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On the Enantioselective Hydrogenation of Isomeric Methyl 3‐Acetamidobutenoates with Rh I Complexes
Author(s) -
Heller Detlef,
Drexler HansJoachim,
You Jingsong,
Baumann Wolfgang,
Drauz Karlheinz,
Krimmer HansPeter,
Börner Armin
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20021115)8:22<5196::aid-chem5196>3.0.co;2-p
Subject(s) - enantioselective synthesis , chemistry , asymmetric hydrogenation , catalysis , ligand (biochemistry) , enantiomer , substrate (aquarium) , solvent , enantiomeric excess , chirality (physics) , stereochemistry , medicinal chemistry , organic chemistry , chiral symmetry , biochemistry , oceanography , receptor , nambu–jona lasinio model , physics , quantum mechanics , quark , geology
The enantioselective hydrogenation of E ‐ and Z ‐methyl 3‐acetamidobutenoate, key intermediates in the synthesis of a pharmaceutically important chiral β ‐amino acid, with Rh I catalysts in MeOH as solvent has been investigated in detail. As chiral ligands, Et‐DuPHOS, Me 4 ‐BASPHOS, DIPAMP, DIOP, HO‐DIOP and Et‐FerroTANE 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 H 2 pressure. Kinetic investigations with [Rh(diphosphane)(MeOH) 2 ]BF 4 , taking into consideration the special nature of the precatalyst {[Rh(cod) 2 ]BF 4 /ligand versus [Rh(cod)ligand)]BF 4 }, NMR spectroscopic measurements and the H 2 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 H 2 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.