{"id":{"repo_id":"whiterose","oai_identifier":"oai:etheses.whiterose.ac.uk:1549"},"canonical_url":"https://search.dev.ndltd.org/etd/whiterose/oai:etheses.whiterose.ac.uk:1549","repository":{"repo_id":"whiterose","name":"White Rose University Consortium","base_url":"https://etheses.whiterose.ac.uk/cgi/oai2"},"display":{"title":"New lithiation methodologies to 2-substituted nitrogen heterocycles","abstract":"This thesis describes the development of methodologies for lithiation-trapping and lithiation-arylation of N-Boc heterocycles in the position α to nitrogen as well as in situ infra-red spectroscopic monitoring of lithiation reactions and the application of lithiation-arylation in total synthesis. Chapter 2 details the use of in situ infra-red spectroscopy to monitor the lithiation of N-Boc pyrrolidine, N-Boc piperidine, N-Boc homopiperidine, an N-Boc acetal piperidine, N-Boc-Nʹ-benzyl piperazine, N-Boc-Nʹ-i-Pr imidazolidine and an O-alkyl carbamate in diethyl ether using s-BuLi and the diamines TMEDA, (–)-sparteine, or the (+)-sparteine surrogate. Chapter 3 describes the expansion of a previously reported two-ligand catalytic lithiation-trapping procedure for N-Boc pyrrolidine, discussing the optimisation of catalytic lithiation conditions, the use of new bispidine-derived diamine ligands and examples of two-ligand catalytic lithiation-arylation of N-Boc pyrrolidine. The application of stoichiometric and catalytic lithiation-arylation of N-Boc pyrrolidine in total synthesis is presented in chapter 4. Lithiation-arylation is used to complete the shortest and most efficient synthesis of (S)-nicotine to date, as well as the shortest synthesis of SIB1508Y and to attempt the first asymmetric synthesis of (R)-dihydroshihunine. Additionally, a protocol for the lithiation-vinylation of N-Boc pyrrolidine is developed and used to carry out the first asymmetric synthesis of (R)-maackiamine. Chapter 5 details the development of a new diamine-free racemic lithiation procedure for the lithiation-trapping and lithiation-arylation of N-Boc pyrrolidine, N-Boc-Nʹ-i-Pr imidazolidine and N-Boc-Nʹ-benzyl piperazine. Additionally, diamine-free lithiations are monitored using in situ infra-red spectroscopy. In chapter 6, benzylic lithiation-trapping of N-Boc-2-phenyl pyrrolidine is described. Lithiation-trapping of rac-N-Boc-2-phenyl pyrrolidine is first discussed, followed by lithiation-trapping of enantioenriched (R)-N-Boc-2-phenyl pyrrolidine, giving access to products bearing enantioenriched quaternary stereocentres. The use of in situ infra-red spectroscopic monitoring was integral to the development of this methodology.","abstract_html":"This thesis describes the development of methodologies for lithiation-trapping and lithiation-arylation of N-Boc heterocycles in the position α to nitrogen as well as in situ infra-red spectroscopic monitoring of lithiation reactions and the application of lithiation-arylation in total synthesis. Chapter 2 details the use of in situ infra-red spectroscopy to monitor the lithiation of N-Boc pyrrolidine, N-Boc piperidine, N-Boc homopiperidine, an N-Boc acetal piperidine, N-Boc-Nʹ-benzyl piperazine, N-Boc-Nʹ-i-Pr imidazolidine and an O-alkyl carbamate in diethyl ether using s-BuLi and the diamines TMEDA, (–)-sparteine, or the (+)-sparteine surrogate. Chapter 3 describes the expansion of a previously reported two-ligand catalytic lithiation-trapping procedure for N-Boc pyrrolidine, discussing the optimisation of catalytic lithiation conditions, the use of new bispidine-derived diamine ligands and examples of two-ligand catalytic lithiation-arylation of N-Boc pyrrolidine. The application of stoichiometric and catalytic lithiation-arylation of N-Boc pyrrolidine in total synthesis is presented in chapter 4. Lithiation-arylation is used to complete the shortest and most efficient synthesis of (S)-nicotine to date, as well as the shortest synthesis of SIB1508Y and to attempt the first asymmetric synthesis of (R)-dihydroshihunine. Additionally, a protocol for the lithiation-vinylation of N-Boc pyrrolidine is developed and used to carry out the first asymmetric synthesis of (R)-maackiamine. Chapter 5 details the development of a new diamine-free racemic lithiation procedure for the lithiation-trapping and lithiation-arylation of N-Boc pyrrolidine, N-Boc-Nʹ-i-Pr imidazolidine and N-Boc-Nʹ-benzyl piperazine. Additionally, diamine-free lithiations are monitored using in situ infra-red spectroscopy. In chapter 6, benzylic lithiation-trapping of N-Boc-2-phenyl pyrrolidine is described. Lithiation-trapping of rac-N-Boc-2-phenyl pyrrolidine is first discussed, followed by lithiation-trapping of enantioenriched (R)-N-Boc-2-phenyl pyrrolidine, giving access to products bearing enantioenriched quaternary stereocentres. The use of in situ infra-red spectroscopic monitoring was integral to the development of this methodology.","abstract_has_math":false,"creators":["Barker, Graeme"],"institution":"University of York","degree_name":"Ph.D","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["O'Brien, Peter"],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-06","date_published":"2011-06","updated_at":"2026-07-24T06:04:44Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["uk.bl.ethos.557181"],"render_values":[{"text":"uk.bl.ethos.557181","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["O'Brien, Peter"]},{"key":"dc:creator","label":"Author","values":["Barker, Graeme"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-06"]},{"key":"dc:date.issued","label":"Date","values":["2011-06"]},{"key":"dc:publisher.commercial","label":"Dc Publisher Commercial","values":["University of York"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Chemistry (York)"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of York"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://etheses.whiterose.ac.uk/id/eprint/1549/"]},{"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","label":"Identifier","values":["uk.bl.ethos.557181"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://etheses.whiterose.ac.uk/id/eprint/1549/1/Graeme%27s_Thesis_Corrected.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This thesis describes the development of methodologies for lithiation-trapping and lithiation-arylation of N-Boc heterocycles in the position α to nitrogen as well as in situ infra-red spectroscopic monitoring of lithiation reactions and the application of lithiation-arylation in total synthesis. Chapter 2 details the use of in situ infra-red spectroscopy to monitor the lithiation of N-Boc pyrrolidine, N-Boc piperidine, N-Boc homopiperidine, an N-Boc acetal piperidine, N-Boc-Nʹ-benzyl piperazine, N-Boc-Nʹ-i-Pr imidazolidine and an O-alkyl carbamate in diethyl ether using s-BuLi and the diamines TMEDA, (–)-sparteine, or the (+)-sparteine surrogate. Chapter 3 describes the expansion of a previously reported two-ligand catalytic lithiation-trapping procedure for N-Boc pyrrolidine, discussing the optimisation of catalytic lithiation conditions, the use of new bispidine-derived diamine ligands and examples of two-ligand catalytic lithiation-arylation of N-Boc pyrrolidine. The application of stoichiometric and catalytic lithiation-arylation of N-Boc pyrrolidine in total synthesis is presented in chapter 4. Lithiation-arylation is used to complete the shortest and most efficient synthesis of (S)-nicotine to date, as well as the shortest synthesis of SIB1508Y and to attempt the first asymmetric synthesis of (R)-dihydroshihunine. Additionally, a protocol for the lithiation-vinylation of N-Boc pyrrolidine is developed and used to carry out the first asymmetric synthesis of (R)-maackiamine. Chapter 5 details the development