Evaluating N-difluoromethyltriazolium triflate as a precursor for the synthesis of high molar activity [ F]fluoroform.

The trifluoromethyl group is a prominent motif in biologically active compounds and therefore of great interest for the labeling with the positron emitter fluorine-18 for positron emission tomography (PET) imaging. Multiple labeling strategies have been explored in the past; however, most of them suffer from low molar activity due to precursor degradation. In this study, the potential of 1-(difluoromethyl)-3-methyl-4-phenyl-1H-1,2,3-triazol-3-ium triflate as precursor for the synthesis of the [ F]trifluoromethylation building block [ F]fluoroform with high molar activity was investigated.

Synthesis of aliphatic α-ketoamides from α-substituted methyl ketones a Cu-catalyzed aerobic oxidative amidation.

α-Ketoamides are an important key functional group and have been used as versatile and valuable intermediates and synthons in a variety of functional group transformations. Synthetic methods for making aryl α-ketoamides as drug candidates have been greatly improved through metal-catalyzed aerobic oxidative amidations. However, the preparation of alkyl α-ketoamides through metal-catalyzed aerobic oxidative amidations has not been reported because generating α-ketoamides from aliphatic ketones with two α-carbons theoretically provides two distinct α-ketoamides.

Mechanistic study of nucleophilic fluorination for the synthesis of fluorine-18 labeled fluoroform with high molar activity from -difluoromethyltriazolium triflate.

The synthesis of fluorine-18 labeled fluoroform with high molar activity has grown in importance for the development of fluorine-18 labeled aryl-CF radiopharmaceuticals that are useful as diagnostic radiotracers for the powerful technique of positron emission tomography (PET). We designed a strategy of synthesizing fluorine-18 labeled fluoroform from 1-difluoromethyl-3-methyltriazolium triflate (1) S2 fluorination without stable fluorine isotope scrambling. Fluoroform was generated at rt in 10 min by fluorination of the triazolium precursor with TBAF (6 equiv.