Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
J Org Chem. 2011 Apr 15;76(8):2753-61. doi: 10.1021/jo200125c. Epub 2011 Mar 10.
Using an intramolecular [4 + 2] cycloaddition/rearrangement cascade of 3-(1,4-dioxaspiro[4.4]non-7-en-7-yl)-N-furan-2-ylpropionamide (23) as the key step, the BCD core of the lycopodium alkaloid fawcettidine was constructed. Heating the initially formed Diels-Alder cycloadduct at 180 °C results in a nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the ensuing zwitterion to give a rearranged hexahydroindolinone. Our attempts to induce a related intramolecular furan Diels-Alder reaction (IMDAF) from the corresponding ketone of 23 failed to give any cycloaddition product. Instead, the only product obtained corresponded to a cyclopentenone derivative derived by isomerization of the double bond into the thermodynamically more stable α,β-position. Efforts toward construction of the final skeleton of fawcettidine by ring A closure of the rearranged cycloadduct derived from furanyl amide 23 are discussed.
利用 3-(1,4-二恶螺[4.4]壬-7-烯-7-基)-N-呋喃-2-基丙酰胺（23）的分子内[4+2]环加成/重排级联作为关键步骤，构建了石松生物碱法氏啶的 BCD 核心。将最初形成的 Diels-Alder 环加成产物在 180°C 下加热，导致氮辅助开环，随后是随之而来的两性离子的去质子化/再质子化，得到重排的六氢吲哚酮。我们试图从 23 的相应酮诱导相关的呋喃 Diels-Alder 反应（IMDAF），但未能得到任何环加成产物。相反，唯一得到的产物对应于通过双键异构化到热力学上更稳定的α,β-位得到的环戊烯酮衍生物。讨论了通过重排环加成产物的环 A 闭合来构建法氏啶的最终骨架的努力。
