Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation

Abstract: This thesis covers the development of two new methods for the asymmetric reduction of ketones and ketone intermediates. The protocols developed are based on the use of a ruthenium pseudo-dipeptide catalyst that previously has been shown to be efficient and selective in the asymmetric reduction of carbonyl compounds.The first part of this thesis describes the development of an efficient protocol for sequential isomerization and asymmetric reduction of allylic alcohols into saturated chiral alcohols in a one-pot procedure. This transformation has previously been reported at high temperature and with long reaction times, yielding the products in poor enantioselectivity. In the current project, the same transformation was investigated, however, with a significally more active catalyst. As a result we were able to use milder reaction conditions which yielded higher enantioselectivity in comparison to previously published protocols. The scope was investigated and the mechanism was briefly studied.The second part of this thesis describes the asymmetric reduction of sterically demanding ketones with the same metal complex as in the first part. It was found that longer reaction times in combination with the use of potassium tert-butoxide facilitate the reduction of sterically hindered ketones, to yield secondary alcohols with high enantioselectivity. The scope and the role of potassium were investigated, and a plausible new transition state was postulated.