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Employing the Structural Diversity of Nature: Development of Modular Dipeptide‐Analogue Ligands for Ruthenium‐Catalyzed Enantioselective Transfer Hydrogenation of Ketones
Author(s) -
Pastor Isidro M.,
Västilä Patrik,
Adolfsson Hans
Publication year - 2003
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/chem.200304900
Subject(s) - transfer hydrogenation , enantioselective synthesis , chemistry , acetophenone , stereocenter , dipeptide , catalysis , amino acid , noyori asymmetric hydrogenation , alanine , ruthenium , stereochemistry , ligand (biochemistry) , aryl , alcohol , combinatorial chemistry , alkyl , organic chemistry , biochemistry , receptor
A library of novel dipeptide‐analogue ligands based on the combination of tert ‐butoxycarbonyl( N ‐Boc)‐protected α ‐amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [{RuCl 2 ( p‐ cymene)} 2 ] and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2‐propanol as the hydrogen donor. Excellent enantioselectivity of 1‐phenylethanol (up to 98 % ee ) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L ‐amino acids generated S ‐configured products, and catalysts based on D ‐amino acids favored the formation of the R ‐configured alcohol. The combination N ‐Boc‐ L ‐alanine and ( R )‐phenylglycinol ( Boc‐ L ‐Ab ) or its enantiomer ( N ‐Boc‐ D ‐alanine and ( S )‐phenylglycinol, Boc‐ D ‐Aa ) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee , was obtained.