Rhodium-Catalyzed Enantioselective and Diastereoselective Hydrogenation of β-Ketoenamides: Efficient Access to anti 1,3-Amino Alcohols

摘要

Chiral 1,3-amino alcohols are interesting structural motifs prevalent in pharmaceutical products as well as in important chiral auxiliaries and ligands for asymmetric synthesis. Currently, the most common strategy for their synthesis is based on the diastereoselective reduction of an enantiomer-ically pure substrate, whereby the chirality of the substrate controls the formation of the new stereogenic center (substrate-controlled asymmetric reduction). In this context, we wondered whether asymmetric hydrogenation could be used to afford chiral 1,3-amino alcohols from readily prepared substrates (reagent-controlled asymmetric reduction).'7'8' Herein, we report a rhodium-catalyzed highly enantioselective (up to 99% ee) and diastereoselective (up to d.r. 99:1) hydrogenation of β-ketoenamides as an efficient entry to enantiomerically pure anti 1,3-amino alcohols containing two stereogenic centers.