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Author Lyle, Michael P. A
Title Design, synthesis and evaluation of chiral nonracemic ligands and catalysts for asymmetric synthesis
book jacket
Descript 340 p
Note Source: Dissertation Abstracts International, Volume: 67-03, Section: B, page: 1448
Thesis (Ph.D.)--Simon Fraser University (Canada), 2005
The work described in this thesis concerns the design, synthesis and evaluation of new chiral nonracemic ligands and catalysts for use in asymmetric reactions
A series of chiral nonracemic chloroacetals were prepared from 2-chloro-4-methyl-6,7-dihydro-5 H-[1]pyrindine-7-one and a variety of C2-symmetric and chiral nonracemic 1,2-ethanediols (R = Me, i-Pr and Ph). These chloroacetals were further elaborated, in a modular fashion, to provide a series of chiral ligands and catalysts
A new class of C2-symmetric 2,2'-bipyridyl ligands were prepared in one step from the chloroacetals via a nickel(0)-mediated homo-coupling reaction. These ligands were then evaluated as chiral directors in copper(I)-catalyzed asymmetric cyclopropanation reactions of styrene and diazoesters (up to 44% ee)
A chiral pyridine N-oxide and a C 2-symmetric 2,2'-bipyridyl N,N'-dioxide were also prepared by direct oxidation of the corresponding pyridine and the 2,2'-bipyridine, respectively. These chiral N-oxides were evaluated as chiral catalysts in desymmeterization reactions of cis-stilbene oxide (up to 20% ee)
A series of pyridylphosphine ligands (P,N-ligands) were subsequently prepared in two steps from the chloroacetals via a Suzuki coupling reaction with ortho-fluorophenylboronic and on subsequent displacement of the fluoride with the potassium anion of diphenylphosphine. These ligands were then evaluated in palladium-catalyzed asymmetric allylic substitution reactions of racemic 3-acetoxy-1,3-diphenyl-1-propene with dimethyl malonate. Optimization of the reaction conditions resulted in the formation of the alkylated product in excellent yield (91%) and in high enantiomeric excess (90%)
A related chiral nonracemic and C2-symmetric 2,2'-bipyridyl ligand was prepared from 2-chloro-4-methyl-5H-[1]pyrindine. This pyrindine was prepared from a common intermediate that was used in the synthesis of the first generation of ligands. The chirality of this second generation ligand was installed by a Sharpless asymmetric dihydroxylation reaction (90% ee). The subsequently elaborated 2,2'-bipyridyl ligand (enriched to >99% ee) was then evaluated in copper(I)-catalyzed asymmetric cyclopropanation reactions of alkenes and diazoesters. In the case of the reaction of para-fluorostyrene and tert-butyl diazoacetate, the corresponding cyclopropane was formed in good diastereoselectivity (92:8) and in excellent enantioselectivity (99% ee). This ligand was also evaluated in copper(II)-catalyzed asymmetric Friedel-Crafts alkylation reactions of various substituted indoles (up to 90% ee) and in copper(I)-catalyzed asymmetric allylic oxidation reactions of cyclic alkenes with tert-butyl peroxybenzoate (up to 91% ee)
School code: 0791
Host Item Dissertation Abstracts International 67-03B
Subject Chemistry, Organic
Alt Author Simon Fraser University (Canada)
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