{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/26271"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/26271","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"The development of palladium-catalyzed cross-coupling reactions of allylic silanolate salts with aromatic bromides","abstract":"The palladium-catalyzed cross-coupling of allylic silanolate salts with a wide variety of aromatic bromides was developed. The coupling of sodium allyldimethylsilanolate and 2-butenyldimethylsilanolate required extensive optimization to deliver the expected products in high yields. The reaction of the allyldimethylsilanolate takes place at 85 °C under “ligand-less’ conditions in 1,2-dimethoxyethane with allylpalladium chloride dimer (2.5 mol %) to afford 73–95% yields of the allylation products. Both electron-rich and sterically hindered bromides reacted smoothly, whereas electron-poor bromides cross-coupled in poor yield because of a secondary isomerization to the 1-propeneyl isomer (or concommitant polymerization). A modified protocol that employs an electron-rich phosphine ligand (SPhos), a lower reaction temperature (40 °C), and a less polar solvent (toluene) delivers the expected products from electron-poor bromides without isomerization. The 2-butenyldimethylsilanolate (E/Z, 80:20) required additional optimization to maximize the formation of the branched (gamma-coupled) product and resulted in the development of two distinct protocols for gamma-selective coupling. The first protocol took advantage of a remarkable influence of added alkenes (dibenzylideneacetone and norbornadiene) and led to good selectivities for a large number of electron-rich and electron-poor bromides in 40–83% yields. However, bromides containing coordinating groups (particularly in the 2-position) gave lower, and in one case even reversed, site-selectivity. Electron-rich aromatic bromides reacted sluggishly under this protocol and led to lower product yields. The second protocol employed a sterically bulky phosphonium tetrafluoroborate salt (t-BuCy2PH+BF4−) and resulted in 73–94% yields and excellent site-selectivity (gamma/alpha, 25:1–>99:1) in the coupling of electron-rich, electron-poor, sterically hindered, and heteroaromatic bromides. The use of a configurationally homogeneous (Z)-silanolate and nontransferable diethyl groups were critical to achieving excellent results. A unified mechanistic picture involving initial gamma-transmetalation followed by direct reductive elimination or sigma–pi isomerization can rationalize all of the observed trends. The stereochemical course of palladium-catalyzed cross-coupling reactions of an enantioenriched, alpha-substituted, allylic silanolate salt with aromatic bromides was determined. The allylic silanolate salt was prepared in high geometrical (Z/E, 94:6) and high enantiomeric (94:6 er) purity by a copper-catalyzed SN2’ reaction of a resolved carbamate. Eight different aromatic bromides underwent cross-coupling with excellent constitutional site-selectivity and excellent stereospecificity. Stereochemical correlation established that the transmetalation event proceeds through a syn SE’ mechanism with is interpreted in terms of an intramolecular delivery of the arylpalladium electrophile through a key intermediate that contains a discrete Si–O–Pd linkage. The catalytic, asymmetric palladium-catalyzed cross-coupling of sodium 2-butenylsilanolate with aromatic bromides was investigated. A wide range of chiral ligands including olefin, bidentate phosphine, monodentate phosphine, and cyclic and acyclic stereogenic at phosphorus ligands were evaluated. Commonly used chiral, bidentate phosphine ligands provided ineffective palladium-catalysts for the coupling of 2-butenyldimethylsilanolate with aromatic bromides. A catalyst derived from the monodentate phosphine ligand neomenthyldiphenylphosphine (20 mol %) and Pd(dba)2 (5 mol %) provided moderate enantioselectivity (75:25 er) and modest site-selectivity (5.7:1 gamma/alpha) in the coupling. Increased site-selectivity (up to >99:1) was obtained from reactions employing bulky di or trialkylphosphine ligands.","abstract_html":"The palladium-catalyzed cross-coupling of allylic silanolate salts with a wide variety of aromatic bromides was developed. The coupling of sodium allyldimethylsilanolate and 2-butenyldimethylsilanolate required extensive optimization to deliver the expected products in high yields. The reaction of the allyldimethylsilanolate takes place at 85 °C under “ligand-less’ conditions in 1,2-dimethoxyethane with allylpalladium