Chiral transition-metal complexes as Brønsted-acid catalysts for the asymmetric Friedel-Crafts hydroxyalkylation of indoles.

The Friedel-Crafts reaction between 3,3,3-trifluoropyruvates and indoles is efficiently catalysed by the iridium complex [(η5-C 5Me5)Ir{(R)-Prophos}(H2O)][SbF 6]2 (1) with up to 84% ee. Experimental data and theoretical calculations support a mechanism involving the Brønsted-acid activation of the pyruvate carbonyl by the protons of the coordinated water molecule in 1. Water is not dissociated during the process and, therefore, the catalytic reaction occurs with no direct interaction between the substrates and the metal. This journal is © the Partner Organisations 2014.The authors acknowledge the Ministerio de Economía y Competitividad (MINECO, Grants CTQ2006-03030/BQU, CTQ2009-10303/BQU, CTQ2011-27033 and Consolider Ingenio 2010 CSD2006-003), Gobierno de Aragón (Grupo Consolidado: Catálisis Homogénea Enantioselectiva), Generalitat de Catalunya (2009SGR0259) and the ICIQ foundation for financial support. A. S. and R. R. acknowledge MINECO for predoctoral fellowships. S. D.-G. acknowledges MINECO for a “Torres Quevedo” contract.Peer Reviewe

Mechanistic Studies on Gold-Catalyzed Direct Arene C–H Bond Functionalization by Carbene Insertion: The Coinage-Metal Effect

The catalytic functionalization of the Csp 2-H bond of benzene by means of the insertion of the CHCO2Et group from ethyl diazoacetate (N2=CHCO2Et) has been studied with the series of coinage metal complexes IPrMCl (IPr = IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene) and NaBArF 4 (BArF 4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate). For Cu and Ag, these examples constitute the first of such metals toward this transformation, that also provides ethyl cyclohepta-2,4,6-trienecarboxylate as by-product from the so-called Buchner reaction. In the case of methyl-substituted benzenes, the reaction exclusively proceeds onto the aromatic ring, the Csp 3-H bond remaining unreacted. A significant coinage metal effect has been observed, since the gold catalyst favors the formation of the insertion product into Csp 2-H bond whereas copper and silver preferentially induce the formation of the cycloheptatriene derivative. Experimental studies and theoretical calculations have explained the observed selectivity in terms of the formation of a common Wheland intermediate, resembling an electrophilic aromatic substitution, from which the reaction pathway evolves into two separate routes to each product.We thank the Spanish MINECO for CTQ2014-52769-C3-1-R, CTQ2014-57761-R, RED INTECAT CTQ2014-52974-REDC and Severo Ochoa Excellence Accreditation 2014-2018 SEV-2013-0319 and the ICIQ Foundation for financial support

Photolytic activation of late-transition-metal-carbon bonds and their reactivity toward oxygen

The photolytic activation of palladium(II) and platinum(II) complexes [M(BPI)(R)] (R = alkyl, aryl) featuring the 1,3-bis(2-pyridylimino)isoindole (BPI) ligand has been investigated in various solvents. In the absence of oxygen, the formation of chloro complexes [M(BPI)Cl] is observed in chlorinated solvents, most likely due to the photolytic degradation of the solvent and formation of HCl. The reactivity of the complexes toward oxygen has been studied both experimentally and computationally. Excitation by UV irradiation (365 nm) of the metal complexes [Pt(BPI)Me] and [Pd(BPI)Me] leads to distortion of the square-planar coordination geometry in the excited triplet state and a change in the electronic structure of the complexes that allows the interaction with oxygen. TD-DFT computational studies suggest that, in the case of palladium, the Pd(III) superoxide intermediate [Pd(BPI)(κ1-O2)Me] is formed and, in the case of platinum, the Pt(IV) peroxide intermediate [Pt(BPI)(κ2-O2)Me]. For alkyl complexes where metal–carbon bonds are sufficiently weak, the photoactivation leads to the insertion of oxygen into the metal–carbon bond to generate alkylperoxo complexes: for example [Pd(BPI)OOMe], which has been isolated and structurally characterized. For stronger M–C(aryl) bonds, the reaction of [Pt(BPI)Ph] with O2 and light results in a Pt(IV) complex, tentatively assigned as the peroxo complex [Pt(BPI)(κ2-O2)Ph], which in chlorinated solvents reacts further to give [Pt(BPI)Cl2Ph], which has been isolated and characterized by scXRD. In addition to the facilitation of oxygen insertion reactions, UV irradiation can also affect the reactivity of other components in the reaction mixture, such as the solvent or other reaction products, which can result in further reactions. Labeling studies using [Pt(BPI)(CD3)] in chloroform have shown that photolytic reactions with oxygen involve degradation of the solvent

Thermally activated site exchange and quantum exchange coupling processes in unsymmetrical trihydride osmium compounds

