Asymmetric Synthesis of Cyclic Amino Alcohols via Dynamic Kinetic Resolution

Significance

Asymmetric hydrogenation of racemic α-substituted ketones via dynamic kinetic resolution (DKR) is an efficient synthetic approach towards chiral alcohols with two adjacent stereo-centers. In the paper the authors report a successful application of this concept to a highly enantioselective synthesis of cis-β-N-alkyl/aryl­amino cyclic alcohols. The use of catalyst 1 allowed the preparation of a variety of products with high yields (>90%) and excellent enantio- and dia­stereoselectivities (cis/trans ratio from 97:3 to >99:1, 91-99% ee). This method provides access to enantiomerically enriched 2-(1-hydroxyalkyl)piperidines, an ubiquitous structural units in natural products. The described protocol was applied to the short and practical synthesis of all four isomers of the natural alkaloid conhydrine; the previously described synthetic protocols suffered from some tedious steps and low yields. The advantage of complex 1 seems to be apparent.