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.