Asymmetric reduction using C2-symmetric metal complexes
Subtitle: the first autocatalytic asymmetric reduction.
Contributors: University of Toronto.  Dept. of Chemistry
Published: 2004
Language: eng
Number of pages: 231
Description: A pybox-zinc (II) complex was used as a catalyst for the asymmetric reduction of a few challenging substrates possessing prochiral ketones with good to high enantioselectivities (60%--96% ee). The complexation of pybox to zinc in [1:1] stoichiometric ratio was shown to be solvent dependent. The sense and extent of stereoselectivities were examined with a variety of counteranions on the zinc metal centre. Although the sense of stereoselectivity in these reductions was predictable and independent of the counteranion used, the extent of stereoselectivity was greatly influenced by the zinc salt. The best results in the asymmetric reduction was with zinc trifluoromethanesulfonate. These reactions were studied systematically to explore the mutual influence of each of the reaction components. More specifically, the roles of the zinc catalyst, the stoichiometric reductant and the solvent were investigated on the asymmetric reduction of these substrates.We have also uncovered a rare example of an autocatalytic asymmetric reaction. The C2-symmetric diol, 2,6-bis(1-hydroxyethyl)pyridine, or BHEP, in conjunction with zinc trifluoromethanesulfonate can act as a chiral catalyst for the reduction of 2,6-diacetylpyridine and produce more of the diol BHEP with the same configuration in an enantiomerically and diastereomerically enriched form (40% ee, 47% de). This is the first example of an autocatalytic asymmetric reduction. We have identified the active reductant in this catalytic system, which is produced from a combination of sodium triacetoxyborohydride and p-nitrophenol.We have also studied the mechanism of this unique autocatalytic reduction in an effort to understand the origin of stereoselectivity. The role of each reagent in the reaction and its influence on the stereoselectivity was examined. The proposed mechanism is in agreement with our experimental and computational investigations and describes a stepwise reduction where the enantioselectivity of the product is dependent on the catalyst but the diastereoselectivity is independent of the catalyst. The diastereoselectivity was shown to be inherent to the substrate and the reductive system used. This novel autocatalytic system has the potential for asymmetric autoamplification.
Notes: Advisor: Jik Chin

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 66-06, Section: B, page: 3139.