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/BH3 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. © 2008 Elsevier Ltd. All rights reserved.