of a new diamine-free racemic lithiation procedure for the lithiation-trapping and lithiation-arylation of N-Boc pyrrolidine, N-Boc-Nʹ-i-Pr imidazolidine and N-Boc-Nʹ-benzyl piperazine. Additionally, diamine-free lithiations are monitored using in situ infra-red spectroscopy. In chapter 6, benzylic lithiation-trapping of N-Boc-2-phenyl pyrrolidine is described. Lithiation-trapping of rac-N-Boc-2-phenyl pyrrolidine is first discussed, followed by lithiation-trapping of enantioenriched (R)-N-Boc-2-phenyl pyrrolidine, giving access to products bearing enantioenriched quaternary stereocentres. The use of in situ infra-red spectroscopic monitoring was integral to the development of this methodology."]},{"key":"dc:format","label":"Dc Format","values":["other"]},{"key":"dc:title","label":"Title","values":["New lithiation methodologies to 2-substituted nitrogen heterocycles"]}]}],"canonical_facts":{"dc:contributor.advisor":["O'Brien, Peter"],"dc:creator":["Barker, Graeme"],"dc:date":["2011-06"],"dc:date.issued":["2011-06"],"dc:description.abstract":["This thesis describes the development of methodologies for lithiation-trapping and lithiation-arylation of N-Boc heterocycles in the position α to nitrogen as well as in situ infra-red spectroscopic monitoring of lithiation reactions and the application of lithiation-arylation in total synthesis. Chapter 2 details the use of in situ infra-red spectroscopy to monitor the lithiation of N-Boc pyrrolidine, N-Boc piperidine, N-Boc homopiperidine, an N-Boc acetal piperidine, N-Boc-Nʹ-benzyl piperazine, N-Boc-Nʹ-i-Pr imidazolidine and an O-alkyl carbamate in diethyl ether using s-BuLi and the diamines TMEDA, (–)-sparteine, or the (+)-sparteine surrogate. Chapter 3 describes the expansion of a previously reported two-ligand catalytic lithiation-trapping procedure for N-Boc pyrrolidine, discussing the optimisation of catalytic lithiation conditions, the use of new bispidine-derived diamine ligands and examples of two-ligand catalytic lithiation-arylation of N-Boc pyrrolidine. The application of stoichiometric and catalytic lithiation-arylation of N-Boc pyrrolidine in total synthesis is presented in chapter 4. Lithiation-arylation is used to complete the shortest and most efficient synthesis of (S)-nicotine to date, as well as the shortest synthesis of SIB1508Y and to attempt the first asymmetric synthesis of (R)-dihydroshihunine. Additionally, a protocol for the lithiation-vinylation of N-Boc pyrrolidine is developed and used to carry out the first asymmetric synthesis of (R)-maackiamine. Chapter 5 details the development of a new diamine-free racemic lithiation procedure for the lithiation-trapping and lithiation-arylation of N-Boc pyrrolidine, N-Boc-Nʹ-i-Pr imidazolidine and N-Boc-Nʹ-benzyl piperazine. Additionally, diamine-free lithiations are monitored using in situ infra-red spectroscopy. In chapter 6, benzylic lithiation-trapping of N-Boc-2-phenyl pyrrolidine is described. Lithiation-trapping of rac-N-Boc-2-phenyl pyrrolidine is first discussed, followed by lithiation-trapping of enantioenriched (R)-N-Boc-2-phenyl pyrrolidine, giving access to products bearing enantioenriched quaternary stereocentres. The use of in situ infra-red spectroscopic monitoring was integral to the development of this methodology."],"dc:format":["other"],"dc:identifier":["uk.bl.ethos.557181"],"dc:identifier.uri":["https://etheses.whiterose.ac.uk/id/eprint/1549/1/Graeme%27s_Thesis_Corrected.pdf"],"dc:publisher.commercial":["University of York"],"dc:publisher.department":["Chemistry (York)"],"dc:publisher.institution":["University of York"],"dc:relation.isreferencedby":["https://etheses.whiterose.ac.uk/id/eprint/1549/"],"dc:title":["New lithiation methodologies to 2-substituted nitrogen heterocycles"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D"]},"updated_at":"2026-07-24T06:04:44Z"}