316
2
General Synthetic Methods
C-branched sugar aceric acid [32] ( > Scheme 21), 3-ulose 68 was treated with 2-(trimethylsilyl) thiazole (2-TST) in THF under thermodynamic control, followed by desilylation with
tetra-n-butylammonium fluoride (TBAF), led to a 5:1 mixture of endo- and exo-adducts 69
and 71, respectively. In contrast, addition of 2-thiazolyl lithium to compound 68 gave only the
adduct 71, arising from sterically controlled exo-addition to the trioxabicylo[3.3.0]octane ring
system in an unoptimized 40% yield. Benzylation of isomeric adducts 69 and 71 afforded 3-Obenzyl derivatives 70 and 72, respectively. The stereochemistry of thiazole addition to 3-ulose
68 was established by X-ray structural analyses of compounds 69 and 72, which revealed that
72 has the required C-3 configuration for aceric acid synthesis.
The stereoselectivity in the reaction of 3-ketofuranose 68 and 2-thiazolyl lithium can be
attributed to the kinetic control and steric hindrance from endo-face addition. The thiazolyl
group of compounds 70 and 72 was converted into the formyl functionalized sugars 73 and 74
using essentially a one-pot, three-step literature method [38,39].
⊡ Scheme 21
⊡ Scheme 22
2
General Synthetic Methods
C-branched sugar aceric acid [32] ( > Scheme 21), 3-ulose 68 was treated with 2-(trimethylsilyl) thiazole (2-TST) in THF under thermodynamic control, followed by desilylation with
tetra-n-butylammonium fluoride (TBAF), led to a 5:1 mixture of endo- and exo-adducts 69
and 71, respectively. In contrast, addition of 2-thiazolyl lithium to compound 68 gave only the
adduct 71, arising from sterically controlled exo-addition to the trioxabicylo[3.3.0]octane ring
system in an unoptimized 40% yield. Benzylation of isomeric adducts 69 and 71 afforded 3-Obenzyl derivatives 70 and 72, respectively. The stereochemistry of thiazole addition to 3-ulose
68 was established by X-ray structural analyses of compounds 69 and 72, which revealed that
72 has the required C-3 configuration for aceric acid synthesis.
The stereoselectivity in the reaction of 3-ketofuranose 68 and 2-thiazolyl lithium can be
attributed to the kinetic control and steric hindrance from endo-face addition. The thiazolyl
group of compounds 70 and 72 was converted into the formyl functionalized sugars 73 and 74
using essentially a one-pot, three-step literature method [38,39].
⊡ Scheme 21
⊡ Scheme 22