Project description
A new method for linking organic compounds
Cross-coupling reactions are one of the most sophisticated tools available to chemists for synthesising complex organic molecules. They offer a way of creating carbon–carbon bonds, which are the staple of modern drug development. However, the ability to form carbon atoms joined by sp3–sp3 bonds with predictable site selectivity, precise control of the stereochemistry of a reaction and nearly zero waste production has eluded chemists for decades. The EU-funded NOVOFLAT project will offer a pioneering approach for forging sp3–sp3 bonds via a triple cascade reaction that enables the intramolecular decarboxylation of simple and available carboxylic acid esters, releasing CO2 as the sole by-product. NOVOFLAT will not only change the way sp3–sp3 bonds are formed but also increase our understanding of chain-walking reactions.
Objective
Although cross-coupling reactions have become one of the pillars of modern chemical synthesis, the ability to forge sp3–sp3 bonds with improved flexibility, practicality, predictable site-selectivity, preparative utility, stereocontrol and with nearly zero-generation of waste has eluded chemists for decades, remaining a major challenge and an uncharted cartography in catalytic endeavours. The successful realization of this goal will represent a paradigm shift from the standard logic of organic synthesis in both basic and applied research, as increasing the number of sp3-hybridized carbon atoms has become a necessary goal in the drug discovery pipeline. NOVOFLAT offers a pioneering approach for forging sp3–sp3 linkages via a triple catalytic cascade that enables an unprecedented intramolecular decarboxylation of simple and available carboxylic acid esters with CO2 as the sole byproduct. As ester derivatives simply derive from naturally-occurring carboxylic acids and alcohols, this proposal will allow to rapidly access sp3–sp3 linkages with different electronic and steric requirements, thus providing an invaluable opportunity to streamline the discovery of important architectures with applications across the molecular sciences. Preliminary results demonstrate the feasibility to provide “a la carte” predictable tool that chemists could use to control the site where the sp3–sp3 bond-formation takes place in both aliphatic and cyclic frameworks, even at remote sp3 sites. In addition, our general principle offers an unrecognized opportunity to simultaneously construct sp3–sp3 linkages and control the stereochemistry at remote sp3 sites. In this manner, NOVOFLAT will not only provide new dogmas in retrosynthetic analysis by fundamentally altering the way sp3–sp3 bonds are made, but also open new vistas in “chain-walking” reactions, as the incorporation of chirality throughout the alkyl side-chain constitutes “terra incognita” in these technologies.
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
43007 Tarragona
Spain