Catálisis de oxidación inspirada en metaloenzimas

La formación y la escisión del enlace O-O es posiblemente la reacción más importante en los organismos vivos. La rotura reductora del enlace O-O se lleva a cabo en el citocromo C oxidasa. [1] Esta reacción constituye el componente básico de la respiración celular en organismos aeróbicos, y representa una fuente primaria de energía. La escisión del enlace O-O también tiene lugar en oxigenasas, [2] y resulta en la generación de especies de metal-oxo con altos estados de oxidación, altamente electrófilos, responsables de transformaciones oxidativas. Por otro lado, la formación del enlace O-O se lleva a cabo en un clúster Mn4Ca en el Centro generador de oxígeno Evolving del Fotosistema II (PSII) de las plantas verdes y algunas bacterias. En ambas enzimas oxidativas y de respiración, participan especies metálicas donde los iones metálicos adoptan estados elevados de oxidación; en las oxigenasas como resultado de reacciones de escisión del enlace O-O, mientras que en el PSII éstas son responsables de la formación del enlace O-O. [3] Complejos de coordinación que reproducen aspectos estructurales de sitios activos enzimáticos han demostrado ser competentes para catalizar reacciones análogas, y recientemente algunos de estos complejos se han convertido en herramientas muy atractivas para la síntesis orgánica. [4-8] Además, el estudio de los mecanismos de acción de estos catalizadores ha arrojado luz en los detalles moleculares de los sistemas enzimáticos. Nuestro grupo de investigación lleva a cabo este enfoque y tiene como objetivo el estudio de la química de los complejos de coordinación de hierro con ligandos nitrogenados químicamente robustos y que pueden sostener altos estados de oxidación.[5-8] Nuestros avances en este tema se discuten en la conferencia. [1] S. Ferguson-Miller, G. T. Babcock, Chem. Rev. 1996, 96, 2889-2907. [2] a) M. Costas, M. P. Mehn, M. P. Jensen, L. Que, Jr., Chem. Rev. 2004, 104, 939-986. B) B. J. Wallar, J. D. Lipscomb, Chem. Rev. 1996, 96, 2625-2658. C) E. I. Solomon, et al. Angew. Chem. Int. Ed. 2001, 40, 4570. d) S. Shaik, et al. Chem. Rev. 2010, 110, 949-1017. e) E. G. Kovaleva, J. D. Lipscomb, Nat. Chem. Biol. 2008, 4, 186-193. [3] Y. Umena, K. Kawakami, J.-R. Shen, N. Kamiya, Nature 2011, 55. [4] a) L. Que, W. B. Tolman, Nature 2008, 455, 333-340. b) A. Company, et al. in Iron-Containing Enzymes, Versatile Catalysts of Hydroxylation Reactions in Nature (S. P. De Visser, D. Kumar), RSC, Cambridge, 2011. [5] a) A. Company et al. J. Am. Chem. Soc. 2007, 129, 15766. b) L. Gomez et al Angew. Chem. Int. Ed. 2009, 48, 5720. [6] a) O. Cusso et al. J. Am. Chem. Soc. 2013, 135, 14871 b) I. Prat et al. Nat. Chem. 2011, 3, 788. [7] O. Cussó et al. Org. Lett. 2013, 15, 6158 [8] a) J. Lloret-Fillol Nat. Chem. 2011, 3, 897, b) Company et al. J. Am. Chem. Soc. 2014, 136, 4624Decanato de la Facultad de Ciencias, Vicerrectorado de Investigación, Sección Territorial de la Real Sociedad Española de Química, Asociación de Químicos de Andalucía. Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tec

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Carboxylic Acid Directed γ-Lactonization of Unactivated Primary C-H Bonds Catalyzed by Mn Complexes: Application to Stereoselective Natural Product Diversification

