{"title":"Development of Asymmetric Reductive Amination of Unfunctionalized Ketone with Primary Amine","authors":"Xiangyu Liu, Ensheng Zhan, Zhi Wang, Guoliang Dong, Gaochao Dong, Shuai Wu, Yunlin Zhang, Jingrui Chen, Jialin Wen* and Lei Zhang, ","doi":"10.1021/acs.oprd.4c00095","DOIUrl":null,"url":null,"abstract":"<p >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 (<i>R</i>)-2-((1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)amino)ethan-1-ol (<b>1</b>). The formation of diastereomeric salt from the crude chiral amine with <i>L</i>-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.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00095","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
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.
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.