Chandrasoma Nalin, Pathmanathan Sivadarshini, Buszek Keith R
Department of Chemistry, University of Missouri, 205 Kenneth A. Spencer Chemical Laboratories, 5100 Rockhill Road, Kansas City, MO 64110.
Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), University of Kansas, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047.
Tetrahedron Lett. 2015 Jun 3;56(23):3507-3510. doi: 10.1016/j.tetlet.2015.02.064.
A practical, multi-gram 10-step synthesis of racemic herbindole A, B, and C from a common intermediate is described. The key step features a remarkably regioselective C-7 metal-halogen exchange and elimination from a Bartoli-generated --butyldimethylsilyl-4,6,7-tribromo-5-methylindole scaffold to afford the 6,7-indole aryne. Cycloaddition with cyclopentadiene, oxidative cleavage, and Fujimoto reduction gave a common intermediate from which all three herbindoles were readily derived. A final Pd(0)-catalyzed Negishi and Stille cross-coupling reaction at the C-4 bromide afforded each of the herbindoles on a multigram scale.
描述了一种从常见中间体出发，实用的、多克规模的外消旋herbindole A、B和C的十步合成方法。关键步骤的特点是从Bartoli生成的叔丁基二甲基甲硅烷基-4,6,7-三溴-5-甲基吲哚骨架进行显著区域选择性的C-7金属-卤素交换和消除反应，以得到6,7-吲哚芳炔。与环戊二烯的环加成、氧化裂解和藤本还原反应得到了一个常见中间体，所有三种herbindole均可容易地从该中间体衍生而来。在C-4溴化物上进行的最终钯(0)催化的根岸和施蒂勒交叉偶联反应，以多克规模得到了每种herbindole。
