Stereoselective Desymmetrization of Cyclohexadienone-Tethered Enones: Efficient Access to Highly Strained Polycyclic Indoles

A highly regioselective and stereoselective cascade annulation of indoles with C2-symmetric enone tethered-cyclohexadienones provides rapid access to complex indole alkaloid-like scaffolds in high yields. Interestingly, a different reaction course was observed with 3-substituted indoles giving C-2/N annulation products with similar complexity via intramolecular aza-Michael addition. This desymmetrization approach is highly practical and allows atom-economical synthesis of natural product-like molecules containing several contiguous stereocenters with broad range of substrate scope and high functional-group tolerance. The synthetic utility of the products was demonstrated with various chemoselective, regioselective, and diastereoselective transformations on the highly strained polycyclic indoles to elaborate the value of this tandem reaction.吲哚（indoles）与C2对称烯酮连接型环己二烯酮之间的高区域选择性、立体选择性级联环化反应，可高产率快速构建复杂的类吲哚生物碱骨架。值得注意的是，3位取代的吲哚展现出不同的反应路径，可通过分子内氮杂-迈克尔（aza-Michael）加成反应生成具有类似复杂度的C-2/N位环化产物。该去对称化策略实用性极强，可实现含多个连续手性中心的类天然产物分子的原子经济性合成，且底物适用范围广、官能团耐受性优异。研究人员通过对高度张力的多环吲哚产物进行多种化学选择性、区域选择性及非对映选择性转化反应，验证了该类产物的合成实用性，并阐明了该串联反应的应用价值。