Abstract
Since the presence of contiguous stereocentres in a natural product or pharmaceutical target often presents an impediment to its synthesis, particularly if one or more of these stereocentres are quaternary, new methodologies for their stereoselective construction are of great importance to synthetic chemists. This thesis outlines the development of two novel and conceptually distinct methodologies for the organolithium-mediated assembly of 5-membered rings bearing contiguous stereocentres.The diastereoselective synthesis of cyclopentyl boronic esters bearing two contiguous fully substituted stereocentres was achieved through the electrophile-induced ring contractive 1,2-metallate rearrangement of enantioenriched 6-membered cyclic alkenyl boronate complexes. A remarkable solvent-induced diastereodivergence was observed, allowing the synthesis of complementary diastereomeric pairs. Using this novel ring contractive methodology and through the subsequent stereospecific functionalisation of the boronic ester moiety, the asymmetric total synthesis of (+)-herbertene-1,14-diol was accomplished.
Additionally, the diastereoselective synthesis of 1,2,3-trifunctionalised pyrrolidines was realised through the formation, lithiation, functionalisation and ring-opening of novel strain-release reagent 1-azabicyclo[2.1.0]pentane (ABP). The lithiation/functionalisation of ABP proved highly regio- and diastereoselective and, upon electrophilic activation, ABP was shown to be more susceptible to nucleophilic attack than its lower and higher homologues.
| Date of Award | 3 Oct 2023 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Varinder K Aggarwal (Supervisor) & Robin B Bedford (Supervisor) |
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