Synthesis of Chiral Trispirocyclic Oxindoles via Organic-Base/Au(I)-Catalyzed Sequential Reactions

Chiral
spirooxindole is the core structure of a large number of
natural and unnatural products with biological activities. However,
the construction of trispirocyclic oxindoles remains challenging because
of the difficulty in the assembly, the complex skeleton, and control
of the stereoselectivities of the multiple quaternary stereocenters.
Herein, we present the organic base/Au­(I)-catalyzed sequential asymmetric
1,2-addition/cascade hydroamination/HDA/deisobutene reactions for
the elaboration of various trispirocyclic N,O-ketal tethered oxindoles and bisoxindoles in excellent
optical purities (91–99% ee). Key to the success
of this methodology is Au­(I)-catalyzed hetero-Diels–Alder reactions
utilizing N-Boc-iminooxindoles as the heterodienes.

手性螺环氧化吲哚（Chiral spirooxindole）是大量具备生物活性的天然与非天然产物的核心结构。然而，三螺环氧化吲哚的构建仍极具挑战，原因在于其骨架组装难度大、结构复杂，且难以精准调控多个季碳手性中心的立体选择性。在此，我们报道了有机碱/金(I)（Au(I)）催化的连续不对称1,2-加成/串联氢胺化/杂狄尔斯-阿尔德（hetero-Diels–Alder，简称HDA）/脱异丁烯反应，可用于构建各类带有N,O-缩酮桥联的三螺环氧化吲哚与双氧化吲哚，产物光学纯度优异（91%~99% ee，对映体过量（enantiomeric excess））。该方法学成功的关键在于，以N-叔丁氧羰基亚胺基氧化吲哚（N-Boc-iminooxindoles）作为杂双烯体，通过金(I)催化的杂狄尔斯-阿尔德反应完成关键转化。