Rationale on the Abnormal Effect of Temperature on the Enantioselectivity in the Asymmetric Borane Reduction of Ketones Catalyzed by <scp>L</scp>‐Prolinol

Abstract

Abstract The effect of temperature on the enantioselectivity of the oxazaborolidine‐catalyzed asymmetric borane reduction of ketones was investigated in the presence of (5 S )‐3‐oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane (=(3a S )‐tetrahydro‐1 H ,3 H ‐pyrolo[1,2‐ c ][1,3,2]oxazaborole; 1a ) and its 2‐methoxy derivative ( 1b ) as catalysts, which were synthesized from L ‐prolinol with borane and trimethyl borate, respectively. The results indicate that the two catalysts induce a different temperature‐dependent enantioselectivity. The enantioselectivity of the B ‐unsubstituted (5 S )‐3‐oxa‐1‐aza‐borabicyclo[3.3.0]octane ( 1a ) increases with increasing temperature, while its B ‐methoxy‐substituted derivative 1b shows the highest enantioselectivity at ca. 50°. (5 S )‐3‐Oxa‐1‐aza‐2‐borabicyclo[3.3.0]octane ( 1a ) is more likely to dimerize than its 2‐methoxy derivative 1b . The conversion rates of L ‐proline to L ‐prolinol in the presence of different amounts of borane were also determined in this study.