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Asymmetric Synthesis of 2‐Methyl Cyclohexane Carboxylic Acids by Heterogeneous Catalysis: Mechanistic Aspects
Author(s) -
Besson Michèle,
Delbecq Françoise,
Gallezot Pierre,
Neto Samuel,
Pinel Catherine
Publication year - 2000
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/(sici)1521-3765(20000317)6:6<949::aid-chem949>3.0.co;2-h
Subject(s) - chemistry , cyclohexane , steric effects , methylcyclohexane , diastereomer , catalysis , ruthenium , medicinal chemistry , rhodium , selectivity , organic chemistry
The catalytic hydrogenation of ( S )‐alkyl‐ N ‐(2‐methylbenzoyl)pyroglutamates was studied over supported rhodium and ruthenium catalysts at room temperature and a pressure of 5 MPa. The reaction was diastereoselective with the predominant formation of (1 S ,2 R )‐2‐methylcyclohexane carboxylic acid with a diastereomeric excess ( de ) of up to 96 %. The most stable conformation was determined by means of a combination of modelling calculations, NMR spectroscopy and X‐ray structural determination. In this conformation, the carbonyl group of the pyroglutamate auxiliary shields one face of the aromatic ring. The observed selectivity may thus be explained by a preferential adsorption at the unshielded face which avoids steric repulsion by the C=O group to result in a cis hydrogenation. The addition of an amine, the nature of the support (alumina or active carbon) or of the metal (Rh or Ru) were shown to give additional stabilisation of the adsorption at the unshielded face to increase the diastereoisomeric excess.