chloride dimer (2.5 mol %) to afford 73–95% yields of the allylation products. Both electron-rich and sterically hindered bromides reacted smoothly, whereas electron-poor bromides cross-coupled in poor yield because of a secondary isomerization to the 1-propeneyl isomer (or concommitant polymerization). A modified protocol that employs an electron-rich phosphine ligand (SPhos), a lower reaction temperature (40 °C), and a less polar solvent (toluene) delivers the expected products from electron-poor bromides without isomerization. The 2-butenyldimethylsilanolate (E/Z, 80:20) required additional optimization to maximize the formation of the branched (gamma-coupled) product and resulted in the development of two distinct protocols for gamma-selective coupling. The first protocol took advantage of a remarkable influence of added alkenes (dibenzylideneacetone and norbornadiene) and led to good selectivities for a large number of electron-rich and electron-poor bromides in 40–83% yields. However, bromides containing coordinating groups (particularly in the 2-position) gave lower, and in one case even reversed, site-selectivity. Electron-rich aromatic bromides reacted sluggishly under this protocol and led to lower product yields. The second protocol employed a sterically bulky phosphonium tetrafluoroborate salt (t-BuCy2PH+BF4−) and resulted in 73–94% yields and excellent site-selectivity (gamma/alpha, 25:1–>99:1) in the coupling of electron-rich, electron-poor, sterically hindered, and heteroaromatic bromides. The use of a configurationally homogeneous (Z)-silanolate and nontransferable diethyl groups were critical to achieving excellent results. A unified mechanistic picture involving initial gamma-transmetalation followed by direct reductive elimination or sigma–pi isomerization can rationalize all of the observed trends. The stereochemical course of palladium-catalyzed cross-coupling reactions of an enantioenriched, alpha-substituted, allylic silanolate salt with aromatic bromides was determined. The allylic silanolate salt was prepared in high geometrical (Z/E, 94:6) and high enantiomeric (94:6 er) purity by a copper-catalyzed SN2’ reaction of a resolved carbamate. Eight different aromatic bromides underwent cross-coupling with excellent constitutional site-selectivity and excellent stereospecificity. Stereochemical correlation established that the transmetalation event proceeds through a syn SE’ mechanism with is interpreted in terms of an intramolecular delivery of the arylpalladium electrophile through a key intermediate that contains a discrete Si–O–Pd linkage. The catalytic, asymmetric palladium-catalyzed cross-coupling of sodium 2-butenylsilanolate with aromatic bromides was investigated. A wide range of chiral ligands including olefin, bidentate phosphine, monodentate phosphine, and cyclic and acyclic stereogenic at phosphorus ligands were evaluated. Commonly used chiral, bidentate phosphine ligands provided ineffective palladium-catalysts for the coupling of 2-butenyldimethylsilanolate with aromatic bromides. A catalyst derived from the monodentate phosphine ligand neomenthyldiphenylphosphine (20 mol %) and Pd(dba)2 (5 mol %) provided moderate enantioselectivity (75:25 er) and modest site-selectivity (5.7:1 gamma/alpha) in the coupling. Increased site-selectivity (up to >99:1) was obtained from reactions employing bulky di or trialkylphosphine ligands.","abstract_has_math":false,"creators":["Werner, Nathan S."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Denmark, Scott E.","Moore, Jeffrey S.","Burke, Martin D.","Girolami, Gregory S."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-08-26T15:20:42Z","date_published":"2011-08-26T15:20:42Z","updated_at":"2026-07-22T22:25:26Z","subjects":["palladium-catalyzed","cross-coupling","catalysis","silanol","silanolate","aromatic bromide","allyl arene","allylic","site-selective","asymmetric","enantioselective","stereospecific","diastereoselective","syn SE'","stereochemical course"],"languages":["en"],"rights":["Copyright 2011 Nathan S. Werner"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/26271","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Denmark, Scott E.","Moore, Jeffrey S.","Burke, Martin D.","Girolami, Gregory S."]