The sophisticated molecular machinery found in nature is fundamental to biological processes, enabling life on Earth, and provides inspiration for the development of synthetic small-molecule functional machines for future technologies. All biological molecular machines operate autonomously, away from thermodynamic equilibrium. While modifications to biological machinery have allowed for the modulation of their function, the conditions in which they operate are limited and they are prone to degradation. Consequently, the field of small-molecule synthetic molecular machines has emerged and grown over recent decades. To date, only one example of a truly autonomous, chemically fuelled rotary molecular motor has been reported. Herein, we address the need for autonomous molecular machines and present transition metal catalysis as a platform for the development of rotary molecular motors which exhibit unidirectional rotation about an atropoisomeric biaryl axis. In our design, unidirectional motion is predicated on two non-microscopically reverse chemical steps, each coupled to a 180° rotation of the biaryl axis: a methodologically novel sulfoxide-directed, Pd-catalysed C–H borylation and a boronic ester-mediated protodeboronation, with protodeboronation enabled by activation of the pinacol ester to a borininol. Controlled rotation of the motor is based on the interconversion of the conformationally stable biaryl motif with transient, conformationally labile bridged intermediates. Our studies lay the foundations for the future realisation of an autonomous, chemically fuelled rotary molecular motor which provides unidirectional motion about a C–C single bond using transition metal catalysis. Several design aspects and geometric constraints of the motor are explored with a synergistic computational approach and details into the C–H borylation are addressed with density functional theory, allowing us to eliminate motor designs predictively, before attempting to produce them experimentally. The computational work is supplemented by an independent, detailed study on substituent steric effects where we outline a new steric parameter to qualitatively interpret the ‘size’ of common organic substituents. Finally, the prospects of our work, such as the synthetic utility of our borylation methodology, is explored after a brief summary of the achievements of this project.
Transition metal catalysis for chemically fuelled rotary molecular-level motion
Mcford, A. W. (Author). 6 Dec 2022
Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)