Employing the structural diversity of nature: development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones.
A library of novel dipeptide-analogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected alpha-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.
Pastor
Isidro M
IM
Department of Organic Chemistry The Arrhenius Laboratory Stockholm University, 106 91 Stockholm, Sweden.
Västilä
Patrik
P
Adolfsson
Hans
H
D000098:Acetophenones / Q000737:chemistry*; D002384:Catalysis; D004151:Dipeptides / Q000737:chemistry*; D006865:Hydrogenation; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
D000098:Acetophenones; D004151:Dipeptides; D008024:Ligands; D009942:Organometallic Compounds; D012428:Ruthenium; C038699:acetophenone