Restricted rotation in sterically hindered diarylamines
: Structural requirements, synthesis, and applications of a new class of atropisomers

  • Romain Costil

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Although the stereochemistry of most atropisomers arises from slow rotation about a C–C bond, the ability of the nitrogen atom to adopt a planar geometry promotes conformational rigidity in anilides and aryl ureas. Diarylamines are closely related in architecture to the conformationally stable diaryl ethers and sulfides. However, atropisomerism in this class of compounds had not been reported. Using Dynamic NMR and HPLC techniques, we investigated the factors determining the rates of bond rotation and established the requirements for atropisomerism in diarylamines.
Common methods to synthesise diarylamines, namely metal-catalysed couplings and nucleophilic aromatic substitution reactions, lack tolerance of steric hindrance or generality in structures available, restricting the availability of poly-substituted diarylamines. We developed a N-to-N’ Smiles rearrangement of anthranilamides affording atropisomeric diarylamines with exceptional steric
demand. Incorporating the amide nitrogen of the substrate into a ring allowed the synthesis of 9–12 membered heterocycles by ring expansion. The products adopted a chiral ground state with an intramolecular, transannular hydrogen bond. Their rate of interconversion was found to heavily depend on solvent polarity, ring size and proximate steric hindrance.
Introducing axial chirality into diarylamine-based pincer ligands was attempted in order to study the possibility of atropisomerism to induce enantioselectivity in transition metal-catalysed reactions with this class of ligands.
Finally, restricted rotation in the C–N bonds of anilides was used on rigid aromatic scaffolds to control the relative conformation of extended structures over long distances by dipole repulsion and gain insight on the impact of distance on the communication of stereochemical information by dipoles.
Date of Award23 Jan 2019
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorCraig P Butts (Supervisor) & Jonathan P Clayden (Supervisor)

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