上海交通大学叶俊涛团队报道了双氢原子转移使氘化的内酰胺类光化学脱羧。相关研究成果发表在2024年12月18日出版的国际知名学术期刊《美国化学会杂志》。

近年来，光化学去甲酰化已成为获得高对映体富集化合物的最直接方法之一。虽然激发态事件，如能量转移、单电子转移和配体到金属电荷转移已被用来促进立体烧蚀，但依赖氢原子转移的方法仍然没有得到充分探索，这种方法绕过了外消旋底物的三重态能量和氧化还原势的限制。

从概念上讲，最有吸引力的三级立体中心去中心化方法可能是氢原子提取，然后是氢原子捐赠。然而，实施这种策略带来了重大挑战，主要是因为如果手性催化剂无法区分两种对映体，富集对映体的产物也是反应性的。

该文中，研究人员报告了一种独特的双氢原子转移策略，用于δ-和γ-内酰胺的光化学去酰化，尽管产物具有固有的反应性，但实现了高对映体富集和氘掺入。

机理研究表明，二苯甲酮能够实现非选择性氢原子提取，而四肽衍生的硫醇决定了氢原子供体步骤的对映选择性。更重要的是，研究发现吡啶基醇在促进氢原子提取，以及提高氢原子供体步骤的对映选择性方面起着至关重要的作用。

附：英文原文

Title: Photochemical Deracemization of Lactams with Deuteration Enabled by Dual Hydrogen Atom Transfer

Author: Xiaoyu Yan, Yubing Pang, Yutong Zhou, Rui Chang, Juntao Ye

Issue&Volume: December 18, 2024

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.

DOI: 10.1021/jacs.4c14934

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c14934