(S,S)-(+)-Pseudoephedrine as Chiral Auxiliary
SCHEME 1. Two Most Employed Synthetic
Approaches to â-Amino Acid Derivatives
literature in which acyclic compounds have been used as
chiral auxiliaries in this reaction.6e,j,o However, despite
their conformational unpredictability, the use of acyclic
templates can constitute a very powerful alternative to
other auxiliaries because of their flexibility and potential
for adopting an induced fit type conformation, which can
be controlled at will, provided that the appropriate
experimental conditions are chosen.
Related to this topic, the strategies usually employed
to exert stereocontrol in the newly created stereogenic
centers involve the introduction of the chiral information
either at the conjugate acceptor,6 at the nitrogen nucleo-
phile, as has been brilliantly demonstrated by the groups
of Davies and Enders among others,7 or by incorporating
chiral ligands in the reaction medium in either a sto-
ichiometric8 or catalytic way.9 In the first case, it is
particularly important to remark that only a limited
number of examples can be found in the literature in
which chiral auxiliaries have been used directly attached
to the carbonyl moiety of the acceptor in asymmetric aza-
Michael reactions.6 The main reason for this is that the
chiral information remains located too far away from the
position in which the new stereocenter is going to be
formed. In fact, conformationally fixed cyclic or metal-
chelated rigid auxiliaries have been the systems com-
monly tested, with good results in conjugate additions
in general and aza-Michael reactions in particular. On
the other hand, only a few reports can be found in the
In this context, we and others have proven that the
commercially available and cheap chiral amino alcohol
pseudoephedrine constitutes an extremely useful and
efficient chiral auxiliary in many asymmetric transfor-
mations such as alkylations,10 aldol11 and Mannich
reactions,4 aminations,12 aziridine13 and epoxide14 ring-
opening reactions, and Michael additions.15 In all cases
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