Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents.

In this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information File 1 of this article.

Rhodium(III) and iridium(III) complexes with 1,2-naphthoquinone-1-oximate as a bidentate ligand: synthesis, structure, and biological activity.

The synthesis and characterization of three novel iridium(III) complexes and one rhodium(III) complex with 1-nitroso-2-naphthol (3) chelating as a 1,2-naphthoquinone-1-oximato ligand are described. The reaction of mu(2)-halogenido-bridged dimers [(eta(5)-C(5)Me(5))IrX(2)](2) [X is Cl (1a), Br (1b), I (1c)] and [(eta(5)-C(5)Me(5))RhCl(2)](2) (2a) with 3 in CH(2)Cl(2) yields the mononuclear complexes (eta(5)-C(5)Me(5))IrX(eta(2)-C(10)H(6)N(2)O) (4a, 4b, 4c) and (eta(5)-C(5)Me(5))RhCl(eta(2)-C(10)H(6)N(2)O) (5a). All compounds were characterized by their (1)H and (13)C NMR, IR, and mass spectra, UV/vis spectra were recorded for 4a and 5a. The X-ray structure analyses revealed a pseudo-octahedral "piano-stool" configuration for the metals with bidentate coordination through oximato-N and naphthoquinone-O, forming a nearly planar five-membered metallacycle. The metal complexes 4a and 5a were evaluated in respect to their cytotoxicity and binding affinity toward double-stranded DNA. As determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, both exerted a much stronger cytotoxic effect toward HeLa and HL60 cancer cell lines than did cisplatin. The remarkable cytotoxicity of the compounds tested may be attributed to necrosis, rather than to apoptosis, as it is evidenced by the caspase-3/7 activation assay. No clear evidence was found for interaction with double-stranded DNA. The melting experiments showed no significant differences between thermodynamic parameters of intact DNA and DNA incubated with 3, 4a, or 5a, although these derivatives altered DNA recognition by the BamHI restriction enzyme. Therefore, the screened iridium and rhodium complexes 4a and 5a may still be interesting as potential anticancer drugs owing to their high cytotoxicity toward cancer cell lines, whereas they do not modify DNA in a way similar to that of cisplatin.

Preparation of polyfunctional zinc organometallics using an Fe- or Co-catalyzed Cl/Zn-exchange.

A new Fe- or Co-catalyzed Cl/Zn-exchange reaction allows the direct transformation of aryl, heteroaryl, and also alkyl chlorides into the corresponding zinc reagents. The method tolerates functional groups such as a nitrile or an ester. Remarkably, secondary and tertiary alkyl chlorides are suitable substrates for the Cl/Zn exchange.

Phosphorodiamidate-directed metalation of N-heterocycles using Mg- and Zn-TMP bases.

The strong directing ability of the N,N,N',N'-tetramethyldiaminophosphorodiamidate group has been used to achieve selective metalations on various heterocycles such as pyridines, quinolines and quinoxalines with TMP-derived bases like TMPMgCl x LiCl, TMP(2)Mg x 2 LiCl, and TMP(2)Zn x 2 MgCl(2) x 2 LiCl. This protocol was applied in the synthesis of etoricoxib, talnetant and a P-selectin inhibitor.

Derivatives of 1,5-diamino-1H-tetrazole: a new family of energetic heterocyclic-based salts.

1,5-Diamino-1H-tetrazole (2, DAT) can easily be protonated by reaction with strong mineral acids, yielding the poorly investigated 1,5-diaminotetrazolium nitrate (2a) and perchlorate (2b). A new synthesis for 2 is introduced that avoids lead azide as a hazardous byproduct. The reaction of 1,5-diamino-1H-tetrazole with iodomethane (7a) followed by the metathesis of the iodide (7a) with silver nitrate (7b), silver dinitramide (7c), or silver azide (7d) leads to a new family of heterocyclic-based salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, X-ray structure determination, and initial safety testing (impact and friction sensitivity). Most of the salts exhibit good thermal stabilities, and both the perchlorate (2b) and the dinitramide (7c) have melting points well below 100 degrees C, yet high decomposition onsets, defining them as new (7c), highly energetic ionic liquids. Preliminary sensitivity testing of the crystalline compounds indicates rather low impact sensitivities for all compounds, the highest being that of the perchlorate (2b) and the dinitramide (7c) with a value of 7 J. In contrast, the friction sensitivities of the perchlorate (2b, 60 N) and the dinitramide (7c, 24 N) are relatively high. The enthalpies of combustion (Delta(c)H degrees ) of 7b-d were determined experimentally using oxygen bomb calorimetry: Delta(c)H degrees (7b) = -2456 cal g(-)(1), Delta(c)H degrees (7c) = -2135 cal g(-)(1), and Delta(c)H degrees (7d) = -3594 cal g(-)(1). The standard enthalpies of formation (Delta(f)H degrees ) of 7b-d were obtained on the basis of quantum chemical computations using the G2 (G3) method: Delta(f)H degrees (7b) = 41.7 (41.2) kcal mol(-)(1), Delta(f)H degrees (7c) = 92.1 (91.1) kcal mol(-)(1), and Delta(f)H degrees (7d) = 161.6 (161.5) kcal mol(-)(1). The detonation velocities (D) and detonation pressures (P) of 2b and 7b-d were calculated using the empirical equations of Kamlet and Jacobs: D(2b) = 8383 m s(-)(1), P(2b) = 32.2 GPa; D(7b) = 7682 m s(-)(1), P(7b) = 23.4 GPa; D(7c) = 8827 m s(-)(1), P(7c) = 33.6 GPa; and D(7d) = 7405 m s(-)(1), P(7d) = 20.8 GPa. For all compounds, a structure determination by single-crystal X-ray diffraction was performed. 2a and 2b crystallize in the monoclinic space groups C2/c and P2(1)/n, respectively. The salts of 7 crystallize in the orthorhombic space groups Pna2(1) (7a, 7d) and Fdd2 (7b). The hydrogen-bonded ring motifs are discussed in the formalism of graph-set analysis of hydrogen-bond patterns and compared in the case of 2a, 2b, and 7b.