Insights into LiAlH Catalyzed Imine Hydrogenation.

Commercial LiAlH can be used in catalytic quantities in the hydrogenation of imines to amines with H . Combined experimental and theoretical investigations give deeper insight in the mechanism and identifies the most likely catalytic cycle. Activity is lost when Li in LiAlH is exchanged for Na or K. Exchanging Al for B or Ga also led to dramatically reduced activities. This indicates a heterobimetallic mechanism in which cooperation between Li and Al is crucial. Potential intermediates on the catalytic pathway have been isolated from reactions of MAlH (M=Li, Na, K) and different imines. Depending on the imine, double, triple or quadruple imine insertion has been observed. Prolonged reaction of LiAlH with PhC(H)=NtBu led to a side-reaction and gave the double insertion product LiAlH [N] ([N]=N(tBu)CH Ph) which at higher temperature reacts further by ortho-metallation of the Ph ring. A DFT study led to a number of conclusions. The most likely catalyst for hydrogenation of PhC(H)=NtBu with LiAlH is LiAlH [N] . Insertion of a third imine via a heterobimetallic transition state has a barrier of +23.2 kcal mol (ΔH). The rate-determining step is hydrogenolysis of LiAlH[N] with H with a barrier of +29.2 kcal mol . In agreement with experiment, replacing Li for Na (or K) and Al for B (or Ga) led to higher calculated barriers. Also, the AlH anion showed very high barriers. Calculations support the experimentally observed effects of the imine substituents at C and N: the lowest barriers are calculated for imines with aryl-substituents at C and alkyl-substituents at N.