Premium
Synthesis of Substituted Mandelic Acid Derivatives via Enantioselective Hydrogenation: Homogeneous versus Heterogeneous Catalysis
Author(s) -
Cederbaum Fredrik,
Lamberth Clemens,
Malan Christophe,
Naud Fred,
Spindler Felix,
Studer Martin,
Blaser HansUlrich
Publication year - 2004
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200404022
Subject(s) - chemistry , catalysis , mandelic acid , enantioselective synthesis , homogeneous catalysis , homogeneous , organic chemistry , asymmetric hydrogenation , enantiomer , cinchona , enantiomeric excess , ligand (biochemistry) , heterogeneous catalysis , solvent , medicinal chemistry , biochemistry , physics , receptor , thermodynamics
An extensive screening of both homogeneous and heterogeneous catalysts was carried out for the enantioselective hydrogenation of p ‐chlorophenylglyoxylic acid derivatives. For p ‐chlorophenylglyoxylic amides only homogeneous Rh‐diphosphine complexes gave satisfactory results, ees up to 87% were observed for the cy‐oxo‐pronop ligand. For methyl p ‐chlorophenylglyoxylate both a homogeneous as well as a heterogeneous catalyst performed with ees >90%. A Pt catalyst modified with cinchona derivatives achieved 93% ee for the (R) ‐ and 87% ee for the (S)‐ methyl p ‐chloromandelate. A Ru‐MeObiphep catalyst also reached 93% ee with TONs up to 4000 and TOFs up to 210 h −1 . For all catalytic systems the effects of the metal, the nature of the chiral auxiliary and the solvent as well as of the reaction conditions were investigated. The homogeneous process was scaled up to the kg scale and the enantiomeric purity of the product was enhanced to >99% ee by two recrystallizations of the free p ‐chlorophenylmandelic acid.