| Abstract: | This thesis describes the development of a diastereoselective conjugate addition of
cyanide. Chapter One contains a critical review of reported asymmetric conjugate
additions of cyanide and a brief summary of non-asymmetric conjugate additions of
cyanide to enones. Chapter Two summarises the initial research objective of this
project; namely development of an enantioselective conjugate addition of cyanide to
enones. Chapter Three presents the research undertaken to achieve this objective and
the evolution of the project to the successful diastereoselective hydrocyanation
employing an oxazolidinone as a chiral auxiliary. In Chapter Three, investigation into
the ZnI2 and YbCb catalysed addition of TMSCN to cyclohexenone and other
carbonyl compounds is detailed. Since enantioselective adaptation of this
methodology proved unsuccessful, further research into the hydrocyanation of a,punsaturated
carbonyl compounds under Sm(O'Pr)3 catalysis with the cheap cyanide
source, acetone cyanohydrin, is detailed. This is followed by adaptation of the
Sm(O'Pr)3 methodology to chiral a,|3-unsaturated W-acyl oxazolidinones to provide a
diastereoselective conjugate addition of cyanide. This section includes a review of
reported asymmetric conjugate additions to chiral a,(3-unsaturated 7V-acyl
oxazolidinones and continues with a discussion of the substrate scope and possible
mechanism of the hydrocyanation. Chapter Three concludes with the application of
this stereoselective hydrocyanation to the synthesis of three drug molecules,
Pregabalin, Baclofen and Rolipram, and includes a brief review of previously reported
syntheses of these molecules. Chapter Four summarises the findings in this thesis and
offers suggestions for future development of this work. Chapter Five gives full
experimental details along with spectroscopic and physical data for all new
compounds. |
1630442_Convine.pdf