Enantioselective Hydrogenation of (E)-and (Z)-Isomeric Ethyl 3-Acetamidobutenoates with Rh-Bisphosphine Complexes: Effects of Substrate Geometry and Solvents on Reaction Rates and Catalyst Reusability

Abstract

Enantiopure β-amino acids are crucial structural features of numerous biologically active natural products as well as important building blocks for the synthesis of β-peptides and β-lactam antibiotics. Numbers of stoichiometric chiral auxilaries and catalytic methods have been developed to make chiral β-amino acids. One of the most promising processes for the convenient preparation of chiral β-amino acids on large scale is the asymmetric hydrogenation of suitable unsaturated precursors such as β-acetamido acrylates with Rh(I) catalysts bearing chiral phosphine ligands. The requisite prochiral substrates are easily available by treatment of β-keto carboxylates with NH4OAc and subsequent acylation. However, while literally thousands of reports are concerned with the Rh-catalyzed enantioselective hydrogenation of related prochiral α-acetamido acrylates, only a few devoted to the hydrogenation of β-analogues as substrates exist. The main reason for this is probably different behavior in the asymmetric hydrogenation, which had for a long time been attributed to particular substrates such as the isomeric ethyl 3-acetoamido butenoates (E)-1 and (Z)-1.