Reactions of Nucleophiles with Electrophiles Bound to Carbohydrate Auxiliaries - Carbohydrates: Tools for Stereoselective Synthesis - page 7

- CN

OPiv

R

Ar

Cu

O

N
O

H

Piv PivO

O

21

Figure 1.2 Proposed transition-state for Strecker reactions of α , β -unsaturated imines bound
to a d-glucose-derived template.

Figure 1.2 shows the proposed transition state 23 leading to products 20. It is
very similar to the one invoked by Kunz for Strecker reactions of galactose-modi-
fied imines. The Lewis acid CuBr is coordinated to both the N-atom of the imine
and one of the O-atoms of the 2- O -pivaloyl group. This would decrease the electron
density at the C-atom of the C=N moiety and direct the attachment of cyanide.

1.3
Ugi Reactions

The terms Ugi four-component reaction (Ugi-4CR) or Ugi four-component con-
densation (U-4CC) usually refer to the reaction of an amine (usually a primary
amine; less frequently ammonia or a secondary amine), a carbonyl compound (an
aldehyde), an isocyanide, and a carboxylic acid [10]. In the course of the reaction
two peptide bonds and one carbon-carbon bond are formed and a new chiral
center is created (Scheme 1.8) [11].

O

R 2

O

N

+R 3 -NC + R 2 -CHO + R 4 -NH 2

R 1 OH

R 1 R 3 N

*

R 4

O

Scheme 1.8

General outline of a four-component Ugi reaction.

A major difficulty in conducting Ugi reactions stereoselectively is that reaction
conditions for the transformations vary considerably (e.g., solvent, temperature,
and highly diverse starting materials) and consequently the reactions follow dif-
ferent mechanisms. In one successful example Kunz employed his galactos-
ylamine auxiliary as chiral template in the Ugi reaction (Scheme 1.9) [12].
When galactosylamine 3 was allowed to react with an aldehyde, an isocyanide,
and a carboxylic acid (preferably formic acid) in the presence of zinc chloride in
THF, N -galactosyl amino acid amide derivatives 24 were obtained in almost quan-
titative yield and high dr. The N -galactosyl amino acid amide derivatives 24 can
be transformed into a series of valuable chiral products, for example, 1,2-diamines
and 78 °C) d-configured

amino acid derivatives 24 were formed with a diastereoselectivity of about 95 : 5

β -amino alcohols. At − 25 °C (for aliphatic imines −