Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore.
Org Biomol Chem. 2019 Jun 26;17(25):6293-6304. doi: 10.1039/c9ob00750d.
The intramolecular oxa-Michael addition giving tetrahydropyrans has been examined experimentally using both acidic and basic catalysis. With acidic catalysis, the diequatorial product is exclusively obtained in a kinetically controlled reaction in all cases. Under basic conditions at low temperature, the reaction is again under kinetic control, but formation of the axial-equatorial isomer is generally favoured with an (E)-Michael acceptor, although isomerisation to the diequatorial isomer is observed at higher temperatures. Computationally, it is found that the acid catalysed reaction has a late transition state and the kinetic favouring of the diequatorial isomer has a steric explanation. In contrast, under strongly basic conditions, an early transition state is found. Electrostatic effects are likely to be the main contributor to the stereoselectivity for the (E)-isomer and steric interactions for the (Z)-isomer.
实验研究了使用酸催化和碱催化的分子内恶唑-Michael 加成生成四氢吡喃。在酸催化条件下，在所有情况下，动力学控制反应均得到完全为对角型产物。在低温碱性条件下，反应再次受到动力学控制，但一般情况下，（E）-Michael 受体有利于生成轴向-赤道型异构体，尽管在较高温度下观察到向对角型异构体的异构化。计算表明，酸催化反应具有后期过渡态，并且动力学有利于对角型异构体具有空间解释。相比之下，在强碱条件下，发现了早期过渡态。静电效应可能是（E）-异构体立体选择性的主要贡献者，而立体相互作用则是（Z）-异构体的主要贡献者。
