Background::
Chiral β-hydroxy esters and α-substituted β-hydroxy esters represent versatile building blocks for
pheromones, β-lactam antibiotics and 1,2- or 1,3-aminoalcohols.
Objective::
Synthesis of versatile α-substituted β-keto esters and their diastereoselective reduction to the corresponding
syn- or anti-α-substituted β-hydroxy esters. Assignment of the relative configuration by NMR-spectroscopy after a CURTIUS
rearrangement of α-substituted β-keto esters to 4-substituted 5-methyloxazolidin-2-ones.
Method::
Diastereoselective reduction was achieved by using different LEWIS acids (zinc, titanium and cerium) in combination
with complex borohydrides as reducing agents. Assignment of the relative configuration was verified by 1H-NMR
spectroscopy after CURTIUS-rearrangement of α-substituted β-hydroxy esters to 4-substituted 5-methyloxazolidin-2-ones.
Results::
For the syn-selective reduction, titanium tetrachloride (TiCl4) in combination with a pyridine-borane complex (py
BH3) led to diastereoselectivities up to 99% dr. High anti-selective reduction was achieved by using cerium trichloride
(CeCl3) and steric hindered reducing agents such as lithium triethylborohydride (LiEt3BH). After CURTIUS-rearrangement
of each α-substituted β-hydroxy ester to the corresponding 4-substituted 5-methyloxazolidin-2-one, the relative configuration
was confirmed by 1H NMR-spectroscopy.
Conclusion::
We have expanded the procedure of LEWIS acid-mediated diastereoselective reduction to bulky α-substituents
such as the isopropyl group and the electron withdrawing phenyl ring.
Primary structure determination of five sialylated oligosaccharides derived from bronchial mucus glycoproteins of patients suffering from cystic fibrosis. The occurrence of the NeuAc alpha(2----3)Gal beta(1----4)[Fuc alpha(1----3)] GlcNAc beta(1----.) structural element revealed by 500-MHz 1H NMR spectroscopy.