A kinetic study of the asymmetric titanocene-catalyzed imine hydrogenation has revealed the rate law to be rate = kob, [Ti][H2], for cyclic imine 2 and acyclic imine 4. This rate law is consistent with a mechanism in which the imine reacts with a titanium hydride in a fast 1,2-insertion step, to form a titanium amide intermediate, followed by slow reaction of the amide complex with hydrogen to produce the amine and regenerate the titanium hydride. Labeling studies for the hydrogenation of 2 and studies using enantiomerically enriched aldimine 6 indicate that 0-H elimination is also slow, relative to hydrogenolysis, for both 2 and 4. The enantiomeric excesses for the hydrogenation of 2 were found to be essentially insensitive to changes in reaction conditions. However, for imine 4, the ee's were dependent on several variables, most significantly hydrogen pressure. This phenomenon has been explained 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 faster than anti-4, a necessary condition for the explanation presented to hold true. A stereochemical model based on steric and electronic considerations has been proposed to account for the observed selectivity. This model can aid in predicting the absolute configurations of the amines formed in this process.The catalytic, asymmetric hydrogenation of unsaturated organic molecules is an efficient method for the synthesis of enantiomerically enriched compounds. Remarkable success has been achieved in the enantioselective reduction of olefins and ketones.' More recently, the hydrogenation of imines with c k a l metal complexes has received increasing attention.2 Several homogeneous hydrogenation catalysts have been studied in detail for both asymmetric3 and nonasymmetric hydrogenation^.^ These studies have provided crucial insight into the mechanism and origin of selectivity for these systems.We recently reported the first early transition metal catalyst for the asymmetric reduction of imine^.^ The catalyst system affords amines in good isolated yields and with good to excellent enantiomeric excesses (Scheme 1). In this paper, we report the results of a kinetic and mechanistic investigation of this process. Hsiao, Y.; Ohta, M.; Tsukamoto, M.; Ohta, T.; Takaya, H.; Noyori, R. and references cited therein. (b) Bakos, J.; Orosz, A,; Heil, B.; Laghmari, M.; Lhoste, P.; Sinou, D. Scheme 1 % 5 mol 7 ' . la; lb; X =CI Results 65-90 X yield 53-90 %
