250605-22-2Relevant academic research and scientific papers
A new family of modular chiral ligands for the catalytic enantioselective reduction of prochiral ketones
Puigjaner, Cristina,Vidal-Ferran, Anton,Moyano, Albert,Pericas, Miquel A.,Riera, Antoni
, p. 7902 - 7911 (2007/10/03)
A family of enantiomerically pure (4R,5R)-2-alkyl-4-phenyl-5-(R- oxymethyl)-1,3,2-oxazaborolidines (5) [boron substituent: H, CH3, n-C4H9; R-oxy group: CH3O, CH3OCH2CH20, CH3(OCH2CH2)2O, PhCH20, Ph2CHO, Ph3CO] has been prepared from (2S,3S)-2,3-epoxy-3-phenylpropanol (2) through a four-step sequence involving protection of the alcohol, regioselective ring-opening of the epoxide with sodium azide in acetonitrile in the presence of LiClO4, reduction of the azido group (H2/Pd-C/MeOH or NaBH4/THF-MeOH), and formation of the oxazaborolidine ring with the appropriate boron reagent. Both the boron substituent and the R-oxy group have been optimized for maximal enantioselectivity in the reduction of prochiral ketones with borane. The optimal oxazaborolidine (5a-Me) [boron substituent: CH3; R-oxy group: CH3O] has been employed (10% molar amount, THF, 0 °C to room temperature) in the reduction of a representative family of 10 substrates comprising alkyl aryl ketones and dialkyl ketones. In these reductions, 5a-Me induces the formation of secondary alcohols of S configuration with high enantioselectivity (93% mean enantiomeric excess). The origin of the enantioselectivity in the reduction has been rationalized by means of semiempirical AM1 calculations.