Reactions that enable selective functionalization of strong aliphatic C-H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific C-H bond by catalyst control . Herein we describe the catalytic site-and stereoselec t i v e gamma-lactonization of unactivated primary C-H bonds in carboxylic acid substrates. The system relies on a chiral Mn catalyst that activates aqueous hydrogen peroxide to promote intramolecula r lactonization under mild conditions, via carboxylate binding to the metal center. The system exhibits high site-select i v i t y and enables the oxidation of unactivated primary gamma-C-H bonds even in the presence of intrinsically weaker and a priori more reactive secondary and tertiary ones at alpha- and beta-carbons. With substrates bearing nonequivalent gamma-C-H bonds, the factors governing site-select i v i t y have been uncovered. Most remarkably, by manipulating the absolute chirality of the catalyst, gamma-lactonization at me t h y l groups in gem-dimethyl structural units of rigid cyclic and bicycli c carboxylic acids can be achieved with unprecedented levels of diastereoselectivity. Such control has been successfully exploited in the late-stage lactonization of natural products such as camphoric, camphanic, ketopinic, and isoketopinic acids. DFT analysis points toward a rebound type mechanism initiated by intramolecular 1,7-HAT from a primary gamma-C-H bond of the bound substrate to a highly reactive MnIV-oxyl intermediate, to del i v e r a carbon radical that rapidly lactonizes through carboxylate transfer. Intramolecular kinetic deuter i u m isotope effect and 18O labeling experiments provide strong support to this mechanistic picture

Introducing Fe and Mn as catalysts for the selective functionalization of Csp2-H bonds of arenes by carbene insertion

Título de la versión post-print: Introducing Fe and Mn as catalysts for the selective functionalization of Csp2-H bonds of arenes by carbene insertionThe first examples of the direct functionalization of non-activated aryl sp(2) C-H bonds with ethyl diazoacetate (N2CHCO2Et) catalyzed by Mn- or Fe-based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are Fe-II or Mn-II complexes bearing the tetradentate pytacn ligand (pytacn = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane). When using alkylbenzenes, the alkylic C(sp(3))-H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp(2) C-H bonds.Support for this work was provided by the MINECO (CTQ2014-52769-C3-R-1, CTQ2014-62234-EXP, CTQ2015-70795-P, CTQ2014-54306-P, and CTQ2014-52525P), and the Junta de Andalucia (P10-FQM-06292). A.C. thanks Junta de Andalucia for a research contract. M.C. acknowledges an ICREA Academia Award, 2014 SGR 862 from Generalitat de Catalunya, and ERC-239910

Sponge-like molecular cage for purification of fullerenes

Since fullerenes are available in macroscopic quantities from fullerene soot, large efforts have been geared toward designing efficient strategies to obtain highly pure fullerenes, which can be subsequently applied in multiple research fields. Here we present a supramolecular nanocage synthesized by metal-directed self-assembly, which encapsulates fullerenes of different sizes. Direct experimental evidence is provided for the 1:1 encapsulation of C 60, C 70, C 76, C 78 and C 84, and solid state structures for the host-guest adducts with C 60 and C 70 have been obtained using X-ray synchrotron radiation. Furthermore, we design a washing-based strategy to exclusively extract pure C 60 from a solid sample of cage charged with a mixture of fullerenes. These results showcase an attractive methodology to selectively extract C 60 from fullerene mixtures, providing a platform to design tuned cages for selective extraction of higher fullerenes. The solid-phase fullerene encapsulation and liberation represent a twist in host-guest chemistry for molecular nanocage structures

Generation, Spectroscopic, and Chemical Characterization of an Octahedral Iron(V)-Nitrido Species with a Neutral Ligand Platform

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Observació directa de cicles redox de Ag(I)/Ag(III) de dos electrons en catàlisi de funcionalització d'halurs d'aril

