Asymmetric catalysis : ligand design and microwave acceleration

• Main Author: Bremberg, Ulf
• Format: Doctoral Thesis
• Language: English
• Published: KTH, Kemi 2000
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2962

This thesis deals partly with the design and synthesis ofligands for use in asymmetric catalysis, and partly with theapplication of microwave heating on metal-based asymmetriccatalytic reactions. Enantiomerically pure pyridyl alcohols and bipyridylalcohols were synthesized from the chiral pool for future usein asymmetric catalysis. Lithiated pyridines were reacted withseveral chiral electrophiles, yielding diastereomeric mixturesthat could be separated without the use of resolutiontechniques. New pyridino- and quinolinooxazolines were synthesized andtested in palladium-catalyzed asymmetric allylation using1,3-diphenyl-2-propenyl acetate and dimethyl malonate. Theconformational preferences of the ligands in palladiumcomplexes were studied with crystallography, 2D-NMR techniquesand DFT calculations. Conclusions about how the chirality wastransferred from the ligand to the substrate could be drawnfrom the conformational analysis. The effect of heating Pd- and Mo-catalyzed asymmetricallylic substitution reactions was investigated with oil bathheating and microwave irradiation. With a few exceptions,ligands with high room temperature selectivity were shown toretain their selectivity on heating. Reaction rates, catalyststability and product selectivities of microwave-heatedreactions were compared with those of reactions performed inoil bath. Palladium-catalyzed asymmetric allylation was studied withseveral ligand types, allylic substrates and nucleophiles. Someof the experimental procedures had to be adapted to microwaveheating conditions. The procedure for asymmetric allylation catalyzed bybispyridylamide molybdenum complexes was developed into aone-pot microwave-mediated reaction. With microwaves, Mo(CO)6could be used as an easily-handled metal sourceand inert conditions could be omitted. Derivatives of thebispyridylamide ligandswere synthesized and tested withmolybdenum as catalysts to investigate the effects ofsubstituents on the pyridine ring. <b>Keywords</b>: ligand, asymmetric catalysis, pyridylalcohols, oxazolines, conformational study, Pd-allyl, fastchemistry, microwave chemistry, Mo-allyl, bispyridylamides.