Cheng Xuan, Yin Quan, Cheng Yi-Fei, Wu Shao-Hua, Sun Xin-Chang, Kong De-Yi, Deng Qing-Hai
The Education Ministry Key Laboratory of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Normal University, Shanghai, 200234, China.
Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China.
Nat Commun. 2024 Aug 20;15(1):7131. doi: 10.1038/s41467-024-51655-5.
Organic nitrates, as effective donors of the signaling molecule nitric oxide, are widely applied in the pharmaceutical industry. However, practical and efficient methods for accessing organic nitrates are still scarce, and achieving high regiocontrol in unactivated alkene difunctionalization remains challenging. Here we present a simple and practical method for highly regioselective halonitrooxylation of unactivated alkenes. The approach utilizes TMSX (X: Cl, Br, or I) and oxybis(aryl-λ-iodanediyl) dinitrates (OAIDN) as sources of halogen and nitrooxy groups, with 0.5 mol % FeCl as the catalyst. Remarkably, high regioselectivity in the halonitrooxylation of aromatic alkenes can be achieved even without any catalyst. This protocol features easy scalability and excellent functional group compatibility, providing a range of β-halonitrates (127 examples, up to 99% yield, up to >20:1 rr). Notably, 2-iodoethyl nitrate, a potent synthon derived from ethylene, reacts smoothly with a variety of functional units to incorporate the nitrooxy group into the desired molecules.
有机硝酸盐作为信号分子一氧化氮的有效供体，在制药工业中得到广泛应用。然而，获取有机硝酸盐的实用且高效的方法仍然稀缺，并且在未活化烯烃的双官能团化反应中实现高区域选择性仍然具有挑战性。在此，我们展示了一种用于未活化烯烃的高度区域选择性卤代硝基氧基化的简单实用方法。该方法利用TMSX（X：Cl、Br或I）和双（芳基-λ-碘二亚基）二硝酸酯（OAIDN）作为卤素和硝基氧基的来源，以0.5 mol%的FeCl作为催化剂。值得注意的是，即使没有任何催化剂，在芳族烯烃的卤代硝基氧基化反应中也能实现高区域选择性。该方案具有易于扩大规模和出色的官能团兼容性的特点，可提供一系列β-卤代硝酸盐（127个实例，产率高达99%，区域选择性高达>20:1）。值得注意的是，硝酸2-碘乙酯是一种由乙烯衍生的有效合成子，它能与多种官能团单元顺利反应，将硝基氧基引入所需分子中。
