Where Does the Fluorine Come From? A Review on the Challenges Associated with the Synthesis of Organofluorine Compounds

“Doubly Orthogonal” Labeling of Peptides and Proteins

Demonstrated herein is the construction of trifluoromethylated quaternary carbon centers by an asymmetric radical transformation. Enantioenriched trifluoromethylated oxindoles were accessed using a hypervalent iodine-based trifluoromethyl transfer reagent in combination with a magnesium Lewis acid catalyst and PyBOX-type ligands to achieve up to 99 % ee and excellent chemical yields. Mechanistic studies were performed by experimental and computational methods and suggest a single-electron transfer induced SN 2-type mechanism. This example is thereby the first report on the construction of enantioenriched trifluoromethylated carbon centers using hypervalent iodine-based reagents proceeding through such a reaction pathway.

Taming Radical Intermediates for the Construction of Enantioenriched Trifluoromethylated Quaternary Carbon Centers.

Advances in the Synthesis and Application of Tetrafluoroethylene‐ and 1,1,2,2‐Tetrafluoroethyl‐Containing Compounds

A method for the synthesis of diversely substituted 3-fluoropyridines from two ketone components is described. The reaction involves photoredox coupling of α,α-difluoro-β-iodoketones with silyl enol ethers catalyzed by fac-Ir(ppy)3 under blue LED irradiation with subsequent one-pot condensation with ammonium acetate. Based on cyclic voltammetry studies, it was determined that α,α-difluoro-β-iodoketones are reduced notably easier compared to 2,2,2-trifluoro-1-iodoethane, which may be ascribed to the influence of the carbonyl group.

Synthesis of 3-Fluoropyridines via Photoredox-Mediated Coupling of α,α-Difluoro-β-iodoketones with Silyl Enol Ethers.

Synthesis of quaternary α-perfluoroalkyl lactams via electrophilic perfluoroalkylation.

A new hypervalent iodine reagent (5) based on 1,2-dihydro-3,3-dimethyl-1,2-benziodoxole containing a 4-methyl-7-tetrafluoroethoxycoumarin unit as a specific UV absorber was prepared and fully characterized, including X-ray crystal structural analysis. The high reactivity of this compound towards thiols has been exploited for the selective tagging of several targets with the UV chromophore coumarin, including e.g. glutathione.

Bruno Commare

Papers

Synthesis of quaternary α-perfluoroalkyl lactams via electrophilic perfluoroalkylation.

Hypervalent Iodine Reagents: Thiol Derivatization with a Tetrafluoroethoxy Coumarin Residue for UV Absorbance Recognition