Enantioselective Addition Reactions Catalyzed by Carbohydrate-Derived Organocatalysts - Carbohydrates: Tools for Stereoselective Synthesis - page 344

reactions in organic synthesis. The adducts can be readily be converted into valu-
able nitrogen-containing building blocks, such as

-amino acids, 1,2-diamines,
and 2-amino alcohols. Therefore, these transformations have received much atten-
tion over the past decades, and considerable effort has been directed towards the
development of enantioselective versions, catalyzed by transition-metal complexes
[9]. In recent years enantioselective, organocatalytic Strecker and Mannich reac-
tions have become a new focus of interest for organic chemists [10].

α - or β

16.2.1
Strecker Reactions

The Strecker reaction constitutes one of the easiest and most efficient methods
for the preparation of -amino acids. Over past decades, many efficient chiral cata-

lysts have been applied in asymmetric Strecker reactions for the production of
optically active

α

-amino acids [10a-d]. Jacobsen and coworkers found that the
combination of chiral 1,2- trans -diaminocyclohexane with urea or thiourea func-
tions as hydrogen bridge-forming groups affords excellent organocatalysis to
promote the hydrocyanation of imines in high enantiomeric excess [3e, 4b, 11].
Based on this concept, Kunz and coworkers developed a series of new interesting
organocatalysts by replacing the chiral 1,2- trans -diaminocyclohexane moiety with
readily available d-glucosamine 1 [12]. In principle, there are four possible ways
of attaching a Schiff base and a urea-derived side chain to the carbohydrate back-
bone (Scheme 16.1: structures A - D ). The synthesis of organocatalyst 2 is shown
in Scheme 16.1. Acetylated

α

-d-glucosamine was prepared from d-glucosamine 1
in three steps. The allyloxycarbonyl (Aloc) group was introduced to furnish allyl
carbamate, which was treated with trimethylsilyl azide to give glycosyl azide. For-
mation of the urea linkage with the l- tert -leucine benzylamide was achieved by a
Staudinger- aza -Wittig-type reaction to give the N -glycosylurea derivative. Subse-
quently, deprotection in the presence of a palladium(0)-complex, and condensation
with a salicylaldehyde furnished catalyst 2. Other imine-urea catalysts were pre-
pared in a similar way. When these derivatives were employed in enantioselective
Strecker reactions, it was found that only the

β

-configured compound 2 with the
urea moiety linked to the anomeric center and the Schiff base at the 2-amino
function exhibited efficient reactivity and enantioselectivity. Other combinations
or modified imine-urea catalysts displayed low enantioselectivities (

β

36% ee). For
many aromatic aldimines formed from substituted benzaldehydes and allyl or
benzyl amine, good to high enantiomeric excesses were observed in the presence
of 2; only the p -nitro aldimine gave low enantioselectivity due to racemization of
the resulting p -nitrophenyl-glycinonitrile. On the other hand, aliphatic aldimines,
ketimines, and the reactive furfuryl derivatives only gave moderate enantioselec-
tivities (Table 16.1).
Shortly afterwards, the Kunz group introduced another type of imine as
organocatalyst for the enantioselective Strecker reaction. These were prepared
from a tetra- O -pivalated d-galactosyl-amine and planar-chiral [2, 2]paracyclophane
derivatives (Scheme 16.2) [13]. When employed in Strecker reactions, N -galactosyl

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