Iodonitrene in Action: Direct Transformation of Amino Acids into Terminal Diazirines and N-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 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, N and N isotopomers can be obtained, emphasizing a key trans-imination step when using NH. In addition, we report the first experimental observation of N/N isotopomers directly creating an asymmetric carbon. Finally, the N-diazirine from l-tyrosine was hyperpolarized by a parahydrogen-based method (SABRE-SHEATH), demonstrating the products' utility as hyperpolarized molecular tag.