Programmable Piperazine Synthesis via Organic Photoredox Catalysis.

IF 14.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Journal of the American Chemical Society Pub Date : 2024-11-13 Epub Date: 2024-11-01 DOI:10.1021/jacs.4c12028
Alexander J Boley, Jason C Genova, David A Nicewicz
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Abstract

Piperazine cores have long been identified as privileged scaffolds in the development of pharmaceutical compounds. Despite this, the facile synthesis of diverse C-substituted piperazines remains a challenge without prefunctionalized substrates/cores. Herein, we describe a programmable approach to highly diversifiable piperazine cores, which circumvents the typical need for radical precursors. The use of organic photoredox catalysis renders this method operationally simple, as direct substrate oxidation followed by 6-endo-trig radical cyclization with in situ generated imines may furnish the product. Additionally, the photoredox-catalyzed anti-Markovnikov hydroamination of readily accessible ene-carbamates provides a modular approach to functionalized diamine starting materials which are shown to generate more complex piperazine cores. A wide range of both carbonyl and amine condensation partners were shown to be compatible with this system in good to excellent yield.

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通过有机光氧化催化合成可编程哌嗪。
长期以来,哌嗪核心一直被认为是开发药物化合物的理想支架。尽管如此,如果没有预官能化的底物/核心,要轻松合成多种 C 取代哌嗪仍然是一项挑战。在本文中,我们介绍了一种可编程的方法来获得高度多样化的哌嗪核心,这种方法避免了对自由基前体的典型需求。有机光氧化催化的使用使这种方法操作简单,因为直接底物氧化,然后与原位生成的亚胺进行 6-endo-trig 自由基环化,就可以得到产物。此外,光氧化催化的反马可夫尼科夫氢化反应还能生成容易获得的烯-氨基甲酸酯,为功能化二胺起始材料提供了一种模块化方法,这种方法能生成更复杂的哌嗪核心。研究表明,多种羰基和胺缩合伙伴都能与该系统兼容,并能获得良好甚至优异的收率。
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来源期刊
CiteScore
24.40
自引率
6.00%
发文量
2398
审稿时长
1.6 months
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.
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