Ruan Jia, Lu Yu-Lin, Hu Peng, Su Cheng-Yong
GBRCE for Functional Molecular Engineering, LIFM, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou 510006, China.
J Am Chem Soc. 2025 Mar 26;147(12):10475-10484. doi: 10.1021/jacs.4c18358. Epub 2025 Mar 14.
Chiral spirocycles possess the ability to undergo diverse modifications in three-dimensional space, offering advantages in terms of physicochemical property and structural variability over conventional organic scaffolds and holding promising potential for the design of biologically active molecules and drugs. Among them, highly strained spirocyclobutanes with multiple chiral center-containing four-membered rings have attracted significant attention, but their viable and efficient synthesis poses a great challenge. By virtue of cage-confined asymmetric photocatalysis, we successfully construct spirocycle and bispirocycle compounds containing multiple quaternary and tertiary chiral carbon centers in cyclobutane rings through cross [2 + 2] photocycloaddition with visible-light-induced and mild reactions. The mechanistic studies unveil that the chiral open pockets of a cage photoreactor facilitate dynamic bimolecular recognition to render preferential heteromolecular cross-cycloaddition with enhanced reactivity, unconventional enantioselectivity, and good substrate tolerance, providing a promising direction for enzyme-mimetic catalyst design for challenging asymmetric photochemical transformations.
手性螺环化合物能够在三维空间中进行多种修饰，与传统有机骨架相比，在物理化学性质和结构多样性方面具有优势，在生物活性分子和药物设计方面具有广阔的潜力。其中，含有多个手性中心的高度张力螺环丁烷四元环引起了广泛关注，但其可行且高效的合成面临巨大挑战。借助笼限不对称光催化，我们通过可见光诱导的温和交叉[2 + 2]光环加成反应，成功构建了环丁烷环中含有多个季碳和叔碳手性中心的螺环和双螺环化合物。机理研究表明，笼式光反应器的手性开放口袋促进了动态双分子识别，从而实现了具有增强反应性、非常规对映选择性和良好底物耐受性的优先异分子交叉环加成，为具有挑战性的不对称光化学转化的仿酶催化剂设计提供了一个有前景的方向。
