Bär Robin M, Kirschner Stefan, Nieger Martin, Bräse Stefan
Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany.
Department of Chemistry, University of Helsinki, P.O. Box 55 (A. I. Virtasen aukio 1, 00014, Helsinki, Finland.
Chemistry. 2018 Jan 26;24(6):1373-1382. doi: 10.1002/chem.201704105. Epub 2017 Dec 18.
Herein the addition of different thiols to the strained carbon-carbon bond of [1.1.1]propellane (1) is reported. The reaction pathway was investigated, addition reactions with substituted thiols, hydrogen sulfide and protected cysteine were performed, and further modifications of the products were verified. The clean reaction proceeds by a radical chain process, which was confirmed by different deuterium labelling experiments. It shows high functional-group tolerance, since halo-, hydroxy-, methoxy-, carboxy-, amino- and nitro-substituted thiols could be added to 1 with few by-products in 16-90 % yield. Oxidation of the products allows tuning of the polarity and subsequent reactions of the products. The click-type reaction proceeds even faster with selenols, as was shown in a proof of concept. Thiol addition to 1 offers a facile tool for surface modification, conjugation and tuning of hydrophilicity in bio- and medicinal chemistry.
本文报道了将不同的硫醇加成到[1.1.1]丙烷（1）的张力碳-碳键上的反应。研究了反应途径，进行了与取代硫醇、硫化氢和保护的半胱氨酸的加成反应，并验证了产物的进一步修饰。该反应通过自由基链过程顺利进行，这一点通过不同的氘标记实验得到了证实。它显示出高官能团耐受性，因为卤代、羟基、甲氧基、羧基、氨基和硝基取代的硫醇可以以16-90%的产率、很少的副产物加成到1上。产物的氧化可以调节极性并进行后续反应。如概念验证所示，点击型反应与硒醇反应进行得更快。硫醇加成到1上为生物和药物化学中的表面修饰、共轭和亲水性调节提供了一种简便的工具。
