轉自：康龍化成

Paired Electro-Synthesis of Remote Amino Alcohols with/in H2O

Xinyue Fang1+, Xinwei Hu1+, Quan-Xin Li2,Shao-Fei Ni2*, andZhixiong Ruan1*

[1] Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, P. R. China.

[2] Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong, Shantou University, Shantou 515063, Guangdong, P. R. China.

[+] These authors contributed equally to this work.

—Angew. Chem. Int. Ed. 2025, 10.1002/anie.202418277

Recommended by Rui Jin

KEY WORDS:electro chemistry, Cu catalysis, ring opening (反應類型), C(sp3)-O(成鍵類型), cyclic amines, peptides,water (原料),amino alcohols (產物), paired electrolysis, CuHspecies, Cu(MeCN)4BF4 (其他)

ABSTRACT:Amino alcohols, particularly remote amino alcohols and peptide alcohols, are valuable due to their functional diversity in biologically active compounds. However, traditional synthesis methods face significant challenges, making electrochemistry an attractive alternative. The authors have developed a mild and biocompatible sequential paired electrolysis strategy, leveraging copper-electrocatalysis to synthesize diverse remote amino alcohols, including unnatural peptide alcohols. Both experimental results and density functional theory (DFT) calculations demonstrated that water serves as both the hydroxyl source and the solvent, facilitating the generation of CuHwith Cu(I) at the cathode, which in turn reduces the aldehyde intermediates formed during the reaction.

Background and this work: (B) Conventional methods to synthesize amino alcohols.(C) Electrochemical synthesis of remote amino alcohols (this work)

Substrate scope: cyclic amine derivatives (selected examples)

Substrate scope: Late-stage modifications of peptides (selected examples)

Proposed mechanism

In summary, Shao-Fei Ni and Zhixiong Ruanet al. have reported a novel electrochemical ring-opening protocolthat enables direct synthesis of remote amino alcoholsthrough copper-mediated sequential paired electrolysisunder mild and biocompatible reaction conditions. This strategy offers expedient access to a wide variety of remote amino alcohols with diverse synthetic functional groups. The unique power of the electro-redox ring-opening approach facilitates the efficient modification and assembly of peptide alcohols. Notably, mechanistic experiments and DFT calculations demonstrate that H2O participates in the formation of CuH and reduces aldehydes to alcohols.

汕頭大學倪紹飛課題組和廣州醫科大學阮志雄課題組共同報道了一種新穎的電化學開環反應，通過銅催化的成對電解，在溫和且生物相容的反應條件下直接合成遠端氨基醇。該策略為合成具有多樣化合成功能團的遠端氨基酸醇提供了便捷途徑。電化學氧化還原開環方法的獨特優勢促進了肽醇的高效修飾和組裝。機理研究和DFT計算表明水（作為溶劑和氫源）參與了CuH陰極活性物種的生成，將中間體醛還原為醇。

（轉自：康龍化成）

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