},{"key":"dc:creator","label":"Author","values":["Werner, Nathan S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-08-26T15:20:42Z","2013-08-27T10:00:18Z","2011-08"]},{"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":["palladium-catalyzed","cross-coupling","catalysis","silanol","silanolate","aromatic bromide","allyl arene","allylic","site-selective","asymmetric","enantioselective","stereospecific","diastereoselective","syn SE'","stereochemical course"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2011 Nathan S. Werner"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/26271"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The palladium-catalyzed cross-coupling of allylic silanolate salts with a wide variety of aromatic bromides was developed. The coupling of sodium allyldimethylsilanolate and 2-butenyldimethylsilanolate required extensive optimization to deliver the expected products in high yields. The reaction of the allyldimethylsilanolate takes place at 85 °C under “ligand-less’ conditions in 1,2-dimethoxyethane with allylpalladium chloride dimer (2.5 mol %) to afford 73–95% yields of the allylation products. Both electron-rich and sterically hindered bromides reacted smoothly, whereas electron-poor bromides cross-coupled in poor yield because of a secondary isomerization to the 1-propeneyl isomer (or concommitant polymerization). A modified protocol that employs an electron-rich phosphine ligand (SPhos), a lower reaction temperature (40 °C), and a less polar solvent (toluene) delivers the expected products from electron-poor bromides without isomerization. The 2-butenyldimethylsilanolate (E/Z, 80:20) required additional optimization to maximize the formation of the branched (gamma-coupled) product and resulted in the development of two distinct protocols for gamma-selective coupling. The first protocol took advantage of a remarkable influence of added alkenes (dibenzylideneacetone and norbornadiene) and led to good selectivities for a large number of electron-rich and electron-poor bromides in 40–83% yields. However, bromides containing coordinating groups (particularly in the 2-position) gave lower, and in one case even reversed, site-selectivity. Electron-rich aromatic bromides reacted sluggishly under this protocol and led to lower product yields. The second protocol employed a sterically bulky phosphonium tetrafluoroborate salt (t-BuCy2PH+BF4−) and resulted in 73–94% yields and excellent site-selectivity (gamma/alpha, 25:1–>99:1) in the coupling of electron-rich, electron-poor, sterically hindered, and heteroaromatic bromides. The use of a configurationally homogeneous (Z)-silanolate and nontransferable diethyl groups were critical to achieving excellent results. A unified mechanistic picture involving initial gamma-transmetalation followed by direct reductive elimination or sigma–pi isomerization can rationalize all of the observed trends. The stereochemical course of palladium-catalyzed cross-coupling reactions of an enantioenriched, alpha-substituted, allylic silanolate salt with aromatic bromides was determined. The allylic silanolate salt was prepared in high geometrical (Z/E, 94:6) and high enantiomeric (94:6 er) purity by a copper-catalyzed SN2’ reaction of a resolved carbamate. Eight different aromatic bromides underwent cross-coupling with excellent constitutional site-selectivity and excellent stereospecificity. Stereochemical correlation established that the transmetalation event proceeds through a syn SE’ mechanism with is interpreted in terms of an intramolecular delivery of the arylpalladium electrophile through a key intermediate that contains a discrete Si–O–Pd linkage. The catalytic, asymmetric palladium-catalyzed cross-coupling of sodium 2-butenylsilanolate with aromatic bromides was investigated. A wide range of chiral ligands including olefin, bidentate phosphine, monodentate phosphine, and cyclic and acyclic stereogenic at phosphorus ligands were evaluated. Commonly used chiral, bidentate phosphine ligands provided ineffective palladium-catalysts for the coupling of 2-butenyldimethylsilanolate with aromatic bromides. A catalyst derived from the monodentate phosphine ligand neomenthyldiphenylphosphine (20 mol %) and Pd(dba)2 (5 mol %) provided moderate enantioselectivity (75:25 er) and modest site-selectivity (5.7:1 gamma/alpha) in the coupling. Increased site-selectivity (up to >99:1) was obtained from reactions employing bulky di or trialkylphosphine ligands.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2011-07-11T19:36:46Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Werner_Nathan.docx: 4840619 bytes, checksum: 73cc057b0da5723f0ac3c9db1a7ea444 (MD5) Werner_Nathan.pdf: 2703275 bytes, checksum: 9dba12df809a3e246b2ec13fa921e7b3 (MD5)","Made available in DSpace on 2011-08-26T15:20:42Z (GMT). 