Biomimetic Organocatalytic C–C-Bond Formations
47
2
Organocatalytic Approach Using Proline
and Its Derivatives
2.1
Asymmetric Biomimetic C–C-Bond Formations
with a DHAP-Equivalent
DHAP (A) is used in nature as a C 3 -methylene component for the efficient and stereoselective formation of carbohydrates (Scheme 1). In
this pathway DHAP reacts with d-glyceraldehyde-3-phosphate (1) via
an enzyme-catalyzed aldol reaction to form 2. After dephosphonylation the aldol adduct 3 is then transformed to various carbohydrates and
derivatives (Calvin 1962).
To mimic the biosynthesis of carbohydrates and other valuable compounds possessing similar structural motifs we used 2,2-dimethyl-1,3dioxan-5-one (4, dioxanone) (Enders and Bockstiegel 1989; Enders
et al. 2002a), which can function as a protected dihydroxy acetoneequivalent (DHA). To use the dioxanone methodology in asymmetric
biomimetic syntheses, two concepts have been developed. First, the
SAMP/RAMP hydrazone methodology was used to form a chiral hydrazone which, after formation of the aza-enolate, can be trapped with
a great variety of electrophiles. In addition, the stoichiometric approach
was extended by using a bulky silyl group in the α-position of the dioxanone (4) as a traceless directing group in order to obtain very high
asymmetric induction in problematic cases. Both methods were successfully applied in C–C-bond forming reactions and in natural product
syntheses (Fig. 1) (for a review see: Enders et al. 2005a). Secondly, an
organocatalytic approach was established that opened up a new entry
to carbohydrates and amino sugars by using proline-catalyzed aldol and
Mannich reactions (Fig. 1).
2.1.1 Direct Organocatalytic De Novo Carbohydrate Synthesis
Inspired by the biosynthesis of carbohydrates we envisaged a direct de
novo synthesis of carbohydrate derivatives by using the DHA-equivalent
4 in a C 3 +C n -strategy. As can be seen from the retrosynthetic analysis,
the desired building blocks 5 should be prepared from the dioxanone
(4) and an aldehyde component 6 in an organocatalytic aldol reaction
47
2
Organocatalytic Approach Using Proline
and Its Derivatives
2.1
Asymmetric Biomimetic C–C-Bond Formations
with a DHAP-Equivalent
DHAP (A) is used in nature as a C 3 -methylene component for the efficient and stereoselective formation of carbohydrates (Scheme 1). In
this pathway DHAP reacts with d-glyceraldehyde-3-phosphate (1) via
an enzyme-catalyzed aldol reaction to form 2. After dephosphonylation the aldol adduct 3 is then transformed to various carbohydrates and
derivatives (Calvin 1962).
To mimic the biosynthesis of carbohydrates and other valuable compounds possessing similar structural motifs we used 2,2-dimethyl-1,3dioxan-5-one (4, dioxanone) (Enders and Bockstiegel 1989; Enders
et al. 2002a), which can function as a protected dihydroxy acetoneequivalent (DHA). To use the dioxanone methodology in asymmetric
biomimetic syntheses, two concepts have been developed. First, the
SAMP/RAMP hydrazone methodology was used to form a chiral hydrazone which, after formation of the aza-enolate, can be trapped with
a great variety of electrophiles. In addition, the stoichiometric approach
was extended by using a bulky silyl group in the α-position of the dioxanone (4) as a traceless directing group in order to obtain very high
asymmetric induction in problematic cases. Both methods were successfully applied in C–C-bond forming reactions and in natural product
syntheses (Fig. 1) (for a review see: Enders et al. 2005a). Secondly, an
organocatalytic approach was established that opened up a new entry
to carbohydrates and amino sugars by using proline-catalyzed aldol and
Mannich reactions (Fig. 1).
2.1.1 Direct Organocatalytic De Novo Carbohydrate Synthesis
Inspired by the biosynthesis of carbohydrates we envisaged a direct de
novo synthesis of carbohydrate derivatives by using the DHA-equivalent
4 in a C 3 +C n -strategy. As can be seen from the retrosynthetic analysis,
the desired building blocks 5 should be prepared from the dioxanone
(4) and an aldehyde component 6 in an organocatalytic aldol reaction