化学
路易斯酸
柯蒂斯重排
位阻效应
四氯化钛
吡啶
药物化学
硼烷
核磁共振波谱
立体化学
有机化学
钛
催化作用
作者
Christian Trapp,Corinna Herrmann,Chris Drewniok,D. Greif,Martin Hofrichter
出处
期刊:Current organocatalysis
[Bentham Science]
日期:2021-08-01
卷期号:8 (2): 238-248
被引量:1
标识
DOI:10.2174/2213337207666201207212540
摘要
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 1 H-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 (TiCl 4 ) 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 (CeCl 3 ) and steric hindered reducing agents such as lithium triethylborohydride (LiEt 3 BH). 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 1 H 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.
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