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.

Terminal Diazirines Enable Reverse Polarization Transfer from 15 N2 Singlets.

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15 N2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long-lived lifetimes. The (-CH15 N2 ) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (-CH15 N2 ) moiety to 1 H, thus combining the advantages of long lifetimes of 15 N polarization with superior sensitivity of 1 H detection. Despite the proximity of 1 H to 15 N nuclei in the diazirine moiety, 15 N T1 times of up to (4.6±0.4) min and singlet lifetimes Ts of up to (17.5±3.8) min are observed. Furthermore, we found terminal diazirines to support hyperpolarized 1 H2 singlet states in CH2 groups of chiral molecules. The singlet lifetime of 1 H singlets is up to (9.2±1.8) min, thus exceeding 1 H T1 relaxation time (at 8.45 T) by a factor of ≈100.

One-Pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-Sulfoximines from Sulfides.

A general efficient one-pot synthesis of S-perfluoroalkylated NH-sulfoximines from sulfides has been developed using phenyliodine diacetate (PIDA) and ammonium carbamate. Remarkable rate enhancement with trifluoroethanol was observed, presumably due to H-bonding effects. These mild and metal-free conditions are compatible with -CH2 F, -CFCl2 , -CF2 H, -CF2 Br, -C4 F9 , and -CF3 groups, in both the alkyl- and aryl series. Based on a 19 F NMR analysis, a λ6 -acetoxysulfanenitrile intermediate was proposed.

Mechanistic investigation of the NH-sulfoximination of sulfide. Evidence for λ6-sulfanenitrile intermediates.

We report a new procedure for the preparation of NH-sulfoximines from sulfides using PIDA as an oxidant and ammonium carbamate as the ammonia source. Excellent yields were obtained with a wide range of sulfides. The formation of acetoxy- and methoxy-λ6-sulfanenitrile as intermediates was proposed, both of which were converted to the NH-sulfoximine by the action of the solvent. The structure of these intermediates was confirmed by 1H, 13C and 15N NMR and HRMS analysis.