Department of Chemistry, McGill University, 801 Sherbrooke W., Montreal, QC, H3A 0B8, Canada.
Angew Chem Int Ed Engl. 2017 Aug 28;56(36):10830-10834. doi: 10.1002/anie.201706273. Epub 2017 Jul 27.
The total synthesis of (-)-virosaine A (1) was achieved in ten steps starting from furan and 2-bromoacrolein. A one-pot Diels-Alder cycloaddition/organolithium addition initiated an efficient sequence to access a key oxime/epoxide intermediate. Heating this intermediate in acetic acid resulted in an intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct the caged core of 1 in a single step. Several methods of C-H functionalization were assessed on the cascade product, and ultimately, a directed lithiation/bromination effected selective C14 functionalization, enabling the synthesis of 1.
(-)-Virosaine A（1）的全合成工作从呋喃和 2-溴丙烯醛出发，经十步反应完成。一锅法 Diels-Alder 环加成/有机锂加成反应有效地构建了关键的肟/环氧化物中间体。该中间体在乙酸中加热，导致分子内环氧化开环/硝酮[3+2]环加成级联反应，一步构建了 1 的笼状核心。对级联产物进行了几种 C-H 官能团化方法的评估，最终，定向锂化/溴化实现了选择性的 C14 官能团化，从而完成了 1 的合成。
