Kinetics and mechanism of the morpholine-borane reduction of methyl alkyl ketones

Abstract

The reaction of morpholine-borane with acetone in aqueous solution at pH 3 and pH 5 and 25º results in the formation of 2-propanol and the evolution of hydrogen. The rate of reduction is enhanced by an increase in acidity and the rate of disappearance of morpholine-borane is described by the following rate law: -d[amine-borane]/d t = [amine-borane][ketone][k1 + k2 (H+)] This rate expression indicates reduction to occur by two pathways, one independent of, and the other first-order in hydrogen ion. For both paths, the total molar quantity of products (2-propanol and hydrogen) equals three times the molar quantity of amine-borane consumed. The number of hydridic hydrogens, per BH3 unit, used for reduction of carbonyl at pH 3 or 5 varies as the acetone concentration is changed. This product distribution is attributed to competition between ketone and water for hydride-containing intermediates, possibly hydroxyboranes, formed after the rate-determining step. In pure acetone, only two-thirds of the available hydride is used for reduction of ketone suggesting that, in the absence of water, diisopropoxyborane may be a reaction product. The reaction of morpholine-borane-d3 with acetone at pH 5 or 3.1 give exclusively the C-deuterated alcohol, (CH3)2CDOH and this shows that hydrogen is transferred from boron to the carbonyl carbon atom in the reduction of acetone by morpholine-borane via both paths. The acid independent reaction exhibits a negligible solvent isotope effect and a small normal B-H substrate isotope effect (k_H/k_D = 1.1) and is presumed to involve the rate-determining attack of amine-borane on the neutral ketone. The acid catalyzed reaction exhibits a small substrate isotope effect (k_H/k_D = 1.2), but shows a pronounced inverse solvent isotope effect (k (D2O)/k (H2O) = 2.8) which suggests a rate-determining attack of amine-borane on a protonated carbonyl which is formed in a rapid pre-equilibrium. For the acid independent reaction, a transition state requiring some specific orientation of reactants is proposed, consistent with activation parameters of Delta H*= 11 kcal mole-1 and Delta S* = -40 e.u. An analogy to certain cycloaddition reactions of dienes is suggested. The observed correlation of rates with Taft sigma-* parameters for C-alkyl substituents in the ketone suggests that boron-oxygen bond formation may be important in this transition state. For the acid dependent reaction, it is speculated that the protonated carbonyl may serve as a general acid promoting decomposition of the amine-borane in a manner analogous to the proposed mechanism for the acid catalyzed amine-borane hydrolysis.