Design and synthesis of ligands based on trans-2,5-disubstitutedpyrrolidines and their application in asymmetric catalytic reactions

Persistent Link:
http://hdl.handle.net/10150/279952
Title:
Design and synthesis of ligands based on trans-2,5-disubstitutedpyrrolidines and their application in asymmetric catalytic reactions
Author:
Chen, Hongfeng
Issue Date:
2002
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
We have designed and synthesized several small libraries of chiral nitrogen-based ligands and tested their ability to provide stereoselectivity in selected transition metal-catalyzed reactions. Chapter 1 provides background for asymmetric catalysis and summarizes applications of trans-2,5-disubstituted pyrrolidine moieties as chiral auxiliaries and as building blocks for chiral ligands. Although these moieties have found many successful applications as chiral auxiliaries in different asymmetric reactions, application of chiral ligands derived from these moieties has been rare. Chapter 2 summarizes the synthesis of several small libraries of chiral ligands derived from trans-2,5-dimethylpyrrolidine and trans-2,5-diarylpyrrolidines. A modular synthetic strategy has been followed to ensure ease in constructing these libraries with diversity. Small libraries of pyridine-pyrrolidine ligands, bidentate N-O and N-S type ligands, bidentate and tridentate Schiff-base ligands, aminoalcohol ligands, tridentate N-N-O type ligands, C2-symmetric diamine ligands, and a cyclopalladated complex have been prepared. Chapter 3 summarizes the results of using these ligands in several transition metal-catalyzed asymmetric processes, including allylic alkylation, cyclopropanation and diethylzinc addition to benzaldehyde. The pyridine-pyrrolidine ligands are effective catalyst precursors for the palladium-catalyzed allylic alkylation and provided moderate to good stereoselectivities. The stereoselectivity of this reaction catalyzed by palladium complexes of the pyridine-pyrrolidine ligands could be adjusted by changing the substituents on the 6-position of the pyridine ring as well as the chelation size of the complexes. Evidence from these experimental results, 1H NMR studies and MM3* calculations suggested that nucleophilic attack to the 1,3-diphenylallyl moiety in the transition state mainly occurred trans to the pyridine ring of the less stable conformation of the palladium complexes. Combinatorial screening has been applied to accelerate the discovery of new catalysts. Although we did not identify effective catalysts for allylic alkylation, results from the combinatorial screening suggested that the chiral Schiff-base ligands were effective catalyst precursors for copper-catalyzed cyclopropanation. The chiral aminoalcohol ligands were found to be active catalysts for the asymmetric diethylzinc addition to benzaldehyde. The substituents at the alpha position of the hydroxy group played an important role in determining the stereoselectivity of the diethylzinc addition to benzaldehyde.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Chemistry, Organic.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
McGrath, Dominic V.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleDesign and synthesis of ligands based on trans-2,5-disubstitutedpyrrolidines and their application in asymmetric catalytic reactionsen_US
dc.creatorChen, Hongfengen_US
dc.contributor.authorChen, Hongfengen_US
dc.date.issued2002en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractWe have designed and synthesized several small libraries of chiral nitrogen-based ligands and tested their ability to provide stereoselectivity in selected transition metal-catalyzed reactions. Chapter 1 provides background for asymmetric catalysis and summarizes applications of trans-2,5-disubstituted pyrrolidine moieties as chiral auxiliaries and as building blocks for chiral ligands. Although these moieties have found many successful applications as chiral auxiliaries in different asymmetric reactions, application of chiral ligands derived from these moieties has been rare. Chapter 2 summarizes the synthesis of several small libraries of chiral ligands derived from trans-2,5-dimethylpyrrolidine and trans-2,5-diarylpyrrolidines. A modular synthetic strategy has been followed to ensure ease in constructing these libraries with diversity. Small libraries of pyridine-pyrrolidine ligands, bidentate N-O and N-S type ligands, bidentate and tridentate Schiff-base ligands, aminoalcohol ligands, tridentate N-N-O type ligands, C2-symmetric diamine ligands, and a cyclopalladated complex have been prepared. Chapter 3 summarizes the results of using these ligands in several transition metal-catalyzed asymmetric processes, including allylic alkylation, cyclopropanation and diethylzinc addition to benzaldehyde. The pyridine-pyrrolidine ligands are effective catalyst precursors for the palladium-catalyzed allylic alkylation and provided moderate to good stereoselectivities. The stereoselectivity of this reaction catalyzed by palladium complexes of the pyridine-pyrrolidine ligands could be adjusted by changing the substituents on the 6-position of the pyridine ring as well as the chelation size of the complexes. Evidence from these experimental results, 1H NMR studies and MM3* calculations suggested that nucleophilic attack to the 1,3-diphenylallyl moiety in the transition state mainly occurred trans to the pyridine ring of the less stable conformation of the palladium complexes. Combinatorial screening has been applied to accelerate the discovery of new catalysts. Although we did not identify effective catalysts for allylic alkylation, results from the combinatorial screening suggested that the chiral Schiff-base ligands were effective catalyst precursors for copper-catalyzed cyclopropanation. The chiral aminoalcohol ligands were found to be active catalysts for the asymmetric diethylzinc addition to benzaldehyde. The substituents at the alpha position of the hydroxy group played an important role in determining the stereoselectivity of the diethylzinc addition to benzaldehyde.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectChemistry, Organic.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMcGrath, Dominic V.en_US
dc.identifier.proquest3050308en_US
dc.identifier.bibrecord.b4272398xen_US
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