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

[ Vol. 8 , Issue. 2 ]

Author(s):

Christian Trapp*, Corinna Herrmann, Chris Drewniok, Dieter Greif and Martin Hofrichter   Pages 238 - 248 ( 11 )

Abstract:


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.

Methods: 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, α-substituted.

Affiliation:

Department of Organic Chemistry, Faculty of Natural and Environmental Sciences University of Applied Science Zittau/ Goerlitz, Theodor-Körner-Allee 16, Zittau 02763, Department of Organic Chemistry, Faculty of Natural and Environmental Sciences University of Applied Science Zittau/ Goerlitz, Theodor-Körner-Allee 16, Zittau 02763, Department of Organic Chemistry, Faculty of Natural and Environmental Sciences University of Applied Science Zittau/ Goerlitz, Theodor-Körner-Allee 16, Zittau 02763, Department of Organic Chemistry, Faculty of Natural and Environmental Sciences University of Applied Science Zittau/ Goerlitz, Theodor-Körner-Allee 16, Zittau 02763, International Graduate School of Zittau, Markt 23, Zittau 02763

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