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In-Depth Information
1
Reactions of Nucleophiles with Electrophiles Bound to
Carbohydrate Auxiliaries
Zhiwei Miao
1.1
Introduction
Carbohydrates are widespread chiral natural products found worldwide and they
have been transformed into diverse, interesting chiral products in ex-chiral pool
syntheses. However, carbohydrates were not used as chiral auxiliaries in stereose-
lective syntheses for a long time. About 30 years ago Vasella reported the earliest
example of carbohydrate auxiliaries tools in organic synthesis [1]. During the fol-
lowing decades, carbohydrates slowly became recognized as versatile starting
materials for chiral auxiliaries in stereoselective reactions, and today a multitude
of structures has been developed and applied to various reactions [2].
1.2
Strecker Reactions
The three-component Strecker reaction as well as the hydrocyanation of imines
(modified Strecker reaction) are fundamental carbon-carbon bond-forming pro-
cesses [3], which are efficient methods for preparing
-amino acids (Scheme 1.1).
In 1987 Kunz and coworkers first reported pivaloyl protected d-galactosyl amine
3
as a very useful tool for asymmetric aminonitrile syntheses [4]. Galactosyl amine
3
can be obtained from penta-
O
-pivaloyl-
α
-d-galactopyranose
1
by reaction with
trimethylsilyl azide/tin tetrachloride to give the galactosyl azide
2
followed by
hydrogenation (Scheme 1.2) [4].
Condensation of
3
with aldehydes
4
yields galactosyl aldimines
5,
which undergo
highly diastereoselective Strecker reactions with trimethylsilyl cyanide (TMSCN)
in the presence of Lewis acids (Scheme 1.3). The observed diastereoselectivity is
a result of the attack of the cyanide anion on the face of the (
E
)-imine opposite to
the sterically demanding 2-
O
-pivaloyl group. Separation of the minor diastereoi-
somer and subsequent hydrolysis with hydrochloric acid affords the corresponding
enantiomerically pure
β
α
-amino acid
7
(R
=
p
-ClC
6
H
4
).
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