Fordyce, Euan Alexander Fraser

2010-11-22T12:18:43Z

2010-11-22T12:18:43Z

2009

A highly diastereoselective nickel-catalysed reductive aldol cyclisation is described. Using Ni(acac)2 as a precatalyst and diethylzinc as a stoichiometric reductant, various α,β-unsaturated carbonyl compounds tethered through an amide or ester linkage to a ketone electrophile underwent efficient cyclisation to afford β-hydroxylactams and β-hydroxylactones respectively. The scope of this process is broad with variation in the α,β-unsaturated carbonyl component, ketone and, where applicable, the nitrogen protecting group all tolerated. A series of experiments, including deuterium-labelling studies, were carried out in an attempt to gain insight into the possible reaction mechanisms that might be operative. II. Development of Novel Methodologies for the Silylation and Stannylation of Base-Sensitive Cyclopropenes Two distinct approaches to the synthesis of silyl- and stannylcyclopropenes are described. Using substoichiometric quantities of Cu(acac)2 and 1,2-bis(diphenylphosphino)ethane in combination with (trifluoromethyl)trimethylsilane, a diverse range of 1,3,3-trisubstituted cyclopropenes underwent direct silylation to afford the corresponding 1-silylcyclopropenes in good to excellent yield. Attempts to adapt these conditions to synthesise the corresponding stannylcyclopropenes proved unsuccessful. However, by employing (pentafluoroethyl)tributylstannane and stoichiometric potassium fluoride, it was possible to access 1-stannylcyclopropenes in comparable yields. It was also demonstrated that both the stannyl- and silylcyclopropene derivatives synthesised using these methodologies were able to serve as precursors for a variety of novel molecules that might otherwise be difficult to access using alternative methods.

http://hdl.handle.net/1842/4377

en

The University of Edinburgh

nickel-catalysed reductive aldol cyclisation

deuterium-labelling studies

synthesis of silylcyclopropenes

silylcyclopropene derivatives

Nickel-catalysed reductive aldol cyclisation: scope and mechanistic insight

Development of novel methodologies for the silylation and stannylation of base-sensitive cyclopropenes

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy