A highly enantioselective iridium-catalyzed hydrogenation of α-keto amides to form α-hydroxy amides has been achieved with excellent results (up to >99% conversion and up to >99% ee, TON up to 100 000). As an example, this protocol was applied to the synthesis of (S)-4-(2-amino-1-hydroxyethyl)benzene-1,2-diol, the enantiomer of norepinephrine, which is widely used as an injectable drug for the treatment of critically low blood pressure. Density functional theory (DFT) calculations were also carried out to reveal the reaction mechanism.
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Heteroaryl-Directed Iridium-Catalyzed Enantioselective C-H Alkenylations of Secondary Alcohols.
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Department of Chemistry, University of Liverpool, Crown Street, Liverpool L69 7ZD, United Kingdom.
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State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
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Article Synopsis
- Chiral nitrogen-containing compounds are essential in various industries, but their synthesis can be challenging due to a vast range of chemical possibilities.
- This research details a selective method to create 3,3-diarylallyl phthalimides, which, when treated with iridium catalysts, transform into 3,3-diarylpropyl amines with very high enantioselectivity (98-99% ee).
- The study highlights the role of alkene purity in achieving high enantioselectivity and illustrates how the resulting chiral propylamines can be used to make important bioactive drugs like tolterodine and tolpropamine.
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