Biomimetic Organocatalytic C–C-Bond Formations
63
2.1.4 Asymmetric Synthesis of Selectively Protected Amino Sugars
and Derivatives via Direct Organocatalytic Mannich
Reaction
In the classic Mannich reaction the corresponding β-aminocarbonyl
compounds are formed from formaldehyde, an amine, and an enolizable carbonyl component (Mannich and Krösche 1912). These so-called
Mannich bases have found broad applications as synthetic building
blocks (Arend et al. 1998; Kobayashi and Ishitani 1999), most importantly in the preparation of natural products and biologically active compounds (Traxler et al. 1995; Dimmock et al. 1993; Kleemann and Engel
1982). The main disadvantage of the classic Mannich reaction has been
the lack of stereocontrol and the formation of by-products. As a result,
the development of more selective and particularly diastereo- and enantioselective protocols for this important C–C bond-forming reaction has
been of substantial interest. In 1985 our research group, in cooperation with Steglich et al., disclosed for the first time a procedure for
a stereoselective Mannich reaction, by which enamines together with
acyliminoacetates could be transformed into diastereo- and enantiomerically pure α-amino-γ-keto esters (Kober et al. 1985). Later on we developed a first practical procedure for the regio- and enantioselective
α-aminomethylation of ketones with the assistance of a directing silyl
group at the α-position to the carbonyl group (Enders et al. 1996d, 2000,
2002b; Enders and Oberbörsch 2002). Interest in catalytic asymmetric
variants of the Mannich reaction has grown considerably in recent years.
In particular, the application of metal-free catalysts is highly desirable in
accomplishing diastereo- and enantioselective Mannich reactions. Special notice should be taken of the proline-catalyzed three-component
Mannich reaction developed by List et al. (List 2000; List et al. 2002).
In this sophisticated organocatalytic method, enolizable aldehydes and
ketones are treated with in situ generated imines to afford the corresponding Mannich products with good-to-excellent stereoselectivities.
Based on our organocatalytic C 3 +C n concept for the direct synthesis of carbohydrates, we envisaged the successful development of a diastereo- and enantioselective Mannich variant that paves the way to
selectively protected amino sugars and their derivatives. These amino
sugars are a class of carbohydrates in which one or more hydroxyl func-
63
2.1.4 Asymmetric Synthesis of Selectively Protected Amino Sugars
and Derivatives via Direct Organocatalytic Mannich
Reaction
In the classic Mannich reaction the corresponding β-aminocarbonyl
compounds are formed from formaldehyde, an amine, and an enolizable carbonyl component (Mannich and Krösche 1912). These so-called
Mannich bases have found broad applications as synthetic building
blocks (Arend et al. 1998; Kobayashi and Ishitani 1999), most importantly in the preparation of natural products and biologically active compounds (Traxler et al. 1995; Dimmock et al. 1993; Kleemann and Engel
1982). The main disadvantage of the classic Mannich reaction has been
the lack of stereocontrol and the formation of by-products. As a result,
the development of more selective and particularly diastereo- and enantioselective protocols for this important C–C bond-forming reaction has
been of substantial interest. In 1985 our research group, in cooperation with Steglich et al., disclosed for the first time a procedure for
a stereoselective Mannich reaction, by which enamines together with
acyliminoacetates could be transformed into diastereo- and enantiomerically pure α-amino-γ-keto esters (Kober et al. 1985). Later on we developed a first practical procedure for the regio- and enantioselective
α-aminomethylation of ketones with the assistance of a directing silyl
group at the α-position to the carbonyl group (Enders et al. 1996d, 2000,
2002b; Enders and Oberbörsch 2002). Interest in catalytic asymmetric
variants of the Mannich reaction has grown considerably in recent years.
In particular, the application of metal-free catalysts is highly desirable in
accomplishing diastereo- and enantioselective Mannich reactions. Special notice should be taken of the proline-catalyzed three-component
Mannich reaction developed by List et al. (List 2000; List et al. 2002).
In this sophisticated organocatalytic method, enolizable aldehydes and
ketones are treated with in situ generated imines to afford the corresponding Mannich products with good-to-excellent stereoselectivities.
Based on our organocatalytic C 3 +C n concept for the direct synthesis of carbohydrates, we envisaged the successful development of a diastereo- and enantioselective Mannich variant that paves the way to
selectively protected amino sugars and their derivatives. These amino
sugars are a class of carbohydrates in which one or more hydroxyl func-