From hydrocarbons to original chiral building blocks: new solutions for sustainable & asymmetric CH functionalization of alkanes

Descripción del proyecto

Rutas sostenibles para la conversión de hidrocarburos simples en las construcciones originales de moléculas quirales

La química ecológica se centra en el diseño de procesos para la síntesis de moléculas orgánicas de interés, a la vez que reduce la generación de desechos y la demanda de recursos raros y escasos. El proyecto AlCHiMIE, financiado con fondos europeos, se centrará en los enfoques complementarios para convertir los hidrocarburos, la materia prima más sencilla, en alcanos quirales de gran valor añadido que podrían convertirse en componentes originales de la química agrícola y médica. El primer enfoque implicará la funcionalización sin metales de hidrocarburos mediante la activación de enlaces C-H estereoselectivos y regioselectivos. El segundo enfoque se ocupará de valorizar los alcanos mediante la activación C(sp3)–H de metales abundantes catalizada por metal. Para lograrlo y superar la cuestión fundamental de la baja reactividad de los enlaces C(sp3)–H, se propondrán los sistemas catalíticos originales implicados en el diseño de ligandos «inteligentes» o en el uso de socios de acoplamiento altamente activados.

Objetivo

Over the last decade, major environmental concerns, a growing worldwide population and an increasing energy demand, combined with the depletion of natural resources, have become crucial issues. Sustainable chemistry-ably to supply society with key chemical products in an eco-compatible manner-has therefore rapidly become an urgent challenge. The AlCHiMIE aims at providing new solutions towards this important defy by developing a set of complementary approaches to convert hydrocarbons, the simplest feedstock, into high value-added chiral alkanes-essential building blocks for medicinal chemistry. Two approaches are thus proposed. First, undirected, metal-free functionalization of hydrocarbons will be achieved by means of regio- and stereo-selective hypervalent bromine-enabled C-H functionalization. This unique reactivity will be attaint by discovering a largely uncharted, yet extremely appealing field of bromanes. The second approach concerns earth-abundant metal-catalyzed C(sp3)-H activation. To obviate the inherent difficulties of this field, namely the low reactivity of alkanes and arduous stereoinduction while using 3d metals, I will develop bifunctional ligands for Co- and Ni-catalyzed C-H activation. In addition to the role of metal coordination, these ligands featuring a second coordinating motif, will enhance the metallation event and will promote the substrate’s activation, thus unlocking the door towards previously inaccessible modes of reactivity. The combination of both strategies will allow unprecedented hydrocarbon valorization by means of undirected, hypervalent bromine-enabled first functionalization followed by exploiting the newly installed coordinating motif to promote directed, asymmetric Co- and Ni-catalyzed C-H activations. Finally, I will also endeavor in establishing new reactivities arising from the application of diversely substituted hypervalent bromines as coupling partners in enantioselective Co- and Ni-catalyzed C-H activations.