Improved Methodology for the Preparation of Chiral Amines

Chapter 3
Reductive Amination
3.1. Historical View:
3.1.1. Reductive Amination Utilizing Heterogeneous Catalyst:
Reductive amination can be defined as the reaction of aldehyde or ketone with ammonia or
with a primary or a secondary amine to give alkylated amines in the presence of a catalyst
under hydrogenation conditions. Reductive amination was first described in the early days of
twentieth century by Mignonac. [1] Since then it was widely applied for the preparation of
different types of amines. The process could be described as reductive alkylation of ammonia
or reductive amination of aldehydes or ketones. [2]
Reductive amination is a powerful methodology for the synthesis of primary, secondary or
tertiary amines. Its main advantage is being a stepwise efficient methodology. It is only two
steps from the carbonyl compound to the primary amine. Due to the significance of this
transformation it was subjected to an intensive investigation by different research groups.
Several obstacles appeared on the surface during developing this methodology. Formation of
alcohol as a main by product resulting in lower yield was one of the major problem. Over
alkylation of the amine was an additional problem. Also side reactions, as aldol condensation
which leads to the formation of side products and lower the overall yield was another major
concern. Despite the fact that most of these problems were solved over the last three decades,
I will try to describe briefly the historical development of this methodology and the problems
associated with its development.
The introduction of catalysis in organic chemistry was the most important breackthrough in
the field in the twentieth century. The use of minute quantity of a catalyst to accelerate the
required reaction, accumulate the product and inhibit side reactions were the main objectives
of the catalyst use. Historically heterogeneous catalysts were first introduced in the main
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