CAT-NAT

Project description

Although cross-coupling reactions have become one of the pillars of modern chemical synthesis, the ability to forge sp3 architectures from naturally-occurring entities or chemical feedstocks with improved flexibility, practicality, predictable site-selectivity, preparative utility and stereocontrol still remains a major challenge in catalytic endeavours.

The successful realization of this goal will contribute to create new logics of organic synthesis when rapidly and reliably building up molecular architectures from simple precursors in both basic and applied research. This is particularly important when building up sp3 linkages in an efficient and catalytic manner, given than an increase of sp3 character in drug candidates improve several molecular attributes that ultimately contribute to clinical success, including solubility, molecular shape (3D-structure) or substrate recognition, among others.

CAT-NAT offers a series of catalytic methodologies for forging sp3 linkages by harnessing native functional groups such as sp3 C-H bonds, aliphatic carboxylic acids, aliphatic alcohols, alpha olefins and CC bonds as adaptative handles for bond-construction, without losing sight the mechanistic implications of these processes. The multidisciplinary nature of the project is illustrated by the merger of organic synthesis, organometallic catalysis and light-induced processes for streamlining the synthesis of valuable structures in the drug discovery pipeline, even in the context of late-stage functionalization, such as carboxylic acids, nitrogen containing heterocycles or fluorinated molecules, among others. In addition, this project will also offer a new enabling technique for the catalytic valorization of N2O, a greenhouse gas with much greater warming potential than CO2, and its conversion to added-value chemicals.

Preliminary results demonstrate the feasibility of many of the tasks delineated in CAT-NAT, constituting a valuable entry point for building up sp3 architectures in a tunable, controllable and general fashion. Given the prospective potential of the technologies included in this proposal, we expect that CAT-NAT will not only provide new dogmas in retrosynthetic analysis by fundamentally altering the way sp3 architectures are made, but also a a la carte technique that industrial and academic chemists can make use of when building up densely functionalized backbones from simple and available precursors.

Proyecto PID2021-123801NB-I00 financiado por MCIN/AEI/10.13039/501100011033/ FEDER, UE