Improved Methodology for the Preparation of Chiral Amines

Phenyl n-propyl N-suilphinyol imine was reduced with 68% yield and >99% ee. p-OMe
phenyl (98% ee, 61% yield), p-CF 3 phenyl (98% ee, 78% yield), p-I phenyl (99% ee, 71%
yield) methyl N-phosphinoyl imines were reduced. The system was also applicable for
heterocyclic derivatives.
The use of Zn/diamine catalyst was reported by Yun. [13] One of the problems related to the
use of Zn for the catalytic enantioselective reduction of imines is the strong Zn-N bond
formed between Zn and amine product. The source of hydride should affect this bond without
affecting the bond between the metal and the diamine. They thought that the choice of the
substituent attached to the imine nitrogen will be crucial, so they selected diphenylphoshinoyl
moiety. Using 5.0 mol % of the catalyst (catalyst 7, figure 2.2), 3.0 equiv of
polymethylhydrosiloxane (PMHS), THF/MeOH, 25 °C, 12 h, the ee was 97% and 86%
isolated yield for phenyl methyl N-phosphinoyl imine (structure 1, figure 2.1). For the phenyl
ethyl N-phosphinoyl imine, they achieved 96% ee with 82% yield (structure 2, figure 2.1). p-
Br phenyl (97% ee, 77% yield) and p-OMe phenyl (96% ee, 83% yield) methyl N-
phosphinoyl imines were reduced (structure 3, figure 2.1)
Zhou used Pd(CF 3 CO 2 ) 2 /(S)-SEGPHOS for reduction of this category of imines. [14] Using 2.0
mol % of the catalyst (catalyst 8, figure 2.2), 69 bar (1015 psi) of H 2 , 2,2,2 trifluroethanol, 25
°C, 8-12 h, the ee was 96% with 98% yield for phenyl methyl N-phosphinoyl imine (structure
1, figure 2.1). His catalyst proved to be highly efficient for the reduction of different
substituted phenyl methyl N-phosphinoyl imines. p-CH 3 phenyl (97% ee, 93% yield), p-F
phenyl (94% ee, 87% yield), p-Cl phenyl (94% ee, 90% yield), p-OMe phenyl (96% ee, 96%
yield), m-OMe phenyl (96% ee, 97% yield), o-OMe phenyl (99% ee, 80% yield) methyl N-
phosphinoyl imines were tested (structure 3, figure 2.1).
Zn-diamino-bis(tert-thiophene) catalyst was tested by Ronchi. [15] Using 5.0 mol % of the
catalyst (catalyst 9, frigure 2.2), 5.0 equiv of PMHS, THF/MeOH, 0 °C, 3 h, the ee was 97%
and 70% yield for phenyl methyl N-Phosphinoyl imine (structure 2, figure 2.1).
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