CATALYTIC ASYMMETRIC HYDROGENATION OF IMINES WITH A CHIRAL TITANOCENECATALYST - KINETIC AND MECHANISTIC INVESTIGATIONS

A kinetic study of the asymmetric titanocene-catalyzed imine hydrogena tion has revealed the rate law to be rate = k(obs)[Ti][H-2]. for cycli c imine 2 and acyclic imine 4. This rate law is consistent with a mech anism in which the imine reacts with a titanium hydride in a fast 1,2- insertion step, to form a titanium amide intermediate, followed by slo w reaction of the amide complex with hydrogen to produce the amine and regenerate the titanium hydride. Labeling studies for the hydrogenati on of 2 and studies using enantiomerically enriched aldimine 6 indicat e that beta-H elimination is also slow, relative to hydrogenolysis, fo r both 2 and 4. The enantiomeric excesses for the hydrogenation of 2 w ere found to be essentially insensitive to changes in reaction conditi ons. However, for imine 4, the ee's were dependent on several variable s, most significantly hydrogen pressure. This-phenomenon has been expl ained on the basis of the interconversion of the syn and anti isomers of 4 during the hydrogenation. It has been shown that syn-4 reacts fas ter than anti-4, a necessary condition for the explanation presented t o hold true. A stereochemical model based on steric and electronic con siderations has been proposed to account for the observed selectivity. This model can aid in predicting the absolute configurations of the a mines farmed in this process.