Modular Access to Spiro-dihydroquinolines via Scandium-Catalyzed Dearomative Annulation of Quinolines with Alkynes,Journal of the American Chemical Society

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Modular Access to Spiro-dihydroquinolines via Scandium-Catalyzed Dearomative Annulation of Quinolines with Alkynes
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-11-23 , DOI: 10.1021/jacs.1c10743
Shao-Jie Lou _{1,

2} , Gen Luo ₃ , Shigeru Yamaguchi ₁ , Kun An ₂ , Masayoshi Nishiura _{1,

2} , Zhaomin Hou _{1,

2}

Affiliation

The catalytic enantioselective construction of three-dimensional molecular architectures from planar aromatics such as quinolines is of great interest and importance from the viewpoint of both organic synthesis and drug discovery, but there still exist many challenges. Here, we report the scandium-catalyzed asymmetric dearomative spiro-annulation of quinolines with alkynes. This protocol offers an efficient and selective route for the synthesis of spiro-dihydroquinoline derivatives containing a quaternary carbon stereocenter with an unprotected N–H group from readily accessible quinolines and diverse alkynes, featuring high yields, high enantioselectivity, 100% atom-efficiency, and broad substrate scope. Experimental and density functional theory studies revealed that the reaction proceeded through the C–H activation of the 2-aryl substituent in a quinoline substrate by a scandium alkyl (or amido) species followed by alkyne insertion into the Sc–aryl bond and the subsequent dearomative 1,2-addition of the resulting scandium alkenyl species to the C═N unit in the quinoline moiety. This work opens a new avenue for the dearomatization of quinolines, leading to efficient and selective construction of spiro molecular architectures that were previously difficult to access by other means.

中文翻译：

通过钪催化喹啉与炔烃的脱芳环化制备螺二氢喹啉

从有机合成和药物发现的角度来看，从平面芳烃（如喹啉）催化对映选择性构建三维分子结构具有重要意义，但仍存在许多挑战。在这里，我们报告了喹啉与炔烃的钪催化不对称脱芳环环化。该协议提供了一种有效且选择性的途径，用于从易于获得的喹啉和多种炔烃中合成含有季碳立体中心和未保护的 N-H 基团的螺二氢喹啉衍生物，具有高产率、高对映选择性、100% 原子效率和广泛的基材范围。实验和密度泛函理论研究表明，该反应通过烷基钪（或酰胺基）物质对喹啉底物中的 2-芳基取代基进行 C-H 活化，然后将炔烃插入 Sc-芳基键和随后的脱芳烃得到的钪烯基物质与喹啉部分的 C=N 单元进行 1,2-加成。这项工作为喹啉的去芳构化开辟了一条新途径，导致高效和选择性地构建以前难以通过其他方式获得的螺分子结构。

更新日期：2021-12-08

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