Rationale on the abnormal effect of temperature on the enantioselectivity in the asymmetric borane reduction of ketones catalyzed by L-prolinol

The effect of temperature on the enantioselectivity of the oxazaborolidine-catalyzed asymmetric borane reduction of ketones was investigated in the presence of (5S)-3-oxa-1-aza-2-borabicyclo[3.3.0] octane (=(3aS)-tetrahydro-1H,3H-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 (5S)-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. 50degrees. (5S)-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.