Reaction of the hexahydride complex OsH6(PiPr3)2 (1) with pyridine-2-thiol leads to the trihydride derivative OsH3{κ-N,κ-S-(2-Spy)}(PiPr3)2 (2). The structure of 2 has been determined by X-ray diffraction. The geometry around the osmium atom can be described as a distorted pentagonal bipyramid with the phosphine ligands occupying axial positions. The equatorial plane contains the pyridine-2-thiolato group, attached through a bite angle of 65.7(1)°, and the three hydride ligands. The theoretical structure determination of the model complex OsH3{κ-N,κ-S-(2-Spy)}(PH3)2 (2a) reveals that the hydride ligands form a triangle with sides of 1.623, 1.714, and 2.873 Å, respectively. A topological analysis of the electron density of 2a indicates that there is no significant electron density connecting the hydrogen atoms of the OsH3 unit. In solution, the hydride ligands of 2 undergo two different thermally activated site exchange processes, which involve the central hydride with each hydride ligand situated close to the donor atoms of the chelate group. The activation barriers of both processes are similar. Theoretical calculations suggest that the transition states have a cis-hydride−dihydrogen nature. In addition to the thermally activated exchange processes, complex 2 shows quantum exchange coupling between the central hydride and the one situated close to the sulfur atom of the pyridine-2-thiolato group. The reactions of 1 with l-valine and 2-hydroxypyridine afford OsH3{κ-N,κ-O-OC(O)CH[CH(CH3)2]NH2}(PiPr3)2 (3) and OsH3{κ-N,κ-O-(2-Opy)}(PiPr3)2 (4) respectively, which according to their spectroscopic data have a similar structure to that of 2. In solution, the hydride ligands of 3 and 4 also undergo two different thermally activated site exchange processes. However, they do not show quantum exchange coupling. The tetranuclear complexes [(PiPr3)2H3Os(μ-biim)M(TFB)]2 [M = Rh (5), Ir (6); H2biim = 2, 2‘-biimidazole; TFB = tetrafluorobenzobarrelene] have been prepared by reaction of OsH3(Hbiim)(PiPr3)2 with the dimers [M(μ-OMe)(TFB)]2 (M = Rh, Ir). In solution the hydride ligands of these complexes, which form two chemically equivalent unsymmetrical OsH3 units, undergo two thermally activated site exchanges and show two different quantum exchange coupling processes.We thank the DGICYT of Spain (Projects PB95-0806 and PB95-0639-CO2-01, Programa de Promocion General del Conocimiento).Peer reviewe

Oxidative addition of group 14 element hydrido compounds to OsH2(h2-CH2=CHEt)(CO)(PiPr3)2: Synthesis and characterization of the first trihydrido-silyl, trihydrido-germyl and trihydrido-stannyl derivatives of Os(IV)

The dihydrido−olefin complex OsH2(η2-CH2CHEt)(CO)(PiPr3)2 (2) reacts with H2SiPh2 to give OsH3(SiHPh2)(CO)(PiPr3)2 (3). The molecular structure of 3 has been determined by X-ray diffraction (monoclinic, space group P21/c with a = 16.375(2) Å, b = 11.670(1) Å, c =18.806(2) Å, β = 107.67(1)°, and Z = 4) together with ab initio calculations on the model compound OsH3(SiH3)(CO)(PH3)2. The coordination geometry around the osmium center can be rationalized as a heavily distorted pentagonal bipyramid with one hydrido ligand and the carbonyl group in the axial positions. The two other hydrido ligands lie in the equatorial plane, one between the phosphine ligands and the other between the SiHPh2 group and one of the phosphine ligands. Complex 3 can also be prepared by reaction of OsH(η2-H2BH2)(CO)(PiPr3)2 (4) with H2SiPh2. Similarly, the treatment of 4 with HSiPh3 affords OsH3(SiPh3)(CO)(PiPr3)2 (5), while the addition of H3SiPh to 4 in methanol yields OsH3{Si(OMe)2Ph}(CO)(PiPr3)2 (6). Complex 2 also reacts with HGeR3 and HSnR3 to give OsH3(GeR3)(CO)(PiPr3)2 (GeR3 = GeHPh2 (7), GePh3 (8), GeEt3 (9)) and OsH3(SnR3)(CO)(PiPr3)2 (R = Ph (10), nBu (11)), respectively. In solution, compounds 3 and 5−11 are fluxional and display similar 1H and 31P{1H} NMR spectra, suggesting that they possess a similar arrangement of ligands around the osmium atom.We thank the DGICYT (Projects PB92-0092, PB92-0621, and PB93-0222, Programa de Promoción General del Conocimiento) and the EU (Project:  Selective Processes and Catalysis involving Small Molecules) for financial support. E.O. thanks the DGA (Diputación General de Aragón) for a grant.Peer reviewe

Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population

BACKGROUND: Retinitis pigmentosa (RP), a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP). Most of these mutations are clustered in a 500 bp region of exon 4 of RP1. METHODS: Denaturing gradient gel electrophoresis (DGGE) analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out. RESULTS: Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population. CONCLUSION: Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations