Improved Methodology for the Preparation of Chiral Amines

8 years beginning from the year 2000.Blaser tested Rh-ferrocenyl-catalyst which he used 1.0
mol % of this catalyst (catalyst 1, figure 2.2), 70 bar (1015 psi) of H 2 , CH 3 OH at 60 °C over
21 h, the ee was 99% with full conversion (structure 1, figure 2.1). [8] He tested also his
system for different substituted phenyl alkyl N-phosphinoyl imines. p-OMe phenyl (62% ee),
p-CH 3 phenyl (97% ee), p-CF 3 phenyl (93% ee) were successfully reduced. For p-Cl phenyl
derivative, the ee was only 28 % and improved to 67% with another chiral ligand (structure 3,
figure 2.1).
Yamada developed the use of 1.0 mol % of cobalt based catalyst (catalyst 2, figure 2.2), 1.5
equiv NaBH 4 in CH 3 Cl, 0 °C, 4 h, providing 97% isolated yield with 90% ee (structure 1,
figure 2.1). [9]
Lipshutz developed the use of the DTBM-SEGPHOS ligand with CuCl (catalyst 3, figure
2.2). [10] He used 6.0 mol % of the catalyst, 3.0 equiv tetramethyldisiloxane (TMDS), 6.0 mol
% NaOMe, 3.3 equiv t-BuOH, toluene, 25 °C, 17 h, the ee for (structure 1, figure 2.1) was
96% with 99% isolated yield. Cooling the reaction to -25 °C increased the ee to 99% with
slightly lower yield (94%) for (structure 2, figure 2.1). Different substituted phenyl alkyl N-
phosphinoyl imines were tested. p-Br phenyl (96% ee, 95% yield), p-C 3 F phenyl (97% ee,
94% yield), p-OMe phenyl (94% ee, 98% yield) were reduced successfully (structure 3,
figure 2.1). They were able to reduce sterically hindered imine (phenyl iso-propyl n-
phosphinoyl imine) with 94% ee with 90% yield. The ee was improved to 97% ee with 93%
yield at -25 °C.
Avecia Limited reported the use of CATHyTM (Catalytic Asymmetric Transfer
Hydrogenation) catalysts (catalyst 4-5, figure 2.1). [11] They utilized 24 equiv of Et 3 N/HCO 2 H
(2:5 ratio) for reduction of phenyl methyl N-phosphinoyl imine (structure 1, figure 2.1) with
86% ee, for 1-acetyl naphthalene derivative the ee was 99% and for 2-octanone derived N-
phosphinoyl imine the ee was 95%.
Toste and coworkers developed a highly efficient chiral ligand for rhenium metal. [12] The use
of this ligand eliminates the need of restrictive inert condition (open flask technique). Using
3.0 mol % of the catalyst (catalyst 6, figure 2.2), 2.0 equiv of diphenylmethylsilane (DPMS-
H), CH 2 Cl 2 , 25 °C over 72 h product ee was provided in >99% albeit in mediocre yield (51%)
(structure 1, figure 2.1). They tested other substituted phenyl alkyl N-phosphinoyl imines.
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