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Title: Tandem reaction sequences on a zirconocene template
Author: Stec, Jozef
ISNI:       0000 0004 2678 0279
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2010
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The novel research work described in this thesis covers three areas of organozirconium chemistry. The first area concerns the synthesis of rigid core structures containing the cis-bicyclo[3.3.0]oct-2-ene skeleton. Zirconocene mediated co-cyclisation of 1,6-enynes provides unsaturated 5-membered zirconacycles which are homologated to 6-membered zirconacycles by insertion of 1,1-dihalo-1-lithio species (dihalogenocarbenoids). Further rearrangement to a novel zirconium-alkenylidene complex driven by acetylides provided a powerful method for a rapid construction of novel bicyclic compounds with the potential for functionalization at multiple sites. Such obtained analogues provided an attractive template for structure-activity studies with respect to investigating the biological function of the human orphan nuclear receptors: LRH-1 and SF-1. Equivalent tandem insertion of 1,1-dihalo-1-lithio species and lithium acetylides into saturated zirconacycles resulted in the synthesis of novel bicyclo[3.3.0]octanes, though in many cases limited by a β-H elimination process. In the second area is presented research work relating to acyclic organozirconocene systems. Insertion of allenyl and propargyl carbenoids into organochlorozirconocenes and bisalkyl/-alkynyl zirconocenes led to 1,2-zirconate rearrangement with expulsion of the corresponding leaving group. Lewis acid promoted insertion of aldehydes and ketones into the resulting allenyl/propargyl zirconocene intermediate gave after hydrolysis a series of propargylic alcohols. Insertion of carbenoids derived from chiral propargyl tosylates into organochlorozirconocenes and further 1,2-metallate rearrangement gave the final alcohols as enantiomerically enriched products. The third area was an attempted total synthesis of the natural product mucosin, whose structure contains a bicyclo[4.3.0]nonane unit with four contiguous stereocentres. Zirconocene mediated co-cyclisation of the appropriate precursor provided four possible diastereoisomers. It was proved that thermodynamic equilibration of the zirconacycle gives the desired bicyclic product as a major isomer. Although the target molecule was not realised, thorough work on Zr-based total synthesis of mucosin has been achieved and a viable route for successful completion of the synthesis has also been proposed.
Supervisor: Whitby, Richard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry