Huang Jie, Yan Xueyuan, Liu Xuanyu, Chen Zhengyang, Jiang Tao, Zhang Lanlan, Ju Guodong, Huang Genping, Wang Chao
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, P. R. China.
Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, P. R. China.
J Am Chem Soc. 2024 Jun 26;146(25):17140-17149. doi: 10.1021/jacs.4c03022. Epub 2024 Jun 12.
Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require the use of activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, and esters, we succeed in realizing a nickel-catalyzed 1,2-borylalkynylation of unactivated alkenes to enable the simultaneous incorporation of a boron entity and an sp-fragment across the double bond. The products contain boryl, alkynyl, and carbonyl functional groups with orthogonal synthetic reactivities, offering three handles for further derivatization to access valuable intermediates. The utility of this ligand-enabled asymmetric protocol has been highlighted through the late-stage decoration of drug-relevant molecules.
烯烃与硼试剂的对映选择性三组分双官能团化反应是构建三维手性有机硼化合物的一种有吸引力的策略。然而,区域和对映选择性控制是这些转化中的关键挑战,这些反应主要需要使用活化的共轭烯烃。在此,通过使用各种羰基导向基团,包括酰胺、亚磺酰胺、酮和酯,我们成功实现了镍催化的未活化烯烃的1,2-硼基炔基化反应,从而能够在双键上同时引入一个硼实体和一个sp片段。产物含有具有正交合成反应性的硼基、炔基和羰基官能团,为进一步衍生化以获得有价值的中间体提供了三种途径。通过与药物相关分子的后期修饰,突出了这种配体介导的不对称方法的实用性。