6-Hydroxy Picolinohydrazides Promoted Cu(I)-Catalyzed Hydroxylation Reaction in Water:机器学习加速配体设计和反应优化。

IF 16.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Angewandte Chemie International Edition Pub Date : 2024-12-20 Epub Date: 2024-10-25 DOI:10.1002/anie.202412552
Lanting Xu, Jiazhou Zhu, Xiaodong Shen, Jiashuang Chai, Lei Shi, Bin Wu, Wei Li, Dawei Ma
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引用次数: 0

摘要

羟基(杂)烷是天然产物、材料和小分子药物中的重要基团,也是合成有机化学中的多功能中间体。在此,我们报告了一种高效的 Cu(I)/6-hydroxy picolinohydrazide 催化的(杂)芳基卤化物(Br、Cl)在水中的羟化反应。通过建立机器学习(ML)模型,有效加快了配体的设计和反应条件的优化。L32(6-HPA-DMCA)对(杂)芳基溴表现出高效率,在 80 °C、催化剂负载量最小为 0.01 mol%(100 ppm)的条件下,可促进羟化反应达到 10000 吨,或在接近室温条件下促进含有敏感官能团的底物(3.0 mol%)的羟化反应;L42(6-HPA-DTBCA)对氯化物底物表现出卓越的反应活性,在 100 °C、催化剂负载量为 2-3 mol%的条件下可促进羟化反应。这代表了铜催化羟化反应中最低催化剂负载量和温度的最新技术水平。此外,该方法还采用了一种可持续发展的环保溶剂系统,适用于多种底物,并显示出开发稳健、可扩展的关键药物中间体合成工艺的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
6-Hydroxy Picolinohydrazides Promoted Cu(I)-Catalyzed Hydroxylation Reaction in Water: Machine-Learning Accelerated Ligands Design and Reaction Optimization.

Hydroxylated (hetero)arenes are privileged motifs in natural products, materials, small-molecule pharmaceuticals and serve as versatile intermediates in synthetic organic chemistry. Herein, we report an efficient Cu(I)/6-hydroxy picolinohydrazide-catalyzed hydroxylation reaction of (hetero)aryl halides (Br, Cl) in water. By establishing machine learning (ML) models, the design of ligands and optimization of reaction conditions were effectively accelerated. The N-(1,3-dimethyl-9H- carbazol-9-yl)-6-hydroxypicolinamide (L32, 6-HPA-DMCA) demonstrated high efficiency for (hetero)aryl bromides, promoting hydroxylation reactions with a minimal catalyst loading of 0.01 mol % (100 ppm) at 80 °C to reach 10000 TON; for substrates containing sensitive functional groups, the catalyst loading needs to be increased to 3.0 mol % under near-room temperature conditions. N-(2,7-Di-tert-butyl-9H-carbazol-9-yl)-6-hydroxypicolinamide (L42, 6-HPA-DTBCA) displayed superior reaction activity for chloride substrates, enabling hydroxylation reactions at 100 °C with 2-3 mol % catalyst loading. These represent the state of art for both lowest catalyst loading and temperature in the copper-catalyzed hydroxylation reactions. Furthermore, this method features a sustainable and environmentally friendly solvent system, accommodates a wide range of substrates, and shows potential for developing robust and scalable synthesis processes for key pharmaceutical intermediates.

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来源期刊
CiteScore
26.60
自引率
6.60%
发文量
3549
审稿时长
1.5 months
期刊介绍: Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.
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