Delivering Hydroacylation as a General Reaction for Synthesis: A Combined Organic and Organometallic Approach
Lead Research Organisation:
University of Oxford
Department Name: Oxford Chemistry
Abstract
The hydroacylation of alkenes and alkynes is a fundamentally simple process involving the addition of an aldehyde across and alkene or an alkyne to generate a ketone-containing product. Although a number of metal catalysts are known to promote the reaction the majority of these systems are inefficient, require harsh reaction conditions and have limited substrate scope. The aim of this proposal is to develop new catalysts systems that will allow the process to deliver products in high yields, using stable, easy to handle complexes that operate under mild conditions, and that function for a wide range of organic substrates. To arrive at this point we propose a collaborative program of research involving both organic and inorganic chemists. We will design new classes of ligands and catalysts that allow stabilisation of the key reactive metal-centre while still allowing the reaction to proceed. Preliminary results from our laboratories have shown that such an approach is valid. Along with catalyst design we will study the mechanism of the process using a variety of characterisation methods, and will build up a detailed understanding of the individual steps of the reaction. This mechanistic information will then be fed into the catalysts design loop to deliver yet more effective catalysts. Applications of the proposed chemistry includes the efficient synthesis of ketone and enone systems, ring-closing reactions to generate cyclic ketones, and the potential application of the chemistry to the synthesis of new polymeric materials.
Publications
Arambasic M
(2013)
Activating group recycling in action: a rhodium-catalyzed carbothiolation route to substituted isoquinolines.
in Organic letters
Castaing M
(2013)
2-Aminobenzaldehydes as versatile substrates for rhodium-catalyzed alkyne hydroacylation: application to dihydroquinolone synthesis.
in Angewandte Chemie (International ed. in English)
Chaplin AB
(2012)
Intermolecular hydroacylation: high activity rhodium catalysts containing small-bite-angle diphosphine ligands.
in Journal of the American Chemical Society
González-RodrĂguez C
(2011)
Rhodium-catalyzed branched-selective alkyne hydroacylation: a ligand-controlled regioselectivity switch.
in Angewandte Chemie (International ed. in English)
Hooper J
(2013)
Carbon-carbon bond construction using boronic acids and aryl methyl sulfides: orthogonal reactivity in Suzuki-type couplings
in Chemical Science
Hooper JF
(2012)
Aryl methyl sulfides as substrates for rhodium-catalyzed alkyne carbothiolation: arene functionalization with activating group recycling.
in Journal of the American Chemical Society
Hooper JF
(2013)
Traceless chelation-controlled rhodium-catalyzed intermolecular alkene and alkyne hydroacylation.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Hooper JF
(2016)
a-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation.
in Journal of the American Chemical Society
Parsons S
(2011)
O -Substituted Alkyl Aldehydes for Rhodium-Catalyzed Intermolecular Alkyne Hydroacylation: The Utility of Methylthiomethyl Ethers
in Organic Letters
Pawley R
(2012)
Intermolecular Alkyne Hydroacylation. Mechanistic Insight from the Isolation of the Vinyl Intermediate That Precedes Reductive Elimination
in Organometallics
Description | Efficient new catalysts for intermolecular hydroacylation |
Exploitation Route | These catalysts will be use by others |
Sectors | Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology |