Zou Hui-Na, Huang Meng-Lin, Huang Ming-Yao, Su Yu-Xuan, Zhang Jing-Wei, Zhang Xin-Yu, Zhu Shou-Fei
Frontiers Science Center for New Organic Matter, State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University Tianjin 300071 China
Chem Sci. 2023 Aug 8;14(34):9186-9190. doi: 10.1039/d3sc03266c. eCollection 2023 Aug 30.
Chiral fluorinated reagents provide new opportunities for the discovery of drugs and functional materials because the introduction of a fluorinated group significantly alters a molecule's physicochemical properties. Chiral -difluoroalkyl fragments (R-CF-C*) are key motifs in many drugs. However, the scarcity of synthetic methods and types of chiral -difluoroalkyl reagents limits the applications of these compounds. Herein, we report two types of chiral -difluoroalkyl reagents chiral -difluoroalkyl propargylic borons and -difluoroalkyl α-allenols and their synthesis by means of methods involving rhodium-catalyzed enantioselective B-H bond insertion reactions of carbenes and Lewis acid-promoted allenylation reactions. The mild, operationally simple method features a broad substrate scope and good functional group tolerance. These two types of reagents contain easily transformable boron and alkynyl or allenyl moieties and thus might facilitate rapid modular construction of chiral molecules containing chiral -difluoroalkyl fragments and might provide new opportunities for the discovery of chiral -difluoroalkyl drugs and other functional molecules.
手性氟化试剂为药物和功能材料的发现提供了新的机遇，因为引入氟代基团会显著改变分子的物理化学性质。手性二氟烷基片段（R-CF-C*）是许多药物中的关键结构单元。然而，手性二氟烷基试剂的合成方法和种类稀缺，限制了这些化合物的应用。在此，我们报道了两种手性二氟烷基试剂——手性二氟烷基炔丙基硼和二氟烷基α-联烯醇，以及通过涉及铑催化的卡宾对映选择性B-H键插入反应和路易斯酸促进的联烯基化反应的方法来合成它们。该温和、操作简便的方法具有广泛的底物范围和良好的官能团耐受性。这两种试剂含有易于转化的硼以及炔基或联烯基部分，因此可能有助于快速模块化构建含有手性二氟烷基片段的手性分子，并可能为发现手性二氟烷基药物和其他功能分子提供新的机遇。
