A Leap in Ligand Technology: The Development and Valorization of Novel Chiral Diphosphine Ligands

Descrizione del progetto

Catalisi chirale avanzata

Le molecole chirali esistono in due forme speculari e la precisione nella loro struttura è essenziale nei prodotti farmaceutici, nelle fragranze e nei prodotti agrochimici. Per fabbricarli in modo efficiente, i chimici utilizzano catalizzatori e ligandi chirali che consentono trasformazioni chimiche fondamentali; ciononostante, la diversità strutturale dei ligandi a disposizione è limitata, il che ne limita le applicazioni, e la loro produzione è spesso dispendiosa in termini di tempo e denaro. Per risolvere questo problema, il progetto AziPhos, finanziato dal CER, si basa su una scoperta rivoluzionaria di una nuova classe di ligandi fosfinici chirali che possono essere sintetizzati in un paio di passaggi attraverso l’implementazione di un solido processo catalitico, secondo un approccio che dovrebbe far progredire significativamente la sintesi asimmetrica, aprendo la strada allo sviluppo di nuovi farmaci chirali.

Obiettivo

The search for innovative and efficient chiral catalysts and ligands for producing enantiopure molecules remains a vital priority across the pharmaceutical, flavours and fragrances, and agrochemical sectors. A significant majority of newly developed drugs are chiral, creating an increasing demand for advancements in asymmetric synthesis and the development of chiral ligands and metal complexes, which is driving substantial progress in asymmetric catalysis. Despite these advances, the number of chemical transformations required to produce chiral molecules continues to grow, while only a small fraction of the hundreds of chiral ligands developed for use in chiral catalysts have been commercialized, and even fewer have been successfully scaled for industrial applications.
The most successful ligands, often referred to as ‘privileged phosphine ligands,’ have achieved notable success in various transformations. However, their structural diversity is limited, constraining further expansion of reactivity, and their production costs remain high. Most of these successful chiral phosphine ligands require multi-step, time-consuming, and costly non-catalytic synthetic routes.
In this context, this proposal aims to build upon a recent breakthrough—the discovery of a completely new class of highly efficient chiral phosphine ligands. Notably, these ligands offer a significant advantage by being producible via a robust catalytic synthesis that requires only 1-2 steps. Moreover, the structure of this new ligand family is highly modular, allowing for rapid diversification and the creation of a library of related ligands.
These promising features suggest that our discovery holds the potential to develop a product with a compelling value proposition, representing a significant advancement over current competing solutions in the market.