通过 C-C 活化实现环丙烷的对映选择性去对称化和平行动力学解析:手性 β-内酰胺的合成

IF 19.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Chem Pub Date : 2024-09-05 DOI:10.1016/j.chempr.2024.08.005
Hao Wu, Yiyao Wang, Shiyuan Sui, Gongming Chen, Lei Wang, Jiaxin Yang, Junbiao Chang, Dachang Bai
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引用次数: 0

摘要

β-内酰胺是药物化学中极具吸引力的特异主题。在此,我们报告了通过 Rh(I) 催化的不对称 C-C 键活化,对氨基环丙烷进行对映体选择性去对称化和平行动力学解析,以合成手性 β-内酰胺。手性 Rh(I) 首先催化氨基环丙烷的 C-C 键裂解,然后进行 β-酸酐消除,生成π-烯丙基氢化铑(III)中间体,该中间体可被系链炔烃单元捕获,并以优异的区域和对映体选择性(90%-99% ee)得到各种手性β-内酰胺。此外,通过 C-C 键活化,使用带有预先存在的 C2-stereocenters 的不对称氨基环丙烷时,实现了平行动力学解析,在一锅中制备出两种类型的 β-内酰胺,对映体过量率极高。值得注意的是,这些系统实现了完全的原子和步骤经济性。获得的对映体富集的 β-内酰胺具有进行多种立体特异性转化的能力。理论计算揭示了对映体选择性的来源,并支持炔烃单元插入烯丙基 Rh(III) -C 键的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Enantioselective desymmetrization and parallel kinetic resolution of cyclopropanes via C–C activation: Synthesis of chiral β-lactams

β-Lactams are privileged and appealing motifs in medicinal chemistry. Herein, we report enantioselective desymmetrization and parallel kinetic resolution of aminocyclopropanes for the synthesis of chiral β-lactams through Rh(I)-catalyzed asymmetric C–C bond activation. The chiral Rh(I) catalyzed C–C bond cleavage of aminocyclopropanes first and then underwent β-hydride elimination to generate π-allylic hydridorhodium(III) intermediates, which could be trapped by tethered alkyne units, and gave various strained chiral β-lactams with excellent regio- and enantioselectivity (90%–99% ee). Moreover, parallel kinetic resolution was realized when using unsymmetrical aminocyclopropanes with pre-existing C2-stereocenters through C–C bond activation, delivering two types of β-lactams in one pot with excellent enantiomeric excesses. Notably, these systems achieve complete atom and step economy. The obtained enantioenriched β-lactams exhibit the capability to undergo a variety of stereospecific transformations. Theoretical calculations reveal the origin of enantioselectivity and support the alkyne unit insertion to allylic Rh(III) –C bond mechanisms.

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来源期刊
Chem
Chem Environmental Science-Environmental Chemistry
CiteScore
32.40
自引率
1.30%
发文量
281
期刊介绍: Chem, affiliated with Cell as its sister journal, serves as a platform for groundbreaking research and illustrates how fundamental inquiries in chemistry and its related fields can contribute to addressing future global challenges. It was established in 2016, and is currently edited by Robert Eagling.
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