Homogenous transition metal
Date
2006-10-26T07:23:57Z
Authors
Zeevaart, Jacob
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Abstract
The application of homogenous transition metal catalysis to the arylation of enolates to
develop new synthetic procedures which are more environmentally benign, atomefficient
and economically viable than current methods was the motivation behind the
current work. The specific choice of molecules with an aromatic group in the a-
position of a ketone, carboxylic acid, amide or other electron-withdrawing group arose
from the fact that many natural products, pharmaceutical actives and synthetic
intermediates contain such a substructure while the syntheses of these substructures are
often cumbersome.
The application of homogenous catalysis to various types of enolates was explored and
in the process several developments were achieved and discoveries made. These
included the use of inorganic bases under phase transfer conditions for the Heck
reaction of acrylic acid as well as the synthesis and application of phosphine and
phosphite ligands in the Heck reaction of acrylic acid esters. The successful use of low
palladium loadings (as low as 0.01mol%) in the arylation of diethyl malonate using
aryl chlorides and the application to the synthesis of ketoprofen and phenobarbital was
demonstrated. The novel application of palladium catalysis to the arylation of
methanesulfonamides and the first example of a bromoindole derivative as the aryl
halide partner in an enolate arylation reaction was demonstrated. Ligand-free
palladium catalysed phenylation of pinacolone followed by Baeyer Villiger oxidation
led to a proposed novel synthetic route to tert-butyl esters of 2-arylacetic acids. The
palladium and copper catalysed arylation of acetoacetate esters, with in situ
decarbonylation, provided a different route to 2-arylacetic acid esters which are useful
in the preparation of non-steroidal anti-inflammatory compounds.
Description
Faculty of Science
School of Chemistry
0100505x
jzeevaart@csir.co.za
Keywords
Arylation, Aryl Halide, Bromobenzene, Acetoacetate, Enolate