Transition Metal Lewis Acids as Chiral Catalysts: Mechanistic and Synthetic Studies
Final Report Abstract
Chiral Ru-catalysts 1 and 2 are very good catalysts for enals and enones in asymmetric Diels-Alder reactions, dipolare cyclo- additions, and Michael additions with thiophenols. To broaden the scope of the catalysts, during my work Mukaiyama-Michael additions and Friedel-Crafts alkylations were tested. After numerous variations on conditions, substrates, solvents and additives, it turned out that Ru-catalysts 1 and 2 are not active enough to efficiently catalyze those reactions. For Mukaiyama-Michael additions only racemic products were formed, most probably through catalysis with Si-species formed during the reaction, whereas Friedel-Crafts alkylations gave at least slightly enantiomeric enriched products but even after long reaction times still in low yields. More successful were the mechanistic studies: With NOESY experiments, differences of the stereochemical outcome for enals and enones in Diels-Alder reactions with Ru-catalyst 1 were explained. The enantioselectivity for enals had been explained before by models of the substrate-catalyst-complex derived from X-ray analyses, where the substrate coordinates to the catalyst in an anti-s-trans conformation. Even if α-unsubstituted enones show an analogous conformation in X-ray structures, not all of them gave the therefrom expected enantiomer as major product. During this work it has been shown that in solution both enals and enones coordinate in two different conformations to the catalyst. For enals, the second conformation is anti-s-cis, which in regard to the products observed is less reactive for all substrates. In contrast, enones can react in both conformations, anti- and syn-s-trans, which have been observed in solution in NOESY experiments. α-Unsubstituted enones preferentially react with catalyst 1 in syn-s-trans conformations. Changing from cyclopentadienyl-Ru (CpRu) catalyst 1 to indenyl-Ru (IndRu) catalyst 2 forces α-unsubstituted enones to react in an anti-s-trans conformation because the bigger Ind-roof (in comparison to Cp) of the catalyst leads to sterical hinderance of the approaching diene in syn-s-trans conformation. Very intrestingly, those results were not only observed for asymmetrical enones, but also for symmetrical divenylketone. This proves that the difference in reactivity is really due to the sterical accessibility and not due to different populations of the two possible conformations.
