Descripción del proyecto
Una innovadora catálisis combinada allana el camino para una novedosa funcionalización farmacéutica
Los químicos sintéticos siempre están buscando formas de acceder a funcionalidades novedosas de un modo eficiente y sostenible. La funcionalización remota, que aprovecha la reactividad de un grupo funcional en una molécula para generar una reacción en una posición diferente, podría ser la clave para prácticamente cualquier derivado, pero sigue siendo un gran desafío. En particular, la funcionalización remota de alcoholes alifáticos es una ruta importante, pero poco desarrollada, de obtener compuestos relevantes para la industria y el sector farmacéutico. El proyecto ALCO2-FUNC, financiado con fondos europeos, está combinando una avanzada catálisis fotorredox y la catálisis de níquel para aprovechar las ventajas de ambas. Las reacciones en condiciones moderadas permitirán obtener productos de gran valor a partir de precursores sencillos y abundantes, con importantes beneficios para la industria farmacéutica.
Objetivo
The ability to introduce functionality into molecules in a regio- and chemoselective selective manner is of primary importance in the construction of high value molecular compounds but still remains a major challenge for synthetic chemists. The utilization of functionalities present in readily available and inexpensive starting materials to direct the introduction of further complexity is an attractive strategy which has become increasingly popular. Despite recent advances, the remote-functionalization of aliphatic alcohols still remains largely underdeveloped. Considering their prevalence in natural products, compounds displaying important biological activities and chemical feedstocks, efforts to address this problem are deemed necessary. ALCO2-FUNC will make use of an easily installed α bromo-silyl tether to direct functionalization at neighbouring sites. The tether will partake in single electron transfer with a suitable nickel catalyst, initiating a directed radical rebound cascade. The merger of (reductive) nickel catalysis with photoredox catalysis will exploit advantages of both disciplines, enabling the development of a divergent strategy by careful control of key catalytic steps. Furthermore, carbon dioxide will be utilized as a C1 synthon to provide a valuable carboxylation strategy. To such end, simple alcohols will be converted to their β-carboxylated counterparts (via regioselective 1,5 hydrogen atom transfer) or remotely-carboxylated (following a nickel chain-walking sequence). Taken together, the synergy between photoredox and nickel catalysis will be employed in ALCO2-FUNC to develop novel synthetic strategies to access high value compounds from simple precursors. The proposed methodology is expected to operate under mild conditions (room temperature, low-energy irradiation) increasing functional group compatibility and setting the basis for the implementation in the late-stage functionalization of advanced pharmaceuticals.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
43007 Tarragona
España