美国波士顿大学Hoveyda Amir H.团队报道了具有三氟甲基和氟取代碳中心的化合物的双立体和对映选择性合成。相关研究成果发表在2022年11月14日出版的国际知名学术期刊《自然—化学》。

含有一个或多个氟原子的分子对药物的发现至关重要。已有选择性合成不同有机氟化合物的方案，包括具有氟取代或三氟甲基取代立体碳中心的有机氟化合物。然而，合成具有三氟甲基和氟取代基立体碳中心的化合物的方法远不常见。因此，这组具有潜在影响力的分子仍然严重不发达。

该文中，研究人员介绍了一种催化区域、非对映和对映选择性策略，用于制备具有与三氟甲基和氟原子结合的立体碳中心的高烯丙醇。该工艺包括聚氟烯丙基硼酸酯，并由原位形成的有机锌络合物催化，可用于非对映异构制备四氟单糖，包括抗病毒药物sofosbuvir（Sovaldi）的核糖核心类似物。意外的反应性/选择性分布可能源自三氟甲基和氟取代的碳位点，该发现预示着其他未知的独特化学。

附：英文原文

Title: Diastereo- and enantioselective synthesis of compounds with a trifluoromethyl- and fluoro-substituted carbon centre

Author: Xu, Shibo, del Pozo, Juan, Romiti, Filippo, Fu, Yue, Mai, Binh Khanh, Morrison, Ryan J., Lee, KyungA, Hu, Shaowei, Koh, Ming Joo, Lee, Jaehee, Li, Xinghan, Liu, Peng, Hoveyda, Amir H.

Issue&Volume: 2022-11-14

Abstract: Molecules that contain one or more fluorine atoms are crucial to drug discovery. There are protocols available for the selective synthesis of different organofluorine compounds, including those with a fluoro-substituted or a trifluoromethyl-substituted stereogenic carbon centre. However, approaches for synthesizing compounds with a trifluoromethyl- and fluoro-substituent stereogenic carbon centre are far less common. This potentially impactful set of molecules thus remains severely underdeveloped. Here we introduce a catalytic regio-, diastereo- and enantioselective strategy for the preparation of homoallylic alcohols bearing a stereogenic carbon centre bound to a trifluoromethyl group and a fluorine atom. The process, which involves a polyfluoroallyl boronate and is catalysed by an in situ-formed organozinc complex, can be used for diastereodivergent preparation of tetrafluoro-monosaccharides, including ribose core analogues of the antiviral drug sofosbuvir (Sovaldi). Unexpected reactivity/selectivity profiles, probably originating from the trifluoromethyl- and fluoro-substituted carbon site, are discovered, foreshadowing other unique chemistries that remain unknown.

DOI: 10.1038/s41557-022-01054-4

Source: https://www.nature.com/articles/s41557-022-01054-4