La plata és avui dia àmpliament utilitzada en catàlisi homogènia per a la síntesi de compostos orgànics a causa del seu caràcter d'àcid de Lewis i el seu poder oxidant. La Ag(I) és un potent oxidant monoelectrònic que troba utilitat en un gran nombre de processos catalítics. Tanmateix, els cicles catalítics de dos electrons, molt comuns en la química organometàl·lica dels metalls nobles, no han estat mai considerats possibles per a la plata. En aquest estudi descrivim un cicle catalític Ag(I)/Ag(III) que és operatiu en una reacció model d'acoblament creuat per a la formació d'enllaços C–O. Espècies aril–Ag(III) han estat inequívocament identificades com a intermedis d'aquest cicle catalític. L'estudi de la síntesi i la reactivitat de l'esmentat complex ha permès per primera vegada la caracterització de les etapes d'addició oxidant i eliminació reductiva de formació d'enllaços carboni–nucleò- fil en centres monometàl·lics de plata. El present treball demostra que els processos d'eliminació reductiva en espècies aril–Ag(III) són efectius en reaccions d'acoblament creuat per a la formació d'enllaços C–O, C–N, C–S, C–C i C–halur, incloses les reaccions de fluoració d'arils. Aquest estudi suposa un punt de partida per a l'expansió de la química redox Ag(I)/Ag(III) a noves metodologies per a la síntesi orgànica, en analogia a la química d'acoblament creuat del coure o el pal·ladi. A més, els resultats descrits proporcionen una comprensió mecanística fonamental única en les reaccions d'acoblament creuat catalitzades per plata i refuten la concepció generalment acceptada que la química redox de la plata només pot provenir de processos d'un sol electró.Silver is extensively used in homogeneous catalysis for organic synthesis owing to its Lewis acidity and unique high oxidation power. The high oxidation potential of Ag(I) makes it a powerful one-electron oxidant that finds utility in a large number catalytic processes. However, two-electron redox catalytic cycles, most common in noble metal organometallic reactivity, have never been considered. Herein we show that an Ag(I)/Ag(III) catalytic cycle is operative in a model C–O cross-coupling reaction. Aryl–Ag(III) species have been unequivocally identified as an intermediate in the catalytic cycle. The study of the synthesis and reactivity of this complex has enabled for the first time the direct characterization of aryl halide oxidative addition and carbon–nucleophile bond-forming reductive elimination steps at monometallic silver centers. This report demonstrates that reductive elimination processes at aryl–Ag(III) species are effective for C–O, C–N, C–S, C–C and C–halide coupling reactions, including aryl fluorination. We anticipate our study as the starting point for expanding Ag(I)/Ag(III) redox chemistry into new methodologies for organic synthesis, resembling well-known copper or palladium cross-coupling catalysis. Furthermore, findings described herein provide a unique fundamental mechanistic understanding of Ag-catalyzed cross-coupling reactions and dismiss the generally accepted conception that silver redox chemistry can only arise from one-electron processes

Evidence of otitis media and mastoiditis in a Medieval Islamic skeleton from Spain and possible implications for ancient surgical treatment of the condition

Objective To evaluate lesions on a cranium from the Iberian Peninsula and assess its medico-historical and paleopathological significance. Materials The skeletal remains of a juvenile individual found in a Medieval Islamic grave (10th -16th century) in Eastern Spain. Methods Macroscopic examination of the left and right temporal bones, binocular microscopy, X-ray, and Scanning Electron Microscopy - Energy Dispersive X-ray Spectroscopy (SEM-EDS) were performed. Results A sub-oval perforation superior to the right mastoid process and pathological changes on the right temporal bone were identified. SEM-EDS confirmed the presence of copper in the surrounding area of the perforation. Conclusions The observed pathological changes are most likely compatible with otitis media and subsequent mastoiditis. The sub-oval perforation could be interpreted either as an abscess or as evidence of a surgical procedure (mastoidectomy) or a combination of both; and the Cu traces may be the result of an associated object or, possibly, the application of a plaster with copper acetate used as medical treatment. Significance This case contributes to the paleopathological record and the interpretation of similar cases, and also helps in the understanding of medical care and treatment in Medieval Islam. Limitations The lack of similar pre-modern cases of surgical intervention limits comparability to clinical cases. Suggestion for further research: Exploration into indicators of health care in past population

Supramolecular fullerene sponges as catalytic masks for regioselective functionalization of C60

Isomer-pure poly-functionalized fullerenes are required to boost the development of fullerene chemistry in all fields. On a general basis, multi-adduct mixtures with uncontrolled regioselectivity are obtained, and the use of chromatographic purification is prohibitively costly and time consuming, especially in the production of solar cells. Single-isomer poly-functionalized fullerenes are only accessible via stoichiometric, multistep paths entailing protecting-unprotecting sequences. Herein, a nanocapsule is used as a supramolecular tetragonal prismatic mask to exert full control on the reactivity and the equatorial regioselectivity of Bingel-Hirsch cyclopropanation reactions of a confined C guest. Thus, equatorial bis-, tris-, and tetrakis-C homo-adducts are exclusively obtained in a stepwise manner. Furthermore, isomer-pure equatorial hetero-tetrakis-adducts or hetero-Th-hexakis-adducts are synthesized at will in one-pot synthesis for the first time. This work provides a synthetically valuable path to produce a plethora of new pure-isomer poly-functionalized C-based compounds as candidates for testing in solar cell devices and biomedical applications