Improved Methodology for the Preparation of Chiral Amines

stream of organic chemistry. Hydrogenation catalysts as nickel, palladium platinum and other
transition metal catalysts received the maximum attention. These catalysts were initially
introduced for alkene hydrogenation and they were later tested for other transformations as
reductive amination. [3]
Reductive alkylation of ammonia was one of the earliest examples described in literatures. It
generally proceeds under mild conditions using heterogeneous catalyst. The reductive
alkylation of ammonia with carbonyl compounds may produce primary, secondary, and
tertiary amines, as well as alcohol as a side product. The origin of product selectivity depends
primarily on the molar ratio of carbonyl compound to ammonia, the nature of catalyst and
structure of the carbonyl compound. The reaction of benzaldehyde in the presence of 1.0
equivalent of ammonia in ethanol over Raney Ni gave benzylamine in an 89.4% yield while
with 0.5 equivalent of ammonia dibenzylamine was obtained in an 80.8% yield. [4]
Reductive amination of aliphatic aldehydes having α-hydrogen atoms, especially of the type
RCH 2 CHO, usually results in lower yields due to the formation of by products through aldol
or other condensation reactions. Also lower aliphatic aldehydes usually produce mixture of
primary, secondary, and tertiary amines. The reaction of butyraldehyde with 0.5 equivalent of
ammonia over Raney Ni also resulted in a mixture of 31% of butylamine, 17% of
dibutylamine, and 8% tributylamine. [5] Higher aldehydes usually react selectively with
ammonia producing less by products. [6]
The reductive alkylation of ammonia with ketones is performed under conditions similar to
those for aldehydes, but appears to proceed with more difficulty. Initially, reductive
amination of ketones with ammonia was tested without any additives resulting in lower
yields. [7,8] Primary amines are considered better neocluophihes compared to ammonia.
Despite their higher nucleophilicity they are more sterically hindered. They were tested in
reductive amination of carbonyl compounds utilizing different heterogeneous catalysts as
nickel, platinum oxide, platinum sulphide and nickel sulphide. The following examples are
some early trials for the preparation of secondary amines from primary amines (scheme
3.1). [9-12] NH 2 CH(CH 2 ) 2 CHO
(0.5mol)
Ni-kieselguhr
125 o C,100 bar H 2 ,1h
(0.55mol) 54
(91%)
NHC 4 H 9