Fluorous Analogue of Chloramine-T: Preparation, X-ray Structure Determination, and Use as an Oxidant for Radioiodination and s-Tetrazine Synthesis.

A fluorous oxidant that can be used to introduce radioiodine into small molecules and proteins and generate iodinated tetrazines for bioorthogonal chemistry has been developed. The oxidant was prepared in 87% overall yield by combining a fluorous amine with tosyl chloride, followed by chlorination using aqueous sodium hypochlorite. A crystal structure of the oxidant, which is a fluorous analogue of chloramine-T, was obtained. The compound was shown to be stable for 7 days in EtOH and for longer than three months as a solid. The oxidant was effective at promoting the labeling of arylstannanes using [125I]NaI, where products were isolated in high specific activity in yields ranging from 46% to 86%. Similarly, iodinated biologically active proteins (e.g., thrombin) were successfully produced, as well as a radioiodinated tetrazine, through a concomitant oxidation-halodemetalation reaction. Because of its fluorous nature, unreacted oxidant and associated reaction byproducts can be removed quantitatively from r...