photoredox catalyst: 2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile (3DPA2FBN). In this approach, benefiting from the merger of organic photoredox catalysis and continuous-flow techniques, a variety of trifluoromethylated heterocycles were rapidly synthesized up to 85 % yield with 80 min residence time under metal- and oxidant-free reaction conditions.     

Cross-Coupling Reactions Enabled by Well-Defined Ag(III) Compounds: Main Focus on Aromatic Fluorination and Trifluoromethylation

Ag^III compounds are considered strong oxidizers of difficult handling. Accordingly, the involvement of Ag catalysts in cross-coupling via 2e⁻ redox sequences is frequently discarded. Nevertheless, organosilver(III) compounds have been authenticated using tetradentate macrocycles or perfluorinated groups as supporting ligands, and since 2014, first examples of cross-coupling enabled by Ag^I/Ag^III redox cycles saw light. This review collects the most relevant contributions to this field, with main focus on aromatic fluorination/perfluoroalkylation and the identification of Ag^III key intermediates. Pertinent comparison between the activity of Ag^IIIR_F compounds in aryl-F and aryl-CF₃ couplings vs. the one shown by its Cu^IIIR_F and Au^IIIR_F congeners is herein disclosed, thus providing a more profound picture on the scope of these transformations and the pathways commonly associated to C−R_F bond formations enabled by coinage metals.     

Domino nucleophilic trifluoromethylations of alkyl perfluorodithioesters

Under nucleophilic initiation, alkyl perfluorodithioesters react with trifluoromethyl(trimethyl)silane in a domino process beginning with a thiophilic addition-β-elimination of fluoride ion which leads to a perfluoroketenedithioacetal. Further addition-elimination steps eventually gives a mixture of mono, bis- and tris(trifluoromethyl) vinyl sulfides. Although they are difficult to separate, these new compounds were fully characterized by ¹⁹F NMR and mass spectrometry.     

In situ kinetic studies of the trifluoromethylation of caffeine with Zn(SO2CF3)2

In situ monitoring of the trifluoromethylation of caffeine using Zn(SO₂CF₃)₂ provides mechanistic insight into this important reaction. The concentration dependences of each of the reagents are probed, along with the effect of various additives. The kinetic profile is characterized by a rapid initial regime followed by a period of slower rate. Increasing the concentration of the Zn reagent extends the initial rapid period to higher conversions. Neither the caffeine concentration nor the concentration of the oxidant has a strong effect on the reaction rate. A multiple aliquot method is introduced to help deconvolute factors associated with each rate regime.     

Synthesis and anticancer activity studies of novel 1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)uracil and (6′-substituted)-7- or 9-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-7H- or 9H-purines

On the basis of a molecular variation on an isosteric replacement (F→H) from the prototype (RS)-1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil, the derivative (RS)-1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)uracil 4 was prepared. Later on, the pyrimidine base was substituted by the purine moiety with the objective of increasing both the lipophilicity and the structural diversity of the target molecules. The 6′-halogen substituent of the (RS)-9- or 7-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-9H- or 7H-purines shows an interesting reactivity, which is presented and discussed. The anticarcinogenic potential of the target molecules is reported against the MCF-7 cancer cell line.     

The synthesis of salts and esters of perfluorinated dithio- and thiocarboxylic acids from carbon disulfide and carbonyl sulfide reacting with RFSiMe3/F

Trimethyl(perfluoroalkyl)silanes react with carbonyl sulfide and carbon disulfide in the presence of fluoride ion to give salts and, after alkylation of the latter, esters of the corresponding perfluorinated thio- and dithiocarboxylic acids.     

Reactions of CF3-substituted boranes with α-diazocarbonyl compounds

Boranes substituted with a CF₃-group can be generated from methyl boronic esters RB(OMe)₂ and Me₃SiCF₃/KF followed by treatment with Me₃SiCl. These boranes are stable only in coordinating solvents, and due to the increased Lewis acidity of boron, react rapidly with α-diazocarbonyl compounds to give the products of transfer of the organic group from boron. Alkyl, aryl, vinyl, and alkynyl boronic esters can be used in this reaction.