Department of New Drug Research and Development, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
Molecules. 2018 Oct 22;23(10):2727. doi: 10.3390/molecules23102727.
An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition path and clarified the dual roles of catalytic pyridine as base and crucial ligand to accelerate the oxidation of Ag(I) to Ag(II), which is likely oxidant responsible for the formation of NCS• radical. These mechanistic results may impact the design and refinement of other radical based reactions proceeding through catalytic oxidations mediated by Ag(I)-pyridine/persulfate. The chemical versatility of thiocyanate moiety was also highlighted via SCN-tailoring chemistry in post-synthetic transformation for new S-C(sp³/sp²/sp), S-P, and S-S bonds constructions. The protocol provides an easy access to many important bioisosteres in medicinal chemistry and an array of sulfur-containing 2-oxindoles that are difficult to prepare by other approaches.
一种高效的 Ag/pyridine 协同介导的通过自由基加成/环化级联过程的活化烯烃的芳基硫氰化反应被开发出来。该反应可以在温和的条件下进行,以良好至优异的收率提供具有生物意义的 3-烷硫基-2-氧吲哚。机理研究表明了一种独特的 NCS•自由基加成途径,并阐明了催化吡啶作为碱和关键配体的双重作用,以加速 Ag(I)到 Ag(II)的氧化,Ag(II)可能是形成 NCS•自由基的氧化剂。这些机理结果可能会影响通过 Ag(I)-吡啶/过硫酸盐介导的催化氧化进行的其他基于自由基的反应的设计和改进。通过后合成转化中的 SCN 调变化学,硫氰酸酯部分的化学多功能性也得到了强调,用于新的 S-C(sp³/sp²/sp)、S-P 和 S-S 键的构建。该方案为药物化学中的许多重要生物等排体以及许多通过其他方法难以制备的含硫 2-氧吲哚提供了一种简单的制备途径。