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阴离子介导双催化多组分烯烃叠氮芳基化反应
作者:小柯机器人 发布时间:2021/9/16 14:58:55

英国剑桥大学Gaunt, Matthew J.团队开发了阴离子双催化多组分烯烃叠氮化芳基化反应。相关研究成果于2021年9月13日发表在《自然》。

含有β-芳基乙胺的分子在调节疼痛、治疗神经系统疾病和阿片类药物成瘾等方面显示出重要的适应症,使其成为药物发现的特权支架。其组装的从头方法依赖于通过耗时多步骤合成将一小类原料转化为目标化合物的转化。合成发明可以推动对该支架周围化学空间的研究,以进一步扩展其生物学能力。

该文中,研究人员报告了双催化平台的开发,该平台能够实现烯烃、芳基亲电试剂和简单的氮亲核试剂的多组分偶联,提供合成多功能和功能多样的β-芳基乙胺的单步途径。在可见光的驱动下,两种分立的铜催化剂协调芳基的形成和叠氮基的转移,这是烯烃叠氮芳基化过程的基础。该过程在烯烃和芳基组分中表现出广泛的范围,叠氮化物阴离子作为氮源和通过内球电子转移介导氧化还原中性双重催化起着多方面的作用。

该阴离子介导的烯烃功能化过程的合成能力可能用于多种药学相关和更广泛的合成应用。

附:英文原文

Title: Multicomponent alkene azido-arylation by anion-mediated dual catalysis

Author: Bunescu, Ala, Abdelhamid, Yusra, Gaunt, Matthew J.

Issue&Volume: 2021-09-13

Abstract: β-Arylethylamine-containing molecules display important indications in the modulation of pain, treatment of neurological disorders and management of opioid addiction, amongst others, making it a privileged scaffold in drug discovery1,2. De novo methods for their assembly are reliant on transformations that convert a small class of feedstocks into the target compounds via time consuming multi-step syntheses3–5. Synthetic invention can drive investigation of the chemical space around this scaffold in order to further expand its capabilities in biology6–9. Here, we report the development of a dual catalysis platform that enables a multi-component coupling of alkenes, aryl-electrophiles and a simple nitrogen-nucleophile, providing single-step access to synthetically versatile and functionally diverse β-arylethylamines. Driven by visible-light, two discrete copper-catalysts orchestrate aryl-radical formation and azido-group transfer, which underpin an alkene azido-arylation process. The process exhibits broad scope in alkene and aryl components and an azide-anion performs a multifaceted role as both nitrogen source and in mediating the redox-neutral dual-catalysis via inner-sphere electron transfer10,11. The synthetic capabilities of this anion-mediated alkene functionalization process are likely to be of use in a variety of pharmaceutically-relevant and wider synthetic applications.

DOI: 10.1038/s41586-021-03980-8

Source: https://www.nature.com/articles/s41586-021-03980-8

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:42.778
官方网址:http://www.nature.com/