New Methodologies in Asymmetric Synthesis Merging

Selectivity and Molecular Diversity

Main focus of the research is the design and synthesis of novel multi-site (pro)nucleophilic and (pro)electrophilic carbon matrices – mainly in the heterocyclic domain – and their exploitation in vinylogous and multivinylogous carbon-carbon bond-forming reactions.

Vinylogy concept: Firstly introduced by R. C. Fuson in 1935, the “Principle of Vinylogy” states that a given functional group within a molecule may relay its function (i.e. its electronic properties) to a distant point in the molecule provided that interposed conjugated unsaturated linkages are present. As an example, g-enolization of α,β-unsaturated carbonyl compounds provides ambident C-nucleophiles where the conventional “normal” C-a nucleophilicity may be usurped by that of the distant, vinylogous C-γ  carbon atom. Extending this concept, a conjugated polyenolate may be regarded as a multi-site C-nucleophile on the alternating α, γ,ε, ..., ω carbon sites. The synthesis of such pluripotent substrates and their use in chemo/regio/stereocontrolled synthesis is a formidable challenge in contemporary organic synthesis.

The aldol/Mannich/Michael chemistry: how vinylogy impacts the product complexity (X=O,NR).

In recent past years, application of the vinylogy concept in asymmetric synthesis enabled us to access diverse collections of high-quality small-molecule scaffolds and targets ranging from unnatural and natural carbasugars and alkaloids to nucleosides, amino acids, peptidomimetics and heterocycles (e.g. γ-butenolides, pyrrolinones, 2-oxindoles). Thus, the exploitation of the “vinylogy concept” is a powerful opportunity to selectively accessing molecular diversity en route to biologically and pharmaceutically relevant molecules.

Representative structures of nucleophilic and pro-nucleophilic vinylogous donor heterocycles in our works. 

Main publications about this subject (2006-2016):