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Article: Highly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: Substrate scope and mechanistic insights
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TitleHighly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: Substrate scope and mechanistic insights
 
AuthorsLiu, XY1
Guo, Z1
Dong, SS1
Li, XH1
Che, CM1
 
Issue Date2011
 
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/chemistry
 
CitationChemistry - A European Journal, 2011, v. 17 n. 46, p. 12932-12945 [How to Cite?]
DOI: http://dx.doi.org/10.1002/chem.201101982
 
AbstractAn efficient method for the synthesis of tertiary amines through a gold(I)-catalyzed tandem reaction of alkynes with secondary amines has been developed. In the presence of ethyl Hantzsch ester and [{(tBu) 2(o-biphenyl)P}AuCl]/AgBF 4 (2 mol %), a variety of secondary amines bearing electron-deficient and electron-rich substituents and a wide range of alkynes, including terminal and internal aryl alkynes, aliphatic alkynes, and electron-deficient alkynes, underwent a tandem reaction to afford the corresponding tertiary amines in up to 99 % yield. For indolines bearing a preexisting chiral center, their reactions with alkynes in the presence of ethyl Hantzsch ester catalyzed by [{(tBu) 2(o-biphenyl)P}AuCl]/AgBF 4 (2 mol %) afforded tertiary amines in excellent yields and with good to excellent diastereoselectivity. All of these organic transformations can be conducted as a one-pot reaction from simple and readily available starting materials without the need of isolation of air/moisture-sensitive enamine intermediates, and under mild reaction conditions (mostly room temperature and mild reducing agents). Mechanistic studies by NMR spectroscopy, ESI-MS, isotope labeling studies, and DFT calculations on this gold(I)-catalyzed tandem reaction reveal that the first step involving a monomeric cationic gold(I)-alkyne intermediate is more likely than a gold(I)-amine intermediate, a three-coordinate gold(I) intermediate, or a dinuclear gold(I)-alkyne intermediate. These studies also support the proposed reaction pathway, which involves a gold(I)-coordinated enamine complex as a key intermediate for the subsequent transfer hydrogenation with a hydride source, and reveal the intrinsic stereospecific nature of these transformations observed in the experiments. Producing tertiary amines: The Au I-catalyzed tandem reaction of alkynes with secondary amines provides simple and efficient access to highly substituted tertiary amines with excellent yields and good to excellent diastereoselectivity. Mechanistic studies confirm that a possible reaction pathway involves intermolecular hydroamination via a monomeric cationic gold(I)-alkyne intermediate and subsequent transfer hydrogenation via a gold(I)-coordinated enamine intermediate. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
 
ISSN0947-6539
2013 Impact Factor: 5.696
 
DOIhttp://dx.doi.org/10.1002/chem.201101982
 
ISI Accession Number IDWOS:000297737900019
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiu, XY
 
dc.contributor.authorGuo, Z
 
dc.contributor.authorDong, SS
 
dc.contributor.authorLi, XH
 
dc.contributor.authorChe, CM
 
dc.date.accessioned2012-10-08T03:21:02Z
 
dc.date.available2012-10-08T03:21:02Z
 
dc.date.issued2011
 
dc.description.abstractAn efficient method for the synthesis of tertiary amines through a gold(I)-catalyzed tandem reaction of alkynes with secondary amines has been developed. In the presence of ethyl Hantzsch ester and [{(tBu) 2(o-biphenyl)P}AuCl]/AgBF 4 (2 mol %), a variety of secondary amines bearing electron-deficient and electron-rich substituents and a wide range of alkynes, including terminal and internal aryl alkynes, aliphatic alkynes, and electron-deficient alkynes, underwent a tandem reaction to afford the corresponding tertiary amines in up to 99 % yield. For indolines bearing a preexisting chiral center, their reactions with alkynes in the presence of ethyl Hantzsch ester catalyzed by [{(tBu) 2(o-biphenyl)P}AuCl]/AgBF 4 (2 mol %) afforded tertiary amines in excellent yields and with good to excellent diastereoselectivity. All of these organic transformations can be conducted as a one-pot reaction from simple and readily available starting materials without the need of isolation of air/moisture-sensitive enamine intermediates, and under mild reaction conditions (mostly room temperature and mild reducing agents). Mechanistic studies by NMR spectroscopy, ESI-MS, isotope labeling studies, and DFT calculations on this gold(I)-catalyzed tandem reaction reveal that the first step involving a monomeric cationic gold(I)-alkyne intermediate is more likely than a gold(I)-amine intermediate, a three-coordinate gold(I) intermediate, or a dinuclear gold(I)-alkyne intermediate. These studies also support the proposed reaction pathway, which involves a gold(I)-coordinated enamine complex as a key intermediate for the subsequent transfer hydrogenation with a hydride source, and reveal the intrinsic stereospecific nature of these transformations observed in the experiments. Producing tertiary amines: The Au I-catalyzed tandem reaction of alkynes with secondary amines provides simple and efficient access to highly substituted tertiary amines with excellent yields and good to excellent diastereoselectivity. Mechanistic studies confirm that a possible reaction pathway involves intermolecular hydroamination via a monomeric cationic gold(I)-alkyne intermediate and subsequent transfer hydrogenation via a gold(I)-coordinated enamine intermediate. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationChemistry - A European Journal, 2011, v. 17 n. 46, p. 12932-12945 [How to Cite?]
DOI: http://dx.doi.org/10.1002/chem.201101982
 
dc.identifier.doihttp://dx.doi.org/10.1002/chem.201101982
 
dc.identifier.epage12945
 
dc.identifier.hkuros205170
 
dc.identifier.isiWOS:000297737900019
 
dc.identifier.issn0947-6539
2013 Impact Factor: 5.696
 
dc.identifier.issue46
 
dc.identifier.pmid22012740
 
dc.identifier.scopuseid_2-s2.0-80555135858
 
dc.identifier.spage12932
 
dc.identifier.urihttp://hdl.handle.net/10722/168581
 
dc.identifier.volume17
 
dc.languageeng
 
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/chemistry
 
dc.publisher.placeGermany
 
dc.relation.ispartofChemistry - A European Journal
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAlkynes - Chemistry
 
dc.subject.meshAmines - Chemical Synthesis - Chemistry
 
dc.subject.meshCatalysis
 
dc.subject.meshGold - Chemistry
 
dc.subject.meshHydrogenation
 
dc.subject.meshMolecular Structure
 
dc.subject.meshStereoisomerism
 
dc.titleHighly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: Substrate scope and mechanistic insights
 
dc.typeArticle
 
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Author Affiliations
  1. Institute of Molecular Technology for Drug Discovery and Synthesis, Hong Kong