Boron-Assisted Synthesis of Conformationally Controlled Hydrocarbons

  • Johan Pradeilles

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

This thesis is composed of two chapters reporting contributions to two different projects.
The first chapter presents a research project aiming to develop a new class of helical molecules which, upon activation from an external stimulus, would be able to reversibly switch from one screw-sense to the other. All-syn methyl-substituted hydrocarbons, as described by Aggarwal in 2014, were shown to adopt helical conformations with very high levels of control. More importantly, one of these unique molecules could access either the M or the P screw-sense, depending on its physical state. Therefore, all-syn methyl-substituted hydrocarbons seemed to be promising candidates for the design of a new class of molecular switches. A diamond lattice-based analysis revealed that the number of syn-pentane and gauche interactions in the chain was one of the key parameters that dictated its conformational preference. A series of six compounds of different chain lengths was designed and synthesised using an efficient bidirectional iterative homologation of C2-symmetric boronic esters. A QM/NMR approach was employed to quantitatively describe the conformational landscape of these molecules and confirmed the diamond lattice-based model with a good degree of confidence. A screening of different substituents at the termini revealed that alkyne, hydroxyl, amino or aromatic groups could be considered as ‘small’ groups, favouring the helical conformer with both terminal dihedral angles in a gauche conformation. However, the combined effects of two tert-butyl groups might force both terminal dihedral angles to adopt an antiperiplanar conformation, thus favouring the opposite screw-sense. These findings set the experimental basis to design a new molecular switch.
The first part of the second chapter describes the development of a new decarboxylative borylation methodology and its application to the synthesis of a-amino boronic esters. Some medicinal chemistry-type examples and three additional natural products have been added to the substrate scope. Key mechanistic experiments were conducted to prove the radical pathway and provide support for an outer sphere radical trapping process. In the second part, a study on the decarboxylative borylation of amino acids was conducted. First, the reaction conditions were optimised on a proline derivative. With these new conditions in hand, other activated amino acids were tested. However, most of them did not afford the desired products. To identify the cause of failure, a number of parameters were investigated (the effects of free N–H bonds, redox potentials and protecting groups). A different mode of activation involving the use of hypervalent iodine derivatives was attempted but failed to provide the desired products. Finally, a limited substrate scope composed of proline derivatives was subjected to the reaction conditions. Unfortunately, none of these examples gave the desired product.
Date of Award24 Jul 2019
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorPaul J Wyatt (Supervisor) & Varinder K Aggarwal (Supervisor)

Keywords

  • boron
  • conformational control
  • hydrocarbons
  • decarboxylative borylation

Cite this

Boron-Assisted Synthesis of Conformationally Controlled Hydrocarbons
Pradeilles, J. (Author). 24 Jul 2019

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)