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Delivering Hydroacylation: A General and Enantioselective Process

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

Reporting period: 2015-04-01 to 2017-03-31

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.
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.
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