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 reaction mixtures by
passing solutions through fluorous solid phase extraction cartridges.
This feature enables rapid and facile purification, which is critical
when working with radionuclides and is similarly beneficial for general
synthetic applications.