Improved Methodology for the Preparation of Chiral Amines

H 2 , toluene, 25 °C, 4 h an ee of 96% with full conversion was reported for phenyl methyl N-
aryl imine and 92% ee for phenyl ethyl N-aryl imnes (structure 1,2 , figure 2.3). Reducing the
catalyst loading to 0.5 mol % resulted in the same enantioselectivity. Lower catalyst loading
(0.1 mol %) the hydrogen pressure had to increase to 50 bar to achieve the same ee with full
conversion. He tested his system for substituted phenyl methyl N-aryl imines. The ee was
96% for p-Me phenyl methyl N-aryl imine, for m-Me phenyl methyl N-aryl imine the ee was
93% and for o-Me phenyl methyl N-aryl imine the ee was 94%. For o-OMe phenyl methyl N-
aryl imine the ee was 90%, for p-OMe phenyl methyl N-aryl imine the ee was 94% and for
m-OMe phenyl methyl N-aryl imine the ee was 96% with full conversion in all cases
(structure 3, figure 2.3).
Pizzano tested Ir-phosphine–phosphites based catalysts for reduction of N-aryl imines. [30]
Using 1.0 mol % of the catalyst (catalyst 11a, figure 2.4), 30 bar (436 psi) of H 2 , CH 2 Cl 2 , 25
°C, 24 h an ee of 82% with complete conversion for phenyl methyl N-aryl imine was
achieved (structure 1, figure 2.3). Later he used another derivative of the catalyst (catalyst
11b, figure 2.3) for reduction of substituted phenyl methyl N-aryl imine. For p-methyl phenyl
methyl N-aryl imine the ee was 72%, for p-OMe phenyl methyl N-aryl imine the ee was 85%,
for p-fluoro phenyl methyl N-aryl imine the ee was 79% and for p-chloro phenyl methyl N-
aryl imine the ee was 82%. [31]
Imamoto reduced N-aryl imines utilizing Ir-phosphine catalyst. [32] Using 0.5 mol % of the
catalyst (catalyst 12, figure 2.4), 1 bar (14.5 psi) of H 2 , CH 2 Cl 2 , 25 °C, 1.5 h, the ee was 99%
with 95% isolated yield for phenyl methyl N-aryl imine (structure 1, figure 2.3). They tested
reduction of p-OMe phenyl methyl N-aryl imine imines with 83% ee and 98% yield within 2
h. For p-fluoro phenyl methyl N-aryl imine the ee was 84% with 92% yield within 1.5 h
(structure 3, figure 2.3).
Dervisi synthesized a new Ir diphosphine catalyst {[(Ir (ddppm)-(COD)]PF 6 } and tested it for
the N-aryl imine reduction. [32] Using 1.0 mol % of the catalyst (catalyst 13, figure 2.4), 1 bar
(14.5 psi) of H 2 , ClCH 2 CH 2 Cl, 25 °C, 24 h, the ee was 84% with 99% yield for phenyl
methyl N-aryl imine (structure 1, figure 2.3). Operating at atmospheric pressure allowed the
hydrogenation to be carried using Schlenk technique instead of high pressure autoclaves.
They expanded their investigation to include p-chloro phenyl methyl N-aryl imines which
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