Iridium-catalysed ortho-H/D and -H/T exchange under basic conditions : C-H activation of unprotected tetrazoles

The first examples of selective ortho-directed C-H activation with unprotected 2-aryltetrazoles are described. A new base-assisted protocol for iridium (I) hydrogen isotope exchange catalysis allows access to ortho-deuterated and tritiated tetrazoles, including the tetrazole-containing pharmaceutical, Valsartan. Preliminary mechanistic studies are also presented

Applications of hydrogen isotopes in the life sciences

Hydrogen isotopes are unique tools for identifying and understanding biological or chemical processes. Hydrogen isotope labeling allows for a traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no change in its chemical structure, physical properties or biological activity. Using deuterium labeled isotopologues to study the unique mass spectrometric (MS)-pattern generated from mixtures of biological relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (3H), in particular, has seen an increased utilization, especially in pharmaceutical drug discovery. The efforts and costs required for the synthesis of labeled compounds are more than compensated for by the enhanced molecular sensitivity for analysis and high reliability of the data obtained. In this review, advances in the applications of hydrogen isotopes in the life sciences are described

Iridium-catalyzed Csp3-H activation for mild and selective hydrogen isotope exchange

The increasing demand for isotopically labeled compounds has provided appreciable impetus for the development of improved methods for the late stage introduction of isotopes of hydrogen (deuterium or tritium). Moreover, sp3-rich molecules are becoming increasingly common in the exploration of chemical space for drug design. Herein, we report an efficient iridium(I) catalysed C-H activation method for the hydrogen isotope exchange of sp3 C-H bonds. A wide range of substrates have been labeled, including active pharmaceutical ingredients, delivering excellent levels of isotope incorporation and predictable regiocontrol, with low catalyst loadings, in short reaction times, and under mild reaction conditions

The Hydrogen–Deuterium Exchange at α-Carbon Atom in N,N,N-Trialkylglycine Residue: ESI-MS Studies

Derivatization of peptides as quaternary ammonium salts (QAS) is a known method for sensitive detection by electrospray ionization tandem mass spectrometry. Hydrogens at α-carbon atom in N,N,N-trialkylglycine residue can be easily exchanged by deuterons. The exchange reaction is base-catalyzed and is dramatically slow at lower pH. Introduced deuterons are stable in acidic aqueous solution and are not back-exchanged during LC-MS analysis. Increased ionization efficiency, provided by the fixed positive charge on QAS group, as well as the deuterium labeling, enables the analysis of trace amounts of peptides

Expanded applicability of iridum(I) NHC-phosphine catalysts in hydrogen isotope exchange processes with pharmaceutically-relevant heterocycles

An assessment of emerging C-H activation catalysts of the type [(COD)Ir(IMes)(PR3)]PF6 in the deuteration of N-heterocycles is divulged. Substrate scope, competition experiments, and labelling of drug type molecules have revealed PR3 = PPh3 provides a broadly more applicable and widely effective catalyst system compared to other available complexes in the present serie