Institute of Organic Chemistry & MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510006, P. R. China.
J Am Chem Soc. 2022 Sep 14;144(36):16490-16501. doi: 10.1021/jacs.2c05668. Epub 2022 Sep 2.
Electrophilic halogenation of alkenes is a powerful transformation offering a convenient route for the construction of valuable functionalized molecules. However, as a highly important reaction in this field, catalytic asymmetric intermolecular iodinative difunctionalization remains a formidable challenge. Herein, we report that an efficient Lewis basic chiral sulfide-catalyzed approach enables this reaction. By this approach, challenging substrates such as γ,γ-disubstituted allylic sulfonamides and 1,1-disubstituted alkenes with an allylic sulfonamide unit undergo electrophilic iodinative difunctionalization to give a variety of iodine-functionalized chiral molecules in good yields with excellent enantio- and diastereoselectivities. A series of free phenols as nucleophiles are successfully incorporated into the substrates. Aside from phenols, primary and secondary alcohols, fluoride, and azide also serve as efficient nucleophiles. The obtained iodinated products are a good platform molecule, which can be easily transformed into various chiral compounds such as α-aryl ketones, chiral secondary amines, and aziridines via rearrangement or substitution. Mechanistic studies revealed that the chiral sulfide catalyst displays a superior effect on control of the reactivity of electrophilic iodine and the enantioselective construction of the chiral iodiranium ion intermediate and catalyst aggregates might be formed as a resting state in the reactions.
烯烃的亲电卤化反应是一种强大的转化反应,为构建有价值的功能化分子提供了一种便捷的途径。然而,作为该领域的一个非常重要的反应,催化不对称的分子间碘化双官能化反应仍然是一个巨大的挑战。在此,我们报告了一种有效的路易斯碱性手性硫化物催化方法可以实现这一反应。通过这种方法,具有挑战性的底物,如γ,γ-二取代烯丙基磺酰胺和带有烯丙基磺酰胺单元的 1,1-二取代烯烃,可以经历亲电碘化双官能化反应,以优异的对映选择性和非对映选择性得到各种碘官能化的手性分子,产率良好。一系列游离酚类作为亲核试剂成功地被引入到底物中。除了酚类,伯醇和仲醇、氟化物和叠氮化物也可以作为有效的亲核试剂。获得的碘化产物是一个良好的平台分子,通过重排或取代,可以很容易地转化为各种手性化合物,如α-芳基酮、手性仲胺和氮丙啶。机理研究表明,手性硫化物催化剂在手性碘亲电试剂的反应性控制和手性碘𬭩离子中间体的对映选择性构建方面具有优越的效果,反应中可能形成催化剂聚集体作为静止状态。