Insights into LiAlH₄ Catalyzed Imine Hydrogenation

Abstract

Commercial LiAlH₄ can be used in catalytic quantities in the hydrogenation of imines to amines with H₂ . Combined experimental and theoretical investigations give deeper insight in the mechanism and identifies the most likely catalytic cycle. Activity is lost when Li in LiAlH₄ 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 MAlH₄ (M=Li, Na, K) and different imines. Depending on the imine, double, triple or quadruple imine insertion has been observed. Prolonged reaction of LiAlH₄ with PhC(H)=NtBu led to a side-reaction and gave the double insertion product LiAlH₂ [N]₂ ([N]=N(tBu)CH₂ 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 LiAlH₄ is LiAlH₂ [N]₂ . Insertion of a third imine via a heterobimetallic transition state has a barrier of +23.2 kcal mol^-1 (ΔH). The rate-determining step is hydrogenolysis of LiAlH[N]₃ with H₂ with a barrier of +29.2 kcal mol^-1 . In agreement with experiment, replacing Li for Na (or K) and Al for B (or Ga) led to higher calculated barriers. Also, the AlH₄ ^- 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.