Highly Enantioselective Ruthenium‐Catalyzed Reduction of Ketones Employing Readily Available Peptide Ligands

Abstract
Highly efficient and selective catalysts for the asymmetric reduction of aryl alkyl ketones under hydrogen‐transfer conditions (2‐propanol) were obtained by combining a novel class of pseudo‐dipeptide ligands with [{RuCl2(p‐cymene)}2]. A library of 36 dipeptide‐like ligands was prepared from N‐Boc‐protected α‐amino acids and the enantiomers of 2‐amino‐1‐phenylethanol and 1‐amino‐2‐propanol. The catalyst library was evaluated with the reduction of acetophenone and excellent enantioselectivity of 1‐phenylethanol was obtained with several of the novel catalysts. A ligand based on the combination of N‐Boc‐L‐alanine and (S)‐1‐amino‐2‐propanol (ligand A‐(S)‐4) was found to be particular effective. When the situ formed ruthenium complex of this ligand was employed as the catalyst in the hydrogen‐transfer reaction of various aryl alkyl ketones, the corresponding alcohol products were achieved in excellent enantioselectivity (up to 98 % ee).

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