Item – Theses Canada

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OCLC number
728824755
Link(s) to full text
LAC copy
LAC copy
Author
Hadei, Niloufar.
Title
N-heterocyclic carbenes in the alkyl-alkyl Negishi cross-coupling reaction and its application toward the synthesis of rhizochalin.
Degree
Ph. D. -- York University, 2009
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2010]
Description
3 microfiches
Notes
Includes bibliographical references.
Abstract
An efficient method for the alkyl-alkyl Negishi cross-coupling reaction of unactivated primary alkyl halides with alkyl organozinc reagents using an N-heterocyclic carbene-based Pd catalyst has been developed. A number of N-heterocyclic carbenes (NHCs) were prepared and evaluated as ligands for a range of cross-couplings. Among these, 1,3-bis (2,6-diisopropylphenyl) imidazolium chloride (IPr·HCl) demonstrated the highest reactivity when used in combination with Pd2(dba)3. This initial work eventually led to the development of an air- and moisture-stable NHC-Pd pre-catalyst, Pd-PEPPSI-IPr (Pyridine-Enhanced Precatalyst Preparation, Stabilization, and Initiation) which was shown to be superior to the 'in-situ' generated catalyst in terms of improved reproducibility and catalyst turn-over number. The optimized protocol using Pd-PEPPSI-IPr allowed for the coupling of a variety of alkyl- and aryl- halides, and pseudohalides with organozinc reagents providing the corresponding products in some of the highest isolated yields reported to date for this chemical transformation. Moreover, the developed protocol is generally applicable and tolerant of a variety of functional groups including esters, nitriles, and amides. Further investigations confirmed similar reactivity of Pd-PEPPSI-IPr in aryl-aryl Kumada-Tamao-Corriu cross-coupling reaction. The developed methodology was then applied to the synthesis of the naturally occurring sphingolipid rhizochalin, using the Pd-PEPPSI-IPr catalyzed alkyl-alkyl Negishi cross-coupling reaction as a key-step.
ISBN
9780494540268
0494540265