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Proton motion and chirality transfer in modal aza-Morita-Baylis-Hillman reaction systems

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posted on 28.03.2022, 22:48 by Ryan Thomas Kenny
Proton transfer is a ubiquitous process in organic and biological chemistry, particularly prevalent in biological or designed asymmetric catalysis. Our initial work developed an acid regulated, asymmetric organocatalysis of a model proton-transfer reaction known as the aza-Morita-Baylis-Hillman (aza-MBH) reaction, in which three catalytic motifs cooperate, within a BINAP chiral framework, to catalyse the aza-MBH reaction between methyl vinyl ketone and aryl N-tosyl imines only when activated by external benzoic acid (BzOH). New questions now focus on the exact nature of this switchable catalytic proficiency. This thesis work will uncover mechanistic details that underpin this switchability. In Chapter 2, the origin of the acid-regulated catalytic proficiency in our trifunctional aza-MBH reaction was investigated by a combination of 2D NMR spectroscopy, molecular mechanics and DFT calculations. An ensemble solution structure of a new proton-shuttling ground state intermediate was identified and elucidated. In Chapter 3, the role of the acid additive in the C-C bond formation and proton transfer was investigated, and a new conjugative mode of catalysis was revealed after discovering a surprising role of the substrate in commanding the proton shuttle for the subsequent steps of C-C bond formation and proton transfer. In Chapter 4, new substrates for this conjugative mode of catalysis in the aza-MBH reaction were identified. Finally, in Chapter 5, kinetic differentiation of cognate substrates through this conjugative mode of catalysis in the aza-MBH reaction was propagated by the Soai reaction to create an asymmetric ripple for superior chiral amplification outcomes. It was then demonstrated that chemical diversity and chirality can both expand through chemical assemblies that undergo conjugative catalysis driven by coordinated proton transfer.


Table of Contents

Chapter 1 Model systems for chirality transfer by asymmetric catalysis -- Chapter 2 Mechanistic investigations of a proton shuttle in trifunctional organocatalysis of an aza-MBH model system -- Chapter 3 Conjugative catalysis from an aza-MBH proton shuttle -- Chapter 4 Scope of the trifunctional conjugative catalysis in the aza-MBH model system -- Chapter 5 Propagation of chirality via an aza-MBH-Soai asymmetric ripple -- chapter 6 Conclusions and future directions


Includes bibliographic references Theoretical thesis.

Awarding Institution

Macquarie University

Degree Type

Thesis PhD


PhD, Macquarie University, Faculty of Science and Engineering, Department of Molecular Sciences

Department, Centre or School

Department of Molecular Sciences

Year of Award


Principal Supervisor

Fei Liu


Copyright Ryan Thomas Kenny 2020. Copyright disclaimer: http://mq.edu.au/library/copyright




1 online resource (xxiv, 235, 116 pages) illustrations

Former Identifiers

mq:72355 http://hdl.handle.net/1959.14/1284015