Controlled Single and Double Iodofluorination of Alkynes with DIH- and HF-Based Reagents

A novel protocol for the regio- and stereoselective iodofluorination of internal and terminal alkynes using 1,3-diiodo-5,5,-dimethylhydantoin and HF-based reagents is disclosed. This approach is used to prepare a fluorinated tamoxifen derivative in two steps from commercially available starting materials. A facile method enabling controlled regioselective double iodofluorination of terminal alkynes is also presented

Enhanced Aqueous Suzuki–Miyaura Coupling Allows Site-Specific Polypeptide ¹⁸F‑Labeling

The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki–Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [¹⁸F]­4-fluorophenylboronic acid. These findings now enable site-specific protein ¹⁸F-labeling under biologically compatible conditions using a metal-triggered reaction

Highly Diastereoselective Synthesis of Trifluoromethyl Indolines by Interceptive Benzylic Decarboxylative Cycloaddition of Nonvinyl, Trifluoromethyl Benzoxazinanones with Sulfur Ylides under Palladium Catalysis

A highly diastereoselective synthesis of trifluoromethyl-substituted indolines under palladium catalysis is disclosed. The reaction proceeds by interceptive decarboxylative benzylic cycloaddition (IDBC) of nonvinyl, trifluoromethyl benzoxazinanones with sulfur ylides. The palladium−π-benzyl zwitterionic intermediates are suggested for this transformation, and this would be the first example of an IDBC reaction

Photoredox Nucleophilic (Radio)fluorination of Alkoxyamines

Herein, we report a photoredox nucleophilic (radio)fluorination using TEMPO-derived alkoxyamines, a class of substrates accessible in a single step from a diversity of readily available carboxylic acids, halides, alkenes, alcohols, aldehydes, boron reagents, and C–H bonds. This mild and versatile one-electron pathway affords radiolabeled aliphatic fluorides that are typically inaccessible applying conventional nucleophilic substitution technologies due to insufficient reactivity and competitive elimination. Automation of this photoredox process is also demonstrated with a user-friendly and commercially available photoredox flow reactor and radiosynthetic platform, therefore expediting access to labeled aliphatic fluorides in high molar activity (Am) for (pre)clinical evaluation

Portland Daily Press: November 07,1862

https://digitalmaine.com/pdp_1862/1111/thumbnail.jp

Selective Radical Trifluoromethylation of Native Residues in Proteins

The incorporation of fluorine can not only significantly facilitate the study of proteins but also potentially modulate their function. Though some biosynthetic methods allow global residue-replacement, post-translational fluorine incorporation would constitute a fast and efficient alternative. Here, we reveal a mild method for direct protein radical trifluoromethylation at native residues as a strategy for symmetric-multifluorine incorporation on mg scales with high recoveries. High selectivity toward tryptophan residues enhanced the utility of this direct trifluoromethylation technique allowing ready study of fluorinated protein constructs using ¹⁹F-NMR

Catalytic Hydrotrifluoromethylation of Unactivated Alkenes

A visible-light-mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as the CF₃ source and MeOH as the reductant is disclosed. This effective transformation operates at room temperature in the presence of 5 mol % Ru­(bpy)₃Cl₂; the process is characterized by its operational simplicity and functional group tolerance

Trifluoromethylation of Allylsilanes under Photoredox Catalysis

A new catalytic method to access allylic secondary CF₃ products is described. These reactions use the visible light excited Ru(bpy)₃Cl₂·6H₂O catalyst and the Togni or Umemoto reagent as the CF₃ source. The photoredox catalytic manifold delivers enantioenriched allylic trifluoromethylated products not accessible under Cu(I) catalysis

¹⁸F‑Trifluoromethylation of Unmodified Peptides with 5-¹⁸F‑(Trifluoromethyl)dibenzothiophenium Trifluoromethanesulfonate

The ¹⁸F-labeling of 5-(trifluoromethyl)-dibenzothiophenium trifluoromethanesulfonate, commonly referred to as the Umemoto reagent, has been accomplished applying a halogen exchange ¹⁸F-fluorination with ¹⁸F-fluoride, followed by oxidative cyclization with Oxone and trifluoromethanesulfonic anhydride. This new ¹⁸F-reagent allows for the direct chemoselective ¹⁸F-labeling of unmodified peptides at the thiol cysteine residue