Frontiers Science Center for New Organic Matter, the State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
J Am Chem Soc. 2022 Jan 12;144(1):515-526. doi: 10.1021/jacs.1c11072. Epub 2021 Dec 22.
Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C-H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.
有机锌试剂是现代合成化学中最常用的有机金属试剂之一，多功能有机锌试剂可以通过炔烃碳锌化作用从结构简单、易得的有机锌试剂合成得到。然而，该方法对末端炔烃的容忍度较差，新引入的有机基团的转化也较为困难，这限制了其应用。在此，我们报道了一种新型铁催化剂催化末端炔烃的乙烯基锌化反应方法，该催化剂带有 1,10-菲咯啉-亚胺配体。该方法可以从易得的乙烯基锌试剂和末端炔烃高效合成具有多种结构和官能团的新型有机锌试剂。该方法具有出色的官能团容忍度（可容忍的官能团包括氨基、酰胺、氰基、酯基、羟基、砜基、缩醛、膦酸酯、吡啶基）、广泛的底物范围（适用的末端炔烃包括带有各种官能团的芳基、烯基和烷基炔烃）以及高的化学选择性、区域选择性和立体选择性。该方法可显著提高多种重要生物活性分子（包括维生素 A）的合成效率。机理研究表明，本研究中开发的新型铁-1,10-菲咯啉-亚胺催化剂具有极其拥挤的反应口袋，这促进了乙烯基向炔烃的高效转移，不利于锌试剂与末端 C-H 键之间的取代反应，并阻止了产物的进一步反应。我们的研究结果表明，在使用合适的配体时，铁催化剂在活性、化学选择性、区域选择性和立体选择性方面可以优于其他金属催化剂。
