Generally, there are two different strategies for asymmetric pinacol couplings. One is to take enantiopure carbonyl compounds as starting materials and the other to introduce chirality using chiral coupling reagents. In this Ph. D. thesis both strategies were investigated. Using the SAMP / RAMP hydrazone method several a-chiral aldehydes and ketones were obtained in a four step procedure in moderate to excellent enantiomeric excesses (ee = 56 - ³98%). The reductive coupling of these a-chiral carbonyl compounds succeeded with several metal reducing agents only partly. The best results were obtained using a coupling reagent of TiCl3 and TMEDA in tetrahydrofuran resulting in the desired product in a yield of 20%, a diastereomeric excess of 92% and an enantiomeric excess of 7%. As side reactions the McMurry reaction or the pinacol rearrangement were observed. A more elegant method, however, is to introduce chirality with the coupling reagent. This method allows to use easy accessible achiral carbonyl compounds and results in stereomeric enriched products. In order to test this strategy complexes of TiCl3 and enantiopure amines or hydrazines in tetrahydrofuran were investigated as chiral coupling reagents. The pinacol coupling of benzaldehyde leads to the hydrobenzoin in yields of 0 - 100%, diastereomeric excesses of dl:meso = 46:54 - 96:4 and enantiomeric excesses of 6 - 72%. The best results were obtained with (R)-1-Methyl-3-phenyl-propylamine (ee = 72%) and SMP (ee = 65%) as chiral amines. With these additives a variety of aromatic aldehydes were coupled. The non-linear temperature effect observed in the pinacol coupling of benzaldehyde with TiCl3 and SMP was first explained with the principle of isoinversion. Nevertheless after the analysis of the coupling reagents in solution with ESR- and IR-experiments it became obvious that there were three different active species in different relations depending on the temperature. Finally the advantages of solid-phase supported ligands were transferred to this type of reaction. Two different SMP-resins were used in the same pinacol coupling reaction as additives. After filtration the resins can be reused without any loss of reactivity. The yields depend on the reaction time and the enantiomeric excesses were probably due to the different loadings of the resins.
info:eu-repo/classification/ddc/540, Chemie
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