{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/21368"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/21368","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Intermolecular and intramolecular asymmetric induction at the beta-benzylic position of carboxamides in directed lithiation-substitution sequences","abstract":"Asymmetric induction at the $\\beta$-benzylic position of secondary carboxamides in directed lithiation-substitution reactions has been achieved intermolecularly by using ($-$)-sparteine as the external chiral ligand and intramolecularly by using $\\alpha$-methylbenzylamine as the covalently attached chiral auxiliary.","abstract_html":"Asymmetric induction at the <span class=\"etd-inline-math\">&beta;</span>-benzylic position of secondary carboxamides in directed lithiation-substitution reactions has been achieved intermolecularly by using ($-$)-sparteine as the external chiral ligand and intramolecularly by using <span class=\"etd-inline-math\">&alpha;</span>-methylbenzylamine as the covalently attached chiral auxiliary.","abstract_has_math":true,"creators":["Du, Hua"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Beak, Peter"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T13:06:38Z","date_published":"2011-05-07T13:06:38Z","updated_at":"2026-07-22T22:25:17Z","subjects":["Chemistry, Organic"],"languages":["eng"],"rights":["Copyright 1995 Du, Hua"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9624337","(UMI)AAI9624337"],"render_values":[{"text":"AAI9624337","href":null,"code":true},{"text":"(UMI)AAI9624337","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/21368","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Beak, Peter"]},{"key":"dc:creator","label":"Author","values":["Du, Hua"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T13:06:38Z","10000-01-01","1995"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Organic"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1995 Du, Hua"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9624337","(UMI)AAI9624337","http://hdl.handle.net/2142/21368"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Asymmetric induction at the $\\beta$-benzylic position of secondary carboxamides in directed lithiation-substitution reactions has been achieved intermolecularly by using ($-$)-sparteine as the external chiral ligand and intramolecularly by using $\\alpha$-methylbenzylamine as the covalently attached chiral auxiliary.","The lithiation of N-methyl-3-phenylpropanamide with sec-butyllithium/($-$)-sparteine followed by reactions with a variety of electrophiles give highly enantioenriched (R)-3-substituted-N-methyl-3-phenylpropanamides. This methodology has been applied to the synthesis of (R)-3-phenylalkanoic acids with enantiomeric excesses of 78% to 88%. The synthetic utility of this methodology is also illustrated by the synthesis of (R-)-3-phenyl-4,4-disubstituted $\\gamma$-lactones with enantiomeric excesses of 54% to 84% and the synthesis of (3R, 5R)-3-phenyl-5-iodomethyl-$\\delta$-lactone with an enantiomeric excess of 80%.","This methodology is extended to N-methyl-3-(o-methoxyphenyl)propanamide. The lithiation-substitution reactions with alkyl halides as the electrophiles give (R)-3-substituted-N-methyl-3-(o-methoxyphenyl)propanamides in yields of 63% to 71% with enantiomeric excesses of 80% to 86%. Asymmetric synthesis of (R)-substituted hydrocoumarins have been achieved in the following hydrolysis and demethylation.","The reaction of racemic lithiated intermediate with the electrophile in the presence of ($-$)-sparteine is shown to proceed in high enantioselectivity. A series of lithium-tin exchange reactions and a study of lithiations of racemic 3-deuterated-N-methyl-3-phenylpropanamide are reported which show that lithiation of N-methyl-3-phenylpropanamide with sec-butyllithium/($-$)-sparteine gives racemic carbanion that is complexed by ($-$)-sparteine and reacts stereoselectively with the electrophiles. Ground state structures of N-lithio-N-methyl-3-lithio-3-phenylpropanamide-($-$)-sparteine and rationalization for the enantioselectivity observed are presented. This work demonstrates that high enantioenrichment can be achieved in the reaction