306
2
General Synthetic Methods
COT
cyclooctatetraene
DLP
dilauoryl peroxide
DMF
dimethylformamide
HDA
hetero-Diels–Alder
HMDS 1,1,1,3,3,3-hexamethyldisilazane
MBH
Morita–Baylis–Hillman
MDA
methyl diazoacetate
MMTr monomethoxytrityl
TBS
tert-butyldimethylsilyl
TBAF tetra-n-butylammonium fluoride
TBAI
tetra-n-butylammonium iodide
TBDPS tertbutyldiphenylsilyl
TEA
triethylamine
TEDMS 2-(trimethylsilyl)ethynyl]dimethylsilyl
THF
tetrahydrofuran
THP
tetrahydropyran
1 Introduction
The carbohydrates represent a structurally diverse group of compounds, which are usually
derivatized with a variety of functional group modifications. C-branched sugar derivatives, in
which a new C–C bond was formed at the non-anomeric center, can provide a versatile compound pool for drug screening. Generally speaking, any chemistry method (traditional or new)
applied to C–C bond formation could be useful in C-branching sugar preparation. Among these
methods are intramolecular alkylation and intramolecular condensation of aldehyde with enolates, phosphonates, and nitro-stabilized anions. Metal-mediated radical reactions, cycloadditions, and rearrangements have also been applied frequently.
2 C–C Bond Formation by Means of Nucleophilic Additions
2.1 Addition of Organometallics to Carbonyl Sugar
Organometallics, such as Grignard reagents and alkyllithium, are the most commonly used
C-nucleophiles in C–C bond formation by addition to a carbonyl-functionalized sugar
( > Scheme 1). Occasionally, organocopper [1] and alkylcerium reagents [2], prepared from
alkyllithium and copper or cerium salts, are applied in this type of reaction. These nucleophilic
additions, especially for Grignard reagents, are usually of high stereoselectivity due to the possible chelate-complexation between the metal ions and oxygenate group in the molecule [3].
The diastereofacial selectivity can be predicted and explained by different models [4]. The
hydroxyl group generated in situ can also be further deoxylated or transformed into other
functional groups.
For synthesizing the C-methyl-branched sugars [5] such as L-axenose, L-cladinose, L-arcannose, and L-vinelose, methylmagnesium bromide and methyllithium are often used to intro-
2
General Synthetic Methods
COT
cyclooctatetraene
DLP
dilauoryl peroxide
DMF
dimethylformamide
HDA
hetero-Diels–Alder
HMDS 1,1,1,3,3,3-hexamethyldisilazane
MBH
Morita–Baylis–Hillman
MDA
methyl diazoacetate
MMTr monomethoxytrityl
TBS
tert-butyldimethylsilyl
TBAF tetra-n-butylammonium fluoride
TBAI
tetra-n-butylammonium iodide
TBDPS tertbutyldiphenylsilyl
TEA
triethylamine
TEDMS 2-(trimethylsilyl)ethynyl]dimethylsilyl
THF
tetrahydrofuran
THP
tetrahydropyran
1 Introduction
The carbohydrates represent a structurally diverse group of compounds, which are usually
derivatized with a variety of functional group modifications. C-branched sugar derivatives, in
which a new C–C bond was formed at the non-anomeric center, can provide a versatile compound pool for drug screening. Generally speaking, any chemistry method (traditional or new)
applied to C–C bond formation could be useful in C-branching sugar preparation. Among these
methods are intramolecular alkylation and intramolecular condensation of aldehyde with enolates, phosphonates, and nitro-stabilized anions. Metal-mediated radical reactions, cycloadditions, and rearrangements have also been applied frequently.
2 C–C Bond Formation by Means of Nucleophilic Additions
2.1 Addition of Organometallics to Carbonyl Sugar
Organometallics, such as Grignard reagents and alkyllithium, are the most commonly used
C-nucleophiles in C–C bond formation by addition to a carbonyl-functionalized sugar
( > Scheme 1). Occasionally, organocopper [1] and alkylcerium reagents [2], prepared from
alkyllithium and copper or cerium salts, are applied in this type of reaction. These nucleophilic
additions, especially for Grignard reagents, are usually of high stereoselectivity due to the possible chelate-complexation between the metal ions and oxygenate group in the molecule [3].
The diastereofacial selectivity can be predicted and explained by different models [4]. The
hydroxyl group generated in situ can also be further deoxylated or transformed into other
functional groups.
For synthesizing the C-methyl-branched sugars [5] such as L-axenose, L-cladinose, L-arcannose, and L-vinelose, methylmagnesium bromide and methyllithium are often used to intro-