英国布里斯托大学Lennox, Alastair J. J.团队报道了非对映性亲核-亲核烯烃氯氟化。相关研究成果发表在2024年7月1日出版的《自然—化学》。

烯烃的选择性杂二卤代为广泛的化学应用提供了有用的构建块。与同二卤代不同，选择性杂二卤代反应，特别是氟卤代反应并不发达。目前的方法将亲电卤素源与亲核卤素源相结合，这必然导致反加成，并且区域选择性仅使用高度活化的烯烃实现。

该文中，研究人员描述了一种替代的亲核试剂-亲核试剂方法，该方法以高度区域选择性、化学选择性和非对映选择性的方式在未活化的烯烃上添加氯离子和氟离子。研究人员发现了反应机制中一个奇怪的开关，它触发了非对映选择性的完全逆转，以促进反加成或顺加成。

这些条件在一系列药物相关化合物上得到了证明，详细的机制研究表明，顺非对映异构体和反非对映体之间的选择性和切换，是基于不同的活性碘以及两种卤化物中哪一种首先加入。

附：英文原文

Title: Diastereodivergent nucleophile–nucleophile alkene chlorofluorination

Author: Doobary, Sayad, Lacey, Andrew J. D., Sweeting, Stephen G., Coppock, Sarah B., Caldora, Henry P., Poole, Darren L., Lennox, Alastair J. J.

Issue&Volume: 2024-07-01

Abstract: The selective hetero-dihalogenation of alkenes provides useful building blocks for a broad range of chemical applications. Unlike homo-dihalogenation, selective hetero-dihalogenation reactions, especially fluorohalogenation, are underdeveloped. Current approaches combine an electrophilic halogen source with a nucleophilic halogen source, which necessarily leads to anti-addition, and regioselectivity has only been achieved using highly activated alkenes. Here we describe an alternative, nucleophile–nucleophile approach that adds chloride and fluoride ions over unactivated alkenes in a highly regio-, chemo- and diastereoselective manner. A curious switch in the reaction mechanism was discovered, which triggers a complete reversal of the diastereoselectivity to promote either anti- or syn-addition. The conditions are demonstrated on an array of pharmaceutically relevant compounds, and detailed mechanistic studies reveal the selectivity and the switch between the syn- and anti-diastereomers are based on different active iodanes and which of the two halides adds first.

DOI: 10.1038/s41557-024-01561-6

Source: https://www.nature.com/articles/s41557-024-01561-6