Development of Asymmetric Reductive Amination of Unfunctionalized Ketone with Primary Amine

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2024-05-22 DOI:10.1021/acs.oprd.4c00095

Xiangyu Liu, Ensheng Zhan, Zhi Wang, Guoliang Dong, Gaochao Dong, Shuai Wu, Yunlin Zhang, Jingrui Chen, Jialin Wen* and Lei Zhang,

引用次数: 0

Abstract

Direct asymmetric reductive amination provides a straightforward approach to preparing α-chiral amine synthons. We herein disclose a chemical process to produce α-chiral secondary amine from alkyl (hetero)aryl ketone, primary amine, and molecular hydrogen. By using high-throughput screening technology, an iridium/bisphosphine catalyst was selected that gives a turnover number of ∼1000 and a ee value of 91–92% in the production of (R)-2-((1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)amino)ethan-1-ol (1). The formation of diastereomeric salt from the crude chiral amine with L-tartaric acid and crystallization upgrade the ee value to >99% and the purity to >99%. The multikilogram production of an enantiopure chiral secondary amine was realized with good reproducibility with this process.

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开发未官能化酮与伯胺的不对称还原胺化反应

直接不对称还原胺化为制备α-手性胺合成物提供了一种直接的方法。我们在此公开一种以烷基（杂）芳基酮、伯胺和分子氢为原料制备 α-手性仲胺的化学工艺。通过使用高通量筛选技术，我们筛选出了一种铱/双膦催化剂，它在生产(R)-2-((1-(2-(双(4-甲氧基苄基)氨基)吡啶-3-基)乙基)氨基)乙-1-醇 (1) 的过程中，转化率可达 1000，ee 值为 91-92%。粗手性胺与 L-酒石酸形成非对映异构盐并结晶后，ee 值升至 99%，纯度升至 99%。该工艺实现了多公斤对映体纯手性仲胺的生产，并具有良好的重现性。

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.

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