{"id":{"repo_id":"soton","oai_identifier":"oai:eprints.soton.ac.uk:72925"},"canonical_url":"https://search.dev.ndltd.org/etd/soton/oai:eprints.soton.ac.uk:72925","repository":{"repo_id":"soton","name":"University of Southampton","base_url":"https://eprints.soton.ac.uk/cgi/oai2"},"display":{"title":"Tandem reaction sequences on a zirconocene template","abstract":"The novel research work described in this thesis covers three areas of organozirconium chemistry.<br/>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 ?-H elimination process.<br/>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.<br/>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.","abstract_html":"The novel research work described in this thesis covers three areas of organozirconium chemistry.&lt;br/&gt;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 ?-H elimination process.&lt;br/&gt;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.&lt;br/&gt;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.","abstract_has_math":false,"creators":["Stec, Jozef"],"institution":"University of Southampton","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Whitby, Richard"],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01","date_published":"2010-01","updated_at":"2026-07-24T04:36:10Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Whitby, Richard"]},{"key":"dc:creator","label":"Author","values":["Stec, Jozef"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-01"]},{"key":"dc:date.issued","label":"Date","values":["2010-01"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Chemistry (pre 2011 reorg)","School of Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Southampton"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://eprints.soton.ac.uk/72925/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://eprints.soton.ac.uk/72925/1/JS_Thesis_26.01.2010_to_upload.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The novel research work described in this thesis covers three areas of organozirconium chemistry.<br/>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 ?-H elimination process.<br/>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.<br/>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."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Tandem reaction sequences on a zirconocene template"]}]}],"canonical_facts":{"dc:contributor.advisor":["Whitby, Richard"],"dc:creator":["Stec, Jozef"],"dc:date":["2010-01"],"dc:date.issued":["2010-01"],"dc:description.abstract":["The novel research work described in this thesis covers three areas of organozirconium chemistry.<br/>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 ?-H elimination process.<br/>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.<br/>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."],"dc:format":["text"],"dc:identifier.uri":["https://eprints.soton.ac.uk/72925/1/JS_Thesis_26.01.2010_to_upload.pdf"],"dc:publisher.department":["Chemistry (pre 2011 reorg)","School of Chemistry"],"dc:publisher.institution":["University of Southampton"],"dc:relation.isreferencedby":["https://eprints.soton.ac.uk/72925/"],"dc:title":["Tandem reaction sequences on a zirconocene template"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D."]},"updated_at":"2026-07-24T04:36:10Z"}