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Current Organocatalysis

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ISSN (Print): 2213-3372
ISSN (Online): 2213-3380

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Research Article

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

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

Volume 8, Issue 2, 2021

Published on: 07 December, 2020

Page: [238 - 248] Pages: 11

DOI: 10.2174/2213337207666201207212540

Price: $65

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.

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