Park Jisook, Jean Alexandre, Chen David Y-K
Department of Chemistry , Seoul National University , Gwanak-1 Gwanak-ro, Gwanak-gu , Seoul 151-742 , South Korea.
J Org Chem. 2018 Jul 6;83(13):6936-6957. doi: 10.1021/acs.joc.7b02426. Epub 2017 Nov 9.
Herein we report the total syntheses of communesin F and putative members of the communesin family of polycyclic bis-aminal alkaloids. The successful strategy featured a novel organocatalytic reaction between two oxindole subunits to cast, after extensive optimization, the all-carbon vicinal quaternary stereocenters of the target molecule with high enantiocontrol. The resulting bis-oxindole intermediate further underwent a Ti(O Pr)-mediated dehydrative skeletal rearrangement to furnish the communesin core structure. Consider the ready availability and low-cost of unsubstituted isatin, and the inferior organocatalytic reaction employing a bromo-substituted substrate, a Pd(OAc)-catalyzed and oxalamide-directed aryl CH-alkenylation reaction was implemented to assemble the complete skeletal backbone of the target molecule. Collectively, the synthetic technologies disclosed herein constitute the first asymmetric organocatalytic approach to the communesins, together with a highly effective late-stage CH-functionalization in stark contrast to the bromoarene substrates employed in all of the past synthetic work.
在此，我们报道了多环双缩醛生物碱类 communesin F 及其推定成员的全合成。成功的策略以两个氧化吲哚亚基之间的新型有机催化反应为特色，经过广泛优化后，以高对映体控制构建目标分子的全碳邻位季碳立体中心。所得的双氧化吲哚中间体进一步经 Ti(O Pr)介导的脱水骨架重排，以提供 communesin 的核心结构。考虑到未取代异吲哚酮的易得性和低成本，以及使用溴代取代底物的较差有机催化反应，实施了钯（乙酸）催化且草酰胺导向的芳基 C-H 烯基化反应来组装目标分子的完整骨架。总体而言，本文所公开的合成技术构成了 communesin 的首个不对称有机催化方法，以及与过去所有合成工作中所使用的溴代芳烃底物形成鲜明对比的高效后期 C-H 官能团化。
