Iodonitrene in Action: Direct Transformation of Amino Acids into Terminal Diazirines and ¹⁵N₂-Diazirines and Their Application as Hyperpolarized Markers.

A one-pot metal-free conversion of unprotected amino acids to terminal diazirines has been developed using phenyliodonium diacetate (PIDA) and ammonia. This PIDA-mediated transformation occurs via three consecutive reactions and involves an iodonitrene intermediate. This method is tolerant to most functional groups found on the lateral chain of amino acids, it is operationally simple, and it can be scaled up to provide multigram quantities of diazirine. Interestingly, we also demonstrated that this transformation could be applied to dipeptides without racemization. Furthermore, ¹⁴N₂ and ¹⁵N₂ isotopomers can be obtained, emphasizing a key trans-imination step when using ¹⁵NH₃. In addition, we report the first experimental observation of ¹⁴N/¹⁵N isotopomers directly creating an asymmetric carbon. Finally, the ¹⁵N₂-diazirine from l-tyrosine was hyperpolarized by a parahydrogen-based method (SABRE-SHEATH), demonstrating the products' utility as hyperpolarized molecular tag.

Duke Scholars

Author Warren S. Warren Chemistry