Mitchell, Aileen Laura

2019-02-15T14:37:16Z

2019-02-15T14:37:16Z

2009

Quaternary carbon centres are ubiquitous in nature, typically in natural products. The task of creating an all carbon quaternary centre, bearing an alkyl moiety with differentiated functionalities and substituents is a desired key step in organic synthesis. A variety of endeavours by research groups have lead to the construction of stereogenic quaternary centres, albeit with narrow scope of substrate. Despite the repertoire of transition metals/ligands, chiral auxiliaries and reagents available at hand, efficient enantioselective and organocatalytic methodologies for the construction of all carbon quaternary centres still remains a daunting challenge for synthetic chemists. One of the most popular methods to install a quaternary centre is via a conjugate addition, the addition of a chiral tertiary enolate to an electron deficient alkene or carbonyl compound has led to high levels of synthetic accomplishment over generations. Our strategy to assemble such quaternary centres focused on an organocatalytic tandem Michael-aldol reaction, as an efficient one-pot strategy to install vicinal quaternary centres with good levels of enantioselective induction. Initial 1,4-conjugate addition of the nucleophile with α-acrolein type Michael acceptors generates the enolate, which is now set up to undergo an intramolecular aldol reaction providing the desired molecules. Molecular complexes of this class are also amenable to further catalytic transformations and synthetic elaborations.

This thesis presents our investigations towards organocatalytic enantioselective strategies for the assembly of fully substituted quaternary centres.

http://hdl.handle.net/1842/35355

The University of Edinburgh

Annexe Thesis Digitisation Project 2019 Block 22

Already catalogued

Asymmetric synthesis of quaternary centres using organocatalysis

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy