OXAZABOROLIDINE CATALYZED BORANE REDUCTIONS OF KETONES - A SIGNIFICANT EFFECT OF TEMPERATURE ON SELECTIVITY

The effect of temperature on the selectivity of oxazaborolidine catalyzed borane reductions of ketones has been studied. For two model ketones, acetophenone (2a) and cyclohexylmethyl ketone (2b), and two different oxazaborolidine catalysts [derived from n-butyl- and phenylboronic acids with (S)-diphenylprolinol], these reductions were carried out over a range of temperatures in THF and toluene. Our results show that in general there is an increase in selectivity with increasing temperature until 30-50-degrees-C where the selectivity then begins to decrease. As a result of these findings, die amount of catalyst for the reduction of acetophenone was reduced from 10 % to 1 % with only a small decrease in selectivity (96 % and 94 % respectively). We obtained the highest selectivity ever reported for the reduction of acetophenone by a borane-phenyl substituted diphenylprolinol derived catalyst (98 % ee using the catalyst 1c at 40-degrees-C). In addition, we obtained the highest reported selectivity for the reduction of cyclohexylmethyl ketone by a diphenylprolinol derived catalyst (89 % ee using n-butyl-substituted borane catalyst 1b at 50-degrees-C).