Abstract
The generally accepted monoacyloxyboron mechanism of boron-catalysed direct amidation is brought into question in this study, and new alternatives are proposed. We have carried out a detailed investigation of boron-catalysed amidation reactions, through study of the interaction between amines/carboxylic acids and borinic acids, boronic acids and boric acid, and have isolated and characterised by NMR/X-ray crystallography many of the likely intermediates present in catalytic amidation reactions. Rapid reaction between amines and boron compounds was observed in all cases, and it is proposed that such boron-nitrogen interactions are highly likely to take place in catalytic amidation reactions. These studies also clearly show that borinic acids are not competent catalysts for amidation, as they either form unreactive amino-carboxylate complexes, or undergo protodeboronation to give boronic acids. It therefore seems that at least three free coordination sites on the boron atom are necessary for amidation catalysis to occur. However, these observations are not consistent with the currently accepted 'mechanism' for boron-mediated amidation reactions involving nucleophilic attack of an amine onto a monomeric acyloxyboron intermediate, and as a result of our observations and theoretical modelling, alternative proposed mechanisms are presented for boron-mediated amidation reactions. These are likely to proceed via the formation of a dimeric B-X-B motif (X = O, NR), which is uniquely able to provide activation of the carboxylic acid, whilst orchestrating the delivery of the amine nucleophile to the carbonyl group. Quantum mechanical calculations of catalytic cycles at the B3LYP+D3/Def2-TZVPP level (solvent = CH2Cl2) support the proposal of several closely related potential pathways for amidation, all of which are likely to be lower in energy than the currently accepted mechanism.
Highlights
Boron compounds have a rich, fascinating and complex structural chemistry, especially related to clusters, cages, complexes and anions associated with B–O1 and B–N2 containing systems
We have investigated carboxylic acid/amine/boron catalyst systems experimentally and computationally and have shown
We have demonstrated that whereas boronic acids can catalyse amidation reactions, borinic acids are ineffective as catalysts
Summary
Boron compounds have a rich, fascinating and complex structural chemistry, especially related to clusters, cages, complexes and anions associated with B–O1 and B–N2 containing systems. Such systems are well known to “have a distinct tendency to disproportionate, apparently more so than those of any other nonmetallic elements”.1a This observation means that identifying and controlling the role played by boron in reactions and catalytic processes is challenging and has proved so on many occasions. In the catalytic asymmetric CBS reduction system[3] both nitrogen and oxygen ligands aCentre for Sustainable Chemical Processes, Department of Chemistry, Durham University, Science Site, South Road, Durham, DH1 3LE, UK.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.