Diastereoselective Reduction of Selected α-substituted β-keto Esters and the Assignment of the Relative Configuration by 1H-NMR Spectroscopy

(E-pub Ahead of Print)

Author(s): Christian Trapp*, Corinna Schuster, Chris Drewniok, Dieter Greif, Martin Hofrichter

Journal Name: Current Organocatalysis

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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.

Keywords: Diastereoselectivity, Keto esters, β-Hydroxy esters, Stereoselective reduction, NMR Spectroscopy

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/2213337207666201207212540
Price: $95