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New enantioselective reactions in Palladium Catalysis

(2007) Gini, Francesca

Chiral molecules exist in two different forms called enantiomers, which are non-superimposable mirror images of each other. Enantiomers often show different physiological properties and therefore the selective synthesis of enantiomers is important. This thesis describes the use of asymmetric catalysis based on chiral palladium complexes for the synthesis of enantioenriched molecules.

The complex formed from Pd(OCOCF3)2 in combination with the chiral bisphosphine ligand Me-DUPHOS was successfully used in the conjugate addition of arylboronic acids to α,β-unsaturated carbonyl compounds. The conjugate addition of aryltriethoxysilanes instead was achieved using the Pd(CH3CN)4(BF4)2/Me-DUPHOS complex. In both cases ee’s up to 99% were obtained. These reactions have been widely investigated using Rh-based catalysts, whereas palladium is rarely employed due to its tendency to afford the Heck coupling product as side product. In the reaction conditions described here, instead, the desired conjugate addition product was selectively formed without any traces of the Heck product.

The complex formed from Pd(OCOCF3)2 and Josiphos catalysed the asymmetric transfer hydrogenation using 2-propanol both as solvent and hydrogen donor. The presence of t-BuOK was required to increase the reaction rate. In this preliminary investigation with prochiral α,β-unsaturated carbonyl compounds ee’s up to 45% were achieved.

Finally the Pd(II) catalysed asymmetric hydroacylation of terminal olefins in the presence of syngas was investigated. The aim of the research was the synthesis of enantioenriched α-methyl ketones, difficult to synthesize by other catalytic methods. A major drawback was found in the low chemo- and regioselectivity of the reaction and the almost complete absence of enantioselectivity.