Saint Petersburg State University, Saint Petersburg, 199034 Russian Federation.
Org Biomol Chem. 2021 May 5;19(17):3829-3833. doi: 10.1039/d1ob00534k.
A series of medicinally important dihydropyridin-2(1H)-ones have been prepared via a novel [4 + 2]-formal cycloaddition reaction of chalcone imines and homophthalic anhydrides, which is a rare example of lactam construction from an imine acting as a four-atom building block. In contrast to previous studies on the reactivity of homophthalic anhydrides towards similar substrates, N-tosyl chalcone imines, we found the possibility of switching chemoselectivity by changing substituents at the nitrogen atom, which leads to the formation of heterocycles instead of the expected carbocycles. This reaction is very similar in appearance to the classic 1,2-addition of cyclic anhydrides to imines, often referred to as the Castagnoli-Cushman reaction, but differs in mechanistic details (representing a 1,4-reaction of imine). The developed atom-economical, stereoselective and catalyst- and chromatography-free protocol provided facile access to 28 structurally diverse heterocyclic products (in up to 88% yield) including synthetically challenging annelated tricyclic and previously unreported pentaaryl-substituted dihydropyridin-2(1H)-ones.
已经通过查耳酮亚胺和均苯四甲酸酐的新型[4 + 2]-形式环加成反应制备了一系列具有医学重要性的二氢吡啶-2(1H)-酮，这是酰胺环从作为四原子砌块的亚胺构建的罕见实例。与以前关于均苯四甲酸酐对类似底物（N-对甲苯磺酰基查耳酮亚胺）的反应性的研究相比，我们发现通过改变氮原子上的取代基有可能改变化学选择性，从而导致形成杂环而不是预期的碳环。该反应在外观上与环状酸酐向亚胺的经典 1,2-加成非常相似，通常称为 Castagnoli-Cushman 反应，但在机理细节上有所不同（代表亚胺的 1,4-反应）。开发的原子经济性、立体选择性和无催化剂及无色谱的方案为 28 种结构多样的杂环产物（最高产率达 88%）的简便合成提供了途径，包括具有挑战性的稠合三环和以前未报道的五芳基取代的二氢吡啶-2(1H)-酮。
