Descrizione del progetto
Un’innovativa catalisi combinata apre le porte a una nuova funzionalizzazione farmaceutica
I chimici sintetici sono alla costante ricerca di modi per accedere a funzionalità nuove e che siano anche efficienti e sostenibili. La funzionalizzazione remota, che sfrutta la reattività di un gruppo funzionale in una molecola per generare una reazione in una posizione differente, possiede il potenziale per aprire la strada praticamente qualsiasi derivato, ma rimane ancora piuttosto difficoltosa. In particolare, la funzionalizzazione remota degli alcoli alifatici è un percorso significativo, sebbene sottosviluppato, per importanti composti di rilevanza industriale e farmaceutica. Il progetto ALCO2-FUNC, finanziato dall’UE, sta combinando catalisi fotoredox e catalisi del nichel all’avanguardia, sfruttando i benefici di ognuna. Le reazioni in condizioni blande creeranno prodotti di valore elevato da precursori semplici e abbondanti, con risultati importanti per l’industria farmaceutica.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
43007 Tarragona
Spagna