Aliphatic strained rings have been increasingly applied in medicinal chemistry due to their beneficial physicochemical and pharmacokinetic properties. However, the divergent synthesis of enantioenriched cyclobutane derivatives with various structural patterns continues to be a significant challenge. Here, we disclose a palladium-catalyzed enantioselective desymmetrization of cyclobutenes, resulting in a series of hydroarylation and 1,2- and 1,3-diarylation products via the interceptions of a common Heck intermediate. Mechanistic investigations provide valuable insights into understanding the catalytic mode of the palladium catalysts and the observed variations in the deuterium-responsive behavior during reactions. Furthermore, the synthetic utility is demonstrated in the syntheses of deuterated drug candidate belaperidone skeletons and pseudosymmetrical truxinic acid-type derivatives.

中文翻译：

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钯催化环丁烯的发散对映选择性官能化

脂肪族紧张环由于其有益的物理化学和药代动力学特性而在药物化学中得到越来越多的应用。然而，具有各种结构模式的对映体富集环丁烷衍生物的不同合成仍然是一个重大挑战。在这里，我们公开了钯催化的环丁烯的对映选择性去对称化，通过截获常见的 Heck 中间体产生一系列加氢芳基化以及 1,2- 和 1,3-二芳基化产物。机理研究为理解钯催化剂的催化模式以及反应过程中观察到的氘响应行为的变化提供了宝贵的见解。此外，该合成效用在氘代候选药物贝拉哌酮骨架和假对称楚辛酸型衍生物的合成中得到了证明。