Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, 221 00 Lund, Sweden.
Org Lett. 2021 May 7;23(9):3536-3540. doi: 10.1021/acs.orglett.1c00955. Epub 2021 Apr 8.
The first syntheses of the isomeric dioxafenestrene natural products (-)-asperaculin A and (-)-penifulvin D are reported. Each target is formed selectively by choice of oxidant in a final divergent bioinspired Baeyer-Villiger (BV) reaction. Density functional theory calculations reveal that electrostatic interactions between the oxidant leaving group and the lactone motif accounts for a reversal of selectivity with HO/HO compared to peracids. Synthetic features include forging the polycyclic carbon framework with a diastereoselective -photocycloaddition biased by an ether substituent at the aryl α-position. The encumbered tertiary alcohol was installed by cyanation of a ketone intermediate followed by nonaqueous hydrolysis of the resulting delicate cyanohydrin.
报道了异构二氧菲斯特伦天然产物（-）-asperaculin A 和（-）-penifulvin D 的首次全合成。每个目标都是通过选择氧化剂在最终的发散仿生 Baeyer-Villiger（BV）反应中选择性形成的。密度泛函理论计算表明，与过酸相比，氧化剂离去基团和内酯基序之间的静电相互作用解释了选择性的反转。合成特点包括通过在芳基α位的醚取代基偏置的立体选择性 -光环加成来锻造多环碳框架。通过酮中间体的氰化反应，然后对得到的脆弱的氰醇进行非水水解，安装了受阻的叔醇。
