Xiaoyu Yan, Yubing Pang, Yutong Zhou, Rui Chang, Juntao Ye
{"title":"Photochemical Deracemization of Lactams with Deuteration Enabled by Dual Hydrogen Atom Transfer","authors":"Xiaoyu Yan, Yubing Pang, Yutong Zhou, Rui Chang, Juntao Ye","doi":"10.1021/jacs.4c14934","DOIUrl":null,"url":null,"abstract":"Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such as energy transfer, single electron transfer, and ligand-to-metal charge transfer have been leveraged to promote stereoablation, approaches relying on hydrogen atom transfer, which circumvent the limitations imposed by the triplet energy and redox potential of racemic substrates, remain underexplored. Conceptually, the most attractive method for tertiary stereocenter deracemization might be hydrogen atom abstraction followed by hydrogen atom donation. However, implementing such a strategy poses significant challenges, primarily because the enantioenriched products are also reactive if the chiral catalyst is unable to differentiate between the two enantiomers. Herein we report a distinct dual hydrogen atom transfer strategy for photochemical deracemization of δ- and γ-lactams, achieving high enantioenrichment and deuterium incorporation despite the inherent reactivity of the products. Mechanistic studies reveal that benzophenone enables nonselective hydrogen atom abstraction while a tetrapeptide-derived thiol dictates the enantioselectivity of the hydrogen atom donation step. More importantly, a pyridine-based alcohol was found to play crucial roles in facilitating the hydrogen atom abstraction as well as enhancing the enantioselectivity of the hydrogen atom donation step.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"17 1","pages":""},"PeriodicalIF":14.4000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/jacs.4c14934","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Photochemical deracemization has emerged as one of the most straightforward approaches to access highly enantioenriched compounds in recent years. While excited-state events such as energy transfer, single electron transfer, and ligand-to-metal charge transfer have been leveraged to promote stereoablation, approaches relying on hydrogen atom transfer, which circumvent the limitations imposed by the triplet energy and redox potential of racemic substrates, remain underexplored. Conceptually, the most attractive method for tertiary stereocenter deracemization might be hydrogen atom abstraction followed by hydrogen atom donation. However, implementing such a strategy poses significant challenges, primarily because the enantioenriched products are also reactive if the chiral catalyst is unable to differentiate between the two enantiomers. Herein we report a distinct dual hydrogen atom transfer strategy for photochemical deracemization of δ- and γ-lactams, achieving high enantioenrichment and deuterium incorporation despite the inherent reactivity of the products. Mechanistic studies reveal that benzophenone enables nonselective hydrogen atom abstraction while a tetrapeptide-derived thiol dictates the enantioselectivity of the hydrogen atom donation step. More importantly, a pyridine-based alcohol was found to play crucial roles in facilitating the hydrogen atom abstraction as well as enhancing the enantioselectivity of the hydrogen atom donation step.
期刊介绍:
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.