On the enantioselective hydrogenation of isomeric methyl 3-acetamidobutenoates with RhI complexes

Abstract

The enantioselective hydrogenation of E- and Z-methyl 3-acetamidobutenoate, key intermediates in the synthesis of a pharmaceutically important chiral β-amino acid, with RhI catalysts in MeOH as solvent has been investigated in detail. As chiral ligands, Et-DuPHOS, Me4-BASPHOS, DIPAMP, DIOP, HO-DIOP and Et-Ferro-TANE have been employed. The particular role of oxyfunctionalization in some diphosphine catalysts is addressed in relation to the E/Z geometry of the substrate and the dependency of the ee on the H2 pressure. Kinetic investigations with [Rh(diphosphane)(MeOH)2]-BF4, taking into consideration the special nature of the precatalyst {[Rh-(cod)2]BF4/ligand versus [Rh(cod)ligand)]BF4}. NMR spectroscopic measurements and the H2 pressure dependence of the observed enantioselectivity provide evidence that the reaction proceeds via an "unsaturated route" mechanism. This mechanism correlates to catalytic features found in the past for the hydrogenation of related unsaturated α-amino acid precursors. The influence of the temperature was similarly investigated. A nonlinear dependency of the enantiomeric ratio as a function of the reciprocal of the temperature has been found. The correlation between temperature and H2 pressure and their effects on the enantioselectivity is discussed. In general, the highest enantioselectivities for the hydrogenation of both isomeric substrates can be achieved at room temperature and below, whereas the fastest conversion takes place at 30-50°C.