Abstract
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.
