School of Chemistry and Materials Science, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, University of Science and Technology of China, Hefei, 230026, China.
Angew Chem Int Ed Engl. 2022 Aug 1;61(31):e202205537. doi: 10.1002/anie.202205537. Epub 2022 Jun 14.
Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel-catalyzed switchable site-selective alkene hydroalkylation. The selection of reaction temperatures leads to protocols that provide regiodivergent hydroalkylated products starting from a single alkene substrate. This protocol allows the convenient synthesis of α- and β-branched protected amines, both of which are important to the fields of pharmaceutical chemistry and biochemistry. In addition, enantioenriched β-branched alkylamines can be accessed in a catalytic asymmetric variant. Preliminary mechanistic studies indicate that the formation of a more stable nickelacycle provides the driving force of migration. The thermodynamic and kinetic properties of different reduction elimination intermediates are responsible for the switchable site-selectivity.
从同一原料出发，生成区域异构体的区域选择性烯烃官能化是人们所期望的。在此，我们报道了镍催化的可切换位选择性烯烃氢烷基化反应。通过选择反应温度，可以从单个烯烃底物出发，得到区域选择性不同的氢烷基化产物。该方法可方便地合成α-和β-支链保护胺，这两者在药物化学和生物化学领域都非常重要。此外，还可以通过催化不对称变体来获得对映体富集的β-支链烷基胺。初步的机理研究表明，形成更稳定的镍酰基环提供了迁移的驱动力。不同还原消除中间体的热力学和动力学性质决定了可切换的位选择性。
