Project description
Innovative combo catalysis opens the door to novel pharmaceutical functionalisation
Synthetic chemists are constantly looking for ways to access novel functionalities and to do so efficiently and sustainably. Remote functionalisation that exploits the reactivity of one functional group in a molecule to generate a reaction at a different position has the potential to unlock the door to just about any derivatives, but it is still quite challenging. In particular, the remote functionalisation of aliphatic alcohols is an important yet underdeveloped pathway to important compounds of industrial and pharmaceutical relevance. The EU-funded ALCO2-FUNC project is combining cutting-edge photoredox catalysis and nickel catalysis, exploiting the benefits of each. Reactions under mild conditions will yield products of high value from simple and abundant precursors with important outcomes for the pharmaceutical industry.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
43007 Tarragona
Spain