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镍催化α-取代酰亚胺的不对称还原芳基化反应

Ni-Catalyzed Asymmetric Reductive Arylation of α-Substituted Imides.

作者信息

Chen Li-Ming, Shin Chungkeun, DeLano Travis J, Carretero-Cerdán Alba, Gheibi Golsa, Reisman Sarah E

机构信息

The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.

Division of Theoretical Chemistry & Biology, CBH School, KTH Royal Institute of Technology, Teknikringen 30, Stockholm S-10044, Sweden.

出版信息

J Am Chem Soc. 2024 Oct 30;146(43):29523-29530. doi: 10.1021/jacs.4c09327. Epub 2024 Oct 16.

Abstract

α-Aryl imides are common structural motifs in bioactive molecules and proteolysis-targeting chimeras designed for targeted protein degradation. An asymmetric Ni-catalyzed reductive cross-coupling of imide electrophiles and (hetero)aryl halides has been developed to synthesize enantioenriched α-arylglutarimides from simple starting materials. Judicious selection of electrophile pairs allows for coupling of both electron-rich and electron-deficient (hetero)aryl halides in good yields and enantioselectivities.

摘要

α-芳基酰亚胺是生物活性分子和用于靶向蛋白质降解的蛋白酶靶向嵌合体中常见的结构基序。已开发出一种不对称镍催化的酰亚胺亲电试剂与(杂)芳基卤化物的还原交叉偶联反应,以从简单的起始原料合成对映体富集的α-芳基戊二酰亚胺。对亲电试剂对的明智选择允许富电子和缺电子的(杂)芳基卤化物以良好的产率和对映选择性进行偶联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f30d/11528402/b9f9f8647b8b/ja4c09327_0001.jpg

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