Year
2021
Degree Name
Doctor of Philosophy
Department
School of Chemistry and Molecular Bioscience
Abstract
The design and synthesis of helical diamine, NHC, bis(phosphine) and bis(arsirane) ligand libraries for broad application in asymmetric syntheses was investigated. Previous synthesis of the chiral pool molecule 2,2′-ditosylbiaziridine was optimised and scaled up to a hundred-gram scale using a variety of batch, continuous flow, and microwave strategies. Overall, this synthesis was improved from a total yield of 31% to 56%, with much larger scales, shorter reaction times, and improved safety compared to previous reports.
Subsequent scaling up of ring-opening reactions of 2,2′-ditosylbiaziridine permitted access to larger quantities of enantiomeric materials previously generated in the group, to allow for future comparison of ligands in asymmetric syntheses. Ring-opened products were highly varied in terms of steric and electronic character, with comparable yields on larger scales to previous small-scale reports. Several of the generated diamines were elaborated into corresponding bicyclic systems, and subjected to detosylation to afford diamines. Issues previously encountered with detosylation of produced diamines were investigated, including the generation of 2,2′-dinosylbiaziridine as an alternative with more facile deprotection. The conditions required for consistent detosylation were determined, and (3S,3′S)-3,3′,4,4′-tetrahydro-2H,2′H-3,3′-bibenzo[b][1,4]oxazine developed into the corresponding dihydroimidazolium salt, towards the generation of chiral NHCs. Attempts to form a metal/NHC complex resulted in hydrolysis of the dihydroimidazolium salt, despite efforts to abstract water using 4 Å molecular sieves.
Exhaustive optimisation of the highly unreliable dimerisation previously reported in the group was also undertaken in the pursuit of novel chiral vicinal bis(phosphine) and bis(arsine) ligands. Following many iterations to the methodology described, it was determined that using LDA as a base using higher temperatures afforded more consistent lithiation of phosphine and arsine monomers relative to previous reports. It was also concluded that previously reported non-oxidative conditions for subsequent dimerisation facilitated by THF-soluble Cu(OPiv)2 are incorrect, and it is thought that the procedure requires oxidative conditions.
Recommended Citation
Smyth, Jamie, The Design, Synthesis and Scaling Up of Chiral Helical Ligand Libraries for Asymmetric Syntheses, Doctor of Philosophy thesis, School of Chemistry and Molecular Bioscience, University of Wollongong, 2021. https://ro.uow.edu.au/theses1/1393
FoR codes (2008)
0302 INORGANIC CHEMISTRY, 0305 ORGANIC CHEMISTRY
Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.