Insights into LiAlH4 Catalyzed Imine Hydrogenation

Commercial LiAlH4 can be used in catalytic quantities in the hydrogenation of imines to amines with H-2. 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)CH2Ph) 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) (Delta H). The rate-determining step is hydrogenolysis of LiAlH[N](3) with H-2 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.

Automated summary

Commercial LiAlH4 can be used as a catalyst in the hydrogenation of imines, with cooperation between Li and Al being crucial for activity. Different intermediates have been isolated, with varying imine insertion observed depending on the structure of the imine. Experimental and theoretical investigations provide insights into the mechanism and barriers for the hydrogenation reaction, showing the effects of substituents on the imine structure.