Modern organic chemistry strives to achieve rapid molecular complexity from simple achiral substrates. One method by which this may be achieved is with enolate formation followed by attack on an electrophile which can generate one, two or even more new stereocentres in one step. However regioselective generation of an enolate in the presence of several enolisable sites has always proved problematical. A partial answer to this problem has been provided by the development of the reductive aldol reaction. The first part of this thesis is concerned with describing a highly diastereoselective Co(II)-catalysed reductive aldol reaction between α,β-unsaturated amides and ketones. The reaction proceeds using substoichiometric quantities of cobalt(II) in the presence of a stoichiometric quantity of the reductant diethylzinc. Using both N,Ndimethyl and morpholine amides, the reactions are tolerant of substituted aromatic ketones as well as aliphatic ketones. The reaction also proceeded well when the β-carbon was substituted with both aromatic and aliphatic groups resulting in improved diastereoselection. The racemic work is followed by the development of an asymmetric version of the reaction using oxazolidinone chiral auxiliaries that impart high levels of diastereofacial selectivity. The reaction was found to proceed with a variety of aromatic ketones and once again, substitution of the β-carbon resulted in improved diastereoselectivity. Finally work on formal homo aldol cyclisations using substoichiometric quantities of Ni(II) also in the presence of a stoichiometric quantity of diethylzinc is described. This work aims to develop methodology that involves double cyclisations with the formation of up to five contiguous stereocentres. Although unsuccessful, useful conclusions for future work were made as well as the serendipitous discovery of a apparent base catalysed alternative cyclisation pathway that successfully generated two new rings and four contiguous stereocentres.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:562506 |
| Date | January 2009 |
| Creators | Lumby, Ralph James Richard |
| Contributors | Wai Lam, Hon Wai |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/3890 |
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