Asymmetric reduction of representative ketones with a bis-chiral oxazaborolidine system

In recent years, many optically active β-amino alcohols, mostly derived from naturally occurring α-amino acids, have been incorporated into the asymmetric synthesis as chiral auxiliaries or ligands.1 An effective asymmetric catalysts, the oxazaborolidine-borane reagents, which were originally pioneered by Itsuno and Corey,2 were generally prepared from chiral β-amino alcohols by the reaction with boric acid or formed in situ in the presence of borane. These reagents provide excellent enanti…

Asymmetric reduction of representative ketones with a bis-chiral oxazaborolidine system

In recent years, many optically active β -amino alcohols, mostly derived from naturally occurring α -amino acids, have been incorporated into the asymmetric synthesis as chiral auxiliaries or ligands.1 An effective asymmetric catalysts, the oxazaborolidine-borane reagents, which were originally pioneered by Itsuno and Corey,2 were generally prepared from chiral β -amino alcohols by the reaction with boric acid or formed in situ in the presence of borane. These reagents provide excellent enantioselectivity for the asymmetric reduction of most aromatic prochiral ketones.3 However, to our knowledge, no chiral borane-oxazaborolidine system reported had been applied to the asymmetric reduction of prochiral ketones.In this paper, we report a bis-chiral oxazaborolidine system and its use as a catalyst in the enantioselective borane reduction of prochiral ketones. Significantly higher enantioselectivity was observed in the reduction of representative ketones with chiral diisopinocampheylborane((-)-IPC2BH) in comparison with the common borane(BH3-Me2S).All the experiments were carrued out under argon atmosphere. (-)-IPC2BH was prepared in THF at 0 ℃ (12h) using (+)- α -pinene of 91.6% e.e., following the published procesdure.4 A series of prochiral ketones were reduced with our bis-chiral system in THF at 45 ℃ following the procedure described before.5 The results are summarized in Table 1.The bis-chiral oxazaborolidine system formed in situ with L-proline and (-)-IPC2BH as catalyst for enantioselective borane reduction of aromatic ketones provide moderate to good results. It has two catalytic centers seems especially good at catalyzing the enantioselective reduction of prochiral ketones. Further studies are in progress.