Synthesis of three novel chiral diamines derived from ( S)-proline and their evaluation as precursors of diazaborolidines for the catalytic borane-mediated enantioselective reduction of prochiral ketones

Abstract

A series of chiral diazaborolidine catalysts are readily prepared in situ at 75 °C in toluene solvent and under microwave irradiation (100 W, 15 min, air cooling) using chiral diamines derived from inexpensive and commercially available ( S)-proline and borane-dimethyl sulfide. Special mention deserves the synthesis of potentially versatile diamine ( S)- 8 [( S)-(pyrrolidin-2-yl)diphenylmethanamine], with the key step being the conversion of tertiary alcohol ( S)-(1-benzylpyrrolidin-2-yl)diphenyl methanol, ( S)- 12, to azide ( S)- 13. The chiral diazaborolidine/BH 3 reagent system was successfully employed in the enantioselective reduction of prochiral ketones to give the corresponding secondary alcohols in excellent yield and with up to 96% enantiomeric purities.