Improved Methodology for the Preparation of Chiral Amines

Chapter 5
Stoichiometric Use of Ytterbium
Acetate in Reductive Amination.
5.1. Introduction.
The general lack of literatures describing the synthesis of alkyl-alkyl chiral amines has
encouraged us to try developing a new methodology for their synthesis. Of the commonly
explored strategies for the α-chiral amine synthesis (described earlier), reductive amination
has the advantage of being a stepwise efficient methodology with low waste generation. [1]
The use of atom economic environmentally friendly hydride source (molecular hydrogen) is
routinely practiced by the pharmaceutical industries for achiral C-N bond formations but not
often reported in literatures. (R)- and (S)-α-methylbenzylamine (α-MBA) were chosen as the
chiral amine auxiliary among. Of course there are other available auxiliaries such as (R)-and
(S)- phenylglycinol, (R)- and (S)- phenylglycine amide or (R)- or (S)- t-butylsulfinylamide. α-
MBA was chosen for three reasons: it is inexpensive, already in use by the pharmaceutical
industries and the cleavage (hydrogenolysis) of this auxiliary is well established high yielding
process. [2]
Table 5.1. Sigma-Aldrich Quote may 2006 for Two Common Chiral Ammonia
Equivalents. [3]
Chemical Name Quantity(kg) Price (US dollars)
(S)-N-tert-butansulfinamide 1.0 13.125.00
(R)-N-tert-butansulfinamide 1.0 13.125.00
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