Improved Methodology for the Preparation of Chiral Amines

Chapter 6
Catalytic Lewis Acids in Reductive
Amination.
6.1. Introduction.
Historically Lewis acids were used in reductive amination in stoichiometric quantities.
Through extensive literature search I did not find any previous example for the catalytic use
of Lewis acids in reductive amination. This was one of the limitations for scaling up the use
of Lewis acids in reductive amination. The high diastereoselectivity obtained with the use of
Yb(OAc) 3 in reductive amination motivated us to investigate deeply for the possibility of
using Lewis acids in catalytic quantities. Table 6.1 shows the effect of slowly decreasing the
mol % of dried Yb(OAc) 3 from 110 mol % to 10 mol %. The data shows that 80 mol %
Yb(OAc) 3 produces the same results as 110 mol %, and interestingly 50 mol % Yb(OAc) 3 is
capable of maintaining very similar de (1% less) as compared to 110 mol %. Rapid
deterioration in the diastereoselectivity was noticed when the Yb(OAc) 3 loading was reduced
below 40%. When the Yb(OAC) 3 loading was reduced to 10 mol % no improvement in the
de was noticed the de’s observed were similar to the previously reported with non-Yb(OAc) 3
based methods with α-MBA. [1]
Table 6.1. Relationship Between Mol % of Yb(OAc) 3 and Diastereoselectivity of Amine
Product. a
entry Yb(OAC) 3 mol% de%
1 110 87
2 100 87
3 80 87
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