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科学家首次通过直接去除仲胺的氮来进行骨骼编辑
2021-05-16 16:14

美国芝加哥大学Mark D. Levin小组通过直接去除仲胺的氮来实现骨架编辑。2021年5月12日,国际知名学术期刊《自然》发表了这一成果。

研究人员报告了一种反应,能够从有机分子中“删除”氮。研究人员表明,N-pivaloyloxy-N-alkoxyamide可促进脂族仲胺的分子间活化,从而产生分子内碳-碳偶联产物。机理实验表明,该反应是通过isodiazene中间体进行的,该中间体将氮原子以二氮的形式挤出,从而产生了短寿命的双自由基,该自由基迅速偶联形成新的碳-碳键。该反应显示出广泛的官能团耐受性,能够将常规的胺合成方案转化为碳-碳键结构和环合成的策略。该反应在生物活性化合物的合成和骨架编辑的应用中突显了这一点。

据了解,合成化学旨在从简单的原料中建立分子的复杂性。然而,尽管具有巨大的潜力来扩大可利用的化学空间,但施加精确改变来操纵分子骨架本身连通性的能力仍然受到限制。

附:英文原文

Title: Skeletal editing through direct nitrogen deletion of secondary amines

Author: Sean H. Kennedy, Balu D. Dherange, Kathleen J. Berger, Mark D. Levin

Issue&Volume: 2021-05-12

Abstract: Synthetic chemistry aims to build up molecular complexity from simple feedstocks1. However, the ability to exert precise changes that manipulate the connectivity of the molecular skeleton itself remains limited, despite possessing substantial potential to expand the accessible chemical space2,3. Here we report a reaction that ‘deletes’ nitrogen from organic molecules. We show that N-pivaloyloxy-N-alkoxyamides, a subclass of anomeric amides, promote the intermolecular activation of secondary aliphatic amines to yield intramolecular carbon–carbon coupling products. Mechanistic experiments indicate that the reactions proceed via isodiazene intermediates that extrude the nitrogen atom as dinitrogen, producing short-lived diradicals that rapidly couple to form the new carbon–carbon bond. The reaction shows broad functional-group tolerance, which enables the translation of routine amine synthesis protocols into a strategy for carbon–carbon bond constructions and ring syntheses. This is highlighted by the use of this reaction in the syntheses and skeletal editing of bioactive compounds.

DOI: 10.1038/s41586-021-03448-9

Source: https://www.nature.com/articles/s41586-021-03448-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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