1. Explanation of the work carried out by the beneficiaries and Overview of the progress
The action officially started on November 1, 2018.
Three students, namely Patricia Camarero Gonzalez (Spain), Fabian Herbrik (Germany), Milena Krstic (Serbia) were selected for the three PhD positions and they have been officially enrolled in the Doctorate School of Industrial Chemistry at the Università degli Studi di Milano- Prof. Dr. Maurizio Benaglia (University of Milano) will act as Tutor (Supervisor) and Dr. Miguel Sanz (Taros Chemicals) as co-Tutor (co-Supervisor) of all three students.
They started their own research activities and PhD programme on June 1 2019.
General progress of the action
For the scientific WPs, the following activities done by the ESRs can be summarized
ESR 1, MILENA KRSTIC
In batch and in flow catalytic addition of C1 fragments to C=N bonds
The PhD student worked on the preparation of substrates for cyanide addition (imines) but not really on the synthesis of chiral catalysts for cyanide addition. One chiral catalyst only was prepared but more focus was given on the preliminary exploration of the biomimetic approach and ion pair concept (deliverable D1.6).
Therefore, ESR1 worked on topics related to D1.6 and D1.5 and in parallel, she has started to study other chiral catalysts related to deliverable D1.2 iminophosphoranes, and started to work on the use of flow reactors to develop enantioselective phase transfer catalytic reactions for the preparation of chiral quaternary amino acids, that is the main goal of the project.
ESR 2 – PATRICIA CAMARERO GONZALEZ
Stereoselective reactions of nitroesters with different organocatalysts
First times focused particularly on the synthesis of α,α-disubstitued-nitroacrylates, which have not been extensively studied before. After optimizing the synthesis of α-nitroacrylates, the enantioselective reduction was studied, using diethyl and tert-butyl Hantzsch ester and a thiourea-based catalyst. Enantioselectivities up to 70% were obtained. DFT Computational analysis on the reduction of the model compound has been performed. Future studies will focus on the determination of absolute configuration of the obtained products and study on the scope of the reaction.
ESR 3 – FABIAN HERBRIK
Supported, recyclable chiral catalysts, catalytic and 3D-printed reactors; flow chemistry.
ESR3 has mainly explored the use of in-flow catalytic reactors, but he has also studied the development of a multistep telescoped synthesis of a chiral pharmaceutically relevant molecule.
Continuous flow experiments showed a drastic increase of productivity, up to 100-fold, going from batch to flow chemistry. The proof of concept, i.e. the possibility to perform enantioselective organo-photoredox catalysis with immobilized catalysts, was demonstrated for the first time.
In parallel, the investigation of in-flow photocatalytic reactions under homogeneous conditions was also performed. The light-catalysed alkylation of an aldehyde, promoted by a chiral imidazolidinone, followed by oxidation to carboxylic acid, its activation and condensation with an heterocyclic amine to afford an enantiomerically enriched active pharmaceutically relevant molecule, is the subject of the study of the last six months aimed to realize a multistep telescoped synthesis of a chiral molecule.