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The coupling of sodium allyldimethylsilanolate and 2-butenyldimethylsilanolate required extensive optimization to deliver the expected products in high yields. The reaction of the allyldimethylsilanolate takes place at 85 °C under “ligand-less’ conditions in 1,2-dimethoxyethane with allylpalladium chloride dimer (2.5 mol %) to afford 73–95% yields of the allylation products. Both electron-rich and sterically hindered bromides reacted smoothly, whereas electron-poor bromides cross-coupled in poor yield because of a secondary isomerization to the 1-propeneyl isomer (or concommitant polymerization). A modified protocol that employs an electron-rich phosphine ligand (SPhos), a lower reaction temperature (40 °C), and a less polar solvent (toluene) delivers the expected products from electron-poor bromides without isomerization. The 2-butenyldimethylsilanolate (E/Z, 80:20) required additional optimization to maximize the formation of the branched (gamma-coupled) product and resulted in the development of two distinct protocols for gamma-selective coupling. The first protocol took advantage of a remarkable influence of added alkenes (dibenzylideneacetone and norbornadiene) and led to good selectivities for a large number of electron-rich and electron-poor bromides in 40–83% yields. However, bromides containing coordinating groups (particularly in the 2-position) gave lower, and in one case even reversed, site-selectivity. Electron-rich aromatic bromides reacted sluggishly under this protocol and led to lower product yields. The second protocol employed a sterically bulky phosphonium tetrafluoroborate salt (t-BuCy2PH+BF4−) and resulted in 73–94% yields and excellent site-selectivity (gamma/alpha, 25:1–>99:1) in the coupling of electron-rich, electron-poor, sterically hindered, and heteroaromatic bromides. The use of a configurationally homogeneous (Z)-silanolate and nontransferable diethyl groups were critical to achieving excellent results. A unified mechanistic picture involving initial gamma-transmetalation followed by direct reductive elimination or sigma–pi isomerization can rationalize all of the observed trends. The stereochemical course of palladium-catalyzed cross-coupling reactions of an enantioenriched, alpha-substituted, allylic silanolate salt with aromatic bromides was determined. The allylic silanolate salt was prepared in high geometrical (Z/E, 94:6) and high enantiomeric (94:6 er) purity by a copper-catalyzed SN2’ reaction of a resolved carbamate. Eight different aromatic bromides underwent cross-coupling with excellent constitutional site-selectivity and excellent stereospecificity. Stereochemical correlation established that the transmetalation event proceeds through a syn SE’ mechanism with is interpreted in terms of an intramolecular delivery of the arylpalladium electrophile through a key intermediate that contains a discrete Si–O–Pd linkage. The catalytic, asymmetric palladium-catalyzed cross-coupling of sodium 2-butenylsilanolate with aromatic bromides was investigated. A wide range of chiral ligands including olefin, bidentate phosphine, monodentate phosphine, and cyclic and acyclic stereogenic at phosphorus ligands were evaluated. Commonly used chiral, bidentate phosphine ligands provided ineffective palladium-catalysts for the coupling of 2-butenyldimethylsilanolate with aromatic bromides. A catalyst derived from the monodentate phosphine ligand neomenthyldiphenylphosphine (20 mol %) and Pd(dba)2 (5 mol %) provided moderate enantioselectivity (75:25 er) and modest site-selectivity (5.7:1 gamma/alpha) in the coupling. Increased site-selectivity (up to >99:1) was obtained from reactions employing bulky di or trialkylphosphine ligands.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2011-07-11T19:36:46Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Werner_Nathan.docx: 4840619 bytes, checksum: 73cc057b0da5723f0ac3c9db1a7ea444 (MD5) Werner_Nathan.pdf: 2703275 bytes, checksum: 9dba12df809a3e246b2ec13fa921e7b3 (MD5)","Made available in DSpace on 2011-08-26T15:20:42Z (GMT). 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Werner"],"dc:subject":["palladium-catalyzed","cross-coupling","catalysis","silanol","silanolate","aromatic bromide","allyl arene","allylic","site-selective","asymmetric","enantioselective","stereospecific","diastereoselective","syn SE'","stereochemical course"],"dc:title":["The development of palladium-catalyzed cross-coupling reactions of allylic silanolate salts with aromatic bromides"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:26Z"}