of a racemic carbanion with the electrophile in the presence of an external chiral ligand.","The lithiation and alkylation of (R)-N-$\\alpha$-methylbenzyl-3-(o-methoxyphenyl) propanamide gives $\\beta$-substituted amides in yields of 55% to 72% with diastereomeric excesses of 90% to 96%. The synthesis of (S)-substituted hydrocoumarins is reported.","Made available in DSpace on 2011-05-07T13:06:38Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9624337.pdf: 6935637 bytes, checksum: 88432474b3281e623155db9e3e601a58 (MD5) Previous issue date: 1995","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:50:18Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:22:58-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Intermolecular and intramolecular asymmetric induction at the beta-benzylic position of carboxamides in directed lithiation-substitution sequences"]}]}],"canonical_facts":{"dc:contributor":["Beak, Peter"],"dc:creator":["Du, Hua"],"dc:date":["2011-05-07T13:06:38Z","10000-01-01","1995"],"dc:description":["Asymmetric induction at the $\\beta$-benzylic position of secondary carboxamides in directed lithiation-substitution reactions has been achieved intermolecularly by using ($-$)-sparteine as the external chiral ligand and intramolecularly by using $\\alpha$-methylbenzylamine as the covalently attached chiral auxiliary.","The lithiation of N-methyl-3-phenylpropanamide with sec-butyllithium/($-$)-sparteine followed by reactions with a variety of electrophiles give highly enantioenriched (R)-3-substituted-N-methyl-3-phenylpropanamides. This methodology has been applied to the synthesis of (R)-3-phenylalkanoic acids with enantiomeric excesses of 78% to 88%. The synthetic utility of this methodology is also illustrated by the synthesis of (R-)-3-phenyl-4,4-disubstituted $\\gamma$-lactones with enantiomeric excesses of 54% to 84% and the synthesis of (3R, 5R)-3-phenyl-5-iodomethyl-$\\delta$-lactone with an enantiomeric excess of 80%.","This methodology is extended to N-methyl-3-(o-methoxyphenyl)propanamide. The lithiation-substitution reactions with alkyl halides as the electrophiles give (R)-3-substituted-N-methyl-3-(o-methoxyphenyl)propanamides in yields of 63% to 71% with enantiomeric excesses of 80% to 86%. Asymmetric synthesis of (R)-substituted hydrocoumarins have been achieved in the following hydrolysis and demethylation.","The reaction of racemic lithiated intermediate with the electrophile in the presence of ($-$)-sparteine is shown to proceed in high enantioselectivity. A series of lithium-tin exchange reactions and a study of lithiations of racemic 3-deuterated-N-methyl-3-phenylpropanamide are reported which show that lithiation of N-methyl-3-phenylpropanamide with sec-butyllithium/($-$)-sparteine gives racemic carbanion that is complexed by ($-$)-sparteine and reacts stereoselectively with the electrophiles. Ground state structures of N-lithio-N-methyl-3-lithio-3-phenylpropanamide-($-$)-sparteine and rationalization for the enantioselectivity observed are presented. This work demonstrates that high enantioenrichment can be achieved in the reaction of a racemic carbanion with the electrophile in the presence of an external chiral ligand.","The lithiation and alkylation of (R)-N-$\\alpha$-methylbenzyl-3-(o-methoxyphenyl) propanamide gives $\\beta$-substituted amides in yields of 55% to 72% with diastereomeric excesses of 90% to 96%. The synthesis of (S)-substituted hydrocoumarins is reported.","Made available in DSpace on 2011-05-07T13:06:38Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9624337.pdf: 6935637 bytes, checksum: 88432474b3281e623155db9e3e601a58 (MD5) Previous issue date: 1995","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:50:18Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:22:58-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["AAI9624337","(UMI)AAI9624337","http://hdl.handle.net/2142/21368"],"dc:language":["eng"],"dc:rights":["Copyright 1995 Du, Hua"],"dc:subject":["Chemistry, Organic"],"dc:title":["Intermolecular and intramolecular asymmetric induction at the beta-benzylic position of carboxamides in directed lithiation-substitution sequences"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:17Z"}