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.

手性螺吲哚酮(spirooxindole)是大量具有生物活性的天然及非天然产物的核心骨架。然而，构建三螺环吲哚酮(trispirocyclic oxindoles)仍颇具挑战，这源于其骨架结构复杂、组装难度大，且难以精准调控多个季碳手性中心(quaternary stereocenters)的立体选择性。本文报道了一种有机碱/一价金(Au(I))催化的顺序型不对称1,2-加成/级联氢胺化/杂狄尔斯-阿尔德(HDA, hetero-Diels–Alder)/脱异丁烯反应策略，可高效制备各类连有N,O-缩酮结构的三螺环吲哚酮与双吲哚酮产物，产物具有优异的光学纯度（对映体过量值91%~99% ee）。该方法的关键在于以N-叔丁氧羰基亚胺基吲哚酮(N-Boc-iminooxindoles)作为杂二烯体(heterodienes)，通过一价金(Au(I))催化的杂狄尔斯-阿尔德反应实现核心转化。