Enhancing the Sustainability and Scalability of Transition-Metal-Free Stereoretentive Decarboxylative Amidation with Dioxazolones

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-08-30 DOI:10.1021/acs.oprd.4c0024710.1021/acs.oprd.4c00247

Jeonguk Kweon, Minjeong Lee, Dongwook Kim and Sukbok Chang*,

引用次数: 0

Abstract

Herein, we present an investigation into the scalability and sustainability of decarboxylative amidation for constructing C(sp³)–N bonds using dioxazolones as the amino source under transition-metal-free and ambient conditions. One of the concerns regarding the sustainability of the previously developed amidation protocol, mainly arising from the use of dimethyl sulfoxide (DMSO), was successfully addressed through reoptimization. Ethyl acetate can now serve as an effective, environmentally friendly alternative reaction medium. We also present the results of a sensitivity study of the newly optimized amidation conditions, examining parameters such as O₂ levels, concentrations, water content, and temperatures. The practicability of this stereoretentive decarboxylative amidation has been validated through multigram-scale reactions (5–50 mmol), including optically active carboxylic acids such as (S)-Naproxen.

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增强二恶唑酮无过渡金属立体脱羧酰胺化反应的可持续性和可扩展性

在此，我们介绍了在无过渡金属和环境条件下，使用二恶唑酮作为氨基源，对脱羧酰胺化作用构建 C(sp3)-N 键的可扩展性和可持续性进行的研究。先前开发的酰胺化反应方案主要因使用二甲基亚砜（DMSO）而引起的可持续性问题之一，已通过重新优化成功解决。现在，乙酸乙酯可以作为一种有效、环保的替代反应介质。我们还介绍了对新优化的酰胺化条件进行敏感性研究的结果，研究了氧气水平、浓度、水含量和温度等参数。通过多克级反应（5-50 毫摩尔）验证了这种立体定向脱羧酰胺化反应的实用性，包括光学活性羧酸，如 (S)- 萘普生。

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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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.