Institute of Organic Chemistry, Justus Liebig University, 35392, Giessen, Germany.
Current address: Shenzhen Bay Laboratory, Shenzhen, 518055, China.
Angew Chem Int Ed Engl. 2021 Feb 23;60(9):4823-4832. doi: 10.1002/anie.202012760. Epub 2021 Jan 28.
The well-known Corey-Bakshi-Shibata (CBS) reduction is a powerful method for the asymmetric synthesis of alcohols from prochiral ketones, often featuring high yields and excellent selectivities. While steric repulsion has been regarded as the key director of the observed high enantioselectivity for many years, we show that London dispersion (LD) interactions are at least as important for enantiodiscrimination. We exemplify this through a combination of detailed computational and experimental studies for a series of modified CBS catalysts equipped with dispersion energy donors (DEDs) in the catalysts and the substrates. Our results demonstrate that attractive LD interactions between the catalyst and the substrate, rather than steric repulsion, determine the selectivity. As a key outcome of our study, we were able to improve the catalyst design for some challenging CBS reductions.
著名的 Corey-Bakshi-Shibata（CBS）还原反应是一种从前手性酮不对称合成醇的强大方法，通常具有高产率和优异的选择性。虽然多年来一直认为空间排斥是观察到的高对映选择性的关键因素，但我们表明伦敦色散（LD）相互作用对于对映体选择性至少同样重要。我们通过一系列带有色散能供体（DED）的修饰 CBS 催化剂的详细计算和实验研究来证明这一点，DED 存在于催化剂和底物中。我们的结果表明，催化剂和底物之间的吸引力 LD 相互作用，而不是空间排斥，决定了选择性。作为我们研究的一个关键成果，我们能够改进一些具有挑战性的 CBS 还原反应的催化剂设计。
