Delivering Hydroacylation: A General and Enantioselective Process

Informations projet

DEGENHA

N° de convention de subvention: 656493

DOI

10.3030/656493

Projet clôturé le 8 Janvier 2017

Date de signature de la CE 11 Mars 2015

Date de début 1 Avril 2015

Date de fin 31 Mars 2017

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 183 454,80

Contribution de l’UE

€ 183 454,80

Coordonné par

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom

Periodic Reporting for period 1 - DEGENHA (Delivering Hydroacylation: A General and Enantioselective Process)

Période du rapport: 2015-04-01 au 2017-03-31

Résumé du contexte et des objectifs généraux du projet

This project was focused on the development of a suite of truly general hydroacylation catalysts that demonstrate high levels of functional group tolerance, enantioselectivity, broad applicability and ease of use in the laboratory. These advances were achieved by the development of a new modular ligand system, based on the small-bite angle hemilabile diphosphines. By achieving these advances hydroacylation will become a general and robust disconnection for the synthesis of fine and bulk chemicals, new materials and target molecules.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The work performed during this action can be summarised in four different work packages:

WP1: We have fully explored a new ligand structural type with the aim of expanding the available range of alkene and alkyne substrates for HA, while maintaining a chelating aldehyde. Several new ligands have been successfully synthesised and tested in hydroacylation reactions.
This work is still being further explored within the research group. It has not been disseminated yet.

WP2: We have worked on the possibility of employing enantiomerically enriched ligands to perform enantioselective hydroacylations. We have designed and successfully synthesised a chiral ligand that is now being fully explored for its application in HA reactions.
This work is still being investigated within the research group. It has not been disseminated yet.

WP3: We have worked on improving the need for a chelating substituent for hydroacylation reactions. As a more attractive alternative, we have discovered that a new and interesting class of chelating group can be applied to hydroacylation reactions with excellent results.
This work is almost ready to submit for publication. It has also been disseminated at several scientific conferences.

WP4: With the aim of exploring the potential wide utility of HA reactions in the synthesis of target compounds, we have developed a new and robust methodology to deliver highly substituted and optically active ketone products from the controlled assembly of three readily available fragments. We have exploited the use of a single rhodium complex to promote a sequential alkyne hydroacylation and boronic acid conjugate addition.
This work has been published in Chem. Sci. 2017, 8, 536 (open access, doi: 10.1039/C6SC03066A). It has also been disseminated at several scientific conferences.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

This project has delivered powerful new tools – alkene and alkyne hydroacylation – for synthetic chemistry. By developing user-friendly, efficient, selective and general catalysts, and partnering these with readily available substrates, we have delivered a series of reactions of wide utility that will impact on many areas of science.

The key to the project was the design, and then synthesis, of a completely novel class of small-bite angle hemilabile diphosphine ligands, in both an achiral and chiral series. Although these novel ligands have been designed for their utility in the described hydroacylation chemistry, it is highly likely that they will find application in related processes. These new ligands have allowed the delivery of a number of novel transformations, and they will keep serving us as excellent tools for further developments of more.

Methodology developed during work package 4