Tetrahedron Letters ( IF 1.5 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.tetlet.2020.151601 Sayumi Hirose , Yuji O. Kamatari , Emiko Yanase
Unprecedented diastereoselective synthesis of novel β-lactam-isatin conjugates via a Staudinger [2+2] cycloaddition is described. The electronic nature of substituents on the imine N-phenyl moiety induced high levels of stereocontrol and plausibly controlled the competition between direct ring closure (conrotatory) and isomerization of the azabutadiene intermediate. The presence of electron-donating groups (OCH3 and CH3) at the para-position of the imine N-phenyl moiety increases the electron density of the imine nitrogen atom. This in turn increases direct conrotatory ring closure favoring the cis-isomer. On the other hand, electron-withdrawing groups (NO2 and CF3) at the para-position gave the thermodynamically more stable trans-isomer as the major products by promoting isomerization of the azadiene zwitterionic intermediate presumably due to a decrease in the electron density on the imine nitrogen atom. A varied diastereoselective behavior was observed for meta-position substituents, where OCH3, CH3 and NO2 groups favored the cis-isomer, hence indicating the additional role of steric hindrance in the observed diastereoselectivity. Additionally, the transition states of these reactions computed at the density functional theory (DFT) level were in accordance with the experimental results.
中文翻译:
N-苯基取代基控制的非对映选择性合成β-内酰胺-Isatin共轭物
描述了通过史陶丁格[2 + 2]环加成反应以前所未有的非对映选择性合成新型β-内酰胺-isatin共轭物。亚胺N-苯基部分上的取代基的电子性质引起高水平的立体控制,并且可能控制了氮杂丁二烯中间体的直接闭环(旋转)和异构化之间的竞争。在亚胺N-苯基部分的对位上存在供电子基团(OCH 3和CH 3),增加了亚胺氮原子的电子密度。这反过来又增加了直接旋转环的闭合,有利于顺式异构体。在另一方面,吸电子基团(NO 2和CF 3的)对位上,得到热力学更稳定的反式异构体为主要产物通过促进氮杂二烯两性离子中间体想必的异构化是由于电子密度的减少在亚胺氮原子上。对于间位取代基,观察到多种非对映选择性行为,其中OCH 3, CH 3和NO 2基团倾向于顺式-异构体,因此表明空间位阻在观察到的非对映选择性中具有额外的作用。此外,在密度泛函理论(DFT)级别计算的这些反应的过渡态与实验结果一致。