Improved Methodology for the Preparation of Chiral Amines

secondary amine product and any impurities like α-MBA (3-5%) can be removed easily
through washing with NH 4 Cl. The primary amine is produced in high ee and yield through
hydrogenolysis using Pd-C in MeOH and the ee can be further enhanced through simple
crystallization.
Category 1: Raney-Ni
Category 2: Pt-C
HN
Ph
HN
Ph
HN
Ph
HN
Ph
76% yld,87% de
1,2-dichloroethane
94% yld, 74% de
THF
79% yld, 87% de
hexane
82% yld, 92% de
ethanol
Category 3: Pd-C
Ph
HN
Ph
Ph
HN
Ph
NH 2
H 2 N
89% yld, 80% de
methylenechloride
92% yld, 94% de
ethylacetate
92% ee, overall yld 76%
ethylacetate
76% ee, overall yld 64%
methyl-t-butylether
Figure 3.1. Correlation of Heterogeneous Hydrogenation Catalysts with Ketone Structure
and Product example.
Nugent group also investigated other commercially available Lewis acids and they found that
B(O i Pr) 3 or Al(O i Pr) 3 , can be used to replace Ti(O i Pr) 4 . These Lewis acids are cheaper than
Ti(O i Pr) 4 but must be used in greater quantities. These Lewis acids hold the advantage over
Ti(O i Pr) 4 due to their easier work up procedures. On the work-up of Ti(O i Pr) 4 reaction a
finely dispersed TiO 2 can be formed forcing a celite filtration onscale. If no Lewis acid or the
wrong one is present, large quantities of the alcohol by product can be expected. [52]
3.3.4. Asymmetric Reductive Amination Utilizing Transfer Hydrogenation Conditions
(the Leuchart–Wallach Reaction):
As mentioned before, the source of hydrogen can be molecular hydrogen, hydride or through
utilizing transfer hydrogenation conditions. Transfer hydrogenation conditions were applied
successfully for the reduction of ketones to alcohols. The method is highly successful in
terms of obtaining high ees and high yields. [53] As it is a highly desirable goal several
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